The randomized comparative pediatric critical illness stress-induced immune suppression (CRISIS) prevention trial

Joseph A Carcillo, J Michael Dean, Richard Holubkov, John Berger, Kathleen L Meert, K J S Anand, Jerry Zimmerman, Christopher J L Newth, Rick Harrison, Jeri Burr, Douglas F Willson, Carol Nicholson, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Collaborative Pediatric Critical Care Research Network (CPCCRN), Joseph Carcillo, Michael Bell, Alan Abraham, Annette Seelhorst, Jennifer Jones, J Michael Dean, Jeri Burr, Amy Donaldson, Richard Holubkov, Angie Webster, Stephanie Bisping, Teresa Liu, Brandon Jorgenson, Rene Enriquez, Jeff Yearley, John Berger, Angela Wratney, Jean Reardon, Kathleen L Meert, Sabrina Heidemann, Maureen Frey, K J S Anand, Parthak Prodhan, Glenda Hefley, Jerry Zimmerman, David Jardine, Ruth Barker, Christopher J L Newth, J Francisco Fajardo, Rick Harrison, Douglas F Willson, Carol Nicholson, Tammara Jenkins, Joseph A Carcillo, J Michael Dean, Richard Holubkov, John Berger, Kathleen L Meert, K J S Anand, Jerry Zimmerman, Christopher J L Newth, Rick Harrison, Jeri Burr, Douglas F Willson, Carol Nicholson, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Collaborative Pediatric Critical Care Research Network (CPCCRN), Joseph Carcillo, Michael Bell, Alan Abraham, Annette Seelhorst, Jennifer Jones, J Michael Dean, Jeri Burr, Amy Donaldson, Richard Holubkov, Angie Webster, Stephanie Bisping, Teresa Liu, Brandon Jorgenson, Rene Enriquez, Jeff Yearley, John Berger, Angela Wratney, Jean Reardon, Kathleen L Meert, Sabrina Heidemann, Maureen Frey, K J S Anand, Parthak Prodhan, Glenda Hefley, Jerry Zimmerman, David Jardine, Ruth Barker, Christopher J L Newth, J Francisco Fajardo, Rick Harrison, Douglas F Willson, Carol Nicholson, Tammara Jenkins

Abstract

Objectives: 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.

Design: Randomized, double-blinded, comparative effectiveness trial.

Setting: Eight pediatric intensive care units in the National Institutes of Child Health and Human Development Collaborative Pediatric Critical Care Research Network.

Patients: Two hundred ninety-three long-term intensive care patients (age 1-17 yrs) expected to require >72 hrs of invasive care.

Interventions: 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.

Measurements and main 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).

Conclusion: 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.

Figures

Figure 1
Figure 1
Screening, enrollment, randomization, and study completion.
Figure 2
Figure 2
Top Panel - Freedom from nosocomial sepsis according to assigned treatment for all randomized patients. Numbers above the horizontal time axis denote number of patients remaining at risk at each time point. p=0.29 for logrank test comparing curves between study arms, stratified by immune competent status. Middle Panel - Freedom from nosocomial infection / sepsis according to assigned treatment for patients immunocompromised at study entry. Numbers above the horizontal time axis denote number of patients remaining at risk at each time point. p=0.24 for logrank test comparing curves between study arms. Lower Panel - Freedom from nosocomial infection / sepsis according to assigned treatment for patients who were immune competent at study entry. Numbers above the horizontal time axis denote number of patients remaining at risk at each time point. p=0.16 for logrank test comparing curves between study arms.
Figure 2
Figure 2
Top Panel - Freedom from nosocomial sepsis according to assigned treatment for all randomized patients. Numbers above the horizontal time axis denote number of patients remaining at risk at each time point. p=0.29 for logrank test comparing curves between study arms, stratified by immune competent status. Middle Panel - Freedom from nosocomial infection / sepsis according to assigned treatment for patients immunocompromised at study entry. Numbers above the horizontal time axis denote number of patients remaining at risk at each time point. p=0.24 for logrank test comparing curves between study arms. Lower Panel - Freedom from nosocomial infection / sepsis according to assigned treatment for patients who were immune competent at study entry. Numbers above the horizontal time axis denote number of patients remaining at risk at each time point. p=0.16 for logrank test comparing curves between study arms.

Source: PubMed

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