Efficacy of haloperidol to decrease the burden of delirium in adult critically ill patients: the EuRIDICE randomized clinical trial.

BACKGROUND: The role of haloperidol as treatment for ICU delirium and related symptoms remains controversial despite two recent large controlled trials evaluating its efficacy and safety. We sought to determine whether haloperidol when compared to placebo in critically ill adults with delirium reduces days with delirium and coma and improves delirium-related sequelae. METHODS: This multi-center double-blind, placebo-controlled randomized trial at eight mixed medical-surgical Dutch ICUs included critically ill adults with delirium (Intensive Care Delirium Screening Checklist ≥ 4 or a positive Confusion Assessment Method for the ICU) admitted between February 2018 and January 2020. Patients were randomized to intravenous haloperidol 2.5 mg or placebo every 8 h, titrated up to 5 mg every 8 h if delirium persisted until ICU discharge or up to 14 days. The primary outcome was ICU delirium- and coma-free days (DCFDs) within 14 days after randomization. Predefined secondary outcomes included the protocolized use of sedatives for agitation and related behaviors, patient-initiated extubation and invasive device removal, adverse drug associated events, mechanical ventilation, ICU length of stay, 28-day mortality, and long-term outcomes up to 1-year after randomization. RESULTS: The trial was terminated prematurely for primary endpoint futility on DSMB advice after enrolment of 132 (65 haloperidol; 67 placebo) patients [mean age 64 (15) years, APACHE IV score 73.1 (33.9), male 68%]. Haloperidol did not increase DCFDs (adjusted RR 0.98 [95% CI 0.73-1.31], p = 0.87). Patients treated with haloperidol (vs. placebo) were less likely to receive benzodiazepines (adjusted OR 0.41 [95% CI 0.18-0.89], p = 0.02). Effect measures of other secondary outcomes related to agitation (use of open label haloperidol [OR 0.43 (95% CI 0.12-1.56)] and other antipsychotics [OR 0.63 (95% CI 0.29-1.32)], self-extubation or invasive device removal [OR 0.70 (95% CI 0.22-2.18)]) appeared consistently more favorable with haloperidol, but the confidence interval also included harm. Adverse drug events were not different. Long-term secondary outcomes (e.g., ICU recall and quality of life) warrant further study. CONCLUSIONS: Haloperidol does not reduce delirium in critically ill delirious adults. However, it may reduce rescue medication requirements and agitation-related events in delirious ICU patients warranting further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov (#NCT03628391), October 9, 2017.

Prospective multicentre multifaceted before-after implementation study of ICU delirium guidelines: a process evaluation.

OBJECTIVE: We aimed to explore: the exposure of healthcare workers to a delirium guidelines implementation programme; effects on guideline adherence at intensive care unit (ICU) level; impact on knowledge and barriers, and experiences with the implementation. DESIGN: A mixed-methods process evaluation of a prospective multicentre implementation study. SETTING: Six ICUs. PARTICIPANTS: 4449 adult ICU patients and 500 ICU professionals approximately. INTERVENTION: A tailored implementation programme. MAIN OUTCOME MEASURE: Adherence to delirium guidelines recommendations at ICU level before, during and after implementation; knowledge and perceived barriers; and experiences with the implementation. RESULTS: Five of six ICUs were exposed to all implementation strategies as planned. More than 85% followed the required e-learnings; 92% of the nurses attended the clinical classroom lessons; five ICUs used all available implementation strategies and perceived to have implemented all guideline recommendations (>90%). Adherence to predefined performance indicators (PIs) at ICU level was only above the preset target (>85%) for delirium screening. For all other PIs, the inter-ICU variability was between 34% and 72%. The implementation of delirium guidelines was feasible and successful in resolving the majority of barriers found before the implementation. The improvement was well sustained 6 months after full guideline implementation. Knowledge about delirium was improved (from 61% to 65%). The implementation programme was experienced as very successful. CONCLUSIONS: Multifaceted implementation can improve and sustain adherence to delirium guidelines, is feasible and can largely be performed as planned. However, variability in delirium guideline adherence at individual ICUs remains a challenge, indicating the need for more tailoring at centre level.

Spontaneous Sublingual Haematoma in a 90-year Old Patient: A Complication of Direct Oral Anticoagulants.

Sublingual haematoma is a rare complication of anticoagulants and can be life-threatening. As the number of prescribed anticoagulants is increasing, the incidence of complications of these drugs will continue to increase. A report of a sublingual haematoma in an elderly patient with chronic atrial fibrillation treated with edoxban (Lixiana ©, Daiichi Sankyo Europe GmbH, München, Germany) is reported. A 90-year male presented at the emergency department with an obstructed upper airway due to a sublingual haematoma. The patient received tranexamic acid, prothrombin complex, and fresh frozen plasma. After fiberoptic nasal intubation, the patient was monitored in the intensive care unit. After four days, the patient was extubated, and after six days, the swelling resolved completely. Complications of anticoagulants are rare but can be life-threatening. Recognition of an endangered airway and reversing the effects of the anticoagulant are essential. Surgical evacuation of the haematoma could be considered but is not necessary.

Improved Guideline Adherence and Reduced Brain Dysfunction After a Multicenter Multifaceted Implementation of ICU Delirium Guidelines in 3,930 Patients.

OBJECTIVES: Implementation of delirium guidelines at ICUs is suboptimal. The aim was to evaluate the impact of a tailored multifaceted implementation program of ICU delirium guidelines on processes of care and clinical outcomes and draw lessons regarding guideline implementation. DESIGN: A prospective multicenter, pre-post, intervention study. SETTING: ICUs in one university hospital and five community hospitals. PATIENTS: Consecutive medical and surgical critically ill patients were enrolled between April 1, 2012, and February 1, 2015. INTERVENTIONS: Multifaceted, three-phase (baseline, delirium screening, and guideline) implementation program of delirium guidelines in adult ICUs. MEASUREMENTS AND MAIN RESULTS: The primary outcome was adherence changes to delirium guidelines recommendations, based on the Pain, Agitation and Delirium guidelines. Secondary outcomes were brain dysfunction (delirium or coma), length of ICU stay, and hospital mortality. A total of 3,930 patients were included. Improvements after the implementation pertained to delirium screening (from 35% to 96%; p < 0.001), use of benzodiazepines for continuous sedation (from 36% to 17%; p < 0.001), light sedation of ventilated patients (from 55% to 61%; p < 0.001), physiotherapy (from 21% to 48%; p < 0.001), and early mobilization (from 10% to 19%; p < 0.001). Brain dysfunction improved: the mean delirium duration decreased from 5.6 to 3.3 days (-2.2 d; 95% CI, -3.2 to -1.3; p < 0.001), and coma days decreased from 14% to 9% (risk ratio, 0.5; 95% CI, 0.4-0.6; p < 0.001). Other clinical outcome measures, such as length of mechanical ventilation, length of ICU stay, and hospital mortality, did not change. CONCLUSIONS: This large pre-post implementation study of delirium-oriented measures based on the 2013 Pain, Agitation, and Delirium guidelines showed improved health professionals' adherence to delirium guidelines and reduced brain dysfunction. Our findings provide empirical support for the differential efficacy of the guideline bundle elements in a real-life setting and provide lessons for optimization of guideline implementation programs.

Attitudes, knowledge and practices concerning delirium: a survey among intensive care unit professionals.

BACKGROUND: Delirium is a common form of vital organ dysfunction in intensive care unit (ICU) patients and is associated with poor outcomes. Adherence to guideline recommendations pertaining to delirium is still suboptimal. AIMS: We performed a survey aimed at identifying barriers for implementation that should be addressed in a tailored implementation intervention targeted at improved ICU delirium guideline adherence. DESIGN: The survey was conducted among ICU professionals. METHODS: An online survey was conducted among 360 ICU health care professionals (nurses, physicians and delirium consultants) from six ICUs in the southwest of the Netherlands as part of a multicentre prospective implementation project [response rate: 64% of 565 invited; 283 (79%) were nurses]. RESULTS: Although the majority (83%) of respondents considered delirium a common and major problem in the ICU, we identified several barriers for implementation of a delirium guideline. The most important barriers were knowledge deficit, low delirium screening rate, lack of trust in the reliability of delirium screening tools, belief that delirium is not preventable, low familiarity with delirium guidelines, low satisfaction with physician-described delirium management, poor collaboration between nurses and physicians, reluctance to change delirium care practices, lack of time, disbelief that patients would receive optimal care when adhering to the guideline and the perception that the delirium guideline is cumbersome or inconvenient in daily practice. CONCLUSION: Although ICU professionals consider delirium a serious problem, several important barriers to adhere to guidelines on delirium management are still present today. RELEVANCE TO CLINICAL PRACTICE: Identification of implementation barriers for adherence to guidelines pertaining to delirium is feasible with a survey. Results of this study may help to design-targeted implementation strategies for ICU delirium management.