Discussion
critically ill
CRITICALLY ILL, FLUID OVERLOAD
Similarly to the intention-to-treat analyses [These results are in line with previous findings. While the deleterious effect of fluid overload on mortality has been repeatedly reported in observational studies in critically ill patients [The highest evidence derived from randomized controlled trials (RCT) comes from intention-to-treat analyses of individual RCT [Having a closer look at the components of POINCARE-2 strategy, our results suggest that the proportion of daily weighing performed, as well as the total dose of diuretics, increased with an increasing exposure to the strategy. The daily average fluid intake, however, did not vary in the same way with the score of exposure to the strategy. This suggests that intensivists were more adherent to components of the strategy favoring fluid depletion than those favoring water and salt restriction to control fluid balance. They might also not be aware enough of how much creep fluid accounts for daily fluid intake. These findings are in line with the ones of a cross-sectional study among 524 critical care specialists showing that diuretics were the most frequently prescribed treatment to prevent fluid overload (66%). In this study, most intensivists reported using diuretics to treat fluid overload on at least 50% of days working in ICU [Our study suffers from some limitations. First, although experts agreed to rank the patients with a score of exposure to the strategy > 75 as most exposed, their agreement on exposure to the strategy in patients with lower score of exposure was less consensual. Accordingly, the defined unexposed group mixed unexposed patients and somewhat exposed patients, without us being able to separate the last ones from the first ones. This might have biased our results towards the null. In addition, the highest 60-day mortality was observed both in the lowest ([0–25[) and in the highest ([75–100]) score of exposure categories, which either corroborates a potential bias on measurement of exposure to the strategy in the lowest score category or suggests that the effect of exposure to the strategy on mortality is J-shaped. This would mean that rather than discrediting conservative strategies, we might consider applying them using restrictive therapeutic targets and/or during a limited time window. Second, the participating ICUs were equipped with different weigh scales. Despite our recommendation to tare each scale before each weigh assessment, this might have led to measurement bias. Third, we did not size the trial sample to handle adjustment for multiple confounders or to use an instrumental variable without loss of power. This might have resulted in our inability to detect a significant effect of the strategy.Our study further highlights the difficulty of demonstrating an effect of a conservative strategy in critical care practice, despite evidence of the deleterious effect of fluid overload. Given the dynamic nature of the POINCARE-2 strategy, and because of the constant need to adapt this strategy to patients’ clinical status, which varies over time, alternative statistical methods might be required in future studies. Especially, the target trial emulation approach, by simulating the various possible intervention regimens over time, could help compare the various treatment sequences and determine the most appropriate time to start fluid balance control after ICU admission [Furthermore, the POINCARE-2 strategy relied on multiple components and involved multiple health professionals (i.e., nurses and assistant nurses for weighing and administration of prescribed medications, and intensivists for prescriptions). As thus, it can be considered as a complex intervention, as defined by the Medical Research Council [