Interventions to facilitate weaning from mechanical ventilation in difficult to wean patients due to delirium, agitation or anxiety: a systematic review and meta-analysis
CCCF ePoster library. Williamson D. Nov 1, 2016; 150931; 53 Disclosure(s): Investigator-initiated grant from Pfizer Canada
David Williamson
David Williamson
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Topic: Systematic Review, Meta-analysis, or Meta-synthesis

Interventions to facilitate weaning from mechanical ventilation in difficult to wean patients due to delirium, agitation or anxiety: a systematic review and meta-analysis

Dupuis, Sébastien1; Brindamour, Dave1; Frenette, Anne Julie1,2; Perreault, Marc2,3; Burry, Lisa4; Karzon, Stephanie2; Bellemare, Patrick5,6; Charbonney, Emmanue5,6l; Williamson, David1,2

1Pharmacy department, Hôpital du Sacré-Coeur de Montréal, Montreal, Canada
2Faculté de pharmacie, Université de Montréal, Montreal, Canada
3Pharmacy department, McGill University Health Center, Montreal, Canada
4Pharmacy department, Mount Sinai Hospital, Toronto, Canada
5Critical Care department, Hôpital du Sacré-Coeur de Montréal, Montreal, Canada
6Faculté de médecine, Université de Montréal, Montreal, Canada


Introduction: In mechanically ventilated patients, planning extubation requires a multi-step approach, including the process of weaning patients from mechanical ventilation. Many reversible conditions, such as delirium, agitation or anxiety, complicate weaning and result in increased duration of mechanical ventilation, patient morbidity and healthcare costs.
Objectives: To assess the efficacy and safety of interventions used to facilitate weaning from mechanical ventilation in difficult to wean patients due to delirium, agitation or anxiety.
Methods: A systematic review was performed according to the PRISMA statement. Protocol was registered on PROSPERO (CRD42016042528). In July 2016, randomized controlled trials and observational studies were identified by searching MEDLINE, EMBASE and PubMed from the earliest accessible dates. The strategy also included manually searching  the last three years’ conference proceedings of six different scientific meetings and searching bibliographies of included studies. Studies evaluating mechanically ventilated patients deemed difficult-to-wean due to delirium, agitation or anxiety, and comparing the effects of any pharmacological intervention or complimentary and alternative medicine strategies to placebo, standard treatment or another active comparator were sought. The definition of difficult-to-wean used was the one defined by study authors in each paper. Two independent reviewers screened all citations based on titles and abstracts. Full-text articles of selected citations were then retrieved for eligibility assessment. Each study was then evaluated independently and in duplicate. A third independent reviewer resolved any disagreement. Methodological quality was assessed using the rating instrument developed by the Cochrane Handbook for Systematic Reviews of Interventions for RCTs. Non-randomized trials were evaluated using the Newcastle - Ottawa Quality Assessment Scale. Primary outcome evaluated was time-to-extubation while the secondary outcome was ICU length of stay. Whenever possible, outcomes were pooled (RevMan 5.3) to conduct a meta-analysis. A fixed-effect model was used unless there was significant heterogeneity, in which case a random effect model was used.
Results: A total of 9892 studies were identified. After removing duplicates and records with irrelevant topic, 62 full-text articles were assessed for eligibility. From these, 9 studies met the inclusion criteria. Six of them assessed dexmedetomidine while the remaining three assessed loxapine, biofeedback and music therapy. A high risk of bias was found for the majority of the included studies. Pooled analysis of studies assessing dexmedetomidine as the intervention reduced the time to extubation (6 studies, n=303) by 7.7 hours (95%CI  2.63-12.83, p =0.003; I2=93%) and ICU length of stay (4 studies, n=191) by 2.58 days (95%CI 1.86-3.31, p<0.001; I2=0%). Bradycardia and hypotension were the most frequently reported adverse effects in the dexmedetomidine group. The respective studies assessing loxapine, biofeedback and music therapy did not identify improvements in time to extubation.
Conclusion: This systematic review and meta-analysis suggest that dexmedetomidine reduces the time to extubation and ICU length of stay in patients difficult to wean due to their state of delirium, agitation or anxiety. The low quality of the data assessed merits further evaluation in a large randomized controlled trial.


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