Therapy Early (PN top-up of EN) versus Late Parenteral Nutrition (top-up of EN) in Critically Ill Adults.
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Summary
Posted By:	Gordon S. Doig
E-Mail:	Gordon.Doig@EvidenceBased.net
Posted Date:	19 July 2011
Title:	Early (PN top-up of EN) versus Late Parenteral Nutrition (top-up of EN) in Critically Ill Adults.
Authors:	Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, Van Cromphaut S, Ingels C, Meersseman P, Muller J, Vlasselaers D, Debaveye Y, Desmet L, Dubois J, Van Assche A, Vanderheyden S, Wilmer A, Van den Berghe G.
Reference:	N Engl J Med. 2011 Jun 29. [Epub ahead of print]
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Abstract:	Background Controversy exists about the timing of the initiation of parenteral nutrition in critically ill adults in whom caloric targets cannot be met by enteral nutrition alone. Methods In this randomized, multicenter trial, we compared early initiation of parenteral nutrition (European guidelines) with late initiation (American and Canadian guidelines) in adults in the intensive care unit (ICU) to supplement insufficient enteral nutrition. In 2312 patients, parenteral nutrition was initiated within 48 hours after ICU admission (early-initiation group), whereas in 2328 patients, parenteral nutrition was not initiated before day 8 (late-initiation group). A protocol for the early initiation of enteral nutrition was applied to both groups, and insulin was infused to achieve normoglycemia. Results Patients in the late-initiation group had a relative increase of 6.3% in the likelihood of being discharged alive earlier from the ICU (hazard ratio, 1.06; 95% confidence interval [CI], 1.00 to 1.13; P=0.04) and from the hospital (hazard ratio, 1.06; 95% CI, 1.00 to 1.13; P=0.04), without evidence of decreased functional status at hospital discharge. Rates of death in the ICU and in the hospital and rates of survival at 90 days were similar in the two groups. Patients in the late-initiation group, as compared with the early-initiation group, had fewer ICU infections (22.8% vs. 26.2%, P=0.008) and a lower incidence of cholestasis (P<0.001). The late-initiation group had a relative reduction of 9.7% in the proportion of patients requiring more than 2 days of mechanical ventilation (P=0.006), a median reduction of 3 days in the duration of renal-replacement therapy (P=0.008), and a mean reduction in health care costs of €1,110 (about $1,600) (P=0.04). Conclusions Late initiation of parenteral nutrition was associated with faster recovery and fewer complications, as compared with early initiation. (Funded by the Methusalem program of the Flemish government and others; EPaNIC ClinicalTrials.gov number, NCT00512122 .).
Are the Results Valid?
1. Was the assignment of patients to treatments randomized? ( Was allocation concealment maintained?)
	Yes. The authors report the use of sequentially numbered, sealed, opaque envelopes at first, followed by a 'digital' system later.
2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?
2a. Was followup complete?
	Yes. Figure 1 (page 3) demonstrates complete follow-up.
2b. Were patients analyzed in the groups to which they were randomized?
	Yes. Even though 15 'late PN' patients received 'early PN', they were still analyzed in the 'late PN' group as per ITT principles.
3. Were patients, health workers, and study personnel blind to treatment?
	No. Blinding was not attempted.
4. Were the groups similar at the start of the trial?
	Table 1 demonstarates that all characteristics except weight were well balanced.
5. Aside from the experimental intervention, were the groups treated equally?
	Treatment for refeeding syndrome was not reported.
What are the Results?
1. How large was the treatment effect?
	Median ICU stay was 1 day longer in patients who received PN to top up EN intake 'early' (HR=1.06, P=0.04). Fewer patients in the late-initiation group acquired a new infection (in the airways or lungs, bloodstream, or wound) in the ICU: Any infection (22.8% late PN top-up vs 26.2%, p=0.008 Airway or lung (16.4% late PN top-up vs 19.3, p=0.009) Bloodstream 6.1% late PN top-up vs 7.5%, p=0.05) Wound (2.7% late PN top-up vs 4.2%, p=0.006) There was no difference in mortality (11.2% vs 11.2% Day 90, p=1.00)
2. How precise was the estimate of the treatment effect?
	A 95% confidence interval around the difference in ICU stay was not reported. Other 95% CIs are reported above.
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care?
	In Australia and New Zealand, it is unusual for a patient to start EN and be topped up to goal with PN on the first day of EN. Analysis of this clinical question for the ANZ Nutrition Guideline suggested patient harm (non significant). The practice of topping up PN on day 1 of EN is not common.
2. Were all clinically important outcomes considered?
	Yes. Although it is very good to see functional outcomes reported in nutrition trials, it is possible the results presented here are biased due to excessive loss to follow-up for this measure.
3. Are the likely treatment benefits worth the potential harms and costs?
	There is no evidence to support this intervention (top up to goal with PN on first day of EN).
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