Combination of Haloperidol and Magnesium for Delirium Prevention in Critically Ill Elderly

Combination of Haloperidol and Magnesium for Delirium Prevention in Critically Ill Elderly Patients After Elective Major Surgery

Objective: The aim of this randomized double blinded study is to investigate the effectiveness and safety of the prophylactic use of haloperidol with or without magnesium (Mg) for delirium in high risk elderly patients postoperatively.

Patients and methods: 135 patients aged ≥ 65< 80 years old with PRE-DELIRIC Score 50% or more (20) were admitted to the ICU non-intubated following major non cardiac surgeries randomized into 3 groups, Group I received 1 mg haloperidol intravenously 3 times daily and magnesium sulfate 4 g intravenous infusion (IVI) in 1st day (diluted in 50 ml D5W over 24 hours) then 2g IVI over 24 hours (diluted in 50 ml D5W over 24 hours) for 3 days, Group II received 1 mg haloperidol intravenously 3 times ,Group III received 1 mL 0.9% of sodium chloride intravenously 3 times daily. The primary outcome of the study will be the incidence of delirium.

Study Overview

• Status: Completed
• Conditions: Delirium in Old Age
• Intervention / Treatment: Drug: Haloperidol Injection

Detailed Description

This prospective randomized double-blind placebo-controlled study will be conducted in Ain Shams university surgical ICU on 135 patients aged ≥ 65< 80 years old with PRE-DELIRIC Score 50% or more (20) who are admitted to the ICU non-intubated following major non cardiac surgeries and anticipated intensive care unit (ICU) stay of at least 2 days as estimated by the attending intensivist after the approval of the research ethical committee and obtaining patients' or patients ' relatives written informed consent.

The study medications are continued until ICU discharge or until delirium occurred. In the latter case, study medications are stopped, and patients could be treated with dexmedetomidine.

For delirium prevention non-pharmacological interventions are also implemented like early mobilization, improving patient circadian rhythm, noise reduction are parts of the daily ICU care.

Patients will receive fentanyl infusion for analgesia. Those patients achieving a RASS score of ± 1 or 0 are monitored daily for delirium using the Confusion Assessment Method for the ICU (CAM-ICU). Patients are diagnosed with delirium if they have at least 1 positive CAM-ICU without RASS -4/-5 during a complete day. Clinicians collecting data on delirium are all experienced in delirium assessment using the CAM-ICU. All patients are screened at least three times daily, and more often if required.

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Ainshams university hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- PRE-DELIRIC Score 50% or more (20) who are admitted to the ICU non-intubated following major non cardiac surgeries and anticipated intensive care unit (ICU) stay of at least 2 days as estimated by the attending intensivist

Exclusion Criteria:

• sustained RASS of -4/-5 during the complete ICU admission
• primary neurologic event/injury with GCS ≤ 9 during the first 48 hours of ICU
• delirium prior to inclusion, Parkinson disease, dementia, alcohol abuse, an acute neurological condition, history of a psychiatric disease and use of antipsychotic agents
• history of clinically relevant ventricular arrhythmia in the last 12 months, QTc time of at least 500 milliseconds
• recent MI or cardiac decompensation, 2nd or 3rd AV block
• Known allergy or intolerance to haloperidol or magnesium sulphate.
• 80 years or older, had a body weight of 50 kg or less, or had liver failure (serum bilirubin level >2.9 mg/dL) or serum creatinine level >150 μmol/L
• Intubated patients at the time of ICU admission.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group I (number of patients = 45): will receive 1 mg haloperidol intravenously 3 times daily and magnesium sulfate 4 g intravenous infusion (IVI) in 1st day (diluted in 50 ml D5W over 24 hours) then 2g IVI over 24 hours (diluted in 50 ml D5W over 24 hours) for 3 days postoperatively starting the first dose 2- 4 hours after surgery. If the first prophylactic dose is delayed for more than 4 hours post admission, patient is excluded from the study.	Drug: Haloperidol Injection; to evaluate the efficacy and safety of short-term intravenous combination of low-dose haloperidol and magnesium for delirium prevention in critically ill elderly patients after elective major surgery.; Other Names: Magnesium Sulphate
Experimental: Group II (number of patients= 45): will receive 1 mg haloperidol intravenously 3 times daily and 50 ml of D5W IVI infusion over 24 hours for 4 days postoperatively starting the first dose 2- 4 hours after surgery.	Drug: Haloperidol Injection; to evaluate the efficacy and safety of short-term intravenous combination of low-dose haloperidol and magnesium for delirium prevention in critically ill elderly patients after elective major surgery.; Other Names: Magnesium Sulphate
Placebo Comparator: Group III (number of patients = 45); will receive 1 mL 0.9% of sodium chloride intravenously 3 times daily and 50 ml of D5W IVI infusion for 4 days postoperatively starting the first dose 2- 4 hours after surgery.	Drug: Haloperidol Injection; to evaluate the efficacy and safety of short-term intravenous combination of low-dose haloperidol and magnesium for delirium prevention in critically ill elderly patients after elective major surgery.; Other Names: Magnesium Sulphate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the incidence of delirium	Patients will receive fentanyl infusion for analgesia. Those patients achieving a RASS score of ± 1 or 0 are monitored daily for delirium using the Confusion Assessment Method for the ICU (CAM-ICU). Patients are diagnosed with delirium if they have at least 1 positive CAM-ICU without RASS -4/-5 during a complete day.	for 3 days postoperatively starting the first dose 2- 4 hours after surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The occurrence of extra-pyramidal symptoms.	The occurrence of extra-pyramidal symptoms, such as dystonia, tremor, myoclonus, tics, rigidity, and akathisia.	during 3 days postoperative

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Actual): October 24, 2023
• Study Completion (Actual): November 4, 2023

Study Registration Dates

• First Submitted: December 5, 2023
• First Submitted That Met QC Criteria: December 5, 2023
• First Posted (Estimated): December 13, 2023

Study Record Updates

• Last Update Posted (Estimated): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Dopamine Agents; Dopamine Antagonists; Anticonvulsants; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Anti-Dyskinesia Agents; Magnesium Sulfate; Haloperidol; Haloperidol decanoate
• Other Study ID Numbers: FMASU R168/2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: share the protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes