There are almost no evidence-based data to establish the optimal hemoglobin level for critically ill children with severe sepsis and septic shock. Aiming to achieve an adequate oxygen delivery in children with sepsis, most pediatric intensivists

Pediatr Crit Care Med 2012 Vol. 13, No. 4 To the Editor: There are almost no evidence-based data to establish the optimal hemoglobin level for critically ill children with severe sepsis and septic shock. Aiming to achieve an adequate oxygen delivery in children with sepsis, most pediatric intensivists use values around 10 mg/dL to indicate red blood cell transfusion. Such transfusional practice, associated with aggressive fluid resuscitation and inotropic support aiming target venous mixed venous saturation of 70% in the early management of sepsis, has resulted in the reduction of 20% in mortality in the last decade, as demonstrated in dozens of clinical trials (1). Contrary to this idea, a recent randomized controlled trial (RCT) by Karam and colleagues (2) analyzed 137 children with stabilized sepsis, defined as systemic mean arterial ≥2 sd of the normal mean for age, and no recent change in cardiovascular support. This study did not show any difference in the development of new multiple organ dysfunction syndrome (18.8% vs. 19.1%; p = .97) between the group of restrictive transfusion (hemoglobin level threshold for transfusion of 7 g/dL) and the control group of liberal transfusion (hemoglobin level threshold of 9.5 g/dL). The authors conclude that “hemoglobin level of 7 g/dL may be safe stabilized for children with sepsis” (2). This was a subgroup analysis of a large, prospective multicenter RCT (2) in which 5,399 patients enrolled with a detailed statistical analysis. Nevertheless, two concerns have risen when this subgroup study was analyzed: the insufficient statistical power and a potential increase in the reported mortality. The decision to analyze a subgroup (n = 137) with statistical power lesser than one quarter of the necessary (626 patients, as described in Statistical Analysis) (2) could favor the occurrence of type II error (3), which means, it assumed that both groups (restrictive/liberal) were statistically similar, when actually they could be not. This concern becomes particularly important when the outcome is mortality, the most important outcome in RCTs. The CONSORT (CONsolidated Standards Of Reporting Trials) Statement (4) is intended to improve the reporting of an RCT, enabling readers to understand a trial’s design, conduct, analysis, and interpretation, and to assess the validity of its results. As no particular reference was made to mortality in the conclusion of that study, we calculated the values of the main describers of binary outcomes of CONSORT Statement 2010 (4) to estimate this outcome when we compare the 28-day mortality rate in restrictive group with the liberal group: absolute risk increase of 7.2%, relative risk increase of 244.9%, and number-needed-to-hazard of 13.8 (Table 1). These numbers made us wonder what the results would be if the study was not underpowered. By keeping constant the values of mortality rate, it is possible to estimate exactly the level of statistical significance (p value) with a large population (for example: N = 4n): there would be a higher mortality in the restrictive group when compared with the liberal group, not only in the intensive care unit (7.25% vs. 2.94%; p = .022; odds ratio 2.578 [95% confidence interval 1.11–5.959]) (Table 1) but also in 28-day mortality (10.14% vs. 2.94%; p = .0007; odds ratio 3.726 [95% confidence interval 1.666 to 8.330]) (Table 1). Such results, despite theoretical, are quite worrying. Although only sufficiently powered RCT can answer this question, one should take special attention to the reported mortality of RCT. To note, in a large RCT of severe sepsis (n = 477), the occurrence of serious bleeding events in only a few children (10 × 2; p = .04) (5) and the lack of efficacy in the reduction of mortality of the medication under study were sufficient to recommend against the routine use of