INTERSEPT study: we still need more clarity

recent issues of Critical Care, we read with concern the article by Pontes-Arruda and colleagues [1] and the fi rst author's reply to the letter from Machado (the latter two of which appear in [2]). Th e article and subsequent letters address eicosapentaenoic acid/gamma-linolenic acid (EPA/GLA) use in sepsis patients in the INTERSEPT (Investigating Nutritional Th erapy with EPA, GLA and Antioxidants Role in Sepsis Treatment) study. We served as the principal investigators of this trial and come from sites that did not successfully include any patients or that included only a small number of patients. From this vantage point, we believe that Pontes-Arruda's reply to Machado's comments [2] did not clarify several important points. As stated in the article [1], only fi ve of the 12 sites successfully enrolled patients. However, the fi rst author's site was responsible for the inclusion of about 100 of the 106 patients. We believe that this imbalance is relevant and that readers of Critical Care need to be aware of it. We disagree with Pontes-Arruda's response [2] that all relevant limitations were already mentioned in the Discussion [1]. We found it diffi cult to understand his affi rmation that the results were unaff ected by the unbalanced distribution pattern of the patients, as any statistical analysis of the few patients from the other four sites would obviously be under powered. We also think he should clearly state the strategies that were used at his site to successfully enroll patients given that the 11 other sites, most of which are very skilled at performing intervention studies, failed to enroll similar numbers of patients. Th e author's explanation [2] of the Sequential Organ Failure Assessment (SOFA) fi ndings is also not clear. We agree that it is perfectly possible for some patients to have a high SOFA score that may be insuffi cient to fulfi ll the inclusion criteria. However, the median and inter quartile values shown in Table 3 [1] indicate that 75% of all patients had a SOFA score of more than 4. Th is would be a very unusual fi nding in sepsis patients without signifi cant organ dysfunction. Moreover, the interquartile interval in Table 3 indicates that at least 75% of the patients had platelet levels of more than 144 × 10 9 cells per liter, a bilirubin level of less than 1.5 mg/dL, and a creatinine level of less than …