Daily sedation interruption versus no daily sedation interruption for critically ill adult patients requiring invasive mechanical ventilation
Editorial Group: Cochrane Anaesthesia Group
Published Online: 9 JUL 2014
Assessed as up-to-date: 25 FEB 2014
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
Burry L, Rose L, McCullagh IJ, Fergusson DA, Ferguson ND, Mehta S. Daily sedation interruption versus no daily sedation interruption for critically ill adult patients requiring invasive mechanical ventilation. Cochrane Database of Systematic Reviews 2014, Issue 7. Art. No.: CD009176. DOI: 10.1002/14651858.CD009176.pub2.
- Publication Status: Edited (no change to conclusions)
- Published Online: 9 JUL 2014
Daily sedation interruption (DSI) is thought to limit drug bioaccumulation, promote a more awake state, and thereby reduce the duration of mechanical ventilation. Available evidence has shown DSI to either reduce, not alter, or prolong the duration of mechanical ventilation.
The primary objective of this review was to compare the total duration of invasive mechanical ventilation for critically ill adult patients requiring intravenous sedation who were managed with DSI versus those with no DSI. Our other objectives were to determine whether DSI influenced mortality, intensive care unit (ICU) and hospital lengths of stay, adverse events, the total doses of sedative drug administered, and quality of life.
We searched, from database inception to February 2014, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1); MEDLINE (OvidSP); EMBASE (OvidSP); CINAHL (EBSCOhost); Latin American and Caribbean Health Sciences Literature (LILACS); Web of Science Science Citation Index; Database of Abstracts of Reviews of Effects (DARE); the Health Technology Assessment Database (HTA Database); trial registration websites, and reference lists of relevant articles. We did not apply language restrictions. The reference lists of all retrieved articles were reviewed for additional, potentially relevant studies.
We included randomized controlled trials that compared DSI with sedation strategies that did not include DSI in mechanically ventilated, critically ill adults.
Data collection and analysis
Two authors independently extracted data and three authors assessed risk of bias. We contacted study authors for additional information as required. We combined data in forest plots using random-effects modelling. A priori subgroups and sensitivity analyses were performed.
Nine trials were used in the analysis (n = 1282 patients). These trials were found to be predominantly at low risk of bias. We did not find strong evidence of an effect of DSI on the total duration of ventilation. Pooled data from nine trials demonstrated a 13% reduction in the geometric mean, with relatively wide confidence intervals (CI) indicating imprecision (95% CI 26% reduction to 2% increase, moderate quality evidence). Similarly, we did not find strong evidence of an effect on ICU length of stay (-10%, 95% CI -20% to 3%, n = 9 trials, moderate quality evidence) or hospital length of stay (-6%, 95% CI -18% to 8%, n = 8 trials, moderate quality evidence). Heterogeneity for these three outcomes was moderate and statistically significant. The risk ratio for ICU mortality was 0.96 (95% CI 0.77 to 1.21, n = 7 trials, moderate quality evidence), for rate of accidental endotracheal tube removal 1.07 (95% CI 0.55 to 2.12, n = 6 trials, moderate quality evidence), for catheter removal 1.48 (95% CI 0.76 to 2.90, n = 4 trials), and for incidence of new onset delirium 1.02 (95% CI 0.91 to 1.13, n = 3 trials, moderate quality evidence). Differences in the doses of any drug used or quality of life score (Short Form (SF)-36) did not reach statistical significance. Tracheostomy was performed less frequently in the DSI group (RR 0.73, 95% CI 0.57 to 0.92, n = 6 trials, moderate quality evidence). Sensitivity analysis of unlogged data resulted in similar findings. Post hoc analysis to further explain heterogeneity, based on study country of origin, showed that studies conducted in North America resulted in a reduction in the duration of mechanical ventilation (-21%, 95% CI -33% to -5%, n = 5 trials).
We have not found strong evidence that DSI alters the duration of mechanical ventilation, mortality, length of ICU or hospital stay, adverse event rates, drug consumption, or quality of life for critically ill adults receiving mechanical ventilation compared to sedation strategies that do not include DSI. We advise that caution should be applied when interpreting and applying the findings as the overall effect of treatment is always < 1 and the upper limit of the CI is only marginally higher than the no-effect line. These results should be considered unstable rather than negative for DSI given the statistical and clinical heterogeneity identified in the included trials.
Plain language summary
Does daily sedation interruption reduce the time critically ill adults spend on breathing machines compared to other sedation strategies?
Background: critically ill patients require life-support technologies such as mechanical ventilation (breathing machines) and can experience pain, anxiety, and sleep deprivation related to their illness. Good pain control and adequate sedation are important but too much sedative drug can increase the time on breathing machines and the chance of harmful effects such as pneumonia.
Medications that are available have many properties that make them difficult to use in critically ill patients. Without careful adjustments these properties can lead to a build up of drug in the body. These medications are given as continuous infusions, so that blood levels remain stable, and dose changes are left to clinician judgement. In order to avoid drug build up, several methods can be used to adjust doses. Some studies claim that an interruption, or stopping the drug for a period of time each day, will allow the body to clear the drugs and lead to patients being more awake and ready for earlier liberation from the breathing machine.
Search date: current to February 2014.
Study characteristics: we included nine studies involving 1282 critically ill patients receiving mechanical ventilation. Studies compared daily sedation interruption to strategies that did not include an interruption. Studies were conducted worldwide and involved both medical and surgical critically ill patients.
Key results: we did not find strong evidence that daily sedation interruption reduced the duration of mechanical ventilation, length of stay in the intensive care unit (ICU) or hospital, death, or the amount of drug used. The effect on adverse events such as accidental removal of the breathing tube or invasive devices, or the rate of delirium was uncertain. However, tracheostomy was performed less often in those who were managed with daily sedation interruption. Sedation practices are known to vary worldwide, and as such an analysis of studies conducted in North America showed a reduction in time on the breathing machine for those who were managed with daily sedation interruption compared to those who were not.
Quality of the evidence: we advise caution should be applied when interpreting and applying our study findings. The results are based upon a small number of studies that were heterogeneous or not uniform in terms of methods, patients studied, and clinical management and our overall results only marginally crossed the no-effect line.