Effect of nicotine replacement therapy on mortality, delirium, and duration of therapy in critically ill smokers: A systematic review and meta-analysis

Objective: Nicotine replacement therapy is widely used in critically ill smokers and its effect on delirium, mortality and duration of Intensive Care Unit is unknown. The aims of this review were to determine whether the management of nicotine withdrawal with nicotine replacement therapy reduces delirium, mortality or length of stay in the critically ill smokers in intensive care unit. Primary outcome was incidence of author-defined intensive care unit delirium. Secondary outcomes were intensive care unit or hospital mortality, intensive care unit free days at day 28, and intensive care unit or hospital length of stay. Design: Systematic Review and Meta-analysis. Data sources: Medline, EMBASE, CINAHL, the Cochrane Database of Systematic reviews for randomised controlled trials and observational studies. Review Methods: Clinical trials, observational studies and systematic reviews comparing nicotine replacement therapy with placebo or no treatment were included. Case reports, case series, non-systematic reviews and studies that involved children were excluded. Results: Eight studies were eligible (n=2,636) for inclusion in the data synthesis. In a meta-analysis of observational studies, nicotine replacement therapy was associated with increased delirium (three studies; n=908; I2= 0%; FEM: OR 4.03 [95% CI 2.64, 6.15]; ρ<0.001). There was no difference in intensive care unit mortality (three studies; n=1309; ρ=0.10, I2= 44%; FEM: OR 0.58; 95%CI 0.31, 1.10) and hospital mortality or 28-day intensive care unit free days. Conclusions: In the absence of a high quality data, nicotine replacement therapy cannot currently be recommended for routine use to prevent delirium or to reduce hospital or intensive care unit mortality in critically ill smokers.