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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Current therapy of septic/vasodilatory cardiovascular failure includes volume resuscitation and infusion of inotropic and vasopressor agents. Norepinephrine is the first-line vasoconstrictor, and can stabilize hemodynamic variables in most patients. Nonetheless, irreversible cardiovascular failure which is resistant to conventional hemodynamic therapies still is the main cause of death in patients with severe sepsis and septic shock. In such advanced, catecholamine-resistant shock states, arginine-vasopressin (AVP) has repeatedly caused an increase in mean arterial blood pressure, a decrease in toxic norepinephrine-dosages, as well as further beneficial hemodynamic, endocrinologic and renal effects. Although AVP exerted negative inotropic effects in previous clinical trials and in selected animal experiments, a continuous low-dose AVP infusion during advanced septic/vasodilatory shock caused a decrease in cardiac index only in patients with a hyperdynamic circulation. Adverse effects on gastrointestinal circulation and the systemic microcirculation can not be excluded, but have not yet been confirmed in clinical prospective trials. Negative side effects of a supplementary AVP therapy are an increase in total bilirubin concentrations, and a decrease in platelet count. A transient increase in hepatic transaminases during AVP infusion is most likely related to preceding hypotensive episodes. Important points which must be considered when using AVP as a "rescue vasopressor" in septic/vasodilatory shock states are: 1) AVP infusion only in advanced shock states that can not be adequately reversed by conventional hemodynamic therapy (e.g. norepinephrine >0,5-0,6 mug/kg/min), 2) presence of normovolemia, 3) AVP infusion only in combination with norepinephrine, 4) strict avoidance of bolus injections and dosages >4 IU/h. Effects of a supplementary AVP infusion in advanced vasodilatory shock on survival are currently examined in a large, prospective multicenter trial in North America and Australia.
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PMID:[Arginine-vasopressin in septic and vasodilatorial shock]. 1715 83

In patients with cirrhosis, acute renal failure is due to prerenal failure (a result of decreased renal perfusion) and tubular necrosis. There are 3 main causes of prerenal failure: 'true hypovolemia' (which complicates hemorrhage, gastrointestinal or renal fluid losses), sepsis, and type 1 hepatorenal syndrome (HRS). Prerenal failure may also be due to the administration of non-steroidal antiinflammatory drugs, or intravascular radiocontrast agents. Prerenal failure is reversible after restoration of renal blood flow. Treatments target the cause of hypoperfusion, and fluid replacement is used to treat 'non-HRS' prerenal failure. In patients with type 1 HRS with very low short-term survival rate, liver transplantation is the ideal treatment. Systemic vasoconstrictor therapy with terlipressin (combined with intravenous human albumin), noradrenaline (combined with albumin and furosemide) or midodrine (combined with octreotide and albumin) may improve renal function in patients with type 1 HRS waiting for liver transplantation. MARS (for Molecular Adsorbent Recirculating System) and the transjugular intrahepatic portosystemic shunt may also improve renal function in these patients. In patients with cirrhosis, acute tubular necrosis is mainly due to an ischemic insult to the renal tubules. Studies are needed on the natural course and treatment (e.g., renal-replacement therapy) of acute tubular necrosis in patients with cirrhosis.
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PMID:Diagnosis and treatment of acute renal failure in patients with cirrhosis. 1722

The use of catecholamines to defend and resuscitate patients with septic shock remains a cornerstone of intensive care medicine. The pharmacological support of the failing circulation during sepsis and septic shock should be directed at augmenting perfusion of vital organs and facilitating venous return, rather than peripheral arterial vasoconstriction. There appears to be a teleological rationale for primary use of catecholamines to augment failing endogenous neurohumoral and neuroendocrine cardiovascular systems. To this end, it seems intuitive to use the predominant naturally occurring catecholamine, noradrenaline, as the first-line agent for circulatory failure, although there are no definitive clinical trials to support this. Adrenaline has an established place in many parts of the world, particularly low-income countries, and appears to be equivalent to noradrenaline for reversing septic shock. There is increasing evidence for adverse neuroendocrine and immunological effects of dopamine, warranting circumspection about its use. The use of synthetic inotropes and vasopressors for septic shock remains limited, with little biological rationale. Clinicians should wait for definitive outcome-based trials of these expensive agents before incorporating them into practice. Supplemental endocrine replacement therapy with low-dose corticosteroids and vasopressin appears biologically plausible and has an emerging role. Results of large-scale, high-quality trials of endogenous catecholamines for sepsis and septic shock are awaited. These may provide additional, important information for evidence-based guidelines, which currently remain of limited clinical utility.
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PMID:An appraisal of selection and use of catecholamines in septic shock - old becomes new again. 1722 75

Volatile anesthetics such as isoflurane have been shown to offer anti-inflammatory effects during experimental endotoxemia whereas the alpha-adrenergic vasopressor norepinephrine exhibits proinflammatory properties on systemic cytokine release under the same conditions. However, during major surgery and in patients with systemic inflammatory response syndrome or sepsis both agents are frequently administered concurrently. We therefore aimed to investigate the influence of preexisting i.v. administration of noradrenaline or vasopressin on the anti-inflammatory effects of isoflurane during experimental endotoxemia. Anesthetized, ventilated Sprague-Dawley rats (n=7 per group) were randomly treated. In the LPS-only group, animals received lipopolysaccharide (LPS, 5 mg/kg, i.v.) with no further specific treatment. In the LPS-isoflurane group, isoflurane inhalation at 1 MAC was initiated simultaneously with induction of endotoxemia (LPS 5 mg/kg, i.v.). Animals in the LPS-isoflurane-norepinephrine group received norepinephrine infusion at 50 microg/kg/h 10 min prior to injection of LPS and inhalation of isoflurane. In the LPS-isoflurane-vasopressin group, vasopressin was administered at 0.5 IE/kg/h 10 min prior to LPS and isoflurane. In the LPS-norepinephrine and the LPS-vasopressin groups the infusion of each vasopressor was started prior to LPS injection without any application of isoflurane. A Sham group served as the control. After 4 h of endotoxemia, plasma levels of TNFalpha, IL-1beta and IL-10 were measured. Alveolar macrophages (AM) were cultured ex vivo for nitrite assay. Induction of endotoxemia resulted in a significant rise in measured plasma cytokines and nitrite production from cultured AM. Inhalation of isoflurane significantly attenuated plasma levels of TNFalpha (-65%) and IL-1beta (-53%) compared to the LPS-only group whereas it had no effect on nitrite production from cultured AM. Preexisting infusions of norepinephrine or vasopressin abolished the anti-inflammatory effects of isoflurane. The data demonstrate that the administration of norepinephrine or vasopressin both counteracted the anti-inflammatory effects of inhaled isoflurane on proinflammatory cytokine release during experimental endotoxemia in rats.
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PMID:Norepinephrine and vasopressin counteract anti-inflammatory effects of isoflurane in endotoxemic rats. 1778 93

Cardiovascular dysfunction in septic shock (SS) is ascribed to the release of inflammatory mediators. Norepinephrine (NE) is often administered to treat low MAP in SS. We recently found that lysozyme c (Lzm-S) released from leukocytes was a mediator of myocardial depression in an Escherichia coil model of SS in dogs. This effect can be blocked in an in vitro preparation by chitobiose, a competitive inhibitor of Lzm-S. In the present study, we examined whether chitobiose treatment can reverse myocardial depression and obviate NE requirements in two respective canine E. coli preparations. In a 6-h study, we administered chitobiose after 3.5 h of E. coli bacteremia and compared stroke work (SW) and MAP at 6 h with a sepsis control group. In a 12-h study, we determined whether chitobiose treatment can reduce the need for NE requirements during 12 h of bacteremia. In the latter study, either chitobiose or NE was given when MAP decreased approximately 20% from the presepsis value in respective groups. In anesthetized, mechanically ventilated dogs, we monitored hemodynamic parameters during continuous E. coli infusion. In the 6-h study, chitobiose improved SW and MAP at the 6-h period as compared with the nontreated sepsis group. In the 12-h study, SW and MAP increased after chitobiose without the necessity of NE administration. These results suggest that inhibitors of Lzm-S such as chitobiose may improve myocardial depression and reduce the need for NE requirements in SS.
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PMID:N,N'-diacetylchitobiose, an inhibitor of lysozyme, reverses myocardial depression and lessens norepinephrine requirements in Escherichia coli sepsis in dogs. 1788 42

Severe sepsis and septic shock have an increasing incidence and unchanged high mortality. Early diagnosis is necessary to slow the progression of organ dysfunction and improve outcome. Early administration of broad-spectrum antimicrobial therapy, early and aggressive hemodynamic therapy, and surgical source control are the most promising therapeutic approaches. Norepinephrine is the first choice as a vasopressor. Starches for volume resuscitation, intensive insulin therapy (aiming at 80-110 mg/dl), and low-dose hydrocortisone are not recommended outside randomized trials. Recombinant activated protein C is one choice for certain patients. The German Sepsis Competence Network (SepNet) is currently investigating other open questions.
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PMID:[Sepsis therapy: present guidelines and their application]. 1832 Jan 53

Catecholamines are frequently used in sepsis, but their interaction with mitochondrial function is controversial. We incubated isolated native and endotoxin-exposed swine liver mitochondria with either dopamine, dobutamine, noradrenaline or placebo for 1 h. Mitochondrial State 3 and 4 respiration and their ratio (RCR) were determined for respiratory chain complexes I, II and IV. All catecholamines impaired glutamate-dependent RCR (p = 0.046), predominantly in native mitochondria. Endotoxin incubation alone induced a decrease in glutamate-dependent RCR compared to control samples (p = 0.002). We conclude that catecholamines and endotoxin impair the efficiency of mitochondrial complex I respiration in vitro.
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PMID:Effects of endotoxin and catecholamines on hepatic mitochondrial respiration. 1960 62

Calcium plays an important role in determining vascular smooth muscle tone. Norepinephrine (NE)-induced vascular contraction contains two components: 1) Ca2+ release from the sarcoplasmic reticulum as the fast phase and 2) Ca2+ influx via a voltage-dependent calcium channel as the slow phase. This study used functional isometric tension recording to evaluate mediators contributing to abnormal NE-induced Ca2+ handling and reactivity in isolated thoracic aortas from septic rats. Sepsis was induced by cecal ligation and puncture (CLP), and thoracic aortas were removed at 18 h after CLP. Our results showed that rats that received CLP for 18 h manifested severe hypotension and vascular hyporeactivity to NE in vivo. This vascular hyporeactivity to NE was also observed in the aorta obtained from CLP-induced sepsis rat. Both the fast and slow phases of NE-induced contraction were reduced in aortas from sepsis rats. To clarify what possible mediators contribute to the abnormal Ca2+ handling in aortas from sepsis animals, inhibitors of Ca2+ channel and release were used. Inhibition by 2-aminoethoxy-diphenyl borane, ryanodine, and cyclopiazonic acid of the NE-induced contraction in Ca2+-free solution was greater in the aorta from sepsis rats and inhibitions of cyclopiazonic acid and ryanodine, but not of 2-aminoethoxy-diphenyl borane, were attenuated by NOS inhibitor N[omega]-nitro-l-arginine methyl ester. In addition, the attenuation of NE-induced contraction by nifedipine in the aorta was also greater in the CLP group. Our results suggest that abnormal NE-induced Ca2+ handling associated with vascular hyporeactivity in the CLP-induced sepsis is caused by a major decrease in sarcoplasmic reticulum function and a minor impairment of voltage-dependent Ca2+ channels on membrane to Ca2+ handling, at least, in the aorta, and this could be attributed to an overproduction of NO in sepsis.
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PMID:NO contributes to abnormal vascular calcium regulation and reactivity induced by peritonitis-associated septic shock in rats. 1974 6

High-volume hemofiltration (HVHF) and coupled plasma filtration adsorption (CPFA) have shown potential to improve the treatment of sepsis in animals, but there have been no studies comparing these two treatments in humans. Our aim was to compare the hemodynamic effects of HVHF and CPFA in septic shock patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT). We performed a cross-over study enrolling patients with septic shock and AKI who were receiving CRRT. Patients were treated with pulse HVHF and continuous veno-venous hemofiltration (CVV H) on day 1 and CPFA and CVV H on day 2 or vice versa. HVHF was performed for 8-10 hours with a replacement fluid rate of 85 mL/kg/h. CPFA was performed for 8-10 hours with a plasma flow rate of 15%. CVV H was performed for the rest of the day with a replacement fluid rate of 35 mL/kg/h. The primary endpoints were changes in mean arterial pressure, vasopressor requirement (expressed as vasopressor score, VS), and noradrenaline dose after pulse HVHF and CPFA. The two treatments were compared using nonparametric tests. We enrolled 8 patients (median age 70.5 years, SOFA 12.5, SAPS II 69.5). There was a trend towards a reduction in VS with HVHF and CPFA (HVHF p=0.13, CPFA p<0.05). There was no significant difference between the two treatments in terms of percentage change in VS score (p=0.22). The data from this pilot study provide no evidence for a difference in hemodynamic effects between pulse HVHF and CPFA in patients with septic shock already receiving CRRT. A larger sample size is needed to adequately explore this issue.
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PMID:[A pilot study comparing pulse high volume hemofiltration (pHVHF) and coupled plasma filtration adsorption (CPFA) in septic shock patients]. 1991 52

It has been proposed that vasodilatory therapy may increase microcirculatory blood flow and improve tissue oxygenation in septic shock. The authors aimed to evaluate the effects of levosimendan in systemic and splanchnic hemodynamics in a porcine model of septic shock in a randomized animal controlled study. This study was performed in an animal research facility in a university hospital. Anesthetized pigs were monitored with a pulmonary artery catheter and an ultrasonic blood flow probe in the portal vein for measurement of systemic and portal blood flows and with a tonometer placed in the small intestine for measurement of the intramucosal-arterial PCO2 gap. Three groups of pigs were studied: nonseptic (n = 7), septic (n = 7), and septic treated with levosimendan (n = 7). Levosimendan was administered i.v. at t = -10 min (200 microg/kg in i.v. bolus followed by 200 microg/kg per h). Sepsis was induced at t = 0 min by the administration of live Escherichia coli. Vascular reactivity was tested by the hemodynamic response to noradrenaline. Levosimendan markedly attenuated the sepsis-induced increase in pulmonary vascular resistance, decrease in portal/systemic blood flow, oliguria, impairment in oxygenation, hyperkalemia, and the widened intramucosal-arterial PCO2 gap. Systemic blood pressure and vascular resistance did not differ as compared with the septic untreated group. Responses to noradrenaline significantly improved in animals treated with levosimendan. Treatment with levosimendan in this animal model of sepsis attenuated pulmonary vasoconstriction and improved portal blood flow, intestinal mucosal oxygenation, pulmonary function, and vascular reactivity.
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PMID:Levosimendan increases portal blood flow and attenuates intestinal intramucosal acidosis in experimental septic shock. 1999 54


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