DOI: 10.1097/PCC.0b013e31823c9a3e

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PMID: 22391830

Issn Print: 1529-7535

Publication Date: 2012/03/01


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Preventing a CRISIS: No magic cocktail yet*

Margaret M. Parker

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Excerpt

Critical illness stress-induced immune suppression (otherwise known as CRISIS), manifested as depletion or dysfunction of lymphocytes, has been associated with deficiencies in zinc and selenium, as well as deficiencies of amino acids and hypoprolactinemia (1–4). It is reasonable to hypothesize that dietary supplementation of some or all of these substances might improve immune function and reduce the incidence of nosocomial infection, although data in critically ill children are lacking (5–7). To try to address this question, the Collaborative Pediatric Critical Care Research Network performed a randomized, double-blind, comparative efficacy trial in 293 critically ill children. The results of this carefully designed study are reported in this issue of Pediatric Critical Care Medicine (8). They compared the administration of enteral zinc, selenium, and glutamine and intravenous metoclopramide (to increase prolactin) (ZSGM group) with the administration of enteral whey protein and intravenous saline (whey group) in critically ill children who had one or more invasive catheters/tubes. The primary outcome was the time (in hours) from admission to the pediatric intensive care unit to the occurrence of nosocomial infection or clinical sepsis. Enrollment was stopped at the second interim analysis because of futility. No difference was found in the time until nosocomial infection/sepsis, the rate of infection, or prolonged lymphopenia between the two groups. There was a reduction in the rate of nosocomial infection/sepsis in immunocompromised patients who received ZSGM compared to immunocompromised patients who received whey, but the number of immunocompromised patients in the study was small. This population is certainly one that warrants further study. It is also worth noting that infants (younger than age 1 yr) were not included in this study.
This study did not include a control group. As noted by the authors, zinc, selenium, and protein are part of standard nutritional practice, especially in patients receiving total parenteral nutrition. Approximately 40% of the patients in the whey group were also receiving standard supplementation with zinc or selenium or both, as were approximately 40% of the patients in the ZSGM group. Because it was felt not to be ethical to include a true placebo arm, this is a comparative efficacy trial comparing two active therapies. No benefit of one treatment over the other was demonstrated. Similarly, there was no difference in adverse events with one therapy compared to the other.
Baseline deficiencies in zinc and selenium were common in both groups, with 89% and 55% of children in the ZSGM group and 79% and 57% in the whey group having low zinc and selenium levels, respectively. Low prolactin levels were much less common. At day 7, the levels of zinc and selenium were higher in the ZSGM group patients than the whey group patients, although 23% of the ZSGM group patients were still zinc-deficient and 12% were still selenium-deficient. Disappointingly, the increase in zinc and selenium levels was not translated into a delay or decrease in nosocomial infection in the ZSGM group.
Why did the treatment with ZSGM not work or at least not work better than protein supplementation? It is difficult to answer this question. Because of the complexity of the patients and of the study, it is difficult to make a firm conclusion about the efficacy, or lack thereof, of dietary supplementation with ZSGM to increase prolactin in preventing nosocomial infection. There were many children in both arms receiving supplementation as part of routine care with total parenteral nutrition. Two-thirds of the patients had infection or sepsis at entry, perhaps marking them as a particularly high-risk population.

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