Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Norepinephrine (NE) is mostly used to treat severe hypotension. However, NE has potentially adverse vasoconstrictive effects on regional vascular beds of kidney, liver, and gut, with a potential for ensuing organ dysfunction. NE therefore is considered as a last reserve in otherwise refractory hypotension. During sepsis, a loss of catecholamine responsiveness occurs that is often interpreted as down-regulation of catecholamine receptors. Therefore, the doses of NE needed to maintain or restore blood pressure may be extremely high. Surprisingly, no adverse vasoconstriction with subsequent hypoperfusion occurs during sepsis, despite the high doses of NE administered. Instead, NE rather causes an increase in blood flow and oxygen delivery.
...
PMID:Norepinephrine in septic patients--friend or foe? 1271 59

In December 2000 and February 2001, two children with suspected meningococcal disease were admitted to our pediatric intensive unit. Their Glasgow Meningococcal Septicaemia Prognostic score was 12 points. General treatment including antibiotics, steroids in case of meningitis, and fluid replacement, was performed. Despite appropriate volume replacement, intubation and ventilation, noradrenaline and adrenaline continuous infusions < or =1.0 microg/kg/min, and additional bolus infusions, cardiac output deteriorated within minutes in both children. Calcium and bicarbonate were given without sustained effect. Echocardiography demonstrated no pericardial effusion and shortening fraction was <10%. External cardiac massage had to be performed immediately in one case for electromechanical uncoupling. Both patients received a bolus of enoximone 2 mg/kg and 5 mg/kg body weight, respectively, followed by a continuous infusion of 20-23 microg/kg/min. Thereafter, both children had an adequate blood pressure and their shortening fraction increased to >30%. Within minutes, the catecholamine infusion could be reduced in both patients. The children completely recovered from their life-threatening situations. In patients with severe prolonged catecholamine and volume refractory endotoxin shock in Waterhouse-Friderichsen syndrome, even with electromechanical uncoupling and complete myocardial arrest, enoximone can immediately restore myocardial contractility.
...
PMID:Cardiac rescue with enoximone in volume and catecholamine refractory septic shock. 1452 45

The action of endotoxin to alter gastrointestinal motility in vivo may reflect a direct effect on the gut or result from vascular and other systemic manifestations of this sepsis model. Here we examined whether in vivo pretreatment of guinea-pigs with endotoxin modifies peristalsis in the isolated gut and influences the antipropulsive action of adrenoceptor agonists. Distension-induced peristalsis was recorded in fluid-perfused segments of the small intestine taken from animals pretreated intraperitoneally with endotoxin (1 mg kg(-1)Escherichia coli lipopolysaccharide) or vehicle 4 or 20 h before. Clonidine, adrenaline, noradrenaline, dopamine and dobutamine inhibited peristalsis with differential potency. Endotoxin pretreatment lowered the peristaltic pressure threshold and altered other parameters of baseline peristalsis in a time-related manner. The potency and efficacy of clonidine to inhibit peristalsis were markedly decreased after endotoxin administration, while the potency of the other test drugs was less attenuated. The antipropulsive action of clonidine in control segments was reduced by yohimbine and prazosin, whereas in segments from endotoxin-pretreated animals it was antagonized by yohimbine but not prazosin. We conclude that systemic endotoxin pretreatment of guinea-pigs modifies baseline peristalsis by an action on the gut and inhibits the antipropulsive action of adrenoceptor agonists through changes in adrenoceptor activity.
...
PMID:Endotoxin pretreatment modifies peristalsis and attenuates the antipropulsive action of adrenoceptor agonists in the guinea-pig small intestine. 1508 75

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.
...
PMID:Differing effects of epinephrine, norepinephrine, and vasopressin on survival in a canine model of septic shock. 1531 5

A 22 year old female was admitted to the emergency department with high fever up to 41,5 degrees C, tachycardia, and arterial hypotension. Clinically, she presented with bilateral pulmonary coarse crackles. Diagnosis on admission was pneumonia with septic shock. Intriguingly, procalcitonin (PCT) was increased early, reaching up to 435 ng/mL, while C-reactive protein levels were only moderately increased, with several days delay. The sepsis was originated from a multi-resistant pseudomonas aeruginosa pneumonia. Remarkably, the course of PCT levels reflected the severity of septic shock in that it paralleled noradrenaline demand. Ten months previously, the patient had been diagnosed with acute disseminated brainstem encephalitis (ADEM), and had received two cycles of intravenous cyclophosphamide. Our case illustrates that PCT is an early marker for sepsis and it indicates that PCT may also be a valuable marker for the severity of sepsis in immunosuppressed patients.
...
PMID:[Procalcitonin as a marker for severe sepsis in an immunosuppressed patient]. 1571

Previously, we have reported that the susceptibility of burned patients to infectious complications is increased when the production of CC-chemokine ligand 3 (CCL3) is impaired. In this study, the role of the sympathetic nervous system on impaired CCL3 production and antibacterial resistance following burn injuries was investigated. Normal mice were resistant (65% survival) to cecal ligation and puncture (CLP)-induced sepsis, while the same CLP killed 90% of thermally injured mice (TI-mice). However, TI-mice resisted CLP-induced sepsis (60% survival) when they were previously treated with CCL3 or sympathectomized with 6-hydroxydopamine (6-OHDA). Augmentation of host resistance against CLP-induced sepsis by 6-OHDA was abrogated by anti-CCL3 mAb treatment. Norepinephrine (NE) production was increased in circulation of TI-mice, and treatment of TI-mice with 6-OHDA resulted in the inhibition of NE secretion. CCL3 production was impaired in cultures of T cells from TI-mice or normal T cells treated with NE, even when stimulated with anti-CD3 mAb. However, CCL3 was produced by mAb-stimulated T cells from TI-mice previously treated with 6-OHDA. These results indicated that by inhibiting CCL3 production the sympathetic nervous system contributes to the increased susceptibility of TI-mice to sepsis.
...
PMID:Contribution of the sympathetic nervous system on the burn-associated impairment of CCL3 production. 1576 Jun 77

Acute renal failure (ARF) requiring renal replacement therapy (RRT) has been associated with an excess risk of mortality in adult patients with septic shock, but it is unknown whether this is also applicable to pediatric patients. We therefore conducted a retrospective pilot study. All children presenting with septic shock between 1st January 1998 and 1st April 2004 were analyzed. Patients with fluid refractory-dopamine resistant shock, necessitating the use of noradrenaline, were included. ARF was defined as the deterioration of renal function to the extent that renal replacement therapy was required (ARF group). This ARF group was compared with patients without ARF (non-ARF group). Out of the 22 children with severe septic shock, seven developed ARF. PIM2 and PRISM scores upon admission were comparable between both groups. Mortality rates were significantly higher in patients with ARF (57.1% vs 6.7%; p=0.02). Pediatric patients with severe septic shock developing ARF have excess mortality compared to pediatric patients who do not develop ARF, although on diagnosis, severity of underlying disease and calculated risk of mortality were comparable. A multicenter trial is necessary to confirm these findings and to determine the contribution of ARF to pediatric sepsis mortality.
...
PMID:Effect of acute renal failure on outcome in children with severe septic shock. 1594 82

Septic shock occurs in 6 % of paediatric cancer patients with neutropenia and fever. The mortality of the septic shock is 40 % in BMT patients and 5 % in others. One third of paediatric ARDS cases affect immunocompromised individuals with a total mortality of 45 % and 80 % after BMT. Septic shock is caused by gram-negative bacteria in more than 75 %. ARDS is due to pneumonia in more than 50 %, sepsis in about 25 %. This article provides the recommendations of the Infectious Diseases Working Party of the German Society for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric Hematology/Oncology (GPOH) for treatment of septic shock and ARDS. Therapy of septic shock includes early antibiotic therapy and volume expansion (> or = 40 ml/kg initially). Refractory shock requires vasopressors (noradrenaline), followed by a judicious circulatory management. Hydrocortisone is indicated in patients with high probability of adrenal insufficiency. Mainstay of ARDS therapy is ventilation with sufficient end-expiratory pressure (PEEP) to prevent loss of functional residual capacity and with limited tidal volumes (< or = 6 ml/kg) and limited inspiratory pressure (< 35 cm H(2)O) respectively, to minimize ventilator induced lung injury. Volume therapy consists of maintenance of sufficient preload to counteract the impaired venous return, induced by positive pressure ventilation. Diuretics and eventually veno-venous haemofiltration are used to reduce free lung water. Surfactant application may be considered in severe cases. Steroids are indicated in pneumocystis carinii pneumonia and in engraftment pneumonitis.
...
PMID:[Management of septic shock and acquired respiratory distress syndrome in pediatric cancer patients]. 1628 59

Limited information is available about selection of the threshold for arterial blood pressure in critically ill patients, particularly in sepsis when normal organ blood flow autoregulation may be altered. The present experimental study investigated whether increasing perfusion pressure using norepinephrine in normotensive hyperdynamic porcine bacteremia affects intestinal macro- and microcirculation. Nine pigs received continuous i.v. administration of Pseudomonas aeruginosa (PSAE) to develop hyperdynamic, normotensive (mean arterial pressure [MAP] 65 mm Hg) sepsis. Norepinephrine was used to achieve 10-15 % increase in MAP. Mesenteric arterial blood flow (Q(gut)), ileal mucosal microvascular perfusion (LDF(gut)) and ileal-end-tidal PCO(2) gap (PCO(2) gap) were measured before norepinephrine, after 60 min of norepinephrine infusion and 60 min after norepinephrine infusion had been discontinued. During a 12 h period of PSAE infusion all pigs developed hyperdynamic circulation with significantly decreased MAP. Although the mesenteric blood flow remained unchanged, infusion of PSAE resulted in a gradual fall of ileal microvascular perfusion, which was associated with progressively rising PCO(2) gap. Norepinephrine which induced a 10-15 % increase in perfusion pressure (i.e. titrated to attain near baseline values of MAP) affected neither Q(gut) nor the intestinal blood flow distribution (Q(gut)/CO). Similarly, norepinephrine did not change either LDF(gut) or PCO(2) gap. In this hyperdynamic, normotensive porcine bacteremia, norepinephrine-induced increase in perfusion pressure exhibited neither beneficial nor deleterious effects on intestinal macrocirculatory blood flow and ileal mucosal microcirculation. The lack of changes suggests that the gut perfusion was within its autoregulatory range.
...
PMID:Perfusion pressure manipulation in porcine sepsis: effects on intestinal hemodynamics. 1634 46

"Severe sepsis" is defined by organ dysfunction due to infection-induced hypoperfusion. "Septic shock" is defined by hypotension refractory to fluid resuscitation, associated with organ dysfunctions or hypoperfusion. Mortality from severe sepsis and from septic shock is high. Guidelines to help physicians improve the survival of patients with severe sepsis comprise one part of an international project called the Surviving Sepsis Campaign. They bring together treatment innovations based on monitoring aimed at ensuring comprehensive management of tissue oxygen levels (central venous oxygen saturation: SvcO2). They are based on the optimization of early treatment, during the first six hours of severe sepsis, and ensuring no delay in fluid resuscitation. In case of septic shock, fluid resuscitation must be rapidly accompanied by administration of vasoconstrictive catecholamines. Noradrenaline is preferred to dopamine. Dobutamine is recommended when the cardiac index is less than 2.5 L x min(-1) x m(-2). Because of the relative adrenal insufficiency that occurs during septic shock, corticoids are recommended, after a synacthen test. Activated protein C is currently the only therapy produced by biotechnology that reduces mortality from severe sepsis. Global management of septic shock must form an integral part of resuscitation guidelines and include protocols for, among other things, sedation, ventilation, strict glycemic control, and prophylaxis for deep vein thrombosis and stress ulcers.
...
PMID:[Non-infective treatments for septic shock]. 1678 62


<< Previous 1 2 3 4 5 6 7 8 9 Next >>