Online Letters to the Editor
The authors reply:
O
ur cohort study was designed to evaluate the body mass index (BMI)-mortality outcome association in critically ill patients who had a nutrition assessment by a registered dietitian (RD). We evaluated the obesity paradox and found that malnutrition was an effect modifier and confounder of the BMI-mortality association (1). As the study cohort was limited to patients examined by an RD (a subset of all ICU admissions), the study was not designed to examine the prevalence of malnutrition or the prevalence of malnutrition in obesity. Although prevalence studies of others are cited in the introduction (2–4), nowhere in our results or discussion is prevalence of malnutrition in the obesity presented or discussed. The malnutrition-mortality association of the entire cohort is a different study design from the one published but has been explored by our group with preliminary observations presented in abstract form (5). Regarding potential bias in our cohort study, ascertainment bias may be present as we only included patients who were evaluated by an RD. We did not include critically ill patients who did not have an RD evaluation as the BMI data were obtained via the RD assessment. The cohort under study has a 30-day mortality rate of 19%, which is higher than the parent ICU cohort of 14% (6). Attrition bias and detection bias were absent as mortality was obtained via the Social Security Death Master File. Trauma patients were not excluded from the study and were included in all analyses. As noted in the Methods section, the study cohort includes 6,518 ICU patients who were evaluated by an RD. Six hundred eight patients (9.8%) in the cohort were trauma patients, of which 108 were obese. As we note in the article, specific addition of a term for trauma did not materially alter the significance of the observed BMI-mortality relationship with or without additional adjustment for nutrition status. Although we appreciate the suggestion by Mittwede et al (7) of analyzing only trauma patients with obesity, the small sample size of 108 obese trauma patients in our cohort will not allow us to produce reliable or precise estimates of differences in outcome relative to the obese nontrauma critically ill patients. Dr. Robinson provided expert testimony for Berkowitz Law Firm. Dr. Mogensen served as a board member for ThriveRx (he is a member of the Nutrition Advisory Board for ThriveRx, which is a home infusion company); lectured for the Massachusetts Dietetic Association (MDA), American Society for Parenteral and Enteral Nutrition (ASPEN) (honoraria for lectures at state meeting [MDA, April 2014]), and Clinical Nutrition Week 2015 (ASPEN); and received royalties from Wolf Rinke Associates (royalties for the publication/continuing education self-study course “Nutritional Support of the Critically Ill Adult”). Dr. Christopher lectured for the ASPEN and the International Symposium on Intensive Care and Emergency Medicine. His institution received grant support from ASPEN (Norman Yoshimura Grant). Malcolm K. Robinson, MD, Kris M. Mogensen, MS, RD, LDN, CNSC, Kenneth B. Christopher, MD, Department of Surgery, Department of Nutrition and the Renal Division, Brigham and Women’s Hospital, Boston, MA e322
www.ccmjournal.org
REFERENCES
1. Robinson MK, Mogensen KM, Casey JD, et al: The relationship among obesity, nutritional status, and mortality in the critically ill. Crit Care Med 2015; 43:87–100 2. Kaidar-Person O, Person B, Sz omstein S, et al: Nutritional deficiencies in morbidly obese patients: A new form of malnutrition? Part A: Vitamins. Obes Surg 2008; 18:870–876 3. Kaidar-Person O, Person B, Szomstein S, et al: Nutritional deficiencies in morbidly obese patients: A new form of malnutrition? Part B: Minerals. Obes Surg 2008; 18:1028–1034 4. Schweiger C, Weiss R, Berry E, et al: Nutritional deficiencies in bariatric surgery candidates. Obes Surg 2010; 20:193–197 5. Christopher KB, Rawn JD, Mogensen KM: Nutrition status and outcomes in noncardiogenic acute respiratory failure: A cohort study. Crit Care Med 2014; 42:A1379 6. Bazick HS, Chang D, Mahadevappa K, et al: Red cell distribution width and all-cause mortality in critically ill patients. Crit Care Med 2011; 39:1913–1921 7. Mittwede PN, Bergin PF, Clemmer JS, et al: Obesity, Malnutrition, and the Response to Critical Illness. Crit Care Med 2015; 43:e321 DOI: 10.1097/CCM.0000000000001104
Invasive Candida Infections in Critically Ill Patients To the Editor:
I
n a recent issue of Critical Care Medicine, we read with great interest the article by Jensen et al (1) who investigated the impact of antibacterial drug on invasive Candida infections in critically ill patients. They found that invasive Candida infections were only significant associated with the use of ciprofloxacin-containing regimen (adjusted hazard ratio, 3.4; 95% CI, 1.4–8.0; p = 0.006). In contrast, no other antibacterial agents, including meropenem, piperacillin/tazobactam, and cefuroxime, and antifungal agents—fluconazole—was found to have significant association with invasive Candida infections. However, we had two concerns about this major finding. First, although the author had adjusted several risk factors of Candida infections, including age, Acute Physiology and Chronic Health Evaluation II score, surgery, autoimmune disease, cancer status, Charlson comorbidity score, body mass index, gender, and the use of mechanical ventilation at baseline in this study, some important risk factors, such as total parenteral nutrition, the exposure of central venous catheter, prior abdominal surgery, and renal failure, were not enrolled for multivariate analysis. Without adjusting these common factors, the results may not truly reflect the real situation. Second, the impact of fluconazole on the development of Candida infections should need more discussion. The antifungal activity of fluconazole against each Candida species is variable. For example, most of Candida krusei clinical isolates were resistant to fluconazole, but most Candida albicans isolates were susceptible to fluconazole (2). As a result, the effect of fluconazole use on the subsequent development of Candida infections should be different according to each Candida species. However, the author only investigated the use of fluconazole on all Candida infections in this study, and their findings may be limited. The authors have disclosed that they do not have any potential conflicts of interest. August 2015 • Volume 43 • Number 8
Copyright © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
The authors reply:
O
ur cohort study was designed to evaluate the body mass index (BMI)-mortality outcome association in critically ill patients who had a nutrition assessment by a registered dietitian (RD). We evaluated the obesity paradox and found that malnutrition was an effect modifier and confounder of the BMI-mortality association (1). As the study cohort was limited to patients examined by an RD (a subset of all ICU admissions), the study was not designed to examine the prevalence of malnutrition or the prevalence of malnutrition in obesity. Although prevalence studies of others are cited in the introduction (2–4), nowhere in our results or discussion is prevalence of malnutrition in the obesity presented or discussed. The malnutrition-mortality association of the entire cohort is a different study design from the one published but has been explored by our group with preliminary observations presented in abstract form (5). Regarding potential bias in our cohort study, ascertainment bias may be present as we only included patients who were evaluated by an RD. We did not include critically ill patients who did not have an RD evaluation as the BMI data were obtained via the RD assessment. The cohort under study has a 30-day mortality rate of 19%, which is higher than the parent ICU cohort of 14% (6). Attrition bias and detection bias were absent as mortality was obtained via the Social Security Death Master File. Trauma patients were not excluded from the study and were included in all analyses. As noted in the Methods section, the study cohort includes 6,518 ICU patients who were evaluated by an RD. Six hundred eight patients (9.8%) in the cohort were trauma patients, of which 108 were obese. As we note in the article, specific addition of a term for trauma did not materially alter the significance of the observed BMI-mortality relationship with or without additional adjustment for nutrition status. Although we appreciate the suggestion by Mittwede et al (7) of analyzing only trauma patients with obesity, the small sample size of 108 obese trauma patients in our cohort will not allow us to produce reliable or precise estimates of differences in outcome relative to the obese nontrauma critically ill patients. Dr. Robinson provided expert testimony for Berkowitz Law Firm. Dr. Mogensen served as a board member for ThriveRx (he is a member of the Nutrition Advisory Board for ThriveRx, which is a home infusion company); lectured for the Massachusetts Dietetic Association (MDA), American Society for Parenteral and Enteral Nutrition (ASPEN) (honoraria for lectures at state meeting [MDA, April 2014]), and Clinical Nutrition Week 2015 (ASPEN); and received royalties from Wolf Rinke Associates (royalties for the publication/continuing education self-study course “Nutritional Support of the Critically Ill Adult”). Dr. Christopher lectured for the ASPEN and the International Symposium on Intensive Care and Emergency Medicine. His institution received grant support from ASPEN (Norman Yoshimura Grant). Malcolm K. Robinson, MD, Kris M. Mogensen, MS, RD, LDN, CNSC, Kenneth B. Christopher, MD, Department of Surgery, Department of Nutrition and the Renal Division, Brigham and Women’s Hospital, Boston, MA e322
www.ccmjournal.org
REFERENCES
1. Robinson MK, Mogensen KM, Casey JD, et al: The relationship among obesity, nutritional status, and mortality in the critically ill. Crit Care Med 2015; 43:87–100 2. Kaidar-Person O, Person B, Sz omstein S, et al: Nutritional deficiencies in morbidly obese patients: A new form of malnutrition? Part A: Vitamins. Obes Surg 2008; 18:870–876 3. Kaidar-Person O, Person B, Szomstein S, et al: Nutritional deficiencies in morbidly obese patients: A new form of malnutrition? Part B: Minerals. Obes Surg 2008; 18:1028–1034 4. Schweiger C, Weiss R, Berry E, et al: Nutritional deficiencies in bariatric surgery candidates. Obes Surg 2010; 20:193–197 5. Christopher KB, Rawn JD, Mogensen KM: Nutrition status and outcomes in noncardiogenic acute respiratory failure: A cohort study. Crit Care Med 2014; 42:A1379 6. Bazick HS, Chang D, Mahadevappa K, et al: Red cell distribution width and all-cause mortality in critically ill patients. Crit Care Med 2011; 39:1913–1921 7. Mittwede PN, Bergin PF, Clemmer JS, et al: Obesity, Malnutrition, and the Response to Critical Illness. Crit Care Med 2015; 43:e321 DOI: 10.1097/CCM.0000000000001104
Invasive Candida Infections in Critically Ill Patients To the Editor:
I
n a recent issue of Critical Care Medicine, we read with great interest the article by Jensen et al (1) who investigated the impact of antibacterial drug on invasive Candida infections in critically ill patients. They found that invasive Candida infections were only significant associated with the use of ciprofloxacin-containing regimen (adjusted hazard ratio, 3.4; 95% CI, 1.4–8.0; p = 0.006). In contrast, no other antibacterial agents, including meropenem, piperacillin/tazobactam, and cefuroxime, and antifungal agents—fluconazole—was found to have significant association with invasive Candida infections. However, we had two concerns about this major finding. First, although the author had adjusted several risk factors of Candida infections, including age, Acute Physiology and Chronic Health Evaluation II score, surgery, autoimmune disease, cancer status, Charlson comorbidity score, body mass index, gender, and the use of mechanical ventilation at baseline in this study, some important risk factors, such as total parenteral nutrition, the exposure of central venous catheter, prior abdominal surgery, and renal failure, were not enrolled for multivariate analysis. Without adjusting these common factors, the results may not truly reflect the real situation. Second, the impact of fluconazole on the development of Candida infections should need more discussion. The antifungal activity of fluconazole against each Candida species is variable. For example, most of Candida krusei clinical isolates were resistant to fluconazole, but most Candida albicans isolates were susceptible to fluconazole (2). As a result, the effect of fluconazole use on the subsequent development of Candida infections should be different according to each Candida species. However, the author only investigated the use of fluconazole on all Candida infections in this study, and their findings may be limited. The authors have disclosed that they do not have any potential conflicts of interest. August 2015 • Volume 43 • Number 8
Copyright © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
