Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This is a review of the management of septic shock that suggests an approach to treatment (ABCDEF: Airway, Breathing, Circulation, Drugs, Evaluate the source of sepsis, Fix the source of sepsis) for clinicians. The incidence of septic shock is increasing and mortality ranges from 30% to 70%. The commonest sources of infection are lung (25%), abdomen (25%), and other sources. Septic shock occurs because of highly complex interactions between the infecting microorganism(s) and the responses of the human host. The innate immune response is rapidly followed by the more specific adaptive immune response. Septic shock is characterized by alterations in the coagulant/anticoagulant balance such that there is a more pro-coagulant phenotype. Lung protective ventilation (which means the use of relatively low tidal volumes of 4 -6 mL/kg ideal body weight) is recommended for treatment of patients who have septic shock. Rivers early goal-directed therapy is recommended because it showed a significant increase in survival. Surviving Sepsis guidelines recommend resuscitation of septic shock with either crystalloid or colloid. Patients who have septic shock should be treated with intravenous broad-spectrum antibiotics as rapidly as possible and certainly within one hour. Activated protein C (APC) is a vitamin K dependent serine protease that is an anticoagulant and is also cytoprotective and anti-inflammatory. APC (24 mg/kg/hour infusion for 96 hours) decreased mortality (APC 25% vs placebo 31%, relative risk 0.81P=0.005) and improved organ dysfunction in patients at high risk of death (e.g. APACHE II >25 [APC 31% vs placebo 44%]). APC is not recommended to treat surgical patients who have one organ system dysfunction. In 2006, the European regulatory authority indicated that there must be another randomized placebo-controlled trial of APC to further establish efficacy as assessed by mortality reduction. Vasopressin is a key stress hormone in response to hypotension. The VASST study was a randomized trial of vasopressin versus norepinephrine in septic shock. There was no difference in mortality between vasopressin versus norepinephrine-treated patients (35% versus 39% respectively). In patients who had less severe septic shock, patients treated with vasopressin may have lowered mortality compared with norepinephrine (26% vs 36%). Annane et al. found that hydrocortisone plus fludrocortisone (compared to placebo) was associated with lower mortality in patients who had an inadequate response to corticotropin stimulation test (mortality 53% vs 63% respectively). Sprung et al. did a randomized controlled trial of hydrocortisone (50 mg intravenously every 6 hours) compared to placebo (CORTICUS) to address lingering questions regarding the Annane trial. There was no difference in mortality (39.2% hydrocortisone vs 36.1%) or organ dysfunction. Several randomized controlled trials of intensive insulin versus conventional insulin in the critically ill have yielded conflicting results and do not support the routine use of intensive insulin in the ancillary management of septic shock. A recent randomized controlled trial of intensive versus less intensive renal support in patients who had acute kidney injury found no difference in mortality (53.6% vs 51.5% respectively), duration of renal support, or rates of recovery of renal and non-renal organ dysfunction.
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PMID:The current management of septic shock. 1897 11

The hemodynamics of septic shock is characterized by a primary reduction of vascular tone, which defines vasoplegia. Septic vasoplegia is due to reduced endogenous production of vasopressin, as well as to the overproduction of vasodilating molecules (nitric oxide, prostacyclin, peroxynitrite and kynurenine) and the opening of ATP-sensitive potassium channels. Treatment is supportive and includes primarily alpha-adrenergic catecholamines. Vasopressin may also be useful, although its place is still controversial. Further agents can improve the vascular responsiveness to catecholamines, most notably low doses hydrocortisone, and, to a lesser extent, activated protein C. Further, innovative therapies, based on recent understanding of pathophysiological mechanisms, might become useful agents to treat septic vasoplegia in the future.
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PMID:[Pathophysiological mechanisms and treatment of septic shock-induced vasoplegia]. 2227 61

Severe sepsis and septic shock remains the most urgent problem. In severe sepsis and septic shock should be early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition; -appropriate diagnostic studies to ascertain causative organisms before starting antibiotics; -early administration of broad-spectrum antibiotic therapy; -reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate; -a usual 7-10 days of antibiotic therapy guided by clinical response; -source control with attention to the method that balances risks and benefits; -equivalence of crystalloid and colloid resuscitation; aggressive fluid challenge to restore mean circulating filling pressure; -vasopressor preference for norepinephrine and dopamine; -cautious use of vasopressin pending further studies; -avoiding low-dose dopamine administration for renal protection; consideration of dobutamine inotropic therapy in some clinical situations; -stress-dose steroid therapy for septic shock; use of recombinant activated protein C in patients with severe sepsis and high risk for death; -with resolution of tissue hypoperfusion and in the absence of coronary artery disease or acute hemorrhage, targeting a hemoglobin of 7-9 g/dL; -a low tidal volume and limitation of inspiratory plateau pressure strategy for acute lung injury and acute respiratory distress syndrome; -application of a minimal amount of positive end-expiratory pressure in acute lung injury/acute respiratory distress syndrome; -protocols for weaning and sedation, using either intermittent bolus sedation or continuous infusion sedation with daily interruptions/lightening; -avoidance of neuromuscular blockers, if at all possible; -maintenance of blood glucose <150 mg/dL after initial stabilization.
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PMID:[Protocol of the management of patients with severe sepsis and septic shock]. 2322 Nov 37

Sapru et al. show in this issue of Critical Care that variants of thrombomodulin and the endothelial protein C receptor, but not protein C, are associated with mortality and organ dysfunction (ventilation-free and organ failure-free days) in ARDS. Hundreds of gene variants have been found prognostic in sepsis. However, none of these prognostic genomic biomarkers are used clinically. Predictive biomarker discovery (pharmacogenomics) usually follows a candidate gene approach, utilizing knowledge of drug pathways. Pharmacogenomics could be applied to enhance efficacy and safety of drugs used for treatment of sepsis (e.g., norepinephrine, epinephrine, vasopressin, and corticosteroids). Pharmacogenomics can enhance drug development in sepsis, which is very important because there is no approved drug for sepsis. Pharmacogenomics biomarkers must pass three milestones: scientific, regulatory, and commercial. Huge challenges remain but great opportunities for pharmacogenomics of sepsis are on the horizon.
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PMID:Genomics and pharmacogenomics of sepsis: so close and yet so far. 2721 12


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