CI: Enteral Nutrition vs. Parenteral Nutrition (2012)


Kutsogiannis J, Alberda C, Gramlich L, Cahill NE, Wang M, Day AG, Dhaliwal R, Heyland DK. Early use of supplemental parenteral nutrition in critically ill patients: Results of an international multicenter observational study. Crit Care Med. 2011 Jul 14. [Epub ahead of print] PMID: 21765355.

PubMed ID: 21765355
Study Design:
Prospective Cohort Study
B - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

To determine whether the use of early supplemental parenteral nutrition had any impact on clinical outcomes of critically ill patients, as well as the effect of using of supplemental parenteral nutrition (early or late) in patients at risk of protein-calorie malnutrition (body mass index less than 20, early and persistent intolerance to enteral nutrition, or gastrointestinal admission diagnosis). 

Inclusion Criteria:
  • Hospital Intensive Care Units (ICUs) were included if:
    • Unit had access to healthcare professional with adequate knowledge of nutrition therapy (such as a Registered Dietitian)
    • Had a minimum of eight beds
  • Smaller units were permitted to participate on a case-by-case basis
  • Patients were included if:
    • Started on EN or PN after admission in ICU
    • Received EN within 48 hours of ICU admission
    • Did not progress to oral intake within 72 hours of ICU admission. 
Exclusion Criteria:
  •  Hospital Intensive Care Units (ICUs) were excluded if:
    • Unit did not have access to healthcare professional with adequate knowledge of nutrition therapy (such as a Registered Dietitian)
    • Had fewer than eight beds
  • Patients were excluded if:
    • Started on EN or PN before admission in ICU
    • Did not receive EN within 48 hours of ICU admission
    • Progressed to oral intake within 72 hours of ICU admission. 
Description of Study Protocol:


An invitation to participate was e-mailed to membership lists of national critical care and nutrition societies and to clinicians who had previously participated in quality improvement work at the Clinical Evaluation Research Unit.


  • Two international, prospective, observational studies were conducted in 2007 and 2008; the data were combined to make a larger dataset for analysis.
  • Participating ICUs provided data on their hospital and unit characteristics and aimed to collect data on 20 mechanically ventilated critically ill patients who stayed in the ICU more than 72 hours.
  • Data collected on patients included baseline demographics, APACHE II score and nutrition assessment; these data were abstracted from hospital records and entered on to a secure web-based system.
  • Information was also collected daily on the type and amount of nutrition received, feeding interruptions due to high gastric residual volumes and morning blood glucose levels.
  • If enteral nutrition was contraindicated, the rationale was recorded and included mechanical bowel obstruction, bowel ischemia, small bowel ileus, small bowel fistulas, GI perforation and short gut syndrome.
  • Daily nutrition information was recorded for a maximum of 12 days or until death or discharge from the ICU.
  • The nutrition plan of care for all patients was determined by the local clinical team treating the patient.
  • Patients were followed in the hospital for a maximum of 60 days to determine ICU and hospital outcomes.
  • Patients were categorized into three groups:
    • Early enteral nutrition alone
    • Early enteral nutrition and early parenteral nutrition
    • Early enteral nutrition and late parenteral nutrition.
  • The primary objective of the study was to compare characteristics, nutrition processes and clinical outcome variables (ICU/hospital length of stay and mortality) between the three groups. 

Statistical Analysis

The Rao-Scott adjusted chi-squared method was used to compare categorical variables to adjust for potential heterogeneity between ICUs. Length of stay variables were compared between groups by the score test with robust standard errors. Continuous variables were compared between groups by a linear mixed-effect model. Both a single predictor and multiple-predictor Cox proportional hazards model was used to model the rate of living hospital discharge within 60 days of ICU admission.  

Data Collection Summary:

Timing of Measurements

Daily information was collected on the type and amount of nutrition received, feeding interruptions due to high gastric residual volumes and morning blood glucose levels for up to 12 days per patient. Patient outcomes were recorded after 60 days.

Dependent Variables

Time from ICU admission to discharge alive from hospital.

Independent Variables

Based on type of nutrition support received, patients were categorized into three groups:

  • Early enteral nutrition alone
  • Early enteral nutrition and early parenteral nutrition
  • Early enteral nutrition and late parenteral nutrition.
Description of Actual Data Sample:
  • Initial N: 2,920 patients from 260 intensive care units in 28 countries
  • Attrition (final N): 2,920 patients; 2,562 (87.7%) in the early EN group, 188 in the early PN group (6.4%) and 170 (5.8%) in the late PN group
  • Age:
    • Mean age was 58.4 years±17.9 in the early EN group
    • The early supplemental parenteral group, mean age was 62.3±17.9 years
    • In the late supplemental parenteral nutrition group, mean age was 56.4±17.5 years (P=0.02 for all three groups)
  • Other relevant demographics:
    • In the early EN group there were:
      • 999 females (39.0%)
      • 1,563 males (61.0%)
    • In the early supplemental PN group, there were:
      • 67 females (35.6%)
      • 121 males (64.4%)
    • In the late supplemental PN group, there were:
      • 65 females (38.2%)
      • 105 males (61.8%)
    • Patients with a medical admission:
      • 1,873 patients in the early EN group (73.1%)
      • 100 patients in the early supplemental PN group (53.2%)
      • 105 patients in the late supplemental PN group (61.8%)
    • Patients with a surgical admission:
      • 689 patients in the enteral nutrition group (26.9%)
      • 88 patients in the early supplemental parenteral group (46.8%)
      • 65 patients in the late supplemental parenteral nutrition group (38.2%) (P<0.0001 for both admission categories)
    • Mean APACHE II scores were:
      • 22.0±7.9 for the early enteral nutrition group
      • 22.6±8.4 for the early supplemental parenteral nutrition group
      • 23.3±7.9 for the late supplemental parenteral nutrition group (P=0.11)
    • The majority of patients in each group did not have acute respiratory distress syndrome:
      • 89.1% in the early enteral group
      • 80.3% in the early supplemental parenteral group
      • 82.9% in the late supplemental parenteral group (P<0.002)
    • Patients with gastrointestinal dysfunction within 48 hours:
      • 8.0% in the early EN group
      • 11.7% in the early supplemental PN group
      • 17.7% in the late supplemental PN group (P<0.0003)
    • Patients with persistent gastrointestinal dysfunction more than two consecutive days:
      • 11.3% in the early EN group
      • 12.2% in the early supplemental PN group
      • and 39.4% in the late supplemental PN group (P<0.0001)
  • Anthropometrics:
    • Body mass index was:
      • 27.2±7.0 for the early EN group
      • 24.5±4.7 for the early supplemental PN nutrition group
      • and 27.0±6.9 for the late supplemental PN group (P<0.0001)
  • Location: 260 intensive care units in 28 countries. 


Summary of Results:



Early EN


Early Supplemental PN


Late Supplemental PN


Statistical Significance
Patient died (within 60 days) 712 (27.8% 65 (34.6%) 60 (35.3%) P<0.02
Patient still hospitalized at day 60 (%)  423 (22.8%) 37 (31.1%) 38 (34.5%) P<0.01
Length of hospital stay (days), median (IQR) 27.1 (14.9 to 55.5) 33.4 (16.8 to undefined*) 35.3 (23.0 to undefined*) P<0.004

* Undefined as more than 30% of patients remained hospitalized at day 60.

Key Findings

  • Adequacy of calories and protein from total nutrition was highest in the early PN group (81.2% and 80.1%) and lowest in the early EN group (63.4% and 59.3%; P<0.0001)
  • The 60-day mortality rate was significantly lower in those receiving early EN (27.8%) compared to those receiving early PN (34.6%) or late PN (35.3%) (P=0.02)
  • There were significant differences in days on mechanical ventilation (P=0.007), length of ICU stay (P=0.003) and duration of hospital stay (P=0.004) between the three groups; in all cases best outcomes were achieved in those receiving early EN
  • The rate of being discharged alive from hospital was lower in the group that received early PN (hazard ratio, 0.75; 95% CI: 0.59 to 0.96) and late parenteral nutrition (hazard ratio, 0.64; 95% CI: 0.51 to 0.81) as compared with early enteral nutrition (P=0.0003)
  • In patients with early and persistent EN intolerance, there was no suggestion of benefit associated with either early PN (hazard ratio, 0.69; 95% CI: 0.35 to 1.14) or late PN (hazard ratio, 0.74; 95% CI: 0.53 to 1.0)
  • In patients with a gastrointestinal admission diagnosis, both early PN and late PN were associated with a slower rate to discharged alive (hazard ratio, 0.35; 95% CI: 0.19 to 0.63 and hazard ratio, 0.62; 95% CI: 0.41 to 0.94, respectively). 

Other Findings

  • The use of motility agents, small bowel tubes and the adequacy of glycemic control were similar across all three groups (P=0.73, P=0.18 and P=0.20, respectively)
  • There was no significant evidence that the effect of supplemental PN varied according to patient body mass index
  • In the sub-groups of patients with a GI admission diagnosis and early or persistent GI dysfunction, both early and late PN were associated with worse outcomes, independent of other confounding variables measured.
Author Conclusion:

There was no clinical benefit from use of either early or late PN which was associated with a longer hospital length of stay and with increased mortality and lower rate of discharge alive at 60 days. However, energy and protein intakes were higher when PN was used.

Funding Source:
Reviewer Comments:
  • The authors discuss several strengths and limitations to this study. The size and international scope is a strength and lends to the generalizability of the results. Lack of randomization and blinding is a limitation, however.
  • Also, because of the post-hoc analyses causality cannot be demonstrated between the types of nutrition support and hospital survival.
  • The authors also state that they cannot be certain of the validity of individual patients' caloric prescription since calorimetry was not available to assess most patients.
  • Based on the results of this study, the authors recommend other strategies to enhance tolerance to enteral nutrition before initiating parenteral nutrition, such as using motility agents, small bowel feedings and increasing the gastric residual volume threshold during the first week of ICU admission.
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) N/A
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) N/A
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? Yes
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) No
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? No
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? Yes
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? Yes
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes