Effectiveness and harms of pharmacological interventions for the treatment of delirium in adults in intensive care units after cardiac surgery: a systematic review.

Abstract

OBJECTIVE The objective of this review was to synthesize the best available evidence on the effectiveness and harms of pharmacological interventions for the treatment of delirium in adult patients in the intensive care unit (ICU) after cardiac surgery. INTRODUCTION Patients who undergo cardiac surgery are at high risk of delirium (incidence: 50-90%). Delirium has deleterious effects, increasing the risk of death and adversely affecting recovery. Clinical interventional trials have been conducted to prevent and treat postoperative delirium pharmacologically including antipsychotics and sedatives. These trials have provided some evidence about efficacy and influenced clinical decision making. However, much reporting is incomplete and provides biased assessments of efficacy; benefits are emphasized while harms are inadequately reported. INCLUSION CRITERIA Participants were ≥ 16 years, any sex or ethnicity, who were treated postoperatively in a cardiothoracic ICU following cardiac surgery and were identified as having delirium. Any pharmacological intervention for the treatment of delirium was included, regardless of drug classification, dosage, intensity or frequency of administration. Outcomes of interest of this review were: mortality, duration and severity of delirium, use of physical restraints, quality of life, family members' satisfaction with delirium management, duration/severity of the aggressive episode, associated falls, severity of accidental self-harm, pharmacological harms, harms related to over-sedation, ICU length of stay, hospital length of stay (post ICU), total hospital length of stay, need for additional intervention medication and need for rescue medication. Randomized controlled trials were considered first and in their absence, non-randomized controlled trials and quasi-experimental would have been considered, followed by analytical observational studies. METHODS A search was conducted in PubMed, Embase, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials, Scopus, Epistemonikos, Australian New Zealand Clinical Trials Registry, ClinicalTrials.gov, Clinical Trials in New Zealand, and ProQuest Dissertations and Theses to locate both published and unpublished studies. There was no date limit for the search. A hand search for primary studies published between January 1, 2012 and November 17, 2018 in relevant journals was also conducted. Only studies published in English were considered for inclusion. Two reviewers independently assessed the methodological quality using standardized critical appraisal instruments from JBI and McMaster University. Quantitative data were extracted using the standardized JBI data extraction tool. A meta-analysis was not performed, as there was too much clinical and methodological heterogeneity in the included studies. Results have been presented in a narrative form. Standard GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) evidence assessment of outcomes has been reported. RESULTS Three RCTs investigating morphine versus haloperidol (n = 53), ondansetron versus haloperidol (n = 72), and dexmedetomidine versus midazolam (n = 80) were included. Due to heterogeneity and incomplete reporting, a meta-analysis was not feasible. Overall, the methodological quality of these studies was found to be low. Additionally, this review found reporting of harms to be inadequate and superficial for all three studies and did not meet the required standards for harms reporting, as defined by the CONSORT statement extension for harms. CONCLUSIONS It was not possible to draw any valid conclusions regarding the effectiveness of morphine vs haloperidol, ondansetron vs haloperidol or dexmedetomidine vs midazolam in treating delirium after cardiac surgery. This is due to the low number of studies, the poor methodological quality in conducting and reporting and the heterogeneity between the studies.