Pathophysiology 15 (2008) 123–134 Influence of obesity on sepsis Vidula Vachharajani ∗ Department of Anesthesiology, Medical Center Blvd, Wake Forest University School of Medicine, Winston-Salem, NC 27157, United States Received 12 February 2008; received in revised form 3 April 2008; accepted 30 April 2008 Abstract Sepsis is the leading cause of death in non-coronary intensive care units worldwide, with a very high cost of care. There is a growing body of evidence suggesting that the increase in morbidity associated with severe obesity in critically ill patients results in increased resource utilization adding further to the cost of care. There is a relative paucity of information regarding the pathophysiology and treatment of obese critically ill patients, especially with sepsis. Obesity as an exclusion criterion in landmark trials is partly responsible for this paucity. While the preventive strategies for obesity will be the most definitive long-term solution, it will take a long time to affect outcomes in our intensive care units. In the meantime, our hospitals, including the intensive care units must continue to treat obese/morbidly obese critically ill patients with sepsis, making it essential to study and understand the pathophysiology and develop treatment strategies for obese with sepsis. Available laboratory data suggests an increased inflammatory response in obese septic individuals. However, the association between obesity and sepsis in the clinical setting is unclear due to controversial results. This article reviews the available clinical and laboratory data that addresses the effects of obesity on sepsis. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Obesity; Sepsis; Critical care; Leukocyte adhesion 1. Sepsis and septic shock Sepsis has been known to mankind for 2700 years [1]. The modern day definition of sepsis was derived from the con- sensus conference between the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) in 1992 [2] as described in Table 1. Sepsis is defined as a systemic inflammatory response to infection, which, when associated with one or more organ systems, is consid- ered as severe failure. When sepsis is associated with shock, which is refractory to fluid resuscitation, the patient is con- sidered to be in septic shock. Sepsis and septic shock are the leading causes of death in the non-coronary artery disease intensive care units worldwide with substantial cost of care [3]. Not only has the rate of hospitalization due to sepsis dou- bled over the last decade and has exceeded the expected rate of hospitalization, but the overall mortality has also increased considerably during that period [4]. This clearly underscores ∗ Tel.: +1 336 716 4498; fax: +1 336 716 8190. E-mail address: vvachhar@wfubmc.edu. the fact that morbidity and mortality associated with sepsis causes an economic burden on the society. 1.1. Pathophysiology of sepsis and septic shock The pathophysiology of sepsis consists of a well- orchestrated host response to invading organisms. This response, which is a local process initially, becomes an over- whelming systemic response in cases of severe sepsis and septic shock. The inability of the host to recognize self from non-self can be viewed as a critical central theme to this exaggerated response. Host response is implicated in the excessive morbidity and mortality associated with sepsis due to the collateral damage that it causes in the form of multiple organ failure. There are several findings that support the view that host response is the most critical determinant of outcome in sepsis. (1) Mortality is comparable in culture negative and culture positive patients with sepsis [5]. (2) Mortality with sepsis and septic shock is directly proportional to the number of organ systems involved in the multiple organ failure [6]. (3) There is a direct correlation between the number 0928-4680/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pathophys.2008.04.008