Maximizing oxygen delivery in critically ill patients: A methodologic appraisal of the evidence

Objective: To systematically review the effect of interventions designed to achieve supraphysiologic Values of cardiac index, oxygen delivery (Do(2)), and oxygen consumption (Vo(2)) in critically ill patients. Data Sources: Computerized bibliographic search of published research, citation review of relevant articles, and contact with primary investigators. Study Selection: We included all randomized clinical trials of adult intensive care unit (ICU) patients that evaluated interventions (fluids, inotropes, and vasoactive drugs) designed to achieve supraphysiologic values of cardiac index, Do(2), and/or Vo(2). Independent review of 64 articles identified seven relevant studies of 1,016 patients. Data Extraction: We abstracted data on the population, interventions, outcomes, and methodologic quality of the studies by duplicate independent review, Agreement was high (weighted kappa 0.73); differences were resolved by consensus. Data Synthesis: Targeting therapy to achieve supraphysiologic end points in critically ill patients is associated with a nonstatistically significant trend toward decreased mortality rates (relative risk 0.86, 95% confidence intervals 0.62 to 1.20). For the two studies in which supraphysiologic goals were initiated preoperatively, the relative risk was 0.20 (95% confidence intervals 0.07 to 0.55). This value differed significantly from the combined estimate of the remaining studies, in which the intervention was started after ICU admission (relative risk 0.98, 95% confidence intervals 0.79 to 1.22; p < .01). However, there are several methodologic problems with the primary studies. In no trials were caregivers or outcome assessors blinded to treatment allocation. Only three of seven trials analyzed patients according to the group to which they were allocated. None adequately controlled for cointerventions, and there was considerable crossover between groups (patients in the control group achieved the goals of the intervention group and Vice versa). Conclusions: Interventions designed to achieve supraphysiologic goals of cardiac index, Do(2), and Vo(2) did not significantly reduce mortality rates in all critically ill patients. However, there may be a benefit in those patients in which the therapy is initiated preoperatively. Methodologic limitations weaken the inferences that can be drawn from these studies and preclude any evidence-based clinical recommendations.