Enteral Nutrition article summary
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\nPrepare a 3 page summary that concludes with a final nutritional reflection of the article.
\nUse of a concentrated enteral nutrition solution to increase
\ncalorie delivery to critically ill patients: a randomized, double-blind,
\nclinical trial1\u20133
\nSandra L Peake, Andrew R Davies, Adam M Deane, Kylie Lange, John L Moran, Stephanie N O\u2019Connor, Emma J Ridley,
\nPatricia J Williams, and Marianne J Chapman for the TARGET investigators and the Australian and New Zealand Intensive
\nCare Society Clinical Trials Group
\nABSTRACT
\nBackground: Critically ill patients typically receive w60% of estimated
\ncalorie requirements.
\nObjectives: We aimed to determine whether the substitution of
\na 1.5-kcal\/mL enteral nutrition solution for a 1.0-kcal\/mL solution
\nresulted in greater calorie delivery to critically ill patients and establish
\nthe feasibility of conducting a multicenter, double-blind,
\nrandomized trial to evaluate the effect of an increased calorie delivery
\non clinical outcomes.
\nDesign: A prospective, randomized, double-blind, parallel-group,
\nmulticenter study was conducted in 5 Australian intensive care
\nunits. One hundred twelve mechanically ventilated patients expected
\nto receive enteral nutrition for $2 d were randomly assigned
\nto receive 1.5 (n = 57) or 1.0 (n = 55) kcal\/mL enteral nutrition
\nsolution at a rate of 1 mL\/kg ideal body weight per hour for 10 d.
\nProtein and fiber contents in the 2 solutions were equivalent.
\nResults: The 2 groups had similar baseline characteristics (1.5 compared
\nwith 1.0 kcal\/mL). The mean (6SD) age was 56.4 6 16.8
\ncompared with 56.5 6 16.1 y, 74% compared with 75% were men,
\nand the Acute Physiology and Chronic Health Assessment II score was
\n23 6 9.1 compared with 22 6 8.9. The groups received similar
\nvolumes of enteral nutrition solution [1221 mL\/d (95% CI: 1120,
\n1322 mL\/d) compared with 1259 mL\/d (95% CI: 1143, 1374 mL\/d);
\nP = 0.628], which led to a 46% increase in daily calories in the
\ngroup given the 1.5-kcal\/mL solution [1832 kcal\/d (95% CI: 1681,
\n1984 kcal\/d) compared with 1259 kcal\/d (95% CI: 1143, 1374 kcal\/d);
\nP , 0.001]. The 1.5-kcal\/mL solution was not associated with larger
\ngastric residual volumes or diarrhea. In this feasibility study, there was
\na trend to a reduced 90-d mortality in patients given 1.5 kcal\/mL
\n[11 patients (20%) compared with 20 patients (37%); P = 0.057].
\nConclusions: The substitution of a 1.0- with a 1.5-kcal\/mL enteral
\nnutrition solution administered at the same rate resulted in a 46%
\ngreater calorie delivery without adverse effects. The results support
\nthe conduct of a large-scale trial to evaluate the effect of increased
\ncalorie delivery on clinically important outcomes in the critically ill.
\nThis trial was registered at Australian New Zealand Clinical Trials
\n(https:\/\/monkessays.com\/write-my-essay\/anzctr.org.au\/) as ACTRN 12611000793910. Am J
\nClin Nutr 2014;100:616\u201325.
\nINTRODUCTION
\nThe optimal calorie delivery for critically ill patients is unclear.
\nIt is widely believed that calorie delivery should approximate
\nenergy expenditure; however, the direct measurement of energy
\nexpenditure is rarely performed in routine clinical practice because
\nit is difficult and impractical. The calorie requirement is
\nusually estimated by using a variety of predictive equations,
\nwhich are believed to approximate energy expenditure, with
\nw25\u201330 kcal $ kg21 $ d21 generally recommended. There are 2
\nmajor difficulties in this approach. First, it has been universally
\nimpossible to consistently deliver this amount of calories enterally
\n(1\u20134). Second, although such an approach is both logical
\nand plausible, the evidence to support the concept that matching
\nenergy expenditure with calorie delivery improves clinical outcomes
\nhas been limited to observational studies and small,
\nrandomized, controlled trials (4, 5). Although it is logical that
\nenergy delivery should match energy consumption (6), the
\nbenefits of such matching remain to be confirmed by a robust,
\nhigh-quality clinical trial.
\nEnteral calorie delivery during critical illness has frequently
\nand consistently been shown to provide substantially less than the
\nfull-recommended calorie requirement (3, 4, 7), mainly because
\nof gastrointestinal dysmotility, particularly delayed gastric
\nemptying (8), as well as fasting for procedures, surgery, and
\nradiology (9). In an attempt to increase calorie delivery, many
\nstrategies have been tried with limited success, including promotility
\ndrugs (10, 11), small intestinal catheters (12), aggressive
\nnutrition protocols (7), and supplemental intravenous nutrition
\n(13). Thus, there is a sizable and well-established dissociation
\n1 From the Queen Elizabeth Hospital (SLP, JLM, and PJW), the Royal
\nAdelaide Hospital (AMD, SNO, and MJC), the Discipline of Acute Care
\nMedicine, University of Adelaide, Adelaide, Australia; the Department of
\nEpidemiology and Preventive Medicine, Australian and New Zealand Intensive
\nCare Research Centre, Monash University, Victoria, Australia (ARD and
\nEJR); and the Centre for Research Excellence in Translating Nutritional
\nScience into Good Health, National Health and Medical Research Council,
\nUniversity of Adelaide, Adelaide, Australia (KL).
\n2 Supported by the Royal Adelaide Hospital and the Australian and New
\nZealand College of Anaesthetists. Provision and blinding of the study feed and
\nimportation and delivery to the sites was provided by Fresenius Kabi (Germany).
\n3 Address correspondence to MJ Chapman, Intensive Care Unit, Royal
\nAdelaide Hospital, North Terrace, Adelaide, SA 5000, Australia. E-mail:
\nmarianne.chapman@health.sa.gov.au.
\nReceived February 24, 2013. Accepted for publication May 29, 2014.
\nFirst published online June 25, 2014; doi: 10.3945\/ajcn.114.086322.
\n616 Am J Clin Nutr 2014;100:616\u201325. Printed in USA. 2014 American Society for Nutrition
\nDownloaded from ajcn.nutrition.org at TEXAS WOMENS UNIVERSITY on February 3, 2016
\nbetween the recommended calorie requirement and calories actually
\ndelivered. Concentrated formulae have been used frequently in
\nclinical practice (14),mainly to provide calories while limiting fluidvolume
\nadministration; however, the safety and efficacy of the
\nadministration of a concentrated formula at a higher delivery rate to
\ndeliver 100% calorie goals has not been reported to our knowledge.
\nThe primary aim of this study was to determine whether the
\nsubstitution of a 1.0-kcal\/mL enteral nutrition solution with a 1.5-
\nkcal\/mL solution delivered at the same rate resulted in the delivery of
\nmore calories to critically ill patients over the first 10 d of their
\nenteral nutrition therapy. A secondary aim was to provide data to
\ninform the design of a large-scale, multicenter double-blind, randomized,
\ncontrolled trial to investigate whether additional enteral
\ncalorie delivery to critically ill adults affects clinically important
\noutcomes by 1) establishing that the intervention could be blinded,
\n2) ensuring that the intervention could be safely delivered, 3) determining
\nevent rates of various outcomes for the selected patient
\npopulation, 4) determining the recruitment rate, and 5) determining
\nthe size of the treatment effect for the phase III primary outcome of
\ninterest (90-d mortality).
\nSUBJECTS AND METHODS
\nSetting
\nThis study was conducted in 5 Australian university-affiliated,
\ntertiary-referral, intensive care units (ICUs).
\nPatients
\nPatients aged $18 y who were undergoing invasive mechanical
\nventilation and expected to receive enteral nutrition for $2 d were
\nrandomly assigned to receive either a 1.5- or 1.0-kcal\/mL enteral
\nnutrition solution. Patients were excluded if they had already received
\n.12 h enteral or parenteral nutrition during their ICU stay or
\nfor whom the study goal rate was contraindicated (eg, requirement
\nfor fluid restriction), or there was a requirement for a specific enteral
\nnutrition solution (as determined by the treating clinician).
\nEligible patients were randomly assigned in a 1:1 ratio by using
\na permuted block method with variable block sizes stratified by site.
\nAllocation concealment was maintained by using a centralized,
\nWeb-based randomization schedule accessible 24 h a day.
\nPatients were recruited between 23 January and 4 May 2013,
\nand the study was carried out in accordance with the Helsinki
\nDeclaration of 1975 as revised in 1983. All participating institutional
\nethics committees approved the study and allowed
\ndelayed consent to be sought from either the next of kin or the
\npatient. [Australian and New Zealand Clinical Trials Registry
\n(https:\/\/monkessays.com\/write-my-essay\/anzctr.org.au\/); ACTRN 12611000793910].
\nStudy design
\nThis was a multicenter, randomized, controlled, parallel-group,
\nclinical feasibility trial. Patients, clinicians, and all study personnel
\nwere blinded to caloric contents of study enteral nutrition solutions.
\nIntervention
\nThe blinded enteral nutrition solutions were supplied by
\nFresenius Kabi in identical 1-L bags, which differed only in terms
\nof the caloric concentration (Fresubin 2250 Complete 1.5 kcal\/mL
\ncompared with Fresubin 1000 Complete 1.0 kcal\/mL; Fresenius
\nKabi Deutschland GmbH) (Table 1). This difference in the caloric
\nconcentration was shared between fat (0.058 compared
\nwith 0.027 g\/mL) and carbohydrate (0.18 compared with
\n0.125 g\/mL). Protein and fiber contents in the study solutions
\nwere similar at 0.056 compared with 0.055 g\/mL and 0.015
\ncompared with 0.02 g\/mL for the 1.5- and 1.0-kcal\/mL solutions,
\nrespectively. The 2 study interventions were clinically
\nindistinguishable in color and packaging. The effectiveness of
\nthe blinding was confirmed in a formal bedside study at participating
\nsites. In addition, to confirm the successful delivery of
\nallocated enteral nutrition solutions, an independent analysis of
\nthe osmolality of the 1.5-kcal\/mL (430 mOsm\/kg H2O) and
\n1.00-kcal\/mL (360 mOsm\/kg H2O) solutions was obtained for
\na random sample of 261 study bags by using freezing point
\ndepression osmometry.
\nThe study enteral nutrition was delivered at a goal rate of
\n1 mL $ kg ideal body weight (IBW)21 $ h21 in both groups.
\nIBW was calculated from measured height as follows (8):
\nIBWfor men \u00bc \u00bdheight\u00f0cm\u00de 152:430:9 \u00fe 50 \u00f01\u00de
\nIBWwomen \u00bc \u00bdheight\u00f0cm\u00de 152:430:9 \u00fe 45:5 \u00f02\u00de
\nPatients received study enteral nutrition for the duration of
\ntheir ICU stay up to a maximum of 10 d unless enteral nutrition
\nwas ceased earlier. To reduce risk of potential overnutrition
\n(15\u201317), the maximum goal rate was 100 mL\/h for all patients;
\nand at the discretion of treating clinicians, study enteral nutrition
\ncould be ceased if the goal rate was achieved for 5 consecutive
\ndays. Patients for whom consent to continue the study intervention
\nwas withdrawn were analyzed according to the intention-to-treat
\nprinciple unless consent for data collection was refused.
\nOther than the goal rate, the duration and method of enteral
\nnutrition delivery were at the discretion of the treating clinician
\naccording to the usual unit nutrition protocols, including the
\ncommencement rate, increments, use of promotility drugs, and
\nsmall-intestinal feeding tubes. It was recommended that the goal rate
\nbe achieved within 48 h of the commencement of enteral nutrition. If
\nsupplemental parenteral nutrition was deemed necessary (eg, enteral
\nnutrition intolerance), it was assumed that patients were receiving
\na 1.25-kcal\/mL enteral nutrition solution to calculate the total calorie
\ndelivery and determine the amount of parenteral nutrition to administer.
\nStool sampleswere obtained from all patients with diarrhea
\nduring the intervention period and screened for infectious causes and
\nClostridium difficile toxin. Diarrhea was defined as $4 loose-bowel
\nactions within a 24-h period or the use of a fecal management
\nsystem for diarrhea control.
\nBlood glucose management was standardized, with the aim of
\na blood glucose concentration #10 mmol\/L. Blood glucose concentrations
\n#2.2 mmol\/L were defined as a serious adverse event.
\nData collection
\nBaseline data included patient demographics (age, sex, and
\nideal and actual weights); ICU admission diagnosis, category
\n(elective or emergency surgical, medical), and Acute Physiology
\nand Chronic Health Assessment II score; chronic comorbidities
\nINCREASED CALORIE DELIVERY TO THE CRITICALLY ILL 617
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\n(including diabetes); and a dietitian assessment of nutritional
\nrequirements. Data were collected daily for up to 14 d after
\nrandomization included: study enteral nutrition, nonstudy nutrition
\nadministration [parenteral nutrition, incidental calories
\n(eg, 50% dextrose and propofol), intolerance to enteral nutrition
\n(gastric residual volumes, diarrhea, and promotility agents),
\nhighest and lowest blood glucose concentrations, and insulin
\nadministration].
\nOutcomes
\nThe primary outcome was the daily calorie delivery (kcal\/d)
\nfrom study enteral nutrition. Secondary outcomes were as follows:
\n1) the daily total calorie delivery from enteral nutrition,
\nparenteral nutrition, and incidental calories; 2) daily enteral and
\ntotal calorie delivery calculated per unit of IBW (kcal $ kg21 $
\nd21); 3) ICU and hospital length of stay; 4) ventilator-free days
\n(defined as the number of days between successful weaning
\nfrom mechanical ventilation and day 28 after study enrollment
\nin patients who survived to 28 d); and 5) ICU, hospital, and
\n28- and 90-d mortality.
\nStatistical analysis
\nThe sample size of 112 patients for the feasibility trial was
\nbased on data from previous studies by our group and other
\nnutrition studies conducted in Australia and New Zealand (7).
\nWith the assumption of a mean (6SD) daily calorie delivery with
\nenteral nutrition of 1300 6 400 kcal\/d in the 1.0-kcal\/mL (usual
\ntreatment) group, the expectation of at least a 20% increase in
\ncalorie delivery with the higher-concentration 1.5-kcal\/mL solution,
\nand with the use of a 2-group t test at 5% significance and
\n80% power, the estimated minimum required sample size was
\n38 patients\/ group (ie, 76 patients in total). To allow for morereliable
\nestimates of the recruitment rate and baseline mortality
\nand compensate for some recruited patients receiving less than
\nthe anticipated 2 d of enteral nutrition, 112 patients (56 patients\/
\ngroup) were enrolled.
\nAll analyses were conducted according to the intention-to-treat
\nprinciple. No stopping rules or interim analyses were planned.
\nFor missing data, the number of available observations was
\nreported, and missing values were not imputed. Continuous
\nvariables are reported as means (6SDs) or median (IQRs).
\nProportions are reported as percentages with 95% CIs. Differences
\nbetween groups were analyzed, as appropriate, by using
\nStudent\u2019s t test, Wilcoxon\u2019s rank tests or Mann-Whitney U tests
\nfor continuous variables and Pearson\u2019s chi-square or Fisher\u2019s
\nexact test for categorical variables. The overall calorie delivery
\nwas calculated as total intake divided by the number of days fed
\nand expressed as intake per 24 h Daily intakes were analyzed in
\nlinear mixed-effects models with fixed effects for group, day,
\nand the group by day interaction with a heterogeneous first-order
\nautoregressive covariance structure for repeated measurements.
\nVentilator-free days to day 28 were calculated as previously
\ndescribed (18). Patients who died before day 28 were assigned
\nzero ventilator-free days. Absolute risk differences with 95% CIs
\nfor 90-d all-cause mortality are reported. The survival time from
\nrandom assignment to day 90 was compared using a Kaplan-
\nMeier analysis and the log-rank test. The length of stay was
\nanalyzed by using log rank tests with death considered a
\nTABLE 1
\nComposition of the enteral nutrition solutions1
\n1.0 kcal\/mL 1.5 kcal\/mL
\nNutritional composition (\/100 mL)
\nEnergy (kcal) 100 150
\nProtein (g) 5.5 5.6
\nCarbohydrate (g) 12.5 18
\nSugars (g) 1.1 1.2
\nLactose (g) #0.04 #0.03
\nFat (g) 2.7 5.8
\nSFAs (g) 0.23 0.5
\nMUFAs (g) 1.73 3.7
\nPUFAs (g) 0.74 1.6
\nEPA and DHA (g) 0.05 0.03
\nFiber (g) 2 1.5
\nWater (mL) 83 76
\nOsmolarity (mOsm\/L) 300 325
\nOsmolality (mOsm\/kg H2O) 360 430
\nMinerals and trace elements (\/100 mL)
\nSodium [mg (mmol)] 153 (6.7) 100 (4.3)
\nPotassium [mg (mmol)] 213 (5.4) 207 (5.3)
\nChloride [mg (mmol)] 153 (4.3) 153 (4.3)
\nCalcium [mg (mmol)] 85 (2.1) 67 (1.7)
\nPhosphorus [mg (mmol)] 66 (2.1) 53 (1.7)
\nMagnesium [mg (mmol)] 35 (1.4) 24 (1)
\nIron (mg) 2 1.33
\nZinc (mg) 1.5 1.2
\nCopper (mg) 0.2 0.13
\nManganese (mg) 0.4 0.27
\nIodide (mg) 2.0 13.3
\nChromium (mg) 10 6.7
\nMolybdenum (mg) 15 10
\nFluoride (mg) 0.2 0.13
\nSelenium (mg) 10 6.7
\nVitamins and other nutrients (\/100 mL)
\nVitamin A (mg) 105 70
\nb-Carotene (mg) 0.2 0.13
\nVitamin D (mg) 1.5 1
\nVitamin E (mg) 2 3
\nVitamin K (mg) 10 6.67
\nThiamine (mg) 0.2 0.13
\nRiboflavin (mg) 0.26 0.17
\nNiacin (mg) 2.4 1.6
\nVitamin B-6 (mg) 0.24 0.16
\nVitamin B-12 (mg) 0.4 0.27
\nPantothenic acid (mg) 0.7 0.47
\nBiotin (mg) 7.5 5
\nFolic acid 40 26.7
\nVitamin C (mg) 10 6.67
\nCholine (mg) 55 36.7
\nTypical fatty acid profile (g\/mL)
\n14 (myristic acid) \u2014 0.009
\n16 (palmitic acid) 0.16 0.291
\n16:n27 (palmitoeic acid) 0.02 0.011
\n18 (stearic acid) 0.09 0.144
\n18:1n29 (oleic acid) 1.95 3.486
\n18:2n26 (linoleic acid) 0.56 1.101
\n18:3 (a-linolenic acid) 0.23 0.418
\n20:5n23 (EPA) 0.03 0.029
\n22:6n23 (DHA) 0.02 0.019
\nn26:n23 ratio 2:1 2.3:1
\nTypical amino acid profile (g\/100 mL)
\nEssential
\nLysine 0.46 0.44
\n(Continued)
\n618 PEAKE ET AL
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\ncompeting event that precluded discharge. Deaths were censored
\nat values after the last observed discharge for ICU and
\nhospital stays.
\nStatistical analyses were performed with IBM SPSS Statistics
\nsoftware (version 20, 2011; IBM Inc). Statistical significance was
\ndefined as P ,0.05.
\nRESULTS
\nStudy patients
\nOf 415 patients assessed for eligibility, 112 patients were
\nenrolled (1.5 patients per site per week) and randomly assigned to
\nreceive 1.5 kcal\/mL (57 patients) or 1.0 kcal\/mL (55 patients)
\nenteral nutrition solution (Figure 1). All patients were assessed
\nfor the primary outcome. One patient in the 1.5-kcal\/mL group
\nrequested to be withdrawn from the study on day 4, and one
\npatient in the 1.0-kcal\/mL group was lost to follow-up by day 90.
\nBaseline characteristics
\nThe mean age was 56.4 6 16.4 y, and the majority (74%) of
\npatients were men (74%) with an Acute Physiology and Chronic
\nHealth Assessment II score of 23 6 9.0. Seventy-one percent of
\npatients had a medical condition, and 14% of patients had an
\nemergency surgical condition. No differences in baseline characteristics
\nwere observed between the 2 groups (Table 2). The
\ntime from ICU admission to random assignment was not different
\n(21 h for both). A dietitian assessment of calorie requirements
\nwas performed on 88 patients (79%), most
\ncommonly by using a fixed prescription of 20\u201325 kcal\/kg in 43
\npatients (48%) or Schofield\u2019s equation (with or without a stress
\nfactor) in 40 patients (45%). Dietitian-estimated daily calorie
\nrequirements for the 1.5- and 1.0-kcal\/mL groups were 19096
\n312 and 1840 6 318 kcal\/d, respectively (P = 0.306).
\nCalorie delivery
\nThe number of days study enteral nutrition was delivered over
\nthe 10-d intervention period was 7 d (4\u20139 d) and 4 d (3\u20139 d) for
\nthe 1.5- and 1.0-kcal\/mL groups, respectively (P = 0.245). On
\nday 10, 15 patients (27%) and 14 patients (25%) were still receiving
\nstudy enteral nutrition in the 1.5- and 1.0-kcal\/mL
\ngroups respectively. Between days 11 and 14, 33 patients continued
\nto receive enteral nutrition [17 patients (30%) in the 1.5-
\nkcal\/mL group; 16 patients (29%) in the 1.0-kcal\/mL group].
\nThe daily volume of study enteral nutrition delivered in the 2
\ngroups was similar [1.5 compared with 1.0 kcal\/mL:1221 mL
\n(95% CI: 1120, 1322 mL) compared with 1259 mL (95% CI:
\n1143, 1374) mL, respectively; P = 0.628] (Table 3). Overall,
\nthere were a total of 364 feeding days in the 1.5-kcal\/mL group,
\nand a daily goal rate (on the basis of 1 mL $ kg IBW21 $ h21)
\nwas achieved on 136 d (37%). In the 1.0-kcal\/mL group, there
\nwere a total of 311 feeding days, and daily goal rate was achieved
\non 137 d (44%). The number of patients who achieved
\na goal rate on $1 d was 45 (82% of patients) and 47 (85% of
\npatients) in the 1.5- and 1.0-kcal\/mL groups, respectively. The
\ntime to achieve the goal rate was the same for both groups at 2
\nd (1\u20133 d). Reasons for not achieving the goal rate on any day
\nwere similar between the 2 groups and included a planned endotracheal
\nextubation or procedure outside the ICU (63% of
\npatients), vomiting or regurgitation (22% of patients), large
\ngastric residual volumes (26% of patients) and enteral tube removal
\nor blockage (16% of patients).
\nThe administration of the 1.5-kcal\/mL enteral nutrition formula
\nresulted in a 46% greater daily calorie delivery [1832 kcal
\n(95% CI: 1681, 1984 kcal) compared with 1259 kcal (95% CI:
\n1143, 1374 kcal); P , 0.001) (Figure 2). The proportion of
\nestimated daily calorie requirements (on the basis of the dietitian\u2019s
\nassessment) delivered by the study enteral nutrition was
\n102% and 72% for the 1.5- and 1.0-kcal\/mL groups, respectively
\n(P , 0.001). The number of patients who achieved their estimated
\ndaily caloric requirements on one or more study feeding
\ndays was 40 patients (89%) and 7 patients (16%) in the 1.5- and
\n1.0-kcal\/mL groups, respectively (Figure 3). Protein delivery
\nwas the same for both groups (Table 3), with 75% of that estimated
\nby the dietitian in the 1.5-kcal\/mL group and 79% of that
\nestimated in the 1.0-kcal\/mL group.
\nEnteral nutrition calories delivered per kilogram of IBW were
\nsubstantially greater in the group given 1.5 kcal\/mL than for
\nthe group who received 1.0 kcal\/mL (27.3 6 7.4 compared with
\n19.0 6 6.0 kcal $ kg21 $ d21, respectively; P , 0.001) (Table 3).
\nTotal daily calorie delivery from study solution, parenteral nutrition
\nand other calorie sources combined was also higher for
\nthe 1.5-kcal\/mL group (P , 0.001).
\nTABLE 1 (Continued)
\n1.0 kcal\/mL 1.5 kcal\/mL
\nThreonine 0.26 0.26
\nMethionine 0.16 0.13
\nPhenalanine 0.29 0.32
\nTryptophan 0.08 0.08
\nValine 0.40 0.39
\nLeucine 0.55 0.56
\nIsoleucine 0.32 0.33
\nConditionally essential \u2014 \u2014
\nTyrosine 0.3 0.28
\nCysteine 0.03 0.05
\nTaurine \u2014 \u2014
\nHistidine 0.16 0.17
\nArginine 0.20 0.34
\nNonessential
\nGlycine 0.10 0.21
\nAlanine 0.18 0.24
\nProline 0.55 0.48
\nSerine 0.34 0.36
\nGlutamine 0.52 0.52
\nGlutamic acid \u2014 0.73
\nGlutamine and glutamic acid 0.68 \u2014
\nAspartic acid and asparagine 0.41 0.58
\nTypical carbohydrate profile (g\/100 mL)
\nGlucose 0.2 0.2
\nFructose 0.08 0.03
\nMaltose 0.72 0.93
\nSucrose 0.06 0.04
\nLactose #0.04 #0.03
\nPolysaccharides and oligosaccharides 11.5 17.4
\nStarch \u2014 0.2
\n1 Formulae: 1 kcal\/mL (Fresubin 1000 Complete tube feed; Fresenius
\nKabi Deutschland GmbH); 1.5 kcal\/mL (Fresubin 2250 Complete tube feed;
\nFresenius Kabi Deutschland GmbH).
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\nAn independent analysis of the osmolality of a random sample of
\nstudy bags confirmed the delivery of the allocated solutions [1.5
\nkcal\/mL (n = 147); median (IQR): 496 mOsm\/kg H2O (488\u2013507
\nmOsm\/kg H2O) compared with 1.0 kcal\/mL (n = 114); 383 mOsm\/
\nkg H2O (377\u2013388 mOsm\/kg H2O); P , 0.001]. The 2 blinded
\nfeeds were clinically indistinguishable (P = 1.0; Fisher\u2019s exact test).
\nClinical outcomes
\nAt 90 d, 11 patients (20%) in the 1.5-kcal\/mL group and 20
\npatients (37%) in the 1.0-kcal\/mL group had died (P = 0.057;
\nFisher\u2019s exact test) (Table 4). The absolute risk reduction in
\nmortality for the 1.5-kcal group compared with the 1.0-kcal\/mL
\ngroup was 17% (95% CI: 0.6, 33). The survival time from
\nrandom assignment to day 90 tended to be longer in patients
\nwho received the 1.5-kcal\/mL formula (P = 0.057) (Figure 4),
\nand there was no difference in the proximate cause of death (P =
\n0.882) (Table 3). ICU, hospital, and 28-d mortality were not
\ndifferent between the 2 treatment groups. One patient in the 1.5-
\nkcal\/mL group and 6 patients in the 1.0-kcal\/mL group died
\nafter hospital discharge. The number of mechanical ventilationfree
\ndays to day 28, ICU, and hospital length of stay (for survivors
\nonly) and destination at hospital discharge were also not
\ndifferent (Table 3).
\nComplications of therapy
\nEnteral nutrition was never ceased because of treating clinician
\nconcerns of overnutrition. Supplemental parenteral nutrition was
\nadministered to 4 patients (1.5 kcal\/mL, 2 patients; 1.0 kcal\/mL, 2
\npatients). There was no difference between groups in terms of
\ngastrointestinal intolerance (large gastric residual volumes, use of
\npromotility or laxative agents, and diarrhea) (Table 3). Two of 40
\npatients with diarrhea had Clostridium difficile toxin detected.
\nThe increased calorie delivery in the 1.5-kcal\/mL group was
\nassociated with a trend to a slightly higher peak blood glucose
\nconcentration over the 10-d study period (1.5 kcal\/mL; 12.4 6
\n3.9 mmol\/L compared with 1.0 kcal\/mL; 12.0 6 3.9 mmol\/L;
\nP = 0.056); but the number of patients who required insulin on
\n$1 d was no greater in the 1.5-kcal\/mL group [1.5 kcal\/mL (54%)
\ncompared with1.0 kcal\/mL (42%); P = 0.183]. No episodes of
\nhypoglycemia (#2.2 mmol\/L) were reported.
\nDISCUSSION
\nIn this multicenter, randomized, double-blind study, the administration
\nof a 1.5-kcal\/mL enteral nutrition formula resulted in
\na near 50% increase in calorie delivery compared with a 1.0-kcal\/mL
\nformula in mechanically ventilated patients. To our knowledge,
\nFIGURE 1. Patient flow diagram. Numbers of patients enrolled in the study, randomly assigned to receive 1.5- or 1.0-kcal\/mL enteral nutrition solution,
\nand included in the final analysis. *1n = 1 lost to follow-up and excluded from the secondary outcome analysis: 90-d mortality; *2n = 1 withdrawal of consent
\non study day 4. (Included in the intention-to-treat analysis of the primary endpoint, but data were not available beyond study day 4 for secondary outcomes.)
\nEN, enteral nutrition; PN, parenteral nutrition.
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\nthis is the first study in this patient population to describe the use
\nof a concentrated enteral nutrition formula to deliver more calories
\nto patients in a double-blind fashion. Furthermore, in this
\nfeasibility study, we have confirmed the effectiveness of the
\nblinding process, identified a cohort of critically ill patients
\nwhose outcome may be improved by increased calorie delivery
\n(ie, longer-stay, mechanically ventilated patients with a 90-
\nd mortality w28%), and established the potential recruitment
\nrate and treatment-effect size necessary for sample-size calculations
\nfor a large-scale trial.
\nPrevious studies designed to deliver more calories to critically
\nill patients have used techniques including nutrition protocols (7,
\n19\u201321) and small-intestinal feeding catheters (12, 22, 23). Both
\nstrategies have had small effects on calorie delivery. The administration
\nof promotility drugs or supplemental parenteral
\nnutrition has resulted in a greater calorie delivery, but it is unclear
\nif this method offers advantages in terms of clinically
\nmeaningful outcomes (10, 13, 24, 25). It is also possible that
\npotential benefits from an increased calorie delivery may be
\noutweighed by adverse effects from the method used. In the
\nEDEN study, a difference in enteral calorie delivery was achieved,
\nbut in the full-feeding group, only 1300 kcal\/d were delivered,
\nwhich was a similar amount of calories as was given to
\nour 1.0-kcal\/mL group (1259 kcal\/d; 19.0 kcal $ kg21 $ d21) (26).
\nIn contrast, we have shown that .1800 kcal\/d (27 kcal $ kg
\nIBW21 $ d21) was delivered to a heterogeneous population of
\ncritically ill patients by using a 1.5-kcal\/mL enteral nutrition
\nsolution. Although the EDEN study results suggested there was no
\ndifference in clinical outcomes when the administration of 1300
\ncompared with 400 kcal\/d was compared for the first week of ICU
\nnutrition therapy, it remains a plausible hypothesis that the delivery
\nof 1800 kcal\/d (which is closer to expected requirements)
\ncould be associated with improved clinical outcomes.
\nThe use of concentrated enteral nutrition solutions has become
\nmore popular in recent years in ICU patients (14). Concentrated
\nsolutions may be prescribed when a patient is intolerant to enteral
\nnutrition on the assumption that the delivery of lower volume,
\ngreater caloric content solutions may be better tolerated to allow
\nincreased calorie delivery (14). This premise has never been
\nproven. Conversely, it is possible that concentrated solutions may
\nbe less-well tolerated because of the formula being emptied more
\nslowly from the stomach into the small intestine, leading to
\nincreased gastric residual volumes (27). There have also been
\nconcerns that concentrated enteral nutrition solutions may be
\nassociated with increased osmotic diarrhea (28); although studies
\nhave refuted this association (29). The effects of concentrated
\nsolutions on clinical outcomes, including mortality, have also
\nbeen questioned in an observational study of critically ill trauma
\nTABLE 2
\nBaseline characteristics of the study patients1
\nVariable 1.5 kcal\/mL (n = 57) 1.0 kcal\/mL (n = 55) P2
\nAge (y) 56.4 6 16.83 56.5 6 16.1 0.964
\nM 42 6 74 41 6 75 0.917
\nAPACHE II score 23 6 9.1 22 6 8.9 0.560
\nAPACHE III diagnostic code [n (%)] 0.442
\nCardiovascular 12 (21) 8 (15)
\nRespiratory 9 (16) 12 (22)
\nGastrointestinal 4 (7) 3 (6)
\nNeurological 8 (14) 15 (27)
\nSepsis 7 (12) 4 (7)
\nTrauma 11 (19) 6 (11)
\nOther 6 (11) 7 (13)
\nICU admission category [n (%)] 0.095
\nEmergency operative 11 (19) 5 (9)
\nEmergency nonoperative 35 (61) 44 (80)
\nElective operative 11 (19) 6 (11)
\nPast medical history diabetes mellitus [n (%)] 13 (23) 13 (24) 0.917
\nBMI (kg\/m2) 27.8 6 7.9 26.2 6 6.4 0.241
\nActual weight4 (kg) 83 6 23.2 77 6 16.4 0.118
\nIBW5 (kg) 67 6 9.2 67 6 9.1 0.675
\nEnergy requirements6 (kcal\/d) 1909 6 312 1840 6 318 0.306
\nProtein requirements6 (g\/d) 91 6 16 87 6 12 0.178
\nTime from ICU admission to random assignment7 (h) 21 (13\u201336) 21 (13\u201341) 0.836
\nSI tube [n (%)] 4 (7) 1 (2) 0.364
\n1 APACHE, Acute Physiology and Chronic Health Assessment; IBW, ideal body weight; ICU, intensive care unit; SI,
\nsmall intestinal.
\n2A chi-square test was used to determine differences in baseline categorical variables, and a Student\u2019s t test was used
\nfor all continuous variables except time from ICU admission to random assignment (Mann-Whitney U test).
\n3 Mean 6 SD (all such values).
\n4 Actual weight was measured or estimated if not possible.
\n5 IBW was calculated by using the measured height and the following formulae: IBW for men = [height (cm) \u2013 152.4)
\n3 0.9 + 50; IBW for women = [height (cm) \u2013 152.4] 3 0.9 + 45.5.
\n6 Energy and protein requirements were estimated by the dietitians at the site at study entry.
\n7Values are medians; IQRs in parentheses.
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\nTABLE 3
\nNutrition data1
\nVariable 1.5 kcal\/mL (n = 57) 1.0 kcal\/mL (n = 55) P2
\nCalories (overall\/24-h study period)
\nStudy EN (kcal) 1832 6 3813 1259 6 428 , 0.001
\nStudy EN\/kg (kcal\/kg) 27.3 6 7.4 19.0 6 6.0 , 0.001
\nStudy EN 2 GRV (kcal) 1699 6 682 1194 6 454 ,0.001
\nEN + PN + other (kcal) 2040 6 578 1504 6 573 , 0.001
\n(EN + PN + other) 2 GRV (kcal) 1617 6 740 1291 6 623 0.014
\nProtein (overall\/24-h study period)
\nStudy EN (g) 68 6 21 69 6 24 0.847
\nStudy EN\/kg (g\/kg) 1.02 6 0.28 1.05 6 0.33 0.618
\nEN + PN + other (g) 70 6 20 74 6 30 0.395
\nVolume (overall\/24-h study period)
\nStudy EN (mL) 1221 6 381 1259 6 428 0.628
\nGastric residual volume (mL)
\nTotal volume\/24 h 166 (48\u2013324)4 80 (37\u2013261) 0.260
\nReturned\/24 h 126 (41\u2013262) 70 (29\u2013145) 0.050
\nLargest individual measurement 200 (50\u2013360) 105 (40\u2013278) 0.129
\nRegurgitation (over study period) [n (%)] 12 (21) 13 (24) 0.743
\nPromotility drugs (over study period) [n (%)] 28 (49) 25 (46) 0.697
\nLaxative drugs (over study period) [n (%)] 36 (63) 29 (53) 0.263
\nFecal management system [n (%)] (over study period) 8 (14) 13 (24) 0.193
\nDiarrhea [n (%)] 20 (35) 20 (36) 0.888
\nDay first had diarrhea 5 (3\u20138) 4 (2\u20136) 0.369
\nInsulin dose, mean dose\/d (IU) 55 (22\u2013131) 43 (24\u201367) 0.308
\nBlood glucose concentration #2.2 mmol\/L [n (%)] 0 (0) 0 (0) \u2014
\n1 In variables, \u201cother\u201d refers to incidental calorie intake provided by propofol and dextrose infusions. EN, enteral nutrition; GRV, gastric residual volume;
\nPN, parenteral nutrition.
\n2 Differences between 1.5- and 1.0-kcal\/mL enteral nutrition solutions were assessed by using a Student\u2019s t test for all continuous variables except for
\nmeasures of gastric residual volume, the day the patient first had diarrhea, and insulin dose (Mann-Whitney U test), and a chi-square test was used for
\ncategorical variables.
\n3 Mean 6 SD (all such values).
\n4 Median; IQR in parentheses (all such values).
\nFIGURE 2. Mean (6SD) daily calorie delivery over the 10-d study-intervention period. A: Calories provided by the study enteral solution (kcal). B:
\nCalories per kilogram of ideal body weight provided by the study enteral solution (kcal\/kg). C: Calories provided by study enteral solution (kcal) minus the
\ngastric residual volume (kcal). D: Total calories provided by the study enteral solution (kcal) plus intravenous nutrition, propofol, and glucose infusions (kcal).
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\nand surgical patients (22). This current study has shown that the
\nuse of a concentrated solution is both effective and safe in delivering
\nmore calories. There was no difference in enteral intolerance
\n(gastric residual volumes, regurgitation, use of
\npromotility drugs, or diarrhea) or glucose control between the 2
\nenteral nutrition solutions. Although our study was not powered
\nto detect differences in adverse effects, the sample size was
\nsufficient to observe useful numbers of events for these important
\npotential complications. The results also provide information to
\ndetermine the sample size for an adequately powered, future,
\nlarge-scale study for these outcomes.
\nTo our knowledge, this is the first enteral nutrition study to
\nsuccessfully blind the study intervention in this patient population
\n(26, 30). The concealment of the intervention was important
\nto prevent inadvertent bias (31). In previous studies,
\nblinding of the intervention has not been undertaken, which raises
\nconcerns about reported differences in outcomes, particularly
\nwhen outcomes were subject to an ascertainment bias (eg,
\nnosocomial infections and functional outcomes) (6, 24, 25). We
\nwere able to overcome the substantial logistical problems of
\ndesigning a double-blind enteral nutrition study by using 2
\ncommercially available enteral nutrition solutions that were
\nsimilar in color, indistinguishable at the bedside, and delivered at
\nthe same flow rate and volume to both study groups.
\nThis feasibility study had several limitations. The study was
\nnot powered to detect a mortality difference. However, as noted
\nby the Australian and New Zealand Clinical Trials Group consensus
\npanel meeting on endpoints for phase II trials, a signal for
\nimproved survival supports the conduct of a phase III trial with
\n90-d survival as the primary outcome of interest (32). Nevertheless,
\nnote that there were less deaths at 90 d numerically in the
\ngroup who received more calories. If calorie delivery affects
\noutcomes, it is likely to be late, possibly after ICU discharge. Our
\nfindings suggest that the effects of nutritional interventions on
\npost\u2013ICU-discharge mortality should be rigorously sought.
\nAnother limitation of our study is that we did not assess
\nfunctional outcomes. However, there was no difference between
\nthe 2 groups in the destination after hospital discharge, which
\ncould be considered a crude measure of the functional outcome.
\nFIGURE 3. Mean (6SD) estimated goal calories delivered per day from
\n1.5- and 1.0-kcal\/mL enteral nutrition solutions. Estimated daily caloric requirements
\nwere based on the dietitian\u2019s assessment at study entry [available
\nfor 88 patients (79%)].
\nTABLE 4
\nClinical outcome data1
\nVariable 1.5 kcal\/mL (n = 57) 1.0 kcal\/mL (n = 55) P
\nNumber of ventilator-free days to day 28 21.1 (3.4\u201325.0)2 18.7 (0\u201325.6) 0.638
\nDuration of ICU stay (d)3 9.6 (5.9\u201322.6) 11.8 (6.9\u201322.8) 0.408
\nDuration of hospital stay (d) 34.5 (16.9\u201383.6) 30.6 (15.2\u2013undefined)4 0.700
\nDestination at hospital discharge [n (%)]
\nHome 21 (48) 19 (50) 0.953
\nRehabilitation facility 10 (23) 7 (18)
\nAnother acute care hospital 9 (21) 9 (24)
\nChronic care facility 4 (9) 3 (8)
\nMortality [n (%)]
\nICU mortality 6 (11) 9 (16) 0.419
\nHospital mortality [n (%)] 10 (19) 14 (27) 0.357
\n28-d mortality [n (%)] 11 (20) 18 (33) 0.135
\n90-d mortality [n (%)] 11 (20) 20 (37) 0.057
\nDuration of survival (d) 77 6 4.55 68 6 5.6 0.057
\nProximate cause of death [n (%)]
\nCardiovascular 4 (36) 6 (30) 0.882
\nRespiratory 2 (18) 6 (30)
\nNeurologic 4 (36) 7 (35)
\nOther 1 (9) 1 (5)
\n1 Differences between 1.5- and 1.0-kcal\/mL enteral nutrition solutions were assessed by using a Mann-Whitney U test
\nfor continuous variables, a chi-square test for categorical variables, and a Fisher\u2019s exact test for mortality. ICU, intensive
\ncare unit.
\n2 Median; IQR in parentheses (all such values).
\n3 ICU, intensive care unit.
\n4 The IQR was undefined when .25% of patients died or were not discharged from the primary hospital.
\n5 Mean 6 SE (all such values).
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\nThe National Heart, Lung and Blood Institute Acute Respiratory
\nDistress Syndrome Clinical Trials Network group looked at
\nfunctional outcomes in a subset of patients enrolled in the
\nEDEN study and showed that there was no benefit in the administration
\nof 1300 compared with 400 kcal\/d on functional
\noutcomes at 12 mo, albeit only 174 patients were included in
\nthis subgroup analysis (33). Future studies that investigated the
\neffect of nutrition in this population should also include
\nfunctional outcomes.
\nFinally, it is important to emphasize that the optimal dose of
\nprotein administration in critical illness is unclear. In this study,
\nboth groups of patients receivedw1 g $ kg21 $ d21. Establishing
\nthe feasibility of delivering 2 enteral nutrition solutions with
\ndifferent caloric contents but the same protein contents would
\nallow additional investigation on the isolated effects of calorie
\ndelivery. However, it should be noted that the difference in
\ncalorie delivery achieved in this study reflected a difference in
\ncarbohydrate and lipid concentrations in the 2 formulae, and the
\neffect of the macronutrient composition on clinical outcome is
\nan area that needs additional attention. Future clinical studies
\nthat examined the effect of enteral nutrition on clinical outcomes
\nwill need to carefully consider the calorie and protein balance.
\nIn conclusion, the substitution of a standard 1.0-kcal\/mL enteral
\nnutrition solution with a concentrated 1.5-kcal\/mL solution, administered
\nat the same rate, resulted in anw50% increase in calorie
\ndelivery. The delivery of more calories was achieved in a blinded
\nfashion and was also associated with a trend to improved survival.
\nThese data support the conduct of a large, multicenter, randomized,
\ndouble-blind trial to determine whether the delivery of more calories
\nby using a concentrated enteral nutrition solution can result in
\nimproved survival and functional outcomes for critically ill patients.
\nWe are grateful for the Helpance provided by Donna Goldsmith for the
\nunblinded management of study formulae distribution. Participating site investigators
\n(in alphabetical order) were as follows\u2014Austin Health: Rinaldo
\nBellomo, Leah Peck, and Helen Young; Royal Adelaide Hospital: SNO,
\nJustine A Rivett, and Sonya L Kloeden; Royal Prince Alfred Hospital: Suzie
\nFerrie, Heidi Buhr, and Megan Keir; The Canberra Hospital: Sumeet S Rai,
\nHelen Rodgers, and Louise Herlihy; and The Queen Elizabeth Hospital: SLP,
\nJoanne McIntyre, and Jennie Phillips-Hughes.
\nThe authors\u2019 responsibilities were as follows\u2014MJC, ARD, AMD, SNO,
\nSLP, EJR, and PJW: were management committee members and designed the
\nresearch (project ( help with nursing paper writing from experts with MSN & DNP degrees) conception, development of overall research plan, and study
\noversight); MJC, ARD, AMD, KL, JLM, SNO, SLP, and EJR: formed the
\nwriting committee and were responsible for drafting the manuscript; RB,
\nMJC, SF, SSR, and SLP: were involved in the study design, and management;
\nother participating site investigators: conducted the research (hands-on conduct
\nof experiments and data collection); KL and JLM: were involved in the
\nstudy design, analyzed data, performed statistical analyses, and participated in
\nthe preparation of the manuscript; SLP and MJC: co-chaired the management
\nand writing committees, had responsibility for the final content of the manuscript.
\nFresenius Kabi had no influence over the study protocol or the analysis
\nor interpretation of the results. None of the authors had a conflict of interest.
\nREFERENCES
\n1. De Beaux, Chapman M, Fraser R, Finnis M, De Keulenaer B, Liberalli
\nD, Satanek M. Enteral nutrition in the critically ill: a prospective survey
\nin an Australian intensive care unit. Anaesth Intensive Care 2001;
\n29:619\u201322.
\n2. De Jonghe B, Appere-De-Vechi C, Fournier M, Tran B, Merrer J,
\nMelchior JC, Outin H. A prospective survey of nutritional support
\npractices in intensive care unit patients: what is prescribed What is
\ndelivered Crit Care Med 2001;29:8\u201312.
\n3. NICE-SUGARStudy Investigators, Finfer S, Chittock DR, Su SY, Blair
\nD, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, et al. Intensive
\nversus conventional glucose control in critically ill patients. N Engl J
\nMed 2009;360:1283\u201397.
\n4. Alberda C, Gramlich L, Jones N, Jeejeebhoy K, Day AG, Dhaliwal R,
\nHeyland DK. The relationship between nutritional intake and clinical
\noutcomes in critically ill patients: results of an international multicenter
\nobservational study. Intensive Care Med 2009;35:1728\u201337.
\n5. Taylor SJ, Fettes SB, Jewkes C, Nelson R. Prospective, randomized,
\ncontrolled trial to determine the effect of early enhanced enteral nutrition
\non clinical outcome in mechanically ventilated patients suffering
\nhead injury. Crit Care Med 1999;27:2525\u201331.
\n6. Singer P, Anbar R, Cohen J, Shapiro H, Shalita-Chesner M, Lev S,
\nGrozovski E, Theilla M, Frishman S, Madar Z. The tight calorie control
\nstudy (TICACOS): a prospective, randomized, controlled pilot study of
\nnutritional support in critically ill patients. Intensive Care Med 2011;37:
\n601\u20139.
\n7. Doig GS, Simpson F, Finfer S, Delaney A, Davies AR, Mitchell I,
\nDobb G. Effect of evidence-based feeding guidelines on mortality of
\ncritically ill adults: a cluster randomized controlled trial. JAMA 2008;
\n300:2731\u201341.
\n8. Chapman MJ, Besanko LK, Burgstad CM, Fraser RJ, Bellon M,
\nO\u2019Connor S, Russo A, Jones KL, Lange K, Nguyen NQ, et al. Gastric
\nemptying of a liquid nutrient meal in the critically ill: relationship
\nbetween scintigraphic and carbon breath test measurement. Gut 2011;
\n60:1336\u201343.
\n9. Passier RH, Davies AR, Ridley E, McClure J, Murphy D, Scheinkestel
\nCD. Periprocedural cessation of nutrition in the intensive care unit:
\nopportunities for improvement. Intensive Care Med 2013;39:1221\u20136.
\n10. Nguyen NQ, Chapman M, Fraser RJ, Bryant LK, Burgstad C, Holloway
\nRH. Prokinetic therapy for feed intolerance in critical illness: one
\ndrug or two Crit Care Med 2007;35:2561\u20137.
\n11. Nguyen NQ, Chapman MJ, Fraser RJ, Bryant LK, Holloway RH.
\nErythromycin is more effective than metoclopramide in the treatment
\nof feed intolerance in critical illness. Crit Care Med 2007;35:483\u20139.
\n12. Davies AR, Morrison SS, Bailey MJ, Bellomo R, Cooper DJ, Doig GS,
\nFinfer SR, Heyland DK. A multicenter, randomized controlled trial
\ncomparing early nasojejunal with nasogastric nutrition in critical illness.
\nCrit Care Med 2012;40:2342\u20138.
\n13. Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt
\nG, Van Cromphaut S, Ingels C, Meersseman P, Muller J, et al. Early
\nversus late parenteral nutrition in critically ill adults. N Engl J Med
\n2011;365:506\u201317.
\n14. Peake SL, Chapman MJ, Davies AR, Moran JL, O\u2019Connor S, Ridley E,
\nWilliams P. Enteral nutrition in Australian and New Zealand intensive
\ncare units: a point-prevalence study of prescription practices. Crit Care
\nResusc 2012;14:148\u201353.
\n15. Kreymann KG, Berger MM, Deutz NE, Hiesmayr M, Jolliet P,
\nKazandjiev G, Nitenberg G, van den Berghe G, Wernerman J, Ebner C,
\nFIGURE 4. Kaplan-Meier estimates of survival time to day 90.
\n624 PEAKE ET AL
\nDownloaded from ajcn.nutrition.org at TEXAS WOMENS UNIVERSITY on February 3, 2016
\net al. ESPEN guidelines on enteral nutrition: intensive care. Clin Nutr
\n2006;25:210\u201323.
\n16. Martindale RG, McClave SA, Vanek VW, McCarthy M, Roberts P,
\nTaylor B, Ochoa JB, Napolitano L, Cresci G. Guidelines for the provision
\nand assessment of nutrition support therapy in the adult critically
\nill patient: Society of Critical Care Medicine and American Society for
\nParenteral and Enteral Nutrition: executive summary. Crit Care Med
\n2009;37:1757\u201361.
\n17. Heyland DK, Dhaliwal R, Drover JW, Gramlich L, Dodek P. Canadian
\nclinical practice guidelines for nutrition support in mechanically ventilated,
\ncritically ill adult patients. JPEN J Parenter Enteral Nutr 2003;27:355\u201373.
\n18. Schoenfeld DA, Bernard GR. Statistical Assessment of ventilator-free
\ndays as an efficacy measure in clinical trials of treatments for acute
\nrespiratory distress syndrome. Crit Care Med 2002;30:1772\u20137.
\n19. Martin CM, Doig GS, Heyland DK, Morrison T, Sibbald WJ. Multicentre,
\ncluster-randomized clinical trial of algorithms for critical-care
\nenteral and parenteral therapy (ACCEPT). CMAJ 2004;170:197\u2013204.
\n20. Heyland DK, Cahill NE, Dhaliwal R, Wang M, Day AG, Alenzi A,
\nAris F, Muscedere J, Drover JW, McClave SA. Enhanced proteinenergy
\nprovision via the enteral route in critically ill patients: a single
\ncenter feasibility trial of the PEP uP protocol. Crit Care 2010;14:R78.
\n21. Heyland DK, Murch L, Cahill N, McCall M, Muscedere J, Stelfox HT,
\nBray T, Tanguay T, Jiang X, Day AG. Enhanced protein-energy provision
\nvia the enteral route feeding protocol in critically ill patients:
\nresults of a cluster randomized trial. Crit Care Med 2013;41:2743\u201353.
\n22. White H, Sosnowski K, Tran K, Reeves A, Jones M. A randomised
\ncontrolled comparison of early post-pyloric versus early gastric feeding
\nto meet nutritional targets in ventilated intensive care patients. Crit
\nCare 2009;13:R187.
\n23. Deane AM, Dhaliwal R, Day AG, Ridley EJ, Davies AR, Heyland DK.
\nComparisons between intragastric and small intestinal delivery of
\nenteral nutrition in the critically ill: a systematic review and metaanalysis.
\nCrit Care 2013;17:R125.
\n24. Heidegger CP, Berger MM, Graf S, Zingg W, Darmon P, Costanza MC,
\nThibault R, Pichard C. Optimisation of energy provision with supplemental
\nparenteral nutrition in critically ill patients: a randomised
\ncontrolled clinical trial. Lancet 2013;381:385\u201393.
\n25. Doig GS, Simpson F, Sweetman EA, Finfer SR, Cooper DJ, Heighes
\nPT, Davies AR, O\u2019Leary M, Solano T, Peake S. Early parenteral nutrition
\nin critically ill patients with short-term relative contraindications
\nto early enteral nutrition: a randomized controlled trial. JAMA 2013;
\n309:2130\u20138.
\n26. Rice TW, Wheeler AP, Thompson BT, Steingrub J, Hite RD, Moss M,
\nMorris A, Dong N, Rock P. Initial trophic vs full enteral feeding in
\npatients with acute lung injury: the EDEN randomized trial. JAMA
\n2012;307:795\u2013803.
\n27. Chapman M, Fraser R, Vozzo R, Bryant L, TamW, Nguyen N, Zacharakis
\nB, Butler R, Davidson G, Horowitz M. Antro-pyloro-duodenal motor
\nresponses to gastric and duodenal nutrient in critically ill patients. Gut
\n2005;54:1384\u201390.
\n28. Montejo JC. Enteral nutrition-related gastrointestinal complications in
\ncritically ill patients: a multicenter study. The Nutritional and Metabolic
\nWorking Group of the Spanish Society of Intensive Care Medicine
\nand Coronary Units. Crit Care Med 1999;27:1447\u201353.
\n29. Edes TE, Walk BE, Austin JL. Diarrhea in tube-fed patients: feeding
\nformula not necessarily the cause. Am J Med 1990;88:91\u20133.
\n30. Arabi YM, Tamim HM, Dhar GS, Al-Dawood A, Al-Sultan M,
\nSakkijha MH, Kahoul SH, Brits R. Permissive underfeeding and intensive
\ninsulin therapy in critically ill patients: a randomized controlled
\ntrial. Am J Clin Nutr 2011;93:569\u201377.
\n31. Crossley NA, Sena E, Goehler J, Horn J, van der Worp B, Bath PM,
\nMacleod M, Dirnagl U. Empirical evidence of bias in the design of
\nexperimental stroke studies: a metaepidemiologic approach. Stroke
\n2008;39:929\u201334.
\n32. Young P, Hodgson C, Dulhunty J, Saxena M, Bailey M, Bellomo R,
\nDavies A, Finfer S, Kruger P, Lipman J, et al. End points for phase II
\ntrials in intensive care: recommendations from the Australian and New
\nZealand Clinical Trials Group consensus panel meeting. Crit Care
\nResusc 2012;14:211\u20135.
\n33. Needham DM, Dinglas VD, Morris PE, Jackson JC, Hough CL,
\nMendez-Tellez PA, Wozniak AW, Colantuoni E, Ely EW, Rice TW,
\net al. Physical and cognitive performance of patients with acute lung
\ninjury 1 year after initial trophic versus full enteral feeding. EDEN
\nTrial Follow-up. Am J Respir Crit Care Med 2013;188:567\u201376.
\nINCREASED CALORIE DELIVERY TO THE CRITICALLY ILL 625
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