Sepsis

Guidelines

Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008;36:296-327. This update of the 2004 guidelines utilized a new approach for grading the evidence underlying recommendations. Noteworthy changes include elimination of the  cosyntropin stim test and downgrading the recommendation to “weak” for hydrocortisone in patients with persistent shock and for activated protein C in patients with severe sepsis. http://www.ncbi.nlm.nih.gov/pubmed/18158437?ordinalpos=10&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Hydrocortisone therapy

Annane D, Sebile V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002;288; 862-71.  Placebo-controlled RCT of 300 septic patients found the subgroup of patients failing to respond to 250 mcg cosyntropin but receiving 50mg HC q6 and 50mcg fludrocortisone qd had significantly reduced morality compared to the non-responders given placebo (53% vs. 63%). No benefit was seen in giving steroid to corticotropin-responsive patients.   http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12186604

Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med  2008; 358:111-24. RCT (N = 499) found no 28-day mortality benefit to “physiologic” doses of hydrocortisone administered within 72 hours of sepsis onset, independent of the response to a corticotropin stim test. Difficulty with patient recruitment and lower than expected mortality led to the study having a power of < 35% to detect a 20% reduction in relative risk of death. http://www.ncbi.nlm.nih.gov/pubmed/18184957?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Activated protein C

Bernard GR, Vincent JL, Laterre PE, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699-709. Large, phase III multicenter RCT found patients randomized to APC had an absolute mortality reduction of 6%, but may have a greater risk of bleeding. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11236773

Abraham E, Laterre PF, Garg R, et al. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death.  N Engl J Med. 2005; 353:1332-41.  Multi-center RCT (N= 2613) of placebo vs. DrotAA (24 mg/kg/hr x 96 hours) found an increased incidence of serious bleeding complications without mortality benefit with use of DrotAA.  The authors conclude DrotAA should not be used in patients with severe sepsis who are at low risk for death, such as those with single-organ failure or an APACHE II score less than 25. http://www.ncbi.nlm.nih.gov/pubmed/16192478?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus

Early resuscitation                                                                                                               

Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368-77. This RCT of 263 patients found benefit from early (in E.D.) aggressive resuscitation (in-hospital mortality of 30% in the goal-directed group compared to 46% in the standard therapy group). The intervention arm was noteworthy for prn use of blood transfusion and/or inotropes to maintain central venous O2 sat >70%. Authors speculate the earlier aggressiveness accounts for better outcomes than previous studies of goal-directed hemodynamic optimization. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11794169                                                                                                                   
The Safe Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004; 350:2247-56. A high-quality study involving 6997 patients assigned to receive albumin or saline found no difference in 28-day mortality, single or multiple organ dysfunction, days spent in ICU, days spent in the hospital, mechanical ventilation days, and days spent on renal replacement therapy. Although the debate over the use of crystalloids vs. colloids will likely rage on, these results make a strong case against the routine use of colloids given the added expense. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15163774                                                                                                                                 
Durairaj L, Schmidt GA. Fluid therapy in resuscitated sepsis: less is more.  Chest 2008;133:252-63.  Thoughtful review of fluid management after the first six hours of early goal directed therapy.  There are figures and examples demonstrating both static and dynamic measurements for evaluating the patient’s fluid status and the likelihood of the patient being “fluid responsive.”  http://www.ncbi.nlm.nih.gov/pubmed/18187750?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

***See also “Prevention and Treatment” of Ventilator-associated Pneumonia