deamino-arginine-vasopressin and Hyponatremia

Desmopressin acetate was recommended for nocturia in benign prostatic hyperplasia (BPH) patients recently, but its effect and safety is still controversial. We aimed to establish a systematic review and meta-analysis to confirm its effect on symptom relief and adverse effects.. A systematic search was performed in PubMed, Cochrane Library, EMBASE, Medline, Web of Science and Science Direct databases from January 2000 to October 2021 for controlled trials of BPH patients comparing oral desmopressin with control groups. The mean difference (MD) and odds ratio (OR) were meta-analyzed.. Four articles with 500 patients were included. Significantly greater benefit was detected for the desmopressin group in the improvement of nocturia (P = .004), international prostate symptom score - storage (IPSS-S) (P = .03), and quality of life (QoL) (P = .04) scores. Patients treated with desmopressin were at higher risk than the control group for short-term adverse events (P < .001), including nausea (4.71%, P = .04), headache (20%, P < .00001), dizziness (5.88%, P = .02) and hyponatremia (4.71%, P = .04), but the long-term incidence might decrease.. Desmopressin acetate can reduce nocturia frequency and improve the IPSS-S and QoL score in BPH patients. Some adverse reactions of desmopressin, such as hyponatremia, headache, dizziness and nausea, may be mild and short-term. No significant difference of desmopressin was found in improving the overall IPSS score and maximum urine flow.

Topics: Deamino Arginine Vasopressin; Dizziness; Headache; Humans; Hyponatremia; Male; Nausea; Nocturia; Prostatic Hyperplasia; Quality of Life; Treatment Outcome

This review aims to provide prescribing clinicians a deeper appreciation of desmopressin's clinical indications and formulation types, to better balance efficacy and safety through proper formulation selection.. Since its discovery 50 years ago, desmopressin's antidiuretic properties have been used for central diabetes insipidus, primary monosymptomatic nocturnal enuresis and adult nocturnal polyuria, while its coagulant effects are useful for mild hemophilia A and von Willebrand Disease. During this time, newer formulations of desmopressin have also been introduced to the market raising questions on interchangeability, dose conversion and safety. The wide array of clinical indications and variable pharmacokinetic properties of different desmopressin preparations raises the possibility of medication error, especially the risk of hyponatraemia.. A narrative review to explore clinically relevant aspects of desmopressin therapy, synthesising information obtained from searches of published literature.. We identified that the risk factors for developing hyponatremia include extremes of age, existing comorbidity, drug interaction, intranasal formulations and intercurrent illness. We describe the dose equivalence between all formulations to facilitate conversion. We highlight that in view of inter-subject variability, close monitoring is recommended when switching preparations. We found that paediatric data remains limited, leading to recent proposals for age- and weight-based dosing regimens.. The risk of hyponatremia, albeit small, can be reduced by adhering to the indication-specific doses and taking steps to govern the safe prescription of the drug. Further paediatric clinical trials are awaited to expand the evidence base of childhood desmopressin therapy.

Topics: Administration, Intranasal; Administration, Oral; Adult; Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Humans; Hyponatremia

The treatment of central diabetes insipidus has not changed significantly in recent decades, and dDAVP and replacement of free water deficit remain the cornerstones of treatment. Oral dDAVP has replaced nasal dDAVP as a more reliable mode of treatment for chronic central diabetes insipidus. Hyponatraemia is a common side effect, occurring in one in four patients, and should be avoided by allowing a regular break from dDAVP to allow a resultant aquaresis. Hypernatraemia is less common, and typically occurs during hospitalization, when access to water is restricted, and in cases of adipsic DI. Management of adipsic DI can be challenging, and requires initial inpatient assessment to establish dose of dDAVP, daily fluid prescription, and eunatraemic weight which can guide day-to-day fluid targets in the long-term.

Topics: Body Weight; Deamino Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Humans; Hypernatremia; Hyponatremia; Neurophysins; Protein Precursors; Vasopressins

Diabetes insipidus and the syndrome of inappropriate antidiuretic hormone secretion lie at opposite ends of the spectrum of disordered renal handling of water. Whereas renal retention of water insidiously causes hypotonic hyponatremia in syndrome of inappropriate antidiuretic hormone secretion, diabetes insipidus may lead to free water loss, hypernatremia, and volume depletion. Hypernatremia and hyponatremia are associated with worse outcomes and longer intensive care stays. Moreover, pathologies causing polyuria and hyponatremia in patients in intensive care may be multiple, making diagnosis challenging. We provide an approach to the diagnosis and management of these conditions in intensive care patients.

Topics: Antidiuretic Agents; Critical Care; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hypernatremia; Hyponatremia; Inappropriate ADH Syndrome; Male; Practice Guidelines as Topic; Water-Electrolyte Balance

Nocturia is a common urinary condition experienced by both men and women. While desmopressin has historically been utilized to treat conditions such as central diabetes insipidus and primary nocturnal enuresis, there is an increased interest in the use of desmopressin in the management of adult nocturia. Areas covered: This article provides a review on the pathophysiology of nocturia and the clinical outcomes and safety profile of desmopressin in the management of adult nocturnal voiding dysfunction. Expert opinion: To date, desmopressin is the only anti-diuretic hormone that is approved for nocturia. Published literature on desmopressin demonstrate good clinical efficacy in terms of number of nocturnal voids, voided volume and sleep period. Newer formulations have shown that a minimum dosage of 25 μg orally disintegrating sublingual desmopressin appears to be ideal for women, whereas men usually benefit from a minimum of 50 μg. Of the known adverse drug reactions, hyponatremia remains a major concern especially in patients over 65 years of age. At present, long term data on desmopressin remains scarce. Lastly, it is important to stress that no single treatment deals with nocturia in all contexts, and careful assessment remains essential to identify the appropriate and safest treatment in each patient.

Topics: Antidiuretic Agents; Aquaporins; Clinical Trials as Topic; Deamino Arginine Vasopressin; Government Regulation; Humans; Hyponatremia; Nocturia; Treatment Outcome

Inherited bleeding disorders increase the risk of bleeding in the obstetric patient. Randomized controlled trials to compare prophylactic or therapeutic interventions are rare, and guidance documents rely heavily on expert opinion. Here we report the results of a systematic review of the literature for the treatment and prevention of peripartum bleeding in women with an inherited bleeding disorder. The highest-quality evidence is for the use of tranexamic acid in postpartum hemorrhage, which has been shown to decrease bleeding-related mortality in women without bleeding disorders. There is limited evidence for prophylactic use of this agent in women with inherited bleeding disorders. Desmopressin has also been used in observational studies of patients with von Willebrand disease and carriers of hemophilia A with some success, although concerns about the risk of hyponatremia persist. In patients with deficiencies of specific factors, replacement is generally the preferred approach, and concentrates have been studied in deficiencies of VWF and factors VII, VIII, IX, XI, and XIII as well as in patients with fibrinogen deficiency. Because of the small size of these studies, neither safety nor efficacy is well established, although the literature suggests that bleeding history may be more predictive of outcomes than factor levels in many cases. Goal factor levels have not been studied or systematically established in any of these diseases, although observational data suggest that achieving normal levels may be inadequate, particularly for VWF and factor VIII, which are physiologically elevated in pregnancy. For factor deficiencies in which no specific concentrate is available, such as factors II (prothrombin) and V, prothrombin complex concentrate or fresh frozen plasma may be used, and for platelet defects or deficiencies, such as Glanzmann thrombasthenia or Bernard-Soulier syndrome, platelet transfusion is generally first line, although use of recombinant FVIIa has been reported in patients with Glanzmann thrombasthenia to avoid development of, or treat patients with, antibodies to platelet glycoprotein IIbIIIa. Ultimately, data are lacking to definitively support an evidence-based approach to management in any of these disorders, and prospective, controlled studies are desperately needed.

Topics: Blood Coagulation; Deamino Arginine Vasopressin; Female; Fibrinolytic Agents; Hematology; Hemophilia A; Heterozygote; Humans; Hyponatremia; Obstetrics; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications, Hematologic; Tranexamic Acid; Treatment Outcome; von Willebrand Diseases

Topics: Adult; Aged; Antidiuretic Agents; Deamino Arginine Vasopressin; Humans; Hyponatremia; Incidence; Middle Aged; Nasal Sprays; Nocturia; Off-Label Use

Central pontine myelinolysis (CPM) is a rare condition usually caused by rapid sodium correction in hyponatraemia after a severe neurological syndrome. Only few cases have been reported during pregnancy, most of which were reported in patients with hyperemesis. We describe the successful management of the first case of twin pregnancy in a patient who presented with CPM after treatment for premature labour and then review the literature on CPM in pregnancy (aetiology, diagnosis and management). Our patient required emergency delivery to achieve electrolyte and fluid balance. At six months, the twins remained asymptomatic and the mother had minor sequelae. The aetiology is not clear, and there is no evidence regarding the optimal treatment or prognosis of CPM. In our patient, desmopressin-contaminated atosiban showed a certain probability in the Karch-Lasagne algorithm of a causality relationship between hyponatraemia and the drug. To our knowledge, this is the first case of myelinolysis reported in a twin pregnancy possibly related to desmopressin-contaminated atosiban.

Topics: Adult; Antidiuretic Agents; Antiemetics; Brain; Cesarean Section; Deamino Arginine Vasopressin; Dexamethasone; Drug Contamination; Female; Humans; Hyponatremia; Infant, Newborn; Magnetic Resonance Imaging; Myelinolysis, Central Pontine; Obstetric Labor, Premature; Pregnancy; Pregnancy, Twin; Tocolytic Agents; Ultrasonography, Prenatal; Vasotocin; Water-Electrolyte Balance

Hyponatremia causes significant morbidity, mortality, and disability. This review considers the literature of the past 18 months to improve understanding of these complications and to identify therapeutic strategies to prevent them.. Acute hyponatremia causes serious brain swelling that can lead to permanent disability or death. A 4-6 mEq/l increase in serum sodium is sufficient to reverse impending herniation. Brain swelling is minimal in chronic hyponatremia, and to avoid osmotic demyelination, correction should not exceed 8 mEq/l/day. In high-risk patients, correction should not exceed 4-6 mEq/l/day. Inadvertent overcorrection of hyponatremia is common and preventable by controlling unwanted urinary water losses with desmopressin. Even mild chronic hyponatremia is associated with increased mortality, attention deficit, gait instability, osteoporosis, and fractures, but it is not known if the correction of mild hyponatremia improves outcomes.. Controlled trials are needed to identify affordable treatments for hyponatremia that reduce the need for hospitalization, decrease hospital length of stay, and decrease morbidity. Such trials could also help answer the question of whether hyponatremia causes excess mortality or whether it is simply a marker for severe, lethal, underlying disease.

Topics: Animals; Brain Edema; Cognition Disorders; Deamino Arginine Vasopressin; Fractures, Bone; Gait Disorders, Neurologic; Humans; Hypernatremia; Hyponatremia; Osteoporosis; Saline Solution, Hypertonic; Sodium; Sodium Chloride

Treatment with desmopressin diacetate arginine vasopressin (DDAVP) and its withdrawal are associated with side effects. We present a rare case of severe biphasic adverse reactions induced by DDAVP and its withdrawal in a 63-year-old female patient. A lump in the left axillary region was biopsied, and she received DDAVP after surgery. The following day, she lost consciousness, with foaming at the mouth and seizures. Hypotonic encephalopathy was considered. DDAVP was ceased, and she received electrolytes. On day 1, she displayed low blood pressure and increased urine output. She received DDAVP and dopamine as well as electrolytes. The patient was ambulatory on day 7 and was discharged without brain abnormalities on MRI. In conclusion, severe hyponatremia induced by DDAVP and massive polyuria and hypovolemic shock induced by DDAVP withdrawal are life-threatening conditions. This case underlines the need to be vigilant when administering DDAVP and to monitor for any side effects.

Topics: Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Middle Aged; Polyuria; Shock

Hyponatremia is common among inpatients and is associated with severe adverse outcomes such as osmotic demyelination syndrome. Current guidelines recommend serum sodium concentration correction targets of no more than 8 mEq/L per day in patients at high risk of osmotic demyelination syndrome. Desmopressin is recommended to control high rates of serum sodium concentration correction in severe hyponatremia. However, recommendations are based on limited data. The objective of this study is to review current strategies for DDAVP use in severe hyponatremia.. Systematic literature search of 4 databases of peer-reviewed studies was performed and study quality was appraised.. The literature search identified 17 observational studies with 80 patients. We found 3 strategies for desmopressin administration in hyponatremia: 1) proactive, where desmopressin is administered early based on initial serum sodium concentration; 2) reactive, where desmopressin is administered based on changes in serum sodium concentration or urine output; 3) rescue, where desmopressin is administered after serum sodium correction targets are exceeded or when osmotic demyelination appears imminent. A proactive strategy of desmopressin administration with hypertonic saline was associated with lower incidence of exceeding serum sodium concentration correction targets, although this evidence is derived from a small case series.. Three distinct strategies for desmopressin administration are described in the literature. Limitations in study design and sample size prevent definitive conclusions about the optimal strategy for desmopressin administration to correct hyponatremia. There is a pressing need for better quality research to guide clinicians in managing severe hyponatremia.

Topics: Acute Disease; Antidiuretic Agents; Deamino Arginine Vasopressin; Humans; Hyponatremia; Sodium

Rapid correction of severe hyponatremia carries the risk of osmotic demyelination. Two recently introduced methods of correction of hyponatremia have diametrically opposite effects on aquaresis. Inhibitors of vasopressin V2 receptor (vaptans) lead to the production of dilute urine, whereas infusion of desmopressin causes urinary concentration. Identification of the category of hyponatremia that will benefit from one or the other treatment is critical. In general, vaptans are effective in hyponatremias presenting with concentrated urine and, with the exception of hypovolemic hyponatremia, can be used as their primary treatment. Desmopressin is effective in hyponatremias presenting with dilute urine or developing urinary dilution after saline infusion. In this setting, desmopressin infusion helps prevent overcorrection of the hyponatremia. Monitoring of the changes in serum sodium concentration as a guide to treatment changes is imperative regardless of the initial treatment of severe hyponatremia.

Topics: Animals; Deamino Arginine Vasopressin; Disease Management; Humans; Hyponatremia; Infusions, Intravenous; Saline Solution, Hypertonic; Severity of Illness Index; Vasopressins

Dilutional hyponatremia is a serious adverse effect of desmopressin, a vasopressin analog that is widely prescribed to manage monosymptomatic enuresis. The presentation of hyponatremia, largely related to cerebral dysfunction, can include severe signs like altered mental status and seizures.. We reviewed the literature dealing with altered mental status or seizures in enuretic subjects on desmopressin. The retained publications included patients who were described individually, revealing data on mode of administration, further identifiable factors predisposing to hyponatremia, presentation and clinical course.. We found 54 cases of hyponatremia secondary to desmopressin treatment presenting with altered mental status or seizures. In most cases the complication developed 14 days or less after starting desmopressin. An intranasal formulation had been used in 47 patients. Excess fluid intake was documented as a contributing factor in at least 22 cases. In 6 cases severe signs of hyponatremia developed in the context of intercurrent illnesses.. Altered mental status or seizures are very rare but recognized complications of desmopressin in enuresis. This complication mostly develops in subjects managed with the intranasal formulation 14 days or less after starting the medication, following excess fluid intake and during intercurrent illnesses.

Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Enuresis; Humans; Hyponatremia; Lethargy; Seizures; Severity of Illness Index

Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Deamino Arginine Vasopressin; Humans; Hyperkalemia; Hypernatremia; Hyponatremia; Inappropriate ADH Syndrome; Membrane Potentials; Morpholines; Osmolar Concentration; Potassium; Randomized Controlled Trials as Topic; Sodium; Spiro Compounds; Survival Rate; Tolvaptan; Water-Electrolyte Imbalance

Hyponatremia is the most common electrolyte abnormality encountered in children. In the past decade, new advances have been made in understanding the pathogenesis of hyponatremic encephalopathy and in its prevention and treatment. Recent data have determined that hyponatremia is a more serious condition than previously believed. It is a major comorbidity factor for a variety of illnesses, and subtle neurological findings are common. It has now become apparent that the majority of hospital-acquired hyponatremia in children is iatrogenic and due in large part to the administration of hypotonic fluids to patients with elevated arginine vasopressin levels. Recent prospective studies have demonstrated that administration of 0.9% sodium chloride in maintenance fluids can prevent the development of hyponatremia. Risk factors, such as hypoxia and central nervous system (CNS) involvement, have been identified for the development of hyponatremic encephalopathy, which can lead to neurologic injury at mildly hyponatremic values. It has also become apparent that both children and adult patients are dying from symptomatic hyponatremia due to inadequate therapy. We have proposed the use of intermittent intravenous bolus therapy with 3% sodium chloride, 2 cc/kg with a maximum of 100 cc, to rapidly reverse CNS symptoms and at the same time avoid the possibility of overcorrection of hyponatremia. In this review, we discuss how to recognize patients at risk for inadvertent overcorrection of hyponatremia and what measures should taken to prevent this, including the judicious use of 1-desamino-8d-arginine vasopressin (dDAVP).

Topics: Brain; Brain Diseases, Metabolic; Child; Deamino Arginine Vasopressin; Fluid Therapy; Humans; Hyponatremia; Hypotonic Solutions; Iatrogenic Disease; Isotonic Solutions; Prospective Studies; Sodium Chloride

Many patients with mild inherited bleeding disorders such as von Willebrand disease (VWD), mild haemophilia A (HA) and platelet function defects (PFD) undergo adenoidectomy and/or tonsillectomy (AT) procedures each year. Management of bleeding in these patients can be challenging, as little published data exist to guide haemostatic management during these relatively common procedures. Therefore, the literature was reviewed to identify AT procedures in patients with 1-deamino-8-D-argine vasopressin responsive mild bleeding disorders. The review revealed no randomized prospective trials of haemostatic management in this patient population. Case reports and small case series identified 144 patients who had AT procedures. Frequency of desmopressin and antifibrinolytic dosing varied widely. Fifteen percentage of patients experienced postoperative bleeding with nearly half being early (<24 h) bleeding and half being late (>24 h) bleeding. Hyponatraemia complicated the procedures in 47% of cases and six hyponatremic seizures were reported. Issues identified by this review that need to be addressed in future clinical trials include type and amount of fluid restriction when utilizing desmopressin, duration of antifibrinolytic therapy and duration and frequency of desmopressin dosing.

Topics: Adenoidectomy; Adolescent; Adult; Antifibrinolytic Agents; Child; Child, Preschool; Deamino Arginine Vasopressin; Hemophilia A; Hemostatics; Humans; Hyponatremia; Middle Aged; Postoperative Hemorrhage; Tonsillectomy; von Willebrand Diseases; Young Adult

We review literature from the past 18 months on the treatment of hyponatremia. Therapy must address both the consequences of the untreated electrolyte disturbance (including fatal cerebral edema due to acute water intoxication) and the complications of excessive therapy (the osmotic demyelination syndrome).. Correction of hyponatremia by 4-6 mEq/l within 6 h, with bolus infusions of 3% saline if necessary, is sufficient to manage the most severe manifestations of hyponatremia. Planning therapy to achieve a 6 mEq/l daily increase in the serum sodium concentration can avoid iatrogenic brain damage by staying well clear of correction rates that are harmful. Conservative correction goals are wise because inadvertent overcorrection is common. Administration of desmopressin to halt a water diuresis can help prevent overcorrection; if overcorrection occurs, therapeutic relowering of the serum sodium concentration is supported by data in experimental animals and was found to be safe in a small observational clinical trial. Even mild and apparently asymptomatic hyponatremia may lead to falls because of impaired gait, and an increased likelihood of fracture because of hyponatremia-induced osteoporosis, a newly described entity. Recently approved vasopressin antagonists now make it possible to normalize the serum sodium concentration on a chronic basis, but practical considerations have limited their use.

Topics: Animals; Deamino Arginine Vasopressin; Humans; Hyponatremia; Sodium; Vasopressins

Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are dire neurological disorders, characterized by severe damage to the myelin sheath of neurons, which typically result from rapid correction or overcorrection of systemic hyponatremia. For many years, both conditions have been considered universally fatal, though survivors have been reported more recently. Pediatric cases are rare. We present a 13-year-old boy with panhypopituitarism secondary to repair of a nasofrontal encephalocele in infancy, managed on long-term corticosteroid, deamino arginine vasopressin and thyroid hormone. He presented with severe hyponatremia (116 mEq/l), which during correction rapidly and unexpectedly increased to 176 mEq/l, resulting in profoundly impaired consciousness. Brain imaging revealed multiple bilateral changes in the basal ganglia, thalamus, pons and cerebral white matter, consistent with both CPM and EPM. Malignant cerebellar edema necessitated emergent suboccipital craniectomy, with subsequent improvement in level of consciousness and imaging postoperatively. However, he succumbed to acute cardiorespiratory arrest 8 weeks later. Nine similar cases from the literature are reviewed.

Topics: Adolescent; Antidiuretic Agents; Brain Edema; Cerebellum; Deamino Arginine Vasopressin; Humans; Hyponatremia; Magnetic Resonance Imaging; Male; Myelinolysis, Central Pontine; Osmotic Pressure

Oxytocin (OT) and vasopressin (AVP) mediate their biological actions by acting on four known receptors: The OT (uterine) and the AVP V(1a) (vasopressor), V(1b) (pituitary), V(2) (renal) receptors and a fifth putative AVP V(1c)? (vasodilating) receptor. This presentation will summarize some highlights of the recent progress, in the design and synthesis of selective peptide agonists, antagonists, radioiodinated ligands, fluorescent ligands and bivalent ligands for these receptors. Here we present published and unpublished pharmacological data on the most widely used agonists, antagonists and labelled ligands. The pharmacological properties of promising new selective OT antagonists and V(1b) agonists are also presented. This review should serve as a useful guide for the selection of the most appropriate ligand for a given study. The current status of non-peptide OT and AVP antagonists and agonists is also summarized. The relative merits of peptide and non-peptide AVP and OT agonists and antagonists as: (1) research tools and (2) therapeutic agents will be evaluated. Many of the receptor selective peptide agonists and antagonists from this and other laboratories are far more widely used as pharmacological tools for studies on the peripheral and central effects of OT and AVP than their non-peptide counterparts. In addition to OT and to a lesser extent AVP (pitressin), a number of OT and AVP analogues; such as carbetocin (OT agonist) dDAVP (desmopressin, V(2) agonist), terlipressin (V(1a) agonist), felypressin (V(1a) agonist) and atosiban (Tractocile OT antagonist) are also in clinical use. Despite much early promise, no non-peptide V(1a) or OT antagonists are currently in clinical trials. While a number of orally active non-peptide V(2) antagonists (Vaptans); notably, Tolvaptan, Lixivaptan and Satavaptan, are currently in Phase III clinical trials; to date, only the mixed V(2)/V(1a), antagonist Conivaptan (Vaprisol), has been approved by the US FDA for clinical use (by i.v. administration), for the treatment of euvolemic and hypervolemic hyponatremia in hospitalized patients. Promising new non-peptide V(1b) and OT antagonists, as well as non-peptide V(2) and OT agonists are now in pre-clinical development.

Topics: Animals; Antidiuretic Agents; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Clinical Trials as Topic; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Lypressin; Oligopeptides; Oxytocin; Peptides; Rats; Receptors, Oxytocin; Receptors, Vasopressin; Structure-Activity Relationship; Terlipressin; Uterus; Vasodilator Agents; Vasopressins

In this article, the authors highlight the circumstances surrounding the death of a young adult neurosurgical patient, recently reported to ISMP Canada. The incident signals the need for enhanced safeguards for patients receiving desmopressin (also known as dDAVP) and intravenous therapy. The authors present information from a recent ISMP Canada Safety Bulletin relevant to critical care, including an outline of potential contributing factors and suggested recommendations.

Topics: Adverse Drug Reaction Reporting Systems; Brain Neoplasms; Canada; Critical Care; Deamino Arginine Vasopressin; Diabetes Insipidus; Drug Monitoring; Fatal Outcome; Humans; Hyponatremia; Hypotonic Solutions; Infusions, Intravenous; Medication Errors; Nursing Assessment; Postoperative Care; Renal Agents; Safety Management

Desmopressin acetate is the synthetic analogue of the antidiuretic hormone arginine vasopressin. It has been employed clinically for >30 years in a range of formulations: intranasal solution (since 1972), injectable solution (since 1981), tablets (since 1987), and most recently, an oral lyophilisate (since 2005). The antidiuretic properties of desmopressin have led to its use in polyuric conditions including primary nocturnal enuresis, nocturia, and diabetes insipidus. While a large body of clinical data is available for desmopressin, and despite its widespread use, comprehensive reviews of the safety of desmopressin are lacking (although some case series have attempted to correlate patient and/or dosing characteristics with the occurrence of adverse reactions). The purpose of this paper is to review the safety of desmopressin, based on analyses of both published data (MedLine) and of adverse reactions reported to Ferring Pharmaceuticals, the major manufacturer of desmopressin. Based on the findings, suggested strategies to reduce the risk of adverse reactions are proposed. Treatment with intranasal and oral formulations of desmopressin is generally well tolerated, and side effects are usually minor. The risk of hyponatraemia, although small, can be reduced by adhering to the indications, dosing recommendations and precautions when prescribing desmopressin.

Topics: Adverse Drug Reaction Reporting Systems; Antidiuretic Agents; Clinical Trials as Topic; Deamino Arginine Vasopressin; Humans; Hyponatremia; Nocturia; Nocturnal Enuresis; Risk Factors

Desmopressin is a well established and effective therapy for nocturnal enuresis. Water intoxication leading to hyponatremia is an infrequent but serious adverse event associated with desmopressin. We assessed the safety of desmopressin in children 18 years or younger with nocturnal enuresis with a focus on the relative safety of the oral compared with the intranasal formulation.. Published data (MEDLINE) from December 1972 to August 2006 and post-marketing safety data from December 1972 to June 2005 were analyzed.. A total of 21 clinical trials on desmopressin use in children with nocturnal enuresis were identified. There were no reports of hyponatremia. A total of 21 publications were identified that included 48 case reports of hyponatremia in children with nocturnal enuresis. In all case reports patients were treated with intranasal desmopressin. Post-marketing safety data included 151 cases of hyponatremia in children with nocturnal enuresis, of whom 145 were treated with intranasal desmopressin and 6 were treated with the tablet formulation. Prodromal symptoms of hyponatremia were identified as headache, nausea and vomiting.. Data suggest that there is a decreased risk of hyponatremia with oral desmopressin compared with intranasal desmopressin. Identifiable and preventable risk factors for hyponatremia are inappropriately high fluid intake, administration of a larger than recommended dose, young age (less than 6 years) and concomitant administration of another medication. When desmopressin is prescribed, patients should be instructed to avoid high fluid intake when the medication is ingested, not ingest a higher than recommended dose and promptly discontinue the medication and seek assessment if headache, nausea or vomiting develops.

Topics: Administration, Intranasal; Administration, Oral; Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Humans; Hyponatremia; Nocturnal Enuresis; Osmolar Concentration; Risk Factors

DDAVP is a drug that should be used with caution for each patient individually. Particular care is needed to avoid fluid overload and rapid fluctuations in sodium concentration. Not only families but physicians as well should be educated and aware of the adverse effects of DDAVP, especially in high risk patients. Extreme caution is needed in children with severe neurological and developmental problems who cannot control their fluid intake themselves. Similarly, caution is needed in patients with hypodipsia and DI who have difficulty in balancing water intake and DDAVP dose. The treatment of DI is water; however, DDAVP is given to avoid a large fluid intake which can result in medullary washout. Frequent home monitoring of body weight and regular determinations of serum sodium may help to disclose the early phase of over-hydration or dehydration. DDAVP therapy should be temporarily interrupted during acute illness, febrile episodes, hot days and other conditions with increased water intake. It should be used with considerable caution in patients with cystic fibrosis, or renal or cardiovascular diseases. In patients with enuresis, it is recommended that DDAVP medication should not be continued for longer than 3 months without stopping for 1 week for full reassessment. Fluid intake should be limited 1 hour before and 8 hours after the dose. Generally, undertreatment with vasopressin analogue is safer than overtreatment. A simple measure to avoid overtreatment is to miss one dose once a week; a rapid onset diuresis ('washout' effect) provides considerable reassurance.

Topics: Adolescent; Antidiuretic Agents; Brain Edema; Child; Deamino Arginine Vasopressin; Diabetes Insipidus; Drinking; Enuresis; Hemostatics; Humans; Hyponatremia; Myelinolysis, Central Pontine; Sodium; Water Intoxication

Desmopressin is widely used in primary nocturnal enuresis, bleeding disorders, central diabetes insipidus and diagnostic urine concentration testing. Hyponatremic hypervolemia leading to seizures has been reported as a rare but potentially life threatening side effect of desmopressin therapy. We sought to identify factors that predispose patients to hyponatremia and to find predictive factors associated with increased risk of water intoxication.. We report 13 novel cases of desmopressin associated water intoxication and review the literature. A total of 93 instances of symptomatic hyponatremia during desmopressin treatment in children were identified. Specific data were reported in 58 of 93 cases. These 58 cases, in addition to our 13 novel cases, were further analyzed.. All children were treated with intranasal or intravenous desmopressin. No patient received oral desmopressin. Younger children are at greater risk for water intoxication than older children. The risk is particularly high at the beginning of desmopressin therapy. A total of 45 patients (63%) had prodromal symptoms, eg nausea, vomiting and headache. In 10 cases (14%) desmopressin was prescribed without an evident need.. Based on this analysis, we conclude that the use of desmopressin should be cautiously considered, careful monitoring should be performed during the initiation of therapy, and particular care should be taken when treating young children and when prodromal symptoms such as nausea, vomiting and headaches occur.

Topics: Adolescent; Child; Child, Preschool; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Hypovolemia; Male; Renal Agents; Water Intoxication

To estimate the incidence of hyponatremia in older adults who use nasal or oral desmopressin to treat nocturia.. A systematic review and meta-analysis of cohort studies and randomised controlled trials of the use of nasal or oral desmopressin for older adults with nocturia. The incidence of hyponatremia was estimated by a random effects model for binomial data.. Seventy-five papers were identified by the literature review of which 14 were reports of randomised trials or cohort studies. Seven studies reported the incidence of hyponatremia. The pooled estimate for the incidence of hyponatremia was 7.6% (95% CI 3.7-15.1).. Hyponatremia is a relatively common adverse effect of the use of desmopressin for the treatment of nocturia and caution and regular monitoring should be part of the use of this management option for nocturia in older adults.

Topics: Administration, Intranasal; Administration, Oral; Aged; Clinical Trials as Topic; Deamino Arginine Vasopressin; Humans; Hyponatremia; Incidence; Renal Agents; Risk Assessment; Urination Disorders

Hypothermia has been demonstrated to induce pancytopenia in animals, but whether this association exists in humans is unknown. The authors report the case of an 8-year-old girl in whom hypothermia (temperature 33 degrees C-35 degrees C) is the cause of pancytopenia. The patient developed thermoregulatory dysfunction subsequent to surgical resection of a craniopharyngioma. Her recurrent cytopenias could not be explained by any etiology except chronic hypothermia. The pancytopenia improved upon rewarming the patient to a temperature of 36 degrees C. This association between hypothermia and pancytopenia has rarely been reported in humans and may be underdiagnosed especially in cases of transient or milder presentations. The authors recommend careful hematologic monitoring of patients with thermoregulatory dysfunction.

Topics: Adrenal Insufficiency; Blood Cell Count; Cerebral Infarction; Child; Chronic Disease; Consciousness Disorders; Craniopharyngioma; Deamino Arginine Vasopressin; Dehydration; Diabetes Insipidus; Female; Frontal Lobe; Humans; Hyponatremia; Hypophysectomy; Hypopituitarism; Hypothalamus; Hypothermia; Hypothyroidism; Pancreatitis; Pancytopenia; Pituitary Neoplasms; Postoperative Complications; Seizures; Sleep Stages

Topics: Adult; Aged; Clinical Trials, Phase III as Topic; Deamino Arginine Vasopressin; Humans; Hyponatremia; Middle Aged; Renal Agents; Risk Factors; Treatment Outcome; Urination Disorders

Hyponatraemia is a common finding in patients with acute cerebral insults. The main differential diagnosis is between syndrome of inappropriate ADH secretion and cerebral salt wasting. Our aim is to review the topic of hyponatraemia in patients with acute cerebral insults and suggest a clinical approach to diagnosis and management.

Topics: Acute Disease; Algorithms; Brain Diseases; Child, Preschool; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Female; Fluid Therapy; Humans; Hyponatremia; Hypothalamic Neoplasms; Inappropriate ADH Syndrome; Postoperative Complications; Renal Agents; Sodium

We present a case of a 29-year-old woman with a long history of nocturnal enuresis who developed symptomatic hyponatremia from water intoxication shortly after beginning desmopressin. A MEDLINE search in the English language revealed 13 prior case reports. All patients presented with seizure, mental status changes, or both. Two distinct presentations occurred: one group of patients maintained a stable course with desmopressin and developed symptoms related to an outside factor. The other group of patients were new to desmopressin and had a profound water intoxication response from its use. While the underlying cause was from simple overhydration, the quickness of this unanticipated adverse effect is noteworthy. The importance of counseling to ensure a family's and a patient's understanding of the effects of desmopressin as well as monitoring electrolytes periodically may help identify and prevent this serious iatrogenic complication.

Topics: Administration, Intranasal; Adolescent; Adult; Child; Child, Preschool; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Hyponatremia; Infant; Male; Renal Agents; Water Intoxication

Hyponatremia following acute or chronic central nervous system injury which is due to excessive Na+ loss in the urine without an increase in the body fluid, has been described as Cerebral Salt Wasting Syndrome (CSWS). This syndrome is often confused with dilutional hyponatremia secondary to inappropriate ADH secretion. Accurate diagnosis and management are mandatory for to improve the course of the disease. In this study a patient with CSW Syndrome is presented and the treatment and diagnosis of this syndrome are discussed in view of the literature.

Topics: Adenoma; Adult; Deamino Arginine Vasopressin; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Pituitary Neoplasms; Postoperative Complications; Saline Solution, Hypertonic; Sodium

Treatment of nocturnal enuresis with DDAVP is associated with a low incidence of adverse effects. The only reported serious adverse effect is seizure or altered level of consciousness due to water intoxication. We reviewed 14 articles that reported data on serum sodium in patients treated with DDAVP for nocturnal enuresis and 11 articles that reported patients who developed a seizure or altered level of consciousness during treatment with DDAVP for nocturnal enuresis. Excess fluid intake was identified as a contributing factor in 6 of the 11 case reports.. Hyponatremia is a potential adverse effect in patients with nocturnal enuresis who are treated with DDAVP. To prevent this adverse effect we recommend that the patients prescribed DDAVP for nocturnal enuresis should be counseled not to ingest more than 240 ml (8 ounces) of fluid on any night that DDAVP is administered.

Topics: Adolescent; Child; Child, Preschool; Deamino Arginine Vasopressin; Enuresis; Humans; Hyponatremia; Renal Agents

To explore risk factors for desmopressin-induced hyponatraemia and evaluate the impact of a serum sodium monitoring plan.. This was a meta-analysis of data from three clinical trials of desmopressin in nocturia. Patients received placebo or desmopressin orally disintegrating tablet (ODT; 10-100 μg). The incidence of serum sodium <130 mmol/L was recorded by age, sex and dose. Potential predictors of clinically significant hyponatraemia were identified using multivariate analysis in a Cox proportional hazards model.. Dose, age, baseline serum sodium level and kidney function, according to estimated GFR clearance, were significant risk factors for hyponatraemia in both sexes; similar to the known risk factors associated with hyponatraemia in the general population. In men, arthritis and use of drugs for bone disease were also predictive of hyponatraemia, while in women, raised monocytes and absence of lipid-modifying drugs increased the risk of hyponatraemia. Use of the proposed monitoring scheme and the minimum effective dose would have omitted all patients with clinically significant hyponatraemia from further treatment.. The incidence of hyponatraemia can be reduced by using minimum effective gender-specific dosing with the ODT formulation of desmopressin (25 μg in women, 50 μg in men). A sodium monitoring plan is proposed whereby baseline sodium must be ≥135 mmol/L (especially important in the elderly), with additional monitoring at week 1 and month 1 for those at elevated risk because they are aged ≥65 years or receiving concomitant medication associated with hyponatraemia. This monitoring plan would help to prevent some at-risk patients developing hyponatraemia; retrospective application of the monitoring plan showed that, once at-risk patients were appropriately screened out, only mild, non-clinically significant hyponatraemia was observed, within ranges of other drugs associated with hyponatraemia and similar to the background prevalence in the treatment population.

Topics: Adult; Aged; Aged, 80 and over; Antidiuretic Agents; Deamino Arginine Vasopressin; Double-Blind Method; Drug Monitoring; Female; Humans; Hyponatremia; Male; Middle Aged; Network Meta-Analysis; Nocturia; Retrospective Studies; Sodium; Young Adult

Central diabetes insipidus (CDI) is associated with arginine vasopressin (AVP) deficiency with resultant polyuria and polydipsia. Intranasal desmopressin provides physiological replacement but oral formulations are preferred for their ease of administration. This study aimed to demonstrate the efficacy and safety of desmopressin orally disintegrating tablet (ODT) in the treatment of Japanese patients with CDI, and confirm that antidiuresis is maintained on switching from intranasal desmopressin to desmopressin ODT. A total of 20 patients aged 6-75 years with CDI were included in this 4-week multicenter, open-label study. Following observation, patients switched from intranasal desmopressin to desmopressin ODT with titration to optimal dose over ≤5 days at the study site. Following three consecutive doses with stable patient fluid balance, patients were discharged with visits at Weeks 2 and 4. Following titration from intranasal desmopressin to ODT, the mean 24-hour urine volume was unchanged, indicating similar antidiuresis with both formulations. The proportion of patients with endpoint measurements (urine osmolality, 24-hour urine volume, hourly diuresis rate and urine-specific gravity) within normal range at Days 1-2 (intranasal desmopressin) and Week 4 (desmopressin ODT) was similar. The mean daily dose ratio of intranasal desmopressin to desmopressin ODT (Week 4) was 1:24 but a wide range was observed across individuals to maintain adequate antidiuretic effect. Hyponatraemia was generally mild and managed by dose titration. Desmopressin ODT achieved sufficient antidiuretic control compared to intranasal therapy and was well tolerated over long-term treatment. The wide range of intranasal:ODT dose ratios underline the importance of individual titration.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antidiuretic Agents; Chemical Phenomena; Child; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Diuresis; Dose-Response Relationship, Drug; Drug Monitoring; Female; Follow-Up Studies; Humans; Hyponatremia; Japan; Male; Mechanical Phenomena; Middle Aged; Tablets; Young Adult

Increased age and female gender are well-known risk factors for the development of desmopressin-induced hyponatremia. However, little focus has been on exploring gender differences in the antidiuretic response to desmopressin. Based on an exploratory analysis from three clinical trials, we report a significant gender difference in the effects of desmopressin on nocturnal urine volume that could not be explained by pharmacokinetic differences. Mean desmopressin concentration profiles were tested for covariates, and age and gender were not statistically significant and only weight was significant for log(C(max)) (P = 0.0183) and borderline significant for log(AUC) (P = 0.0571). The decrease in nocturnal urine volume in nocturia patients treated with desmopressin over 28 days was significantly larger for women at the lower desmopressin melt doses of 10 and 25 μg than for men. The ED(50) for men was modeled to be 43.2 μg and 16.1 μg for women, with the ED(50) men/women estimated to be 2.7 (1.3-8.1 95% CI), corresponding to significantly higher sensitivity to desmopressin in women. An increasing incidence of hyponatremia with increasing dose was found, and at the highest dose level of 100 μg decreases in serum sodium were approximately twofold greater in women over 50 yr of age than in men. A new dose recommendation stratified by gender is suggested in the treatment of nocturia: for men, 50- to 100-μg melt is an efficacious and safe dose, while for women a dose of 25 μg melt is recommended as efficacious with no observed incidences of hyponatremia. Areas for further research are proposed to uncover pathophysiological mechanism(s) behind these gender differences.

Topics: Adolescent; Adult; Age Factors; Aged; Antidiuretic Agents; Controlled Clinical Trials as Topic; Cross-Over Studies; Deamino Arginine Vasopressin; Diuresis; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hyponatremia; Male; Middle Aged; Nocturia; Risk Assessment; Risk Factors; Sex Factors; Sodium; Time Factors; Treatment Outcome; Urodynamics; Young Adult

To (1) identify abnormalities in arginine vasopressin (AVP, a water-conserving hormone) secretion and release in nursing home (NH) residents with nighttime urinary incontinence (UI); and (2) perform a pilot test of desmopressin acetate (ddAVP, a synthetic analog of the naturally occurring hormone) replacement in these residents.. Diagnostic evaluation and open-label treatment trial.. Two community nursing homes in a metropolitan area.. Male and female NH residents 65 years of age and older with nighttime UI.. Characterizations of AVP status followed by a 7-day open-label trial of oral ddAVP (either 0.1 mg or 0.2 mg).. Water deprivation test results, AVP levels, voided volumes, number of voids, incontinent episodes, number of nighttime checks found wet (out of 6 total checks per night).. All participants had measurable AVP levels of 2.0 pg/mL or higher. Six of 10 individuals had an abnormal water deprivation test. Two of 4 participants on 0.2 mg of ddAVP and 2 of 6 participants on 0.1 mg had a 200 mL or more mean reduction in nighttime urine volume. Both ddAVP dosages yielded a mean reduction of 0.7 fewer nighttime wet checks found wet. One participant in each group developed hyponatremia (1 of 6 on 0.1 mg and 1 of 4 on 0.2 mg). Hyponatremia resolved with discontinuation of the drug.. Both 0.1 mg and 0.2 mg of ddAVP given to carefully screened NH residents for 7 days produced a modest average reduction in nighttime urine volume and number of nighttime incontinent episodes that is likely of little clinical importance. The role of ddAVP in this population requires further research.

Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Antidiuretic Agents; Arginine Vasopressin; Deamino Arginine Vasopressin; Diapers, Adult; Enuresis; Female; Geriatric Assessment; Humans; Hyponatremia; Male; Nursing Homes; Pilot Projects; Sodium; Time Factors; Treatment Outcome; Urodynamics; Water Deprivation

The purpose of this study was to investigate the efficacy and safety of oral desmopressin in the treatment of nocturia in women.. Women aged 18 years or older with nocturia (>or=2 voids per night with a nocturia index score >1) received desmopressin (0.1 mg, 0.2 mg, or 0.4 mg) during a 3-week dose-titration period. After a 1-week washout period, patients who responded in this period received desmopressin or placebo in a double-blind fashion for 3 weeks.. In double-blind phase, 144 patients were randomly assigned to groups (desmopressin, n=72; placebo, n=72). For desmopressin, 33 (46%) patients had a 50% or greater reduction in nocturnal voids against baseline levels compared with 5 (7%) patients receiving placebo (P<.0001). The mean number of nocturnal voids, duration of sleep until the first nocturnal void, nocturnal diuresis, and ratios of nocturnal per 24 hours and nocturnal per daytime urine volumes changed significantly in favor of desmopressin versus placebo (P<.0001). In the dose-titration phase headache (22%), nausea (8%), and hyponatremia (6%) were reported. Two deaths occurred, although neither could be directly associated with the study drug.. Oral desmopressin is an effective and well-tolerated treatment for nocturia in women.

Topics: Adult; Aged; Deamino Arginine Vasopressin; Double-Blind Method; Female; Headache; Humans; Hyponatremia; Middle Aged; Nausea; Renal Agents; Urination Disorders

We report our experience with the incidence of adverse events during the use of Stimate brand intranasal desmopressin acetate (IN DDAVP) for patients with haemophilia A (HA) or von Willebrand disease (vWD) after noting two severe adverse events in one adult patient. All patients with documented vWD (type 1 or 2 A) or haemophilia A (mild, moderate or symptomatic carrier) from the Emory Comprehensive Hemophilia Center who had IN DDAVP challenge testing or were using Stimate for treatment of bleeding were evaluated for adverse events by patient report or nursing observation of clinical signs and symptoms. Forty patients were studied. Sixty-eight per cent (27/40) experienced clinical signs and/or symptoms. The majority of these symptoms were mild, however several patients reported moderate to severe side-effects and one adult patient required medical intervention for symptomatic hyponatraemia. In our experience, two-thirds of patients tested experienced adverse signs and/or symptoms with the use of Stimate; considerably higher than that reported from preliminary results in the literature. Young age did not correlate positively with adverse reactions. Severe adverse events requiring medical intervention were rare, however symptoms such as moderate to severe headache, nausea, vomiting and weakness may necessitate evaluation for hyponatraemia. This is the first report of symptomatic hyponatraemia in an adult patient with recommended dosing of Stimate. Side-effects may be minimized if patients adhere to instructions regarding fluid intake and composition while using IN DDAVP.

Topics: Administration, Intranasal; Adolescent; Adult; Age Factors; Child; Child, Preschool; Deamino Arginine Vasopressin; Fatigue; Female; Headache; Hemophilia A; Hemostatics; Heterozygote; Humans; Hyponatremia; Male; Menorrhagia; Middle Aged; Nausea; Potassium; Sex Factors; Sodium; von Willebrand Diseases; Weight Gain

To examine the safety and efficacy of desmopressin in three doses given to women with multiple sclerosis to treat nocturia with or without enuresis.. Eight women with clinically confirmed multiple sclerosis and nocturia with or without enuresis were entered as in-patients into an open, nonrandomized, placebo-controlled study of incremental doses of 20, 40 and 60 micrograms desmopressin. Urinary and serum sodium, plasma arginine vasopressin and urine osmolality were monitored every 4 h for 24 h. A single dose of placebo or desmopressin was given during each of four 24-h periods.. There was a significant decrease in nocturnal urinary volumes and a significant increase in nocturnal urinary osmolalities in patients taking desmopressin when compared with those taking a placebo, but there was no difference among the desmopressin doses. There was no significant difference in serum sodium level between the desmopressin doses. However, at the end of the 24-h period with the 60 micrograms dose, serum sodium was decreased significantly.. Neither a significant decrease in nocturnal urinary volumes nor an increase in urinary osmolality was achieved by doses of desmopressin > 20 micrograms. A dose of 60 g was associated with a decreased serum sodium level at the end of the 24-h period but there was no biochemical hyponatraemia. Because there were no benefits and a possibility of clinical hyponatraemia with higher doses, doses of > 20 micrograms desmopressin cannot be recommended.

Topics: Adult; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Female; Humans; Hyponatremia; Middle Aged; Multiple Sclerosis; Osmolar Concentration; Renal Agents; Sodium; Urination; Urination Disorders

Because the formation of sickle cells is dependent on the intracellular concentration of deoxyhemoglobin S, we investigated the possibility of altering or preventing sickle-cell crises by reducing serum sodium so as to cause red cells to swell. In three patients with sickle-cell anemia who had been disabled by recurrent painful crises, sustained dilutional hyponatremia was induced by 1-desamino-8-D-arginine vasopressin (DDAVP) in combination with a high fluid intake. Mean corpuscular hemoglobin concentration fell, and the degree of sickling at low partial oxygen pressure was reduced, as determined by morphologic criteria and by increased oxygen affinity of blood. Chronic hyponatremia (serum sodium, 120 to 125 mmol per liter) reduced the frequency of painful crises, whereas acutely induced hyponatremia abbreviated the duration of crises. These results, although preliminary, are encouraging enough to warrant further study of the safety and effectiveness of induced hyponatremia in the prevention and treatment of sickle-cell crises.

Topics: Adult; Anemia, Sickle Cell; Arginine Vasopressin; Clinical Trials as Topic; Deamino Arginine Vasopressin; Female; Fluid Therapy; Hemoglobin, Sickle; Humans; Hyponatremia; Male; Oxygen; Sodium

We aim to make desmopressin a safe treatment option for (older) patients at risk for hyponatremia, by introducing a new way of sodium monitoring. The goal is to reduce the risk of hyponatremia, enhance patient safety and ultimately introduce self-monitoring of sodium levels. The first step in the aforementioned is to validate capillary sodium.. 100 randomly selected patients admitted to the urology department received a single finger prick to collect capillary blood (250 µl) in a lithium-heparin tube. Each patient acted as its own control for the capillary and venous blood sample. Venous and capillary plasma sodium were analyzed by indirect ion-selective electrode measurement. The primary outcome was the agreement between capillary and venous sodium measurements, measured by the intra-class correlation coefficient (ICC).. One hundred paired blood samples were obtained of which four were excluded. There was no significant statistical difference observed between venous and capillary sodium (-0.23 mmol/L, p = 0.374). The ICC for single measures between capillary and venous sodium was 0.82 (95% confidence interval 0.75-0.88). Inter-method differences analyzed by a Bland-Altman plot and a Passing-Bablock regression did not reveal a statistically significant difference between both groups.. We demonstrated that venous and capillary sodium levels are interchangeable, taken into account the inter- and intravariability between analyses. We provided the first step towards a simple and safe solution for frequent sodium monitoring through a minimal invasive capillary blood collection. The results are of direct clinical relevance to safely use desmopressin in (older) patients at risk.

Topics: Capillaries; Deamino Arginine Vasopressin; Humans; Hyponatremia; Risk Factors; Sodium

Hypothalamic-pituitary region lymphoma is rare and diabetes insipidus (DI) represents one of the most common endocrine manifestations. We report the first case of hypothalamic lymphoma associated with both the syndrome of inappropriate antidiuresis (SIAD) and DI.. A 64-year-old woman with a history of stage IV large B-cell non-Hodgkin lymphoma, underwent atypical right lung resection for pulmonary nodules. A few days after surgery, the patient presented severe normovolemic hyponatremia and serum hypo-osmolarity, therefore, we suspected a paraneoplastic syndrome (SIAD) related to the lung neoplasm, histologically diagnosed as typical carcinoid. The brain magnetic resonance imaging (MRI) showed a 9 mm lesion in the hypothalamic region that significantly increased one month later with the onset of neurological symptoms. A trans-sphenoidal biopsy showed localization of the large B-cell lymphoma. After surgery, the patient presented with polyuria and polydipsia, so desmopressin therapy was started. In the following days, serum osmolarity and sodium fluctuated between normal and low values, then DI was excluded, and SIAD became more likely. Desmopressin therapy was discontinued and hyponatremia was treated with sodium infusion. Hypothalamic lymphoma was treated with chemotherapy and radiotherapy with substantial shrinkage. The hyponatremia persisted during anticancer treatments and improved only after radiotherapy, confirming paraneoplastic SIAD.. Lymphomas of the hypothalamic region can cause electrolyte imbalance for various causes. The differential diagnosis between SIAD, DI and impaired thirst centers may not be straightforward and the electrolyte disorders must be evaluated step by step in all different stages of the disease.

Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Diabetes Mellitus; Electrolytes; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Lymphoma; Middle Aged; Sodium

Hyponatremia is the most frequent electrolytic disorder in clinical practice. In addition to neurological symptoms, hyponatremia, even when mild/moderate and chronic, has been related to other manifestations, such as bone demineralization and increased risk of fractures. To better elucidate tissue alterations associated with reduced serum sodium concentration [Na. Overall, these findings shed new light on the possible consequences of chronic hyponatremia and prompt a more thorough evaluation of hyponatremic patients.

Topics: Animals; Deamino Arginine Vasopressin; Hyponatremia; Inappropriate ADH Syndrome; Liver; Male; Mice; Sodium; Spermatogenesis; Vasopressins

There is no consistent opinion on the optimal initial dose of desmopressin for patients with nocturnal polyuria. Over a period of 12 weeks, we investigated the safety and efficacy of an initial dose of 50 μg of desmopressin for elderly men.. Eighty patients (mean age: 78.8 years) were started on an initial dose of 50 μg of desmopressin for nocturia associated with nocturnal polyuria. Safety and efficacy were evaluated after 1, 4, and 12 weeks using a frequency-volume chart, Athens Insomnia Scale, Patient Global Impression of Improvement scale, physical examination, blood tests, and a body composition analyzer.. Along with reduction in the frequency and volume of night-time urination, improvements in hours of undisturbed sleep, nocturnal polyuria index, and International Prostate Symptom Score, and Overactive Bladder Symptom Scores on quality of life measures were also observed. Hyponatremia was observed in 15 patients (18.7%). However, only 5.0% of patients had hyponatremia after the dose was reduced to 25 μg, and the continuation rate at 12 weeks was high at 87.5%. Age and other physical factors, such as body mass index, body water content, body fat mass, and muscle mass were not significant predictors of adverse events.. Our study suggests that an initial dose of 50 μg is more effective than a uniformly minimum dose based on factors such as age and physique. Furthermore, a high continuation rate can be achieved by appropriately reducing the dose, if adverse events occur.

Topics: Aged; Antidiuretic Agents; Deamino Arginine Vasopressin; East Asian People; Humans; Hyponatremia; Male; Nocturia; Polyuria; Quality of Life

the identification and minimization of hyponatraemia-inducing medication (HIM) usage is among the effective strategies for preventing hyponatraemia. However, the differential risk of severe hyponatraemia is unknown.. to evaluate the differential risk of severe hyponatraemia associated with newly started and concurrently used HIMs in older people.. a case-control study using national claims databases.. we identified patients aged >65 years with severe hyponatraemia as those hospitalised with a primary diagnosis of hyponatraemia or who had received tolvaptan or 3% NaCl. A 1:20 matched control with the same visit date was constructed. Multivariable logistic regression was performed to assess the association of newly started or concurrently used HIMs comprising 11 medication/classes with severe hyponatraemia after covariate adjustment.. among 47,766,420 older patients, we identified 9,218 with severe hyponatraemia. After adjusting for covariates, all HIM classes were found to be significantly associated with severe hyponatraemia. Compared with persistently used HIMs, newly started HIMs increased the likelihood of severe hyponatraemia for eight classes of HIMs, with the highest increase being observed for desmopressin (adjusted odds ratio: 3.82, 95% confidence interval: 3.01-4.85). Concurrent use increased the risk of severe hyponatraemia compared to that with individually administered HIMs: thiazide-desmopressin (4.86, 3.90-6.07), medications causing the syndrome of inappropriate anti-diuretic hormone secretion (SIADH)-desmopressin (2.65, 2.25-3.11), medications causing SIADH-thiazides (1.87, 1.75-1.98) and combination among medications causing SIADH (1.36, 1.28-1.45).. in older adults, newly started and concurrently used HIMs increased the risk of severe hyponatraemia compared with persistently and singly used HIMs.

Topics: Aged; Case-Control Studies; Databases, Factual; Deamino Arginine Vasopressin; Humans; Hyponatremia; Inappropriate ADH Syndrome; Thiazides

Experience with nasogastric administration of oral DDAVP [desamino-D-arginine-8-vasopressin] lyophilisate (ODL) for central diabetes insipidus (CDI) in disabled children with swallowing coordination difficulties is limited.. We aimed to assess the safety and efficacy of nasogastric use of ODL in disabled children with CDI. Time to serum sodium normalisation was compared with that of children with normal intellect and CDI treated with sublingual DDAVP.. Clinical, laboratory and neuroimaging characteristics were evaluated for 12 disabled children with CDI treated with ODL through nasogastric tube at Dr Behcet Uz Children's Hospital, Turkey, between 2012 and 2022.. Six boys and six girls with a mean (±SD) age of 43 (± 40) months were evaluated. These children (mean [±SD] weight standard deviation score [SDS] - 1.2 ± 1.7; mean [±SD] height SDS - 1.3 ± 1.4) presented with failure to thrive, irritability, prolonged fever, polyuria and hypernatraemia (mean serum sodium 162 [±3.6] mEq/L). At diagnosis, mean serum and urine osmolality were 321 (± 14) mOsm/kg and 105 (± 7.8) mOsm/kg, respectively. Arginine vasopressin (AVP) levels were undetectable (< 0.5 pmol/L) at diagnosis in all patients. Nasogastric tube administration of DDAVP lyophilisate (120 µg/tablet) dissolved in water (10 mL) was commenced at a dose of 1-5 µg/kg/day in two divided doses together with controlled water intake to avoid hyponatraemia. The frequency and dose of DDAVP were titrated based on urine output and serum sodium concentration. Serum sodium declined at a rate of 0.11 ± 0.03 mEq/L/h and reached normal range in a mean duration of 174 ± 46.5 h. Serum sodium declined faster in children with normal intellect and CDI treated with sublingual DDAVP (1.28 ± 0.39 mEq/L/h; p = 0.0003). Three disabled children needed rehospitalisation because of hypernatraemia due to unintentional DDAVP omission by caregivers. No episode of hyponatraemia was observed. Weight gain and growth were normal during the median (± interquartile range) follow-up duration of 32 ± 67 months.. Nasogastric administration of oral DDAVP lyophilised formulation was safe and effective in the treatment of CDI in disabled children in this small retrospective series.

Topics: Child; Child, Preschool; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Diabetes Mellitus; Disabled Children; Female; Humans; Hypernatremia; Hyponatremia; Male; Retrospective Studies; Sodium

Hypertonic saline has been used for the treatment of hyponatremia for nearly a century. There is now general consensus that hypertonic saline should be used in patients with hyponatremia associated with moderate or severe symptoms to prevent neurological complications. However, much less agreement exists among experts regarding other aspects of its use. Should hypertonic saline be administered as a bolus injection or continuous infusion? What is the appropriate dose? Is a central venous line necessary? Should desmopressin be used concomitantly and for how long? This article considers these important questions, briefly explores the historical origins of hypertonic saline use for hyponatremia, and reviews recent evidence behind its indications, dosing, administration modality and route, combined use with desmopressin to prevent rapid correction of serum sodium, and other considerations such as the need and degree for fluid restriction. The authors conclude by offering some practical recommendations for the use of hypertonic saline.

Topics: Deamino Arginine Vasopressin; Goals; Humans; Hyponatremia; Saline Solution, Hypertonic

Chronic hyponatremia has been reported to be associated with low solute intake and low creatinine excretion (reflecting likely sarcopenia). We wanted to study the effect, on the long term, of correction of hyponatremia on solute and creatinine excretion in chronic SIADH.. We made a retrospective review of clinical and biochemical data of patients with euvolemic hyponatremia. We analyzed 24-h urine solute and creatinine excretion in volunteers with hyponatremia induced by dDAVP over 4 days, in 12 patients with chronic SIADH (>1 month) before and after a few days of SNa correction and in 12 patients (6 women and 6 men) before and after 3 months of SNa correction by a vaptan or urea.. We confirm a low urine creatinine and solute excretion only in patients with chronic hyponatremia (>1 month). Correction of SNa (from 127 ± 2.3 mEq/L to 139 ± 2.8 mEq/L) for >3 months, in the 12 patients (mean age 58 ± 18), was associated with an increase in 24-h creatinine excretion (from 986 ± 239 to 1,238 ± 220 mg; p < 0.02) and in patients treated with a vaptan (n = 5) solute excretion increased from 656 ± 207 mmol/24 h to 960 ± 193 mmol/24 h (p < 0.02). Sodium excretion increased also in the 12 patients (from 100 ± 53 mEq/24 h to 169 ± 38 mEq/24 h; p < 0.01).. Chronic hyponatremia (>1 month) is associated with a decrease in solute output (or intake) and in creatinine excretion. In many patients, these abnormalities are reversible in the long term.

Topics: Adult; Aged; Benzamides; Creatinine; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Male; Middle Aged; Pyrroles; Retrospective Studies

Central diabetes insipidus is a rare neuroendocrine condition. Data on treatment-associated side-effects, psychological comorbidities, and incorrect management are scarce. The aim of this study was to investigate patients' perspectives on their disease.. This study used a cross-sectional, web-based, anonymous survey, developed by endocrinologists and patient representatives, to collect the opinions of patients with central diabetes insipidus on management and complications of their disease, psychological comorbidities, degree of knowledge and awareness of the condition among health-care professionals, and renaming the disease to avoid confusion with diabetes mellitus (diabetes).. Between Aug 23, 2021, and Feb 7, 2022, 1034 patients with central diabetes insipidus participated in the survey. 91 (9%) participants were children and adolescents (37 [41%] girls and 54 [59%] boys; median age 10 years [IQR 6-15]) and 943 (91%) were adults (757 [80%] women and 186 [20%] men]; median age 44 years [34-54]). 488 (47%) participants had isolated posterior pituitary dysfunction and 546 (53%) had combined anterior and posterior pituitary dysfunction. Main aetiologies were idiopathic (315 [30%] of 1034 participants) and tumours and cysts (pre-surgical 217 [21%]; post-surgical 254 [25%]). 260 (26%; 95% CI [0·23-0·29]) of 994 patients on desmopressin therapy had hyponatraemia leading to hospitalisation. Patients who routinely omitted or delayed desmopressin to allow intermittent aquaresis had a significantly lower prevalence of hyponatraemia compared with those not aware of this approach (odds ratio 0·55 [95% CI 0·39-0·77]; p=0·0006). Of patients who had to be hospitalised for any medical reason, 71 (13%; 95% CI 0·10-0·16) of 535 patients did not receive desmopressin while in a fasting state (nil by mouth) without intravenous fluid replacement and reported symptoms of dehydration. 660 (64%; 0·61-0·67) participants reported lower quality of life, and 369 (36%; 0·33-0·39) had psychological changes subjectively associated with their central diabetes insipidus. 823 (80%; 0·77-0·82) participants encountered a situation where central diabetes insipidus was confused with diabetes mellitus (diabetes) by health-care professionals. 884 (85%; 0·83-0·88) participants supported renaming the disease; the most favoured alternative names were vasopressin deficiency and arginine vasopressin deficiency.. This is the largest survey of patients with central diabetes insipidus, reporting a high prevalence of treatment-associated side-effects, mismanagement during hospitalisation, psychological comorbidities, and a clear support for renaming the disease. Our data are the first to indicate the value of routinely omitting or delaying desmopressin.. Swiss National Science Foundation, Swiss Academy of Medical Sciences, and G&J Bangerter-Rhyner-Foundation.

Topics: Adolescent; Adult; Arginine; Child; Cross-Sectional Studies; Deamino Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diabetes Mellitus; Female; Humans; Hyponatremia; Internet; Male; Middle Aged; Morbidity; Quality of Life

Bowel preparation prior to colonoscopic examination is generally considered a safe process. Hyponatremia is a complication that has been reported in literature during bowel preparation. Individuals who develop severe symptomatic hyponatremia are often older and have comorbidities such as hypothyroidism, chronic kidney disease, or adrenal insufficiency. However, other mechanisms and circumstances can also lead to this potentially fatal complication.. We present a unique case of a patient who developed seizure prior to colonoscopy due to acute hyponatremia without any well-known risk factors. With the subsequent diagnosis of water intoxication, the use of desmopressin was believed to have contributed to this serious complication.. In addition to the use of certain well-documented medications and the presence of comorbidities that can lead to hyponatremia, clinicians should also be aware of the use of desmopressin as an important risk factor. Thorough history taking can guide individualized bowel preparation regimens to minimize the risk of undesired complications.

Topics: Colonoscopy; Deamino Arginine Vasopressin; Humans; Hyponatremia; Seizures; Water Intoxication

Topics: Deamino Arginine Vasopressin; Demyelinating Diseases; Humans; Hyponatremia; Magnetic Resonance Imaging; Sodium; Syndrome

Patients with a history of alcohol use disorder are at an increased risk of hematoma expansion following intracranial hemorrhage (ICH) due to the effects of alcohol on platelet aggregation. Desmopressin (DDAVP) improves platelet aggregation and may decrease hematoma expansion in patients with ICH. However, DDAVP may also increase the risk of hyponatremia and thrombotic events. Evidence is limited regarding the safety and efficacy of DDAVP in alcohol use (AU)-associated ICH.. This was a retrospective chart review of adult patients with radiographic evidence of ICH and a confirmed or suspected history of alcohol use upon admission. Patients were categorized into groups based on DDAVP administration. Safety outcomes included hyponatremia (serum sodium <135 mEq/L or decrease in serum sodium of ≥ 5 mEq/L for patients with baseline sodium <135 mEq/L) within 24 hours of ICH and thrombotic events within 7 days of ICH. The primary efficacy outcome was the incidence of hematoma expansion, defined as any expansion of the hemorrhage noted on repeat imaging within 32 hours.. In total, 52 patients were included in the safety analysis (27 DDAVP and 25 non-DDAVP). Although hyponatremia was numerically higher in the DDAVP group, there was no significant difference between groups (19.2% vs 4.2%,. The administration of DDAVP was not associated with adverse safety events, but did not significantly reduce the incidence of hematoma expansion in patients with AU-associated ICH.

Topics: Adult; Cerebral Hemorrhage; Deamino Arginine Vasopressin; Hematoma; Humans; Hyponatremia; Intracranial Hemorrhages; Retrospective Studies; Sodium

Initiation of desmopressin acetate (DDAVP) for untreated diabetes insipidus (DI) in Wolfram syndrome (WS) causes abrupt volume expansion resulting in particularly high secretion of Atrial Natriuretic Peptide (ANP) and/or Brain Natriuretic Peptide (BNP), which in turn blocks all stimulators of zona glomerulosa steroidogenesis, resulting in secondary mineralocorticoid deficiency and acute hyponatremia, causing renal salt wasting (RSW). Two sisters, a 19-y-old girl (A) and a 7-y-old girl (B) with WS, presented with severe polyuria-polydipsia due to never treated DI. Both had neurogenic bladder and "B" had severe hydronephrosis secondary to untreated grade III bilateral vesicoureteral reflux. They initiated therapy with oral melt DDAVP which resulted in RSW. ANP was found ×50 and BNP ×2-4 fold elevated. Fludrocortisone 100-200 × 2 μg/d controlled natriuresis and restored electrolytes to normal within 48 h. Fludrocortisone treatment rescues otherwise potentially life-threatening hyponatremia due to RSW and the secondary mineralocorticoid deficiency driven by elevated ANP and/or BNP, caused by sudden volume expansion following DDAVP initiation.

Topics: Atrial Natriuretic Factor; Child; Deamino Arginine Vasopressin; Female; Fludrocortisone; Humans; Hyponatremia; Wolfram Syndrome; Young Adult

Apelin and arginine-vasopressin (AVP) are conversely regulated by osmotic stimuli. We therefore hypothesized that activating the apelin receptor (apelin-R) with LIT01-196, a metabolically stable apelin-17 analog, may be beneficial for treating the Syndrome of Inappropriate Antidiuresis, in which AVP hypersecretion leads to hyponatremia. We show that LIT01-196, which behaves as a potent full agonist for the apelin-R, has an in vivo half-life of 156 minutes in the bloodstream after subcutaneous administration in control rats. In collecting ducts, LIT01-196 decreases dDAVP-induced cAMP production and apical cell surface expression of phosphorylated aquaporin 2 via AVP type 2 receptors, leading to an increase in aqueous diuresis. In a rat experimental model of AVP-induced hyponatremia, LIT01-196 subcutaneously administered blocks the antidiuretic effect of AVP and the AVP-induced increase in urinary osmolality and induces a progressive improvement of hyponatremia. Our data suggest that apelin-R activation constitutes an original approach for hyponatremia treatment.

Topics: Amino Acid Sequence; Animals; Apelin; Apelin Receptors; Arginine Vasopressin; Blood Glucose; Blood Pressure; Cell Line; Colforsin; Cyclic AMP; Deamino Arginine Vasopressin; Disease Models, Animal; Diuresis; Electrolytes; Half-Life; Hyponatremia; Kidney Tubules, Collecting; Male; Mice; Models, Biological; Myocardial Contraction; Peptides; Phosphorylation; Rats, Sprague-Dawley; Tolvaptan

Severe hyponatremia, defined as serum sodium concentration ([sNa]) ≤ 120 mEq/L, requires aggressive treatment to prevent potentially fatal cerebral edema, seizures, and other sequelae, but overcorrection can also result in life-threatening cerebral hemorrhage and demyelination. We compared the safety and efficacy of nasal desmopressin to conventional management for the prevention of [sNa] overcorrection.. This retrospective analysis compared 47 patients treated with desmopressin to 17 patients treated conventionally at a university hospital ICU in Japan between 2013 and 2018 using propensity score-based approaches. The primary outcome was safe [sNa] correction, defined as a ≤ 8 mEq/L difference between baseline and follow-up [sNa] at any time within 24h of diagnosis.. The 24-h safe correction rate was significantly greater in the desmopressin group than the conventional treatment group (68% [32/47] vs. 41% [7/17], P = 0.039), and dose-response analysis indicated a positive association between cumulative 24-h desmopressin dose and safe correction at 24 h (P = 0.003). Few overcorrections precluded reliable assessment at 48 h. Exacerbation of hyponatremia was comparable in the two treatment groups.. Intranasal desmopressin therapy increased the safe correction of severe hyponatremia. Large prospective trials are warranted to confirm this result.

Topics: Cohort Studies; Deamino Arginine Vasopressin; Humans; Hyponatremia; Propensity Score; Prospective Studies; Retrospective Studies

Desmopressin (DDAVP) is often used for hyponatremia management but has been associated with increases in hospital length of stay and duration of hypertonic saline use. The purpose of this study was to evaluate hyponatremia management strategies and their effect on sodium correction in critically ill patients requiring 3% hypertonic saline (3HS).. This retrospective, single-center study included critically ill patients with hyponatremia (serum sodium ≤ 125 mEq/L) receiving 3HS from May 31 2015, to May 31 2019. Patients were divided into those who received 3HS for hyponatremia management (HTS) and those who received proactive or reactive DDAVP in addition to 3HS (D-HTS). Patients in either group could receive rescue DDAVP. The primary outcome was the percentage of patients achieving goal sodium correction of 5-10 mEq/L 24 h after 3HS initiation.. Goal sodium correction was achieved in 52.5% of patients in HTS compared to 65.6% of patients in D-HTS (p = 0.21). Patients in HTS had a shorter duration of 3HS infusion (p = 0.0022) with no difference in ICU length of stay, free water intake, urine output, or serum sodium increases 12 and 24 h after receiving 3HS. Overcorrection during any 24- or 48 h period was not statistically different between groups.. Patients in HTS and D-HTS had similar rates of achieving goal sodium correction at 24 h. A proactive or reactive DDAVP strategy led to an increase in 3HS duration and total amount with no significant difference in rates of overcorrection. Prospective, randomized studies assessing standardized strategies for hyponatremia management and DDAVP administration are warranted.

Topics: Aged; Aged, 80 and over; Antidiuretic Agents; Critical Illness; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Male; Middle Aged; Retrospective Studies; Saline Solution, Hypertonic

Topics: Deamino Arginine Vasopressin; Humans; Hyponatremia; Saline Solution, Hypertonic; Sodium

The most used experimental mouse model of hyponatremia and elevated intracranial pressure (ICP) is intraperitoneal injection of water in combination with antidiuretics. This model of water intoxication (WI) results in extreme pathological changes and death within 1 h. To improve preclinical studies of the pathophysiology of elevated ICP, we characterized diuresis, cardiovascular parameters, blood ionogram and effects of antidiuretics in this model. We subsequently developed a new mouse model with mild hyponatremia and sustained increased ICP. To investigate the classical protocol (severe WI), C57BL/6mice were anesthetized and received an intraperitoneal injection of 20% body weight of MilliQ water with or without 0.4 µg·kg

Topics: Animals; Antidiuretic Agents; Deamino Arginine Vasopressin; Disease Models, Animal; Hyponatremia; Injections, Intraperitoneal; Intracranial Hypertension; Intracranial Pressure; Male; Mice; Mice, Inbred C57BL; Water Intoxication

Topics: Biopsy; Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; Hyponatremia

Topics: Achlorhydria; Adult; Cyclophosphamide; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Female; Hormones; Humans; Hypogonadism; Hyponatremia; Hypophysitis; Lupus Erythematosus, Systemic; Methylprednisolone; Treatment Outcome; Young Adult

COVID-19 has changed the nature of medical consultations, emphasizing virtual patient counseling, with relevance for patients with diabetes insipidus (DI) or hyponatraemia. The main complication of desmopressin treatment in DI is dilutional hyponatraemia. Since plasma sodium monitoring is not always possible in times of COVID-19, we recommend to delay the desmopressin dose once a week until aquaresis occurs allowing excess retained water to be excreted. Patients should measure their body weight daily. Patients with DI admitted to the hospital with COVID-19 have a high risk for mortality due to volume depletion. Specialists must supervise fluid replacement and dosing of desmopressin. Patients after pituitary surgery should drink to thirst and measure their body weight daily to early recognize the development of the postoperative syndrome of inappropriate antidiuresis (SIAD). They should know hyponatraemia symptoms. The prevalence of hyponatraemia in patients with pneumonia due to COVID-19 is not yet known, but seems to be low. In contrast, hypernatraemia may develop in COVID-19 patients in ICU, from different multifactorial reasons, for example, due to insensible water losses from pyrexia, increased respiration rate and use of diuretics. Hypernatraemic dehydration may contribute to the high risk of acute kidney injury in COVID-19. IV fluid replacement should be administered with caution in severe cases of COVID-19 because of the risk of pulmonary oedema.

Topics: Antidiuretic Agents; Brain Injuries; Coronavirus Infections; COVID-19; Deamino Arginine Vasopressin; Dehydration; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Disease Management; Fluid Therapy; Humans; Hypernatremia; Hyponatremia; Hypotonic Solutions; Inappropriate ADH Syndrome; Neurosurgical Procedures; Pandemics; Pneumonia, Viral; Postoperative Complications; Practice Guidelines as Topic; Saline Solution; Shock

There is an increasing and compelling need for early recognition of features of osmotic demyelination syndrome (ODS), and a further attempt at correcting this even where presentation is late.. A 49-year-old male admitted into the emergency department with a complaint of lethargy and severe hyponatremia, with subsequent ODS supervening on initial attempts at correction.. Rapid rise in serum sodium concentration (121 mmol/L in 8 hours from a nadir of 101 mmol/L), concomitant deterioration in patient's conscious level support the diagnosis of ODS.. Concomitant administration of 5% dextrose water with desmopressin with a therapeutic objective of gradual relowering of serum sodium concentration.. Significant improvement in patients' conscious level and motor function with the commencement of sodium relowering therapy. The patient was eventually discharged home.. Regardless of the temporal profile of neurologic sequelae following ODS due to hyponatremia, its worthwhile attempting initial sodium relowering with dextrose 5% and desmopressin and then monitoring of biochemical and neurologic markers.

Topics: Antidiuretic Agents; Brain; Deamino Arginine Vasopressin; Demyelinating Diseases; Drug Therapy, Combination; Glucose; Humans; Hyponatremia; Iatrogenic Disease; Lethargy; Magnetic Resonance Imaging; Male; Middle Aged; Osmolar Concentration; Saline Solution, Hypertonic; Sodium; Sweetening Agents; Tomography, X-Ray Computed; Treatment Outcome

Delayed parkinsonism and dystonia are recognized phenomena in osmotic demyelinating syndrome (ODS). Dopamine receptor agonists and levodopa have been reported to benefit select patients.. We report a patient with ODS with severe pseudobulbar deficits, parkinsonism and dystonia, poorly responsive to levodopa, who experienced a remarkable improvement with pramipexole.. A marked response to pramipexole with lack of response to levodopa suggests a pre-synaptic source for his deficits coupled with injuries to non-nigral compensatory structures.. This case highlights a dramatic response of osmotic demyelination-induced parkinsonism/dystonia to pramipexole. A lack of response to levodopa suggests deficits in the pre-synaptic nigral as well as non-nigral compensatory structures.

Topics: Adult; Antiparkinson Agents; Deamino Arginine Vasopressin; Demyelinating Diseases; Dystonia; Epistaxis; Hemostatics; Humans; Hyponatremia; Levodopa; Locked-In Syndrome; Male; Myelinolysis, Central Pontine; Osmotic Pressure; Parkinsonian Disorders; Postoperative Hemorrhage; Pramipexole; Pseudobulbar Palsy; Rhinoplasty; Tetrahydronaphthalenes; Thiophenes; Treatment Failure; Treatment Outcome; von Willebrand Disease, Type 1

Desmopressin was approved by the Food and Drug Administration (FDA) in 1978 for use in diabetes insipidus and bleeding disorders, but it is also prescribed off-label for patients with nocturia. Quantifying the potential risks facing adult patients taking desmopressin has taken on added importance because a new intranasal formulation of desmopressin was approved by the FDA in 2017. Like the old formulation, the main active ingredient is desmopressin acetate, but the new formulation also contains an excipient designed to enhance absorption. Our objective was to quantify the rate of hyponatremia in routine clinical care for patients prescribed the older formulation of desmopressin.. We conducted a population-based new-user cohort study from 1 February 2006 to 1 February 2017 using a nationwide commercial health plan database. Patients newly prescribed the older formulation of desmopressin were propensity-score (PS)-matched to patients newly prescribed oxybutynin. As a sensitivity analysis, tamsulosin was used as the comparator rather than oxybutynin. The primary outcome was a primary position diagnosis of hyponatremia. Proportional hazard models after 1:1 PS matching were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). We identified 3,137 adults who were newly prescribed desmopressin and matched them to 3,137 adults who were newly prescribed oxybutynin. Mean age was 70, 55% were male, 13% filled a prescription for a diuretic during the baseline time period, and the mean baseline sodium prior to receiving either study drug was 140 mmol/L (normal: 135-145). The rate of hyponatremia was 146 per 1,000 person-years for adults prescribed desmopressin compared to 11 per 1,000 person-years for adults prescribed oxybutynin, corresponding to a 13-fold higher rate (HR 13.19; 95% CI 6.69, 26.01; p < 0.01). When follow-up was truncated at 30 days, a similar increased rate was observed (HR 19.41; 95% CI 7.11, 52.99; p < 0.01). A higher rate of hyponatremia was also observed with desmopressin when tamsulosin was the comparator (HR 12.10; 95% CI 6.54, 22.37; p < 0.01). Important limitations of our study include unmeasured confounding (for example, over-the-counter medication use, dietary intake), missing data (i.e., only 20% of patients had a baseline serum sodium), and a lack of data on the newer formulation of desmopressin.. Use of an older formulation of desmopressin was associated with a marked increased rate of subsequent hyponatremia compared to use of other medications indicated for lower urinary tract symptoms. Such risks should be clearly communicated to patients prescribed this formulation of desmopressin.

Topics: Administration, Intranasal; Aged; Aged, 80 and over; Cohort Studies; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Hyponatremia; Male; Mandelic Acids; Middle Aged; Nocturia; Propensity Score; Proportional Hazards Models; Risk Factors; Tamsulosin; Treatment Outcome

Topics: Accidents, Traffic; Arm Injuries; Deamino Arginine Vasopressin; Electroencephalography; Hematoma; Hemorrhage; Hemostatics; Humans; Hyponatremia; Male; Middle Aged; Multiple Trauma; Nasal Bone; Saline Solution, Hypertonic; Seizures; Skull Fractures; von Willebrand Diseases

Topics: Biopsy; Deamino Arginine Vasopressin; Hemorrhage; Humans; Hyponatremia; Kidney; Uremia

Desmopressin is used to reduce bleeding complications for kidney biopsies with azotemia but little is known about desmopressin-induced hyponatremia in these individuals. We aimed to evaluate the impact of desmopressin prophylaxis on severe hyponatremia and bleeding after kidney biopsies in individuals with renal impairment.. This is a single-center retrospective cohort study of consecutive adults with serum creatinine ≥ 150 µmol/L and had ultrasound-guided percutaneous native or transplant kidney biopsies between June 2011 and July 2015. Data were retrieved from electronic medical records. Primary outcomes were the use of desmopressin prophylaxis and severe hyponatremia (serum sodium ≤ 125 mmol/L) within 7 days post-biopsy. Secondary outcome was post-biopsy bleeding.. Pre-biopsy desmopressin was associated with severe hyponatremia in individuals with renal impairment; hence, susceptible patients given desmopressin should be closely monitored.

Topics: Biopsy; Cohort Studies; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Hyponatremia; Kidney; Male; Middle Aged; Postoperative Hemorrhage; Retrospective Studies; Treatment Outcome

People with schizophrenia and medical comorbidities are often on multiple medications to manage their symptoms. Herein we present a case of drug-drug interaction (meloxicam and desmopressin), in a patient also on clozapine, that ultimately resulted in hyponatremia and seizure.. The patient provided consent to have his case published. We searched PubMed and after reviewing 321 articles, 11 were chosen for relevance.. Meloxicam enhanced the adverse effect (hyponatremia) of desmopressin and was the likely culprit.. In a patient with higher ADH levels, as in our patient taking desmopressin, the addition of an NSAID could further increase water retention and worsen hyponatremia; indeed, meloxicam was the only new medication added to the patient's regimen, and a drug interaction calculator supports the desmopressin-meloxicam drug-drug interaction as the culprit. We urge clinicians to avoid the use of desmopressin in patients with schizophrenia as this can lead to water intoxication. As meloxicam may worsen desmopressin-induced hyponatremia and could result in seizure, one should avoid using NSAIDs in patients with schizophrenia whom are also prescribed vasopressin/desmopressin. Serum sodium levels should be closely monitored in patients with schizophrenia whose regimen includes desmopressin.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antidiuretic Agents; Deamino Arginine Vasopressin; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Humans; Hyponatremia; Male; Meloxicam; Middle Aged

In the syndrome of inappropriate antidiuretic hormone secretion (SIADH), hyponatremia is limited by onset of vasopressin-escape caused by loss of the water channel aquaporin-2 in the renal collecting duct despite high circulating vasopressin. Here, we use the methods of systems biology in a well-established rat model of SIADH to identify signaling pathways activated at the onset of vasopressin-escape. Using single-tubule RNA-Seq, full transcriptomes were determined in microdissected cortical collecting ducts of vasopressin-treated rats at 1, 2, and 4 days after initiation of oral water loading in comparison to time-control rats without water loading. The time-dependent mRNA abundance changes were mapped to gene sets associated with curated canonical signaling pathways and revealed evidence of perturbation of transforming growth factor β signaling and epithelial-to-mesenchymal transition on Day 1 of water loading simultaneous with the initial fall in Aqp2 gene expression. On Day 2 of water loading, transcriptomic changes mapped to Notch signaling and the transition from G0 into the cell cycle but arrest at the G2/M stage. There was no evidence of cell proliferation or altered principal or intercalated cell numbers. Exposure of vasopressin-treated cultured mpkCCD cells to transforming growth factor β resulted in a virtually complete loss of aquaporin-2. Thus, there is a partial epithelial-to-mesenchymal transition during vasopressin escape with a subsequent shift from quiescence into the cell cycle with eventual arrest and loss of aquaporin-2.

Topics: Animals; Aquaporin 2; Cell Proliferation; Cells, Cultured; Cellular Senescence; Deamino Arginine Vasopressin; Disease Models, Animal; Drinking; Epithelial-Mesenchymal Transition; Gene Expression Profiling; Gene Expression Regulation; Hyponatremia; Inappropriate ADH Syndrome; Kidney Tubules, Collecting; Male; Rats, Sprague-Dawley; Receptors, Notch; RNA, Messenger; Sequence Analysis, RNA; Signal Transduction; Systems Biology; Time Factors; Transcription, Genetic; Transcriptome; Transforming Growth Factor beta

Overcorrection of plasma sodium in severe hyponatremia is associated with osmotic demyelination syndrome. Desmopressin (DDAVP) can prevent overcorrection of plasma sodium in hyponatremia. The objective of this study was to compare outcomes in hyponatremia according to DDAVP usage.. This was a retrospective observational study including all admissions to internal medicine with hyponatremia (plasma sodium concentration <123 mEq/L) from 2004 to 2014 at 2 academic hospitals in Toronto, Canada. The primary outcome was safe sodium correction (≤12 mEq/L in any 24-hour and ≤18 mEq/L in any 48-hour period).. We identified 1450 admissions with severe hyponatremia; DDAVP was administered in 254 (17.5%). Although DDAVP reduced the rate of change of plasma sodium, fewer patients in the DDAVP group achieved safe correction (174 of 251 [69.3%] vs 970 of 1164 [83.3%]); this result was driven largely by overcorrection occurring before DDAVP administration in the rescue group. Among patients receiving DDAVP, most received it according to a reactive strategy, whereby DDAVP was given after a change in plasma sodium within correction limits (174 of 254 [68.5%]). Suspected osmotic demyelination syndrome was identified in 4 of 1450 admissions (0.28%). There was lower mortality in the DDAVP group (3.9% vs 9.4%), although this is likely affected by confounding. Length of stay in hospital was longer in those who received DDAVP according to a proactive strategy.. Although observational, these data support a reactive strategy for using DDAVP in patients at average risk of osmotic demyelination syndrome, as well as a more stringent plasma sodium correction limit of 8 mEq/L in any 24-hour period for high-risk patients. Further studies are urgently needed on DDAVP use in treating hyponatremia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antidiuretic Agents; Deamino Arginine Vasopressin; Drug Administration Schedule; Female; Humans; Hyponatremia; Length of Stay; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Treatment Outcome; Young Adult

Topics: Antidiuretic Agents; Chronic Disease; Deamino Arginine Vasopressin; Humans; Hyponatremia

Glioblastoma is a devastating malignancy with a dismal survival rate. Currently, there are limited prognostic markers of glioblastoma including IDH1, ATRX, MGMT, PTEN, EGFRvIII, and others. Although these biomarkers for tumor prognosis are available, a surgical biopsy must be performed for these analyses, which has morbidity involved. A non-invasive and readily available biomarker is sought after which provides clinicians prognostic information. Sodium is an electrolyte that is easily and quickly obtained through analysis of a patient's serum. Hyponatremia has been shown to have a predictive and negative prognostic indication in multiple cancer types, but the role of glioblastoma patients' serum sodium at the time of diagnosis in predicting glioblastoma patient survival has not been determined. We assessed whether hyponatremia at the time of glioblastoma diagnosis correlates to patient survival and show that in our cohort of 200 glioblastoma patients, sodium, at any level, did not significantly correlate to glioblastoma survival, unlike what is seen in multiple other cancer types. We further demonstrate that inducing hyponatremia in an orthotopic murine model of glioblastoma has no effects on tumor progression and survival.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antidiuretic Agents; Brain Neoplasms; Child; Child, Preschool; Deamino Arginine Vasopressin; Disease Models, Animal; Female; Glioblastoma; Humans; Hyponatremia; Male; Middle Aged; Sodium; Young Adult

Exercise-associated hyponatraemia (EAH) always involves a component of overhydration relative to available exchangeable sodium stores. In the majority of cases, this is purely due to excessive consumption of fluids during exercise. In a lesser number of cases, it is apparent that excessive sodium loss through sweat may play a role by decreasing the amount of acutely available exchangeable sodium. Two cases demonstrating the latter, one in an individual with cystic fibrosis (CF) and another in an endurance athlete without CF, demonstrate how elevated dermal sweat losses may contribute to a

Topics: Adult; Aftercare; Anticonvulsants; Antidiuretic Agents; Confusion; Cystic Fibrosis; Deamino Arginine Vasopressin; Diagnosis, Differential; Exercise; Female; Heat Exhaustion; Hospitalization; Humans; Hyponatremia; Iontophoresis; Lorazepam; Male; Nausea; Osmolar Concentration; Seizures; Sodium; Sweat; Treatment Outcome

Patients with end-stage liver disease are often hyponatremic due to multiple physiological processes associated with hepatic failure. For severely hyponatremic patients undergoing liver transplantation, intraoperative management of serum sodium concentration ([Na]s) is challenging. [Na]s tends to increase during transplantation by the administration of fluids with higher sodium concentration than the patient's [Na]s. An overly rapid increase in [Na]s (>1 mEq·L·hour) is difficult to avoid and increases the risk of serious perioperative complications. We report the successful use of intravenous desmopressin to reverse an overly rapid rise in [Na]s during living donor liver transplantation.

Topics: Deamino Arginine Vasopressin; End Stage Liver Disease; Hemostatics; Humans; Hyponatremia; Intraoperative Care; Liver Transplantation; Living Donors; Risk Factors; Sodium

Correction of profound hyponatremia requires careful planning and close monitoring to reduce the risks of neurologic injury. Although there are various suggested treatment strategies in the setting of a medical ward or intensive care unit, reports of intraoperative management to prevent rapid increases in serum sodium are lacking. We present a case of profound hyponatremia of 102 mmol/L in a patient who required emergent operative repair for bowel obstruction. This is the first case to our knowledge that demonstrates a perioperative fluid and desmopressin treatment strategy to prevent overly rapid changes of sodium concentration in a patient with severe hyponatremia.

Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Intestinal Obstruction; Middle Aged

Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Humans; Hyponatremia

Topics: Deamino Arginine Vasopressin; Humans; Hyponatremia

Hyponatraemia is a well-known side effect of desmopressin therapy. Nocturia in elderly patients can be treated with desmopressin, which usually induces mild and reversible hyponatraemia. This case report is about two patients, in which severe hyponatriaemia, at least partly induced by desmopressin, was observed. The patients were affected by nausea, vomiting and confusion. These symptoms are caused by brain swelling, which can result in coma and death. The case reports illustrate the importance in measuring baseline P-sodium concentration during therapy and examining current medication before prescribing desmopressin.

Topics: Aged, 80 and over; Antidiuretic Agents; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Nocturia; Sodium

The indirect water-deprivation test is the current reference standard for the diagnosis of diabetes insipidus. However, it is technically cumbersome to administer, and the results are often inaccurate. The current study compared the indirect water-deprivation test with direct detection of plasma copeptin, a precursor-derived surrogate of arginine vasopressin.. From 2013 to 2017, we recruited 156 patients with hypotonic polyuria at 11 medical centers to undergo both water-deprivation and hypertonic saline infusion tests. In the latter test, plasma copeptin was measured when the plasma sodium level had increased to at least 150 mmol per liter after infusion of hypertonic saline. The primary outcome was the overall diagnostic accuracy of each test as compared with the final reference diagnosis, which was determined on the basis of medical history, test results, and treatment response, with copeptin levels masked.. A total of 144 patients underwent both tests. The final diagnosis was primary polydipsia in 82 patients (57%), central diabetes insipidus in 59 (41%), and nephrogenic diabetes insipidus in 3 (2%). Overall, among the 141 patients included in the analysis, the indirect water-deprivation test determined the correct diagnosis in 108 patients (diagnostic accuracy, 76.6%; 95% confidence interval [CI], 68.9 to 83.2), and the hypertonic saline infusion test (with a copeptin cutoff level of >4.9 pmol per liter) determined the correct diagnosis in 136 patients (96.5%; 95% CI, 92.1 to 98.6; P<0.001). The indirect water-deprivation test correctly distinguished primary polydipsia from partial central diabetes insipidus in 77 of 105 patients (73.3%; 95% CI, 63.9 to 81.2), and the hypertonic saline infusion test distinguished between the two conditions in 99 of 104 patients (95.2%; 95% CI, 89.4 to 98.1; adjusted P<0.001). One serious adverse event (desmopressin-induced hyponatremia that resulted in hospitalization) occurred during the water-deprivation test.. The direct measurement of hypertonic saline-stimulated plasma copeptin had greater diagnostic accuracy than the water-deprivation test in patients with hypotonic polyuria. (Funded by the Swiss National Foundation and others; ClinicalTrials.gov number, NCT01940614 .).

Topics: Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Female; Glycopeptides; Humans; Hyponatremia; Male; Middle Aged; Osmolar Concentration; Polydipsia; Polyuria; ROC Curve; Saline Solution, Hypertonic; Sensitivity and Specificity; Urine; Water Deprivation

A 79-year-old woman without any cerebral hernia symptoms was hospitalized with hyponatremia. After syndrome of inappropriate antidiuretic hormone induced by drugs was diagnosed and water restriction implemented, the patient became comatose during overcorrection caused by the generation of a large volume of electrolyte-free urine. Once the serum sodium concentration was immediately relowered by the administration of desmopressin and 5% glucose solution, the patient's level of consciousness improved dramatically without osmotic demyelination syndrome (ODS) developing. This outcome suggests that, similar to the findings in rat models, relowering the serum sodium concentration as early as possible to counter a disturbance of consciousness during the overcorrection of hyponatremia prevents ODS.

Topics: Aged; Animals; Antidiuretic Agents; Consciousness; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Rats; Sodium; Treatment Outcome

Topics: Administration, Inhalation; Adult; Advisory Committees; Child; Deamino Arginine Vasopressin; Drug Approval; Humans; Hyponatremia; Nocturia; Product Surveillance, Postmarketing; United States; United States Food and Drug Administration

We describe three cases of severe hyponatraemia in the setting of primary polydipsia that were managed in our centre in 2016. Despite receiving different solute loads, large volume diuresis and rapid correction of serum sodium occurred in all cases. Given the potentially catastrophic consequence of osmotic demyelination, we highlight the judicious use of desmopressin and hypotonic fluid infusion to mitigate sodium overcorrection in this setting.

Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Middle Aged; Polydipsia, Psychogenic; Sodium; Young Adult

Topics: Administration, Intranasal; Contusions; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Middle Aged; Seizures; Tongue

A reset osmostat as a cause of hyponatremia can be found in a variety of clinical settings, including pulmonary and neurologic diseases, as well as in physiologic circumstances such as pregnancy. This teaching case describes a 72-year-old white man with a long-standing history of self-medicating with desmopressin acetate (DDAVP) who presented with profound hyponatremia. On discontinuation of DDAVP treatment, he was found to have a reset osmostat. The mild hyponatremia persisted on follow-up. We theorize that the reset osmostat may have developed secondary to long-standing DDAVP use.

Topics: Aged; Antidiuretic Agents; Atrial Fibrillation; Deamino Arginine Vasopressin; Humans; Hyponatremia; Hypothalamus; Male; Osmolar Concentration; Polyuria; Self Medication; Urinalysis

Topics: Aged; Antidiuretic Agents; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Infusions, Intravenous; Sodium

Despite the availability of subcutaneous desmopressin (1-deamino-8-d-arginine vasopressin, SC-DDAVP) as a haemostatic agent for children with mild bleeding disorders, few publications specifically address the safety or efficacy of this mode of administration.. Our aim was to assess whether a defined fluid restriction protocol was effective in preventing hyponatremia in children receiving perioperative SC-DDAVP, and to document adequate biological and clinical response in this setting.. We retrospectively analysed a cohort of children with mild bleeding disorders prescribed SC-DDAVP over a 5-year period following institution of a 'two-thirds maintenance' fluid restriction protocol.. Sixty-nine patients received SC-DDAVP following this protocol, including 15 with mild haemophilia A, 49 with von Willebrand disease (VWD) and five with platelet storage pool disorder. In patients who underwent formal preoperative assessment a complete or partial response was observed in 28/29 with type 1 VWD and 14/15 with mild haemophilia A. Perioperative SC-DDAVP provided excellent haemostasis in all patients, with no requirement for factor concentrate or blood products. Mild asymptomatic hyponatremia was detected in seven children who received multiple doses of DDAVP (lowest sodium 129 mmol L(-1) ); however, adherence to the prescribed fluid restriction protocol was questionable in six of these cases. Symptomatic hyponatremia was not observed.. Subcutaneous desmopressin was well-tolerated, with no serious side-effects observed, and good biological responses in preoperative trials. A two-thirds maintenance fluid regimen was effective at preventing symptomatic hyponatremia in our cohort, and is now the standard protocol for fluid restriction post-DDAVP administration in our centre.

Topics: Adolescent; Blood Coagulation Disorders, Inherited; Child; Child, Preschool; Deamino Arginine Vasopressin; Hemophilia A; Hemostatics; Humans; Hyponatremia; Injections, Subcutaneous; Platelet Storage Pool Deficiency; Retrospective Studies; Severity of Illness Index; von Willebrand Diseases

Central diabetes insipidus (CDI), which is characterized by polyuria and polydipsia, is caused by a deficiency of the antidiuretic hormone arginine vasopressin (AVP). While CDI is treated with desmopressin, an analogue of AVP, the intranasal formulation is inconvenient and CDI patients reportedly prefer the oral formulation to the intranasal one. In Japan, intranasal desmopressin had been the only formulation for the treatment of CDI until 2012, when the desmopressin orally disintegrating tablet (ODT) was approved for treatment. In this study we analyzed 26 patients with CDI in whom intranasal desmopressin was switched to desmopressin ODT. The mean daily dose of intranasal desmopressin was 10 ± 8 μg/day, and that of desmopressin ODT was 142 ± 59 μg/day. The mean serum sodium levels were 140 ± 5 mmol/L and 140 ± 3 mmol/L with intranasal desmopressin and desmopressin ODT, respectively, and there were no significant differences between these values. The frequency of hyponatremia (<135 mmol/L) with intranasal desmopressin was 11.7% and that with desmopressin ODT was 7.6%, while the frequency of hyponatremia (<130 mmol/L) with intranasal desmopressin was 4.2% and that with desmopressin ODT was 1.3%. Statistical analyses revealed that incidence of hyponatremia was significantly decreased after the switch to desmopressin ODT. Thus, it is suggested that water balance is better controlled with desmopressin ODT than with intranasal desmopressin in patients with CDI.

Topics: Administration, Intranasal; Administration, Oral; Adolescent; Adult; Aged; Antidiuretic Agents; Child; Child, Preschool; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Drug Approval; Drug Monitoring; Electronic Health Records; Female; Hospitals, University; Humans; Hyponatremia; Incidence; Japan; Male; Middle Aged; Risk; Young Adult

Patients with cranial diabetes insipidus (CDI) are at risk of developing both hypernatraemia and hyponatraemia, due to the condition itself or secondary to treatment with vasopressin-analogues or during administration of i.v. fluids. We aimed to assess the frequency and impact of dysnatraemias in the inpatient (INPT) and outpatient (OPT) setting in desmopressin-treated CDI, comparing those with normal thirst with those with abnormal thirst.. The study included 192 patients with cranial diabetes, who were identified from the Beaumont Pituitary Database, a tertiary referral centre. Retrospective case note audit was performed and the clinical and biochemical information of 147 patients with CDI were available for analysis.. A total of 4142 plasma sodium measurements for 137 patients with normal thirst, and 385 plasma sodium measurements for ten patients with abnormal thirst were analysed. In those with normal thirst, the most common OPT abnormality was mild hyponatraemia (pNa(+) 131-134  mmol/l) in 27%, while 14.6% had more significant hyponatraemia (pNa(+) ≤130  mmol/l). Of those patients with normal thirst, 5.8% were admitted due to complications directly related to hyponatraemia. Compared with patients with normal thirst, those with abnormal thirst were more likely to develop significant OPT hypernatraemia (20% vs 1.4%, P=0.02) and significant INPT hyponatraemia (50% vs 11.1%, P 0.02).. OPT management of CDI is complicated by a significant incidence of hyponatraemia. In contrast, OPT hypernatraemia is almost exclusively a complication seen in adipsic CDI, who also had more frequent INPT hyponatraemia. CDI associated with thirst disorder requires increased physician attention and patient awareness of potential complications.

Topics: Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hypernatremia; Hyponatremia; Male; Middle Aged; Retrospective Studies; Sodium; Young Adult

Dysnatremias are common and prognostically serious in neurocritical care. We studied whether a standardized sodium protocol would improve our neurocritical care of dysnatremias.. A 5-year prospective study of a standardized sodium protocol for 1,560 patients admitted with various brain diseases in an adult neurologic-neurosurgical intensive care unit (NNICU) was compared with a 5-year retrospective analysis of 1,440 patients without the sodium protocol. Hyponatremia was defined as serum sodium (SNa(+)) < 135 mmol/L and hypernatremia SNa(+ )> 150 mmol/L. The sodium protocol involved measuring SNa(+), serum, and urine osmolality, measured and calculated renal function parameters, fluid intake 40 mL/kg weight/day without hypotonic saline, thiazide, and desmopressin acetate in all normonatremic NNICU patients.. In the protocol study, hyponatremia occurred slightly less often (15.7 versus 16.3% of patients; p = 0.684), hypernatremia was significantly higher (respectively 8.5% versus 5.2% of patients; p < 0.001), and no differences were noted in hypo/hypernatremia (p = 0.483). There were no differences in the incidence of hypo-osmolal hyponatremia (respectively 3.5% versus 3.5% of patients; p = 0.987), cerebral salt wasting (CSW; respectively 1.7% versus 1.7% of patients; p = 0.883), syndrome of inappropriate secretion of antidiuretic hormone (SIADH; respectively 0.1% versus 0.3% of patients; p = 0.152), central diabetes insipidus (CDI; respectively 1.0% versus 0.6% of patients; p = 0.149). In hyponatremia there were no differences in the Glasgow Coma Scale (GCS) score upon onset of hyponatremia (p = 0.294), NNICU mortality (respectively 1.0% versus 0.4% patients; p = 0.074), and bad outcome upon discharge from NNICU (respectively 5.1% versus 6.5% of patients; p = 0.101), but in hypernatremia GCS score upon onset (p < 0.001), mortality (respectively 2.8% versus 1.0%; p < 0.001), and bad outcome from NNICU (respectively 6.7% versus 2.7% patients; p < 0.001) were significantly higher. Multivariate logistic regression analysis showed that hypernatremia, compared with hyponatremia, was a significant predictor of mortality during NNICU stay (respectively odds ratio [OR]: 1.14; p = 0.003 versus OR; 5.3; p = 0.002).. The standard sodium protocol lowered the frequency of SIADH, which was encountered in only one patient over 5 years. However, it did not significantly reduce the incidence and improve the outcome of hyponatremia. Hypernatremia occurred more often and had a higher mortality and worse outcome than hyponatremia, but these patients were neurologically worse upon its onset. The prospective study confirmed that CSW, SIADH, and CDI were not common in our neurocritical care.

Topics: Aged; Critical Care; Deamino Arginine Vasopressin; Diuretics; Female; Humans; Hypernatremia; Hyponatremia; Hypotonic Solutions; Iatrogenic Disease; Incidence; Male; Middle Aged; Nervous System Diseases; Osmolar Concentration; Prospective Studies; Renal Agents; Retrospective Studies; Sodium; Thiazides; Treatment Outcome

Topics: Deamino Arginine Vasopressin; Demyelinating Diseases; Diabetes Insipidus, Neurogenic; Female; Humans; Hyponatremia; Saline Solution, Hypertonic; Syndrome; Young Adult

Desmopressin is used for treating nocturnal polyuria, but hyponatremia is an associated concern in the elderly due to impaired urinary dilution. This study was undertaken to characterize hyponatremia occurring in adults using desmopressin for nocturnal polyuria.. Data from 172 patients who were prescribed desmopressin for nocturnal polyuria at a urology clinic from September 2010 through February 2013 were retrospectively analyzed. Demographic and laboratory parameters were investigated to examine the risk factors for desmopressin-associated hyponatremia.. The average follow-up serum sodium measured 21 ± 22 days after using desmopressin was 138 ± 5 mmol/l. Hyponatremia (<135 mmol/l) was found in 24 patients (14%), and it was severe in 7 (<126 mmol/l). In the hyponatremic patients, serum sodium decreased by 11 ± 6 mmol/l. Patients with hyponatremia were older than those with normonatremia (78 ± 7 vs. 68 ± 9 years, p < 0.0001). The presence of either hyponatremia-predisposing comorbidities or concurrent medications was associated with hyponatremia. Patients with hyponatremia had lower basal hemoglobin (11 ± 2 vs. 13 ± 2 g/dl, p < 0.001) and serum sodium (139 ± 2 vs. 140 ± 2 mmol/l, p < 0.05) than those with normonatremia. Multivariate logistic regression after adjustment for basal serum sodium showed that advanced age (OR 1.15; 95% CI 1.03-1.27) and lower hemoglobin level (OR 0.64; 95% CI 0.43-0.94) were independently associated with hyponatremia.. Hyponatremia is not infrequently associated with desmopressin use. Those with advanced age (≥65 years) and lower hemoglobin are at risk of desmopressin-associated hyponatremia and need to be carefully monitored.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antidiuretic Agents; Comorbidity; Deamino Arginine Vasopressin; Female; Hemoglobins; Humans; Hyponatremia; Logistic Models; Male; Middle Aged; Nocturia; Polyuria; Retrospective Studies; Risk Factors; Sodium

Excessive correction of chronic and profound hyponatremia may result in central pontine myelinolysis and cause permanent brain damage. In the case of foreseeable or established hyponatremia overcorrection, slowing down the correction rate of sodium plasma levels (PNa) or reinducing mild hyponatremia may prevent this neurologic complication.. This retrospective and observational study was performed with 20 consecutive patients admitted to two intensive care units for severe hyponatremia, defined by PNa <120 mmol/L and/or neurologic complications ascribable to hyponatremia and subsequently treated by desmopressin acetate (DDAVP) during correction of hyponatremia when the rate of correction was overtly or predictably excessive. The primary endpoint was the effectiveness of DDAVP on PNa control.. DDAVP dramatically decreased the rate of PNa correction (median 0.81 mmol/L per hour [interquartile range, 0.46, 1.48] versus -0.02 mmol/L per hour [-0.16, 0.22] before and after DDAVP, respectively; P<0.001) along with a concurrent decrease in urine output (650 ml/h [214, 1200] versus 93.5 ml/h [43, 143]; P=0.003), and a rise in urine osmolarity (86 mmol/L [66, 180] versus 209 mmol/L [149, 318]; P=0.002). The maximal magnitude of PNa variations was also markedly reduced after DDAVP administration (11.5 mmol/L [8.25, 14.5] versus 5 mmol/L [4, 6.75]; P<0.001). No patient developed seizures after DDAVP or after subsequent relowering of PNa that occurred in 11 patients.. Desmopressin acetate is effective in curbing the rise of PNa in patients admitted in the intensive care unit for severe hyponatremia, when the initial rate of correction is excessive.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Intensive Care Units; Male; Middle Aged; Paris; Retrospective Studies; Severity of Illness Index; Sodium; Time Factors; Treatment Outcome

Desmopressin is used widely to treat nocturnal polyuria (NP), but there is concern of hyponatremia especially in elderly patients. This study aimed to evaluate the safety and efficacy of long-term desmopressin treatment in elderly patients with NP.. Patients who were ≥65 years old with NP were analyzed. All patients were started on 0.1 mg desmopressin, and the dose was escalated to 0.2 mg depending on patient symptoms. All patients were educated the mechanism of desmopressin. The voiding diary and serum sodium levels were evaluated at baseline, 3-7 days after starting treatment and every 3-6 months. Safety was evaluated by hyponatremia, hyponatremic symptoms and other adverse drug events. The mean changes in number of nocturia and nocturnal urine volume (NUV) were evaluated for efficacy.. A total of 68 patients were included. The mean age was 72.6 (66-85) years. The mean night-time frequency was 3.0 ± 1.8 day, and the mean serum sodium level was 141.2 ± 2.1 mEq/L at baseline. The mean follow-up period was 27.9 months. The mean decrease in serum sodium level was 1.3 ± 3.4 mEq/L at the last follow-up (p = 0.003). Hyponatremia incidence was 4.4 %, and all patients recovered by stopping medication. Severe adverse events were not observed. The mean night-time frequency had decreased by 2.1, and the NUV had decreased by 374.2 ± 261.3 mL at the last follow-up (p < 0.001).. Desmopressin at doses below 0.2 mg is safe and effective in elderly patients with NP if patients are well informed and are closely followed up.

Topics: Aged; Aged, 80 and over; Antidiuretic Agents; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Humans; Hyponatremia; Male; Nocturia; Sodium; Time Factors

Overly rapid correction of chronic hyponatremia can cause osmotic demyelination syndrome (ODS). Minocycline protects ODS associated with overly rapid correction of chronic hyponatremia with hypertonic saline infusion in rats. In clinical practice, inadvertent rapid correction frequently occurs due to water diuresis, when vasopressin action suddenly ceases. In addition, vasopressin receptor antagonists have been applied to treat hyponatremia. Here the susceptibility to and pathology of ODS were evaluated using rat models developed to represent rapid correction of chronic hyponatremia in the clinical setting. The protective effect of minocycline against ODS was assessed. Chronic hyponatremia was rapidly corrected by 1 (T1) or 10 mg/kg (T10) of tolvaptan, removal of desmopressin infusion pumps (RP), or administration of hypertonic saline. The severity of neurological impairment in the T1 group was significantly milder than in other groups and brain hemorrhage was found only in the T10 and desmopressin infusion removal groups. Minocycline inhibited demyelination in the T1 group. Further, immunohistochemistry showed loss of aquaporin-4 (AQP4) in astrocytes before demyelination developed. Interestingly, serum AQP4 levels were associated with neurological impairments. Thus, minocycline can prevent ODS caused by overly rapid correction of hyponatremia due to water diuresis associated with vasopressin action suppression. Increased serum AQP4 levels may be a predictive marker for ODS.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Aquaporin 4; Astrocytes; Behavior, Animal; Benzazepines; Biomarkers; Brain; Chemokines; Cytokines; Cytoprotection; Deamino Arginine Vasopressin; Demyelinating Diseases; Disease Models, Animal; Diuresis; Hyponatremia; Intracranial Hemorrhages; Male; Matrix Metalloproteinases; Minocycline; Neuroprotective Agents; Osmosis; Rats, Sprague-Dawley; Saline Solution, Hypertonic; Sodium; Therapeutics; Time Factors; Tolvaptan; Water-Electrolyte Balance

Topics: Aged; Deamino Arginine Vasopressin; Diuresis; Dose-Response Relationship, Drug; Drinking; Elective Surgical Procedures; Female; Health Personnel; Humans; Hyperparathyroidism, Primary; Hyponatremia; Parathyroidectomy; Postoperative Complications; Seizures; von Willebrand Diseases

Desmopressin (DDAVP) 1-deamino-8-D-arginine vasopressin is used in patients with bleeding disorders, including mild factor VIII deficiency, types 1 and 2 von Willebrand disease, and platelet function defects, undergoing surgeries to help control bleeding. We conducted a retrospective chart review of bleeding disorder patients undergoing inpatient surgery at Toledo Children's Hospital, OH, from 2005 to 2009. Our study population included 107 patients aged 2 to 19 years with platelet function defects and von Willebrand disease. Our study aimed to evaluate the extent of hyponatremia caused by DDAVP and to propose a safe and effective treatment regimen for these patients. The mean change in sodium level before and after DDAVP was statistically significant within each age group. Thirteen patients had second dose of DDAVP withheld, and 11 patients had postoperative sodium levels ≤ 130 mEq/L. There were 2 patients with significant complications: a 6-year-old with postoperative bleeding and a 2-year-old with post-DDAVP tonic-clonic seizures. We conclude that DDAVP causes significant hyponatremia, despite appropriate fluid restrictions. On the basis of our analysis, we recommend monitoring sodium levels before each dose of DDAVP and fluid restriction. These patients should be observed in the hospital setting after DDAVP administration for complications such as seizures and postoperative bleeding.

Topics: Adolescent; Blood Coagulation Disorders; Blood Loss, Surgical; Blood Platelet Disorders; Child; Child, Preschool; Deamino Arginine Vasopressin; Hemophilia A; Hemostatics; Humans; Hyponatremia; Intraoperative Period; Postoperative Complications; Postoperative Period; Retrospective Studies; Sodium; von Willebrand Diseases; Water-Electrolyte Imbalance; Young Adult

Topics: Adult; Antidiuretic Agents; Brain Edema; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Humans; Hyponatremia; Magnetic Resonance Imaging; Male; Myelinolysis, Central Pontine; Syndrome

Desmopressin (DDAVP) is typically prescribed for central diabetes insipidus, von Willebrands disease and for enuresis. DDAVP-associated hyponatremia is a known complication of DDAVP therapy. The currently recommended treatment for this condition calls for discontinuing DDAVP as part of the initial therapy. This recommendation could lead to a water diuresis and potentially over-correction of the serum sodium.. The 15 patients in this case series developed symptomatic DDAVP-associated hyponatremia and were admitted to acute care hospitals. Thirty-eight percent presented with symptomatic hyponatremia and 62% developed symptomatic hyponatremia due to concomitant DDAVP and hypotonic intravenous fluid administration during a hospital stay. Group 1 patients (n = 13) were treated by withholding DDAVP and providing intravenous saline. Group 2 patients (n = 2) were treated by continuing DDAVP and providing DDAVP and intravenous hypertonic saline.. Among Group 1 patients, in whom DDAVP was withheld as initial management of DDAVP-associated hyponatremia (n = 13), the mean change in serum sodium in the first 2 days of treatment was 37.1 ± 8.1 mEq/L. The ultimate outcome in this group was death in 23%, severe brain damage in 69% and moderate brain damage in 8%. In Group 2 patients, in whom DDAVP was continued (n = 2) as part of the initial management strategy, the mean change in serum sodium was 11.0 ± 0 mEq/L in the first 2 days. The ultimate outcome was survival without neurological sequelae in both cases.. Discontinuing DDAVP in a patient with symptomatic DDAVP-associated hyponatremia can lead to rapid correction of the serum sodium and resultant severe neurological injury. In contrast, continuing the medication while correcting DDAVP-associated hyponatremia may lead to better outcomes by avoiding over-correction of the serum sodium. Thus, an alternative approach that we propose is to continue DDAVP as part of the initial management of this disorder.

Topics: Adolescent; Adult; Aged; Antidiuretic Agents; Brain; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Humans; Hyponatremia; Male; Middle Aged; Myelinolysis, Central Pontine; Risk Factors; Saline Solution, Hypertonic; Young Adult

Desmopressin is a synthetic replacement for vasopressin, which is used to reduce perioperative blood loss. However, seizure attacks were observed in patients after administration of desmopressin. Here, we reported two cases of adult Chinese patients experienced generalized tonic-clonic seizures associated with severe hyponatremia caused by intravenously administered desmopressin after surgery. The patients' neurological conditions returned to baseline quickly and completely following discontinuation of desmopressin, control of the seizures, and fluid intake restriction. These cases illustrate the importance of periodic monitoring of electrolyte concentrations and fluid intake during use of desmopressin.

Topics: Administration, Intravenous; Adult; Deamino Arginine Vasopressin; Epilepsy, Tonic-Clonic; Female; Hemostatics; Humans; Hyponatremia; Male; Middle Aged

Binding of vasopressin to its type 2 receptor in renal collecting ducts induces cAMP signaling, transcription and translocation of aquaporin (AQP)2 water channels to the plasma membrane, and water reabsorption from the prourine. Demeclocycline is currently used to treat hyponatremia in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Demeclocycline's mechanism of action, which is poorly understood, is studied here. In mouse cortical collecting duct (mpkCCD) cells, which exhibit deamino-8-D-arginine vasopressin (dDAVP)-dependent expression of endogenous AQP2, demeclocycline decreased AQP2 abundance and gene transcription but not its protein stability. Demeclocycline did not affect vasopressin type 2 receptor localization but decreased dDAVP-induced cAMP generation and the abundance of adenylate cyclase 3 and 5/6. The addition of exogenous cAMP partially corrected the demeclocycline effect. As in patients, demeclocycline increased urine volume, decreased urine osmolality, and reverted hyponatremia in an SIADH rat model. AQP2 and adenylate cyclase 5/6 abundances were reduced in the inner medulla but increased in the cortex and outer medulla, in the absence of any sign of toxicity. In conclusion, our in vitro and in vivo data indicate that demeclocycline mainly attenuates hyponatremia in SIADH by reducing adenylate cyclase 5/6 expression and, consequently, cAMP generation, AQP2 gene transcription, and AQP2 abundance in the renal inner medulla, coinciding with a reduced vasopressin escape response in other collecting duct segments.

Topics: Adenylyl Cyclases; Animals; Anti-Bacterial Agents; Aquaporin 2; Cells, Cultured; Cyclic AMP; Deamino Arginine Vasopressin; Demeclocycline; Disease Models, Animal; Hyponatremia; In Vitro Techniques; Inappropriate ADH Syndrome; Kidney Medulla; Male; Mice; Minocycline; Rats; Rats, Wistar; Vasopressins

Desmopressin acetate (DDAVP), a medication used in the treatment of bleeding and polyuric disorders, has the potential to cause hyponatremia when free water is not appropriately restricted with its use. This free water retention is reversible when DDAVP is discontinued. We report a case of symptomatic DDAVP-induced hyponatremia in which discontinuation of DDAVP led to a rapid increase of serum sodium. In order to prevent rapid free water excretion, DDAVP and hypertonic saline were used concurrently. With close monitoring, this can be an effective treatment strategy in patients with DDAVP-induced hyponatremia.

Topics: Aged; Aged, 80 and over; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Saline Solution, Hypertonic

Introducing a consensus on pharmacological treatment of male LUTs to be applied to Urology Primary Care. EVIDENCE COMPILATION: The consensus has been created by an expert committee based on the latest recommendations by the European and American Guides for male LUTs treatment. Also, a bibliographic review of the latest advances in the therapeutical approach to these patients has been carried out.. Although the prevalence of both LUTs and overactive bladder is high, and its impact on the quality of life and social cost have been widely described, the number of patients treated is low. On the other hand, current clinical practice doesn't necessarily match the Guides and for this reason false perceptions of the available treatments circulate. For instance, men with storage LUTS are often treated inadequately with α-blockers or 5-α-reductase inhibitors due to underlying obstructive disorders. However, it is known that the incidence of real obstruction tends to be low. Current evidence, though limited, shows that antimuscarinic drugs may be used safely by men with LUTs, and are not associated with an increase in the prevalence of high urinary retention.. We propose an algorithm for the management of male LUTs in which various levels of clinical evaluation are shown for a specific diagnose, as well as for choosing the most appropriate treatment.

Topics: 5-alpha Reductase Inhibitors; Adrenergic alpha-Antagonists; Algorithms; Deamino Arginine Vasopressin; Drug Interactions; Drug Therapy, Combination; Humans; Hyponatremia; Lower Urinary Tract Symptoms; Male; Muscarinic Antagonists; Prostatism; Severity of Illness Index; Sodium Potassium Chloride Symporter Inhibitors; Urinary Retention

Prompt correction of severe hyponatremia is important, but correction also must be limited to avoid iatrogenic osmotic demyelination. Expert opinion recommends that serum sodium level not be increased by more than 10-12 mEq/L in any 24-hour period and/or 18 mEq/L in any 48-hour period. However, inadvertent overcorrection is common, usually caused by the unexpected emergence of a water diuresis.. Quality improvement report.. All 25 patients admitted to a community teaching hospital between October 1, 2008, and September 30, 2011, who were treated for serum sodium level <120 mEq/L with concurrently administered desmopressin and hypertonic saline solution.. Concurrently administered desmopressin (1-2 µg parenterally every 6-8 hours) and hypertonic saline with weight-based doses adjusted to increase the serum sodium concentration by 6 mEq/L, avoiding inadvertent overcorrection of severe hyponatremia.. Rate of correction of hyponatremia, predictability of response to the combination, adverse events related to therapy.. Rate of correction of hyponatremia at 4, 24, and 48 hours; administered dose of 3% saline solution, salt tablets, and potassium; predicted increase in serum sodium level.. Mean changes in serum sodium levels during the first and second 24 hours of therapy were 5.8 ± 2.8 (SD) and 4.5 ± 2.2 mEq/L, respectively, without correction by >12 mEq/L in 24 hours or >18 mEq/L in 48 hours and without a decrease during therapy. There was no significant difference between actual and predicted increases during the first 24 hours. There was no adverse effect associated with therapy.. Without concurrent controls, we cannot be certain that outcomes are improved. Balance studies were not performed.. Combined 3% saline solution and desmopressin appears to be a valid strategy for correcting severe hyponatremia, but studies comparing the regimen with other therapeutic strategies are needed.

Topics: Aged; Aged, 80 and over; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Middle Aged; Retrospective Studies; Saline Solution, Hypertonic

The renal vasopressin V(2) receptor (V(2)R) plays a critical role in physiological and pathophysiological processes associated with arginine vasopressin (AVP)-induced antidiuresis. Because clinical data suggests that females may be more prone to hyponatremia from AVP-mediated antidiuresis, we investigated whether there are sex differences in the expression and function of the renal V(2)R. In normal Sprague-Dawley rat kidneys, V(2)R mRNA and protein expression was 2.6- and 1.7-fold higher, respectively, in females compared with males. To investigate the potential physiological implications of this sex difference, we studied changes in urine osmolality induced by the AVP V(2)R agonist desmopressin. In response to different doses of desmopressin, there was a graded increase in urine osmolality and decrease in urine volume during a 24-h infusion. Females showed greater mean increases in urine osmolality and greater mean decreases in urine volume at 0.5 and 5.0 ng/h infusion rates. We also studied renal escape from antidiuresis produced by water loading in rats infused with desmopressin (5.0 ng/h). After 5 days of water loading, urine osmolality of both female and male rats escaped to the same degree physiologically, but V(2)R mRNA and protein in female kidneys was reduced to a greater degree (-63% and -73%, respectively) than in males (-32% and -48%, respectively). By the end of the 5-day escape period, renal V(2)R mRNA and protein expression were reduced to the same relative levels in males and females, thereby abolishing the sex differences in V(2)R expression seen in the basal state. Our results demonstrate that female rats express significantly more V(2)R mRNA and protein in kidneys than males, and that this results physiologically in a greater sensitivity to V(2)R agonist administration. The potential pathophysiological implications of these results are that females may be more susceptible to the development of dilutional hyponatremia because of a greater sensitivity to endogenously secreted AVP.

Topics: Animals; Antidiuretic Agents; Aquaporin 2; Arginine Vasopressin; Deamino Arginine Vasopressin; Diuresis; Female; Humans; Hyponatremia; Male; Osmolar Concentration; Rats; Receptors, Vasopressin; Sex Factors; Urine

  The incidence, severity, and risk factors for the development of hyponatremia in patients undergoing craniosynostosis surgery are not well known..   To determine the incidence and severity of hyponatremia as a complication in surgical correction of craniosynostosis and to identify risk factors for postoperative hyponatremia..   A retrospective medical record review for 2003-2008 of the Cleft and Craniofacial Database was made. Specific data collected included sodium values, age, weight, type of surgery, duration of surgery, administration of DDAVP, composition and volume of pre-operative, intra-operative, postoperative parenteral fluids, volume of blood, colloid, and crystalloid transfused, estimated blood loss (EBL), medications, comorbidities, pre-operative signs of elevated intracranial pressure (ICP), syndromic vs nonsyndromic craniosynostosis, and the complications associated with hyponatremia..   A total of 72 records were reviewed. The incidence of postoperative hyponatremia was 30.6%. There was no intra-operative hyponatremia. While hospital stay was not prolonged, ICU stay was significantly longer (1.9 vs 2.9 days, P = 0.001). Elevated ICP was significantly associated with hyponatremia (P < 0.002). A greater volume of blood loss (EBL) was associated with postoperative hyponatremia (P = 0.019). Patients with normal pre-operative ICP were more likely to become hyponatremic if they were female (relative risk = 2.43; P < 0.05). The average decrease in sodium was greater in patients receiving hyponatremic (hypotonic) vs normonatremic (isotonic) postoperative IVF's (5.5 vs 3.2 mEq·l(-1), P = 0.039). There were no postoperative complications related to hyponatremia..   The incidence of postoperative hyponatremia after calvarial vault remodeling was determined to be 30.6%. Hyponatremia was significantly associated with increased pre-operative ICP, blood loss, and female gender (normal pre-operative ICP). The average decrease in sodium was greater in patients receiving hyponatremic postoperative IVF's.

Topics: Anesthesia; Blood Loss, Surgical; Blood Substitutes; Blood Volume; Child; Child, Preschool; Comorbidity; Craniosynostoses; Deamino Arginine Vasopressin; Female; Fluid Therapy; Humans; Hyponatremia; Infant; Intracranial Pressure; Logistic Models; Male; Monitoring, Intraoperative; Plastic Surgery Procedures; Postoperative Complications; Retrospective Studies; Risk Factors; Skull; Sodium

To analyze the incidence and severity of hyponatremia in patients receiving synthetic desmopressin (DDAVP) in the perioperative setting of oropharyngeal surgery in the treatment of von Willebrand disease and to propose a standardized protocol for perioperative fluid resuscitation and postoperative sodium monitoring after DDAVP administration.. Retrospective medical record review.. A retrospective medical record review in an academic pediatric medical center was conducted. From October 1, 2002, to February 1, 2009, all patients undergoing adenotonsillectomy and receiving DDAVP preoperatively for the treatment of von Willebrand disease were identified. A total of 76 patients were identified by initial database review; 63 patients were included in the study, and 13 patients were excluded secondary to incomplete data. DDAVP dose and timing, perioperative fluid volume and composition, and postoperative sodium levels were collected. Extreme adverse events related to hyponatremia were recorded.. Forty-seven of 63 (74.6%) patients developed some degree of hyponatremia after DDAVP administration, and six of 63 (9.5%) patients developed extreme hyponatremia, with the degree of hyponatremia related to the volume of perioperative fluid resuscitation. The sodium nadir occurred within 9 to 20 hours after DDAVP administration. No serious adverse events related to hyponatremia were recorded during the study period.. The incidence of hyponatremia in children receiving DDAVP for prophylaxis of intraoperative bleeding following oropharyngeal surgery is high. The degree of hyponatremia is related to the perioperative fluid volume administered. A protocol for DDAVP administration, perioperative fluid resuscitation, and postoperative sodium monitoring that aims to reduce the incidence of hyponatremia in this population is proposed.

Topics: Academic Medical Centers; Adenoidectomy; Adolescent; Blood Loss, Surgical; Child; Child, Preschool; Cohort Studies; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Humans; Hyponatremia; Incidence; Male; Perioperative Care; Postoperative Complications; Postoperative Hemorrhage; Preoperative Care; Retrospective Studies; Risk Assessment; Severity of Illness Index; Tonsillectomy; Treatment Outcome; von Willebrand Diseases

Desmopressin is occasionally used to reduce the frequency of nocturnal toilet visits. We describe an 86-year-old woman with nocturnal incontinence due to a urinary tract infection, and a 49-year-old man with frequent toilet visits in the night, known to consume excessive amounts of alcohol. They were admitted to hospital with neurological symptoms due to severe hyponatraemia, 114 and 102 mmol/l respectively, while using desmopressin. After the desmopressin had been discontinued and the fluid balance restored, they recovered completely. Hyponatraemia is inherent to the mechanism of action of desmopressin. Desmopressin should be prescribed only on sound indication, and risk factors for developing severe hyponatraemia should always be taken into consideration. Proper instruction and follow-up are important to prevent severe complications.

Topics: Aged, 80 and over; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Male; Middle Aged; Nocturia

A 61-year-old woman was admitted with history of vomiting, diarrhoea and severe hyponatraemia (Na(+) 109). The cause of the hyponatraemia was due to intravascular volume depletion resulting in a non-osmotic release of antidiuretic hormone (ADH) with the added effects of a thiazide diuretic. She was also on fluoxetine which may induce inappropriate secretion of ADH. Despite cautious fluid replacement, the patient's serum sodium increased by 12 mmol/l over the first 18 h (and by 10 mmol/l over 12 h). This trajectory, coupled with the rapid decrease in urine osmolality, suggested that this patient was at risk of significant brain injury due to rapid correction of serum sodium. The use of desmopressin slowed the rise in serum sodium allowing brain adaptive mechanisms time to protect against osmotic demyelination.

Topics: Adaptation, Physiological; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Middle Aged; Sodium

Acute hyponatremia is a serious condition, which poses major challenges. Of particular importance is what determines plasma sodium concentration ([Na(+)]). Edelman introduced an explicit model to describe plasma [Na(+)] in a population as [Na(+)] = alpha.(exchangeable Na(+) + exchangeable K(+))/(total body water) - beta. Evidence for the clinical utility of the model in the individual and in acute hyponatremia is sparse. We, therefore, investigated how the measured plasma [Na(+)] could be predicted in a porcine model of hyponatremia. Plasma [Na(+)] was estimated from in vivo-determined balances of water, Na(+), and K(+), according to Edelman's equation. Acute hyponatremia was induced with desmopressin acetate and infusion of a 2.5% glucose solution in anesthetized pigs. During 480 min, plasma [Na(+)] and osmolality were reduced from 136 (SD 2) to 120 mmol/l (SD 3) and from 284 (SD 4) to 252 mosmol/kgH(2)O (SD 5), respectively. The following interpretations were made. First, Edelman's model, which, besides dilution, takes into account Na(+) and K(+), fits plasma [Na(+)] significantly better than dilution alone. Second, a common value of alpha = 1.33 (SD 0.08) and beta = -13.04 mmol/l (SD 7.68) for all pigs explains well the plasma [Na(+)] in the individual animal. Third, measured exchangeable Na(+) and calculated exchangeable Na(+) + K(+) per weight in the pigs are close to Edelman's findings in humans, whereby the methods are cross-validated. In conclusion, plasma [Na(+)] can be explained in the individual animal by external balances, according to Edelman's construct in acute hyponatremia.

Topics: Acute Disease; Animals; Antidiuretic Agents; Cations; Deamino Arginine Vasopressin; Female; Hyponatremia; Models, Animal; Models, Biological; Potassium; Sodium; Swine; Time Factors; Water-Electrolyte Balance

Hyponatremia is among the most common biochemical abnormalities in hospital inpatients. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of several causes of hyponatremia, particularly in patients with pulmonary diseases. The mechanism of SIADH associated with pulmonary infection is, however, poorly understood. We report an unusual case of hyponatremia in a man with pulmonary TB and central diabetes insipidus with biochemical evidence of ectopic antidiuretic hormone production as a possible mechanism causing hyponatremia.

Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Follow-Up Studies; Humans; Hyponatremia; Male; Middle Aged; Sodium; Tuberculosis, Pulmonary; Vasopressins

Hyponatremic encephalopathy is a potentially lethal condition with numerous reports of death or permanent neurological injury. The optimal treatment for hyponatremic encephalopathy remains controversial. We have introduced a unified approach to the treatment of hyponatremic encephalopathy which uses 3% NaCl (513 mEq/L) bolus therapy. Any patient with suspected hyponatremic encephalopathy should receive a 2 cc/kg bolus of 3% NaCl with a maximum of 100 cc, which could be repeated 1-2 times if symptoms persist. The approach results in a controlled and immediate rise in serum sodium with little risk of inadvertent overcorrection.

Topics: Brain; Brain Diseases, Metabolic; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Drug Overdose; Humans; Hypernatremia; Hyponatremia; Iatrogenic Disease; Sodium Chloride

It has recently became apparent that severe primary monosymptomatic nocturnal enuresis (MNE) has a worse prognosis than generally believed, and may have major consequences on the well-being of the child, thus making treatment mandatory. Desmopressin is one of the most widely prescribed medications for MNE, and in this current opinion article we discuss the safety of desmopressin in children with this condition. Following a US FDA request in December 2007 that the prescribing information for desmopressin nasal spray be updated, desmopressin spray is no longer indicated for the treatment of MNE or for use in patients at risk for hyponatraemia. Multiple reports of hyponatraemia in patients with nocturia (mainly the elderly) led to an increased awareness of the risks associated with desmopressin. While the pathogenesis of hyponatraemia in those over 65 years of age relates more to changing renal water and solute handling, we believe that in the young, overdosing and insufficient fluid restriction are usually the major causes. Hyponatraemia is most frequently reported when desmopressin is administered by nasal spray compared with the tablet formulation. This may simply reflect the fact that for more than 10 years the spray was the only available mode of administration in many countries. However, it may also reflect the higher biodisponibility and/or intraindividual variability of pharmacokinetics of the spray compared with the tablet. There are few serious adverse events reported for the melt formulation (oral lyophilisate), but as it has only recently become available on the market, it would be premature to conclude that it has a better safety profile. We believe that desmopressin in all formulations has a good safety profile in children with MNE, provided that treatment is properly prescribed and monitored; improving the training of doctors and patients in the dose-response kinetics of the drug, teaching appropriate restriction of fluid intake and by encouraging the use of desmopressin within a narrow dose range (10-20 microg spray, 120-240 microg melt and 200-400 microg tablet) when used in primary-care settings. Titrating higher doses in therapy-resistant patients should probably be carried out in a specialized enuresis centre, and only after documenting adequate morning urinary diluting capacity. In summary, the risk of hyponatraemia is exacerbated by misuse of the drug rather than an inherent danger associated with the drug, which in our opinion should b

Topics: Administration, Intranasal; Administration, Oral; Aged; Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Humans; Hyponatremia; Nocturnal Enuresis; Risk Factors

The effects of stable chronic hyponatremia on the central nervous system are largely unknown, clinically, or in experimental animals. The aim of this study was to identify and characterize these effects in rats. Tolvaptan, a vasopressin V(2) receptor antagonist, was used to correct hyponatremia and determine any potential benefits of such treatment in this condition. Stable chronic hyponatremia was induced by combination of the continuous vasopressin V(2) receptor stimulation and liquid food intake. The hyponatremic rats did not exhibit significant changes in general symptoms or neurological functions assessed by modified Irwin's method, or in motor function assessed by the rotarod test. In passive avoidance test, however, rats with moderate and severe hyponatremia had significantly reduced step-through latency, indicating impairment in memory. This reduced step-through latency was improved by the treatment of tolvaptan (0.25-8 mg/kg daily doses), a vasopressin V(2) receptor antagonist. This improvement is associated with normalization of plasma sodium concentrations in hyponatremic rats. In conclusion, these data suggest that chronic hyponatremia may impair memory, and treatments that normalize sodium level, such as vasopressin V(2) receptor antagonists, may be beneficial to patients with hyponatremia.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Avoidance Learning; Benzazepines; Body Water; Brain; Deamino Arginine Vasopressin; Hyponatremia; Male; Memory; Memory Disorders; Motor Activity; Rats; Rats, Sprague-Dawley; Reaction Time; Receptors, Vasopressin; Sodium; Tolvaptan

Dysnatremias (hypo- and hypernatremia) are common in patients admitted to the intensive care unit (ICU) with a prevalence approaching 20-30% in some studies. Recent data reveals that both hypo- and hypernatremia present on admission to or developing in the ICU are independent risk factors for poor prognosis. The origin of hypernatremia in the ICU is often iatrogenic and due to inadequate free water replacement of ongoing water losses. The pathogenesis of hyponatremia in the ICU is more complicated but often is related to the combination of dysregulated arginine vasopressin production and concomitant inappropriate hypotonic fluid administration. Both the dysnatremia itself and the treatment of the electrolyte disturbance can be associated with morbidity and mortality making careful monitoring for and treatment of sodium disorders an imperative in the critically ill patient. Formulae have been devised to guide the therapy of severe hypo- and hypernatremia, but these formulae regard the patient as a closed system and do not take into account ongoing fluid losses that can be highly variable. Thus, a cornerstone of proper therapy is serial measurements of serum and urine electrolytes. The appropriate use of hypertonic (3%) saline in the treatment of hyponatremic encephalopathy has also shown to be very effective and the use of this therapy is reviewed here. Vasopressin receptor antagonists have also been shown to be effective at increasing serum sodium levels in patients with either euvolemic or hypervolemic hyponatremia and represent another therapeutic option. Recent data demonstrates that proper correction of hyponatremia is associated with improved short- and long-term outcomes.

Topics: Austria; Body Water; Deamino Arginine Vasopressin; Fluid Therapy; Humans; Hypernatremia; Hypertonic Solutions; Hyponatremia; Intensive Care Units; Prevalence; Prognosis; Risk Factors; Sodium

Dilutional hyponatremia, although not uncommon, is an underestimated problem in the pediatric population. In most cases, it results from excessive hydration or water retention, also described as the so-called water intoxication. One of the most known causes is the use of desmopressin in enuretic children. This drug enhances the free water reabsorption in the renal collecting ducts. The addition of the anticholinergic agent oxybutynin aggravated the condition by causing a dry mouth with excessive thirst and water intake in our first case. Dietary water overconsumption, either voluntary or involuntary, is a phenomenon seen in formula-fed babies. But in our second case, a game involving forced ingestion of large amounts of water had serious consequences including hyponatremia-related coma. An effort should therefore be made to inform caretakers about the risks of these games. These cases, provoked by rather unusual and peculiar causes, illustrate again that electrolytes and especially serum [Na(+)] are key points to be determined in a child with diminished consciousness. Moreover, an accurate history including the intake of medication and dietary information should be made.

Topics: Antidiuretic Agents; Child; Cholinergic Antagonists; Deamino Arginine Vasopressin; Drug Therapy, Combination; Electrocardiography; Female; Humans; Hyponatremia; Male; Mandelic Acids; Nocturnal Enuresis; Water Intoxication

An alcoholic patient presented with profound hyponatremia (serum sodium concentration, 96 mEq/L) caused by the combined effects of a thiazide diuretic, serotonin reuptake inhibitor, beer potomania, and hypovolemia. A computed tomographic scan of the brain was indistinguishable from one obtained 3 weeks earlier when he was normonatremic. Concurrent administration of 3% saline solution and desmopressin controlled the rate of correction to an average of 6 mEq/L daily and resulted in full neurologic recovery without evidence of osmotic demyelination. This case illustrates the value of controlled correction of profound hyponatremia.

Topics: Alcohol-Related Disorders; Blood Chemical Analysis; Brain Diseases; Deamino Arginine Vasopressin; Demyelinating Diseases; Follow-Up Studies; Humans; Hyponatremia; Male; Middle Aged; Risk Assessment; Saline Solution, Hypertonic; Severity of Illness Index; Sodium; Tomography, X-Ray Computed; Treatment Outcome

The efficacy of DDAVP (1-deamino-8-D-arginine-vasopressin, desmopressin) in mild haemophilia A and von Willebrand disease (VWD) has been established and the use of this well tolerated drug has become clinical routine. In case of increased fluid intake and based on very rarely occurring hyponatraemia, the indication of administration of DDAVP intravenously (i. v.) has to be performed diligently in elderly patients and in children below the age of five years. Aim, patients: Due to clinical practice we were interested in finding prospective parameter potentially correlating with adverse reactions of DDAVP and initiated this study. From 2007 to 2008, we included 49 patients suspicious to suffer from mild haemophilia A (n = 1) or VWD (n = 48) and investigated efficacy and safety of DDAVP after intravenous administration (mean: 0.29±0.032 μg/kg body weight). They underwent clinical and laboratory investigation and were questioned with regard to potential adverse reactions immediately and three days after administration of DDAVP.. Most adverse reactions were mild and no serious adverse drug reactions were either observed or reported by the subjects. We identified significant changes of heart rate, blood pressure and leucocytes after conduct of the DDAVP test. The value of these findings has to be investigated in later prospective randomized studies. Further research on identification of prospective parameter is currently ongoing.

Topics: Aged; Child, Preschool; Deamino Arginine Vasopressin; Heart Rate; Hematocrit; Hemophilia A; Hemostatics; Humans; Hyponatremia; Injections, Intravenous; Leukocyte Count; Platelet Count; Prothrombin Time; Safety

Desmopressin, a synthetic analog of the antidiuretic hormone, is used in the treatment of enuresis nocturna in children and increasingly also in adults. Nocturia in the elderly causes sleeping disorders and is associated with a higher risk of falling and increased mortality. Desmopressin leads to a significant decrement of nocturia and consequently, a better sleep quality and is for this reason increasingly prescribed in the old. Desmopressin causes borderline hyponatremia (130-135 mmol/l) in 15% and severe hyponatremia in 5% of all adult users. Factors that predispose to hyponatremia are a higher dose, age > 65 years, a low-normal serum sodium, a high 24-hour urine volume and co-medication (thiazide diuretics, tricyclic antidepressants, serotonin-reuptake-inhibitors, chlorpromazine, carbamazipine, loperamide, Non-Steroidal-Anti-Inflammatory-Drugs). Hyponatremia is associated with headache, nausea, vomiting, dizziness, and can cause somnolence, loss of consciousness and death. We present two cases where initiation of desmopressin led to hyponatremia, requiring hospitalization. In view of the high risk of desmopressin-associated hyponatremia in the older population, alternative treatment strategies for nocturia must be considered first. If desmopressin is prescribed, strict follow-up of serum sodium levels is necessary.

Topics: Aged; Aged, 80 and over; Antidiuretic Agents; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Nocturia; Risk Assessment; Risk Factors; Sodium

Topics: Adult; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Hyponatremia; Seizures; von Willebrand Diseases

The diagnosis and management of hyponatremia can be intimidating, for both trainees and clinicians alike. We present five clinical scenarios of patients with hyponatremia. These discussions reinforce concepts reviewed elsewhere in this issue of Seminars in Nephrology and/or emphasize specific causes and management issues.

Topics: Adult; Aged; Benzazepines; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Male; Middle Aged; Saline Solution, Hypertonic; Tolvaptan; Treatment Outcome

Topics: Antidiuretic Agents; Coma; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Infusions, Intravenous; Middle Aged; von Willebrand Disease, Type 2

The aims of this study were to analyze the prescription pattern of desmopressin before and after the new indication was approved for treatment of nocturia in the elderly in Sweden in 2002 and to analyze to what extent other drugs potentially inducing hyponatremia were prescribed in combination with desmopressin.. We conducted epidemiological analyzes of the Swedish Prescribed Drug Register from 2000 to March 2007. All patients older than 60 years who were prescribed desmopressin in Sweden during the study period were included.. A marked increase in filled prescriptions of desmopressin in elderly patients was noticed after the new approval in 2002. The therapeutic intensity peaked in 2005 and has thereafter markedly decreased. The magnitude of concurrent treatment with any of the following drugs was assessed: diuretics, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRI), chlorpromazine, carbamazepine, loperamide, and nonsteroid anti-inflammatory drugs. More than half of the patients on desmopressin during July 2005 and March 2007 filled a prescription of any of the potentially harmful drugs within 30 days of a filled prescription of desmopressin.. The use of desmopressin in the elderly after the new approval in 2002 showed a similar prescription pattern to any newly introduced drug or after a changed indication. A large part of the elderly on desmopressin also receives other drugs that are potentially harmful in combination with desmopressin. Increased awareness of potentially interacting concomitant medication can improve medication safety in this fragile group.

Topics: Aged; Databases, Factual; Deamino Arginine Vasopressin; Drug Interactions; Drug Prescriptions; Drug Utilization; Female; Humans; Hyponatremia; Male; Middle Aged; Nocturia; Renal Agents; Sweden

Adherence to therapeutic guidelines for the treatment of hyponatremia becomes difficult when water diuresis emerges during therapy. The objective of this study was to assess the effectiveness and safety of desmopressin acetate as a therapeutic agent to avoid overcorrection of hyponatremia and to lower the plasma sodium concentration again after inadvertent overcorrection.. Retrospective chart review was conducted of all patients who were given desmopressin acetate during the treatment of hyponatremia during 6 yr in a 528-bed community teaching hospital.. Six patients (group 1) were given desmopressin acetate after the 24-h limit of 12 mmol/L had already been reached or exceeded; correction was prevented from exceeding the 48-h limit of 18 mmol/L in five of the six. Fourteen patients (group 2) were given desmopressin acetate in anticipation of overcorrection after the plasma sodium concentration had increased by 1 to 12 mmol/L. In all 14 patients who were treated with desmopressin acetate as a preventive measure, correction was prevented from exceeding either the 24- or 48-h limits. After desmopressin acetate was administered, the plasma sodium concentration of 14 of the 20 patients fell by 2 to 9 mmol/L. In all six group 1 patients and in five of the group 2 patients, the plasma sodium concentration was actively lowered again by the concurrent administration of desmopressin acetate and 5% dextrose in water; no serious adverse consequences from this maneuver were observed.. Desmopressin acetate is effective in preventing and reversing inadvertent overcorrection of hyponatremia.

Topics: Adult; Aged; Aged, 80 and over; Antidiuretic Agents; Deamino Arginine Vasopressin; Female; Humans; Hypernatremia; Hyponatremia; Male; Middle Aged; Retrospective Studies

A recent study has revealed that acute and chronic administration of the vasopressin V2 receptor (V2R) agonist dDAVP induced a marked increase of urinary albumin excretion (UAE) in healthy rats and humans (Bardoux P et al. Nephrol Dial Transplant 2003; 18: 497-506). The occurrence of an elevation of UAE among patients with chronic syndromes of inappropriate antidiuresis has not been reported.. We looked for the elevation of UAE in 24-h urine samples of the following patients: nine chronic SIADH patients, two patients with acute post-operative SIADH, three patients of the same family with nephrogenic syndrome of inappropriate antidiuresis (NSAID) and two patients with hyponatraemia due to surdosage of dDAVP in the setting of central diabetes insipidus.. There was no elevation of UAE in our patients (whether they presented with hyponatraemia or not), apart from a patient treated with supra-physiological doses of dDAVP. When she received 80 microg/day of dDAVP, her UAE was 42 mg/day. In this patient, UAE returned to the normal range (21 mg/day) when doses of dDAVP were tapered (20 microg/day).. The present study shows that chronic V2R stimulation generally does not result in a rise in UAE. The discrepancy between our results and those of the above-mentioned study could be explained by a dose-dependent effect of V2R stimulation on UAE.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Antidiuretic Agents; Chronic Disease; Circadian Rhythm; Deamino Arginine Vasopressin; Diabetes Insipidus; Dose-Response Relationship, Drug; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Incidence; Male; Middle Aged; Mutation; Receptors, Vasopressin

Topics: Blood Coagulation Disorders; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Hyponatremia; Middle Aged; Seizures

Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Humans; Hyponatremia; Male; Middle Aged; Recurrence; Substance-Related Disorders

Topics: Administration, Intranasal; Antidiuretic Agents; Deamino Arginine Vasopressin; Drinking; Half-Life; Humans; Hyponatremia; Nocturnal Enuresis

Hyponatraemia is among the more common electrolyte abnormalities encountered in the ED. Both the primary disturbance and its correction can result in life-threatening neurological sequelae. Osmotic myelinolysis syndrome is one such complication and is associated with the rapid correction of hyponatraemia. The present case report describes the mechanism of severe hyponatraemia in a patient taking deamino arginine vasopressin, and the subsequent development of both central pontine and extrapontine myelinolysis after rapid correction of sodium levels. Implications for the emergency management of such patients are discussed.

Topics: Adult; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Myelinolysis, Central Pontine; Osmosis; Sodium; Syndrome

Against the background of the approval of the use of desmopressin in the treatment of nocturia in adults, the aim of the present study was to describe patterns of its use in elderly patients in Denmark from 2000 to 2004.. Data were obtained from the Danish Register of Medicinal Product Statistics on nationwide sales of desmopressin and two commonly used measures of drug utilisation: 1-year prevalence (number of patients treated at least once during 1 year/1000 inhabitants) and therapeutic intensity (Daily Defined Doses (DDD)/1000 inhabitants/day).. In 2002, the 1-year prevalence rose ranging from a 5-fold increase among men aged 60-69 years to a 14-fold increased prevalence in men >/=90 years. In women, relative increases of the same magnitude were noted. Similarly, marked increases of the therapeutic intensities were observed in both men and women in 2002, this was followed by steady growth in most age groups. By the end of the study period in 2004, the highest therapeutic intensities were observed in men (1.06 DDD/1000 inhabitants/day) and women (0.92 DDD/1000 inhabitants/day) aged 80-89 years.. After approval in 2002 of the use of desmopressin in the management of nocturia in adults, a substantial increased utilisation was observed in patients >/=80 years. Given the high prevalence of risk factors for hyponatremia in these elderly patients, the pattern of utilisation is noteworthy and may need to be reviewed.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Age Factors; Aged; Antidiuretic Agents; Community Pharmacy Services; Deamino Arginine Vasopressin; Denmark; Drug Monitoring; Female; Humans; Hyponatremia; Male; Middle Aged; Nocturia; Prevalence; Registries; Reproducibility of Results; Risk Factors; Time Factors

To explore the incidence, severity, time course, and risk factors of clinically significant hyponatremia in desmopressin treatment for nocturia.. Data from three multi-center phase III trials were pooled. Hyponatremia was categorised as borderline (134-130 mmol/L) or significant (<130 mmol/L). Risk factors were explored with logistic regression and subgroup analysis performed to explore threshold values for contra-indication.. In total 632 patients (344 men, 288 women) were analyzed. During dose-titration, serum sodium concentration below normal range was recorded in 95 patients (15%) and 31 patients (4.9%) experienced significant hyponatremia. The risk increased with age, lower serum sodium concentration at baseline, higher basal 24-hr urine volume per bodyweight and weight gain at time of minimum serum sodium concentration. Age was the best single predictor. Elderly patients (>or=65 years of age) with a baseline serum sodium concentration below normal range were at high risk (75%). Limiting treatment in elderly with normal basal serum sodium concentration to those below 79 years and with a 24-hr urine output below 28 ml/kg would reduce the risk from 8.1% to 3.0% at the cost of 34% fulfilling the contra-indication.. The majority of nocturia patients tolerate desmopressin treatment without clinically significant hyponatremia. However, the risk increases with increasing age and decreasing baseline serum sodium concentration. Treatment of nocturia in elderly patients with desmopressin should only be undertaken together with careful monitoring of the serum sodium concentration. Patients with a baseline serum sodium concentration below normal range should not be treated.

Topics: Adult; Aged; Databases, Factual; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Logistic Models; Male; Middle Aged; Randomized Controlled Trials as Topic; Renal Agents; Risk Factors; Sodium; Urination Disorders

Nasal desmopressin (DDAVP) is a commonly prescribed antidiuretic hormone (ADH) analogue used for treatment of diabetes insipidus, polyuria and nocturnal enuresis. Although it is generally well tolerated, it can cause severe electrolyte imbalance. Numerous reports exist on cases of mild to moderate DDAVP-induced hyponatremia, yet few reports describe severe hyponatremia (Na<115 mEq/L). We present a case of a 52-year-old woman with nearly symptom-free, DDAVP-induced hypotonic hyponatremia of 104 mEq/L following a gastrointestinal illness. We describe the appropriate correction of her hyponatremia and conclude by raising awareness of the potential for severe cases of desmopressin-associated hyponatremia, even in the rather symptom-free patient.

Topics: Administration, Intranasal; Antidiuretic Agents; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Middle Aged

Enuresis nocturna is regularly treated by desmopressin, a vasopressin analog. Its side effects, notably neurological, are fortunately rare. We comment on 5 enuretic children on desmopressin who suffered from hyponatremic encephalopathy (natremia 115-127, median 117 mmol/l).. Side effects appeared at therapeutic doses (10-40 mg/d intranasal). An excessive fluid intake at night was often noted, leading to a dilutional hyponatremia. This may be due to a lack of correct information to the parents. These children presented after a period of warning symptoms, such as headache, vomiting and altered consciousness. Parents could have sought earlier medical attention if they had been informed about these symptoms.. In the absence of fluid restriction, severe hyponatremia can occur in enuretic children on desmopressin. It is therefore mandatory for the prescribing doctor to adequately inform patients and parents to limit fluids at night when desmopressin is used, and seek medical help quickly if any sign of intracranial hypertension appears.

Topics: Administration, Intranasal; Antidiuretic Agents; Child; Child, Preschool; Coma; Confusion; Deamino Arginine Vasopressin; Drinking; Enuresis; Female; Glasgow Coma Scale; Humans; Hyponatremia; Intracranial Hypertension; Male; Seizures; Time Factors

Topics: Adult; Antidiuretic Agents; Deamino Arginine Vasopressin; Fatigue; Female; Fluid Therapy; Humans; Hyponatremia; Munchausen Syndrome; Treatment Outcome

Topics: Adult; Anticonvulsants; Antidiuretic Agents; Brain; Brain Edema; Craniocerebral Trauma; Craniotomy; Deamino Arginine Vasopressin; Diazepam; Fatal Outcome; Hematoma, Subdural; Humans; Hyponatremia; Intubation, Intratracheal; Male; Nocturnal Enuresis; Phenytoin; Saline Solution, Hypertonic; Seizures; Sodium; Tomography, X-Ray Computed

We report a case of a 65 year old Malay lady with long-standing diabetes mellitus, who presented to our institution with a one month history of worsening neck pain and progressive upper and lower limb weakness. She was stable despite severe hyponatraemia which was initially treated as syndrome of inappropriate anti-diuretic hormone (SIADH). This was consistent with her underlying illness which was concluded as cervical tuberculosis (TB) with spinal cord compression. She underwent decompression and bone grafting. Despite continuous treatment her serum sodium levels remained low. There were no other problems with her adrenals or thyroid. A water loading and hypertonic saline perfusion test was performed and supported the diagnosis of reset osmostat. Her serum sodium remained below the normal range and she was discharged well.

Topics: Aged; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Muscle Weakness; Saline Solution, Hypertonic; Spinal Cord Compression; Tuberculosis, Central Nervous System

Central pontine myelinolysis (CPM) is a serious demyelination disease commonly associated with the rapid correction of hyponatremia. Although its pathogenesis remains unclear, the disruption of the blood-brain barrier (BBB) as a consequence of a rapid increase in serum sodium concentration is considered to play a critical role. Since glucocorticoids are known to influence BBB permeability and prevent its disruption as a result of hypertension or hyperosmolarity, we investigated whether dexamethasone (DEX) could protect against osmotic demyelination in an animal model of CPM. Hyponatremia was induced in rats by liquid diet feeding and dDAVP infusion. Seven days later, the animals' hyponatremia was rapidly corrected by injecting a bolus of hypertonic saline intraperitoneally. Rats subjected to this treatment displayed serious neurological impairment and 77% died within 5 days of rapid correction of their hyponatremia; demyelinative lesions were observed in various brain regions in these animals. On the other hand, rats that were treated with DEX (2 mg/kg, 0 and 6 h after hypertonic saline injection) exhibited minimal neurological impairment and all were alive after 5 days. Demyelinative lesions were rarely seen in the brains of DEX-treated rats. A marked extravasation of endogenous IgG was observed in the demyelinative lesions in the brains of rats that did not receive DEX, indicating disruption of the BBB, but was not observed in DEX-treated rats. Furthermore, Evans blue injection revealed a significant reduction in staining in the brains of DEX-treated rats (P < 0.05). These results indicate that early DEX treatment can prevent the BBB disruption that is caused by the rapid correction of hyponatremia and its associative demyelinative changes, and suggest that DEX might be effective in preventing CPM.

Topics: Animals; Blood-Brain Barrier; Brain; Deamino Arginine Vasopressin; Dexamethasone; Disease Models, Animal; Hypernatremia; Hyponatremia; Immunoglobulin G; Male; Myelinolysis, Central Pontine; Nerve Fibers, Myelinated; Rats; Rats, Sprague-Dawley; Saline Solution, Hypertonic; Water-Electrolyte Balance

Severe hyponatremia is most frequently caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Although the expressional alteration of the kidney-specific apical water channel, aquaporin 2 (AQP2), in the collecting duct has been demonstrated to be involved in the development of hyponatremia and the subsequent physiologic reaction that is resistant to arginine vasopressin (AVP; vasopressin escape) in SIADH, the complete pathogenesis of and the appropriate medical treatment for hyponatremia have yet to be elucidated.. Hyponatremia was induced in male Sprague-Dawley rats by water loading and subcutaneous infusion of 1-deamino-8-D-arginine vasopressin (dDAVP). For the treatment, a selective AVP V(2) receptor antagonist (OPC-31260) and/or a loop diuretic (furosemide) were administered orally. Protein expression of AQP2 and rat bumetanide-sensitive cotransporter (rBSC1) was examined by Western blotting during the hyponatremia and the subsequent treatment.. We noted a markedly high expression of rBSC1 during the development of hyponatremia, and a relatively low expression during vasopressin escape. OPC-31260 administration elevated serum sodium level in a dose-dependent manner. The therapeutic effect, however, declined with increasing number of treatment days, and doses higher than 15 mg/kg/day induced severe toxicity. The physiologic parameters and the alterations of AQP2 and rBSC1 expression during the treatment demonstrated reactions that were completely opposite to those of vasopressin escape. Combination of a furosemide (100 mg/kg/day) and a low dose of OPC-31260 (5 mg/kg/day) additively elevated serum sodium level and sustained the elevated serum sodium level by significantly reducing sodium accumulation in the renal medulla.. AVP-induced alterations of rBSC1 expression, as well as those of AQP2, are involved in the pathogenesis of SIADH. The pharmacologic blockade of AVP stimulus in SIADH limits its therapeutic efficacy by discontinuing the vasopressin escape, and the selective inhibition of rBSC1 complements this limitation.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Aquaporin 2; Aquaporins; Benzazepines; Deamino Arginine Vasopressin; Diuretics; Furosemide; Hyponatremia; Inappropriate ADH Syndrome; Kidney Medulla; Male; Potassium; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Sodium; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Potassium-Chloride Symporters; Solute Carrier Family 12, Member 1; Urea; Water

Topics: Adolescent; Antidiuretic Agents; Brain Diseases; Deamino Arginine Vasopressin; Diabetes Insipidus; Electroencephalography; Enuresis; Female; Humans; Hyponatremia; Male; Middle Aged

Lately, desmopressin (dDAVP) administered orally has been demonstrated to be an effective alternative in the management of nocturia in adults. Although the safety profile of dDAVP is well known, much of the experience originates from studies in enuretic children and younger adults, and it may not be readily extrapolated to elderly patients. In order to identify factors associated with an increased risk of hyponatremia in elderly patients treated with dDAVP for nocturia, we analysed spontaneous reports accrued from clinical practice in Denmark and Sweden.. Following a selection procedure, the study base comprised 15 case reports. From the included reports, information was sought on concurrent diseases, concomitant medications and other factors that may predispose elderly patients to hyponatremia when treated with desmopressin.. The median age amongst the cases was 81 years (range 61-93 years) and 80% were females. For seven of the patients, the hyponatremia occurred during the first 3 weeks of treatment. The symptoms presented by the patients led to hospitalisation in all but one case. Among patients with information available on concomitant medication, half of them were treated with cyclooxygenase inhibitors. An excessive fluid intake could only be ascertained in one case; all 15 patients eventually recovered.. In elderly patients treated with dDAVP for nocturia, an increased risk of hyponatremia exists in the first weeks of treatment. Compared with younger subjects, risk factors other than excessive intake of fluid appear to contribute to this adverse drug reaction.

Topics: Age Factors; Aged; Aged, 80 and over; Deamino Arginine Vasopressin; Denmark; Female; Humans; Hyponatremia; Incidence; Male; Middle Aged; Renal Agents; Retrospective Studies; Risk Factors; Sweden; Time Factors; Urination Disorders

A decrease in urine volume is considered the therapeutic goal of the treatment of central diabetes insipidus (DI) with desmopressin (dDAVP). A low urine volume is a risk factor for kidney stone formation. This is the first report of nephrolithiasis in association with DI. It is likely that successful therapy with dDAVP and the patient's own purposeful decreased fluid intake contributed to calcium oxalate stone formation. Prevention of stone recurrence requires an increase in urine volume. The patient's compliance with this recommendation led to an episode of acute hyponatremia, a well-known complication of dDAVP therapy. The challenge of the management of stones in the setting of DI requires balancing the conflicting goals of both decreasing and increasing urine volume.

Topics: Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hyponatremia; Kidney Calculi

Desmopressin (DDAVP) is used to improve hemostasis in patients with bleeding disorders. The side effects of DDAVP in adults and children are benign. However, there has been concern regarding the development of hyponatremia and seizures after the use of DDAVP in young children. The authors describe three children under 3 years of age who developed hyponatremia (two also developed seizures) following intravenous administration of DDAVP at a standard dose of 0.3 mug/kg. Fluid restriction, avoidance of hypo-osmolar fluid, and close monitoring of fluid and electrolytes for 12 to 24 hours after the administration of DDAVP in children younger than 3 years of age is recommended.

Topics: Child, Preschool; Deamino Arginine Vasopressin; Female; Hemorrhage; Hemostatics; Humans; Hyponatremia; Infant; Male; Seizures; Treatment Outcome

Topics: Adenoidectomy; Child, Preschool; Deamino Arginine Vasopressin; Enuresis; Female; Fluid Therapy; Hemophilia A; Humans; Hyponatremia; Postoperative Care; Postoperative Complications; Renal Agents; Seizures; Tonsillectomy; Water Intoxication

A 30-year-old man known to have a factor-IX deficiency was presented at the emergency department with unexplained coma. After immediate treatment with factor IX, a CT-scan of the brain revealed no intracerebral haemorrhage. However, blood tests showed severe hyponatraemia, low serum osmolarity and high urine-sodium excretion consistent with the Syndrome of Inappropriate Antiduretic Hormone Secretion (SIADH). Therapy with hypertonic saline was instituted resulting in a gradual rise in the serum-sodium concentration. The cause of the hyponatraemia however remained unclear. After repeat history taking the patient mentioned the use of desmopressin for nocturia. Hyponatraemia as a complication of desmopressin use occurs in 8% of adult patients treated for nocturia. Direct availability of a patient's drug history, by means of an electronic record for instance, could avoid unnecessary tests and delay in diagnosis.

Topics: Adult; Coma; Deamino Arginine Vasopressin; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Saline Solution, Hypertonic; Urination Disorders

Topics: Antidiuretic Agents; Antipsychotic Agents; Clozapine; Deamino Arginine Vasopressin; Enuresis; Glasgow Coma Scale; Humans; Hyponatremia; Male; Middle Aged; Schizophrenia; Severity of Illness Index; Sodium

Managing children with diabetes insipidus (DI) in the perioperative period is complicated and frequently associated with electrolyte imbalance compounded by over- or underhydration. In this study the authors developed and prospectively evaluated a multidisciplinary approach to the perioperative management of DI with a comparison to 19 historical control children. Eighteen children either with preoperative DI or undergoing neurosurgical operations associated with a high risk for developing postoperative DI were identified and managed using a standardized protocol. In all patients in whom DI occurred during or after surgery, a continuous intravenous infusion of aqueous vasopressin was initiated and titrated until antidiuresis was established. Intravenous fluids were given as normal saline and restricted to two thirds of the estimated maintenance rate plus amounts necessary to replace blood losses and maintain hemodynamic stability. In all children managed in this fashion, perioperative serum sodium concentrations were generally maintained between 130 and 150 mEq/L, and no adverse consequences of this therapy developed. In the 24-hour period evaluated, the mean change in serum sodium concentrations between the historical controls was 17.6 +/- 9.2 mEq/L versus 8.36 +/- 6.43 mEq/L in those children managed by the protocol. Hyponatremia occurred less frequently in the children managed with this protocol compared with historical controls.

Topics: Adolescent; Child; Child, Preschool; Clinical Protocols; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hyponatremia; Hypotonic Solutions; Infusions, Intravenous; Male; Neurosurgical Procedures; Perioperative Care; Postoperative Complications; Prospective Studies; Renal Agents; Seizures; Sodium; Vasopressins; Water-Electrolyte Balance

Managing children with diabetes insipidus (DI) in the perioperative period is complicated and frequently associated with electrolyte imbalance compounded by over- or underhydration. In this study the authors developed and prospectively evaluated a multidisciplinary approach to the perioperative management of DI with a comparison to 19 historical control children. Eighteen children either with preoperative DI or undergoing neurosurgical operations associated with a high risk for developing postoperative DI were identified and managed using a standardized protocol. In all patients in whom DI occurred during or after surgery, a continuous intravenous infusion of aqueous vasopressin was initiated and titrated until antidiuresis was established. Intravenous fluids were given as normal saline and restricted to two thirds of the estimated maintenance rate plus amounts necessary to replace blood losses and maintain hemodynamic stability. In all children managed in this fashion, perioperative serum sodium concentrations were generally maintained between 130 and 150 mEq/L, and no adverse consequences of this therapy developed. In the 24-hour period evaluated, the mean change in serum sodium concentrations between the historical controls was 17.6 +/- 9.2 mEq/L versus 8.36 +/- 6.43 mEq/L in those children managed by the protocol. Hyponatremia occurred less frequently in the children managed with this protocol compared with historical controls.

Topics: Adolescent; Child; Child, Preschool; Clinical Protocols; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Hyponatremia; Hypotonic Solutions; Infusions, Intravenous; Male; Neurosurgical Procedures; Perioperative Care; Postoperative Complications; Prospective Studies; Renal Agents; Seizures; Sodium; Vasopressins; Water-Electrolyte Balance

A patient was referred to the intensive care unit with sudden delirium and a serum sodium level of 111 mEq/L (mmol/L). A computerized tomographic scan revealed marked cerebral edema. Laboratory values were highly consistent with the action of the antidiuretic hormone. She had received desmopressin acetate (DDAVP) for 4 days preoperatively and postoperatively for putative van Willebrand's disease. Hyponatremia as a sequel to DDAVP treatment is an unusual complication and the medication is generally safe. However, our patient nevertheless teaches that vigilance equals avoidance.

Topics: Brain Edema; Deamino Arginine Vasopressin; Delirium; Drug Administration Schedule; Female; Humans; Hyponatremia; Middle Aged; Ovarian Cysts; Premedication; Sodium; Tomography, X-Ray Computed; von Willebrand Diseases

Topics: Antidiuretic Agents; Child; Coma; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Hyponatremia; Seizures

We describe a novel missense mutant of arginine vasopressin (AVP)-dependent neurohypophyseal diabetes insipidus in an autosomal dominant family. A 54-year-old woman was admitted to our hospital because of thyroidectomy for thyroid cancer. After thyroidectomy she was found to have hypernatremia and polyuria and polydipsia both of which had been present from childhood. She had no obstructive hydronephrosis. Her father, father's younger sister and her third son also had polyuria and polydipsia. Basal plasma AVP concentration at normal plasma osmolality was normal but did not respond to increased plasma osmolality despite hyperosmolality during infusion of hypertonic saline infusion, indicating that plasma AVP secretion was impaired. Sodium concentration in urine and urine osmolality were low and increased after nasal administration of DDAVP. There was a diminished but bright signal of pituitary posterior gland on magnetic resonance T1 weighted image. Molecular genetic analysis demonstrated that the patient and her son had a single heterozygous missense mutation (G-->A) at nucleotide 1829 in 1 AVP allele, yielding an abnormal AVP precursor with lacking Glu-47 in its neurophysin II moiety. The abnormal AVP precursor may be related to the impaired AVP secretion.

Topics: Adult; Base Sequence; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Female; Humans; Hyponatremia; Male; Middle Aged; Molecular Sequence Data; Mutation, Missense; Neurophysins; Pedigree; Polyuria; Protein Precursors; Sequence Analysis, DNA; Vasopressins

A middle-aged woman was admitted to the hospital after being found unconscious at home. A brain CT scan excluded an intracranial bleed or other focal abnormality. Laboratory analysis showed hyponatraemia (sodium: 121 mmol L(-1)) and a low plasma osmolality, with normal sodium excretion and urine osmolality. A diagnosis of hyponatraemic coma was made. The patient was treated with water restriction; 24 h later the sodium was 135 mmol L(-1) and the patient was neurologically fully recovered. The patient, who suffered from von Willebrand's disease, had received desmopressin and ibuprofen for analgesia 2 days before after a dental intervention. She had received desmopressin several times in the past without any complications. A few patients treated with desmopressin for coagulation abnormalities have been reported to develop water intoxication and severe hyponatraemia resulting in seizures and coma. By inhibiting prostaglandin synthesis, non-steroid anti-inflammatory agents (NSAIDs) potentiate the effect of water reabsorption in the renal tubules of vasopressin, therefore enhancing water retention. Desmopressin and NSAIDs should not be used in combination in patients with bleeding disorders, but it is often followed in clinical practice. In addition, this is probably not an unusual situation in patients treated with desmopressin for other 'non-haemorrhagic' indications. This report emphasizes the need for practitioners to be aware of this rare but severe complication.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Coma; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Humans; Hyponatremia; Ibuprofen; Middle Aged; Renal Agents; von Willebrand Diseases

Maternal administration of DDAVP induces maternal and fetal plasma hyponatremia, accentuates fetal urine flow, and increases amniotic fluid volume. Fetal hemorrhage represents an acute stress that results in fetal AVP secretion and reduced urine flow rate. In view of the potential therapeutic use of DDAVP for pregnancies with reduced amniotic fluid volume, we sought to examine the impact of maternal hypotonicity during acute fetal hemorrhage. Chronically catheterized pregnant ewes (130 +/- 2 days) were allocated to control or to DDAVP-induced hyponatremia groups. In the latter group, tap water (2,000 ml) was administered intragastrically to the ewe followed by DDAVP (20 microg bolus, 4 microg/h) and a maintenance intravenous infusion of 5% dextrose water for 4 h to achieve maternal hyponatremia of 10-12 meq/l. Thereafter, ovine fetuses from both groups were continuously hemorrhaged to 30% of estimated blood volume over a 60-min period. DDAVP caused similar degree of reductions in plasma sodium and osmolality in pregnant ewes and their fetuses. In response to hemorrhage, DDAVP fetuses showed greater reduction in hematocrit than control fetuses (14 vs. 10%). Both groups of fetuses demonstrated similar increases in plasma AVP concentration. However, the AVP-hemorrhage threshold was greater in DDAVP fetuses (22.5%) than in control (17.5%). Hemorrhage had no significant impact on plasma osmolality, electrolyte levels, or cardiovascular responses in either group of fetuses. Despite similar increases in plasma AVP, DDAVP fetuses preserved fetal urine flow rates, with values threefold those of control fetuses. These results suggest that under conditions of acute fetal stress of hemorrhage, maternal DDAVP may preserve fetal urine flow and amniotic fluid volume.

Topics: Acute Disease; Animals; Deamino Arginine Vasopressin; Diuresis; Female; Fetal Diseases; Hematocrit; Hemorrhage; Hyponatremia; Kidney; Maternal-Fetal Exchange; Pregnancy; Sheep, Domestic; Water

To investigate the short-term safety of desmopressin in elderly patients with nocturia, with special focus on the risk of hyponatraemia, and to assess the short-term effects on urine output, sleep and voiding patterns.. Patients (72) were recruited from a study using frequency-volume charts, which in turn was preceded by a questionnaire study. Each patient took one 0.2 mg desmopressin tablet at bedtime for three consecutive nights and kept a frequency-volume chart. Serum sodium was assessed in the morning after the first and the third dose. Patients with a mean serum sodium level during treatment deviating more than five units from baseline were considered sensitive to change in serum sodium. Potential predictors for sodium sensitivity and response were investigated with logistic and multiple regression.. All 72 enrolled patients completed the trial; no serious adverse events occurred and no adverse events of severe intensity were recorded. Six patients were sensitive to change in serum sodium. The risk (odds ratio, 95% confidence interval) increased with increasing age (1.3, 1.1-1.6), concomitant cardiac disease (10.0, 0.9-105.8) and increasing baseline 24-h urine output (1.2, 1.0-1.5). Patients sensitive to change in serum sodium were pharmacological responders and desmopressin had a greater effect on their 24-h diuresis, indicating that the drug effect was not limited to the night only.. Desmopressin was well tolerated in elderly patients with nocturia, but the results suggest that serum sodium should be measured before and after a few days of treatment.

Topics: Aged; Aged, 80 and over; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Male; Regression Analysis; Renal Agents; Sleep; Sodium; Urination; Urination Disorders

Topics: Administration, Intranasal; Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Hemostatics; Histiocytosis, Langerhans-Cell; Humans; Hyponatremia; Severity of Illness Index; Water Intoxication

Desmopressin diacetate arginine vasopressin (DDAVP) is a synthetic analogue of the mammalian arginine vasopressin used in the treatment of central diabetes insipidus, bleeding disorders, and incontinence. The primary adverse reaction associated with DDAVP is hypotonic hyponatremia. Hyponatremia has been reported in adults treated with DDAVP for Von Willebrand's disease and hemophilia and in children treated for enuresis, but as yet few cases of hyponatremia developing in enuretic adults treated with DDAVP have been reported. We report the cases of two elderly women taking DDAVP for nocturnal polyuria who developed severe hyponatremia. One patient died in the hospital.

Topics: Aged; Aged, 80 and over; Deamino Arginine Vasopressin; Enuresis; Fatal Outcome; Female; Humans; Hyponatremia; Polyuria; Renal Agents

Topics: Carcinoma, Papillary; Carcinoma, Renal Cell; Deamino Arginine Vasopressin; Female; Hemorrhagic Disorders; Humans; Hyponatremia; Kidney Neoplasms; Laparoscopy; Middle Aged; Neoplasms, Multiple Primary; Nephrectomy; Postoperative Complications; Seizures; Thyroid Neoplasms; Thyroidectomy; von Willebrand Diseases

Seven cases of cerebral oedema have been observed in enuretic children during low-dose desmopressin (DDAVP) treatment given in a dose of 7-21 microg daily in the Czech Republic between 1995 and 1999, after the drug started to be marketed for this indication and delivered in simple bottles with a dropper. All seven children (age 5-11 years, four boys) experienced a period of unconsciousness but all recovered without sequelae. In most cases, safety measures were underestimated and natraemia was not regularly controlled. Two children developed cerebral oedema after excessive water intake in preparation for uroflowmetry, another one drank much during a hot summer day, in one diabetes insipidus was not recognised and two children were clearly non-compliant with reduced fluid intake on a long-term basis. Only in one child, no risk factor was found. Conclusion. Proper selection and instruction of patients is needed to avert cerebral oedema during treatment with desmopressin for nocturnal enuresis.

Topics: Brain Edema; Child; Child, Preschool; Consumer Product Safety; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Hyponatremia; Male; Renal Agents; Water Intoxication

Desmopressin, a synthetic analogue of the antidiuretic hormone, is an effective medication for primary nocturnal enuresis for both children and adults. Its safety is well established. Although it has a favorable side effect profile, because of its pharmacological effect, intranasal desmopressin can rarely induce water intoxication with profound hyponatremia if given without adequate restriction of water intake. The authors describe an adult patient with water intoxication and severe hyponatremia accompanied by loss of consciousness and seizures after 2-day intranasal administration of desmopressin. The present and the previously reported cases emphasize the need for greater awareness of the development of this serious and potentiallyfatal complication. In addition, to adjust the drug to the lowest required dosage, adequate restriction of water intake is recommended, and serum levels of sodium should be measured periodically to allow for early detection of water intoxication and hyponatremia.

Topics: Administration, Intranasal; Adult; Coma; Deamino Arginine Vasopressin; Drinking; Enuresis; Female; Humans; Hyponatremia; Seizures; Water Intoxication

Topics: Adult; Deamino Arginine Vasopressin; Enuresis; Humans; Hyponatremia; Intellectual Disability; Male; Renal Agents; Seizures

More than 250,000 patients with nocturnal enuresis have been treated with DDAVP in the United States since 1989. It adequately controls nocturnal enuresis in over half of patients with significant improvement in their quality of life. Although the overall incidence of adverse effects associated with treatment of nocturnal enuresis with DDAVP is low, it is not a benign drug particularly when used in patients at extreme of age. A review of the literature and the present case demonstrate that the potential risk factors for hyponatremia following administration of DDAVP include hepatic disease, surgery, stress, pain, renal disorder, excessive fluid intake, and increased dose of DDAVP. Potentially serious side effects of DDAVP administration such as hyponatremia and seizure may be prevented by close monitoring of serum electrolytes, urine output, as well as fluid restriction and avoidance of solutions with low-sodium content.

Topics: Adult; Cerebral Palsy; Deamino Arginine Vasopressin; Drug Monitoring; Enuresis; Humans; Hyponatremia; Intellectual Disability; Male; Renal Agents; Risk Factors; Sodium

How does a neuron, challenged by an increase in synaptic input, display a response that is independent of the initial level of activity? Here we show that both oxytocin and vasopressin cells in the supraoptic nucleus of normal rats respond to intravenous infusions of hypertonic saline with gradual, linear increases in discharge rate. In hyponatremic rats, oxytocin and vasopressin cells also responded linearly to intravenous infusions of hypertonic saline but with much lower slopes. The linearity of response was surprising, given both the expected nonlinearity of neuronal behavior and the nonlinearity of the oxytocin secretory response to such infusions. We show that a simple computational model can reproduce these responses well, but only if it is assumed that hypertonic infusions coactivate excitatory and inhibitory synaptic inputs. This hypothesis was tested first by applying the GABA(A) antagonist bicuculline to the dendritic zone of the supraoptic nucleus by microdialysis. During local blockade of GABA inputs, the response of oxytocin cells to hypertonic infusion was greatly enhanced. We then went on to directly measure GABA release in the supraoptic nucleus during hypertonic infusion, confirming the predicted rise. Together, the results suggest that hypertonic infusions lead to coactivation of excitatory and inhibitory inputs and that this coactivation may confer appropriate characteristics on the output behavior of oxytocin cells. The nonlinearity of oxytocin secretion that accompanies the linear increase in oxytocin cell firing rate reflects frequency-facilitation of stimulus-secretion coupling at the neurohypophysis.

Topics: Animals; Bicuculline; Computer Simulation; Deamino Arginine Vasopressin; Electrophysiology; Excitatory Postsynaptic Potentials; GABA Antagonists; gamma-Aminobutyric Acid; Hyponatremia; Infusions, Intravenous; Male; Microdialysis; Models, Neurological; Neural Inhibition; Neurons; Osmolar Concentration; Oxytocin; Rats; Rats, Sprague-Dawley; Rats, Wistar; Saline Solution, Hypertonic; Sodium; Stimulation, Chemical; Supraoptic Nucleus; Vasopressins

In a state of chronic arginine vasopressin (AVP) excess, the action of antidiuresis has been attenuated, resulting in some water diuresis. This state has been termed an "AVP escape" phenomenon. The present study was designed to determine what mechanisms underlie this attenuation in renal concentrating ability, which is found in chronic AVP excess, both in the presence and absence of volume expansion.. Two groups of experimental rats were established. One group received solid chow with water ad libitum. The second group received chow, which was offered as a liquid diet. Both groups received subcutaneous administration of 1-deamino-8-D-arginine vasopressin (dDAVP) at 5 ng/h for the entire observation period of one week. Over the course of the observation period, tissue levels of aquaporin-2 (AQP-2) mRNA and protein were measured. Levels of AVP V2 receptor were monitored, both by measuring mRNA levels and by ligand-binding studies using [3H]AVP. Tissue levels of cAMP also were determined.. Experimental rats with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) had severe hyponatremia below 120 mmol/L, and impaired urinary concentrating ability, during the seven-day observation period. In contrast, the dDAVP-excess rats, given solid chow, maintained maximally concentrated urine and normal levels of serum sodium. The down-regulation of AVP V2 receptor function was comparable in the two groups. The maximal binding capacity (Bmax) fell to the nadir on day 2 and was thereafter suppressed at approximately 60% of control rats during the experiment. Up-regulation of AQP-2 mRNA expression was found, but this up-regulation was significantly less in the SIADH rats compared with the dDAVP-excess rats (153.5 +/- 29.8% vs. 323.7 +/- 23.8% on day 7, P < 0.05). This differential response between these two groups was affirmed by measured differences in AQP-2 protein levels, both in tissue and in urinary excretion.. These results indicate that the attenuated regulation of the AQP-2 gene leads to the decrease in urinary concentrating ability in the experimental SIADH rats, suffering from hypervolemic state, compared with the normonatremic rats receiving AVP. Either hypervolemia or hypotonicity may diminish the post-receptor signaling of AVP in renal collecting duct cells, under the chronic AVP excess state found in SIADH.

Topics: Animals; Aquaporin 2; Aquaporin 6; Aquaporins; Arginine Vasopressin; Cyclic AMP; Deamino Arginine Vasopressin; Diuresis; Gene Expression; Hyponatremia; Inappropriate ADH Syndrome; Kidney Concentrating Ability; Kidney Medulla; Male; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Renal Agents; RNA, Messenger; Time Factors

Hyponatremia is a common complication of intracranial disease or surgery. An evaluation should be undertaken to determine whether cerebral salt wasting (CSW) or inappropriate secretion of antidiuretic hormone is present as a cause. Since the treatment principles are completely different in the two pathological states, differential diagnosis is very important. CSW is defined as the renal loss of sodium leading to hyponatremia and decreased extracellular fluid volume. In the literature, it has been noted that mineralocorticoid administration can be useful in CSW cases. We herein present an 11-year-old boy who developed hyponatremic seizures after intracranial tumor resection. He was diagnosed with CSW on the basis of high urinary sodium excretion and increased urine output, together with signs and symptoms of dehydration. Despite intensive fluid and salt therapy, we were unable to decrease the urinary output. Therefore, fludrocortisone therapy was administered and his urinary output and sodium excretion were decreased and his serum sodium level was normalized. In conclusion, in addition to fluid and salt replacement, mineralocorticoid supplementation also seems to be a safe and effective treatment for CSW.

Topics: Astrocytoma; Brain Neoplasms; Child; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Drug Administration Schedule; Fludrocortisone; Follow-Up Studies; Humans; Hyponatremia; Male; Natriuresis; Postoperative Complications

Correction of hyponatremia can be complicated by brisk free water diuresis with a rise in the serum sodium (s-Na) in excess of the generally accepted rate of 10-15 mmol/l/24 hours. We describe this complication and its treatment with desmopressin (dD-AVP), in a 56-year-old female with severe hyponatremia secondary to polydipsia and antidiuretic (ADH) activity. The patient developed a large free water diuresis with a markedly dilute urine (urine osmolality 61 mmol/kg) and a rise in the serum sodium of 19 mmol/l in 19 hours despite the addition of large volumes of free water intravenously and orally. To reduce the free water excretion, desmopressin (dD-AVP) 8 microg was given intravenously. This resulted in a rise in the urinary osmolality, a reduction in the urine volume, and a 2 mmol/l reduction in the serum sodium. Thereafter, the serum sodium rose 4 mmol/l in 24 hours. There were no neurological sequellae. In cases of appropriate but rapid correction of hyponatremia secondary to rapid free water diuresis, dD-AVP can safely reduce the free water excretion, slow the rate of correction of the serum sodium and simplify the fluid therapy of the patient.

Topics: Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Middle Aged; Renal Agents; Time Factors

A 42-year-old female with von Willebrand's disease was managed with desmopressin and tranexamic acid to aid haemostasis following a vaginal hysterectomy. Severe acute hyponatraemia (134 to 108 mmol/l) developed over two days, culminating in a generalized tonic-clonic seizure and cerebral oedema. Fluid restriction, cessation of desmopressin and hypertonic saline administration led to a full recovery. Desmopressin is known to reduce free water elimination and produce hyponatraemia, but its extent and rate of development in this patient was surprising. Close monitoring of serum sodium and fluid balance is recommended in these patients.

Topics: Acute Disease; Adult; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Hyponatremia; Hysterectomy; Postoperative Hemorrhage; Tranexamic Acid; von Willebrand Diseases

We report the cases of two children with cranial diabetes insipidus who were treated with lamotrigine for seizures and who had accompanying changes in desmopressin requirements. Lamotrigine is a new anticonvulsant chemically unrelated to other existing antiepileptic drugs. Studies suggest it acts at voltage-sensitive sodium channels and also decreases calcium conductance. Both of these mechanisms of action are shared by carbamazepine, which can cause hyponatraemia secondary to inappropriate secretion of antidiuretic hormone. It is possible that the effect of lamotrigine on fluid balance in the cases described is also centrally mediated.

Topics: Adolescent; Anticonvulsants; Child; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Dose-Response Relationship, Drug; Female; Humans; Hyponatremia; Hypopituitarism; Lamotrigine; Seizures; Triazines

Topics: Child; Deamino Arginine Vasopressin; Enuresis; Humans; Hyponatremia; Male; Renal Agents; Seizures

The case of a 6 year old child who presented with convulsions and coma after unsupervised self administration of intranasal desmopressin (DDAVP) for nocturnal enuresis is presented. Children with enuresis can be embarassed by their condition and may believe that multiple doses of their nasal spray may bring about a rapid resolution. Water intoxication is an uncommon but serious adverse effect of treatment with intranasal DDAVP. These patients may present with seizure, mental state changes, or both. Basic management consists of stopping the drug, fluid restriction, and suppressive treatment for seizures. Recovery is usually rapid and complete. Administration of the nasal spray in children should be supervised by parents to prevent highly motivated children from accidental overdose. The risks of high fluid intake need to be carefully explained to both parents and children.

Topics: Child; Deamino Arginine Vasopressin; Enuresis; Humans; Hyponatremia; Male; Renal Agents; Seizures

Disturbances of osmoregulation, leading to diabetes insipidus and hyponatraemia are well known complications after surgery in the sella region. This study was performed to examine the prevalence and predictors of polyuria and hyponatraemia after a complete and selective removal of pituitary adenomas was attempted via the transnasal-transsphenoidal approach.. 1571 patients with pituitary adenomas (238 Cushing's disease, 405 acromegaly, 534 hormonally inactive adenomas, 358 prolactinoma, 23 Nelson's syndrome, and 13 thyrotropinoma) were daily examined within a 10-day postoperative inpatient observation period. Prevalence of patterns of polyuria (> 2500 ml) and oliguria/hyponatraemia (< 132 mmol/l) were surveyed as well as predictors of postoperative morbidity.. 487 patients (31%) developed immediate postoperative hypotonic polyuria, 161 patients (10%) showed prolonged polyuria and 37 patients (2.4%) delayed hyponatraemia. A biphasic (polyuria-hyponatraemia) and triphasic (polyuria-hyponatraemia-polyuria) pattern was seen in 53 (3.4%) and 18 (1.1%) patients, respectively. Forty-one patients (2.6%) displayed immediate postoperative (day 1) hyponatraemia. Altogether, 8.4% of patients developed hyponatraemia at some time up to the 10th day postoperative, with symptomatic hyponatraemia in 32 patients (2.1%). Risk analysis showed that patients with Cushing's disease had a fourfold higher risk of polyuria than patients with acromegaly and a 2.8-fold higher risk for postoperative hyponatraemia. Younger age, male sex, and intrasellar expansion were associated with a higher risk of hypotonic polyuria, but this was not considered clinically relevant.. The analysis illustrates that disturbances in osmoregulation resulting in polyuria and pertubations of serum sodium concentration are of very high prevalence and need observation even after selective transsphenoidal surgery for pituitary adenomas, especially in patients with Cushing's disease.

Topics: Acromegaly; Adenoma; Adult; Cushing Syndrome; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Male; Middle Aged; Pituitary Neoplasms; Polyuria; Postoperative Complications; Prevalence; Prolactinoma; Renal Agents; Risk Factors; Water-Electrolyte Imbalance

Desmopressin (DDAVP) may be used to augment the action of factor VIII in mild haemophilia. Its use has been associated with serious adverse effects. We report a case of a three-year-old child with a family history of haemophilia who suffered complications due to severe acute hyponatraemia following the administration of this drug for post-tonsillectomy bleeding.

Topics: Adenoidectomy; Apnea; Blood Loss, Surgical; Child, Preschool; Deamino Arginine Vasopressin; Factor VIII; Hemophilia A; Hemostasis, Surgical; Hemostatics; Humans; Hyponatremia; Male; Postoperative Hemorrhage; Seizures; Tonsillectomy

Recent results indicate that renal escape from vasopressin-induced antidiuresis is accompanied by a marked downregulation of whole kidney aquaporin-2 (AQP-2) protein and mRNA expression. However, in those studies, the escaped animals were also markedly hypo-osmolar compared to controls as a result of water loading during antidiuresis. The present studies evaluated whether systemic or local osmolality contributes to the downregulation of AQP-2 expression in this model. In the first study, two groups of 1-deamino-[8-D-arginine]-vasopressin (dDAVP)-infused rats were water-loaded; after establishment of escape, one group was then water-restricted for 4 d to reverse the escape, whereas the other group continued daily water loading. Whole kidney AQP-2 protein was measured by Western blotting, and inner medulla AQP-2 mRNA was determined by Northern blotting. Results were compared to dDAVP-infused rats fed solid chow. After 4 d of water restriction, urine volume decreased to the same level as in the rats on solid chow; however, plasma sodium concentrations and plasma osmolality remained low. Despite maintenance of significant hypo-osmolality, rats in which escape was subsequently reversed by water restriction reestablished high dDAVP-stimulated kidney levels of AQP-2 after 4 d of water restriction. In the second study, AQP-2 expression was evaluated in different regions of kidneys from water-loaded rats undergoing escape from antidiuresis. Despite markedly different interstitial osmolalities, significant downregulation of AQP-2 expression compared to dDAVP-infused control rats was seen in the inner medulla, outer medulla, and cortex. Thus, neither systemic nor interstitial osmolality appears to appreciably be correlated with downregulation of kidney AQP-2 expression during escape from antidiuresis. These results therefore suggest that additional vasopressin- and osmolality-independent factors, likely related to the effects of extracellular fluid volume expansion, also regulate kidney AQP-2 expression in rats.

Topics: Analysis of Variance; Animals; Aquaporin 2; Aquaporin 6; Aquaporins; Blotting, Northern; Blotting, Western; Culture Techniques; Deamino Arginine Vasopressin; Diuresis; Down-Regulation; Extracellular Space; Hyponatremia; Kidney Medulla; Male; Osmolar Concentration; Rats; Rats, Sprague-Dawley; Renal Agents; RNA; Sensitivity and Specificity; Sodium; Water Deprivation

Intranasal desmopressin has been used extensively to treat primary nocturnal enuresis. While it has proven to be a safe, effective agent for many who are affected by this condition, the potential for complications exists.. To report a case of severe hyponatremia associated with a generalized tonic-clonic seizure in a 10-year-old boy who had been receiving intranasal desmopressin nightly for nocturnal enuresis and to briefly review therapeutic options for nocturnal enuresis; and to present the role of desmopressin.. Georgetown University Medical Center, Washington, DC.. Fluid restriction and intravenous isotonic saline solution with 5% dextrose was administered to raise the serum sodium level.. Prevention of further seizures with normalization of serum sodium levels without any obvious neurological sequelae.. This case illustrates the importance of weighing the benefits and risks of intranasal desmopressin therapy.

Topics: Child; Deamino Arginine Vasopressin; Enuresis; Epilepsy, Tonic-Clonic; Humans; Hyponatremia; Male; Renal Agents

Topics: Child; Deamino Arginine Vasopressin; Enuresis; Humans; Hyponatremia; Male; Renal Agents; Seizures

Topics: Child; Deamino Arginine Vasopressin; Enuresis; Humans; Hyponatremia; Male; Renal Agents; Seizures

To evaluate the effectiveness and mode of action of the osmotic diuretic mannitol to prevent the development of acute hyponatremia in a setting designed to mimic the acute hyponatremia observed on the day of surgery.. Hyponatremia (129+/-1 mM, fall of 10+/-1 mM, p <0.01) was induced by the intraperitoneal administration of half-isotonic saline plus DDAVP to rats (n = 8); hyponatremia was due to a positive balance of electrolyte-free water (EFW). Rats given mannitol (10 mmol/kg body wt) in addition to the hypotonic saline plus DDAVP had only a minor degree of hyponatremia (plasma [Na+] 136+/-1 mM, fall 3+/-2 mM, p >0.05). All the mannitol given was excreted over the 16 h of observation, but the urine volume was not higher in these rats. The higher rate of excretion of EFW was due to a marked reduction in the rate excretion of Na+ with mannitol. This antinatriuresis was also present when mannitol was given intravenously.. Although mannitol increased the excretion of EFW, the mechanism required an enhanced renal reabsorption of Na+ rather than an increase in the urine flow rate.

Topics: Animals; Deamino Arginine Vasopressin; Diuretics, Osmotic; Hyponatremia; Male; Mannitol; Natriuresis; Postoperative Complications; Rats; Rats, Wistar; Renal Agents

Topics: Child; Coma; Deamino Arginine Vasopressin; Drug Therapy, Combination; Enuresis; Humans; Hyponatremia; Male; Seizures

Topics: Administration, Intranasal; Child, Preschool; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Seizures

Topics: Child; Child, Preschool; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Hyponatremia; Infant; Infant, Newborn; Male; Renal Agents; Seizures; Water Intoxication

Axonal injury to hypothalamic magnocellular vasopressin (AVP) and oxytocin (OT) neurons causes degeneration of a substantial subpopulation of these neurons. In this study, we investigated the influence of osmolality on this injury-induced cell death. Normonatremic, chronically hypernatremic, and chronically hyponatremic rats received pituitary stalk compression (SC), which causes degeneration of AVP and OT terminals in the neurohypophysis. Twenty-one days after SC, rats were perfused and hypothalami were serially sectioned and alternately stained for AVP-neurophysin and OT-neurophysin immunoreactivities. Normonatremic and hypernatremic rats exhibited a triphasic pattern of water intake after SC, with peak intakes 3 times higher than those exhibited by sham-operated normonatremic rats. In contrast, hyponatremic SC rats exhibited peak water intakes of 600 ml/24 hr, approximately 9-10 times the water intakes of sham-operated normonatremic rats. In normonatremic rats, SC caused degeneration of 65% of the AVP neuron population in the SON and 73% in the PVN, but only 31% of the OT neuron population in the SON and 35% in the PVN. Similar results were found in hypernatremic rats after SC. However, in hyponatremic rats SC caused degeneration of 97% of the AVP neuron population in the SON and 93% in the PVN, and 90% of the OT neuron population in the SON and 84% in the PVN. Our results, therefore, demonstrate that injury-induced degeneration of magnocellular AVP and OT neurons is markedly exacerbated by chronic hypo-osmolar conditions, but neuronal survival is not enhanced by chronic hyperosmolar conditions.

Topics: Animals; Axons; Cell Count; Cell Death; Cell Survival; Deamino Arginine Vasopressin; Drinking; Hypernatremia; Hyponatremia; Male; Nerve Degeneration; Neurons; Oxytocin; Rats; Rats, Sprague-Dawley; Sodium; Sodium Chloride; Time Factors; Vasopressins

In hyponatremia related to syndrome of inappropriate antidiuretic hormone (SIADH), hypouricemia is explained primarily by the high uric acid clearance rate that results from the decrease in tubular uric acid reabsorption. This modification of tubular handling of uric acid is considered to be induced by the increase in the "effective vascular volume". This study was designed to determine if V1-receptor stimulation participates in the development of a high uric acid clearance rate as in SIADH, in which the antidiuretic hormone acts on V1 and V2 receptors. Therefore, the urate clearance rate was measured in seven volunteers with 1-desamino-8-D-arginine vasopressin (dDAVP)-induced hyponatremia, with dDVAP stimulating exclusively the V2 receptors (Group I), and in six patients with SIADH (Group II) during both normo- and hyponatremia. As expected, in both groups, the serum uric acid concentration decreased during hyponatremia, but did so to a larger extent in the patients with SIADH (-53% versus -29%, P < 0.02). Despite similar levels of hyponatremia (126 +/- 5 mmol/L and 125 +/- 5.5 mmol/L), of hypoproteinemia (64 +/- 5 g/L and 63 +/- 5 g/L) and of salt excretion (FENa, 0.66 +/- 0.28% and 0.73 +/- 0.25%), the urate clearance (8.3 +/- 3.3 mL/min) and the fractional excretion of filtered uric acid (5.7 +/- 2%) in Group I were not significantly different during hyponatremia than during normonatremia (6.4 +/- 1.5 mL/min and 5.4 +/- 0.9%). On the other hand, in Group II, both parameters were increased (17.8 +/- 2.9 mL/min and 19.6 +/- 5.3%; P < 0.001) and both values were higher than in the dDAVP-induced hyponatremia (P < 0.01). Additionally, the administration of a potent V1-receptor agonist (triglycyl-lysine-vasopressin) in a patient with central diabetes insipidus with preexisting dDAVP-induced hyponatremia produced a rapid increase of urate clearance. Because dDAVP acts only on the V2 receptors, these data suggest that the higher urate clearance observed during hyponatremia related to SIADH is not only the consequence of an increased "effective vascular volume," but that V1-receptor stimulation also contributes to it, by a mechanism that remains to be determined.

Topics: Adult; Body Water; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Hyponatremia; Inappropriate ADH Syndrome; Kidney Tubules, Proximal; Lypressin; Male; Metabolic Clearance Rate; Natriuresis; Receptors, Vasopressin; Sodium; Terlipressin; Uric Acid

Desmopressin (DDAVP) is frequently used in the treatment of primary isolated enuresis nocturna if other approaches have failed. We report a further case of hyponatraemia and cerebral convulsion due to water intoxication after intranasal DDAVP application by a 6 year-old boy with enuresis.. Although adverse reactions in DDAVP (e.g. hyponatraemia) are rare, it should not be considered as the first choice treatment of enuresis nocturna and only be used with caution.

Topics: Child; Deamino Arginine Vasopressin; Diseases in Twins; Enuresis; Humans; Hyponatremia; Male; Renal Agents; Seizures; Water Intoxication

A prospective observational study of the pathophysiology of sodium and water disorders in patients with pituitary region tumours after surgical excision was carried out in 20 patients. Serial pre-operative and post-operative fluid and sodium balance, plasma and urine elctrolyte biochemistry and their derived parameters, and circulating hormones associated with fluid balance, atrial natriureic peptide (ANP) and antidiuretic hormone (ADH) were documented to correlate with the patients' clinical conditions. Ten out of these twenty cases developed diabetes insipidus (DI) requiring ADH replacement therapy, although in the majority (6 cases), this way only a transient event. Of the nine patients who developed hyponatraemia, six had symptoms such as impaired consciousness and convulsions. Four patients developed alternating hypoatraemia and hypernatraemia, which constituted a difficult group, where appropriate sodium and fluid management, and ADH replacement therapy were based upon twice daily plasma and urine biochemistry and their derived parameters. Whilst DI in this group of patients was the result of a low circulating ADH level, hyponatraemia was not associated with an exaggerated ADH activity (6.0 +/- 2.3 vs 7.4 +/- 2.3 pmol/ml, mean +/- SEM). Rather, hyponatraemia was strongly associated with an elevated circulating ANP concentration (82.4 +/- 10.5 vs 30.0 +/- 3.1 pmol/ml, mean +/- SEM, p < 0.001), resulting in salt wasting and hypovolaemia.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Child; Creatinine; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Male; Middle Aged; Pituitary Neoplasms; Postoperative Complications; Prospective Studies; Sodium; Urea; Vasopressins; Water; Water-Electrolyte Balance

Hyponatremia is a common electrolyte abnormality that causes symptoms as a result of swelling of brain cells. We evaluated the impact of a negative balance for sodium (Na) and potassium (K) salts on the intracellular fluid (ICF) volume, emphasizing the role of anions excreted with K. Rats (N = 10) were deprived of food and water for 24 hours. They received half-isotonic saline to expand their extracellular fluid (ECF) volume by 20%; a long acting antidiuretic hormone (DDAVP) preparation was given to prevent the excretion of electrolyte-free water. The concentration of Na in plasma fell from 139 +/- 1 mM to 120 +/- 2 mM 24 hours after the infusion of hypotonic saline (P < 0.01). Since these rats had a small negative balance for water (4 +/- 1 ml), hyponatremia was due to their negative balances for Na (2.2 +/- 0.3 mmol) and K (2.2 +/- 0.1). There were negative balances for Cl (2.4 +/- 0.2 mmol) and phosphate (0.7 +/- 0.05 mmol). Despite the negative balance for NaCl, the ECF volume as assessed by 3H-inulin space was not contracted. In this model for acute hyponatremia, its basis was electrolyte loss, but the ECF volume was not contracted, suggesting that water shifted from the ICF to the ECF. Hyponatremia is associated with cell swelling only if its cause is positive water balance and/or is loss of Na from the ECF. It is critical to examine the urine anions to determine the compartment of origin of particles excreted with K and thereby whether hyponatremia will result in overall expansion or contraction of the ICF volume.

Topics: Animals; Anions; Deamino Arginine Vasopressin; Hyponatremia; Hypotonic Solutions; Intracellular Fluid; Male; Osmolar Concentration; Potassium; Rats; Rats, Wistar; Renal Agents; Sodium; Water-Electrolyte Balance

DDAVP-related hyponatremia induces a blood volume expansion, but the analysis of fluid distribution in the vascular compartment has given controversial results in previous animal and human studies. In 5 healthy males, hyponatremia was induced by DDAVP and a free water intake during 3 days. Serum sodium concentration decreased from 138 +/- 0.8 mEq/L to 123 +/- 2.7 mEq/L on day 3. The plasma volume measured by dilution of marked albumin rose from 3033 +/- 230 ml to 3320 +/- 295 ml (p < 0.01). The mean corpuscular volume measured by microhematocrit increased slightly from 91.5 +/- 3.8 pl to 92.6 +/- 3.7 pl (p < 0.02). The red blood cell volume calculated with hematocrit and plasma volume did not change significantly (2565 ml to 2567 ml; not significant). In the present work, we demonstrated that in males the expansion of the plasma compartment almost completely amounted for the water retention in the intravascular volume. The erythrocyte volume increased only slightly, a finding that is consistent with an almost perfect adaptation of the erythrocyte cells to the hypoosmolality.

Topics: Administration, Intranasal; Adult; Blood Volume; Deamino Arginine Vasopressin; Erythrocyte Indices; Erythrocytes; Hematocrit; Hemodynamics; Humans; Hyponatremia; Male; Renal Agents; Reproducibility of Results; Sodium; Water

Both central diabetes insipidus (DI) and a high rate of excretion of sodium (Na) and chloride (Cl) contributed to the development of polyuria and dysnatremia in two patients during the acute postoperative period after neurosurgery. To minimize difficulties in diagnosis and projections for therapy, two available (but not often used) clinical tools were helpful. First, the osmole excretion rate early on revealed the co-existence of central DI and an osmotic diuresis. The osmoles excreted were largely Na salts; after antidiuretic hormone acted, this electrolyte diuresis caused the urine flow rate to be much higher than otherwise anticipated. Interestingly, part of this saline diuresis occurred when the extracellular fluid volume was contracted. The tool to explain the basis for the dysnatremias was a tonicity balance. Hypernatremia, which developed before treatment of central DI, was primarily a result of a positive balance for Na rather than a large negative balance for water. Moreover, hyponatremia that developed once antidiuretic hormone acted was primarily a result of a negative balance for Na; the urine volume was large and its Na concentration was hypertonic. To prevent a further decline in the plasma Na concentration, either the Na concentration in the urine should be decreased by provision of urea or a loop diuretic while replacing all unwanted water and electrolyte losses; alternatively, the fluid infused should have a similar Na concentration and volume as the urine (infuse hypertonic saline).

Topics: Adult; Deamino Arginine Vasopressin; Diabetes Insipidus; Diuresis; Female; Humans; Hypernatremia; Hyponatremia; Male; Natriuresis; Osmosis; Postoperative Complications; Sodium; Vasopressins

Previous studies have demonstrated that in adult rats with chronic hyponatremia, both symptoms of encephalopathy and mortality largely depend upon the gender of the animal and the presence of elevated plasma levels of vasopressin (AVP). Since effects of AVP on blood vessels may be gender dependent, the present study was designed to compare the effects of chronic (4 days) hyponatremia on cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2), and cerebral perfusion index (CPI) in adult male and female rats. CBF (intra-arterial 133Xe injection method) and CMRO2 (arteriovenous difference of cerebral oxygen contentxCBF) were measured in normonatremic and hyponatremic (hyponatremia induced with 140 mmol/L glucose and either AVP or desmopressin [dDAVP], plasma sodium = 100 to 110 mmol/L) adult rats of both genders. The CPI was assessed from magnetic resonance imaging of the transit of magnetic susceptibility contrast agent through the brain. Female rats with AVP-induced chronic hyponatremia had a 36% decrease in CBF and a 60% decrease in CMRO2. In male animals, both parameters were not different from control values. AVP-induced hyponatremia resulted in a 45% decrease in CPI in female rats, but hyponatremia induced with dDAVP did not affect CPI in either male or female rats. Chronic (4 days) administration of AVP did not affect CPI in either male or female normonatremic rats. When rats with AVP-induced chronic hyponatremia were pretreated with estrogen, the CPI in males was not different from that in females. Our results demonstrate that during AVP-induced chronic hyponatremia in female rats, there is significant depression of both oxygen utilization and blood flow in the brain.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Brain; Brain Diseases; Cerebrovascular Circulation; Chronic Disease; Deamino Arginine Vasopressin; Estrogens; Female; Hyponatremia; Magnetic Resonance Imaging; Male; Oxygen Consumption; Potassium; Rats; Sex; Sodium

Rats were infused with a selective agonist of vasopressin V2 receptors (1-desamino-D-arginine vasopressin; DDAVP) at two different doses (1 or 5 ng/h) and fed a liquid formula to produce both moderate (plasma [Na+] = 119-124 mmol/l) and severe (plasma [Na+] = 106-112 mmol/l) hyponatremia. Whole body water and electrolyte contents were analyzed after 1, 7, and 14 days of hyponatremia to assess the relative contributions from water retention and sodium depletion to hyponatremia of varying duration and severity. Body water of the hyponatremic rats was significantly increased over normonatremic control rats after 1 and 7 days; after 14 days, the 1 ng/h DDAVP-infused rats also had elevated body water, but the 5 ng/h DDAVP-infused rats returned to levels not significantly different from controls. Body Na+ and Cl- both decreased significantly after 1 day of hyponatremia, and these decreases were sustained for 14 days; measured decreases were significantly greater in the more hyponatremic rats compared with the less hyponatremic rats. Body K+ of the 1 ng/h DDAVP-infused rats was not different from control rats, but significant K+ decreases occurred in the 5 ng/h DDAVP-infused rats after 7 and 14 days. Analysis of the measured plasma Na+ concentrations vs. those predicted by the changes in body water and sodium showed that both water retention and sodium losses were necessary to predict the final plasma [Na+]. However, the relative contribution from each varied with the duration of induced hyponatremia: acutely, water retention was the major cause of decreased plasma [Na+], but sodium depletion became predominant with longer periods of sustained hyponatremia.

Topics: Animals; Body Water; Body Weight; Chlorides; Deamino Arginine Vasopressin; Disease Models, Animal; Hyponatremia; Inappropriate ADH Syndrome; Male; Potassium; Rats; Rats, Sprague-Dawley; Sodium

Previous studies from this laboratory showed that both acute and chronic hyponatremia impaired active brain buffering. These studies were performed to determine whether correcting the plasma sodium restored normal buffering in hyponatremic rats. Acute (1- and 2-day) and chronic (7- and 14-day) hyponatremia was induced in male Sprague-Dawley rats by constant desmopressin administration combined with a liquid diet. Plasma sodium was corrected by stopping desmopressin for 6 h, substituting solid chow, and allowing free access to water. Studies were performed 24 h later. Uncorrected hyponatremic rats who continued to receive desmopressin and liquid diet served as controls. Brain pH was determined by [31P]NMR in rats anesthetized with N2O and paralyzed with pancuronium. Brain buffering was determined by the response to CO2 loading. Resting brain pH was the same in corrected and uncorrected rats, but the two groups responded differently to CO2 loading. Thus, 55 min after ventilation with 20% CO2, corrected rat brain pH was 0.13 pH units higher than in uncorrected rats despite statistically similar changes in CO2 tension and arterial pH in both groups. Moreover, 15 min into recovery from CO2 exposure, brain pH in corrected rats overshot resting pH by 0.07, whereas no overshoot occurred in uncorrected rats. Buffering in corrected rats was identical to that shown previously in normonatremic rats. The complete restoration of late-phase buffering achieved by normalizing the plasma sodium of hyponatremic rats indicates that at least some portion of active hydrogen ion transport is sodium dependent in the brain.

Topics: Acute Disease; Animals; Brain Chemistry; Buffers; Carbon Dioxide; Chronic Disease; Deamino Arginine Vasopressin; Diet; Hydrogen-Ion Concentration; Hyponatremia; Male; Rats; Rats, Sprague-Dawley; Sodium

The effects of acute and chronic water intoxication induced by the administration of oral water and arginine vasopressin (AVP) or 1-deamino-8-D-arginine-vasopressin (DDAVP) on blood acid-base equilibrium and aldosterone, corticosterone, and thyroxine secretion were studied in rats. Acute hyponatremia (3 hours) was associated with normal bicarbonate and blood acid-base equilibrium and a decrease in aldosterone and thyroxine concentrations, while corticosterone was increased. When similar levels of hyponatremia (serum sodium 110 mEq/L) were maintained for 24 or 72 hours, a normal serum bicarbonate concentration was observed, but blood acid-base equilibrium showed a mixed respiratory and metabolic alkalosis. Blood pH was negatively correlated with serum sodium concentration (R = -0.65; p < 0.001), as was the metabolic alkalosis (base excess; R = -0.64; p < 0.001) and the aldosterone concentration (R = -0.52; p < 0.01), while the PCO2 was positively correlated (R = +0.49; p < 0.01). Hyperaldosteronism was similar whether hyponatremia was induced with AVP or DDAVP and was observed even for mild hyponatremia. When hyponatremia was induced by a high water and salt intake (2.5% D-glucose, 0.45% NaCl; 15% body weight), aldosterone concentration was as high (about three times control values) as in rats with similar levels of hyponatremia but with a salt-free diet. The high salt intake was associated with a more severe metabolic alkalosis (base excess +5,5 mEq/L). In chronic hyponatremia, corticosterone and thyroxine values were normal. In hyponatremia related to syndrome of inappropriate secretion of antidiuretic hormone, the normal serum bicarbonate level is an expected observation; as in acute water intoxication, it stays normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid-Base Equilibrium; Aldosterone; Alkalosis; Animals; Arginine Vasopressin; Bicarbonates; Corticosterone; Deamino Arginine Vasopressin; Hydrogen-Ion Concentration; Hyponatremia; Male; Rats; Rats, Wistar; Thyroxine

Studies from these and other laboratories have shown that hyponatremia causes marked depletion of both electrolytes and organic osmolytes from the brain. The present studies evaluated brain reaccumulation of both classes of solute after correction of chronic hyponatremia. Hyponatremia was induced by subcutaneous infusions of 1-deamino-[8-D-arginine]-vasopressin (dDAVP) in rats fed a balanced liquid diet. After 14 days of sustained hyponatremia the dDAVP minipumps were removed causing rapid correction of plasma sodium concentrations from 104 +/- 1 mmol/l to 139 +/- 1 mmol/l in 24 h. Water and solute contents were measured in brain extracts both before and for 5 days after correction of the hyponatremia, and compared to values in normonatremic rats maintained on the same diet for 14 days. Our results demonstrate that electrolytes, particularly Na+ and Cl-, reaccumulate rapidly in the brain, resulting in a significant overshoot above normal control brain Na+ and Cl- contents as early as 24 h after correction. In contrast, organic osmolyte reaccumulation occurs more slowly, requiring 5 or more days for a return to normal control brain contents in most cases. A prominent exception to this pattern was glutamate, which also returned rapidly to normal brain contents within 24 h similar to the electrolytes. Quantitative analysis of brain water and solute contents after correction of hyponatremia indicated that the reaccumulation of electrolytes and organic osmolytes was sufficient to account for the changes in brain volume that occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Brain; Deamino Arginine Vasopressin; Electrolytes; Glutamates; Glutamic Acid; Hyponatremia; Male; Osmosis; Rats; Rats, Sprague-Dawley; Sodium

Topics: Administration, Intranasal; Child; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Hyponatremia; Male

The present studies evaluated whether previously observed impairments in brain buffering during acute hyponatremia were maintained during chronic hyponatremia as well and whether the impairment was due in part to changes in brain water, brain perfusion, or activation of arginine vasopressin (AVP) V1 receptors. Acute (1 and 2 day) and chronic (7 and 14 day) hyponatremia was induced in male Sprague-Dawley rats by constant desmopressin administration in combination with a liquid diet. Brain pH was determined by 31P nuclear magnetic resonance (NMR) in rats anesthetized with N2O and paralyzed with pancuronium. Brain buffering was evaluated by the response to CO2 loading, and brain perfusion was evaluated by 19F-NMR using trifluoromethane washout. Compared with normonatremic controls fed the same diet, brain pH in both acute and chronic hyponatremics was 0.12 pH units lower after 55 min ventilation with 20% CO2 despite identical decreases of approximately 0.35 units in all groups during the first 15 min. Moreover, in the recovery period brain pH overshot basal levels only in normonatremic controls. Brain water content in chronic hyponatremic rats was equal to controls, and brain perfusion was identical in the five groups during CO2 exposure. These results are analogous to those reported during acute hyponatremia induced with AVP and show that the impairment of active brain buffering is maintained during chronic hyponatremia and is unrelated to brain water content, perfusion, tissue catabolism, or AVP V1 receptor activation.

Topics: Acute Disease; Administration, Inhalation; Animals; Brain; Buffers; Carbon Dioxide; Cerebrovascular Circulation; Chronic Disease; Deamino Arginine Vasopressin; Hydrogen-Ion Concentration; Hyponatremia; Magnetic Resonance Spectroscopy; Male; Phosphorus; Rats; Rats, Sprague-Dawley

We report the development of significant hyponatremia (121 mEq/L) following three daily intravenous doses of desmopressin acetate (DDAVP; 18 micrograms; 0.3 micrograms/kg) in a healthy adult with moderate von Willebrand's disease. Previous reports suggest that clinically important hyponatremia due to DDAVP administration only occurs in the very young, those receiving hypotonic intravenous fluids or those given multiple frequent (e.g., every 8-12 hours) doses of DDAVP. None of these conditions was present in this case. Consideration should be given to monitoring serum sodium levels and fluid balance in patients receiving more than a single dose of DDAVP, even in the absence of previously reported risk factors for the development of hyponatremia.

Topics: Adult; Age Factors; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Female; Humans; Hyponatremia; Injections, Intravenous; Risk Factors; Sodium; von Willebrand Diseases; Water-Electrolyte Balance

Topics: Deamino Arginine Vasopressin; Drinking; Drug Synergism; Humans; Hyponatremia; Imipramine; Methylphenidate

The present study was undertaken to determine whether the non-peptide V2 antidiuretic hormone (ADH) antagonist 5-dimethylamino-1[4-(2- methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (OPC-31260) normalized hyponatremia in rats with an experimental syndrome of inappropriate secretion of ADH (SIADH). Rats were administered V2 agonist 1-deamino-8-D-arginine vasopressin (dDAVP) subcutaneously at a rate of 5 ng/hr using an osmotic minipump and a 40 ml/day liquid diet. Serum sodium levels (SNa) and serum osmolality (SOsm) markedly decreased to 119 mEq/liter and 249 mOsm/kg H2O, respectively, 48 hours after the start of dDAVP administration. Hyponatremia persisted in a similar magnitude during the observation period of 14 days. On days 7 to 13 OPC-31260, administered 5 mg/kg per day orally, promptly raised SNa and SOsm to 134 mEq/liter and 282 mOsm/kg H2O in half a day, respectively, followed by the normalization of SNa and SOsm during the rest of the observation period. The cease of administration of OPC-31260 again decreased SNa and SOsm in rats receiving dDAVP. In contrast, SNa and SOsm were within the normal values in rats receiving 0.15 M NaCl, a vehicle for dDAVP, in the presence or absence of OPC-31260. The administration of OPC-31260 promptly caused marked water diuresis on day 7 in the hyponatremic rats receiving dDAVP, namely 5 mg/kg OPC-31260 markedly increased urinary volume and decreased UOsm. These results indicate that there is dilutional hyponatremia in rats receiving dDAVP and 40 ml/day liquid diets, and that OPC-31260 is an effective therapeutic for hyponatremia associated with dDAVP-induced SIADH.

Topics: Animals; Benzazepines; Deamino Arginine Vasopressin; Hyponatremia; Inappropriate ADH Syndrome; Male; Osmolar Concentration; Rats; Rats, Sprague-Dawley; Sodium; Vasopressins

Secretion of oxytocin into the peripheral circulation of rats is stimulated by suckling and inhibited by hypoosmolality. We compared the oxytocin secretory response to suckling in 1 week post partum lactating rats rendered hyponatremic for 48 h to matched lactating normonatremic cohorts. Pituitary content of oxytocin and peripheral oxytocin secretory responses to suckling were equivalent in normonatremic and hyponatremic animals. We conclude that induction of sustained hyponatremia for 48 h does not inhibit suckling-induced oxytocin release in lactating rats.

Topics: Animals; Animals, Suckling; Deamino Arginine Vasopressin; Female; Hyponatremia; Lactation; Osmolar Concentration; Oxytocin; Rats; Rats, Sprague-Dawley; Reference Values

Topics: Deamino Arginine Vasopressin; Enuresis; Humans; Hyponatremia; Time Factors

The defense of brain volume during hyponatremia cannot be explained by the losses of brain sodium and potassium. We have examined the brain losses of organic osmolytes in rats after 24 h of severe hyponatremia induced by the administration of vasopressin and 5% dextrose in water. Normonatremic controls and animals with intermediate plasma sodium concentration ([Na]) were produced in vasopressin-treated animals by the administration of isocaloric gavages containing varying amounts of NaCl and free water. The animals were killed at 24 h by decapitation, and one brain hemisphere was quickly frozen in liquid nitrogen for organic osmolyte determinations. When compared with controls (plasma [Na] = 139 +/- 1.5 mM), hyponatremic animals (plasma [Na] = 96 +/- 1 mM) had significantly reduced brain contents for sodium, potassium, chloride, glutamate, myo-inositol, N-acetylaspartate, aspartate, creatine, taurine, gamma-aminobutyric acid, and phosphoethanolamine. Plasma [Na] was highly correlated (P < 0.001) with the brain contents for sodium, potassium, and organic osmolytes. Whereas the observed increase in brain water during hyponatremia was only 4.8%, by calculation, brain swelling without brain organic osmolyte losses would have been 11%, an amount that jeopardizes survival.

Topics: Acute Disease; Amino Acids; Animals; Brain; Creatine; Deamino Arginine Vasopressin; Hyponatremia; Inositol; Male; Rats; Rats, Sprague-Dawley; Vasopressins

Topics: Child; Deamino Arginine Vasopressin; Humans; Hyponatremia; Imipramine; Male; Seizures

Previous studies have demonstrated that hyponatremia induced by continuous sc infusion of desmopressin (dDAVP) in combination with a liquid diet allows brain volume adaptation with negligible morbidity and mortality in rats. In contrast, some studies of hyponatremia induced by injections of long-acting preparations of arginine vasopressin (AVP) have reported mortality rates as high as 20 to 80%. To evaluate the possibility that the use of AVP to produce antidiuresis may cause greater mortality as a result of increased brain edema, this study examined brain water and electrolyte contents of male and female rats after varying periods of hyponatremia induced by continuous sc infusions of either dDAVP (5 ng/h) or AVP (100 ng/h). Rats infused with AVP had AVP levels in plasma elevated into ranges reported in patients with the syndrome of inappropriate antidiuretic hormone secretion (17.5 +/- 2.0 pg/mL); however, despite the production of comparably severe degrees of hyponatremia with both AVP and dDAVP infusions (105 to 115 mmol/L), no mortality occurred in any of the rats (N = 40 AVP infused and N = 40 dDAVP infused). AVP- and dDAVP-induced hyponatremia both caused transient brain edema in female and male rats, but brain water content returned to the levels of normonatremic controls after 5 days in the females and 10 days in the males. However, at no time during the 10-day study period did brain water content differ significantly between rats infused with AVP or dDAVP, either in females or males. Decreases in brain electrolytes were also equivalent in the AVP- and dDAVP-infused male and female rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arginine Vasopressin; Body Weight; Brain; Brain Edema; Deamino Arginine Vasopressin; Electrolytes; Female; Hyponatremia; Male; Rats; Rats, Sprague-Dawley; Reference Values; Sodium

We report a case of hyponatremia associated with a grand mal seizure in a 28 month-old child after intra-nasal desmopressin administration for high fluid intake with nocturnal enuresis. In view of the temporary symptomatic action and the seriousness of certain side-effects of desmopressin we recommend that desmopressin be used with caution in childhood enuresis.

Topics: Administration, Intranasal; Aerosols; Child, Preschool; Deamino Arginine Vasopressin; Drinking; Enuresis; Epilepsy, Tonic-Clonic; Humans; Hyponatremia; Male; Water Intoxication

Topics: Child; Deamino Arginine Vasopressin; Drinking; Electrolytes; Enuresis; Humans; Hyponatremia; Male; Osmolar Concentration; Seizures; Water Intoxication

We describe a patient with moderate von Willebrand's disease who developed severe hyponatremia during prophylaxis with 1-deamino-8D-arginine vasopressin (desmopressin) to prevent bleeding in connection with surgery. This is a rare complication to desmopressin treatment in adults. Our present policy is to restrict administration of desmopressin to three 12-hourly infusions, to measure serum sodium before and during the treatment period, to determine body weight daily and to restrict administration of fluids.

Topics: Adult; Deamino Arginine Vasopressin; Female; Humans; Hyponatremia; Infusions, Intravenous; Premedication; von Willebrand Diseases

Topics: Administration, Intranasal; Child, Preschool; Deamino Arginine Vasopressin; Enuresis; Humans; Hyponatremia; Male; Seizures

Brain adaptation to hypoosmolality is known to involve volume regulatory losses of both extracellular and intracellular electrolytes. We studied the effects of acute and chronic hypoosmolality on brain content of organic osmolytes as well as electrolytes in rats to ascertain the relative contributions of different brain solutes to the brain volume regulation that occurs under these conditions. Brains were dissected from rats after 2, 7 and 14 d of sustained hyponatremia induced by continuous infusion of 1-deamino-[8-D-arginine]-vasopressin (DDVAP) in combination with a liquid formula, along with control rats fed the same formula in the absence of DDAVP infusions. One half of each brain was analyzed for organic osmolyte contents and the other half for water and electrolyte contents. Brain Na+, K+ and Cl- and multiple organic osmolytes (glutamate, creatine, taurine, myo-inositol, glutamine and glycerophosphoryl-choline) decreased markedly by 2 d of hyponatremia, and brain electrolyte and most organic osmolyte contents then remained at these reduced levels throughout the duration of the hyponatremia. Although the absolute magnitude of the brain electrolyte losses was greater than the magnitude of the brain organic osmolyte losses, the organic osmolyte losses accounted for approximately 35% of the total measured brain solute losses during sustained hyponatremia. These results demonstrate that organic osmolytes constitute a significant proportion of the brain solute losses that take place during hyponatremia, and indicate that reductions in both organic osmolyte and electrolyte contents are necessary to accomplish brain volume regulation during adaptation to sustained hypoosmolality.

Topics: Animals; Body Water; Brain; Brain Chemistry; Chromatography, High Pressure Liquid; Deamino Arginine Vasopressin; Electrolytes; Hyponatremia; Male; Osmolar Concentration; Rats; Rats, Inbred Strains; Sodium; Water-Electrolyte Balance

Vasopressin is synthesized in the perikarya of magnocellular neurons and is transported down long axons to the storage terminals of the posterior pituitary. To maintain stable pituitary stores following vasopressin secretion, the hypothalamus must synthesize and transport an amount of new vasopressin, equivalent to the amount released. Vasopressin release and synthesis rate can be chronically upregulated or suppressed relative to basal levels, depending on the demand for vasopressin. We studied whether vasopressin transport was similarly regulated during situations of varying demand. During chronic hyponatremia, when synthesis of vasopressin was reduced to undetectable levels, transport of vasopressin was also markedly decreased, as evidenced by continued presence of vasopressin in the transport system. Upregulation of transport was demonstrated by measuring pituitary accumulation of vasopressin in rats whose pituitary stores were initially depleted by hypernatremia and in whom subsequent release was suppressed by hyponatremia. In hypernatremic rats, transport of vasopressin was increased fivefold over baseline as determined by pituitary accumulation, and this elevated rate persisted for 7 days in the absence of release. This study demonstrates that axonal transport of vasopressin is a regulated process and is linked to synthesis rate rather than release.

Topics: Animals; Biological Transport; Colchicine; Deamino Arginine Vasopressin; Hypernatremia; Hyponatremia; Hypothalamus; Male; Pituitary Gland; Rats; Rats, Inbred Strains; Sodium Chloride; Vasopressins

Hyponatremia due to inappropriate secretion of vasopressin is a common disorder in human pathophysiology, but vasopressin synthesis during hypoosmolality has not been investigated. We used a new method to quantitate synthesis of vasopressin in rats after 3, 7, and 14 d of hyponatremia induced by administering dDAVP (a vasopressin agonist) and a liquid diet. Vasopressin synthesis was completely turned off by 7 d. Vasopressin mRNA levels in the hypothalamus paralleled the reduction in synthesis and were reduced to levels of only 10-15% of the content in control rats. When hyponatremia was corrected by withdrawal of dDAVP, vasopressin mRNA slowly returned to normal over 7 d. The observation that vasopressin synthesis can be so completely turned off leads to several conclusions: under normal physiological conditions the neurohypophysis is chronically upregulated; there must be an osmotic threshold for initiation of vasopressin synthesis (and release); the large store of hormone in the posterior pituitary is essential for vasopressin to be available during times of decreased synthesis; and, finally, some nonosmolar stimulus for synthesis must be present during clinical disorders when vasopressin is secreted (and synthesized) despite hypoosmolality.

Topics: Animals; Deamino Arginine Vasopressin; Down-Regulation; Hyponatremia; Male; Neurophysins; Osmolar Concentration; Oxytocin; Pressoreceptors; Rats; Rats, Inbred Strains; RNA, Messenger; Vasopressins

Topics: Celiac Disease; Congenital Hypothyroidism; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Hyponatremia; Hypothyroidism; Infant; Male; Seizures

Desmopressin (DDAVP), a synthetic vasopressin, temporarily corrects bleeding abnormalities associated with mild hemophilia A, von Willebrand disease, and disorders of platelet function. The side effects of DDAVP are considered benign although most of its use has been in adults and older children. We report four children under the age of 2 years who became hyponatremic after intravenous DDAVP administration (0.3 microgram/kg). Three of them developed grand mal seizures. A review of the literature and these cases indicate that associated risk factors for hyponatremia after DDAVP administration include stress, surgery, anesthesia and narcotics (endogenous release of antidiuretic hormone), vomiting (loss of Na+), liver disease (hindered metabolism of DDAVP), renal tubular acidosis (chronically low serum Na+), multiple doses of DDAVP, and overhydration with hyponatremic fluids. DDAVP is not a benign drug in this age group and shows a serious potential for hyponatremia and seizures. Fluid restriction, avoidance of hyponatremic solutions, and close monitoring of serum electrolytes and urine output for at least 15-20 hr after the administration of DDAVP, when used in children under the age of 2 years, is warranted.

Topics: Deamino Arginine Vasopressin; Epilepsy, Tonic-Clonic; Hematologic Diseases; Hemorrhage; Humans; Hyponatremia; Infant; Male

Topics: Administration, Intranasal; Child; Deamino Arginine Vasopressin; Enuresis; Humans; Hyponatremia; Male

We made rats severely hyponatremic, varying the rate of onset and duration of the disturbance, and then compared rapid correction to slow correction. An acute fall in the plasma Na to 106 mEq/liter within seven hours caused seizures and coma, but these findings resolved and survival was 100% after either rapid or slow correction. A more gradual fall in plasma Na to 95 mEq/liter in three days caused neither seizures nor coma. Measurements of brain water and electrolytes showed that adaptive losses of brain Na and K (maximally depleted within seven hours) and slower losses of non-electrolyte solutes progressively reduced brain edema. After three days of hyponatremia, rapid correction to 119 mEq/liter with 1 M NaCl or to 129 mEq/liter by withdrawing DDAVP caused brain dehydration because lost brain K and non-electrolyte solutes were recovered slowly. This treatment was followed by a delayed onset of severe neurologic findings, demyelinating brain lesions and a mortality rate of over 40%. Slow correction (0.3 mEq/liter/hr) avoided these complications and permitted 100% survival. We conclude that the rat adapts quickly to hyponatremia and can survive with extremely low plasma sodium concentrations for prolonged periods. Although rapid correction is well tolerated when hyponatremia is of brief duration, it may cause brain damage in animals that have had time to more fully adapt to the disturbance.

Topics: Animals; Body Water; Brain; Brain Diseases; Deamino Arginine Vasopressin; Dehydration; Fluid Therapy; Hyponatremia; Male; Potassium; Rats; Rats, Inbred Strains; Sodium; Sodium Chloride; Time Factors; Water-Electrolyte Balance

Desmopressin (DDAVP) has recently been found to improve hemostasis in patients with congenital or acquired disorders of coagulation and to reduce operative blood loss in patients with normal hemostasis undergoing certain surgical procedures. Despite its potent antidiuretic effect, severe hyponatremia after the intravenous administration of DDAVP is felt to be rare. We report four cases of severe hyponatremia with serious clinical sequelae occurring in patients with underlying coagulopathies who were treated prophylactically with DDAVP to improve hemostasis prior to surgical procedures. Each patient received multiple (3-22) doses of DDAVP and was given intravenous hydration with hypotonic solutions before developing clinical signs and laboratory evidence of hyponatremia. We believe that the risk of significant hyponatremia after treatment with intravenous DDAVP may be higher than is generally appreciated and that patients undergoing surgical procedures, who often receive multiple doses of DDAVP and intravenous hydration, are at particular risk for this complication. Hypotonic intravenous solutions should be avoided and serum sodium levels should be monitored frequently in those patients receiving multiple doses of DDAVP.

Topics: Adenoidectomy; Adolescent; Adult; Cesarean Section; Child, Preschool; Deamino Arginine Vasopressin; Drainage; Female; Hemophilia A; Hemostasis, Surgical; Humans; Hyponatremia; Male; Thrombocytopenia; Tonsillectomy; von Willebrand Diseases

Topics: Child; Deamino Arginine Vasopressin; Female; Hemostasis, Surgical; Humans; Hyponatremia; Infant; Injections, Intravenous; Male; Osmolar Concentration; Seizures; Time Factors

Topics: Adenoma, Chromophobe; Deamino Arginine Vasopressin; Drug Administration Schedule; Humans; Hyponatremia; Male; Middle Aged; Pituitary Neoplasms; Postoperative Complications; Water Intoxication

An experimental model of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was developed using continuous subcutaneous infusions of arginine vasopressin (AVP) or 1-desamino-8-D-arginine vasopressin (DDAVP) in conscious unrestrained rats drinking 5% dextrose solution. Retention of both ingested water and endogenously generated free water from tissue catabolism was the primary determinant of hyponatremia using either AVP or DDAVP infusions. Natriuresis occurred transiently following water expansion but only slightly further lowered plasma [Na+]. Cessation of antidiuretic infusion resulted in free water excretion with correction of plasma [Na+]. Erythrocyte cell volume was significantly increased in hyponatremic animals and intracellular [K+] and [Na+] both decreased equivalently, consistent with dilution of intracellular fluid by retained water. This model of SIADH differs significantly from those previously described, in that escape from the hydroosmotic effect of AVP and DDAVP does not occur in the absence of high urinary flow rates. The observed results using this model suggest that the retained water in SIADH primarily resides intracellularly following isotonic equilibration of extracellular fluid volume.

Topics: Animals; Arginine Vasopressin; Body Water; Deamino Arginine Vasopressin; Disease Models, Animal; Erythrocyte Count; Hyponatremia; Inappropriate ADH Syndrome; Male; Potassium; Rats; Rats, Inbred Strains; Rodent Diseases; Sodium

Since the rate of polymerization of sickle hemoglobin is exquisitely dependent on its concentration, a small reduction in intracellular hemoglobin concentration should cause a significant inhibition of sickling. In three patients with homozygous sickle cell anemia, sustained hyponatremia was induced by a program consisting of a high fluid intake, a low salt diet and a vasopressin analog, DDAVP. During periods of hyponatremia, mean corpuscular hemoglobin concentration (MCHC) fell 13% and in vitro sickling was reduced as assessed by morphology and oxygen affinity. The frequency and duration of sickle cell crises appeared to be decreased during periods when patients were hyponatremic. These preliminary results indicate that reduction in intracellular hemoglobin concentration is an effective approach to the treatment of sickle cell anemia.

Topics: Anemia, Sickle Cell; Deamino Arginine Vasopressin; Diet, Sodium-Restricted; Erythrocyte Indices; Erythrocytes, Abnormal; Hemoglobin, Sickle; Humans; Hyponatremia; Oxygen; Sodium; Water-Electrolyte Balance

Topics: Arginine Vasopressin; Body Water; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Hypernatremia; Hypoglycemia; Hyponatremia; Inappropriate ADH Syndrome; Pharmacology; Radioimmunoassay; Vasopressins; Water-Electrolyte Imbalance

An analogue of arginine vasopressin (desmopressin, DDAVP) was evaluated for production chronic hyponatremia and prevention of sickle cell crisis. With sodium restriction (100 meq Na + / day) and water loading ( greater than 3 liters/day), persistent hyponatremia could not be achieved, nor could crises be prevented or aborted. Patients would not comply with a regimen of lower salt and higher fluid intake. More rigorous treatment might be practical during acute sickle cell crises, and a regimen similar to that used here might be more effective in children, whose renal concentrating mechanisms are still intact.

Topics: Adult; Anemia, Sickle Cell; Arginine Vasopressin; Deamino Arginine Vasopressin; Erythrocyte Aging; Female; Humans; Hyponatremia; Male; Osmolar Concentration; Pain; Sodium; Urine

Topics: Adult; Deamino Arginine Vasopressin; Hemophilia A; Hemostasis, Surgical; Humans; Hyponatremia; Male; Tooth Extraction; Vasopressins; Water Intoxication