Micronutrient supplementation for critically ill adults : a systematic review of the evidence
Thesis (MNutr (Human Nutrition))--Stellenbosch University, 2008.
Background Critical illness is associated with increased production of reactive oxygen species and oxidative stress, and low levels of most micronutrients with resultant diminished endogenous antioxidant defences. Micronutrient supplementation is thought to be beneficial to the critically ill patient by ameliorating oxidative stress and by improving clinical outcome. Objectives This systematic review assessed the effects of micronutrient supplementation on adults recovering from critical illness. Primary outcomes included clinical endpoints [mortality, infectious complications, length of intensive care unit and hospital stay (LICU and LOS)]. Secondary outcomes included descriptions of practice issues, micronutrient status, morbidity, course of the acute phase response and oxidative stress. Search strategy An electronic bibliographic database search was carried out, bibliographies of retrieved articles were reviewed and personal files searched to obtain additional citations. Databases were searched from inception until 29 February 2008. Selection criteria Randomized controlled trials (RCTs) of micronutrient supplementation (by any route) in adult critically ill patients, given in addition to their routine care, were included. Data collection and analysis Two authors independently extracted data and assessed trial quality. For the primary outcomes the random-effects model was used to estimate overall relative risk / mean difference and effect size due to the presence of study heterogeneity. Selected exploratory analyses were undertaken. Differences at the level of p<0.05 was considered to be statistically significant. The secondary outcomes were sparse and variably recorded such that this data was not formally aggregated. Main results Fifteen RCTs involving 1714 participants and 18 RCTs involving 1849 participants were included for the primary and secondary objectives respectively. The quality of the RCTs, as reported, was disappointing, particularly for allocation concealment. Fourteen trials (n=1468) of micronutrient supplementation showed a statistically significant reduction in overall mortality [relative risk (RR) 0.78, 95% confidence interval (CI) 0.67-0.90, I2=0%, p=0.0009]. An asymmetrical funnel plot necessitates caution when directly interpreting these results. Six RCTs (n=1194) indicated a statistically significant reduction in 28 day mortality (RR 0.75, 95% CI 0.63-0.88, I2=0%, p=0.0006) (symmetrical funnel plot). Micronutrient supplementation in this systematic review was not associated with a reduction in infectious complications, LICU or LOS. In sub-group analyses, single nutrients were associated with borderline statistical significance (RR 0.82, 95% CI 0.66-1.01, I2=0%, p=0.06) in terms of mortality, whist a sensitivity analysis of combined micronutrients indicated a significant reduction in mortality (RR 0.69, 95% CI 0.54-0.90, I2=2%, p= 0.006). This review did not find clear evidence that parenteral is superior to enteral administration in terms of clinical outcomes. The secondary outcomes confirmed that timing, duration and dosing are key factors to ensure optimal clinical benefit. Conclusion This review does suggest potential benefit of micronutrient supplementation in critically ill adults for some clinical outcomes (especially mortality), but also highlights that caution is warranted as nutrient interactions and risk of toxicity are not clearly defined in critical illness. More large multi-centre randomized trials are necessary to assess the effects of different types and doses of micronutrient supplementation in selected groups of patients with different types of critical illness.