When using the propensity score match method to balance variables, effectively control confounding bias, the missing data turn out to be of great significance. In this study, it turns out to be that septic patients with BMI documentation were associated with significantly lower risks of death. If samples with default are simply excluded as in other retrospective studies, the accuracy of the results will be questioned. Patients without documentation of height and weight were associated with significantly higher risks of death. These group of patients are often ignored or excluded in retrospective studies. As the saying goes, “the dead can’t talk”, there may be a survivor bias caused by the silent data in those retrospective research results. Thus, obesity paradox proved by a group of selected populations who obviously have better outcomes is arguable. Obese patients have a greater prevalence of comorbid conditions that may affect outcomes, and they are faced with a new set of care challenges in ICU, for example, airway management, pharmacology, and nutrition management. So, clinicians quite often assume that obese patients in ICU may be faced with poorer outcomes and pay more attention to them. Therefore, it is too early to conclude that obesity paradox exists in patients with sepsis.
Moreover, in those retrospective studies on the obesity paradox, BMI was used as the standard for defining and diagnosing obesity. There is a sense in which obesity paradox seems to be “BMI paradox” from this aspect. BMI only used the ratio of height to weight to reflect the degree of obesity. It could not truly reveal the distribution and accumulation degree of adipose tissue in obese patients, which may be one of the important reasons for the "obesity paradox" in sepsis. With the in-depth study of the anatomical distribution, tissue structure, and biological function of adipose tissue, visceral obesity is closely related to the risk of death in patients with sepsis. Pisitsak et al. retrospectively analyzed 257 septic patients who had undergone abdominal CT, measured the Visceral Adipose Tissue (VAT) and Subcutaneous Adipose Tissue (SAT) area, and calculated the ratio. It was found that the increased VAT/SAT ratio increased the risk of death in septic patients, and there was no significant correlation with BMI. Furthermore, patients with VAT/SAT > 1.21 had longer mechanical ventilation time, renal replacement treatment time and ICU stay time. They also found that the ratio of pro-inflammatory cytokine IL-8 to anti-inflammatory cytokine IL-10 was also higher in septic patients with high VAT/SAT, which indicated that VAT accumulation is a high-risk factor for poor prognosis in septic patients, and VAT increase in obese patients may lead to increased inflammatory response in the body[14]. Other indices such as waist circumference[15], waist-to-hip ratio[15], and body fat ratio[16], could also truly reflect the degree of obesity and truly reveal the distribution and accumulation degree of adipose tissue in obese patients, which may be more suitable for studying “obesity paradox” than BMI.
Obesity is a highly heterogeneous group of diseases[17–19], obesity paradox in sepsis hides an "inaccuracy" in obesity classification. Some researchers[5, 20] remind that the obesity paradox in critically ill patients is not a phenomenon that fits all cases. The obesity paradox in critical patients should be specifically interpreted in a variety of conditions. The pathophysiological mechanism of obesity should be deeply explored in basic research and clinical trials, to provide new ideas for revealing the pathogenesis of sepsis conforming to clinical characteristics, which are of great clinical transformation value. It is too early to tell that obesity paradox exists in septic patients especially drawn from retrospective study in which missing data are deleted roughly.
Some limitations need to be acknowledged in this study. The study was a non-randomized, observational study, due to the retrospective nature of the study, hence suffers from potential selection and ascertainable bias despite robust propensity-score matching. The variables which were not captured in this study may affect the outcomes. Furthermore, as most of the studies, this study uses BMI to assess critical patients’ body shape or composition while critically ill patients may be reported an incorrect BMI due to immobilization. BMI does not assess body composition, which may misclassify critically ill patients. For example, aggressive fluid resuscitation could elevate BMI, thereby misclassify sicker patients as obese. While some chronically ill patients may be reported an artificially low BMI, which is resulted from substantial muscle wasting and a relatively high ratio of adipose tissue to lean muscle mass. A better index to assess body composition and predict the mortality of critically ill patients need to be explored.