deamino-arginine-vasopressin and Acute-Disease

Hypopituitarism refers to deficiency of one or more hormones produced by the anterior pituitary or released from the posterior pituitary. Hypopituitarism is associated with excess mortality, a key risk factor being cortisol deficiency due to adrenocorticotropic hormone (ACTH) deficiency. Onset can be acute or insidious, and the most common cause in adulthood is a pituitary adenoma, or treatment with pituitary surgery or radiotherapy. Hypopituitarism is diagnosed based on baseline blood sampling for thyroid stimulating hormone, gonadotropin, and prolactin deficiencies, whereas for ACTH, growth hormone, and antidiuretic hormone deficiency dynamic stimulation tests are usually needed. Repeated pituitary function assessment at regular intervals is needed for diagnosis of the predictable but slowly evolving forms of hypopituitarism. Replacement treatment exists in the form of thyroxine, hydrocortisone, sex steroids, growth hormone, and desmopressin. If onset is acute, cortisol deficiency should be replaced first. Modifications in replacement treatment are needed during the transition from paediatric to adult endocrine care, and during pregnancy.

Topics: Acute Disease; Adenoma; Adrenocorticotropic Hormone; Chronic Disease; Deamino Arginine Vasopressin; Gonadal Steroid Hormones; Gonadotropins, Pituitary; Hormone Replacement Therapy; Human Growth Hormone; Humans; Hydrocortisone; Hypophysectomy; Hypopituitarism; Pituitary Gland; Pituitary Hormones, Anterior; Pituitary Irradiation; Pituitary Neoplasms; Prolactin; Radiotherapy; Thyrotropin; Thyroxine; Vasopressins

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

Approximately one-fifth of the patients, referred to the acute gastrointestinal bleeding unit took antithrombotic drugs (anticoagulants and antiplatelet agents) in a dose or with an effect, which made the causal relationship with acute bleeding episodes unequivocal. This paper analyzes the data of the first 100 such patients of the ward. The majority used acethyl-salicylic acid derivatives, however, a substantial number were on coumarol, and some bleeding patients with prosthetic heart valves were also observed. Haemostasis was forced by urgent, accurate, intervention based endoscopy along with simultaneous rapid efforts to correct the underlying clotting abnormalities. Prosthetic valve patients needed special care and attendance, and the reinstitution of anticoagulant treatment as soon as possible to maintain valve patency. The experiences and schedules of the authors, as well as the proposals of the literature are reviewed and summarized.

Topics: Acute Disease; Anticoagulants; Aspirin; Coumarins; Deamino Arginine Vasopressin; Gastrointestinal Hemorrhage; Heart Valve Prosthesis; Hemostatics; Heparin; Humans; Thrombolytic Therapy; Ticlopidine

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

1-Deamino-8-D-arginine vasopressin (DDAVP, desmopressin), a synthetic analog of the antidiuretic hormone L-arginine vasopressin, improves hemostasis parameters in cirrhotic patients. Hence its use in combination with a vasoactive drug such as terlipressin might improve the performance of this drug in controlling variceal bleeding. The aim of this trial was to compare the efficacy of desmopressin plus terlipressin with that of terlipressin alone in controlling acute variceal hemorrhage. Cirrhotic patients with active variceal hemorrhage diagnosed endoscopically were randomized within 2 hr of admission to receive desmopressin plus terlipressin or placebo plus terlipressin. Terlipressin (2 mg, intravenous bolus) was given at time 0 and every 4 hr thereafter for 24 hr. Desmopressin (0.3 microgram/kg, intravenously) or placebo was given in saline solution over 30 min at time 0 and at 26 hr. Patients were monitored for 24 hr after cessation of treatment. Treatment failure was defined as recurrence of active bleeding during treatment or within the 24 hr after treatment. After enrolling 51 of the planned 84 patients, we carried out an interim analysis. Treatment failure occurred in 13 of 24 patients randomized to receive desmopressin plus terlipressin (54.2%) and in 6 of 22 patients randomized to receive terlipressin (27.3%) (p = 0.06, Fisher's exact test). The trial was interrupted at this stage because patients treated with the "new" therapy fared worse than those treated with the standard therapy, and the possibility of reversing this trend by completing the trial was deemed remote. The addition of desmopressin does not improve and may worsen the efficacy of terlipressin in controlling acute variceal bleeding in cirrhotic patients.

Topics: Acute Disease; Deamino Arginine Vasopressin; Double-Blind Method; Drug Therapy, Combination; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Lypressin; Male; Middle Aged; Terlipressin; Treatment Failure

Eight patients with sickle cell anemia were treated for acute painful crises with DDAVP and intravenous fluids; five were treated with placebo and the same regimen of fluid administration. Although hyponatremia was produced in both treatment groups, duration of hospitalization did not differ between them, nor did it differ from concurrent hospitalization of other patients who received conventional treatment. Safe induction of hyponatremia required intensive laboratory surveillance, and serum sodium could be lowered without use of DDAVP. These data suggest that a controlled trial hyponatremia for acute sickle cell crises should not be performed.

Topics: Acute Disease; Adult; Anemia, Sickle Cell; Arginine Vasopressin; Deamino Arginine Vasopressin; Female; Fluid Therapy; Humans; Male; Sodium

Acute heparin-induced thrombocytopenia (HIT) patients present a myriad of anticoagulation management challenges, in clinical settings where unfractionated heparin (UFH) is the traditional drug of choice. UFH use in cardiac surgery is a known entity that has been subject to rigorous research. Research has, thus, led to its unparalleled use and the development of well-established protocols for cardiac surgery. In comparison to UFH, bivalirudin use for acute HIT patients requiring urgent cardiac surgery with cardiopulmonary bypass (CPB) is still in its infancy. We describe the tailored post-CPB management of refractory bleeding in a 65-year-old infective endocarditis, acute HIT patient with renal failure who underwent urgent aortic valve replacement and mitral valve repair with bivalirudin anticoagulation. A management approach that entailed a combination of continuous venovenous haemofiltration (CVVH), 4-Factor prothrombin complex concentrate (PCC) (Beriplex), recombinant factor VIIa (rFactor VIIa) and desmopressin (DDAVP) were consecutively used post-operatively in theatre. Based on this case study experience, two modifications to institutional protocols are recommended. The first is the use of CVVH in theatre to eliminate bivalirudin in renal failure patients or in patients where bivalirudin elimination is prolonged. Secondly, a 'rescue therapy/intervention' algorithm for the swift identification of refractory bleeding post-CPB is also recommended. Rescue therapy agents, such as a 4-Factor PCCs and rFactor VIIa, should be incorporated into the protocol after a robust evidence-based search and agreement with the haematologist. The aim of these recommendations is to reduce the risk of bleeding associated with bivalirudin use for inexperienced institutions and experienced institutions alike, until larger randomized, controlled studies provide more in-depth knowledge to expand our clinical practice.

Topics: Acute Disease; Aged; Anticoagulants; Aortic Valve; Blood Coagulation Factors; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Factor VIIa; Hemorrhage; Hemostatics; Heparin; Hirudins; Humans; Male; Mitral Valve; Peptide Fragments; Recombinant Proteins; Renal Insufficiency; Thrombocytopenia

Postpartum, diabetes insipidus (DI) can be part of Sheehan's syndrome or lymphocytic hypophysitis in combination with anterior pituitary hormone deficiencies. In contrast, acute onset of isolated DI in the postpartum period is unusual.. This patient presented at 33 weeks gestation with placental abruption, prompting a cesarean delivery of twins. Immediately after delivery, she developed severe DI. The DI could be controlled with the vasopressinase-resistant 1-deamino-8-D-arginine vasopressin (DDAVP), but not with arginine vasopressin (AVP), and it resolved within a few weeks.. The aim of this study was to demonstrate that the postpartum DI in this patient was caused by the release of placental vasopressinase into the maternal bloodstream.. Cells were transiently transfected with the AVP receptor 2 (AVPR2) and treated with either AVP or DDAVP in the presence of the patient's serum collected postpartum or 10 weeks after delivery. The response to the different treatments was evaluated by measuring the activity of a cAMP-responsive firefly luciferase reporter construct. The in vitro studies demonstrate that the patient's postpartum serum disrupts activation of the AVPR2 by AVP, but not by the vasopressinase-resistant DDAVP.. Placental abruption can rarely be associated with acute postpartum DI caused by release of placental vasopressinase into the bloodstream. This clinical entity must be considered in patients with placental abruption and when evaluating patients presenting with DI after delivery.

Topics: Abruptio Placentae; Acute Disease; Adult; Antidiuretic Agents; Arginine Vasopressin; Cesarean Section; Cystinyl Aminopeptidase; Deamino Arginine Vasopressin; Diabetes Insipidus; Drug Resistance; Female; HEK293 Cells; Humans; Postpartum Period; Pregnancy

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

Patients requiring CSF shunts frequently have comorbidities that can influence water and electrolyte balances. The authors report on a case involving a ventriculoperitoneal shunt in a patient who underwent intravenous hyperhydration and withdrawal of vasopressin substitution prior to scheduled high-dose chemotherapy regimen for a metastatic suprasellar germinoma. After acute neurological deterioration, the patient underwent CT scanning that demonstrated ventriculomegaly. A shunt tap revealed no flow and negative opening pressure. Due to suspicion of proximal shunt malfunction, the comatose patient underwent immediate surgical exploration of the ventricle catheter, which was found to be patent. However, acute severe hypernatremia was diagnosed during the procedure. After correction of the electrolyte disturbances, the patient regained consciousness and made a good recovery. Although rare, the effects of acute severe hypernatremia on brain volume and ventricular size should be considered in the differential diagnosis of ventriculoperitoneal shunt failure.

Topics: Acute Disease; Adult; Antidiuretic Agents; Antineoplastic Agents; Astrocytoma; Brain Stem Neoplasms; Cerebral Ventricles; Chemotherapy, Adjuvant; Cranial Irradiation; Deamino Arginine Vasopressin; Diagnosis, Differential; Diagnostic Errors; Equipment Failure Analysis; Fluid Therapy; Humans; Hydrocephalus; Hypernatremia; Hypertrophy; Male; Neoplasms, Multiple Primary; Pituitary Neoplasms; Postoperative Complications; Substance Withdrawal Syndrome; Tectum Mesencephali; Tomography, X-Ray Computed; Ventriculoperitoneal Shunt

Diabetes insipidus (DI) is a well documented complication observed after traumatic head injuries. We report a case of hyperacute onset DI in a 19-year-old male who sustained a hypothalamic-pituitary injury when he was stabbed in the head with a 30-cm long thin-bladed knife. At CT, our patient showed significant hemorrhagic contusions of the lower hypothalamus. He developed polydipsia, polyuria, and mild hypernatremia in the Emergency Department. Diagnostic digital subtraction angiography showed a hypervascular congestive pituitary gland with prominent draining veins. On the third day his hypernatremia became severe (183mEq/L). He was managed with parenteral fluids and a regimen of intranasal DDAVP (1-desamino 8-d-arginine vasopressin), leading to improved plasmatic sodium levels, urine output, and urinary specific gravity. In patients presenting with hyperacute posttraumatic DI, emergency room physicians and neurosurgeons should rule out direct injury to the hypothalamus and/or the posterior lobe of the pituitary, and initiate early pharmacological treatment.

Topics: Acute Disease; Brain Injuries; Confusion; Craniocerebral Trauma; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Humans; Hypernatremia; Hypoglycemic Agents; Hypothalamo-Hypophyseal System; Hypothalamus; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Male; Polyuria; Tomography, X-Ray Computed; Wounds, Stab; Young Adult

Gastroenteritis due to Escherichia coli O157:H7 occurs in young children and is associated with consumption of under cooked beef. Approximately 5-10% of patients will develop hemolytic uremic syndrome (HUS): renal failure, microangiopathic hemolytic anemia, and thrombocytopenia. A 6-year-old boy was admitted with abdominal pain, guaiac positive stool, decreased urine output and elevated creatinine levels. Hemodialysis was initiated upon rapid progression to anuria. On hospital day # 5 he developed acute abdominal pain, which was different from his initial assessment. Exam revealed focal tenderness in the right lower quadrant with localized guarding and rebound. Ultrasound demonstrated a dilated, fluid filled tubular structure in the RLQ concerning for appendicitis. Based on these findings the patient was taken to the operating room for a laparoscopic appendectomy. The patient had undergone dialysis the previous day and was preoperatively treated with DDAVP to minimize the risk of bleeding. The procedure occurred without complication and final pathology confirmed acute appendicitis. This case highlights the unique clinical scenario in which patients with HUS require operative intervention. Surgical procedures can be performed on these patients, however, all precautions should be taken to minimize the risk of bleeding, including the use of preoperative DDAVP.

Topics: Acute Disease; Appendicitis; Child; Deamino Arginine Vasopressin; Escherichia coli Infections; Escherichia coli O157; Hemolytic-Uremic Syndrome; Hemostatics; Humans; Male; Shiga Toxins; Treatment Outcome

Recently, three multicentre prospective international studies have been carried out to evaluate the clinical efficacy and safety of Fanhdi [high-purity, double-inactivated plasma-derived factor VIII/von Willebrand factor (VWF) concentrate] in patients with von Willebrand's disease (VWD). Pharmacokinetic parameters, clinical efficacy and safety of Fanhdi in acute bleedings episodes or invasive procedures were determined in this population.. Pharmacokinetic parameters observed were similar to previous reported for other highly purified plasma-derived FVIII/VWF concentrate. The mean in vivo recovery (IU dL(-1) per IU kg(-1)) was 1.9 +/- 0.6 for VWF:RCof; 2.1 +/- 0.6 for VWF:Ag and 2.6 +/- 0.6 for FVIII:C. The mean half-life (h) was 14.4 +/- 10.5 for VWF:RCof; 27.5 +/- 11.0 for VWF:Ag and 33.4 +/- 16.4 for FVIII:C. Therapeutic benefit of Fanhdi in VWD patients treated during bleeding episodes was clearly demonstrated. The achievement of haemostasis was excellent or good in 100% of the cases (major or minor bleeding episodes). Also, the clinical efficacy of Fanhdi in preventing excessive bleeding during surgery showed a very good profile. Efficacy was rated as excellent in six cases (three major/three minor surgical procedures) and good in three cases (two major/one minor surgical procedures). In addition, the product was well tolerated and no adverse events potentially related to the study drug were reported.. Fanhdi is an effective and safe plasma-derived FVIII/VWF concentrate that can be used as an alternative to the current replacement therapy in patients with VWD to provide an adequate haemostasis during surgical procedures and treatment of bleeding episodes.

Topics: Acute Disease; Coagulants; Deamino Arginine Vasopressin; Factor VIII; Half-Life; Hemorrhage; Hemostasis, Surgical; Humans; Prospective Studies; von Willebrand Diseases; von Willebrand Factor

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

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

A 26 year old woman presented to the accident and emergency department with a painful right elbow. There had been no history of trauma. Clinical examination suggested an effusion, which was confirmed on radiological examination. Her elbow was aspirated and revealed a haemarthrosis. Subsequent investigations revealed a diagnosis of von Willebrand's disease (vWD). A spontaneously occurring effusion of the elbow may be due to a haemarthrosis. Aspiration of blood in the absence of trauma may lead to a diagnosis of an occult coagulopathy in addition to relieving pain. The diagnosis and treatment of vWD is discussed.

Topics: Acute Disease; Adult; Arthralgia; Deamino Arginine Vasopressin; Diagnosis, Differential; Elbow Joint; Female; Hemarthrosis; Hemostatics; Humans; von Willebrand Diseases

To evaluate the effects of desmopressin on pressure values inside the pelvis and ureter of the rat following acute obstruction.. By means of a microsurgical technique, 24 male Wistar rats were submitted to ureteral obstruction; pressure inside the ureter was recorded using a cannula and a micrometric glass column. In the treatment group (14 animals) 6 mg/kg of desmopressin were administered 30 min before the beginning of the experiment.. Rats pretreated with desmopressin showed a statistically significant reduction in mean intraureteral pressure following acute obstruction (p = 0.05).. In Wistar rats desmopressin demonstrated a powerful antidiuretic effect, reducing the intraureteral pressure. The experimental model is useful for a better understanding of physiopathology of renal colic and acute obstruction.

Topics: Acute Disease; Animals; Deamino Arginine Vasopressin; Disease Models, Animal; Male; Muscle Contraction; Pelvis; Pressure; Rats; Rats, Wistar; Renal Agents; Reproducibility of Results; Ureter; Ureteral Obstruction; Urodynamics

Desmopressin is used for the treatment of nocturnal enuresis. Side effects reported with intranasal desmopressin are transient headache, nausea, abdominal cramps and water intoxication with hyponatremia and grand mal seizure. We report a case of water intoxication with low serum sodium and grand mal seizure in a healthy child treated for enuresis with desmopressin. The child experienced abdominal cramps and nausea prior to the convulsions. A computerised tomography scan of the brain gave the suspicion of increased intracranial pressure ICP. The child recovered fully. We therefore recommend that parents and child are fully informed about the administration and the risk of desmopressin. If a child on desmopressin treatment experiences abdominal cramps, nausea or headache the drug should be discontinued and a physician contacted for control of serum sodium. Temporary withdrawal of desmopressin should also be considered in cases of acute illness influencing water balance.

Topics: Acute Disease; Child; Deamino Arginine Vasopressin; Humans; Male; Renal Agents; Tomography, X-Ray Computed; Water Intoxication

Topics: Acute Disease; Administration, Intranasal; Deamino Arginine Vasopressin; Humans; Renal Agents; Water Intoxication

Vasovagal reflexes, such as hypotension and bradycardia, are induced by rapid hemorrhage and mimic neurocardiogenic reflexes in mammals. We examined the role of vasopressin in the neurocardiogenic responses to mild, rapid hemorrhage (1 mL/100 g for 30 seconds) and severe hemorrhage (1 mL/100 g body wt for 30 seconds repeated three times at 11-minute intervals) in homozygous Brattleboro and Long-Evans rats. Mild, rapid hemorrhage induced severe bradycardia and hypotension only in Long-Evans rats. Exogenous vasopressin (1.85 pmol/kg per minute for 1 hour) restored both the bradycardic and hypotensive responses in Brattleboro rats. DDAVP, a vasopressin V2-receptor agonist (0.19 pmol/kg per minute for 24 hours), did not affect the cardiovascular responses to hemorrhage in Brattleboro rats, although it maintained urine production within normal limits. However, OPC-31260 (21.6 mumol/kg IV), a vasopressin V2-receptor antagonist, attenuated both the hypotensive and bradycardic responses to hemorrhage in Long-Evans rats. A vasopressin V1-receptor antagonist attenuated bradycardia and delayed the recovery of arterial pressure after hemorrhage but did not affect the hypotension that occurred immediately after hemorrhage in Long-Evans rats. Methylatropine also attenuated both the bradycardic and hypotensive responses induced by hemorrhage, but propranolol had no effect on the cardiovascular responses to hemorrhage in Long-Evans rats. The recovery of arterial pressure after repeated hemorrhage was less adequate in Brattleboro rats than in Long-Evans rats. Our results suggest that the neurocardiogenic responses to hemorrhage, especially hypotension, may be related to vasodilation induced by a V2-receptor-mediated mechanism and by the vagal reflex, both of which are substantiated by the existence of vasopressin. The coexistence of V1- and V2-receptor mechanisms may be necessary for the hypotensive response to hemorrhage. We found that a V2-receptor antagonist attenuated the hypotension mediated by the so-called neurocardiogenic reflex.

Topics: Acute Disease; Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Autonomic Nerve Block; Benzazepines; Cardiovascular System; Deamino Arginine Vasopressin; Diabetes Insipidus; Heart; Hemorrhage; Male; Nervous System; Rats; Rats, Brattleboro; Rats, Inbred Strains; Receptors, Vasopressin; Recurrence; Vasopressins

The vasopressin analogue, 1-desamino-8-arginine vasopressin (desmopressin), is a potent antidiuretic without the pressor effects of vasopressin. A total of 18 patients with acute renal colic due to stone disease received 40 microgramsf1p4mopressin intranasal spray with encouraging results. There was a significant decrease in the colic pain intensity from an initial mean visual analogue score of 67 +/- 17 mm. to 39 +/- 36 mm. within 30 minutes (p < 0.001). Eight patients (44.4%) had complete pain relief within 30 minutes of administering intranasal desmopressin spray. Nine of 10 patients who required intramuscular diclofenac sodium achieved complete pain relief within another 30 minutes. In other words, when intranasal desmopressin spray was administered before diclofenac sodium, 94.4% of the patients achieved complete pain relief and were discharged home. The mechanism of analgesic action of desmopressin in renal colic is uncertain. At the peripheral level, desmopressin may alleviate the acute renal colic through its potent antidiuretic effect or by relaxing the renal pelvic and ureteral smooth muscles. The central analgesic effect of desmopressin by stimulating the release of the hypothalamic beta-endorphin is proposed. We conclude that intranasal desmopressin spray can be used successfully in the treatment of renal colic. It may also replace prostaglandin synthetase inhibitors in treating renal colic with the advantage of avoiding the potential side effects. Further studies are needed to investigate whether the combination of desmopressin with analgesics or spasmolytic drugs offers competitive results compared with those achieved by prostaglandin synthetase inhibitors in the treatment of renal colic.

Topics: Acute Disease; Administration, Intranasal; Analgesics, Non-Narcotic; Colic; Deamino Arginine Vasopressin; Diclofenac; Drug Therapy, Combination; Humans; Injections, Intramuscular; Kidney Diseases; Male; Pain Measurement

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 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

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: Acute Disease; Adult; Arginine Vasopressin; Deamino Arginine Vasopressin; Female; Humans; Hypernatremia; Postpartum Period; Pregnancy; Pregnancy Complications

The maximal urine concentration capacity was studied in patients with acute pyelonephritis and in patients with clinically diagnosed acute cystitis. In the former group renal concentration ability was reduced in 16 of 22 patients and improved in all but two patients. Among patients with symptoms of acute cystitis 6 of 22 had a concentration capacity below 2 SD of normal values. Several of these patients had raised acute phase proteins and increased their urine osmolality at follow-up indicating that cases of acute pyelonephritis could have been included. It is concluded that the wide overlap between the groups makes the maximal urinary concentration capacity a method of limited value for level diagnosis in acute UTI infection. The test should be reserved for follow-up to reveal permanent renal damage.

Topics: Acute Disease; Adolescent; Adult; Aged; Bacteriuria; Cystitis; Deamino Arginine Vasopressin; Female; Humans; Kidney Concentrating Ability; Kidney Tubules, Distal; Male; Middle Aged; Osmolar Concentration; Pyelonephritis; Urinary Tract Infections

Glomerular filtration rate (GFR) and tubular involvement were studied in 74 patients with serologically verified nephropathia epidemica (NE). Increased levels of serum creatinine and serum beta 2-microglobulin were documented in 96% and 99% of the patients, respectively. The mean of the lowest estimated GFR was 26 ml/min. Proximal tubular reabsorptive capacity was assessed by urinary loss of beta 2-microglobulin and cell damage by urinary activity of N-acetyl-beta-D-glucosaminidase. Both of these parameters were elevated in most of the patients during the acute phase of the disease. Increased serum levels of Tamm-Horsfall-specific IgG and/or IgA occurred in 72 of 74 patients. No patient required dialysis and there was no mortality. Six months after discharge only three patients had a GFR less than 80 ml/min as estimated by [51Cr]EDTA clearance; two of these had underlying chronic diseases and one had suffered clinically severe NE. Desmopressin tests showed decreased urine osmolarity in three patients 8 months after discharge. These three had chronic diseases, which may have contributed to the impaired tubular function. Thus, there was a markedly decreased GFR and a tubular dysfunction in the acute phase of NE. Most patients recovered within a few months and none showed evidence of chronically impaired renal function due to NE.

Topics: Acetylglucosaminidase; Acute Disease; Adolescent; Adult; Aged; beta 2-Microglobulin; Chronic Disease; Creatinine; Deamino Arginine Vasopressin; Female; Glomerular Filtration Rate; Hemorrhagic Fever with Renal Syndrome; Humans; Immunoglobulin A; Immunoglobulin G; Kidney Tubules; Male; Middle Aged; Mucoproteins; Osmolar Concentration; Uromodulin

The purpose of this study was to determine how acute hyponatremia might augment the excretion of ammonium in dogs with chronic metabolic acidosis. The excretion of ammonium was higher during hyponatremia because the proportion of ammonium produced that was excreted in the urine increased from 66% in controls to 77%. Effects on the production of ammonium are more complex. The rate of renal ammoniagenesis was not increased during hyponatremia in absolute terms nor when expressed per millimole of oxygen consumption. In contrast, this rate was somewhat higher during hyponatremia if expressed per millimole of sodium reabsorbed (9.8 vs. 10.3 mumol). The rate of oxygen consumption by the kidney did not fall, as anticipated, during hyponatremia; when this rate was expressed per millimole of sodium reabsorbed it rose from 46 to 55 mumol. There was no significant change in the rate of extraction of glutamine by the kidney, but there was a significant decrease in the rate of release of alanine during hyponatremia. Hence there appears to be more oxidation (yielding more ammonium) and less transamination of glutamine. We conclude that the renal events which led to a higher rate of excretion of ammonium during hyponatremia were a larger than expected rate of ammonium production owing to a greater rate of oxygen consumption together with lesser rate of transamination of the glutamine extracted by the kidney. In addition, more of the ammonium produced was transferred to the urine.

Topics: Acidosis; Acute Disease; Ammonia; Animals; Chronic Disease; Deamino Arginine Vasopressin; Dogs; Glomerular Filtration Rate; Glutamine; Hypotonic Solutions; Kidney; Osmolar Concentration; Sodium; Sodium Chloride

The effectiveness of desmopressin (1-desamino-8-D-arginine vasopressin) in reducing intraoperative blood loss during lumbar fusions was investigated in 42 patients (52 operations) and compared with a control group of 55 patients (63 operations). The mean hemoglobin and hematocrit levels on admission and discharge were identical for both groups. Patients receiving desmopressin required less than one-half the number of autologous transfusions than the control group. Desmopressin was effective in reducing blood loss in operations in which intraoperative bleeding was greater than 1,000 milliliters, but it is probably not necessary for anticipated losses less than this amount. It may have a role in operations performed on short notice when autologous blood is usually unavailable.

Topics: Acute Disease; Adolescent; Adult; Blood Pressure; Blood Transfusion, Autologous; Deamino Arginine Vasopressin; Drug Evaluation; Female; Fracture Fixation, Internal; Fractures, Bone; Hemostasis, Surgical; Humans; Intraoperative Care; Male; Middle Aged; Prospective Studies; Spinal Fusion; Spinal Injuries