Effects of magnesium, phosphate and zinc supplementation in ICU patients—Protocol for a systematic review

Abstract

Background: Depletion of the trace elements magnesium, phosphate and zinc is common in patients admitted to the intensive care unit (ICU). Observational studies have suggested worse outcome in patients with hypomagnesaemia, hypophosphataemia or hypozincaemia, but also inverse associations with worse outcome with too high serum levels. However, it is unclear whether data from randomised clinical trials (RCTs) confirm this. Accordingly, we plan to assess the balance between benefits and harms of supplementation as compared with placebo or no supplementation in adult ICU patients. Methods:We will conduct a systematic review of RCTs with meta-analysis and trial sequential analysis in accordance with the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement and the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach. We will assess the effects of any supplementation with magnesium, phosphate or zinc vs. placebo or no treatment in adult ICU patients. We will systematically search the Cochrane CENTRAL, Embase, PubMed, and for unpublished trials: ClinicalTrials.gov, the EU clinical TrialsRegister and the WHO International Clinical Trials Registry Platform. The primary outcomes will be days alive without mechanical ventilation and overall mortality.Secondary outcomes include use for mechanical ventilation, tachy-arrhythmias, use of vasopressors, length of hospital stay and use of renal replacement therapy. Discussion:The benefits and harms of supplementation therapy with magnesium, phosphate and zinc in general ICU patients are unknown. This outlined systematic review will provide data on the evidence, on which future recommendations for supplementation may be founded.

Effects of magnesium, phosphate, or zinc supplementation in intensive care unit patients—A systematic review and meta‐analysis

“…We conducted this systematic review in accordance with the Cochrane Handbook for Systematic Reviews of Interventions, 8 the Preferred Reporting Items for Systematic Review and Meta‐Analysis statement 9 (checklist Appendix S1) and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach 10,11 . The protocol was registered with PROSPERO (CRD42019142847) and published 12 …”

“…For categorical outcomes we planned to calculate relative risks (RRs) and absolute risks (ARs) with 95% confidence intervals (CIs), and for continuous outcomes we planned to calculate mean differences with 95% Cis. A pre‐planned adjustment for multiplicity was not relevant 12,14 …”

An update on essential micronutrients in critical illness

“…Supplementation of zinc may be beneficial in subgroups of critically ill patients. There were no benefits in neurocritical patients, whereas a mortality benefit was shown in septic patients with AKI [30,31]. In addition, zinc supplementation in critically ill children with community-acquired pneumonia significantly shortened hospital length of stay and duration of pneumonic effusion [32].…”

Nutrition support for critically ill patients

“…Zinc deficiency can be exacerbated during critical illness, such as sepsis. However, it is unclear whether zinc supplementation benefits critically ill patients 99 …”

“…However, it is unclear whether zinc supplementation benefits critically ill patients. 99 The 2016 ASPEN/SCCM guidelines could not make a recommendation regarding selenium, zinc, and antioxidant supplementation in sepsis, because of conflicting results. 25 The 2018 ESPEN guidelines stated that high-dose antioxidants, such as copper, selenium, zinc, and vitamins E and C, should not be administered in the absence of confirmed deficiency.…”