pituitrin and Critical-Illness

Vasopressin has become an important vasopressor drug while treating a critically ill patient to maintain adequate mean arterial pressure. Diabetes insipidus (DI) is a rare syndrome characterized by the excretion of a large volume of diluted urine, inappropriate for water homeostasis. We noticed that several COVID19 patients developed excessive polyuria suggestive of DI, with a concomitant plasma sodium-level increase and/or low urine osmolality. We noticed a temporal relationship between vasopressin treatment cessation and polyuria periods. We reviewed those cases to better describe this phenomenon.. We retrospectively collected COVID19 ECMO patients' (from July 6, 2020, to November 30, 2021) data from the electronic medical records. By examining urine output, urine osmolality (if applicable), plasma sodium level, and plasma osmolality, we set DI diagnosis. We described the clinical course of DI episodes and compared baseline characteristics between patients who developed DI and those who did not.. Out of 37 patients, 12 had 18 episodes of DI. These patients were 7 years younger and had lower severity scores (APACHE-II and SOFA). Mortality difference was not seen between groups. 17 episodes occurred after vasopressin discontinuation; 14 episodes were treated with vasopressin reinstitution. DI lasted for a median of 21 h, with a median increase of 14 mEq/L of sodium.. Temporary DI prevalence after vasopressin discontinuation in COVID19 ECMO patients might be higher than previously described for vasopressin-treated patients.

Topics: COVID-19; Critical Illness; Diabetes Insipidus; Humans; Polyuria; Retrospective Studies; Sodium; Vasopressins

Hemodynamic management of adults with distributive shock often includes the use of catecholamine-based vasoconstricting medications. It is unclear whether adding vasopressin or vasopressin analogues to catecholamine therapy is beneficial in the management of patients with distributive shock. The purpose of this guideline was to develop an evidence-based recommendation regarding the addition of vasopressin to catecholamine vasopressors in the management of adults with distributive shock.. We summarized the evidence informing this recommendation by updating a recently published meta-analysis. Then, a multidisciplinary panel from the Canadian Critical Care Society developed the recommendation using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.. The updated systematic review identified 25 randomized controlled trials including a total of 3,737 patients with distributive shock. Compared with catecholamine therapy alone, the addition of vasopressin or its analogues was associated with a reduced risk of mortality (relative risk [RR], 0.91; 95% confidence interval [CI], 0.85 to 0.99; low certainty), reduced risk of atrial fibrillation (RR, 0.77; 95% CI, 0.67 to 0.88; high certainty), and increased risk of digital ischemia (RR, 2.56; 95% CI, 1.24 to 5.25; moderate certainty).. After considering certainty in the evidence, values and preferences, cost, and other factors, the expert guideline panel suggests using vasopressin or vasopressin analogues in addition to catecholamines over catecholamine vasopressors alone for the management of distributive shock (conditional recommendation, low certainty evidence).

Topics: Adult; Canada; Critical Care; Critical Illness; Humans; Shock; Vasopressins

Vasopressors are administered to critically ill patients with vasodilatory shock not responsive to volume resuscitation, and less often in cardiogenic shock, and hypovolemic shock.. The objectives are to review safety and efficacy of vasopressors, pathophysiology, agents that decrease vasopressor dose, predictive biomarkers, β1-blockers, and directions for research.. The quality of evidence was evaluated using Grading of Recommendations Assessment, Development, and Evaluation (GRADE).. Vasopressors bind adrenergic: α1, α2, β1, β2; vasopressin: AVPR1a, AVPR1B, AVPR2; angiotensin II: AG1, AG2; and dopamine: DA1, DA2 receptors inducing vasoconstriction. Vasopressor choice and dose vary because of patients and physician practice. Adverse effects include excessive vasoconstriction, organ ischemia, hyperglycemia, hyperlactatemia, tachycardia, and tachyarrhythmias. No randomized controlled trials of vasopressors showed a significant difference in 28-day mortality rate. Norepinephrine is the first-choice vasopressor in vasodilatory shock after adequate volume resuscitation. Some strategies that decrease norepinephrine dose (vasopressin, angiotensin II) have not decreased 28-day mortality while corticosteroids have decreased 28-day mortality significantly in some (two large trials) but not all trials. In norepinephrine-refractory patients, vasopressin or epinephrine may be added. A new vasopressor, angiotensin II, may be useful in profoundly hypotensive patients. Dobutamine may be added because vasopressors may decrease ventricular contractility. Dopamine is recommended only in bradycardic patients. There are potent vasopressors with limited evidence (e.g. methylene blue, metaraminol) and novel vasopressors in development (selepressin).. Norepinephrine is first choice followed by vasopressin or epinephrine. Angiotensin II and dopamine have limited indications. In future, predictive biomarkers may guide vasopressor selection and novel vasopressors may emerge.

Topics: Angiotensin II; Critical Illness; Dopamine; Epinephrine; Humans; Methylene Blue; Norepinephrine; Phenylephrine; Shock; Terlipressin; Vasoconstrictor Agents; Vasopressins

Septic shock remains one of the major causes of morbidity and mortality in the critically ill. Despite early goal therapy and administration of cathecholaminergic agents, up to 30% of patients succumb to the disease. In this manuscript, we first summarize the standard of care of patients with septic shock and current guidelines. We review the physiologic role of vasopressin and its role in septic shock management. We then review the most up-to-date evidence on the potential role of V1a receptor agonists such as Selepressin, in septic shock. Exciting new trials are being completed in order to elucidate the role of V1a receptor agonists as potential first-line vasopressor alternatives in the therapy of circulatory shock in septic patients.

Topics: Critical Illness; Humans; Receptors, Vasopressin; Shock, Septic; Vasoconstrictor Agents; Vasopressins

Hyponatremia is the most frequent electrolyte abnormality seen postoperatively in pediatric patients receiving maintenance fluid therapy. Hyponatremia is also common in acute pediatric illness. The main factors contributing to hyponatremia in these conditions are increased secretion of antidiuretic hormone (ADH) and routine use of sodium hypotonic fluids. An increased ADH secretion results in an impaired ability to excrete free water. If the sodium concentration falls to less than 125 mmol/L hyponatremic encephalopathy might develop, resulting in cerebral edema. This is avoided if hypotonic maintenance fluids are not used perioperatively or for rehydration or maintenance during acute critical illness in children.

Topics: Acute Disease; Child; Critical Illness; Fluid Therapy; Humans; Hyponatremia; Perioperative Care; Postoperative Complications; Practice Guidelines as Topic; Vasopressins

Topics: Blood Glucose; Critical Illness; Glucocorticoids; Hormones; Humans; Prognosis; Survival Rate; Triiodothyronine; Vasopressins

Disturbances in sodium concentration are common in the critically ill patient and associated with increased mortality. The key principle in treatment and prevention is that plasma [Na+] (P-[Na+]) is determined by external water and cation balances. P-[Na+] determines plasma tonicity. An important exception is hyperglycaemia, where P-[Na+] may be reduced despite plasma hypertonicity. The patient is first treated to secure airway, breathing and circulation to diminish secondary organ damage. Symptoms are critical when handling a patient with hyponatraemia. Severe symptoms are treated with 2 ml/kg 3% NaCl bolus infusions irrespective of the supposed duration of hyponatraemia. The goal is to reduce cerebral symptoms. The bolus therapy ensures an immediate and controllable rise in P-[Na+]. A maximum of three boluses are given (increases P-[Na+] about 6 mmol/l). In all patients with hyponatraemia, correction above 10 mmol/l/day must be avoided to reduce the risk of osmotic demyelination. Practical measures for handling a rapid rise in P-[Na+] are discussed. The risk of overcorrection is associated with the mechanisms that cause hyponatraemia. Traditional classifications according to volume status are notoriously difficult to handle in clinical practice. Moreover, multiple combined mechanisms are common. More than one mechanism must therefore be considered for safe and lasting correction. Hypernatraemia is less common than hyponatraemia, but implies that the patient is more ill and has a worse prognosis. A practical approach includes treatment of the underlying diseases and restoration of the distorted water and salt balances. Multiple combined mechanisms are common and must be searched for. Importantly, hypernatraemia is not only a matter of water deficit, and treatment of the critically ill patient with an accumulated fluid balance of 20 litres and corresponding weight gain should not comprise more water, but measures to invoke a negative cation balance. Reduction of hypernatraemia/hypertonicity is critical, but should not exceed 12 mmol/l/day in order to reduce the risk of rebounding brain oedema.

Topics: Critical Illness; Decision Support Techniques; Diuresis; Diuretics; Humans; Hypernatremia; Hyponatremia; Hypothyroidism; Iatrogenic Disease; Inappropriate ADH Syndrome; Plasma Volume; Sodium Chloride Symporter Inhibitors; Vasopressins

Critically ill patients often report distressful episodes of severe thirst, but the complex biochemical, neurohormonal mechanisms that regulate this primal sensation still elude clinicians. The most potent stimuli for thirst are subtle increases in plasma osmolality. These minute changes in osmolality stimulate central osmoreceptors to release vasopressin (also known as antidiuretic hormone). Vasopressin in turn acts on the kidneys to promote the reabsorption of water to correct the increased osmolality. If this compensatory mechanism fails to decrease osmolality, then thirst is triggered to motivate drinking. In contrast, thirst induced by marked volume loss, or hypovolemic thirst, is subject to the tight osmoregulation of the renin-angiotensin aldosterone system and accompanying adrenergic agonists. Understanding the essential role that thirst plays in salt and water regulation can provide clinicians with a better appreciation for the complex physiology that underlies this intense sensation.

Topics: Adrenergic Agonists; Critical Illness; Dehydration; Humans; Hypovolemia; Osmolar Concentration; Perception; Renin-Angiotensin System; Thirst; Vasopressins

Intravenous maintenance fluid therapy aims to replace daily urinary and insensible losses for ill children in whom adequate enteric administration of fluids is contraindicated or infeasible. The traditional determination of fluid volumes and composition dates back to Holliday and Segar's seminal article from 1957, which describes the relationship between weight, energy expenditure, and physiologic losses in healthy children. Combined with estimates of daily electrolyte requirements, this information supports the use of the hypotonic maintenance fluids that were widely used in pediatric medicine. However, using hypotonic intravenous fluids in a contemporary hospitalized patient who may have complex physiologic derangements, less caloric expenditure, decreased urinary output, and elevated antidiuretic hormone levels is often not optimal; evidence over the last 2 decades shows that it may lead to an increased incidence of hyponatremia. In this review, we present the evidence for using isotonic rather than hypotonic fluids as intravenous maintenance fluid.

Topics: Body Water; Child; Critical Care; Critical Illness; Disease Management; Diuresis; Elective Surgical Procedures; Electrolytes; Energy Metabolism; Fluid Therapy; Humans; Hyponatremia; Hypotonic Solutions; Infusions, Intravenous; Isotonic Solutions; Postoperative Care; Randomized Controlled Trials as Topic; Vasopressins; Water-Electrolyte Imbalance

Severe sepsis is a common occurrence in critically ill patients and a major cause of morbidity and mortality in this population. Management relies on the early identification and treatment of the underlying causative infection, adequate and rapid hemodynamic resuscitation, support of associated organ failure and modulation of the immune response with drotrecogin alfa (activated) when it is not contraindicated, and corticosteroids in severe septic shock. We will review current approaches to each of these categories.

Topics: Acute Kidney Injury; Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Critical Illness; Fluid Therapy; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Immunologic Factors; Protein C; Recombinant Proteins; Resuscitation; Sepsis; Vasopressins

Dysnatremias, disorders of sodium concentration, are exceedingly common in critically ill patients and confer increased risk for adverse outcomes including mortality. The physiology that underpins the diagnosis and management of these disorders is complex. This review seeks to discuss current literature regarding the pathophysiology, diagnosis, epidemiology, and management of these disorders.. The role of arginine vasopressin in the maintenance of normal and pathologic plasma osmolality increasingly is refined, improving our ability to diagnose and understand dysnatremia. Identified recent epidemiologic studies highlight the frequent hospital acquisition or exacerbation of dysnatremia, confirm the recognized adverse consequences and explore the potential causality. Despite the complex nature of these disorders, simple consensus treatment strategies have emerged.. Dysnatremia remains a common disorder across the spectrum of critically ill patients. It is frequently hospital acquired. Simplified treatment regimens are proposed and the potential for prevention or earlier recognition and intervention is emphasized. Future directions of interest include further exploration of how dysnatremia contributes to adverse outcomes and new treatment strategies.

Topics: Critical Care; Critical Illness; Humans; Hypernatremia; Hyponatremia; Intensive Care Units; Length of Stay; Prognosis; Risk; United States; Vasopressins

Vasopressin and terlipressin, a long-acting V1a analogue, are increasingly used in intensive care. The main clinical indications are the treatment of patients with septic shock and of patients with cirrhosis, who develop variceal bleeding, the hepatorenal syndrome or both. In this review, we summarize the effects of these drugs on splanchnic hemodynamics and organ function.. A recent systematic meta-analysis of randomized trials suggests that terlipressin may improve renal function in hepatorenal syndrome and thereby reduce mortality by 34%. Moreover, a recent study reported that association of terlipressin and albumin was more effective than terlipressin alone. In patients with variceal bleeding, the bleeding control is significantly improved by early administration of terlipressin. The place of vasopressin in the treatment of patients with septic shock is still discussed, but compared with norepinephrine, vasopressin showed at least an equal efficacy.. The use of vasopressin and its synthetic analogues has shown beneficial effects in the management of patients with cirrhosis, especially in the context of variceal bleeding, the hepatorenal syndrome or both. In both cases, the use of terlipressin improved survival. Therefore, in these clinical indications, terlipressin is a part of recommendations. The role of vasopressin in patients with septic shock remains to be precisely evaluated.

Topics: Critical Care; Critical Illness; Hemodynamics; Hepatorenal Syndrome; Humans; Intensive Care Units; Liver; Liver Cirrhosis; Lypressin; Risk Factors; Shock, Septic; Terlipressin; Varicose Veins; Vasoconstrictor Agents; Vasopressins

Sepsis remains a common problem in critically ill patients.. Considerable advances have been made in our understanding of the pathophysiology of sepsis and recent years have seen a surge of potential new therapeutic agents for sepsis. Definitions have been rethought and strategies proposed to better characterise patients with sepsis as the importance of individually targeted treatment packages has been realised. Current management aims to control infection, to achieve haemodynamic stabilisation, to modulate the immune response and to provide metabolic and organ support. As new therapies are introduced, treatment recommendations will need to be adapted accordingly.

Topics: Anti-Infective Agents; Bacteriological Techniques; Biomarkers; Blood Glucose; Blood Transfusion; Critical Illness; Fluid Therapy; Hemodynamics; Hospital Mortality; Humans; Hydrocortisone; Immunologic Factors; Inflammation Mediators; Intensive Care Units; Oxygen; Prognosis; Protein C; Recombinant Proteins; Resuscitation; Sepsis; Shock, Septic; Vasoconstrictor Agents; Vasopressins

Vasopressin, also called antidiuretic hormone, is a 9 amino-acid peptide, synthesized from a precursor containing neurophysin II, by neurones from the supra-optic and peri-ventricular nuclei, and then stored in the posterior hypophysis. Vasopressin regulates plasmatic osmolality and volaemia via V2 receptors at the levels of the kidney, and vascular smooth muscle tone via V1a arterial receptors. Both its synthesis and release from hypophysis vesicles depend on variations in plasma osmolality, volaemia, and arterial blood pressure. In addition, vasopressin interacts with the main hormonal systems involved in the response to stress, including the hypothalamic-pituitary adrenal axis, other anterior pituitary hormones, mainly prolactin and growth hormone, the renin-angiotensin system, and regulates insulin synthesis and glucose metabolism. Interestingly, during critical illness, exogenous administration of vasopressin showed little effects on the circulating levels of these various hormones, except an increase in prolactin. The absence of endocrine effects of vasopressin during critical illness is unclear and may relate to an already maximal hormonal stimulation or to down-regulation of vasopressin receptors.

Topics: Adrenal Cortex Hormones; Animals; Antidiuretic Agents; Critical Illness; Endocrine Glands; Hormones; Humans; Vasoconstrictor Agents; Vasopressins

To review the physiology and the published literature on the role of vasopressin in shock in children.. We searched MEDLINE (1966-2007), EMBASE (1980-2007), and the Cochrane Library, using the terms vasopressin, terlipressin, and shock and synonyms or related terms for relevant studies in pediatrics. We searched the online ISRCTN-Current Controlled Trials registry for ongoing trials. We reviewed the reference lists of all identified studies and reviews as well as personal files to identify other published studies.. Beneficial effects have been reported in vasodilatory shock and asystolic cardiac arrest in adults. Solid evidence for vasopressin use in children is scant. Observational studies have reported an improvement in blood pressure and rapid weaning off catecholamines during administration of low-dose vasopressin. Dosing in children is extrapolated from adult studies.. Vasopressin offers promise in shock and cardiac arrest in children. However, in view of the limited experience with vasopressin, it should be used with caution. Results of a double-blind, randomized controlled trial in children with vasodilatory shock will be available soon.

Topics: Animals; Cardiopulmonary Resuscitation; Child; Clinical Trials as Topic; Critical Illness; Heart Arrest; Humans; Shock; Vasoconstrictor Agents; Vasopressins

The metabolic support of critically ill patients is a relatively new topic of active research and discussion, and surprisingly little is known about the effects of critical illness on metabolic physiology and activity. The metabolic changes seen in critical illness are highly complex, and how and when to treat them are only just beginning to be determined. Studies have demonstrated that the acute phase and the later phase of critical illness behave differently from a metabolic point of view for many organs, and while many of the alterations in metabolism seen during early critical illness may be appropriate and beneficial responses to cellular stress, whether this is true for all the metabolic alterations in all forms of critical illness is unclear. Currently we face more questions than answers, and further study is needed to elucidate the various components of the metabolic response to acute and chronic critical illness and to develop better techniques to assess and monitor these changes so that we can determine which therapeutic approaches should be used in what combinations and in which patients.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Antagonists; Amino Acids; Blood Glucose; Critical Care; Critical Illness; Human Growth Hormone; Humans; Mitochondria; Multiple Organ Failure; Nutritional Support; Sepsis; Vasopressins

Vasopressin is a neuropeptide hormone which has been used clinically for more than 50 years and plays a major role in circulatory homeostasis and in the regulation of serum osmolality. Recent work has emphasized its role in the treatment of septic shock. This paper reviews the physiology of this neurohormone and the available evidence in favor of its use as a vasodilator for children in shock.. MEDLINE, using the terms vasopressin, vasodilation, shock and septic shock, plus synonyms and related terms. Classic publications on the topic were also reviewed and selected depending on their relevance to the study objectives.. Vasopressin is synthesized in the neurohypophysis and released in response to a decrease in plasma volume or an increase in serum osmolality. The action of vasopressin is mediated by the activation of oxytocin receptors and of several G protein-coupled receptors, which are classified according to their location and intracellular transmission routes as V1 receptors (or V1b), V2 and V3 receptors (or V1b). The main role of vasopressin is to induce vasoconstriction. However, in certain organs, it can also induce selective vasodilation. Several clinical studies in adults and children have reported that the effects of vasopressin for the treatment of vasodilatory septic shock, due to a variety of causes, are both beneficial and safe.. The evidence is restricted. Most studies are retrospective and include a small number of patients. Nevertheless, there is significant experience concerning the use of vasopressin in Pediatrics. Vasopressin has a beneficial clinical effect in children and can be indicated in the treatment of refractory vasodilatory shock, after adequate volume resuscitation and when high doses of other vasopressors are not effective.

Topics: Adult; Animals; Blood Pressure; Child; Critical Illness; Evidence-Based Medicine; Hemodynamics; Humans; Infusions, Intravenous; Randomized Controlled Trials as Topic; Retrospective Studies; Shock, Septic; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents; Vasopressins

Simple, sensitive and specific predictors of mortality in the critically ill remain elusive goals, and brain natriuretic peptide and venous lactate are the subjects of recent studies. The role of vasopressin in sepsis continues to be the focus of much research interest. Dose ranging studies, potential adverse effects, and selective V1 agonists are discussed below in recent trials. Finally the use of erythropoietin in the critically ill continues to be studied but many continue to urge caution for widespread use outside of clinical trials.

Topics: Animals; Critical Illness; Erythropoietin; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Vasoconstrictor Agents; Vasopressins

In critical care medicine, catecholamines are most widely used to reverse circulatory dysfunction and thus to restore tissue perfusion. However, catecholamines not only influence systemic and regional hemodynamics, but also exert a variety of significant metabolic, endocrine, and immunologic effects. Arginine vasopressin is a vasomodulatory hormone with potency to restore vascular tone in vasodilatory hypotension. Although the evidence supporting the use of low doses of vasopressin or its analogs in vasodilatory shock is increasing, lack of data regarding mortality and morbidity prevent their implementation in critical care protocols.

Topics: Catecholamines; Critical Illness; Hemodynamics; Humans; Immune System; Neurosecretory Systems; Receptors, Vasopressin; Regional Blood Flow; Shock; Shock, Septic; Splanchnic Circulation; Stress, Physiological; Vasodilation; Vasopressins

Variceal bleeding is a severe complication of cirrhosis leading to significant morbidity and mortality. Treatment of acute variceal bleeding has improved dramatically since the era of the mechanical balloon tamponade. These advances include endoscopic band ligation or sclerotherapy, and vasoactive pharmacological options such as somatostatin, octreotide, vasopressin and terlipressin. Evidence from a multitude of clinical trials and meta-analyses comparing endoscopic and pharmacological treatments suggests near equivalence in efficacy for initial hemostasis, mortality and rate of rebleeding. This raises the question of whether on-call gastroenterologists should be performing emergency endoscopic treatment in the middle of the night or start pharmacological treatment and delay endoscopy until optimal patient and working conditions the next morning. The present review analyzes the available comparative data between endoscopic and pharmacological treatment options. Although the literature cannot yet definitively answer the question posed, the authors suggest that delaying endoscopic treatment until the next morning may be the most reasonable practical approach.

Topics: Critical Illness; Emergency Treatment; Esophageal and Gastric Varices; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Hemostasis, Endoscopic; Hemostatics; Humans; Ligation; Male; Octreotide; Risk Assessment; Sclerotherapy; Survival Analysis; Time Factors; Treatment Outcome; Vasopressins

Critical illness is characterized by striking alterations in the hypothalamic-anterior-pituitary-peripheral-hormone axes, the severity of which is associated with a high risk of morbidity and mortality. Most attempts to correct hormone balance have been shown ineffective or even harmful because of a lack of pathophysiologic insight. There is a biphasic (neuro)endocrine response to critical illness. The acute phase is characterized by an actively secreting pituitary, but the concentrations of most peripheral effector hormones are low, partly due to the development of target-organ resistance. In contrast, in prolonged critical illness, uniform (predominantly hypothalamic) suppression of the (neuro)endocrine axes contributes to the low serum levels of the respective target-organ hormones. The adaptations in the acute phase are considered to be beneficial for short-term survival. In the chronic phase, however, the observed (neuro)endocrine alterations appear to contribute to the general wasting syndrome. With the exception of intensive insulin therapy, and perhaps hydrocortisone administration for a subgroup of patients, no hormonal intervention has proven to beneficially affect outcome. The combined administration of hypothalamic releasing factors does, however, hold promise as a safe therapy to reverse the (neuro)endocrine and metabolic abnormalities of prolonged critical illness by concomitant reactivation of the different anterior-pituitary axes.

Topics: Acute Disease; Adrenal Glands; Catecholamines; Chronic Disease; Critical Illness; Endocrine System; Gonads; Hormones; Models, Biological; Thyroid Gland; Vasopressins

This article summarizes the effects of catecholamines and vasopressin on the cardiovascular system, focusing on their metabolic and immunologic properties. Particular attention is dedicated to the septic shock condition.

Topics: Catecholamines; Critical Care; Critical Illness; Humans; Shock, Septic; Vasopressins

Disorders of sodium and water homeostasis are among the most commonly encountered disturbances in the critical care setting, because many disease states cause defects in the complex mechanisms that control the intake and output of water and solute. Because body water is the primary determinant of extracellular fluid osmolality, disorders of body water balance can be categorized into hypoosmolar and hyperosmolar disorders depending on the presence of an excess or a deficiency of body water relative to body solute. Because the main constituent of plasma osmolality is sodium, hypoosmolar and hyperosmolar disease states are generally characterized hy hyponatremia and hypernatremia, respectively. After a brief review of normal water metabolism, this article focuses on the diagnosis and treatment of hyponatremia and hypernatremia in the critical care setting.

Topics: Body Water; Critical Illness; Homeostasis; Humans; Hypernatremia; Hyponatremia; Osmolar Concentration; Vasopressins

Many advances have improved the care of critically ill patients, but only a few have been through the use of pharmaceutical agents. Recently, the US Food and Drug Administration (FDA) approved drotrecogin alfa (activated), or recombinant human activated protein C, for the treatment of patients with a high risk of death from severe sepsis. Drotrecogin alfa (activated) has antiinflammatory, antithrombotic and fibrinolytic properties. When given as a continuous intravenous infusion, recombinant human activated protein C decreases absolute mortality of severely septic patients by 6.1%, resulting in a 19.4% relative reduction in mortality. The absolute reduction in mortality increases to 13% if the population treated is restricted to patients with an APACHE II score greater than 24, as suggested by the FDA. The most frequent and serious side effect is bleeding. Severe bleeds increased from 2% in patients given placebo to 3.5% in patients receiving drotrecogin alfa (activated). The risk of bleeding was only increased during the actual infusion time of the drug, and the bleeding risk returned to placebo levels 24 hours after the infusion was discontinued. Patients treated in the intensive care unit frequently develop anemia, usually severe enough to require at least one transfusion of red blood cells. With the recent discovery of the harmful effects of allogeneic red blood cell transfusions and the increasing shortage of available red blood cell products, emphasis has been placed on minimizing transfusions. Patients who receive exogenous recombinant human erythropoietin maintain higher hemoglobin levels, in spite of requiring fewer transfusions during their stay in the intensive care unit. Recombinant human erythropoietin appears to be effective whether it is given as 300 units/kg of body weight subcutaneously every other day or as 40,000 units subcutaneously every week. Differences in hemoglobin values were not apparent until at least one week of therapy, but they continued to diverge after that initial week. Furthermore, the incidence of adverse events was similar to that of patients receiving placebo and there was no difference in mortality, suggesting that avoidance of blood transfusions did not translate into increased survival. Thus, recombinant human erythropoietin appears to be both safe and effective in treating the anemia found in critically ill patients, but it is less clear that such treatment is cost effective, especially in the higher dose regimens

Topics: Critical Care; Critical Illness; Epoetin Alfa; Erythropoietin; Humans; Protein C; Recombinant Proteins; Shock, Septic; Vasopressins

Esophageal varices develop in patients with cirrhosis once portal pressure, measured by hepatic venous pressure gradient, and exceeds 10 mm Hg. At a portal pressure of 12 mm Hg, variceal bleeding may develop that is associated with a mortality of 30% to 50% per episode. In addition to an elevated portal pressure, other risk factors for the development of variceal hemorrhage include: variceal size, endoscopic features on the variceal wall (i.e., red wales), and Child-Pugh class. In patients with suspected variceal hemorrhage, the treatment of the acute episode includes intravascular volume expansion, hemostasis through the use of pharmacological agents and endoscopy, and the prevention and treatment of potential complications associated with variceal hemorrhage such as aspiration pneumonia, spontaneous bacterial peritonitis and hepatic encephalopathy. Given a high rate of rebleeding, long-term prevention through secondary prophylaxis should be instituted in all patients who have survived an episode of variceal bleeding. Current prophylactic options include: non-selective beta-blockers alone (first line) or in combination with long-acting nitrates (isosorbide mononitrate) and/or endoscopic variceal obliteration achieved through sclerotherapy or preferably, band ligation.

Topics: Critical Illness; Diagnosis, Differential; Drug Therapy, Combination; Endoscopy, Gastrointestinal; Esophageal and Gastric Varices; Hemostatics; Hepatitis C, Chronic; Humans; Male; Middle Aged; Nitroglycerin; Sclerotherapy; Vasodilator Agents; Vasopressins

The main clinical characteristics of sepsis and septic shock are derangements of cardiocirculatory and respiratory function. Additionally, profound alterations in metabolic pathways occur leading to hypermetabolism, enhanced energy expenditure, and insulin resistance. The clinical hallmarks are hyperglycemia, hyperlactatemia, and enhanced protein catabolism. These metabolic alterations are even more pronounced during sepsis as a result of cytokine release and subsequent induction of inflammatory pathways. Increased oxygen demands from mitochondrial oxygen utilization and oxygen consumption related to oxygen radical formation may contribute to hypermetabolism. In addition, mitochondrial dysfunction with impaired cellular respiration may be present. Mainstay therapeutic interventions for hemodynamic stabilization are adequate volume resuscitation and vasoactive agents, which, however, have additional impact on metabolic activity. Therefore, beyond hemodynamic effects, specific drug-related metabolic alterations need to be considered for optimal treatment during sepsis. This review gives an overview of the typical metabolic alterations during sepsis and septic shock and highlights the impact of vasoactive therapy on metabolism.

Topics: Adrenergic Agonists; Catecholamines; Critical Illness; Energy Metabolism; Epoprostenol; Glucose; Humans; Lactates; Mitochondria; Sepsis; Vasopressins

The clinical spectrum of sepsis, severe sepsis, and septic shock is responsible for a growing number of deaths and excessive health care expenditures. Until recently, despite multiple clinical trials, no intervention provided a beneficial outcome in septic patients. Within the last 2 years, studies that involved drotrecogin alfa (activated), corticosteroid therapy, and early goal-directed therapy showed efficacy in those with severe sepsis and septic shock. These results have provided optimism for reducing sepsis-related mortality.

Topics: Adrenal Cortex Hormones; Clinical Protocols; Critical Care; Critical Illness; Dopamine; Fibrinolytic Agents; Hemodynamics; Hemostatics; Heparin; Humans; Insulin; Multiple Organ Failure; Protein C; Recombinant Proteins; Respiration, Artificial; Respiratory Distress Syndrome; Sepsis; Shock, Septic; Vasopressins

To investigate the physiologic effects of exogenous vasopressin as a potential alternative to traditional high-dose catecholamine therapy for septic patients with vascular hyporeactivity to catecholamines.. Prospective, case-controlled study.. Intensive care unit of a university hospital.. Vasopressin was infused in 16 critically ill septic patients who remained persistently hypotensive despite infusions of pharmacologic doses of catecholamines.. Continuous intravenous infusion of vasopressin at 0.04 units/min for 16 hrs, in place of escalating the amount of catecholamines being infused.. After administration of vasopressin, systemic vascular resistance and mean arterial pressure were immediately and significantly increased in comparison with the values obtained just before vasopressin. When the vasopressin infusions were discontinued, mean arterial pressure decreased immediately and dramatically. We did not detect any obvious adverse cardiac effects during the vasopressin infusions. Vasopressin had no effect on other hemodynamic parameters or any of the metabolic parameters studied, including measures of oxygenation, plasma glucose, or electrolytes. Urine output increased significantly during the administration of vasopressin, although this effect may be nonspecific. Lactate concentrations decreased, particularly in the survival group, but the decreases were not significant. Overall survival was 56%.. Low-dose vasopressin infusions increased mean arterial pressure, systemic vascular resistance, and urine output in patients with vasodilatory septic shock and hyporesponsiveness to catecholamines. The data indicate that low-dose vasopressin infusions may be useful in treating hypotension in these patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Blood Gas Analysis; Blood Glucose; Critical Illness; Drug Monitoring; Electrolytes; Female; Hemodynamics; Humans; Infusions, Intravenous; Lactic Acid; Male; Middle Aged; Prospective Studies; Renin; Shock, Septic; Survival Analysis; Time Factors; Vasoconstrictor Agents; Vasopressins

In septic shock, vasopressors aim to improve tissue perfusion and prevent persistent organ dysfunction, a characteristic of chronic critical illness (CCI). Adjunctive vasopressin is often used to decrease catecholamine dosage, but the association of vasopressin response with subsequent patient outcomes is unclear. We hypothesized vasopressin response is associated with favorable clinical trajectory.. We included patients with septic shock receiving vasopressin as a catecholamine adjunct in this retrospective cohort study. We defined vasopressin response as a lowering of the catecholamine dose required to maintain mean arterial pressure ≥65 mm Hg, 6 h after vasopressin initiation. Clinical trajectories were adjudicated as early death (ED; death before day 14), CCI (ICU stay ≥14 days with persistent organ dysfunction), or rapid recovery (RR; not meeting ED or CCI criteria). Trajectories were placed on an ordinal scale with ED the worst outcome, CCI next, and RR the best outcome. The association of vasopressin response with clinical trajectory was assessed with multivariable ordinal logistic regression.. In total 938 patients were included; 426 (45.4%) were vasopressin responders. The most frequent trajectory was ED (49.8%), 29.7% developed CCI, and 20.5% had rapid recovery. In survivors to ICU day 14 (those without ED), 59.2% had CCI and 40.8% experienced RR. Compared with vasopressin non-responders, vasopressin responders less frequently experienced ED (42.5% vs. 55.9%) and more frequently experienced RR (24.6% vs. 17.0%;. Vasopressin responsive status was associated with improved clinical trajectory in septic shock patients. Early vasopressin response is a potential novel prognostic marker for short-term clinical trajectory.

Topics: Catecholamines; Critical Illness; Humans; Multiple Organ Failure; Retrospective Studies; Shock, Septic; Vasoconstrictor Agents; Vasopressins

Topics: Critical Illness; Humans; Norepinephrine; Phenylephrine; Retrospective Studies; Shock, Septic; Vasoconstrictor Agents; Vasopressins

Topics: Critical Illness; Humans; Norepinephrine; Phenylephrine; Retrospective Studies; Shock, Septic; Vasoconstrictor Agents; Vasopressins

Topics: Critical Illness; Humans; Norepinephrine; Phenylephrine; Retrospective Studies; Shock, Septic; Vasoconstrictor Agents; Vasopressins

Topics: Critical Illness; Humans; Norepinephrine; Phenylephrine; Retrospective Studies; Shock, Septic; Vasoconstrictor Agents; Vasopressins

This study aims to explore the association between early administration of vasopressors and in-hospital mortality in acute pancreatitis (AP) patients admitted to the ICU.. The MIMIC-IV database was used to identify AP patients who had and had not received vasopressors. Univariate and multivariate logistic regression, propensity score matching (PSM), and inverse probability of treatment weighting (IPTW) were used for statistical analysis.. A total of 894 AP patients admitted to the ICU were included in the study. Among them, AP patients who received vasopressors were associated with an increased risk of in-hospital mortality in the unadjusted model (OR: 7.77, 95% CI 4.92-12.61, p<0.001), multivariable-adjusted model (OR: 2.51,95% CI 1.1-5.76, p<0.05), PSM model (OR: 2.58, 95% CI 1.03-6.85, p<0.05) and IPTW model (OR: 1.82, 95% CI 1.06-3.15, p<0.05) compared with patients who did not receive vasopressors. In the subgroup analysis, age (≥ 65 years old: OR: 2.5, 95% CI 0.82-7.91; <65 years old: OR: 4.63, 95% CI 0.84-26.41), male (OR: 1.19, 95% CI 0.35-4.03), ethnicity (white: OR: 2.49, 95% CI 0.81-7.62; non-white: OR: 4.28, 95% CI 0.85-23.7), usage of norepinephrine (OR: 2.29, 95% CI 0.91-5.78), and single-use of vasopressor (OR: 1.48, 95% CI 0.43-4.95) were not associated with in-hospital mortality in patients with AP, whereas vasopressin (OR: 4.27, 95% CI 1.24-15.13; p<0.05) and phenylephrine usage (OR: 4.75, 95% CI 1.66-13.95; p<0.05), combined vasopressor usage (OR: 4.41, 95% CI 1.55-12.96; p<0.01), and female usage (OR: 7.89, 95% CI 2.03-34.2; p<0.01) were associated with in-hospital mortality.. Early vasopressor use is significantly associated with increased in-hospital mortality among critically ill AP patients. This association might be greater in females, vasopressin, phenylephrine, and combined vasopressor users. Our results may benefit clinicians as they can guide the rational use of vasopressors in critically ill AP patients admitted to the ICU.

Topics: Acute Disease; Aged; Cohort Studies; Critical Illness; Female; Hospital Mortality; Humans; Intensive Care Units; Male; Pancreatitis; Phenylephrine; Retrospective Studies; Vasoconstrictor Agents; Vasopressins

There have been recent advances assessing copeptin levels in adults with suspected disorders of vasopressin release. Very limited data exits on copeptin levels in children and infants, especially in a critically-ill hospitalized population where hyper- and hypo-natremia are very common. Our objective is to describe the institutional experience assessing copeptin levels in hospitalized infants and children with hyper- or hypo-natremia.. We performed a single-center retrospective case series of all infants, children, and adolescents who had an ultrasensitive plasma copeptin level obtained between 2019-2021.. A total of 29 critically ill patients (6 infants) were identified with 38 % of patients having copeptin levels after neurosurgical procedures for tumors or trauma. Approximately 13/17 children with hypernatremia had central diabetes insipidus (central diabetes insipidus) to diagnose CDI, A copeptin level ≤ 4.9 pmol/L resulted in an 88 % sensitivity (95 % CI 47-99 %), and 66 % specificity (95 % CI 30-93 %). Amongst those with hyponatremia levels were more variable, 8/12 children had syndrome of inappropriate antidiuresis (SIAD) with copeptin levels ranging 4.7-72.6 pmol/L.. While difficult to conclude due to multiple limitations, this case series highlights that typical copeptin cutoffs used to diagnose DI in adults in an ambulatory setting may also translate to a critically-ill pediatric population. Large prospective studies are needed to confirm this observation. In addition, postoperative copeptin levels could potentially be utilized as an additional marker to predict permanent from transient DI, but much larger studies are needed. Further work is needed to establish normative copeptin levels in infants and patients with SIAD.

Topics: Adolescent; Child; Critical Illness; Diabetes Insipidus, Neurogenic; Humans; Infant; Retrospective Studies; Vasopressins

Aneurysmal subarachnoid hemorrhage (aSAH) is an important indication for intensive care unit admission and may lead to significant morbidity and mortality. We assessed the ability of C-terminal proarginine vasopressin (CT-proAVP) to predict disease outcome, mortality, and delayed cerebral ischemia (DCI) in critically ill patients with aSAH compared with the World Federation of Neurological Surgeons (WFNS) score and Acute Physiological and Chronic Health Evaluation IV (APACHE IV) model.. C-terminal proarginine vasopressin was collected on admission in this single-center, prospective, observational cohort study. The primary aim was to investigate the relationship between CT-proAVP and poor functional outcome at 1 year (Glasgow Outcome Scale score 1-3) in a multivariable logistic regression model adjusted for WFNS and APACHE IV scores. Secondary aims were mortality and DCI. The multivariable logistic regression model for DCI was also adjusted for the modified Fisher scale.. In 100 patients, the median CT-proAVP level was 24.9 pmol/L (interquartile range 11.5-53.8); 45 patients had a poor 1-year functional outcome, 19 patients died within 30 days, 25 patients died within 1 year, and DCI occurred in 28 patients. Receiver operating characteristics curves revealed high accuracy for CT-proAVP to identify patients with poor 1-year functional outcome (area under the curve [AUC] 0.84, 95% confidence interval [CI] 0.77-0.92, p < 0.001), 30-day mortality (AUC 0.84, 95% CI 0.76-0.93, p < 0.001), and 1-year mortality (AUC 0.79, 95% CI 0.69-0.89, p < 0.001). CT-proAVP had a low AUC for identifying patients with DCI (AUC 0.67, 95% CI 0.55-0.79, p 0.008). CT-proAVP ≥ 24.9 pmo/L proved to be a significant predictor for poor 1-year functional outcome (odds ratio [OR] 8.04, 95% CI 2.97-21.75, p < 0.001), and CT-proAVP ≥ 29.1 pmol/L and ≥ 27.7 pmol/L were significant predictors for 30-day and 1-year mortality (OR 9.31, 95% CI 1.55-56.07, p 0.015 and OR 5.15, 95% CI 1.48-17.93, p 0.010) in multivariable models with WFNS and APACHE IV scores. CT-proAVP ≥ 29.5 pmol/L was not a significant predictor for DCI in a multivariable model adjusted for the modified Fisher scale (p = 0.061).. C-terminal proarginine vasopressin was able to predict poor functional outcome and mortality in critically ill patients with aSAH. Its prognostic ability to predict DCI was low.. Nederlands Trial Register: NTR4118.

Topics: Brain Ischemia; Cerebral Infarction; Cohort Studies; Critical Illness; Humans; Prospective Studies; Subarachnoid Hemorrhage; Vasopressins

To evaluate the outcomes of patients with septic shock treated with a combination of norepinephrine with phenylephrine compared to norepinephrine with vasopressin.. This was a retrospective cohort study including adults admitted between 2002 and 2017 with septic shock according to the Sepsis 3 criteria. We compared outcomes of patients treated with norepinephrine with phenylephrine to those treated with norepinephrine with vasopressin. Multivariate analysis was carried out to evaluate the association of norepinephrine with phenylephrine compared to norepinephrine with vasopressin with in-hospital mortality.. During the study period, 158 patients with septic shock were treated with norepinephrine with phenylephrine and 129 with norepinephrine with vasopressin. Crude in-hospital mortality was not different between the two groups [91/158 (57.6%) versus 80/129 (62.5%), p = 0.40]. There was also no difference in ICU length of stay or hospital length of stay. Multivariate analysis demonstrated no significant association of norepinephrine with phenylephrine with in-hospital mortality compared to norepinephrine with vasopressin (OR 0.62 (95% confidence interval 0.31, 1.23, p = 0.17).. Phenylephrine used as a second-line vasoactive agent combined with norepinephrine may be a reasonable option compared to vasopressin. However, this finding needs to be validated in a randomized controlled trial.

Topics: Adult; Critical Illness; Humans; Norepinephrine; Phenylephrine; Retrospective Studies; Shock, Septic; Vasoconstrictor Agents; Vasopressins

BACKGROUND The aim of this study was to assess the impact of norepinephrine (NE), norepinephrine plus vasopressin (NE+VAS) and dopamine in patients with sepsis and heart failure. MATERIAL AND METHODS Data were extracted from the Medical Information Mart for Intensive Care III database, v1.4. Adults aged >18 years in an Intensive Care Unit (ICU) who had heart failure and took vasopressors were included. The patients were divided into 3 groups: NE, NE+VAS, and dopamine. Differences in survival, treatment time, and organ function among the 3 groups were compared. Propensity score matching (PSM) was used to screen for possible prognostic differences, and regression analysis was used to further analyze and predict prognoses. RESULTS A total of 1864 patients were included. There were significant differences among the 3 groups in 7-, 28-, and 90-day mortality after PSM. The 5-year survival rates among the 3 groups also were significantly different (P<0.001). After Cox regression analysis, NE+VAS was an independent risk factor affecting 5-year survival (P<0.001). After multiple linear regression, dopamine was the factor related to ICU and hospital lengths of stay. CONCLUSIONS Compared with NE or dopamine alone, NE+VAS can reduce survival in patients with sepsis and heart failure who need vasopressors. Compared with the other 2 treatment options, dopamine can shorten ICU and hospital stays for these patients.

Topics: Acute Disease; Aged; Cardiotonic Agents; Cohort Studies; Critical Illness; Dopamine; Female; Heart Failure; Humans; Length of Stay; Male; Norepinephrine; Retrospective Studies; Sepsis; Survival Rate; Vasoconstrictor Agents; Vasopressins

Topics: COVID-19; Critical Illness; Humans; Pilot Projects; SARS-CoV-2; Vasopressins

Topics: Critical Illness; Humans; Hypotension; Incidence; Vasoconstrictor Agents; Vasopressins

Randomised controlled trials (RCTs) enrolling patients with sepsis or acute respiratory distress syndrome (ARDS) generate heterogeneous trial populations. Non-random variation in the treatment effect of an intervention due to differences in the baseline risk of death between patients in a population represents one form of heterogeneity of treatment effect (HTE). We assessed whether HTE in two sepsis and one ARDS RCTs could explain indeterminate trial results and inform future trial design.. We assessed HTE for vasopressin, hydrocortisone and levosimendan in sepsis and simvastatin in ARDS patients, on 28-day mortality, using the total Acute Physiology And Chronic Health Evaluation II (APACHE II) score as the baseline risk measurement, comparing above (high) and below (low) the median score. Secondary risk measures were the acute physiology component of APACHE II and predicted risk of mortality using the APACHE II score. HTE was quantified both in additive (difference in risk difference (RD)) and multiplicative (ratio of relative risks (RR)) scales using estimated treatment differences from a logistic regression model with treatment risk as the interaction term.. The ratio of the odds of death in the highest APACHE II quartile was 4.9 to 7.4 times compared to the lowest quartile, across the three trials. We did not observe HTE for vasopressin, hydrocortisone and levosimendan in the two sepsis trials. In the HARP-2 trial, simvastatin reduced mortality in the low APACHE II group and increased mortality in the high APACHE II group (difference in RD = 0.34 (0.12, 0.55) (p = 0.02); ratio of RR 3.57 (1.77, 7.17) (p < 0.001). The HTE patterns were inconsistent across the secondary risk measures. The sensitivity analyses of HTE effects for vasopressin, hydrocortisone and levosimendan were consistent with the main analyses and attenuated for simvastatin.. We assessed HTE in three recent ICU RCTs, using multivariable baseline risk of death models. There was considerable within-trial variation in the baseline risk of death. We observed potential HTE for simvastatin in ARDS, but no evidence of HTE for vasopressin, hydrocortisone or levosimendan in the two sepsis trials. Our findings could be explained either by true lack of HTE (no benefit of vasopressin, hydrocortisone or levosimendan vs comparator for any patient subgroups) or by lack of power to detect HTE. Our results require validation using similar trial databases.

Topics: Adult; Aged; Anti-Inflammatory Agents; APACHE; Cardiotonic Agents; Critical Illness; Female; Guideline Adherence; Hospital Mortality; Humans; Hydrocortisone; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intensive Care Units; Male; Middle Aged; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome; Sepsis; Simendan; Simvastatin; Treatment Outcome; Vasoconstrictor Agents; Vasopressins

Vasopressin is commonly used as an adjunct vasopressor in shock. However, response to vasopressin varies among critically ill patients.. To identify patient-specific factors that are associated with vasopressin responsiveness in critically ill adults.. This retrospective, multicenter study included adult patients who were admitted to an intensive care unit (ICU) and received vasopressin for shock. Patients were excluded if they received vasopressin for less than 30 minutes, if vasopressin was initiated prior to ICU arrival, or if an additional vasopressor was initiated within 30 minutes of starting vasopressin. Responsiveness was defined as an increase in mean arterial pressure of ≥10 mm Hg or the ability to taper a concurrent catecholamine vasopressor. Patient-specific factors evaluated in a multivariate analysis included age, gender, ethnicity, body mass index, type of shock, serum pH, Sequential Organ Failure Assessment (SOFA) score, and use of stress-dose steroids. These variables were also evaluated in a subgroup analysis of patients with septic shock.. Of 1619 patients screened, 400 patients were included, with 231 identified as vasopressin responsive and 169 as nonresponsive. Vasopressin used as an adjunct vasopressor, as opposed to first line, during shock was the only variable associated with vasopressin responsiveness (odds ratio [OR] = 1.71; 95% CI = 1.10 to 2.65). Among the subgroup of patients with septic shock, female patients had a higher odds of responding than male patients (OR = 2.10; 95% CI = 1.12 to 3.95).. Vasopressin initiated as an adjunct vasopressor, as opposed to first-line therapy, was associated with response.

Topics: Aged; Arterial Pressure; Critical Illness; Female; Humans; Intensive Care Units; Male; Middle Aged; Retrospective Studies; Shock, Septic; Vasoconstrictor Agents; Vasopressins

The objective of this retrospective study was to evaluate the safety of enteral feeding in children receiving vasoactive agents (VAs).. Patients aged 1 month to 18 years with a pediatric intensive care unit stay for ≥96 hours during 2007 and 2008 who received any VA (epinephrine, norepinephrine, vasopressin, milrinone, dopamine, and dobutamine) were included and categorized into fed and nonfed groups. Their demographics, clinical characteristics, type and dose of VA, and presence of gastrointestinal (GI) outcomes were obtained. GI outcomes were compared between the groups by the χ(2) test, Mann-Whitney test, and logistic regression.. In total, 339 patients were included. Of these, 55% were in the fed group and 45% in the nonfed group. Patients in the fed group were younger (median age, 1.05 vs 2.75 years, respectively; P < .001) and tended to have a lower Pediatric Index of Mortality 2 (PIM2) risk of mortality (ROM) than those in the nonfed group (median, 3.33% vs 3.52%, respectively; P = .106). Mortality was lower in the fed group than the nonfed group (6.9% vs 15.9%, respectively; odds ratio [OR], 0.39; 0.18-0.84; P < .01, 95% CI), while GI outcomes did not differ between the groups. The vasoactive-inotropic score (VIS) did not differ between the groups except on day 1 (P = .017). The ROM did not differ between the groups after adjusting for age, PIM2 ROM, and VIS on day 1 (OR, 0.58; 0.26-1.28; P = .18, 95% CI).. Enteral feeding in patients receiving VAs is associated with no difference in GI outcomes and a tendency towards lower mortality. Prospective studies are required to confirm the safety of enteral feedings in patients receiving VAs.

Topics: Adolescent; Cardiovascular Agents; Child; Child, Preschool; Critical Illness; Dobutamine; Dopamine; Enteral Nutrition; Epinephrine; Female; Gastrointestinal Tract; Humans; Infant; Intensive Care Units, Pediatric; Length of Stay; Logistic Models; Male; Milrinone; Norepinephrine; Retrospective Studies; Vasopressins

Vasopressors are lifesaving agents used to raise mean arterial pressure in critically ill patients in shock states. The pharmacodynamics of these agents suggest vasopressors may play a role in development of pressure ulcers; however, this aspect has been understudied.. To examine associations between type, dose, and duration of vasopressors (norepinephrine, epinephrine, vasopressin, phenylephrine, dopamine) and development of pressure ulcers in medical-surgical and cardiothoracic intensive care unit patients and to examine predictors of the development of pressure ulcers in these patients.. A retrospective correlational design was used in a sample of 306 medical-surgical and cardiothoracic intensive care unit patients who received vasopressor agents during 2012.. Norepinephrine and vasopressin were significantly associated with development of pressure ulcers; vasopressin was the only significant predictor in multivariate analysis. In addition, mean arterial pressure less than 60 mm Hg in patients receiving vasopressors, cardiac arrest, and mechanical ventilation longer than 72 hours were predictive of development of pressure ulcers. Patients with a cardiac diagnosis at the time of admission to the intensive care unit were less likely than patients without such a diagnosis to experience pressure ulcers while in the unit.. The addition of vasopressin administered concomitantly with a first-line agent (often norepinephrine) may represent the point at which the risk for pressure ulcers escalates and may be an early warning to heighten strategies to prevent pressure ulcers. Conversely, because vasopressors cannot be terminated to avert development of pressure ulcers, these findings may add to the body of knowledge on factors that potentially contribute to the development of unavoidable pressure ulcers.

Topics: Adult; Aged; Aged, 80 and over; Critical Care; Critical Illness; Female; Humans; Male; Middle Aged; Norepinephrine; Phenylephrine; Pressure Ulcer; Retrospective Studies; Vasoconstrictor Agents; Vasopressins; Young Adult

The objective of this study was to determine the effect of early vs late vasopressin therapy on catecholamine dose and duration.. We conducted a single-center, retrospective chart review of adult patients admitted to the medical intensive care unit between January 2010 and December 2011 with septic shock requiring catecholamine and vasopressin therapy. Patients were included in the early group if vasopressin was initiated within 6 hours and the late group if vasopressin was initiated between 6 and 48 hours of catecholamine(s).. Duration of catecholamine and vasopressin therapy was similar between the 35 patients in the early group and the 36 in the late group. Vasopressin therapy was associated with a decrease in catecholamine requirements in both groups. Early vasopressin was associated with fewer new onset arrhythmias (37.1% vs 62.9%, P<.001). There was no difference in mortality, hospital, or intensive care unit length of stay between the early and late group vasopressin groups (88.6% vs 88.9%, P=1; 14 vs 10 days, P=.48; 9 vs 7 days, P=.71, respectively).. Early initiation of vasopressin therapy in adult critically ill patients with septic shock was associated with no difference in total catecholamine requirements but decreased incidence of new onset arrhythmias.

Topics: Aged; Arginine Vasopressin; Arrhythmias, Cardiac; Catecholamines; Critical Illness; Drug Administration Schedule; Female; Hospital Mortality; Humans; Incidence; Intensive Care Units; Male; Middle Aged; Retrospective Studies; Shock, Septic; Vasopressins

To determine the population pharmacokinetics of unbound hydrocortisone in critically ill neonates and infants receiving IV hydrocortisone for treatment of vasopressor-resistant hypotension and to identify patient-specific sources of pharmacokinetic variability.. Prospective observational cohort study.. Level 3 neonatal ICU.. Sixty-two critically ill neonates and infants receiving IV hydrocortisone as part of standard of care for the treatment of vasopressor-resistant hypotension: median gestational age 28 weeks (range, 23-41), median weight 1.2 kg (range, 0.5-4.4), and 29 females.. None.. Unbound baseline cortisol and postdose hydrocortisone concentrations measured from blood samples being drawn for routine laboratory tests. A one-compartment model best described the data. Allometric weight and postmenstrual age were significant covariates on unbound hydrocortisone clearance and volume of distribution. Final population estimates for clearance, volume of distribution, and baseline cortisol concentration were 20.2 L/hr, 244 L, and 1.37 ng/mL, respectively. Using the median weight and postmenstrual age of our subjects (i.e., 1.2 kg and 28 wk) in the final model, the typical unbound hydrocortisone clearance and volume of distribution were 1.0 L/hr and 4.2 L, respectively. The typical half-life for unbound hydrocortisone was 2.9 hours. A sharp and continuous increase in unbound hydrocortisone clearance was observed at 35 weeks postmenstrual age.. We report the first pharmacokinetic data for unbound hydrocortisone, the pharmacologically active moiety, in critically ill neonates and infants with vasopressor-resistant hypotension. Unbound hydrocortisone clearance increased with body weight and was faster in children with an older postmenstrual age. Unbound hydrocortisone clearance increased sharply at 35 weeks postmenstrual age and continued to mature thereafter. This study lays the groundwork for evaluating unbound hydrocortisone exposure-response relationships and drawing definitive conclusions about the dosing of IV hydrocortisone in critically ill neonates and infants with vasopressor-resistant hypotension.

Topics: Blood Pressure; Body Weight; Critical Illness; Drug Resistance; Female; Gestational Age; Half-Life; Hormones; Humans; Hydrocortisone; Hypotension; Infant; Infant, Newborn; Male; Prospective Studies; Vasopressins

The stress response to surgery, critical illness, trauma, and burns encompasses derangements of metabolic and physiological processes that induce perturbations in the inflammatory, acute phase, hormonal, and genomic responses. Hypermetabolism and hypercatabolism result, leading to muscle wasting, impaired immune function and wound healing, organ failure, and death. The surgery-induced stress response is largely similar to that triggered by traumatic injuries; the duration of the stress response, however, varies according to the severity of injury (surgical or traumatic). This spectrum of injuries and insults ranges from small lacerations to severe insults such as large poly-traumatic and burn injuries. Burn injuries provide an extreme model of trauma induced stress responses that can be used to study the long-term effects of a prolonged stress response. Although the stress response to acute trauma evolved to confer improved chances of survival following injury, in modern surgical practice the stress response can be detrimental.

Topics: Burns; Critical Illness; Growth Hormone; Humans; Hydrocortisone; Inflammation; Muscular Diseases; Stress, Physiological; Surgical Procedures, Operative; Vasopressins; Wound Healing; Wounds and Injuries

Topics: Africa, Eastern; Albumins; Anemia; Child; Coma; Critical Illness; Developing Countries; Dose-Response Relationship, Drug; Drug Administration Schedule; Fever; Fluid Therapy; Humans; Meningitis, Bacterial; Pneumonia; Randomized Controlled Trials as Topic; Resuscitation; Shock; Sodium Chloride; Vasopressins

As vasopressin is a small peptide, its sieving coefficient (SC) and clearance (CL) during continuous renal replacement therapy may be intermediate to those for urea and β2 microglobulin (commonly used markers for small- and middle-molecular weight solutes, respectively).. A prospective, minimal-risk study was undertaken of the SC and CL of vasopressin in critically ill children on the first day of continuous renal replacement therapy using AN69 membrane filters and prefilter replacement fluid. All prefilter plasma (vasopressin) samples were drawn from the arterial port after predilution.. Nine patients with fluid overload, renal failure, or both were recruited (median age, 14 years) during the first day of either continuous venovenous hemofiltration (n = 3) or hemodiafiltration (n = 6). Multiorgan dysfunction syndrome was present in 8 patients, and 3 were in shock (2 were receiving a vasopressin infusion). Median prefilter plasma (vasopressin) was 1.7 pg/mL, although data points were skewed: 5 patients had a low prefilter plasma (vasopressin) (<2 pg/mL), and 4 patients (including 2 receiving a continuous vasopressin infusion) had a prefilter plasma (vasopressin) between 4.2 and 56.4 pg/mL. All those with low prefilter plasma (vasopressin) had an effluent (vasopressin) less than the detection limit (0.6 pg/mL). The median SC was 1 in the 4 patients with a measurable effluent (vasopressin), and their median filter CL was 48 mL/min or 39 mL/(min 1.73 m(2)).. The SC and CL of vasopressin by continuous venovenous hemofiltration or hemodiafiltration in these critically ill children were similar to values for urea.

Topics: Adolescent; beta 2-Microglobulin; Child; Child, Preschool; Critical Care; Critical Illness; Hemodiafiltration; Hemofiltration; Humans; Infant; Metabolic Clearance Rate; Multiple Organ Failure; Prospective Studies; Renal Replacement Therapy; Shock; Urea; Vasopressins; Young Adult

The extent of neuroendocrine dysfunction (NED) has not been well defined in critically ill children and likely varies significantly from that in adults. We sought to define the prevalence of neuroendocrine dysfunction in a group of children in a multidisciplinary pediatric intensive care unit and determine the relationship of neuroendocrine dysfunction with severity of illness and presence of sepsis.. Prospective observational study in a pediatric intensive care unit at a referral childrens hospital. Blood samples were evaluated within 12 hrs of admission for serum cortisol, thyroid stimulating hormone, total triiodothyronine (T3), reverse triiodothyroine (rT3), free thyroxine, and arginine vasopressin. Pediatric risk of mortality, pediatric logistic organ dysfunction scores, and length of stay were calculated.. Seventy-three children were enrolled over a 13-month period. Median patient age was 72 months (range, 3-228 months). Overall prevalence of absolute adrenal insufficiency ranged from 7% to 58% based on cortisol cutoff chosen. Presence of absolute adrenal insufficiency, low T3 syndrome (LT3S), or vasopressin insufficiency did not differ between septic or nonseptic patients. NED did not correlate with pediatric logistic organ dysfunction, Pediatric Risk of Mortality Score III, length of stay, or mortality. Prevalence of multiple NED was 62% (28 of 45 children), where 62% had 2 neurohormonal deficiencies and 24% had 3 neurohormonal deficiencies.. NED is common in both septic and nonseptic critically ill children in a single pediatric intensive care unit. Larger scale studies are necessary to determine whether presence of NED, or specific combinations of neurohormonal dysfunction, is important in predicting outcomes or benefit of early hormonal replacement therapies in critically ill children.

Topics: Adolescent; Age Factors; APACHE; Cause of Death; Chi-Square Distribution; Child; Child, Preschool; Critical Illness; Endocrine System Diseases; Female; Hospital Mortality; Humans; Hydrocortisone; Infant; Intensive Care Units, Pediatric; Male; Multiple Organ Failure; Neurosecretory Systems; Prospective Studies; Risk Assessment; Sensitivity and Specificity; Sepsis; Sex Factors; Statistics, Nonparametric; Survival Analysis; Thyrotropin; Vasopressins

Topics: Child; Child, Preschool; Critical Care; Critical Illness; Endocrine System Diseases; Female; Humans; Hydrocortisone; Incidence; Infant; Intensive Care Units, Pediatric; Male; Prognosis; Risk Assessment; Survival Rate; Vasopressins

Topics: Arginine Vasopressin; Critical Illness; Humans; Receptors, Vasopressin; Shock, Septic; Vasoconstrictor Agents; Vasopressins

To measure arginine vasopressin (AVP) serum concentrations in critically ill patients.. Prospective study.. Twelve-bed general and surgical intensive care unit in a tertiary, university teaching hospital.. Two-hundred-thirty-nine mixed critically ill patients and 70 healthy volunteers.. None.. Demographic data, hemodynamic variables, vasopressor drug requirements, blood gases, AVP serum concentrations within 24 hrs after admission, multiple organ dysfunction score, and outcome were recorded. Twenty-four hours after admission, study patients had significantly higher AVP concentrations (11.9 +/- 20.6 pg/mL) than healthy controls (0.92 +/- 0.38 pg/mL; p < .001). Males had lower AVP concentrations than females (9.7 +/- 19.5 vs. 15.1 +/- 20.6 pg/mL; p = .014). Patients with hemodynamic dysfunction had higher AVP concentrations than patients without hemodynamic dysfunction (14.1 +/- 27.1 vs. 8.7 +/- 10.8 pg/mL; p = .042). Patients after cardiac surgery (n = 96) had significantly higher AVP concentrations when compared to patients admitted for other diagnoses (n = 143; p < .001). AVP concentrations were inversely correlated with length of stay in the intensive care unit (correlation coefficient, -0.222; p = .002). There was no correlation between serum AVP concentrations and the incidence of shock or specific hemodynamic parameters. Four (1.7%) of the 239 study patients met criteria for an absolute AVP deficiency (AVP, <0.83 pg/mL), and 32 (13.4%) met criteria for a relative AVP deficiency (AVP, <10 pg/mL, and mean arterial pressure, <70 mm Hg). In shock patients, relative AVP deficiency occurred in 22.2% (septic shock), 15.4% (postcardiotomy shock), and 10% (shock due to a severe systemic inflammatory response syndrome) (p = .316).. AVP serum concentrations 24 hrs after intensive care unit admission were significantly increased in this mixed critically ill patient population. The lack of a correlation between AVP serum concentrations and hemodynamic parameters suggests complex dysfunction of the vasopressinergic system in critical illness. Relative and absolute AVP deficiency may be infrequent entities during acute surgical critical illness, mostly remaining without significant effects on cardiovascular function.

Topics: Case-Control Studies; Critical Illness; Female; Hospital Mortality; Humans; Intensive Care Units; Male; Middle Aged; Sepsis; Shock; Vasopressins

Topics: Biomarkers; Critical Care; Critical Illness; Female; Humans; Male; Prognosis; Reference Values; Severity of Illness Index; Shock, Septic; Vasopressins

The European Society of Intensive Care Medicine Annual Congress offers the opportunity for basic scientists and clinicians to share recent findings. Apart from the large number of free communications, several sessions of the congress were dedicated to state-of-the-art tutorials given by established speakers. The areas of interest of the attendees were widely distributed as usual, a reflection of the large array of so-called 'critical illnesses'. The results of clinical trials and experimental findings using recently developed drugs were presented, essentially in the fields of inflammation, sepsis, and acute lung injury. The benefits of several new compounds observed experimentally need to be confirmed clinically. The European Society of Intensive Care Medicine Congress is well established as a unique opportunity to implement and to promote a collaboration between European basic scientists and clinicians.

Topics: Anti-Bacterial Agents; Critical Care; Critical Illness; Ethics, Clinical; Ethics, Medical; Europe; Humans; Inflammation; International Cooperation; Nitric Oxide; Respiratory Distress Syndrome; Sepsis; Signal Transduction; Vasopressins

Vasopressin (VP) shows promise as a pressor agent in animals and adult human cardiac arrest and resuscitation, but has not been studied for pressor effect in critically ill or arrested children. VP infusion is routine treatment for diabetes insipidus during brain death evaluation and organ recovery. We hypothesized that low dose VP infusion during organ recovery in critically ill children exerts a pressor effect, without major organ toxicity.. 34 VP-treated and 29 age-matched critically ill controls (C) < or =18 years were retrospectively reviewed during brain death evaluation and organ recovery. VP infusion protocol titrated VP dose clinically to urine output, with high variability. Pressor and inotrope management was titrated clinically to BP, cerebral perfusion and central venous pressures (when available) and peripheral perfusion with similar protocol targets for pre-load in VP and C groups. Outcome measures include dose, type and number of pressors and inotropes. Organ function was assessed at recovery and 48 h post-transplant by independent surgeon and transplant program organ function criteria. Analysis by Odds Ratio (OR), and chi-square.. VP dose averaged 0.041+/-0.069 U/kg/h. Average baseline mean arterial pressure (MAP) before VP infusion was 79+/-17 mmHg VP and 76+/-14 mm Hg C (P=0.6). Subsequent average MAP were: 82+/-21 mmHgVP after VP infusion versus 71+/-16 mmHg C (P=0.01) and 80+/-14 mmHg VP versus 68+/-22 mmHg C (P=0.01). Ability to wean/stop pressors and inotropes was: dopamine (14/23) 42% VP versus (10/26) 38% C (P=0.75), dobutamine (4/7) 57% VP versus (0/6) 0% C (P=0.026), epinephrine (4/5) 80% VP versus (0/6) 0% C (P=0.006), norepinephrine/phenylephrine (4/4) 100% VP versus (2/5) 40% C (P=0. 057). Alpha agonist pressor dependence was successfully weaned from 7/9 (78%) VP versus 0/9 (0%) C: odds ratio=7.3, (P<0.01). There was no VP induced dysrhythmia, hypertension, anuria or toxicity reported. Good organ recovery function was not significantly different at recovery or 48 h post-transplant for kidney (79% VP versus 69% C, P=0.068), liver (87% VP versus 95% C, P=0.533), or heart (90% VP versus 71% C, P=0.11).. Low dose vasopressin infusion exerts a pressor effect in critically ill children treated for diabetes insipidus during brain death and organ recovery. VP treated patients were 7.3 times more likely to wean from alpha agonists than comparably managed age matched controls, without adverse affect on transplant organ function. We speculate that further prospective assessment of VP safety and efficacy as a pressor adjunct for resuscitation of critically ill children is warranted.

Topics: Adolescent; Blood Pressure; Brain Death; Cardiotonic Agents; Case-Control Studies; Child; Child, Preschool; Critical Illness; Dopamine; Female; Humans; Male; Recovery of Function; Retrospective Studies; Thyroxine; Tissue and Organ Harvesting; Tissue Donors; Tissue Survival; Vasoconstrictor Agents; Vasopressins