title: The randomized comparative pediatric critical illness stress-induced immune suppression (CRISIS) prevention trial.
abstract: OBJECTIVE
  Nosocomial infection/sepsis occurs in up to 40% of children requiring long-term intensive care. Zinc, selenium, glutamine, metoclopramide (a prolactin secretalogue), and/or whey protein supplementation have been effective in reducing infection and sepsis in other populations. We evaluated whether daily nutriceutical supplementation with zinc, selenium, glutamine, and metoclopramide, compared to whey protein, would reduce the occurrence of nosocomial infection/sepsis in this at-risk population.
  
  
  METHODS
  Randomized, double-blinded, comparative effectiveness trial.
  
  
  METHODS
  Eight pediatric intensive care units in the National Institutes of Child Health and Human Development Collaborative Pediatric Critical Care Research Network.
  
  
  METHODS
  Two hundred ninety-three long-term intensive care patients (age 1-17 yrs) expected to require >72 hrs of invasive care.
  
  
  METHODS
  Patients were stratified according to immunocompromised status and center and then were randomly assigned to receive daily enteral zinc, selenium, glutamine, and intravenous metoclopramide (n = 149), or daily enteral whey protein (n = 144) and intravenous saline for up to 28 days of intensive care unit stay. The primary end point was time to development of nosocomial sepsis/infection. The analysis was intention to treat.
  
  
  RESULTS
  There were no differences by assigned treatment in the overall population with respect to time until the first episode of nosocomial infection/sepsis (median whey protein 13.2 days vs. zinc, selenium, glutamine, and intravenous metoclopramide 12.1 days; p = .29 by log-rank test) or the rate of nosocomial infection/sepsis (4.83/100 days whey protein vs. 4.99/100 days zinc, selenium, glutamine, and intravenous metoclopramide; p = .81). Only 9% of the 293 subjects were immunocompromised and there was a reduction in rate of nosocomial infection/sepsis with zinc, selenium, glutamine, and intravenous metoclopramide in this immunocompromised group (6.09/100 days whey protein vs. 1.57/100 days zinc, selenium, glutamine, and intravenous metoclopramide; p = .011).
  
  
  CONCLUSIONS
  Compared with whey protein supplementation, zinc, selenium, glutamine, and intravenous metoclopramide conferred no advantage in the immune-competent population. Further evaluation of zinc, selenium, glutamine, and intravenous metoclopramide supplementation is warranted in the immunocompromised long-term pediatric intensive care unit patient.
authors.affiliation: Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA. carcilloja@ccm.upmc.edu
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Carcillo
authors.forename: J Michael
authors.initials: JM
authors.lastname: Dean
authors.forename: Richard
authors.initials: R
authors.lastname: Holubkov
authors.forename: John
authors.initials: J
authors.lastname: Berger
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Meert
authors.forename: K J S
authors.initials: KJ
authors.lastname: Anand
authors.forename: Jerry
authors.initials: J
authors.lastname: Zimmerman
authors.forename: Christopher J L
authors.initials: CJ
authors.lastname: Newth
authors.forename: Rick
authors.initials: R
authors.lastname: Harrison
authors.forename: Jeri
authors.initials: J
authors.lastname: Burr
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Willson
authors.forename: Carol
authors.initials: C
authors.lastname: Nicholson
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness / Q000628:therapy*; D003428:Cross Infection / Q000276:immunology / Q000517:prevention & control*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005973:Glutamine / Q000627:therapeutic use; D006801:Humans; D016867:Immunocompromised Host; D007223:Infant; D015278:Intensive Care Units, Pediatric; D008297:Male; D008787:Metoclopramide / Q000627:therapeutic use; D008894:Milk Proteins / Q000627:therapeutic use; D012643:Selenium / Q000627:therapeutic use; D018805:Sepsis / Q000276:immunology / Q000517:prevention & control*; D013312:Stress, Physiological / Q000276:immunology*; D000067816:Whey Proteins; D015032:Zinc / Q000627:therapeutic use
chemical_list: D008894:Milk Proteins; D000067816:Whey Proteins; D005973:Glutamine; D012643:Selenium; D015032:Zinc; D008787:Metoclopramide
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