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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The reduced pressure response to vasopressin during acute sepsis has directed our interest to the regulation of vasopressin V(1A) receptors. Rats were injected with lipopolysaccharide for induction of experimental gram-negative sepsis. V(1A) receptor gene expression was downregulated in the liver, lung, kidney, and heart during endotoxemia. Inasmuch as the concentrations of proinflammatory cytokines such as interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma were highly increased during sepsis, the influence of these cytokines on V(1A) receptor expression was investigated in primary cultures of hepatocytes and in the aortic vascular smooth muscle cell line A7r5. V(1A) receptor expression was downregulated by the cytokines in a nitric oxide-independent manner. Blood pressure dose-response studies after injection of endotoxin showed a diminished responsiveness to the selective V(1) receptor agonist Phe(2),Ile(3),Orn(8)-vasopressin. Our data show that sepsis causes a downregulation of V(1A) receptors and suggest that this effect is likely mediated by proinflammatory cytokines. We propose that this downregulation of V(1A) receptors contributes to the attenuated responsiveness of blood pressure in response to vasopressin and, therefore, contributes to the circulatory failure in septic shock.
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PMID:Cytokine-mediated downregulation of vasopressin V(1A) receptors during acute endotoxemia in rats. 1189

Vasodilatory shock is a syndrome with high mortality. It is becoming evident that depletion of antidiuretic hormone (ADH) after cardiac surgery or during sepsis plays an important role in the pathogenesis of this condition. Established vasodilatory shock responds well to exogenous ADH infusion. It is possible that preventing ADH depletion at an earlier stage may abrogate the onset of vasodilatory shock, or at least reduce its severity. This paper examines the evidence supporting this concept, and the potential areas of concern in considering this particular type of hormone replacement therapy.
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PMID:Antidiuretic hormone replacement therapy to prevent or ameliorate vasodilatory shock. 1220 65

The antidiuretic hormone (ADH) vasopressin is a simple peptide hormone with a number of complex, essential physiological actions. It is becoming clear that this hormone is developing an important therapeutic role in a number of different conditions. These include vasodilatory shock due to sepsis or cardiac surgery, cardiac arrest, and prolonged/excessive bleeding caused by, for example, variceal haemorrhage. This article reviews the physiology of ADH relevant to these actions and scrutinises the evidence for its therapeutic applications.
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PMID:The physiology and emerging roles of antidiuretic hormone. 1251 Sep 52

Despite advances in supportive care, septic shock remains a major cause of morbidity and mortality. With the identification of the systemic inflammatory response as a major component in the pathogenesis of the septic shock syndrome, much of the recent work has focused on modulating this response. This includes antiendotoxin therapies in patients with Gram-negative sepsis, and therapies to modulate the pro-inflammatory mediators produced in response to infection, such as TNF-alpha, platelet-activating factor and complement. High-flow haemofiltration has the potential advantage of clearing both endotoxin and pro-inflammatory mediators. Antithrombotic strategies have been investigated and have yielded the first major success in the treatment of sepsis with activated protein C. Nitric oxide produces the cardiovascular features of sepsis and investigators have looked at both reducing its production and mopping up the excess. Attempts to reduce apoptosis have been a new focus in the treatment of sepsis. There have also been recent developments in supportive care suggesting a role for vasopressin and replacement corticosteroid therapy.
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PMID:Recent developments in the treatment of sepsis. 1255 10

The extreme disturbance of hemodynamics in shock leads to a minimized oxygen delivery to several vital organs. If this state is not rapidly lifted, a multi-organ-failure can occur. In addition to the removal of the underlying causes, for example, bleeding or septic focus, measures must be started to stabilize hemodynamics. In most cases shock can be successfully treated with standard therapeutic interventions including the use of crystalloid or colloid solutions as well as the infusion of inotropes or vasopressors. Up to now, there is not enough evidence to show that hypertonic/hyperoncotic solutions are better for treating hypovolemic shock than standard infusions, other than in situations, where only an inadequate equipment is available. Experimental data support the use of vasopressin instead of fluid loading in case of uncontrolled intra-abdominal bleeding. According to these studies vasopressin seems to be associated with an improved hemodynamic stabilization and a significantly lower mortality rate. However, no clinical tests have been done so far to confirm these results. In septic shock the plasma-levels of vasopressin are low. It has been shown that the infusion of vasopressin contributes to stabilization of hemodynamics in septic shock, in lower, as well as in higher concentrations. On the other hand vasopressin worsens splanchnic perfusion. Therefore the routine use of vasopressin in the treatment of sepsis can not be recommended.
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PMID:[New therapeutic approaches in the treatment of shock: hypertonic hyperoncotic solutions and vasopressin]. 1499 9

Arginine-vasopressin (VP), also known as the antidiuretic hormone, is essential for water homeostasis. Its synthesis and liberation depends on regulation of osmotic, hypovolemic, hormonal, and nonosmotic stimuli. It has been demonstrated that it is key for maintenance of cardiovascular homeostasis through vasomotor regulation, the determinant of systemic vascular resistance and mean arterial pressure, a process acting through V1 receptors. Shock state with refractory vasodilation seen in sepsis, systemic inflammatory response, hypovolemia, cardiac arrest, polytrauma, etc., is characterized by an initial phase of liberation and increased levels of VP followed by a second phase characterized by inappropriately low levels of this hormone that are associated with refractoriness to management with volume, inotropics, and vasopressors. It has been demonstrated in clinical and experimental studies that exogenous VP treatment under this condition increases systemic vascular resistance, perfusion pressure, and oxygen supply to peripheral tissues, which makes it possible to decrease and to suspend vasopressors and also to increase survival.
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PMID:[Vasopressin use in shock]. 1502 89

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. Hypotension in patients with septic shock is often difficult to correct. Despite enormous dosages of catecholamines, many of these patients continue to have inadequate blood pressures. Inadequate levels of vasopressin have been identified in patients with septic shock, as well as in other patients with hypotension secondary to refractory vasodilatation. Vasopressin is a peptide hormone secreted from the posterior pituitary in response to hyperosmolality, hypovolemia or hypotension. Levels of vasopressin initially rise in patients with septic shock, but as hypotension persists, vasopressin levels fall below normal. Administration of exogenous vasopressin in physiologic dosages significantly increases blood pressure in patients with shock associated with sepsis and other vasodilatory states. This rise in blood pressure is often significant enough that endogenous catecholamines can be decreased and frequently discontinued entirely. Early withdrawal of the vasopressin replacement infusion results in recurrent hypotension. Unfortunately, randomized, blinded, placebo-controlled trials showing improvement in long-term outcomes such as mortality and length of stay are still lacking.
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PMID:New additions to the intensive care armamentarium. 1504 37

During sepsis, limited data on the survival effects of vasopressors are available to guide therapy. Therefore, we compared the effects of three vasopressors on survival in a canine septic shock model. Seventy-eight awake dogs infected with differing doses of intraperitoneal Escherichia coli to produce increasing mortality were randomized to receive epinephrine (0.2, 0.8, or 2.0 microg.kg(-1).min(-1)), norepinephrine (0.2, 1.0, or 2.0 microg.kg(-1).min(-1)), vasopressin (0.01 or 0.04 U/min), or placebo in addition to antibiotics and fluids. Serial hemodynamic and biochemical variables were measured. Increasing doses of bacteria caused progressively greater decreases in survival (P <0.06), mean arterial pressure (MAP) (P <0.05), cardiac index (CI) (P <0.02), and ejection fraction (EF) (P=0.02). The effects of epinephrine on survival were significantly different from those of norepinephrine and vasopressin (P=0.03). Epinephrine had a harmful effect on survival that was significantly related to drug dose (P=0.02) but not bacterial dose. Norepinephrine and vasopressin had beneficial effects on survival that were similar at all drug and bacteria doses. Compared with concurrent infected controls, epinephrine caused greater decreases in CI, EF, and pH, and greater increases in systemic vascular resistance and serum creatinine than norepinephrine and vasopressin. These epinephrine-induced changes were significantly related to the dose of epinephrine administered. In this study, the effects of vasopressors were independent of severity of infection but dependent on the type and dose of vasopressor used. Epinephrine adversely affected organ function, systemic perfusion, and survival compared with norepinephrine and vasopressin. In the ranges studied, norepinephrine and vasopressin have more favorable risk-benefit profiles than epinephrine during sepsis.
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PMID:Differing effects of epinephrine, norepinephrine, and vasopressin on survival in a canine model of septic shock. 1531 5

Septic shock that requires therapy with adrenergic agents is associated with high rates of mortality. Inappropriately normal or low serum concentrations of vasopressin contribute to the development of hypotension during sepsis. We critically evaluated the role of administering exogenous vasopressin to patients with septic shock. A computerized search of MEDLINE from January 1966--December 2003 and a manual search of relevant journals for abstracts were conducted. Eleven retrospective, six prospective cohort, and four prospective randomized studies were identified. Most studies evaluated short-term infusions of vasopressin at 0.08 U/minute or less as add-on therapy in patients requiring adrenergic agents. The results show that starting vasopressin in patients with septic shock increases systemic vascular resistance and arterial blood pressure, thus reducing the dosage requirements of adrenergic agents. These effects are rapid and sustained. Substantial enhancement of urine production, likely due to increased glomerular filtration rate, was shown in several studies. A few studies demonstrated clinically significant reduced cardiac output or cardiac index after vasopressin was begun, necessitating cautious use in patients with cardiac dysfunction. Vasopressin was associated with ischemia of the mesenteric mucosa, skin, and myocardium; elevated hepatic transaminase and bilirubin concentrations; hyponatremia; and thrombocytopenia. Limiting the dosage to 0.03 U/minut or less may minimize the development of these adverse effects. Vasopressin 0.03 U/minute or less should be considered if response to one or two adrenergic agents is inadequate or as a method to reduce the dosage of adrenergic agents. At present, vasopressin therapy should not be started as first-line therapy. Additional studies are needed to determine the optimum dosage, duration, and place in therapy of vasopressin relative to adrenergic agents. A multicenter, comparative study of vasopressin 0.03 U/minute as add-on therapy is under way and should provide mortality data.
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PMID:The role of vasopressin in vasodilatory septic shock. 1533 53

Endocrinopathy during sepsis can manifest as hyperglycemia and insulin resistance or as insufficient production of either adrenal corticosteroids or vasopressin. The results of a recent large clinical trial have demonstrated that tight glycemic control with insulin can confer survival benefit to selected intensive care unit patients. Relative impairment of adrenocortical reserve has been suggested to be an important contributor to the pathogenesis of shock in sepsis. Replacement doses of glucocorticoids and mineralocorticoids have been associated with improved survival in the subset of patients with blunted results on adrenocorticotropin hormone stimulation tests. Posterior pituitary production of vasopressin is diminished in septic shock while sensitivity to its vasopressor effects is enhanced. Clinical trials are underway to determine whether administration of vasopressin can improve outcomes in patients with septic shock. Whether the euthyroid sick syndrome represents an adaptive or a maladaptive response to severe illness remains unclear.
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PMID:The endocrine system during sepsis. 1548 39


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