Marija Barbateskovic1,2, Sara R Krauss1, Marie O Collet2,3, Nina C Andersen-Ranberg2,4, Ole Mathiesen2,4,5, Janus C Jakobsen1,2,6,7, Anders Perner2,3, Jørn Wetterslev1,2. 1. Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen, Denmark. 2. Centre for Research in Intensive Care, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 3. Department of Intensive Care, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 4. Centre for Anaesthesiological Research, Department of Anaesthesiology and Intensive Care, Zealand University Hospital, Koege, Denmark. 5. Department of Clinical Medicine, Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark. 6. Department of Cardiology, Holbaek Hospital, Holbaek, Denmark. 7. Department of Regional Health Research, The Faculty of Heath Sciences, University of Southern Denmark, Odense, Denmark.
Abstract
BACKGROUND: Haloperidol is the most frequently used drug to treat delirium in the critically ill patients. Yet, no systematic review has focussed on the effects of haloperidol in critically ill patients with delirium. METHODS: We conducted a systematic review with meta-analysis and Trial Sequential Analysis of randomized clinical trials (RCTs) assessing the effects of haloperidol vs any intervention on all-cause mortality, serious adverse reactions/events, days alive without delirium, health-related quality of life (HRQoL), cognitive function and delirium severity in critically ill patients with delirium. We also report on QTc prolongation, delirium resolution and extrapyramidal symptoms. RESULTS: We included 8 RCTs with 11 comparisons (n = 951). We adjudicated one trial as having overall low risk of bias. Three trials used rescue haloperidol; excluding these, we did not find an effect of haloperidol vs control on all-cause mortality (RR 1.01; 95% CI 0.33-3.06; I2 = 0%; 112 participants; 3 trials; 4 comparisons; very low certainty) or delirium severity (SMD -0.15; 95% CI -0.61-0.30; I2 = 27%; 134 participants; 3 trials; 4 comparisons; very low certainty). No trials reported adequately on serious adverse reactions/events. Only one trial reported on days alive without delirium, cognitive function and QTc prolongation, and no trials reported on HRQoL. Sensitivity analyses, including trials using rescue haloperidol, did not change the results. CONCLUSIONS: The evidence for the use of haloperidol to treat critically ill patients with delirium is sparse, of low quality and inconclusive. We therefore have no certainty regarding any beneficial, harmful or neutral effects of haloperidol in these patients.
BACKGROUND:Haloperidol is the most frequently used drug to treat delirium in the critically illpatients. Yet, no systematic review has focussed on the effects of haloperidol in critically illpatients with delirium. METHODS: We conducted a systematic review with meta-analysis and Trial Sequential Analysis of randomized clinical trials (RCTs) assessing the effects of haloperidol vs any intervention on all-cause mortality, serious adverse reactions/events, days alive without delirium, health-related quality of life (HRQoL), cognitive function and delirium severity in critically illpatients with delirium. We also report on QTc prolongation, delirium resolution and extrapyramidal symptoms. RESULTS: We included 8 RCTs with 11 comparisons (n = 951). We adjudicated one trial as having overall low risk of bias. Three trials used rescue haloperidol; excluding these, we did not find an effect of haloperidol vs control on all-cause mortality (RR 1.01; 95% CI 0.33-3.06; I2 = 0%; 112 participants; 3 trials; 4 comparisons; very low certainty) or delirium severity (SMD -0.15; 95% CI -0.61-0.30; I2 = 27%; 134 participants; 3 trials; 4 comparisons; very low certainty). No trials reported adequately on serious adverse reactions/events. Only one trial reported on days alive without delirium, cognitive function and QTc prolongation, and no trials reported on HRQoL. Sensitivity analyses, including trials using rescue haloperidol, did not change the results. CONCLUSIONS: The evidence for the use of haloperidol to treat critically illpatients with delirium is sparse, of low quality and inconclusive. We therefore have no certainty regarding any beneficial, harmful or neutral effects of haloperidol in these patients.
Authors: Gladys M Asong; Felix Amissah; Chandrashekhar Voshavar; Augustine T Nkembo; Elizabeth Ntantie; Nazarius S Lamango; Seth Y Ablordeppey Journal: ACS Omega Date: 2020-12-16
Authors: Nina Andersen-Ranberg; Lone M Poulsen; Anders Perner; Johanna Hästbacka; Matthew P G Morgan; Giuseppe Citerio; Marie Oxenbøll-Collet; Sven-Olaf Weber; Anne Sofie Andreasen; Morten H Bestle; Bülent Uslu; Helle B S Pedersen; Louise G Nielsen; Kjeld Damgaard; Troels B Jensen; Trine Sommer; Nilanjan Dey; Ole Mathiesen; Anders Granholm Journal: Acta Anaesthesiol Scand Date: 2022-05-31 Impact factor: 2.274