Indeed, in the Vasopressin in Septic Shock and Catecholamines in Septic Shock CATS trials, the mean MAP achieved during septic shock was about 75 to 80 mmHg (two standard deviations selleck bio up to 110 mmHg) [8] and about 75 (two standard deviations up to 90 to 100 mmHg) [9], respectively. Similarly, the mean norepinephrine dose infused during the first two days after randomization was about 1.1 ��g/kg/min (two standard deviations up to 5 ��g/kg/min) in the CATS trial [8]. Infusion of even higher catecholamine dosages in critically ill patients with septic shock have lately been reported by others [18]. Furthermore, a recent clinical study has suggested that targeting higher MAP by increasing norepinephrine resulted in an increase in global oxygen delivery and tissue oxygenation [19].

Moreover, hemodynamic goals in our study patients other than MAP were comparable with current recommendations [2,13]. Accordingly, the results of our analysis appear to be clinically relevant still today.It is important to note that all statistical models in this analysis were adjusted for factors commonly presumed to influence the association between MAP and mortality. An important covariate was disease severity as assessed by SAPS II, which should have unmasked gross influences of the underlying disease on the association between MAP and mortality. Nonetheless, it is conceivable that although SAPS II is a reliable measure of disease severity and excellent predictor of mortality [14], it may not reflect the true extent of cardiovascular failure and other cofactors that impact on 28-day mortality.

Furthermore, despite including 290 patients into the analysis, the sample sizes in MAP quartiles may have been too small to uncover statistical significance. Nonetheless, given a RR ratio of 0.99 (95% CI, 0.95 to 1.04) per mmHg MAP increase for death at day 28, it is unlikely that significance would have been reached had more patients been included.This analysis included 290 of the 358 patients who were included in the control group of the original trial. Sixty-eight patients had to be excluded because the goal to maintain a MAP of at least 70 mmHg during the shock period could not be achieved. As the hemodynamic protocol of the original trial strictly required a MAP of 70 mmHg or higher, it must be assumed that patients who did not attain this MAP level were either too sick to achieve the target (vasopressor-resistant hypotension) or had undergone violations of the hemodynamic protocol. Both options preclude meaningful comparisons between the 68 patients excluded and the current study population as well as the evaluation of the association between MAP Anacetrapib levels less than 70 mmHg and mortality in septic shock.