Early oral protein-containing diets following elective lower gastrointestinal tract surgery in adults: a meta-analysis of randomized clinical trials.

BACKGROUND: Although current guidelines make consensus recommendations for the early resumption of oral intake after surgery, a recent comprehensive meta-analysis failed to identify any patient-centered benefits. We hypothesized this finding was attributable to pooling studies providing effective protein-containing diets with ineffective non-protein liquid diets. Therefore, the aim of this paper was to investigate the safety and efficacy of early oral protein-containing diets versus later (traditional) feeding after elective lower gastrointestinal tract surgery in adults. METHODS: PubMed, Embase, and the China National Knowledge Infrastructure databases were searched from inception until 1 August 2019. Reference lists of retrieved studies were hand searched to identify randomized clinical trials reporting mortality. No language restrictions were applied. Study selection, risk of bias appraisal and data abstraction were undertaken independently by two authors. Disagreements were settled by obtaining an opinion of a third author. Majority decisions prevailed. After assessment of underlying assumptions, a fixed-effects method was used for analysis. The primary outcome was mortality. Secondary outcomes included surgical site infections, postoperative nausea and vomiting, serious postoperative complications and other key measures of safety and efficacy. RESULTS: Eight randomized clinical trials recruiting 657 patients were included. Compared with later (traditional) feeding, commencing an early oral protein-containing diet resulted in a statistically significant reduction in mortality (odds ratio [OR] 0.31, P = 0.02, I2 = 0%). An early oral protein-containing diet also significantly reduced surgical site infections (OR 0.39, P = 0.002, I2 = 32%), postoperative nausea and vomiting (OR 0.62, P = 0.04, I2 = 37%), serious postoperative complications (OR 0.60, P = 0.01, I2 = 25%), and significantly improved other major outcomes. No harms attributable to an early oral protein-containing diet were identified. CONCLUSIONS: The results of this systematic review can be used to upgrade current guideline statements to a grade A recommendation supporting an oral protein-containing diet commenced before the end of postoperative day 1 after elective lower gastrointestinal surgery in adults.

Evidence summary resources may influence clinical decision making: A case-based scenario evaluation of an evidence summary tool.

PURPOSE: Evidence summary resources are popular with clinicians but it is unknown whether they can influence clinical decision making. We evaluated whether an extremely condensed and explicit evidence summary tool could influence clinical decision making. MATERIALS AND METHODS: An evidence summary tool was developed using a formal mapping exercise and graphic design principles. An invitation to participate was sent to subscribers of a critical care e-mail discussion list. Participants received a study package (evidence summary tool précising prone positioning in severe ARDS; case-based scenario describing a patient with severe ARDS plus evaluation questionnaire). Influence on clinical decisions was captured regarding six competing interventions, with Belief in benefit measured before and after reading the summary tool. RESULTS: Among 93 participants, 87% were male with a mean age of 49.6(SD9.3) years. Mean ICU experience was 20.0(SD9.9) years. The evidence summary tool significantly influenced clinical decision making: belief in benefit of prone positioning increased (P < .001), belief in benefit of higher PEEP decreased (P = .002) and belief in benefit in ECMO decreased (P = .07). CONCLUSIONS: Using a before-after evaluation, we demonstrated an extremely condensed and explicit information format can influence clinical decision making. Evidence summary tools may be a useful adjunct to support closing evidence-practice gaps.

Intravenous amino acid therapy for kidney protection in cardiac surgery patients: A pilot randomized controlled trial.

OBJECTIVE: To determine whether a continuous intravenous infusion of standard amino acids could preserve kidney function after on-pump cardiac surgery. METHODS: Adult patients scheduled to receive cardiac surgery lasting longer than 1 hour on-pump were randomized to standard care (n = 36) or an infusion of amino acids initiated immediately after induction of anesthesia (n = 33). The study's primary outcome measurements assessed renal function. These assessments included duration of renal dysfunction, duration and severity of acute kidney injury (AKI), estimated glomerular filtration rate (eGFR) over time, urine output, and use of renal-replacement therapy. Complications and other measures of morbidity were also assessed. RESULTS: Sixty-nine patients (mean age 71.5 [standard deviation 9.2] years; 19 of 69 women) were enrolled and randomized. Patients received coronary artery bypass graft surgery (37/69), valve surgery (24/69), coronary artery bypass graft and valve surgery (6/69), or other procedures (2/69). Mean on-pump time was 268 [standard deviation 136] minutes. Duration of renal dysfunction did not differ between the groups (relative risk, 0.86; 95% confidence interval [CI], 0.19-3.79, P = .84). However, patients who received the amino acid infusion had a reduced duration of AKI (relative risk, 0.02; 95% CI, 0.005-0.11, P < .0001) and greater eGFR (+10.8%; 95% CI, 1.0%-20.8%, P = .033). Daily mean urine output was also significantly greater in patients who received the amino acid infusion (1.4 ± 0.5 vs 1.7 ± 0.9 L/d; P = .046). CONCLUSIONS: Commencing an infusion of standard amino acids immediately after the induction of anesthesia did not alter duration of renal dysfunction; however, other key measures of renal function (duration of AKI, eGFR and urine output) were significantly improved. These results warrant replication in multicenter clinical trials.

Early Enteral Nutrition Reduces Mortality and Improves Other Key Outcomes in Patients With Major Burn Injury: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To identify, appraise, and synthesize current evidence to determine whether early enteral nutrition alters patient outcomes from major burn injury. DATA SOURCES: Medline, Embase, and the China National Knowledge Infrastructure were searched. The close out date was May 1, 2018. STUDY SELECTION: Early enteral nutrition was defined as a standard formula commenced within 24 hours of injury or admission to ICU or burn unit. Comparators included any form of nutrition support "except" early enteral nutrition. Only randomized controlled trials reporting patient-centered outcomes were eligible for inclusion. DATA EXTRACTION: The primary outcome was mortality. Gastrointestinal hemorrhage, sepsis, pneumonia, renal failure, and hospital stay were evaluated as secondary outcomes. DATA SYNTHESIS: Nine-hundred fifty-eight full-text articles were retrieved and screened. Seven randomized controlled trials enrolling 527 participants with major burn injury were included. Compared with all other types of nutrition support, early enteral nutrition significantly reduced mortality (odds ratio, 0.36; 95% CI, 0.18-0.72; p = 0.003; I = 0%). Early enteral nutrition also significantly reduced gastrointestinal hemorrhage (odds ratio, 0.21; 95% CI, 0.09-0.51; p = 0.0005; I = 0%), sepsis (odds ratio, 0.23; 95% CI, 0.11-0.48; p < 0.0001; I = 0%), pneumonia (odds ratio, 0.41; 95% CI, 0.21-0.81; p = 0.01; I = 63%), renal failure (odds ratio, 0.27; 95% CI, 0.09-0.82; p = 0.02; I = 32%), and duration of hospital stay (-15.31 d; 95% CI, -20.43 to -10.20; p < 0.00001; I = 0%). CONCLUSIONS: The improvements in clinical outcomes demonstrated in this meta-analysis are consistent with the physiologic rationale cited to support clinical recommendations for early enteral nutrition made by major clinical practice guidelines: gut integrity is preserved leading to fewer gastrointestinal hemorrhages, less infectious complications, a reduction in consequent organ failures, and a reduction in the onset of sepsis. The cumulative benefit of these effects improves patient survival and reduces hospital length of stay.

Early Enteral Nutrition Provided Within 24 Hours of ICU Admission: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To identify, appraise, and synthesize the most current evidence to determine whether early enteral nutrition alters patient outcomes from critical illness. DATA SOURCES: Medline and Embase were searched. The close out date was November 20, 2017. STUDY SELECTION: Early enteral nutrition was defined as a standard formula commenced within 24 hours of ICU admission. Comparators included any form of nutrition support "except" early enteral nutrition. Only randomized controlled trials conducted in adult patients requiring treatment in an ICU were eligible for inclusion. DATA EXTRACTION: The primary outcome was mortality. Secondary outcomes included pneumonia, duration of mechanical ventilation, and ICU and hospital stay. DATA SYNTHESIS: Six-hundred ninety-nine full-text articles were retrieved and screened. Sixteen randomized controlled trials enrolling 3,225 critically ill participants were included. Compared with all other types of nutrition support, commencing enteral nutrition within 24 hours of ICU admission did not result in a reduction in mortality (odds ratio, 1.01; 95% CI, 0.86-1.18; p = 0.91; I = 32%). However, there was a differential treatment effect between a priori identified subgroups (p = 0.032): early enteral nutrition reduced mortality compared with delayed enteral intake (odds ratio, 0.45; 95% CI, 0.21-0.95; p = 0.038; I = 0%), whereas a mortality difference was not detected between early enteral nutrition and parenteral nutrition (odds ratio, 1.04; 95% CI, 0.89-1.22; p = 0.58; I = 30%). Overall, patients who were randomized to receive early enteral nutrition were less likely to develop pneumonia (odds ratio, 0.75; 95% CI, 0.60-0.94; p = 0.012; I = 48%). CONCLUSIONS: Overall, there was no difference between early enteral nutrition and all other forms of nutrition support. A priori planned subgroup analysis revealed early enteral nutrition reduced mortality and pneumonia compared with delayed enteral intake; however, there were no clear clinical advantages of early enteral nutrition over parenteral nutrition.

Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial.

BACKGROUND: Equipoise exists regarding the benefits of restricting caloric intake during electrolyte replacement for refeeding syndrome, with half of intensive care specialists choosing to continue normal caloric intake. We aimed to assess whether energy restriction affects the duration of critical illness, and other measures of morbidity, compared with standard care. METHODS: We did a randomised, multicentre, single-blind clinical trial in 13 hospital intensive care units (ICUs) in Australia (11 sites) and New Zealand (two sites). Adult critically ill patients who developed refeeding syndrome within 72 h of commencing nutritional support in the ICU were enrolled and allocated to receive continued standard nutritional support or protocolised caloric restriction. 1:1 computer-based randomisation was done in blocks of variable size, stratified by enrolment serum phosphate concentration (>0·32 mmol/L vs ≤0·32 mmol/L) and body-mass index (BMI; >18 kg/m(2)vs ≤18 kg/m(2)). The primary outcome was the number of days alive after ICU discharge, with 60 day follow-up, in a modified intention-to-treat population of all randomly allocated patients except those mistakenly enrolled. Days alive after ICU discharge was a composite outcome based on ICU length of stay, overall survival time, and mortality. The Refeeding Syndrome Trial was registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR number 12609001043224). FINDINGS: Between Dec 3, 2010, and Aug 13, 2014, we enrolled 339 adult critically ill patients: 170 were randomly allocated to continued standard nutritional support and 169 to protocolised caloric restriction. During the 60 day follow-up, the mean number of days alive after ICU discharge in 165 assessable patients in the standard care group was 39·9 (95% CI 36·4-43·7) compared with 44·8 (95% CI 40·9-49·1) in 166 assessable patients in the caloric restriction group (difference 4·9 days, 95% CI -2·3 to 13·6, p=0·19). Nevertheless, protocolised caloric restriction improved key individual components of the primary outcome: more patients were alive at day 60 (128 [78%] of 163 vs 149 [91%] of 164, p=0·002) and overall survival time was increased (48·9 [SD 1·46] days vs 53·65 [0·97] days, log-rank p=0·002). INTERPRETATION: Protocolised caloric restriction is a suitable therapeutic option for critically ill adults who develop refeeding syndrome. We did not identify any safety concerns associated with the use of protocolised caloric restriction. FUNDING: National Health and Medical Research Council of Australia.

Intravenous amino acid therapy for kidney function in critically ill patients: a randomized controlled trial.

IMPORTANCE: Acute kidney injury (AKI) is characterized by severe loss of glomerular filtration rate (GFR) and is associated with a prolonged intensive care unit (ICU) stay and increased risk of death. No interventions have yet been shown to prevent AKI or preserve GFR in critically ill patients. Evidence from mammalian physiology and small clinical trials suggests higher amino acid intake may protect the kidney from ischemic insults and thus may preserve GFR during critical illness. OBJECTIVE: To determine whether amino acid therapy, achieved through daily intravenous (IV) supplementation with standard amino acids, preserves kidney function in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, phase II, randomized clinical trial conducted between December 2010 and February 2013 in the ICUs of 16 community and tertiary hospitals in Australia and New Zealand. Participants were adult critically ill patients expected to remain in the study ICU for longer than 2 days. INTERVENTIONS: Random allocation to receive a daily supplement of up to 100 g of IV amino acids or standard care. MAIN OUTCOMES AND MEASURES: Duration of renal dysfunction (primary outcome); estimated GFR (eGFR) derived from creatinine; eGFR derived from cystatin C; urinary output; renal replacement therapy (RRT) use; fluid balance and other measures of renal function. RESULTS: 474 patients were enrolled and randomized (235 to standard care, 239 to IV amino acid therapy). At time of enrollment, patients allocated to receive amino acid therapy had higher APACHE II scores (20.2 ± 6.8 vs. 21.7 ± 7.6, P = 0.02) and more patients had pre-existing renal dysfunction (29/235 vs. 44/239, P = 0.07). Duration of renal dysfunction after enrollment did not differ between groups (mean difference 0.21 AKI days per 10 patient ICU days, 95 % CI -0.27 to 1.04, P = 0.45). Amino acid therapy significantly improved eGFR (treatment group × time interaction, P = 0.004), with an early peak difference of 7.7 mL/min/1.73 m(2) (95 % CI 1.0-14.5 mL/min/1.73 m(2), P = 0.02) on study day 4. Daily urine output was also significantly increased (+300 mL/day, 95 % CI 145-455 mL, P = 0.0002). There was a trend towards increased RRT use in patients receiving amino acid therapy (13/235 vs. 25/239, P = 0.062); however, this trend was not present after controlling for baseline imbalance (P = 0.21). CONCLUSION AND RELEVANCE: Treatment with a daily IV supplement of standard amino acids did not alter our primary outcome, duration of renal dysfunction. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12609001015235.

Intensive care specialists' knowledge, attitudes, and professional use of published research evidence: a mail-out questionnaire survey of appropriate use of research evidence in clinical practice.

PURPOSE: This survey investigates the knowledge, attitudes, and use of published research in clinical practice by intensive care specialists. MATERIALS AND METHODS: A mail-out questionnaire was sent to randomly selected intensive care specialists registered with the Australian and New Zealand College of Intensive Care Medicine. RESULTS: The response rate was 55.9% (133/238). The average score for research knowledge was 2.9 of 6. Eighty-five (65.4%) of 130 respondents reported positive feelings toward using published research evidence in clinical practice, with 96.6% (126/130) reporting use of the concepts of evidence-based medicine at least sometimes. Randomized trials were rated as the most frequently read evidence (rank score, 3.7 of 5), with "Information obtained from the Cochrane Library" the least frequently read (rank score, 2.8 of 5). The most inhibiting barrier to use of published research evidence in practice was "a lack of good evidence providing meaningful answers to clinical problems" (rank score, 3.5 of 5). Eighty-eight (67.7%) of 130 respondents appropriately used published research evidence in clinical practice. CONCLUSIONS: Respondents reported generally positive attitudes toward using published research evidence, in clinical practice; however, room for improvement in technical knowledge relating to published research evidence was noted.

Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition: a randomized controlled trial.

IMPORTANCE: Systematic reviews suggest adult patients in intensive care units (ICUs) with relative contraindications to early enteral nutrition (EN) may benefit from parenteral nutrition (PN) provided within 24 hours of ICU admission. OBJECTIVE: To determine whether providing early PN to critically ill adults with relative contraindications to early EN alters outcomes. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, single-blind clinical trial conducted between October 2006 and June 2011 in ICUs of 31 community and tertiary hospitals in Australia and New Zealand. Participants were critically ill adults with relative contraindications to early EN who were expected to remain in the ICU longer than 2 days. INTERVENTIONS: Random allocation to pragmatic standard care or early PN. MAIN OUTCOMES AND MEASURES: Day-60 mortality; quality of life, infections, and body composition. RESULTS: A total of 1372 patients were randomized (686 to standard care, 686 to early PN). Of 682 patients receiving standard care, 199 patients (29.2%) initially commenced EN, 186 patients (27.3%) initially commenced PN, and 278 patients (40.8%) remained unfed. Time to EN or PN in patients receiving standard care was 2.8 days (95% CI, 2.3 to 3.4). Patients receiving early PN commenced PN a mean of 44 minutes after enrollment (95% CI, 36 to 55). Day-60 mortality did not differ significantly (22.8% for standard care vs 21.5% for early PN; risk difference, -1.26%; 95% CI, -6.6 to 4.1; P = .60). Early PN patients rated day-60 quality of life (RAND-36 General Health Status) statistically, but not clinically meaningfully, higher (45.5 for standard care vs 49.8 for early PN; mean difference, 4.3; 95% CI, 0.95 to 7.58; P = .01). Early PN patients required fewer days of invasive ventilation (7.73 vs 7.26 days per 10 patient × ICU days, risk difference, -0.47; 95% CI, -0.82 to -0.11; P = .01) and, based on Subjective Global Assessment, experienced less muscle wasting (0.43 vs 0.27 score increase per week; mean difference, -0.16; 95% CI, -0.28 to -0.038; P = .01) and fat loss (0.44 vs 0.31 score increase per week; mean difference, -0.13; 95% CI, -0.25 to -0.01; P = .04). CONCLUSIONS AND RELEVANCE: The provision of early PN to critically ill adults with relative contraindications to early EN, compared with standard care, did not result in a difference in day-60 mortality. The early PN strategy resulted in significantly fewer days of invasive ventilation but not significantly shorter ICU or hospital stays. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN012605000704695.

Early enteral nutrition reduces mortality in trauma patients requiring intensive care: a meta-analysis of randomised controlled trials.

INTRODUCTION: To determine whether the provision of early standard enteral nutrition (EN) confers treatment benefits to adult trauma patients who require intensive care. MATERIALS AND METHODS: MEDLINE and EMBASE were searched. Hand citation review of retrieved guidelines and systematic reviews was undertaken and academic and industry experts were contacted. Methodologically sound randomised controlled trials (RCTs) conducted in adult trauma patients requiring intensive care that compared the delivery of standard EN, provided within 24 h of injury, to standard care were included.The primary analysis was conducted on clinically meaningful patient-oriented outcomes, which included mortality, functional status and quality of life. Secondary analyses considered vomiting/regurgitation, pneumonia, bacteraemia, sepsis and multiple organ dysfunction syndrome. Meta-analysis was conducted using an analytical method known to minimise bias in the presence of sparse events. The impact of heterogeneity was assessed using the I2 metric. RESULTS: Three RCTs with 126 participants were found to be free from major flaws and were included in the primary analysis. The provision of early EN was associated with a significant reduction in mortality(OR = 0.20, 95% confidence interval 0.04­0.91, I2 = 0). No other outcomes could be pooled. A sensitivity analysis and a confirmatory analysis conducted using a different analytical method confirmed the presence of a mortality reduction. CONCLUSION: Although the detection of a statistically significant reduction in mortality is promising,overall trial quality was low and trial size was small. The results of this meta-analysis should be confirmed by the conduct of a large multi-center trial.

Early enteral nutrition, provided within 24 h of injury or intensive care unit admission, significantly reduces mortality in critically ill patients: a meta-analysis of randomised controlled trials.

PURPOSE: To determine whether the provision of early standard enteral nutrition (EN) confers treatment benefits to critically ill patients. METHODS: Medline and EMBASE were searched. Hand citation review of retrieved guidelines and systematic reviews were undertaken, and academic and industry experts were contacted. Methodologically sound randomised controlled trials (RCTs) conducted in critically ill patient populations that compared the delivery of standard EN, provided within 24 h of intensive care unit (ICU) admission or injury, to standard care were included. The primary analysis was conducted on clinically meaningful patient-oriented outcomes. Secondary analyses considered vomiting/regurgitation, pneumonia, bacteraemia, sepsis and multiple organ dysfunction syndrome. Meta-analyses were conducted using the odds ratio (OR) metric and a fixed effects model. The impact of heterogeneity was assessed using the I (2) metric. RESULTS: Six RCTs with 234 participants were analysed. The provision of early EN was associated with a significant reduction in mortality [OR = 0.34, 95% confidence interval (CI) 0.14-0.85] and pneumonia (OR = 0.31, 95% CI 0.12-0.78). There were no other significant differences in outcomes. A sensitivity analysis and a simulation exercise confirmed the presence of a mortality reduction. CONCLUSION: Although the detection of a statistically significant reduction in mortality is promising, overall trial quality was low, trial size was small, and the findings may be restricted to the patient groups enrolled into included trials. The results of this meta-analysis should be confirmed by the conduct of a large multi-centre trial enrolling diverse critically ill patient groups.