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

BACKGROUND: Low-serum levels of magnesium, phosphate, and zinc are observed in many intensive care unit (ICU) patients, but clinical equipoise exists regarding supplementation strategies. We aimed to assess the desirable and undesirable effects of supplementation with magnesium, phosphate, or zinc in adult ICU patients. METHODS: We conducted a systematic review with meta-analysis of randomised clinical trials assessing the effects of supplementation with magnesium, phosphate, or zinc in adult ICU patients. Primary outcomes were mortality and duration of mechanical ventilation. We registered the protocol, followed the Preferred Reporting Items for Systematic Review and Meta-Analysis statement, used the Cochrane risk of bias 2 tool, and the grading of recommendations, assessment, development and evaluation (GRADE) approach for assessing the certainty of the evidence. RESULTS: We identified no low risk of bias trials. For magnesium supplementation, we included three trials (n = 235); the relative risk (RR) for mortality was 0.54, 95% confidence interval (CI) 0.30-0.96 compared to no supplementation (very low certainty of evidence). For zinc supplementation, two trials were included (n = 168); the RR for mortality was 0.73, 95% CI 0.41-1.28 compared to control. No trials assessed the effects of phosphate supplementation on mortality. For outcomes other than mortality, only zero or one trial was available. CONCLUSIONS: In adult ICU patients, the certainty of evidence for the effects of supplementation with magnesium, phosphate, or zinc was very low. High-quality trials are needed to assess the value of supplementation strategies in these patients.

Abnormal serum levels of magnesium, phosphate, and zinc in ICU patients-Characteristics, management, and outcomes: The WhyTrace cohort study.

BACKGROUND: Abnormal serum levels of magnesium, phosphate, and zinc appear common in intensive care unit (ICU) patients, but the epidemiology, management, and associations with outcomes are less well described. We described these factors and estimated associations with outcomes in a large dataset of Danish ICU patients. METHODS: We included adults who were acutely admitted to 10 general ICUs in Denmark between October 2011 and January 2018. From the dataset, we obtained characteristics of patients who had serum levels measured of magnesium, phosphate, or zinc, including data on supplementation. We used joint models with death as a competing outcome to estimate the associations between abnormal serum levels and time to successful extubation and, for magnesium, also incident tachyarrhythmia. RESULTS: We included 16,517 of 36,514 patients in the dataset. The cumulative probability of hypomagnesemia within 28 days was 64% (95% confidence interval [CI] 62-66); of hypophosphatemia 74% (95% CI 72-75); and of hypozincemia 98% (95% CI 98-98). Supplementation of magnesium was used in 3554 out of 13,506 (26%) patients, phosphate in 2115 out of 14,148 (15%) patients, and zinc in 4465 out of 9869 (45%) patients. During ICU stay, 38% experienced hypermagnesemia, 58% hyperphosphatemia, and 1% hyperzincemia. Low serum levels of magnesium, phosphate, and zinc were associated with shorter time to successful extubation, and high serum magnesium and phosphate and low serum zinc with the competing risk of increased mortality, but too few serum measurements made the results inconclusive. CONCLUSION: In this multicenter cohort study of acutely admitted ICU patients, most experienced low serum levels of magnesium, phosphate, or zinc during ICU stay, many received supplementation, and experiencing both low and high serum levels during ICU stay was not uncommon. Associations between serum levels and clinical outcomes appeared inconclusive because the data proved unfit for these analyses.

Preferences for the measurement and supplementation of magnesium, phosphate and zinc in ICUs: The international WhyTrace survey.

BACKGROUND: Patients admitted to the Intensive Care Unit (ICU) often have low magnesium, phosphate and zinc levels. Monitoring of serum concentrations and supplementation may be important, but there is no consensus on optimal practice. The objective of the WhyTrace survey was to describe current practice regarding the measurement and supplementation of magnesium, phosphate and zinc in ICUs. METHODS: A 54-item electronic questionnaire was developed in accordance with SURGE, SUrvey Reporting GuidelinE, to address international clinical practice in the ICU. National investigators recruited ICUs in ten countries with one physician responding per ICU using a unique e-mail distributed survey-link. RESULTS: The questionnaire was sent to clinicians in 336 ICUs of whom 283 (84%) responded. In 62% of the ICUs, a standard procedure was in place regarding the measurement of serum magnesium levels, in 58% for phosphate and in 9% for zinc. Zinc was never or rarely measured in 64% of ICUs. The frequency of requesting serum levels varied from twice daily to once weekly. Regarding supplementation, 66% of ICUs had a standard procedure for magnesium, 63% for phosphate and 15% for zinc. Most procedures recommended supplementation when serum levels were below the lower reference level, but some used the upper reference levels as the threshold for supplementation and others decided on a case-by-case basis. CONCLUSION: The practice of measuring and supplementing magnesium, phosphate and zinc differed substantially between ICUs. Our findings indicate that there is a need for high-quality prospective data on frequencies of measurements, treatment goals and effects of supplementation on patient-important outcomes.

Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia: The COVID STEROID 2 Randomized Trial.

Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days). Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). Conclusions and Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.

Prolonged job strain and subsequent risk of cancer in women - a longitudinal study, based on the Danish Nurse Cohort.

BACKGROUND: The role of psychological stress in cancer risk is continuously debated. Stress at work is the most common form of stress and previous studies have shown inconsistent results regarding cancer risk. In this longitudinal study, we examined the association between prolonged job strain across six years and subsequent cancer risk. METHODS AND MATERIALS: We used data from 6571 cancer-free women from the Danish Nurse Cohort aged 45-70 years at inclusion, and self-reported questionnaires on job strain at baseline in 1993 and again in 1999. Prolonged job strain was defined as high job busyness and speed, and low control in both 1993 and 1999. Information on cancer diagnosis was obtained from the Danish Cancer Registry. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for overall cancer as well as subgroups of virus immune-related, hormone-related, digestive and lung cancers according to level of prolonged job strain. The women were followed from 1 January 2000 until cancer diagnosis, emigration, death or 31 December 2013 (mean follow-up 13 years) and models were adjusted for potential confounders. Effect modification was examined according to working nightshifts and full time. RESULTS: No significant differences in the risk of overall cancer or any of the cancer subgroups were identified in relation to prolonged busyness, speed, influence, or overall job strain. Effect modification by working full time was observed when examining job influence in relation to overall cancer risk, and by working nightshifts when examining job influence in relation to hormone related cancer risk. However, none of the associations were significant in stratified analyses. CONCLUSION: We found no evidence of an increased risk of any cancer among women with prolonged job strain. Since a large proportion of cancer patients perceive psychological stress as a possible cause of their cancer disease, it is of importance to communicate these findings to the public.