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A systematic review of interventions to facilitate extubation in patients difficult-to-wean due to delirium, agitation, or anxiety and a meta-analysis of the effect of dexmedetomidine

  • Sébastien Dupuis
  • Dave Brindamour
  • Stephanie Karzon
  • Anne Julie Frenette
  • Emmanuel Charbonney
  • Marc M. Perreault
  • Patrick Bellemare
  • Lisa Burry
  • David R. WilliamsonEmail author
Review Article/Brief Review

Abstract

Background

Delirium, agitation, and anxiety may hinder weaning from mechanical ventilation and lead to increased morbidity and healthcare costs. The most appropriate clinical approach to weaning in these contexts remains unclear and challenging to clinicians. The objective of this systematic review was to identify effective and safe interventions to wean patients that are difficult-to-wean from mechanical ventilation due to delirium, agitation, or anxiety.

Methods

A systematic review was performed using MEDLINE, EMBASE, and PubMed. Studies evaluating mechanically ventilated patients deemed difficult-to-wean due to delirium, agitation, or anxiety, and comparing the effects of an intervention with a comparator arm were sought. Time-to-extubation was the primary outcome while the secondary outcome was intensive care unit (ICU) length of stay.

Results

From 10,860 studies identified, eight met the inclusion criteria: six studies assessed dexmedetomidine while the remaining two assessed loxapine and biofeedback. Pooled analysis of studies assessing dexmedetomidine showed reduced time-to-extubation (six studies, n = 303) by 10.9 hr compared with controls (95% confidence interval [CI], -15.7 to -6.1; I2 = 68%) and ICU length of stay (four studies, n = 191) by 2.6 days (95% CI, 1.9 to 3.3; I2 = 0%). Nevertheless, the evidence was deemed to be of low quality given the small sample sizes and high heterogeneity. Studies assessing other interventions did not identify improvements compared with controls. Safety assessment was globally poorly reported.

Conclusions

This systematic review and meta-analysis provides low quality evidence to suggest the use of dexmedetomidine in patients deemed difficult-to-wean due to agitation, delirium, or anxiety. Insufficient evidence was found regarding other interventions to provide any recommendation.

Trial registration

PROSPERO (CRD42016042528); registered 15 July, 2016.

Revue systématique des interventions visant à faciliter l’extubation de patients difficiles à sevrer en raison d’un délirium, d’une agitation ou d’anxiété, et méta-analyse de l’effet de la dexmédétomidine

Résumé

Contexte

Le délirium, l’agitation et l’anxiété peuvent compliquer le sevrage de la ventilation mécanique et aboutir à une augmentation de la morbidité et du coût des soins de santé. L’approche clinique la plus adaptée au sevrage dans ces circonstances n’est pas claire et reste un défi pour les cliniciens. L’objectif de cette étude systématique était d’identifier des interventions efficaces et sécuritaires pour sevrer les patients « difficiles à sevrer » de la ventilation mécanique en raison d’un délirium, d’une agitation ou d’anxiété.

Méthodes

Une revue systématique a été menée en utilisant les bases de données MEDLINE, EMBASE et PubMed. Les études évaluant des patients sous ventilation mécanique jugés difficiles à sevrer en raison d’un délirium, d’une agitation ou d’anxiété, comparant les effets d’une intervention à celle d’un bras comparateur ont été recherchées. Le critère d’évaluation principal a été le délai jusqu’à l’extubation et le critère d’évaluation secondaire a été la durée de séjour en unité de soins intensifs (USI).

Résultats

À partir de 10 860 études identifiées, huit satisfaisaient les critères d’inclusion : six études ont évalué la dexmédétomidine tandis que les deux dernières ont évalué la loxapine et le biofeedback. L’analyse groupée des études évaluant la dexmédétomidine a montré une réduction du délai d’extubation (six études, n = 303) de 10,9 heures comparativement aux contrôles (intervalle de confiance [IC] à 95 % : -15,7 à -6,1; I2 = 68 %) et de la durée du séjour en USI (quatre études, n = 191) de 2,6 jours (IC à 95 % : 1,9 à 3,3; I2 = 0 %). Néanmoins, les résultats sont de faible qualité compte tenu de la petite taille des échantillons et d’une grande hétérogénéité. Les études évaluant d’autres interventions n’ont pas identifié d’améliorations par rapport aux contrôles. D’une manière générale, les évaluations de l’innocuité ont été médiocrement décrites.

Conclusions

Cette étude systématique et la méta-analyse procurent une preuve de qualité basse pour suggérer l’utilisation de la dexmédétomidine chez des patients considérés difficiles à sevrer en raison d’un délirium, d’une agitation ou d’anxiété. Les données probantes concernant les autres interventions ont été jugées insuffisantes pour permettre des recommandations quelconques.

Enregistrement de l’essai clinique

PROSPERO (CRD42016042528); enregistré le 15 juillet 2016.

Notes

Acknowledgements

We thank Patrice Dupont, senior information specialist at University of Montreal, for providing helpful comments on the search strategy.

Competing interests

Dave Brindamour received consulting honoraria from Pfizer; Anne Julie Frenette received speaker honoraria from Pfizer; David R. Williamson is supported by a Fonds de recherche du Québec – Santé (FRQ-S) clinical scientist career grant and received an investigator-initiated research grant from Pfizer. The remaining authors have disclosed that they do not have conflicts of interest.

Editorial responsibility

This submission was handled by Dr. Gregory L. Bryson, Deputy Editor-in-Chief, Canadian Journal of Anesthesia.

Author contributions

Sébastien Dupuis and Dave Brindamour conceived the study design, performed the search, selected studies, extracted and analyzed the data, and wrote the manuscript. Stephanie Karzon performed the search, selected studies, extracted the data, and revised the manuscript. Anne Julie Frenette and David R. Williamson conceived the study design, extracted the data, analyzed the data, and revised the manuscript. Marc M. Perreault, Lisa Burry, Emmanuel Charbonney, and Patrick Bellemare extracted and checked data, helped with the interpretation of data, and critically revised the manuscript.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Supplementary material

12630_2018_1289_MOESM1_ESM.tif (361 kb)
Electronic supplementary material 1 (TIF 361 kb)
12630_2018_1289_MOESM2_ESM.pdf (105 kb)
Electronic supplementary material 2 (PDF 105 kb)

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Copyright information

© Canadian Anesthesiologists' Society 2019

Authors and Affiliations

  • Sébastien Dupuis
    • 1
    • 2
  • Dave Brindamour
    • 1
  • Stephanie Karzon
    • 3
  • Anne Julie Frenette
    • 1
    • 2
    • 4
  • Emmanuel Charbonney
    • 2
    • 5
    • 6
  • Marc M. Perreault
    • 4
    • 7
  • Patrick Bellemare
    • 5
    • 6
  • Lisa Burry
    • 8
    • 9
  • David R. Williamson
    • 1
    • 2
    • 4
    Email author
  1. 1.Pharmacy DepartmentHôpital du Sacré-Cœur-de-MontréalMontrealCanada
  2. 2.Research CenterHôpital du Sacré-Cœur-de-MontréalMontrealCanada
  3. 3.Department of Pharmacology, Faculté de MédecineUniversité de MontréalMontrealCanada
  4. 4.Faculté de PharmacieUniversité de MontréalMontrealCanada
  5. 5.Department of Critical CareHôpital du Sacré-Coeur-de-MontréalMontrealCanada
  6. 6.Department of Medicine, Faculté de médecineUniversité de MontréalMontrealCanada
  7. 7.Pharmacy DepartmentMcGill University Health CenterMontrealCanada
  8. 8.Pharmacy DepartmentMount Sinai HospitalTorontoCanada
  9. 9.Leslie Dan Faculty of PharmacyUniversity of TorontoTorontoCanada

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