Obesity is a significant problem in the United States, where more than two thirds of Americans are classified as overweight (Body Mass Index [BMI] 25 to 29.9 kg/m2) or obese (BMI >30 kg/m2),1 and mortality has been shown to be increased as a result of associated comorbid conditions.2 The obesity epidemic has extended into the intensive care unit (ICU), with the prevalence of obesity in the ICU reaching as high as 25%.3 This, coupled with the fact that 21% of all hospital admissions utilize ICU care, makes obesity in the ICU a very commonly encountered situation.4
Similarly, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are regularly encountered and potentially devastating problems in the ICU, with a combined reported incidence of 78.9 per 100,000 person-years5 and an estimated in-hospital mortality ranging from 25% to 58%.5-8 It is estimated that 190,600 cases of ALI occur annually with a resultant 74,500 deaths.5 Acute lung injury and its more extreme form, ARDS, are both defined by the acute onset of hypoxemia and bilateral pulmonary infiltrates on chest radiography without clinical evidence of left atrial hypertension, but the entities differ in the degree of observed hypoxemia.9 ALI is defined by a partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2:Fio2) ratio of 200 to 300 mm Hg and ARDS by a ratio less than 200 mm Hg.9
The relationship between obesity and critical illness has been explored, with a recent emphasis on the potential links between obesity and ALI/ARDS. The possible associations between obesity and outcomes from ALI/ARDS and some of the factors that may contribute to these differences are explored here.
RESPIRATORY PHYSIOLOGY AND OBESITY
There are well-known changes in respiratory mechanics that occur in obese individuals and must be considered when acute lung injury develops. The most notable is the decrease in the total respiratory compliance. Pelosi and colleagues compared the respiratory mechanics of sedated, paralyzed normal weight and obese subjects.10 They demonstrated a decrease in total respiratory compliance in obese subjects due to a decrease in both lung and chest wall compliance. In addition, they noted that resistance in the total respiratory system and the lungs was increased in obese subjects.
The effects of obesity on pulmonary physiology are manifested on pulmonary function tests as well. The most commonly seen abnormalities are a decrease in the expiratory reserve volume (ERV) and the functional residual capacity (FRC) with an unchanged residual volume (RV) and total lung capacity (TLC).11-13 The changes are seen secondary to the decrease in respiratory compliance as described above. The effects of obesity on total respiratory compliance are greatest in the supine position where the decreased effects of gravity on the abdominal contents result in an increase in the displacement of the diaphragm upward toward the thoracic cavity. The reduced FRC may approach the closing volume, resulting in gas trapping within the lungs. Spirometric values have been reported as both normal and abnormal in obese subjects.14-17 The forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) may be equally decreased, resulting in a preserved or increased FEV1/FVC ratio consistent with restriction.
The diffusing capacity of carbon monoxide (DLco) is normal-to-increased in obese subjects and, when increased, may do so in proportion to increases in weight.12 The normal underlying lung parenchyma still allows for normal gas transfer in obesity. The increase in DLco may be due to an increase in pulmonary blood volume and cardiac output that occurs with obesity.
The changes in pulmonary physiology in obesity must be considered during attempts to liberate patients from mechanical ventilation. The decrease in respiratory compliance in obese individuals is accentuated in the recumbent position when compared to nonobese individuals. Burns and colleagues studied respiratory parameters in 19 intubated patients with obesity, ascites, or intestinal distension and found that the 45-degree reverse Trendelenburg position may be optimal for obese patients during trials of weaning from mechanical ventilation.18
OBESITY AS A RISK FACTOR FOR ACUTE LUNG INJURY
It is possible that obese patients are more prone to ALI/ARDS. The data is conflicting in terms of the role obesity plays as a risk factor for ALI/ARDS, however. Three studies have examined obesity as a potential risk factor for ALI/ARDS, with each study revealing different results.19-21 Thus, it is currently unknown what the presence of obesity does to the risk of developing ALI/ARDS.
OBESITY AND ACUTE LUNG INJURY OUTCOMES
It has been suggested that obesity may affect the outcomes of critical illness, but few trials have focused on acute lung injury specifically. The first study to examine the outcomes of obese patients with acute lung injury was a secondary analysis of three trials of the National Heart, Lung, and Blood Institute (NHLBI) Acute Respiratory Distress Network (ARDSNet).22 These trials examined the effects of low tidal volume versus high tidal volume ventilation (6 mL/kg of predicted body weight [PBW] versus 12 mL/kg, respectively) as well as the effects of ketoconazole and lisofylline versus placebo in patients with acute lung injury.23-25 A total of 902 patients on required mechanical ventilation who met diagnostic criteria for acute lung injury were enrolled. The data for height and weight from enrollment documents was used to calculate BMI. Patients were excluded if they had a weight-to-height ratio (kilograms divided by centimeters) of 1.0 or greater or were classified as underweight (BMI <18.5 kg/m2).
Of the 807 patients included in the analysis, 334 (41.4%) had a normal BMI (18.5 to 24.9 kg/m2), 254 (31.5%) had an overweight BMI (25 to 29.9 kg/m2), and 219 (27.1%) had an obese BMI (>30 kg/m2). The unadjusted analyses revealed no significant differences in 28-day mortality, 180-day mortality, achieving unassisted ventilation by day 28, and ventilator-free days in individuals who were overweight or obese when compared with those with normal BMIs. Similarly, when adjusted for age, severity of illness, Pao2:Fio2 ratio, study group assignment, peak airway pressure at study enrollment, primary lung injury category, and gender, there were no significant differences in mortality, achieving unassisted ventilation, or ventilator-free days. In summary, this study found no significant difference in outcomes between patients with an overweight or obese BMI and acute lung injury when compared to patients with a normal BMI.
The second study to evaluate the association between BMI and outcome in patients with acute lung injury was a retrospective cohort analysis of Project IMPACT, a subscription database for ICU benchmarking.26 Data was collected from 106 ICUs in 84 US hospitals from December 1995 to September 2001. Records were obtained for 1,673 adults (age >18 years old) with admitting diagnoses consistent with ALI requiring mechanical ventilation within 24 hours of admission. Records for 318 patients did not include data that allowed BMI to be calculated. As a result, 1,488 patients (88.9% of the original cohort) were included in the final analysis. Using the NHLBI categories for BMI,27 the cohort consisted of 26.8% of patients with an overweight BMI, 21.9% with an obese BMI, and 8.8% with a severely obese BMI.
The results demonstrated that BMI was associated with hospital mortality. Unadjusted analysis demonstrated a significant difference in BMI between patients surviving to hospital discharge (BMI 28.8±9.39) versus patients dying during the hospitalization (BMI 26.8±8.57). Unadjusted analysis revealed the highest hospital and ICU mortality in the underweight patients and the lowest hospital and ICU mortality in the severely obese patients. There was no difference among the different BMI categories in regard to hospital or ICU length of stay or discharge destination. Adjusted analysis revealed similar findings with the highest hospital mortality in the patients with underweight BMIs and the lowest hospital mortality in patients with obese BMIs.
The most recent study to evaluate outcomes of obese patients with ALI was a prospective cohort study from 21 hospitals in and around King County, Washington.28 Patients were enrolled if they met the American-European Consensus Conference definition of ALI9 and had a height and weight recorded at admission. As a result, 825 patients met inclusion criteria. Overweight and obese patients comprised 57.4% of the study population. Differences in baseline characteristics existed between the different BMI groups for age, ALI risk factor, and tidal volume on day three.
A significant difference in crude mortality was seen with the highest mortality in the underweight patients, and mortality decreased as the BMI increased. There was no difference in unadjusted hospital or ICU length of stay or duration of mechanical ventilation between the different BMI groups. However, after adjusting for age, severity of illness, and risk factor for ALI, no difference in mortality was seen across the different BMI categories. Adjusted analysis demonstrated a significant difference in hospital and ICU length of stay. Severely obese patients remained in the hospital 10.5 days longer (P < 0.001) and in the ICU 5.6 days longer (P = 0.01) than normal weight patients. Severely obese patients also remained on mechanical ventilation 4.1 days longer (P = 0.03) than normal weight patients. Severely obese patients were also more likely to require discharge to a rehabilitation or skilled nursing facility.
DISPARITIES IN CARE
Differences in care received by obese individuals may contribute to potential differences in outcomes during critical illness, including ALI and ARDS. Biases exist toward obese patients in the health care setting29-31 that may affect the care received by these patients.32-33 In addition, routine ICU care may be more challenging in obese patients. The management of central venous catheters is different in obese patients, as demonstrated by a retrospective study that found that central venous catheters were left an average of 7 days longer in obese patients when compared to normal weight patients.34 Nursing care may also become more challenging in obese patients, where patients with a BMI greater than 40 typically require at least four staff members to assist with repositioning compared to two for normal weight patients.35 Radiographic imaging of critically ill obese patients remains a challenge in the ICU where chest radiographs are often inadequate secondary to poor image quality and the use of computed tomography may be limited due to weight limitations of available equipment.36
Obesity may also result in disparities in clinical practice. The ARDSNet trial of low tidal volume ventilation in ALI/ARDS resulted in an 8.8% absolute reduction in mortality in all patients,23 but evidence suggests that at baseline, obese patients with ALI/ARDS may be ventilated with larger tidal volumes than are normal weight patients, possibly affecting clinical and research outcomes. A secondary analysis of the above-mentioned ARDSNet trial demonstrated preenrollment tidal volumes were higher in patients with obese BMIs (10.76 mL/kg PBW) compared to patients with normal BMIs (10.05 mL/kg PBW).22 The prospective cohort study of patients with ALI from King County reported similar results where the day three tidal volume in patients with normal BMIs was 9.9 mL/kg of PBW versus 10.5 and 11.4 mL/kg of PBW in patients with obese and severely obese BMIs, respectively.28 To ensure optimal outcomes, close attention should be paid to the tidal volume settings in patients with ALI, especially obese patients in whom clinicians may be prone to using higher tidal volumes than normal weight patients.
Obese patients do not always receive inferior care when compared to normal weight patients. For example, obese patients may be more likely to receive heparin prophylaxis for venous thromboembolism, which may lead to less morbidity and improved mortality.26
There is a growing body of literature demonstrating that excessive use of sedation and analgesia in the ICU leads to worse outcomes, which include prolonged time on mechanical ventilation, increased incidence of delirium, and higher mortality in those on mechanical ventilation.37-40 Obesity results in altered pharmacokinetics of drugs used for sedation and analgesia in the ICU, which is especially important for those drugs that are lipophilic.41-43
Benzodiazepines are highly lipophilic drugs that have an increased terminal elimination half-life resulting in the potential for drug accumulation.44 Drugs such as propofol and fentanyl are lipophilic but do not have an increased terminal elimination half-life in obese patients.45-46 As a result, obese patients may respond differently to drugs used for sedation and analgesia, which may lead to worse outcomes in these patients.
ALI/ARDS is a commonly encountered problem in the ICU with an associated high mortality rate. Conventional wisdom would allow one to think that obese patients with ALI/ARDS would have worse outcomes compared to normal weight patients. The data is inconclusive, however, and does not definitively support worse outcomes in obese patients. Disparities in care exist between obese and nonobese patients in the ICU, which may worsen or improve outcomes independent of their underlying ALI/ARDS. As the obesity epidemic continues, the number of ALI/ARDS patients with concomitant obesity will increase, which makes understanding the differences between obese and nonobese patients important to ensuring proper care and treatment.
Jennifer McCallister, MD, is assistant professor of internal medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Ohio State University Medical Center, Columbus; Christopher Russell, MD, is fellow and clinical instructor, pulmonary, allergy, critical care, and sleep medicine, Ohio State University Medical Center. For further information, contact [email protected]
- Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999-2008. JAMA. 2010;303:235-41.
- Bray GA. Overweight is risking fate. Definition, classification, prevalence, and risks. Ann N Y Acad Sci. 1987;499:14-28.
- Joffe A, Wood K. Obesity in critical care. Curr Opin Anaesthesiol. 2007;20:113-8.
- Cooper LM, Linde-Zwirble WT. Medicare intensive care unit use: analysis of incidence, cost, and payment. Crit Care Med. 2004;32:2247-53.
- Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury. N Engl J Med. 2005;353:1685-93.
- Brower RG, Lanken PN, MacIntyre N, et al. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med. 2004;351:327-36.
- Estenssoro E, Dubin A, Laffaire E, et al. Incidence, clinical course, and outcome in 217 patients with acute respiratory distress syndrome. Crit Care Med. 2002;30:2450-6.
- Bersten AD, Edibam C, Hunt T, Moran J. Incidence and mortality of acute lung injury and the acute respiratory distress syndrome in three Australian States. Am J Respir Crit Care Med. 2002;165:443-8.
- Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994;149(3 Pt 1):818-24.
- Pelosi P, Croci M, Ravagnan I, et al. The effects of body mass on lung volumes, respiratory mechanics, and gas exchange during general anesthesia. Anesth Analg. 1998;87:654-60.
- Biring MS, Lewis MI, Liu JT, Mohsenifar Z. Pulmonary physiologic changes of morbid obesity. Am J Med Sci. 1999;318:293-7.
- Ray CS, Sue DY, Bray G, Hansen JE, Wasserman K. Effects of obesity on respiratory function. Am Rev Respir Dis. 1983;128:501-6.
- Sahebjami H, Gartside PS. Pulmonary function in obese subjects with a normal FEV1/FVC ratio. Chest. 1996;110:1425-9.
- Lazarus R, Sparrow D, Weiss ST. Effects of obesity and fat distribution on ventilatory function: the normative aging study. Chest. 1997;111:891-8.
- Crapo RO, Kelly TM, Elliott CG, Jones SB. Spirometry as a preoperative screening test in morbidly obese patients. Surgery. 1986;99:763-8.
- Rubinstein I, Zamel N, DuBarry L, Hoffstein V. Airflow limitation in morbidly obese, nonsmoking men. Ann Intern Med. 1990;112:828-32.
- Thomas PS, Cowen ER, Hulands G, Milledge JS. Respiratory function in the morbidly obese before and after weight loss. Thorax. 1989;44:382-6.
- Burns SM, Egloff MB, Ryan B, Carpenter R, Burns JE. Effect of body position on spontaneous respiratory rate and tidal volume in patients with obesity, abdominal distension and ascites. Am J Crit Care. 1994;3:102-6.
- Choban PS, Weireter LJ Jr, Maynes C. Obesity and increased mortality in blunt trauma. J Trauma. 1991;31:1253-7.
- Neville AL, Brown CV, Weng J, Demetriades D, Velmahos GC. Obesity is an independent risk factor of mortality in severely injured blunt trauma patients. Arch Surg. 2004;139:983-7.
- Dossett LA, Heffernan D, Lightfoot M, et al. Obesity and pulmonary complications in critically injured adults. Chest. 2008;134:974-80.
- O’Brien JM Jr, Welsh CH, Fish RH, Ancukiewicz M, Kramer AM. Excess body weight is not independently associated with outcome in mechanically ventilated patients with acute lung injury. Ann Intern Med. 2004;140:338-45.
- Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342:1301-8.
- Randomized, placebo-controlled trial of lisofylline for early treatment of acute lung injury and acute respiratory distress syndrome. Crit Care Med. 2002;30:1-6.
- Ketoconazole for early treatment of acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. The ARDS Network. JAMA. 2000;283:1995-2002.
- O’Brien JM Jr, Phillips GS, Ali NA, Lucarelli M, Marsh CB, Lemeshow S. Body mass index is independently associated with hospital mortality in mechanically ventilated adults with acute lung injury. Crit Care Med. 2006;34:738-44.
- Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults—The Evidence Report. National Institutes of Health. Obes Res. 1998;6(suppl 2):51S-209S.
- Morris AE, Stapleton RD, Rubenfeld GD, Hudson LD, Caldwell E, Steinberg KP. The association between body mass index and clinical outcomes in acute lung injury. Chest. 2007;131:342-8.
- Teachman BA, Brownell KD. Implicit anti-fat bias among health professionals: is anyone immune? Int J Obes Relat Metab Disord. 2001;25:1525-31.
- Maddox GL, Liederman V. Overweight as a social disability with medical implications. J Med Educ. 1969;44:214-20.
- Rand CS, Macgregor AM. Morbidly obese patients’ perceptions of social discrimination before and after surgery for obesity. South Med J. 1990;83:1390-5.
- Hebl MR, Xu J. Weighing the care: physicians’ reactions to the size of a patient. Int J Obes Relat Metab Disord. 2001;25:1246-52.
- Adams CH, Smith NJ, Wilbur DC, Grady KE. The relationship of obesity to the frequency of pelvic examinations: do physician and patient attitudes make a difference? Women Health. 1993;20:45-57.
- El-Solh A, Sikka P, Bozkanat E, Jaafar W, Davies J. Morbid obesity in the medical ICU. Chest. 2001;120:1989-97.
- Winkelman C, Maloney B. Obese ICU patients: resource utilization and outcomes. Clin Nurs Res. 2005;14:303-23.
- Uppot RN, Sahani DV, Hahn PF, Gervais D, Mueller PR. Impact of obesity on medical imaging and image-guided intervention. AJR Am J Roentgenol. 2007;188:433-40.
- Kress JP, Pohlman AS, O’Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000;342:1471-7.
- Girard TD, Kress JP, Fuchs BD, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet. 2008;371:126-34.
- Strom T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet. 2010;375:475-80.
- Pandharipande P, Shintani A, Peterson J, et al. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology. 2006;104:21-6.
- Cheymol G. Clinical pharmacokinetics of drugs in obesity. An update. Clin Pharmacokinet. 1993;25:103-14.
- Cheymol G. Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet. 2000;39:215-31.
- Adams JP, Murphy PG. Obesity in anaesthesia and intensive care. Br J Anaesth. 2000;85:91-108.
- Greenblatt DJ, Abernethy DR, Locniskar A, Harmatz JS, Limjuco RA, Shader RI. Effect of age, gender, and obesity on midazolam kinetics. Anesthesiology. 1984;61:27-35.
- Servin F, Farinotti R, Haberer JP, Desmonts JM. Propofol infusion for maintenance of anesthesia in morbidly obese patients receiving nitrous oxide. A clinical and pharmacokinetic study. Anesthesiology. 1993;78:657-65.
- Scholz J, Steinfath M, Schulz M. Clinical pharmacokinetics of alfentanil, fentanyl and sufentanil. An update. Clin Pharmacokinet. 1996;31:275-92.