(Nejm 2003;348:138; 1993;328:1471; Ann IM 1994;121:1; 1994;120:771; 1990;113:227)

Pathophys: Systemic inflammatory response (SRS) defined by p >90, respir >20, T° >36-38.0°C, pCO₂ <32, WBC >12 000 or <4000; progresses to sepsis, which progresses to septic shock (Jama 1995;273:117). Nitric oxide production may be a mechanism that can be rx'd w inhibitors (Jama 1996;275:1192)

Encephalopathy correllates w severity of sepsis and Glasgow coma scale score (Jama 1996;275:470)

Lab:Plasma triggering receptor expressed on myeloid cells (TREM-1) levels >60 ngm/cc, 96% sens, 89% specif for bacterial/fungal infection (Ann IM 2004;141:9). Pro-calcitonin levels incr w bacterial sepsis, not other acute and/or chronic kinds of inflammation (Jags 2010;58:518)

Rx: of shock, rx with respirator, iv fluids, and antibiotics to cover staph and pseudomonas like 3rd-generation cephalosporin + aminoglycoside (Med Let 1999;41:97); beyond that many treatments have gone through wildly enthusiastic and expensive implementations only to have big doubts raised after several years including:

• Arginine vasopressin drip (Nejm 2004;351:159 vs no help by DBCT Nejm 2008;358:877)
• Steroid support (Nejm 2006;355:1699 vs no improved survival Nejm 2008;358:111, 188)
• NSAIDs help fever but no improvement in survival (Nejm 1997;336:912)
• Insulin iv drip to keep BS 80-110 not helpful and may hurt (Nejm 2008;358:125)
• Monoclonal anti-endotoxins of no help (Jama 2000;283:1723; Ann IM 1994;121:1); but polyclonal iv immunoglobulins may help (NNT = 7) (ACP J Club 2001;135:82)?
• Activated protein C (recombinant human) (Xigris) if shock and multi-organ failure (Nejm 2009;361:2646; 2002;347:993, 1027, 1030) at $7000/rx vs inappropriate overpromotion by manufacturer (Nejm 2006;355:1640)