Obesity and survival in critically ill patients with acute respiratory distress syndrome: a paradox within the paradox

The incidence of obesity is steadily increasing, and its prevalence, defined as a body mass index (BMI) above 30 kg/m, is 13% in the world adult population, and rises to up to 40% in high-income countries [1]. As a consequence, around 20% of the patients admitted to the intensive care unit (ICU) are obese [2]. Obesity and overweight are associated with an increased risk of death in the general population [3], but in specific disease conditions a decrease in mortality has been reported: this is the case of patients with septic shock [4] and acute respiratory distress syndrome (ARDS), and is referred to as the obesity paradox. The association between higher BMI and lower mortality is difficult to interpret and potentially influenced by several confounding factors. In patients with ARDS, this paradox is particularly surprising, as obese patients have peculiar alterations of the respiratory function, such as increased chest wall elastance and lower total respiratory system compliance, posing specific challenges for the clinician when mechanical ventilation is required [5, 6]. The obesity paradox in ARDS patients has been investigated in several studies and two recent meta-analyses [7, 8]. Ni and co-authors [7] analysed the evidence concerning the association between BMI and clinical outcomes in ARDS patients, pooling data from 6268 patients enrolled in five studies, including three prospective observational studies [9–11], a retrospective cohort study [12] and one randomised controlled trial [13]. The authors conclude that obesity and morbid obesity were associated with a lower mortality rate in patients with ARDS, therefore supporting the concept of the obesity paradox. In another recent analysis including four additional studies, Zhi et al. [8] reported that obesity increased ARDS-associated morbidity in the ICU population; however, mortality due to ARDS in obese was lower compared to non-obese patients. An increased mortality among underweight patients was also reported, which could be explained by the worse clinical conditions and comorbidities of patients admitted to the ICU with impaired nutritional status. In the five studies included by Ni et al., [7] obese patients were systematically younger and had lower severity scores compared to the reference group (normal weight), while the opposite was observed in the underweight patients. The analysis by Zhi et al. [8] does not report patients’ severity scores. Figure 1 illustrates the observed unadjusted mortality rates in the different obesity classes for the studies included in the meta-analyses for which severity scores (SAPS II predicted mortality or APACHE III) could be extracted: the trend in mortality in the different obesity classes is similar to that of illness severity. This could suggest that the effect of BMI on mortality might be mediated by other clinical factors. Both meta-analyses present some limitations: 1) inclusion of retrospective studies; 2) lack of adjustment for confounders; 3) most analyses are restricted to studies in which obesity was classified according to the WHO BMI classes; and 4) the presence of heterogeneity in some analyses. The adjustment for potential confounding factors is virtually impossible in a conventional meta-analysis without access to individual patient data, especially when a limited number of studies is included [14]. Indeed, when * Correspondence: [email protected] IRCCS AOU San Martino-IST, Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Largo Rosanna Benzi 8, 16131 Genoa, Italy Full list of author information is available at the end of the article