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Nashville, TN
Dr. Rice is Assistant Professor of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine.
Correspondence to: Todd W. Rice, MD, MSc, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, T-1218 MCN, Nashville, TN 37232-2650; e-mail: todd.rice{at}vanderbilt.edu
Despite aggressive efforts to increase awareness and treatment, the prevalence of obesity continues to grow in both industrialized and developing nations. In the United States, this problem has risen to epidemic levels. The most recent data from the Centers for Disease Control and Prevention indicate that almost two thirds of adults are overweight or obese (body mass index [BMI] > 25 kg/m2), a 50% increase over the last 4 decades.1 Although less common in younger adults and children, obesity in these populations is rising as well. Almost one of every six children and adolescents is overweight. Given its rising prevalence and association with many disease states, it is not surprising that the percentage of critically ill patients who are obese is also increasing.
The most recent data suggest that obesity may have paradoxical effects on health. Epidemiologic studies2 have demonstrated that overweight and obese individuals have an increased risk of death from all causes, while also experiencing higher in-hospital mortality. In fact, obesity represents the second-leading cause of death in the United States, trailing only tobacco use.3 The association between BMI and overall mortality in the general population is J shaped, with the nadir in patients with a normal BMI (20 to 25 kg/m2).2
Emerging data, however, suggest that obesity does not have the same detrimental effect in critically ill patients. Although early epidemiologic data4 supported the common opinion that obesity was associated with worse outcomes in critical illness, subsequent data have questioned this supposition. In fact, some recent studies5 have found that increasing BMI is associated with a lower risk of death in critical illness. In this issue of CHEST (see page 342), Morris and colleagues6 provide additional data that obesity is not independently associated with mortality in acute lung injury, a subpopulation of critically ill patients.
Is it possible that some of the features of obesity that contribute to long-term health problems may be beneficial during critical illness? Most critically ill patients are in a catabolic state, especially during the initial phase of the acute illness. Obese patients possess additional energy stores in the form of adipose tissue that can be utilized for support during this highly catabolic time, allowing the patient to experience less net catabolism and resulting in improved outcomes. In addition, adipocytes possess endocrine properties, producing and secreting bioactive peptides, or adipokines, which act both locally and systemically. Two adipokines elevated in the serum of obese patients, interleukin (IL)-10 and leptin, may be beneficial during critical illness. IL-10, an antiinflammatory cytokine, helps control the initial inflammatory response in critical illness by inhibiting the release of proinflammatory cytokines such as tumor necrosis factor, IL-6, and IL-8 from macrophages. Previous data7 have shown that lower levels of IL-10 in the plasma of patients with acute lung injury are associated with worse outcomes. Similarly, leptin has immunologic effects that may confer a survival advantage. It has been shown8 that survivors of sepsis have significantly higher serum levels of leptin than nonsurvivors.
Overweight and obese patients have higher serum cholesterol and lipid levels compared to normal-weight individuals. Although elevated serum cholesterol levels are detrimental in the long term, they may confer beneficial effects during the acute phase of critical illness. Lipids and lipoproteins, such as cholesterol, bind endotoxin and neutralize its inflammatory effects. This may partly explain the lower prevalence of sepsis as an acute lung injury etiology in overweight and obese patients in the King County Lung Injury cohort.6 Furthermore, low levels of cholesterol and lipoproteins are associated with higher concentrations of inflammatory cytokines and worse clinical outcomes in critically ill patients. In addition, since cholesterols serve as precursors to steroid synthesis in the adrenal glands, higher levels may also be protective against developing adrenal insufficiency in critical illness. Finally, obesity-related diseases result in many patients being treated with medicines, such as statins or angiotension-converting enzyme inhibitors, which may improve clinical outcomes in critical illness by currently undefined mechanisms. For example, pretreatment with statins has been shown to reduce mortality in patients with severe sepsis.9
Why have multiple studies found conflicting results regarding the association between BMI and mortality in critical illness? In addition to differences in methodology and patient populations, differing supportive care may also contribute; for example, mechanical ventilation with lower tidal volumes (ie, 6 mL/kg predicted body weight) improves survival in patients with acute lung injury,10 regardless of BMI.11 However, prior to this discovery, patients often received mechanical ventilation with tidal volumes relative to actual body weight, resulting in higher relative tidal volumes for patients with higher BMIs. In fact, Morris and colleagues6 report the use of larger tidal volumes with increasing BMIs in their cohort. Had they chosen to adjust for tidal volume size in the multivariate analysis, a protective effect of increasing BMI may have been found, similar to that previously shown by O’Brien and colleagues.5 Additionally, BMI calculated only from height and weight may represent a poor surrogate for obesity and/or overall health, correlating poorly with other important factors such as activity level or lean body mass.12
In the King County Lung Injury cohort,6 severely obese patients (BMI 
40 kg/m2) did incur increased morbidity, demonstrated by longer duration of mechanical ventilation as well as ICU and hospital lengths of stay. Unfortunately, the absence of protocolized ventilator weaning during the study renders the longer duration of ventilation difficult to interpret. Concerns about problems reintubating these patients may have contributed to their longer duration of ventilation. The fact that these patients were also more likely to be discharged to inpatient rehabilitation or skilled nursing facilities, however, further suggests that they do experience increased morbidity and that it extends beyond the acute hospital care setting.
The lack of association between BMI and mortality confirms the need for aggressive care in patients regardless of weight. The higher morbidity in severely obese patients suggests that further research should be directed exclusively at this population. This research should be focused on reducing morbidity as well as decreasing the utilization of valuable health-care resources.
Footnotes
Dr. Rice is supported by the National Institutes of Health funding sources K23HL81431 and N01 HR56174.
The author has no financial or other conflicts of interest with any companies that make a product or competitive product of any subject discussed in this editorial.
Received for publication October 20, 2006. Accepted for publication October 23, 2006.
References
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