Publications by authors named "Zheng-Yii Lee"

15 Publications

  • Page 1 of 1

Do we need different predictive equations for the acute and late phases of critical illness? A prospective observational study with repeated indirect calorimetry measurements.

Eur J Clin Nutr 2021 Aug 30. Epub 2021 Aug 30.

Department of Anaesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Background: Predictive equations (PEs) for estimating resting energy expenditure (REE) that have been developed from acute phase data may not be applicable in the late phase and vice versa. This study aimed to assess whether separate PEs are needed for acute and late phases of critical illness and to develop and validate PE(s) based on the results of this assessment.

Methods: Using indirect calorimetry, REE was measured at acute (≤5 days; n = 294) and late (≥6 days; n = 180) phases of intensive care unit admission. PEs were developed by multiple linear regression. A multi-fold cross-validation approach was used to validate the PEs. The best PEs were selected based on the highest coefficient of determination (R), the lowest root mean square error (RMSE) and the lowest standard error of estimate (SEE). Two PEs developed from paired 168-patient data were compared with measured REE using mean absolute percentage difference.

Results: Mean absolute percentage difference between predicted and measured REE was <20%, which is not clinically significant. Thus, a single PE was developed and validated from data of the larger sample size measured in the acute phase. The best PE for REE (kcal/day) was 891.6(Height) + 9.0(Weight) + 39.7(Minute Ventilation)-5.6(Age) - 354, with R = 0.442, RMSE = 348.3, SEE = 325.6 and mean absolute percentage difference with measured REE was: 15.1 ± 14.2% [acute], 15.0 ± 13.1% [late].

Conclusions: Separate PEs for acute and late phases may not be necessary. Thus, we have developed and validated a PE from acute phase data and demonstrated that it can provide optimal estimates of REE for patients in both acute and late phases.

Trial Registration: ClinicalTrials.gov NCT03319329.
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http://dx.doi.org/10.1038/s41430-021-00999-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404185PMC
August 2021

The effect of higher versus lower protein delivery in critically ill patients: a systematic review and meta-analysis of randomized controlled trials.

Crit Care 2021 07 23;25(1):260. Epub 2021 Jul 23.

Department of Critical Care Medicine, Queen's University and the Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, ON, Canada.

Background: The optimal protein dose in critical illness is unknown. We aim to conduct a systematic review of randomized controlled trials (RCTs) to compare the effect of higher versus lower protein delivery (with similar energy delivery between groups) on clinical and patient-centered outcomes in critically ill patients.

Methods: We searched MEDLINE, EMBASE, CENTRAL and CINAHL from database inception through April 1, 2021.We included RCTs of (1) adult (age ≥ 18) critically ill patients that (2) compared higher vs lower protein with (3) similar energy intake between groups, and (4) reported clinical and/or patient-centered outcomes. We excluded studies on immunonutrition. Two authors screened and conducted quality assessment independently and in duplicate. Random-effect meta-analyses were conducted to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes).

Results: Nineteen RCTs were included (n = 1731). Sixteen studies used primarily the enteral route to deliver protein. Intervention was started within 72 h of ICU admission in sixteen studies. The intervention lasted between 3 and 28 days. In 11 studies that reported weight-based nutrition delivery, the pooled mean protein and energy received in higher and lower protein groups were 1.31 ± 0.48 vs 0.90 ± 0.30 g/kg and 19.9 ± 6.9 versus 20.1 ± 7.1 kcal/kg, respectively. Higher vs lower protein did not significantly affect overall mortality [risk ratio 0.91, 95% confidence interval (CI) 0.75-1.10, p = 0.34] or other clinical or patient-centered outcomes. In 5 small studies, higher protein significantly attenuated muscle loss (MD -3.44% per week, 95% CI -4.99 to -1.90; p < 0.0001).

Conclusion: In critically ill patients, a higher daily protein delivery was not associated with any improvement in clinical or patient-centered outcomes. Larger, and more definitive RCTs are needed to confirm the effect of muscle loss attenuation associated with higher protein delivery. PROSPERO registration number: CRD42021237530.
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http://dx.doi.org/10.1186/s13054-021-03693-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300989PMC
July 2021

Correlation between gastric residual volumes and markers of gastric emptying: A post hoc analysis of a randomized clinical trial.

JPEN J Parenter Enteral Nutr 2021 Jul 22. Epub 2021 Jul 22.

Clinical Evaluation Research Unit, Kingston Health Science Centre, Kingston, Ontario, Canada.

Background: The correlation between gastric residual volumes (GRVs) and markers of gastric emptying (GE) in critically ill patients is unclear. This particularly applies to critically ill surgical patients, as they are underrepresented in previous studies.

Methods: We conducted a post hoc analysis of a multicenter trial that investigated the effectiveness of a promotility drug. Pharmacokinetic markers of GE (3-O-methylglucose [3-OMG] and acetaminophen) were correlated with GRV measurements. High GRV was defined as one episode of >400 ml or two consecutive episodes of >250 ml, and delayed GE was defined as <20th percentile of the pharmacokinetic GE marker that had the strongest correlation with GE.

Results: Of 77 patients, 8 (10.4%) had high GRV, and 15 (19.5%) had delayed GE. The 3-OMG concentration at 60 min had the strongest correlation with GRV (ρ = -0.631), and high GRV had low sensitivity (46.7%) but high specificity (98.4%) in discriminating delayed GE. The positive (87.5%) and negative (88.4%) predictive values were similar. Compared with medical patients, surgical patients (n = 14, 18.2%), had a significantly higher incidence of high GRV (29% vs 6%, P = .032) and a trend toward delayed GE (36% vs 16%, P = .132).

Conclusion: GRV reflects GE, and high GRV is an acceptable surrogate marker of delayed GE. From our preliminary observation, surgical patients may have a higher risk of high GRV and delayed GE. In summary, GRV should be monitored to determine whether complex investigations or therapeutic interventions are warranted.
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http://dx.doi.org/10.1002/jpen.2234DOI Listing
July 2021

The authors reply.

Crit Care Med 2021 08;49(8):e804-e805

Department of Anesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

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http://dx.doi.org/10.1097/CCM.0000000000005082DOI Listing
August 2021

Initial development and validation of a novel nutrition risk, sarcopenia, and frailty assessment tool in mechanically ventilated critically ill patients: The NUTRIC-SF score.

JPEN J Parenter Enteral Nutr 2021 May 22. Epub 2021 May 22.

Department of Critical Care Medicine, Queen's University and the Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario, Canada.

Background: Nutrition risk, sarcopenia, and frailty are interrelated. They may be due to suboptimal or prevented by optimal nutrition intake. The combination of nutrition risk (modified nutrition risk in the critically ill [mNUTRIC]), sarcopenia (SARC-F combined with calf circumference [SARC-CALF]), and frailty (clinical frailty scale [CFS]) in a single score may better predict adverse outcomes and prioritize resources for optimal nutrition in the intensive care unit (ICU) METHODS: This is a retrospective analysis of a single-center prospective observational study that enrolled mechanically ventilated adults with expected ≥96 h of ICU stay. SARC-F and CFS questionnaires were administered to patient's next-of-kin and mNUTRIC were calculated. Right calf circumference was measured. Nutrition data were collected from nursing record. The high-risk scores (mNUTRIC ≥ 5, SARC-CALF > 10, or CFS ≥ 4) of these variables were combined to become the nutrition risk, sarcopenia, and frailty (NUTRIC-SF) score (range: 0-3).

Results: Eighty-eight patients were analyzed. Increasing mNUTRIC was independently associated with 60-day mortality, whereas increasing SARC-CALF and CFS showed a strong trend towards a higher 60-day mortality. Discriminative ability of NUTRIC-SF for 60-day mortality is better than its component (C-statistics, 0.722; 95% confidence interval [CI], 0.677-0.868). Every increment of 300 kcal/day and 30 g/day is associated with a trend towards higher rate of discharge alive for high (≥2; adjusted hazard ratio, 1.453 [95% CI, 0.991-2.130] for energy; 1.503 [0.936-2.413] for protein) but not low (<2) NUTRIC-SF score.

Conclusion: NUTRIC-SF may be a clinically relevant risk stratification tool in the ICU.
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http://dx.doi.org/10.1002/jpen.2194DOI Listing
May 2021

The Dose of Protein Bolus Matters.

Chest 2020 12;158(6):2708

Department of Anesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

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http://dx.doi.org/10.1016/j.chest.2020.07.072DOI Listing
December 2020

Association between ultrasound quadriceps muscle status with premorbid functional status and 60-day mortality in mechanically ventilated critically ill patient: A single-center prospective observational study.

Clin Nutr 2021 03 28;40(3):1338-1347. Epub 2020 Aug 28.

Department of Anesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address:

Background & Aims: In critically ill patients, direct measurement of skeletal muscle using bedside ultrasound (US) may identify a patient population that might benefit more from optimal nutrition practices. When US is not available, survey measures of nutrition risk and functional status that are associated with muscle status may be used to identify patients with low muscularity. This study aims to determine the association between baseline and changing ultrasound quadriceps muscle status with premorbid functional status and 60-day mortality.

Methods: This single-center prospective observational study was conducted in a general ICU. Mechanically ventilated critically ill adult patients (age ≥18 years) without pre-existing systemic neuromuscular diseases and expected to stay for ≥96 h in the ICU were included. US measurements were performed within 48 h of ICU admission (baseline), at day 7, day 14 of ICU stay and at ICU discharge (if stay >14 days). Quadriceps muscle layer thickness (QMLT), rectus femoris cross sectional area (RFCSA), vastus intermedius pennation angle (PA) and fascicle length (FL), and rectus femoris echogenicity (mean and standard deviation [SD]) were measured. Patients' next-of-kin were interviewed by using established questionnaires for their pre-hospitalization nutritional risk (nutrition risk screening-2002) and functional status (SARC-F, clinical frailty scale [CFS], Katz activities of daily living [ADL] and Lawton Instrumental ADL).

Results: Ninety patients were recruited. A total of 86, 53, 24 and 10 US measures were analyzed, which were performed at a median of 1, 7, 14 and 22 days from ICU admission, respectively. QMLT, RFCSA and PA reduced significantly over time. The overall trend of change of FL was not significant. The only independent predictor of 60-day mortality was the change of QMLT from baseline to day 7 (adjusted odds ratio 0.95 for every 1% less QMLT loss, 95% confidence interval 0.91-0.99; p = 0.02). Baseline measures of high nutrition risk (modified nutrition risk in critically ill ≥5), sarcopenia (SARC-F ≥4) and frailty (CFS ≥5) were associated with lower baseline QMLT, RFCSA and PA and higher 60-day mortality.

Conclusions: Every 1% loss of QMLT over the first week of critical illness was associated with 5% higher odds of 60-day mortality. SARC-F, CFS and mNUTRIC are associated with quadriceps muscle status and 60-day mortality and may serve as a potential simple and indirect measures of premorbid muscle status at ICU admission.
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http://dx.doi.org/10.1016/j.clnu.2020.08.022DOI Listing
March 2021

A Single-Center Prospective Observational Study Comparing Resting Energy Expenditure in Different Phases of Critical Illness: Indirect Calorimetry Versus Predictive Equations.

Crit Care Med 2020 05;48(5):e380-e390

Department of Anesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Objectives: Several predictive equations have been developed for estimation of resting energy expenditure, but no study has been done to compare predictive equations against indirect calorimetry among critically ill patients at different phases of critical illness. This study aimed to determine the degree of agreement and accuracy of predictive equations among ICU patients during acute phase (≤ 5 d), late phase (6-10 d), and chronic phase (≥ 11 d).

Design: This was a single-center prospective observational study that compared resting energy expenditure estimated by 15 commonly used predictive equations against resting energy expenditure measured by indirect calorimetry at different phases. Degree of agreement between resting energy expenditure calculated by predictive equations and resting energy expenditure measured by indirect calorimetry was analyzed using intraclass correlation coefficient and Bland-Altman analyses. Resting energy expenditure values calculated from predictive equations differing by ± 10% from resting energy expenditure measured by indirect calorimetry was used to assess accuracy. A score ranking method was developed to determine the best predictive equations.

Setting: General Intensive Care Unit, University of Malaya Medical Centre.

Patients: Mechanically ventilated critically ill patients.

Interventions: None.

Measurements And Main Results: Indirect calorimetry was measured thrice during acute, late, and chronic phases among 305, 180, and 91 ICU patients, respectively. There were significant differences (F= 3.447; p = 0.034) in mean resting energy expenditure measured by indirect calorimetry among the three phases. Pairwise comparison showed mean resting energy expenditure measured by indirect calorimetry in late phase (1,878 ± 517 kcal) was significantly higher than during acute phase (1,765 ± 456 kcal) (p = 0.037). The predictive equations with the best agreement and accuracy for acute phase was Swinamer (1990), for late phase was Brandi (1999) and Swinamer (1990), and for chronic phase was Swinamer (1990). None of the resting energy expenditure calculated from predictive equations showed very good agreement or accuracy.

Conclusions: Predictive equations tend to either over- or underestimate resting energy expenditure at different phases. Predictive equations with "dynamic" variables and respiratory data had better agreement with resting energy expenditure measured by indirect calorimetry compared with predictive equations developed for healthy adults or predictive equations based on "static" variables. Although none of the resting energy expenditure calculated from predictive equations had very good agreement, Swinamer (1990) appears to provide relatively good agreement across three phases and could be used to predict resting energy expenditure when indirect calorimetry is not available.
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http://dx.doi.org/10.1097/CCM.0000000000004282DOI Listing
May 2020

Low Muscularity as Assessed by Abdominal Computed Tomography on Intensive Care Unit Admission Is Associated With Mortality in a Critically Ill Asian Population.

JPEN J Parenter Enteral Nutr 2020 03 7;44(3):425-433. Epub 2019 Jun 7.

Department of Anesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Background: Low muscularity (LM) is associated with high mortality in the Caucasian critically ill population. Muscularity can be accurately measured by the skeletal muscle index (SMI; cm /m ) generated by computed tomography (CT). This study aimed to establish the overall and sex-specific cutoff values that predict hospital mortality in an Asian critically ill population.

Methods: This single-center, retrospective, observational study included patients aged ≥18 years with an abdominal CT conducted within 72 hours of admission to the intensive care unit. SMI generated from CT images at the level of the mid-third lumbar vertebra were extracted from the medical records. Area under the receiver operating characteristic curves (AUC) was generated to determine the SMI cutoff values for hospital mortality. Association between LM (defined by SMI cutoff value) and hospital mortality was further evaluated by multivariable logistic regression.

Results: In a sample of 228 patients, the overall SMI cutoff value (cm /m ) for hospital mortality was 42.0 (AUC: 0.637; sensitivity: 66.7%, specificity: 56.8%), whereas it was 46.5 in males and 35.3 in females. More males than females had LM (51.4% vs 37.5%), and >40% of overweight/obese patients had LM. Patients with LM were older and had a longer duration of mechanical ventilation and hospitalization. After adjusting for known confounders, LM independently predicted hospital mortality in the overall sample (adjusted odds ratio: 2.42; 95% CI 1.16-5.03; P = 0.003) and in both sexes.

Conclusion: This study established a set of SMI cutoff values that predict hospital mortality. LM is independently associated with hospital mortality.
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http://dx.doi.org/10.1002/jpen.1666DOI Listing
March 2020

Harm associated with higher energy intake in patients with Low-mNUTRIC score should not be ignored.

Clin Nutr 2019 08 27;38(4):1958-1959. Epub 2019 Apr 27.

Department of Anesthesiology, Faculty of Medicine, University of Malaya, Malaysia. Electronic address:

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http://dx.doi.org/10.1016/j.clnu.2019.04.033DOI Listing
August 2019

Identification of sub-groups that may be harmed or benefit from higher energy intake.

Clin Nutr 2019 06 19;38(3):1477. Epub 2019 Mar 19.

Department of Anesthesiology, Faculty of Medicine, University of Malaya, Malaysia. Electronic address:

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http://dx.doi.org/10.1016/j.clnu.2019.03.011DOI Listing
June 2019

Determination of Nutrition Risk and Status in Critically Ill Patients: What Are Our Considerations?

Nutr Clin Pract 2019 Feb 23;34(1):96-111. Epub 2018 Nov 23.

Department of Critical Care Medicine, Queen's University and Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario, Canada.

The stress catabolism state predisposes critically ill patients to a high risk of malnutrition. This, coupled with inadequate or delayed nutrition provision, will lead to further deterioration of nutrition status. Preexisting malnutrition and iatrogenic underfeeding are associated with increased risk of adverse complications. Therefore, accurate detection of patients who are malnourished and/or with high nutrition risk is important for timely and optimal nutrition intervention. Various tools have been developed for nutrition screening and assessment for hospitalized patients, but not all are studied or validated in critically ill populations. In this review article, we consider the pathophysiology of malnutrition in critical illness and the currently available literature to develop recommendations for nutrition screening and assessment. We suggest the use of the (modified) Nutrition Risk in the Critically Ill (mNUTRIC) for nutrition risk screening and the subjective global assessment (SGA) together with other criteria relevant to the critically ill patients, such as gastrointestinal function, risk of aspiration, determination of sarcopenia and frailty, and risk of refeeding syndrome for nutrition assessment. Further research is needed to identify suitable nutrition monitoring indicators to determine the response to the provision of nutrition.
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http://dx.doi.org/10.1002/ncp.10214DOI Listing
February 2019

Prevalence and duration of reasons for enteral nutrition feeding interruption in a tertiary intensive care unit.

Nutrition 2018 09 31;53:26-33. Epub 2018 Jan 31.

Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Seri Kembangan, Malaysia.

Objectives: Intensive care unit (ICU) enteral nutrition (EN) can involve frequent feeding interruption (FI). The prevalence, causes, and duration of such interruption were investigated.

Methods: Reasons for EN FI identified from extensive literature review were prospectively collected in adult mechanically ventilated critically ill patients. Results were reported by descriptive statistics. Baseline and nutritional characteristics between patients who died and those alive at day 60 were compared.

Results: A total of 148 patients receiving ≥1 day of EN for the full 12-day observational period were included in the analysis. About 332 episodes of EN FI were recorded and contributed to 12.8% (4190 hours) of the total 1367 evaluable nutrition days. For each patient, FI occurred for a median of 3 days and the total duration of FI for the entire ICU stay was 24.5 hours. Median energy and protein deficits per patient due to FI for the entire ICU stay were -1780.23 kcal and -100.58 g, respectively. Duration of FI, days with FI, and the amount of energy and protein deficits due to FI were not different between patients who had died and those who were still alive at day 60 (all P > 0.05). About 72% of the total duration of EN FI was due to procedural-related and potentially avoidable causes (primarily human factors), while only about 20% was due to feeding intolerances.

Conclusions: EN FI occurred primarily due to human factors, which may be minimized by adherence to an evidence-based feeding protocol as determined by a nutrition support team.
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http://dx.doi.org/10.1016/j.nut.2017.11.014DOI Listing
September 2018

Relationship of energy and protein adequacy with 60-day mortality in mechanically ventilated critically ill patients: A prospective observational study.

Clin Nutr 2018 08 19;37(4):1264-1270. Epub 2017 May 19.

Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia. Electronic address:

Background & Aims: The effect of provision of full feeding or permissive underfeeding on mortality in mechanically ventilated critically ill patients in the intensive care unit (ICU) is still controversial. This study investigated the relationship of energy and protein intakes with 60-day mortality, and the extent to which ICU length of stay and nutritional risk status influenced this relationship.

Methods: This is a prospective observational study conducted among critically ill patients aged ≥18 years, intubated and mechanically ventilated within 48 h of ICU admission and stayed in the ICU for at least 72 h. Information on baseline characteristics and nutritional risk status (the modified Nutrition Risk in Critically ill [NUTRIC] score) was collected on day 1. Nutritional intake was recorded daily until death, discharge, or until the twelfth evaluable days. Mortality status was assessed on day 60 based on the patient's hospital record. Patients were divided into 3 groups a) received <2/3 of prescribed energy and protein (both <2/3), b) received ≥2/3 of prescribed energy and protein (both ≥2/3) and c) either energy or protein received were ≥2/3 of prescribed (either ≥2/3). The relationship between the three groups with 60-day mortality was examined by using logistic regression with adjustment for potential confounders. Sensitivity analysis was performed to examine the influence of ICU length of stay (≥7 days) and nutritional risk status.

Results: Data were collected from 154 mechanically ventilated patients (age, 51.3 ± 15.7 years; body mass index, 26.5 ± 6.7 kg/m; 54% male). The mean modified NUTRIC score was 5.7 ± 1.9, with 56% of the patients at high nutritional risk. The patients received 64.5 ± 21.6% of the amount of energy and 56.4 ± 20.6% of the amount of protein prescribed. Provision of energy and protein at ≥2/3 compared with <2/3 of the prescribed amounts was associated with a trend towards increased 60-day mortality (Adjusted odds ratio [Adj OR] 2.23; 95% confidence interval [CI], 0.92-5.38; p = 0.074). No difference in mortality status was found between energy and protein provision at either ≥2/3 compared with <2/3 of the prescribed amounts (Adj OR 1.61, 95% CI, 0.58-4.45; p = 0.357). Nutritional risk status, not ICU length of stay, influenced the relationship between nutritional adequacy and 60-day mortality.

Conclusions: Energy and protein adequacy of ≥2/3 of the prescribed amounts were associated with a trend towards increased 60-day mortality among mechanically ventilated critically ill patients. However, neither energy nor protein adequacy alone at ≥ or <2/3 adequacy affect 60-day mortality. Increased mortality was associated with provision of energy and protein at ≥2/3 of the prescribed amounts, which only affected patients with low nutritional risk.
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http://dx.doi.org/10.1016/j.clnu.2017.05.013DOI Listing
August 2018

Enhanced Protein-Energy Provision via the Enteral Route in Critically Ill Patients (PEP uP Protocol): A Review of Evidence.

Nutr Clin Pract 2016 Feb 18;31(1):68-79. Epub 2015 Sep 18.

Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario, Canada.

Nutrition support is an integral part of care among critically ill patients. However, critically ill patients are commonly underfed, leading to consequences such as increased length of hospital and intensive care unit stay, time on mechanical ventilation, infectious complications, and mortality. Nevertheless, the prevalence of underfeeding has not resolved since the first description of this problem more than 15 years ago. This may be due to the traditional conservative feeding approaches. A novel feeding protocol (the Enhanced Protein-Energy Provision via the Enteral Route Feeding Protocol in Critically Ill Patients [PEP uP] protocol) was proposed and proven to improve feeding adequacy significantly. However, some of the components in the protocol are controversial and subject to debate. This article is a review of the supporting evidences and some of the controversy associated with each component of the PEP uP protocol.
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http://dx.doi.org/10.1177/0884533615601638DOI Listing
February 2016
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