in the previous issue of critical care , sekhon and colleagues conducted a single - center retrospective cohort study to determine whether hemoglobin concentration was associated with outcomes among 273 critically ill adults with severe traumatic brain injury ( tbi ) . after adjusting for age , glasgow coma scale scores , external ventricular drain insertion , and allogeneic red blood cell ( rbc ) transfusion , the authors report that the estimated odds of in - hospital mortality among patients with a mean 7-day hemoglobin concentration < 90 g / l was 3.1 ( 95% confidence interval , 1.5 to 6.3 ) times the estimated odds of in - hospital mortality among those with a mean 7-day hemoglobin concentration 90 g / l . the etiology of icu anemia is multifactorial and includes the negative effects of the systemic inflammatory response on hematopoiesis , frequent phlebotomy , and hemodilution from intravenous fluid resuscitation . among icu patients with tbi , the prevalence of reduced hemoglobin concentration ranges from 22 to 69% , depending on the presence or absence of extracranial hemorrhage and the timing of hemoglobin measurements . although a hemoglobin transfusion threshold > 70 g / l was adopted for icu patients following publication of the transfusion requirements in critical care trial , this target may be poorly tolerated by those with severe tbi . anemia - induced compensatory mechanisms result in cerebral arteriolar dilatation and increased brain blood flow , which could be detrimental for those with cerebral edema or intracranial hypertension . moreover , as brain tissue oxygen tension is dependent on systemic hemoglobin , reduced hemoglobin concentrations among those with tbi could decrease cerebral oxygen delivery and contribute to brain hypoxia . although the findings of the study by sekhon and colleagues provide support for the above physiologic concerns regarding reduced hemoglobin concentrations following brain injury , the adverse relationship between anemia and clinical outcomes is an inconsistent finding among available clinical studies [ 1,5 - 16 ] . of the one randomized controlled trial   and the now 14 available cohort studies of which we are aware ( two of which were based on post - hoc analyses of similar datasets derived from randomized controlled trials ) [ 1,5 - 9,11 - 18 ] , eight reported an association between anemia and an increased risk of poor neurological outcomes or mortality , while the remaining seven observed no such association . moreover , in a recent systematic review of comparative studies , insufficient evidence was found to support a difference in outcomes between higher and lower hemoglobin levels among mostly tbi patients . possible explanations for the inconsistency in results across studies include differences in tbi severity among study patients and inadequate consideration of the effects of anemia during critical time periods . although a set hemoglobin threshold may exist under which harm may occur among those with tbi , adverse outcomes may be more likely to occur during times of low cerebral blood flow , brain hypoxia , and/or ineffective autoregulation . some support for this argument was afforded by the findings of a recent retrospective cohort study , which reported that although anemia alone did not appear to be detrimental among patients with severe tbi , the simultaneous combination of anemia and brain hypoxia was linked with an increased risk of unfavorable outcomes . another significant limitation of the existing literature on this topic has been the absence of a defined disease - exposure relationship among patients with tbi . although it is plausible that development of reduced hemoglobin concentrations may be most important during the first 7 days following severe tbi , the use of the mean as a summary measure of exposure has the potential to result in exposure misclassification . moreover , as the effects of anemia on outcomes following tbi are likely to be small , and a tremendous amount of brain hypoxia due to anemia would probably be needed to increase mortality , a sensitive measure of neurological performance or outcome is probably a more important outcome variable . possibly the most important limitation of the available literature relating anemia to outcomes among those with tbi , however , is the inadequate consideration of the effects of rbc transfusion . although rbc transfusion often results in a small incremental increase in brain tissue oxygen tension in this patient population , transfused blood has important differences from the patients ' own blood and does not always improve cerebral metabolism . moreover , at least five retrospective cohort studies have reported that rbc transfusion increases the risk of death or worsened neurological outcome among those with tbi . admittedly , however , these observations could have been related to selection bias and an unbalanced distribution of outcome determinants between treatment groups . moreover , as anemia and rbc transfusion are probably highly correlated , those studies that used interaction terms for anemia and rbc transfusion in their regression models probably introduced multicollinearity , and therefore their estimated coefficients and odds ratios may be invalid . in summary , although preclinical experiments suggest several potential adverse effects of anemia among patients with tbi , the results of the available clinical studies are conflicting , and it remains unclear whether rbc transfusion may further increase risk of adverse outcomes . however , because anemia is common among adults with severe tbi , and a recent survey reported that clinical equipoise may exist among specialists as to when to transfuse allogeneic rbcs , randomized controlled trials of liberal versus restricted transfusion thresholds are required among adults with severe tbi . these trials will probably require use of multimodal monitoring to understand whether improved outcomes are only witnessed among those with simultaneous signs of brain hypoxia or cerebral ischemia .
in the previous issue of critical care , sekhon and colleagues report that mean 7-day hemoglobin concentration < 90 
 g / l was associated with increased mortality among patients with severe traumatic brain injury ( tbi ) . the adverse relationship between reduced hemoglobin concentrations and outcomes among those with tbi 
 has been an inconsistent finding across available studies . 
 however , as anemia is common among adults with severe tbi , and clinical equipoise may exist between specialists as to when to transfuse allogeneic red blood cells , randomized controlled trials of liberal versus restricted transfusion thresholds are indicated .