The True Obesity Paradox: Obese and Malnourished?* Sigismond Lasocki, MD, PhD Departement Anesthesie-Reanimation CHU Angers LUNAM Universite Universite dAngers Angers, France
besity is becoming pandemic in the United States, affecting more than one third of the population (1). In population-based studies, higher body mass index (BMI) is associated with higher general mortality, making obesity a major health prob lem (2). However, controversies regarding the prognosis value of obesity in the critically ill appeared during the last 2 decades. Indeed, some studies report a detrimental effect of obesity (3, 4), including recent ones (5), whereas others report no (6, 7) or a protective effect (8, 9). Three meta-analyses raised the possibility that obesity is indeed protective (10-12). This phenomenon has been called the “obesity paradox.” Some hypotheses have been drawn to explain this para dox. Adipose tissue may regulate the inflammatory response through the synthesis of adipokines (13). Adipose tissue may also serve as a source of fuel and energy, useful in the presence of highly catabolic states of critical illness. How ever, this paradox may also represent a “statistical artifact,” since heterogeneity is very important in the different meta analysis (10-12). Obesity or higher BMI may not be pro tective. Indeed, the type of obesity (visceral vs peripheral) may be more important than BMI itself (14). In this issue of Critical Care Medicine, Robinson et al (15) challenge the obesity paradox with another factor: the nutritional sta tus. They used a single-center database of 6,618 critically ill adult patients, hospitalized between 2004 and 2011, in medical or surgical ICUs (100 ICU beds in their institu tion) and who benefited from a nutrition consultation by a registered dietitian. In their large database, 31% of patients were overweighed (BMI, 25-29.9 kg/m2), 23% had class I/II obesity (BMI, 30-39.9 kg/m2), and 5% had class III obesity (BMI, S 40 kg/m2), confirming that obesity is a true health problem in the ICU. In a first analysis, they confirmed the “obesity paradox,” with lower adjusted 30-day mortality for class I/II obese patients. The dietitian consultation was done within 24 hours of ICU admission for all these patients. The
O
'See also p. 87. Key Words: body mass index; critical care; malnutrition; mortality; obesity Dr. Lasocki consulted for ViforPharma. Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins
DOI: 10.1097/CCM.0000000000000646 240
w w w .c c m jo u r n a l.o r g
nutritional status of these patients was assessed and sepa rated in six classes, including the nonspecific malnutrition (association of inadequate nutrient intake of kcal, protein, or micronutrient with metabolic stress and/or overt signs of malnutrition) and the protein-energy malnutrition (pres ence of significant, disease-related, weight loss together with predefined values of albumin, transferrin, or total lym phocyte count) (see the supplemental data of the article for more details) (15). The latter two malnutrition classes' were observed in 56% and 12% of the patients, respectively, while only 32% were well nourished. Furthermore, as much as 60% of the obese patients suffered from malnutrition. The authors observed that obesity association of improved 30-day adjusted mortality (odds ratio, OR, 0.8 [95% Cl, 0.67-0.96]) disappeared with adjustment for nutritional sta tus (OR, 0.96 [95% Cl, 0.81-1.15]). In addition, they report that obese patients with malnutrition had a poorer outcome than well-nourished ones (OR for 90-day mortality, 1.67 [95% Cl, 1.29-2.15]). The authors had access to the social security death master file to evaluate 30-day and 90-day mortality, so that their data are robust, even if they could not adjust mortality to the Acute Physiologic and Chronic Health Evaluation II score (assessed in only 146 patients!), but they used the Deyo-Charlson index and a combination of International Classification of Diseases, 9th Edition, Clini cal Modification and specific current procedural terminol ogy codes to evaluate organ failures. Although the database has been prospectively implemented and was dedicated for research purpose, only a quarter of the 25,686 critically ill patients hospitalized during the study period have been evaluated by a dietitian, suggesting a potential bias regarding the observed proportion of respectively well-nourished and malnourished patients. Indeed, the dietitian team may have selected the patients they have examined. Another potential flaw of this study is the definition of malnutrition, which is mainly subjective despite assessment of some biological variables (i.e., albumin, transferrin, and total lymphocyte count). A recent consensus statement has been proposed for the diagnosis of malnutrition (16). It relies essentially on clinical variables (insufficient energy intake; weight loss; muscle mass loss; subcutaneous fat loss; localized or generalized fluid accumulation that may mask weight loss and reduced hand grip strength) and not on biological ones (apart from inflammation assessment) (16). Obviously, all these variables are difficult to assess in the critically ill by a nonspecialist. Thus, the dedicated dietitian team used in the study of Robinson et al (15) is a great strength of the study. The major question raised by this study is whether nutritional status as assessed by the dietitian is solely an epiphenomenon of the disease or if it is a modifiable vari able that may respond to specific nutrition protocols. In the studied cohort of patients, the dietitian made recommenda tions for all patients, so that the nutrition prescribed rather January 2015* Volume 43 • Number 1
Editorials
than the nutritional status itself could be responsible for the worse outcome observed. This may also be a major flaw of the study. However, in a large subset of the patients ( n = 2,572), using the data of a follow-up consultation by the dietitian, the authors report that indeed the percentage of kcal need met (difficult to evaluate in the obese patient) was quite low, around 30%, making room for improvement. In general, the authors made tremendous efforts to adjust and extend their analysis to avoid confounding factors, with two propensity score analysis (for respectively BMI < 30kg/m2 and S 30kg/m2 and for early or late parenteral nutrition), and found consistent results. Their observations are in line with all the studies on BMI and ICU mortality that report a higher mortality in underweighted patients, who usually are malnourished. In addition, they suggest the importance of nutrition, which has been also recently underlined by studies on parenteral nutrition (17). This study opens new perspec tives: instead of just weighing and heightening our patients, to speculate if they will be in a “good” or “bad” BMI class, we probably better evaluate their nutritional status. Robinson et al (15) showed us that the true obesity paradox is that one can be overweighed and malnourished (60% of the patients were!). Further studies are needed to better qualify the nutri tional status and, above all, to assess which nutrition proto cols may alter the prognosis of our patients, obese or not.
REFERENCES 1. Ogden CL, Carroll MD, Kit BK, et al: Prevalence of obesity among adults: United States, 2011 -2012. NCHS Data Brief 2013; 131:1 -8 2. Flegal KM, Kit BK, Orpana H, et al: Association of all-cause mortality with overweight and obesity using standard body mass index catego ries: A systematic review and meta-analysis. JAMA 2013; 309:71-82 3. Bercault N, Boulain T, Kuteifan K, et al: Obesity-related excess mortal ity rate in an adult intensive care unit: A risk-adjusted matched cohort study. Crit Care Med 2004; 32:998-1003 4. Brown CV, Neville AL, Rhee P, et al: The impact of obesity on the outcomes of 1,153 critically injured blunt trauma patients. J Trauma 2005;59:1048-1051
Critical Care Medicine
5. Pickkers P, de Keizer N, Dusseljee J, et al: Body mass index is associ ated with hospital mortality in critically ill patients: An observational cohort study. Crit Care Med 2013; 41:1878—1883 6. Morris AE, Stapleton RD, Rubenfeld GD, et al: The association between body mass index and clinical outcomes in acute lung injury. Chest 2007; 131:342-348 7. Galanos AN, Pieper CF, Kussin PS, et al: Relationship of body mass index to subsequent mortality among seriously ill hospitalized patients. SUPPORT Investigators. The Study to Understand Prognoses and Preferences for Outcome and Risks of Treatments. Crit Care Med 1997; 25:1962-1968 8. O’Brien JM Jr, Phillips GS, Ali NA, et al: Body mass index is indepen dently associated with hospital mortality in mechanically ventilated adults with acute lung injury. Crit Care Med 2006; 34:738-744 9. Hutagalung R, Marques J, Kobylka K, et al: The obesity paradox in surgical intensive care unit patients. Intensive Care Med 2011; 37:1793-1799 10. Akinnusi ME, Pineda LA, El Solh AA: Effect of obesity on intensive care morbidity and mortality: A meta-analysis. Crit Care Med 2008; 36:151-158 11. Hogue CW Jr, Stearns JD, Colantuoni E, et al: The impact of obe sity on outcomes after critical illness: A meta-analysis. Intensive Care Med 2009; 35:1152-1170 12. Oliveros H, Villamor E: Obesity and mortality in critically ill adults: A systematic review and meta-analysis. Obesity (Silver Spring) 2008; 16:515-521 13. Marques MB, Langouche L: Endocrine, metabolic, and morphologic alterations of adipose tissue during critical illness. Crit Care Med 2013;41:317-325 14. Paolini JB, Mancini J, Genestal M, et al: Predictive value of abdominal obesity vs. body mass index for determining risk of intensive care unit mortality. Crit Care Med 2010; 38:1308-1314 15. Robinson MK, Mogensen KM, Casey JD, et al: The Relationship Among Obesity, Nutritional Status, and Mortality in the Critically III. Crit Care Med 2015; 43:87-100 16. White JV, Guenter P, Jensen G, et al; Academy Malnutrition Work Group; A.S.P.E.N. Malnutrition Task Force; A.S.P.E.N. Board of Directors: Consensus statement: Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition: Characteristics recommended for the identification and documenta tion of adult malnutrition (undernutrition). JPEN J Parenter Enteral Nutr 2012; 36:275-283 17. Heidegger CP, Berger MM, Graf S, et al: Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: A randomised controlled clinical trial. Lancet 2013; 38 1:38 5-3 93
www.ccmjournal.org
241
Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
besity is becoming pandemic in the United States, affecting more than one third of the population (1). In population-based studies, higher body mass index (BMI) is associated with higher general mortality, making obesity a major health prob lem (2). However, controversies regarding the prognosis value of obesity in the critically ill appeared during the last 2 decades. Indeed, some studies report a detrimental effect of obesity (3, 4), including recent ones (5), whereas others report no (6, 7) or a protective effect (8, 9). Three meta-analyses raised the possibility that obesity is indeed protective (10-12). This phenomenon has been called the “obesity paradox.” Some hypotheses have been drawn to explain this para dox. Adipose tissue may regulate the inflammatory response through the synthesis of adipokines (13). Adipose tissue may also serve as a source of fuel and energy, useful in the presence of highly catabolic states of critical illness. How ever, this paradox may also represent a “statistical artifact,” since heterogeneity is very important in the different meta analysis (10-12). Obesity or higher BMI may not be pro tective. Indeed, the type of obesity (visceral vs peripheral) may be more important than BMI itself (14). In this issue of Critical Care Medicine, Robinson et al (15) challenge the obesity paradox with another factor: the nutritional sta tus. They used a single-center database of 6,618 critically ill adult patients, hospitalized between 2004 and 2011, in medical or surgical ICUs (100 ICU beds in their institu tion) and who benefited from a nutrition consultation by a registered dietitian. In their large database, 31% of patients were overweighed (BMI, 25-29.9 kg/m2), 23% had class I/II obesity (BMI, 30-39.9 kg/m2), and 5% had class III obesity (BMI, S 40 kg/m2), confirming that obesity is a true health problem in the ICU. In a first analysis, they confirmed the “obesity paradox,” with lower adjusted 30-day mortality for class I/II obese patients. The dietitian consultation was done within 24 hours of ICU admission for all these patients. The
O
'See also p. 87. Key Words: body mass index; critical care; malnutrition; mortality; obesity Dr. Lasocki consulted for ViforPharma. Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins
DOI: 10.1097/CCM.0000000000000646 240
w w w .c c m jo u r n a l.o r g
nutritional status of these patients was assessed and sepa rated in six classes, including the nonspecific malnutrition (association of inadequate nutrient intake of kcal, protein, or micronutrient with metabolic stress and/or overt signs of malnutrition) and the protein-energy malnutrition (pres ence of significant, disease-related, weight loss together with predefined values of albumin, transferrin, or total lym phocyte count) (see the supplemental data of the article for more details) (15). The latter two malnutrition classes' were observed in 56% and 12% of the patients, respectively, while only 32% were well nourished. Furthermore, as much as 60% of the obese patients suffered from malnutrition. The authors observed that obesity association of improved 30-day adjusted mortality (odds ratio, OR, 0.8 [95% Cl, 0.67-0.96]) disappeared with adjustment for nutritional sta tus (OR, 0.96 [95% Cl, 0.81-1.15]). In addition, they report that obese patients with malnutrition had a poorer outcome than well-nourished ones (OR for 90-day mortality, 1.67 [95% Cl, 1.29-2.15]). The authors had access to the social security death master file to evaluate 30-day and 90-day mortality, so that their data are robust, even if they could not adjust mortality to the Acute Physiologic and Chronic Health Evaluation II score (assessed in only 146 patients!), but they used the Deyo-Charlson index and a combination of International Classification of Diseases, 9th Edition, Clini cal Modification and specific current procedural terminol ogy codes to evaluate organ failures. Although the database has been prospectively implemented and was dedicated for research purpose, only a quarter of the 25,686 critically ill patients hospitalized during the study period have been evaluated by a dietitian, suggesting a potential bias regarding the observed proportion of respectively well-nourished and malnourished patients. Indeed, the dietitian team may have selected the patients they have examined. Another potential flaw of this study is the definition of malnutrition, which is mainly subjective despite assessment of some biological variables (i.e., albumin, transferrin, and total lymphocyte count). A recent consensus statement has been proposed for the diagnosis of malnutrition (16). It relies essentially on clinical variables (insufficient energy intake; weight loss; muscle mass loss; subcutaneous fat loss; localized or generalized fluid accumulation that may mask weight loss and reduced hand grip strength) and not on biological ones (apart from inflammation assessment) (16). Obviously, all these variables are difficult to assess in the critically ill by a nonspecialist. Thus, the dedicated dietitian team used in the study of Robinson et al (15) is a great strength of the study. The major question raised by this study is whether nutritional status as assessed by the dietitian is solely an epiphenomenon of the disease or if it is a modifiable vari able that may respond to specific nutrition protocols. In the studied cohort of patients, the dietitian made recommenda tions for all patients, so that the nutrition prescribed rather January 2015* Volume 43 • Number 1
Editorials
than the nutritional status itself could be responsible for the worse outcome observed. This may also be a major flaw of the study. However, in a large subset of the patients ( n = 2,572), using the data of a follow-up consultation by the dietitian, the authors report that indeed the percentage of kcal need met (difficult to evaluate in the obese patient) was quite low, around 30%, making room for improvement. In general, the authors made tremendous efforts to adjust and extend their analysis to avoid confounding factors, with two propensity score analysis (for respectively BMI < 30kg/m2 and S 30kg/m2 and for early or late parenteral nutrition), and found consistent results. Their observations are in line with all the studies on BMI and ICU mortality that report a higher mortality in underweighted patients, who usually are malnourished. In addition, they suggest the importance of nutrition, which has been also recently underlined by studies on parenteral nutrition (17). This study opens new perspec tives: instead of just weighing and heightening our patients, to speculate if they will be in a “good” or “bad” BMI class, we probably better evaluate their nutritional status. Robinson et al (15) showed us that the true obesity paradox is that one can be overweighed and malnourished (60% of the patients were!). Further studies are needed to better qualify the nutri tional status and, above all, to assess which nutrition proto cols may alter the prognosis of our patients, obese or not.
REFERENCES 1. Ogden CL, Carroll MD, Kit BK, et al: Prevalence of obesity among adults: United States, 2011 -2012. NCHS Data Brief 2013; 131:1 -8 2. Flegal KM, Kit BK, Orpana H, et al: Association of all-cause mortality with overweight and obesity using standard body mass index catego ries: A systematic review and meta-analysis. JAMA 2013; 309:71-82 3. Bercault N, Boulain T, Kuteifan K, et al: Obesity-related excess mortal ity rate in an adult intensive care unit: A risk-adjusted matched cohort study. Crit Care Med 2004; 32:998-1003 4. Brown CV, Neville AL, Rhee P, et al: The impact of obesity on the outcomes of 1,153 critically injured blunt trauma patients. J Trauma 2005;59:1048-1051
Critical Care Medicine
5. Pickkers P, de Keizer N, Dusseljee J, et al: Body mass index is associ ated with hospital mortality in critically ill patients: An observational cohort study. Crit Care Med 2013; 41:1878—1883 6. Morris AE, Stapleton RD, Rubenfeld GD, et al: The association between body mass index and clinical outcomes in acute lung injury. Chest 2007; 131:342-348 7. Galanos AN, Pieper CF, Kussin PS, et al: Relationship of body mass index to subsequent mortality among seriously ill hospitalized patients. SUPPORT Investigators. The Study to Understand Prognoses and Preferences for Outcome and Risks of Treatments. Crit Care Med 1997; 25:1962-1968 8. O’Brien JM Jr, Phillips GS, Ali NA, et al: Body mass index is indepen dently associated with hospital mortality in mechanically ventilated adults with acute lung injury. Crit Care Med 2006; 34:738-744 9. Hutagalung R, Marques J, Kobylka K, et al: The obesity paradox in surgical intensive care unit patients. Intensive Care Med 2011; 37:1793-1799 10. Akinnusi ME, Pineda LA, El Solh AA: Effect of obesity on intensive care morbidity and mortality: A meta-analysis. Crit Care Med 2008; 36:151-158 11. Hogue CW Jr, Stearns JD, Colantuoni E, et al: The impact of obe sity on outcomes after critical illness: A meta-analysis. Intensive Care Med 2009; 35:1152-1170 12. Oliveros H, Villamor E: Obesity and mortality in critically ill adults: A systematic review and meta-analysis. Obesity (Silver Spring) 2008; 16:515-521 13. Marques MB, Langouche L: Endocrine, metabolic, and morphologic alterations of adipose tissue during critical illness. Crit Care Med 2013;41:317-325 14. Paolini JB, Mancini J, Genestal M, et al: Predictive value of abdominal obesity vs. body mass index for determining risk of intensive care unit mortality. Crit Care Med 2010; 38:1308-1314 15. Robinson MK, Mogensen KM, Casey JD, et al: The Relationship Among Obesity, Nutritional Status, and Mortality in the Critically III. Crit Care Med 2015; 43:87-100 16. White JV, Guenter P, Jensen G, et al; Academy Malnutrition Work Group; A.S.P.E.N. Malnutrition Task Force; A.S.P.E.N. Board of Directors: Consensus statement: Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition: Characteristics recommended for the identification and documenta tion of adult malnutrition (undernutrition). JPEN J Parenter Enteral Nutr 2012; 36:275-283 17. Heidegger CP, Berger MM, Graf S, et al: Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: A randomised controlled clinical trial. Lancet 2013; 38 1:38 5-3 93
www.ccmjournal.org
241
Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
