Sepsis, severe

TAK-242 Antagonist Severe sepsis Phase III clinical trials... 

Recommendations in this section may change based on results from the recent GLUCONTROL trial and the Volume Substitution and Insulin Therapy in Severe Sepsis Study. Both trials where stopped early due to lack of efficacy and safety concerns. 

The cumulative burden of sepsis complications is the leading factor of mortality. The risk of death increases 20% with failure of each additional organ. Severe sepsis averages two failed organs, with a mortality rate of 40%. 

Sepsis is a continuum of physiologic stages characterized by infection, systemic inflammation, and hypoperfusion with widespread tissue injury.1 The American College of Chest Physicians and the Society of Critical Care Medicine developed definitions to utilize for sepsis (Table 79—l).2 They provide physiologic parameters categorizing patients as having bacteremia, infection, systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, or multiple-organ-dysfunction syndrome (MODS).2 Standardized definitions have been developed for infections in critically ill patients.3... 

Sepsis The systemic inflammatory response syndrome and documented infection (culture or Gram stain of blood, sputum, urine, or normally sterile body fluid positive for pathogenic microorganisms Severe sepsis Sepsis associated with organ dysfunction, hypoperfusion, or hypotension (systolic blood pressure less than 90 mm Hg). Hypoperfusion and perfusion abnormalities may include, but are not limited to, lactic acidosis, oliguria, or acute alteration in mental status. 

Activated protein C in patients with severe sepsis and high risk of death (Acute Physiology, Age, and Chronic Health Evaluation II [APACHE II] score greater than 25). 

Dopamine is a a- and P-adrenergic agent with dopaminergic activity Low doses of dopamine (1 to 5 mcg/kg per minute) maintain renal perfusion, higher doses (greater than 5 mcg/kg per minute) exhibit a- and P-adrenergic activity and are frequently utilized to support blood pressure and to improve cardiac function. Low doses of dopamine should not be used for renal protection as part of the treatment of severe sepsis.24,27-28... 

SIRS, sepsis, severe sepsis, septic shock, or MODS. 

Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States Analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001 29 1303-1310. 

Bernard GR, Vincent JL, Laterre PF, et al. Recombinant Human Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001 344 699-709. 

Dellinger RP, Carlet JM, Masur H, et al. Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004 32 858-873. 

Harbarth S, Garbino J, Pugin J, et al. Inappropriate initial antimicrobial therapy and its effects on survival in a clinical trial of immunomodulating therapy for severe sepsis. Am J Med 2003 115 529-535. 

MacArthur RD, Miller M, Albertson T, et al. Adequacy of early empiric antibiotic treatment and survival in severe sepsis experience from the MONARCS trial. Clin Infect Dis 2004 38 284-288. 

Rivers E, Nguyen B, Havstad S, et al. Early Goal-directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001 345 1368-1377. 

Septic shock Sepsis with hypotension (a systolic blood pressure of <90 mm Hg or a reduction of <40 mm Hg from baseline), despite adequate fluid resuscitation, along with the presence of perfusion abnormalities as seen by severe sepsis. Patients who are receiving inotropic or vasopressor agents may not be hypotensive at the time that perfusion abnormalities are measured. 

B52. Brun-Buisson, C., Doyon, F., Carlet,J., Dellamonica, P., Gouin, F., Lepoutre,A., Mercier, J.-C., Offenstadt, G., and Regnier, B., Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. JAMA 274,968 974 (1995). 

Dl. Damas, P Reuter, A., Gysen, P., Demonty, J., Lamy, M., and Franchimont, P., Tumor necrosis factor and interleukin-1 serum levels during severe sepsis in humans. Crit. Care Med. 17, 975-978 (1989). 

Stiiber, F Petersen, M., Bokelmann, F., and Schade, U A genomic polymorphism within the tumor necrosis factor locus influences plasma tumor necrosis factor-a concentrations and outcome of patients with severe sepsis. Crit. Care Med. 24,381-384 (1996). 

Severe bacterial infection Severe sepsis Severe viral infection Aplastic anaemia3 Acute leukaemia... 

Immediate initial resuscitation of a patient in severe sepsis or sepsis-induced tissue B hypoperfusion should be instituted to achieve central venous pressure 8-12 mm Hg mean arterial pressure >65 mm Hg urine output >0.5 mt/kj hour, central venous or mixed venous oxygen saturation >70%... 

Others Osteoporosis, asthma, cystic fibrosis, acute myocardial infarction, severe sepsis, psoriasis, non-Hodgkin s lymphoma Forteo, Xolair, Puhnozyme, Activase/TNKase, Xigris, Raptiva, Zevahn... 

Xigris (Drotrecogin-a rh activated protein C, produced in a Eli Lilly Severe sepsis 2001 (USA), 2002 (EU)... 

The good bioavailability of orally administered ciprofloxacin obviates the need for the more expensive intravenous formulation. I.v. ciprofloxacin is only given to patients who have severe sepsis or severe nausea and vomiting. Ciprofloxacin s elimination is 50% hepatic and 50% renal. Therefore, dose reduction is recommended only in case creatinine clearance drops to < 10 ml/min. Prevention of food-borne disease requires efforts at many levels. Monitoring safety of food processing, vector control, surveillance of outbreaks, education on personal hygiene and improving sanitation and access to safe water supplies are all necessary measures to reduce the incidence of GTI. 

Systemic infections are those that have microorganisms (bacteria, viruses, yeasts, parasites) spread, usually via the bloodstream, beyond the portal of entry or original site of localized infection to multiple compartments of the body. When infections, either localized or systemic, are accompanied by signs and symptoms of a systemic inflammatory response (fever, rapid pulse, increase in white blood cells) the syndrome is called sepsis. Severe sepsis is defined by the additional occurrence of organ failure (either kidney, liver, brain, lungs), and is a potentially fatal condition (mortality around 50%). If there is hypotension not responding on fluid resuscitation it is called septic shock and the mortally is even higher (60-70%). 

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