Early Parenteral Nutrition in Critically Ill Patients With Short-term Relative Contraindications to Early Enteral Nutrition

Doig. JAMA. 2013;309(20):2130-2138. doi:10.1001/jama.2013.5124

Clinical Question

  • In critically ill patients with relative contraindications to early enteral nutrition (EN), does providing early parenteral nutrition (PN), improve mortality?


  • Randomised controlled trial
  • Block randomisation with variable block sizes
  • Stratified by site, age and BMI
  • Single-blind
  • Intention to treat analysis
  • Power calculation: with baseline mortality of 29.7%, a sample size of 1470 patients required to detect a 7.7% risk difference between groups, with 90% power


  • 31 community and tertiary hospitals in Australasia
  • October 2006 – June 2011


  • Inclusion criteria
    • Adult patients admitted to ICU
    • Considered ineligible for EN by the attending clinician due to a short-term relative contraindication
    • Expected to remain in ICU for >2 days
  • Exclusion criteria
    • Not expected to survive 24 hours, or receiving palliative care
    • Licensing contraindication to PN e.g. pregnancy, allergy
  • 1372 patients randomised
    • 46% Emergency Surgery
    • 20% Elective Surgery
    • Mean APACHE II score 21


  • Early PN (Kabiven G19%, Fresenius Kabi Australia)
    • ‘Early’ defined as within 24 hours of ICU admission
    • Mean time from ICU admission to randomisation was 13.8 hours
    • Mean time from randomisation to PN was 44 minutes
  • Energy target
    • set by Harris-Benedict equation
    • capped at 35kcal/kg/day
    • If BMI 30+ then fed to ideal body weight (BMI = 21)


  • Standard care
    • Not defined by protocol
      • 278 (40.8%) never received EN or PN during their 3.72 (95% C.I. 2.65-5.2) ICU stay
      • 199 (29.2%) started EN after 2 days (95% C.I. 1.43-2.78), of whom 48 eventually received supplemental PN
      • 186 (27.3%) started PN after 2 days (95% C.I. 1.45-2.7)
      • 19 (2.8%) started both EN + PN at the same time after 5.58 days (95% C,I, 3.9-7.96)
      • 13 (1.9%) patients received EN, PN, or oral feed within 24 hours of ICU admission
    • Overall remained unfed for mean 2.8 days  (95% C.I. 2.3-3.4)
    • Of note in Australasia it is NOT accepted practice to infuse isolated glucose solutions to provide caloric intake prior to initiating feeding


  • Primary Outcome
    • 60 day mortality – no significant difference
  • Secondary outcomes
    • Quality of life and physical function
      •  RAND-36 General Health Status –  significant improvement in early PN group, however, magnitude of difference did not exceed one-half the standard deviation, which was defined a priori as clinically meaningful
      • ECOG performance status –  no significant difference
      • RAND 36 physical function – no significant difference
  • Tertiary Outcomes
    • Length of mechanical ventilation – significantly shorter in early PN group
    • ICU stay – no significant difference
    • Hospital stay – no significant difference
    • No differences in any types of infection
  • Subgroup analysis
    • No significant differences in 60 day mortality based on BMI, age or chronic insulin treated DM

Authors’ Conclusions

  • The use of early PN did not result in significant differences in 60 day mortality or infection rates


  • Randomised
  • Intention to treat analysis
  • Multi-centre
  • Early enrollement of patients (mean time from ICU admission to enrolment 13.8hrs)
  • Patients treated with early PN received >90% of target feed
  • Pragmatic study – comparing early parenteral nutrition with standard treatment. However, the downside of this is that standard treatment varies and this trial therefore compares it against all of these.
  • Minimal exclusion criteria leading to high external validity. The downside of this is that in the control group 41% discharged from ICU within 3.72 days (95% CI, 2.65-5.20) without feeding. In these patients it may have been optimistic to hope to find a large mortality benefit. It may be that patients with more prolonged critical illness would be more likely to benefit from early PN.


  • Non-blinding of study intervention and outcome assessment
  • In the standard care group nearly 40% of patients received parenteral nutrition, the majority within a few days. Therefore it is not surprising that there was no difference in infectious complications found

The Bottom Line

  • In critically ill patients with a short-term relative contraindication to enteral nutrition, the use of early parenteral nutrition did not affect 60 day mortality or infection rates compared with starting feeding at ~3 days. I therefore won’t be in a rush to start early PN.

External Links


Summary author: @davidslessor
Summary date: 8th September 2014
Peer-review editor: @DuncanChambler

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