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.

[Arterial thrombosis due to heparin induced thrombocytopenia]. / Arteriële trombose door heparine-geïnduceerde trombocytopenie.

BACKGROUND: Type II heparin induced thrombocytopenia (HIT) is a procoagulant disorder that is caused by IgG-antibodies against platelet factor 4 (PF4)-heparin (H) complex. Clotting tendency is also increased. This is characterized by a ≥ 50% decrease in platelet count between 5-10 days after exposure to unfractionated or low-molecular weight heparin. CASE DESCRIPTION: A 49-year-old woman presented with neurological symptoms and pain in her right hand shortly after hospitalisation in Spain. She had an ischaemic CVA and arterial perfusion difficulties in her right arm due to a large thrombus in the aortic arch and some of its branches. She was treated with thrombolytic therapy and dalteparin. Based on initially mild thrombocytopenia that progressed rapidly after admission and her 7-day exposure to enoxaparin during the previous hospital admission, we diagnosed heparin induced thrombocytopenia (HIT) with arterial thrombosis. CONCLUSION: It can be difficult to diagnose HIT. A clinical probability score based on clinical parameters and laboratory results is useful in this. Quick diagnosis and treatment are of great importance because of the high risk of complications.