132 PART THREE | DELIRIUM dementia) scores for cognitive impairment were ≥4, which shows that long-term decline of cognitive status was highly prevalent. In our study, mean age was <70 years in both treatment arms, and patients with dementia were excluded. To conclude, prescribing of antipsychotic drugs for patients with delirium remains a matter of debate [33]. Future studies need to identify baseline factors indicating which patients will benefit most from upfront treatment with antipsychotic drugs. Overall, the safety profiles of haloperidol and olanzapine in the dose range tested were in line with previous studies in non-ICU patients with delirium [9]. TRAEs of any grade occurred in 32.7% and 26.5% of the patients in the haloperidol and olanzapine arm, respectively. TRAEs grade ≥3 (all leading to drug discontinuation) were reported more frequently in the haloperidol arm: 20.4 % vs. 10.2% in the olanzapine arm; however, this difference was not statistically significant. The most common grade ≥3 TRAE was sedation in both treatment arms. EPS grade ≥3 was uncommon, occurring in 4% of the patients in the haloperidol arm. Only three patients in the olanzapine arm experienced low grade EPS; EPS grade ≥3 did not occur in the olanzapine arm. All TRAEs resolved without sequelae when the study drug was discontinued. The use of antipsychotics is associated with QTc prolongation, which can lead to life-threatening arrhythmia [34-36]. In this study with routine ECG assessment only one atrioventricular block episode was reported in the haloperidol arm. Previous reports indicate high levels of delirium-related distress in patients and their caregivers [5-7]. In our study, exploratory analysis showed that mean stress scores reported by patients were just above 2 (on a 4 point rating scale) in both treatment arms. As expected, stress scores reported by spouses and care-givers were high: 2.7 vs. 3.0 in the haloperidol and olanzapine arm, respectively. Scores reported by attending nurses were low in both treatment arms. This could be the effect of improved professional education, providing nurses with educational resources and opportunities to apply knowledge with regard to delirium, which increases confidence in identification and management of delirium [37, 38]. This study has some limitations. First, our study did not include a placebo control group. The absence of a comparative placebo control group with active treatment groups limits the interpretation of our findings. Second, the DOS was completed not on a daily basis, but at fixed times twice-weekly, or whenever deliriumwas suspected. Daily assessments were not feasible given the high workload of the nursing staff. Consequently, some delirious cases may have remained undetected. Third, although the rater of the DRS-R-98 scores was blinded to the study drug, as the rater knew that all subjects were receiving active treatment, DRS-R-98 ratings could have been affected. Fourth, non-pharmacological interventions for the prevention and treatment of delirium were not standardized across the participating 5 sites in this study. However, it should be noted that for most nonpharmacological interventions, there is limited research evidence on which to base clinical recommendations. Interventions based on the Hospital Elder Life Program (HELP) [39] have been successfully implemented in all Dutch healthcare institutions. Fifth, the decision of stopping this trial early for futility was adopted as a consequence of the results of the interim analysis, which demonstrated that it was highly unlikely that the trial would
RkJQdWJsaXNoZXIy MjY0ODMw