title: Intravenous immunoglobulin for treating sepsis and septic shock.
abstract: BACKGROUND
  Death from severe sepsis and septic shock is common, and researchers have explored whether antibodies to the endotoxins in some bacteria reduces mortality.
  
  
  OBJECTIVE
  To estimate the effects of intravenous immunoglobulin (IVIG) in patients with bacterial sepsis or septic shock on mortality, bacteriological failure rates, and duration of stay in hospital.
  
  
  METHODS
  We searched the Cochrane Infectious Diseases Group specialized register up to November 2001; the Cochrane Controlled Trials Register, The Cochrane Library issue 4, 2001; MEDLINE 1966 to November 2001; and EMBASE 1988 to September 2001. We contacted investigators active in the field for unpublished data.
  
  
  METHODS
  Randomised trials comparing intravenous immunoglobulin (monoclonal or polyclonal) with placebo or no intervention, in patients with bacterial sepsis or septic shock.
  
  
  METHODS
  Inclusion criteria, trial quality assessment, and data abstraction were done in duplicate. We conducted pre-specified subgroup analyses by type of immunoglobulin preparation.
  
  
  RESULTS
  Twenty-seven out of 55 studies met our inclusion criteria. Pooled analysis of all types of IVIG preparations revealed a significant trend toward reduction of mortality (n= 8,856; RR=0.91; 95%CI 0.86-0.96). Overall mortality was reduced in patients who received polyclonal IVIG (n=492; RR=0.64; 95% CI 0.51 to 0.80). For the two high-quality trials on polyclonal IVIG, the RR for overall mortality was 0.30, but the confidence interval was wide (95% CI 0.09 to 0.99, n=91). Mortality was not reduced among patients who received monoclonal antibodies such as anti-endotoxins (n=2,826 in 5 good-quality studies; RR=0.97; 95% CI 0.88 to 1.07) or anti-cytokines (n=4,318; RR=0.93; 95% CI 0.86 to 1.01). A few studies measured secondary outcomes (deaths from sepsis or length of hospitalisation) but no differences in the intervention and control groups were identified except among those who received polyclonal IVIG, where sepsis-related mortality was significantly reduced (n=161; RR=0.35; 95% CI 0.18 to 0.69).
  
  
  CONCLUSIONS
  Polyclonal IVIG significantly reduced mortality and and is a promising adjuvant in the treatment of sepsis and septic shock. However, all the trials were small and the totality of the evidence is insufficient to support a robust conclusion of benefit. Adjunctive therapy with monoclonal IVIGs remains experimental.
authors.affiliation: Clinical Epidemiology Unit, University of the Philippines Manila, College of Medicine, 547 P. Gil St., Ermita, Manila, Philippines, 1000. mlansang@pacific.net.ph
authors.forename: M M
authors.initials: MM
authors.lastname: Alejandria
authors.forename: M A
authors.initials: MA
authors.lastname: Lansang
authors.forename: L F
authors.initials: LF
authors.lastname: Dans
authors.forename: J B
authors.initials: JB
authors.lastname: Mantaring
mesh_terms: D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality
chemical_list: D016756:Immunoglobulins, Intravenous