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1 Journal Meeting Early versus Late Parenteral Nutrition in Critically Ill Adults Reporter: 姜厚任 2011/08/15 本檔僅供內部教學使用檔案內所使用之照片之版權仍屬於原期刊公開使用時, 須獲得原期刊之同意授權

2 N Engl J Med Background Controversy exists about the timingof the initiation of parenteral nutrition in critically ill adults in whom caloric targets cannot be met by enteral nutrition alone.

3 Critical illness induces anorexia and the inability to eat normally serious nutritional deficits, muscle wasting, weakness, and delayed recovery The administration route The time until the initiation of artificial nutrition The number of calories The type of nutrients

4 Enteral nutrition is associated with fewer complications than parenteral nutrition and is less expensive to administer. Simpson F,. Intensive Care Med 2005;31: Underfeeding Weakness, infection, an increased duration of mechanical ventilation, and death Dvir D, Clin Nutr 2006;25: Overfeeding Liver dysfunction, infection, and prolonged ventilatory support Grau T, Crit Care 2007;11:R10.

5 Expert opinion European Society of Parenteral and Enteral Nutrition (ESPEN): Initiating parenteral nutrition within 2 days after admission to the intensive care unit (ICU) for patients who cannot be adequately fed enterally. American and Canadian guidelines: (1) Early initiation of enteral nutrition Singer P, Clin Nutr 2009; 28: (2) Hypocaloric nutrition be tolerated during the first week in patients who are not malnourished at baseline Martindale RG, Crit Care Med 2009;37:

6 In this study Late initiation of parenteral nutrition (American and Canadian guidelines) v.s. Early initiation of parenteral nutrition (ESPEN guidelines) Rates of deathand complicationsin adultsin the ICU who were nutritionally at risk (except chronically malnourished, BMI>=17)

7 METHODS

8 Study Design and Oversight The Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) study : A prospective, randomized, controlled, parallelgroup, multicenter trial that was initiated by the investigators. (Baxter Healthcare provided an unrestricted research grant that covered less than a third of the costs of the study.)

9 Patients (1) From August 1, 2007 November 8, (2) All adults admitted to one of the seven participating ICUs (3) 3 or more on nutritional risk screening (NRS) (4) Did not meet any of the exclusion criteria

10 Nutritional Risk Screening (NRS)

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14 Study Procedures Early-initiation group : On day 1 Intravenous 20% glucose solution; Total energy intake was 400 kcal/day On day kcal/day On day 3 Parenteral nutrition (OliClinomel or Clinimix, Baxter) 100% of the caloric goal through combined enteral and parenteral nutrition

15 The maximum caloric goal for all patients was 2880 kcalper day

16 Late-initiation group: On day 1~7 5% glucose solution in a volume equal to that of the parenteral nutrition administered in the early-initiation. On day 8 Parenteral nutrition was initiated to reach the caloric goal.

17 Total Energy Levels

18 Enteral Nutritions Mainly Osmolite,(Abbott). Semirecumbent position unless medically contraindicated Prokinetic agents and duodenal feeding tubes Avoid micronutrient depletion on refeeding: Parenteral trace elements, minerals(potassium, phosphate, and magnesium), and vitaminsearly in their ICU stay.

19 Blood Sugar Control Continuous insulin infusion Blood glucose level of 80 to 110 mg per deciliter Guidelines for ventilator weaning were followed in all participating ICUs Two senior ICU physicians and the referring specialist made end-of-life decisions by consensus

20 OUTCOME MEASURES

21 Safety End Points

22 Primary Efficacy End Points The time to discharge from the ICU as the time by which patients were ready for ICU discharge.

23 Secondary Efficacy End Points

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26 RESULTS

27 Study Intervention Late-initiation group: Median of 31 IU insulin per day mean blood glucose level of 102±14 mg/dl Early-initiation group: Median of 58 IUinsulin per day mean blood glucose level of 107±18mg /dl

28 Safety Outcomes Death in the ICU in the hospital at 90 days Discharged alive from the ICU within 8 days Lateinitiation Earlyinitiation Higher proportion Lower Hypoglycemia development More Less

29 Primary Outcomes ---Time to Discharge from the ICU The median stay in the ICU was 1 day shorterin the late-initiation group.

30 Secondary Outcomes New infection in Airways/lungs/ bloodstream/wound Acute inflammatory response Duration of mechanical ventilation Course of renalreplacement therapy Fewer More Shorter Shorter Lateinitiation Earlyinitiation More Less Longer Longer

31 Secondary Outcomes ---Time to Discharge from the Hospital The median duration of hospitalization was 2 days shorter in the late-initiation group.

32 Total Health Care Costs Late initiation of parenteral nutrition : reduction in total health care costs of 1,110 (about $1,600) per patient.

33 In post hoc subgroup analyses Early enteral nutrition was surgically contraindicated. (517 patients) Median of 0 kcal/day of enteral nutrition by day 7 Rate of infection in the late-initiation group (29.9%) in the early-initiation group (40.2%) In the late-initiation group: Relative increase of 20% in the likelihood of earlier discharge alive from the ICU.

34 DISCUSSION

35 Previous observational studies Earlier achievement of nutritional targets improves the outcome. Early initiation of enteral tube feeding. Insufficient enteral nutrition - Early parenteral supplementation. Dvir D. Clin Nutr 2006;25: Alberda C, Intensive Care Med 2009;35: In our study, all primary and secondary morbidity end points indicated that early parenteral nutrition was not beneficial.

36 Early enteral nutrition surgically contraindicated (N=517) In the early-initiationgroup received the largest amount of parenteral nutrition Suppression of autophagy Inadequate clearance of cell damage and microorganisms Increased rates of infection Delayed recovery from organ failure Withholding ofmacronutrientsin the early stages of a critical illness

37 Limitations of Study (1) No Glutamine or other immune-modulating compounds (2) Standardized, premixed parenteral-nutrition products ---- low protein-to- energy ratio (3)Because of the nature of the study, patients or their designated representatives and their ICU providers were aware of study-group assignments.

38 Conclusion ICU admission in severely ill patients at risk for malnutrition : Late parenteral nutrition : Fewer ICU infections(22.8% vs. 26.2%, P = 0.008) Enhanced recovery Lower health care costs (about $1,600)

39 THANKS FOR YOUR ATTENTION~