Abstract
Background:
Anesthesia-related complications, specifically depth of sedation, choice of sedative and delirium have increasingly been identified as a major contributor to long-term morbidity in critically ill patients. Evidence shows that early deep sedation, longer exposure to gamma aminobutyric acid (GABA)-ergic sedatives, and ICU delirium have a significant relationship with increased mortality and cognitive dysfunction after discharge. However, long-term outcomes associated with anesthesia-related factors within the intensive care unit (ICU) are still not sufficiently synthesized by high quality primary studies.
Objectives:
To systematically assess the incidence, risk factors, and long-term effects of anesthesia-related complications of critically ill adults, and quantify the effect of early deep sedation on long-term mortality using meta-analysis.
Methodology:
After a systematic search and eligibility criteria, five original studies were included two studies capable of obtaining quantitative data on depth of sedation and long-term mortality, and three qualitative longitudinal studies, which reported long-term cognitive, psychological, and functional outcomes of delirium and delirium exposure to sedatives. Data extraction was performed independently for study design, population, exposure, outcomes and effect measures. A meta-analysis with a fixed-effect model and inverse-variance weighting was conducted with hazard ratios from the two eligible studies on early deep sedation and long-term mortality. The other three studies were narratively synthesized because of heterogeneity for outcomes and measurement tools.
Results:
Across the 5 included studies, early deep sedation in the first 24-48 hours of mechanical ventilation was a significant anesthesia-related risk factor. Meta-analysis of the two quantitative studies showed early deep sedation to be associated with a 10% increase in long-term mortality (pooled HR 1.10; 95% CI 1.05-1.15). The remaining three studies were synthesized qualitatively to reveal that the long-term cognitive impairment was high (up to 60-68% at 6-12 months), there was ongoing executive dysfunction and psychological sequelae were prominent that comprised of post-traumatic stress symptoms. Delirium duration (which is greatly affected by sedation practices) was found to be the best predictor of these long-term neurocognitive outcomes.
Conclusion:
Anesthesia-related complications, especially early deep sedation and delirium, have a significant impact on long-term outcome of critically ill patients. Early deep sedation is associated with a significant risk of long-term mortality and ICU delirium that contributes to chronic cognitive and psychological impairment. These results support the necessity of reducing deep sedation and adopting sedation-sparing measures and preventive and aggressive management of delirium to enhance survivorship curves. Further large scale longitudinal studies are warranted to standardize the outcome measures and assess specific anesthetic agents in long term prognostication.