CCR - Mar16 Combined.indb

Objectives: To determine the effect of calorie delivery on hospital mortality among critically ill adults receiving enteral nutrition (EN). Secondary outcomes included the effect of calorie delivery on intensive care unit and hospital length of stay (LOS), duration of mechanical ventilation (MV) and incidence of new-onset pneumonia. Methods: We identifi ed randomised clinical trials of EN, with or without supplemental parenteral nutrition (PN), involving adult ICU patients for whom mortality data were available, and when there was a signifi cant difference in calorie supplementation between intervention arms (P < 0.05). We searched English language electronic databases (1946–2014), bibliographies of nutrition society guidelines and high-impact nutrition and critical care journals. We calculated summary odds ratio (OR) estimates and 95% confi dence intervals using a random effects estimator, and used meta-regression to assess the effect on mortality of average calories delivered. Results: Of 1545 articles identifi ed, 16 eligible studies involving 3473 patients were included. Five studies involved supplemental PN. Mean calorie delivery ranged from 126 kcal/day (SD, 115 kcal/day) to 2086 kcal/day (SD, 460 kcal/day). Mortality was 26.0% in the lower calorie delivery group and 26.5% in the higher calorie delivery group. There was no effect of increased calorie delivery on mortality (OR, 1.02; 95% CI , 0.85–1.24; P = 0.27; I2 = 16.3%). ICU and hospital LOS and incidence of newonset pneumonia did not differ between groups. Duration of MV was decreased with lower calorie delivery (weighted mean difference, 2.92 days; 95% CI, −4.49 to -1.35 days; P < 0.001; I2 = 14.7%). Meta-regression analysis did not show an overall effect on mortality of average calories delivered (P = 0.73; I2 = 40.8%). Conclusion: Delivery of increased calories via the enteral route, with or without supplemental PN, was not associated with a survival benefi t. Crit Care Resusc 2016; 18: 17-24 The generally accepted goals of artifi cial nutrition support in the critically ill are to prevent nutrient defi ciencies by providing adequate macronutrients and micronutrients, preferably via the enteral route, and to avoid metabolic disturbances and delivery-associated complications such as vomiting and aspiration.1-8 Studies examining the relationship between calorie delivery and outcome have yielded confl icting results. Observational studies have suggested that a cumulative calorie defi cit is associated with adverse clinical outcomes, including increased infectious complications and a prolonged length of stay (LOS) in the intensive care unit.9,10 In critically ill patients with sepsis, the delivery of an additional 1000 kcal/day has also been associated with decreased hospital mortality (censored at 60 days; odds ratio [OR], 0.61; 95% CI, 0.48–0.77).11 Similarly, in a double-blind, randomised feasibility trial conducted in 112 patients on mechanical ventilation (MV), Peake and colleagues reported that enteral delivery of 100% of estimated calorie requirements was associated with a trend towards improved 90-day survival, compared with delivery of 70% of requirements (OR, 0.62; 95% CI, 0.25–1.55).12 Conversely, a lower calorie intake has also been associated with improved clinical outcomes in critically ill patients. In 2003, a small observational study of 187 patients suggested a negative relationship between fullfeeding and mortality.13 Receipt of 33%–66% of estimated calorie requirements was associated with increased survival. Subsequent randomised controlled trials (RCTs) have reported that increased calorie delivery was not associated with decreased mortality, morbidity or duration of MV;14-18 but, importantly, none of these trials was blinded, and the Eden study15 was not powered to detect a mortality difference. Braunschweig and colleagues, in a single-centre RCT, recently reported that receiving more than 75% of estimated energy and protein requirements was associated with signifi cantly higher in-hospital mortality in critically ill patients with acute lung injury.17 The question of how many calories should be given to critically ill patients to optimise survival and functional outcomes therefore remains unanswered. The primary aim of our systematic review and meta-analysis was to examine the relationship between calories delivered and mortality in critically ill adult patients. Secondary aims were to determine the effect of calorie delivery on the other clinically important outcomes of ICU and hospital LOS, and incidence of newonset pneumonia. CCR Mar16 Combined.indb 17 16/02/2016 1:18:10 PM Critical Care and Resuscitation • Volume 18 Number 1 • March 2016 ORIGINAL ARTICLES