Impact Dexmedetomidine on Postoperative Delirium in Patients After Intracranial Operation for Brain Tumor

Impact of Prophylactic Use of Dexmedetomidine on Postoperative Delirium in Patients After Intracranial Operation for Brain Tumor: a Pilot Randomized Controlled Trial

Postoperative delirium is one of the most common serious complications after major surgery and is associated with undesirable consequences. Prevention of postoperative delirium is recommended in the clinical guidelines and consensus statements. Dexmedetomidine, a highly selective α2-adrenergic receptor agonist, has been investigated as a pharmacological intervention to prevent postoperative delirium. Several randomized controlled trials have shown that prophylactic use of low-dose dexmedetomidine may decrease the incidence of postoperative delirium in patients after cardiac and non-cardiac operations. However, neurosurgical patients are often excluded from previous studies due to potential consciousness and cognition impairment. The investigators design this pilot study aiming to clarify the feasibility and safety of use of low-dose dexmedetomidine for prevention of postoperative delirium in patients after intracranial operation for brain tumor.

Study Overview

• Status: Completed
• Conditions: Central Nervous System Diseases
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Normal saline group

Detailed Description

Postoperative delirium is one of the most common serious complications after major surgery and is associated with undesirable consequences. Prevention of postoperative delirium is recommended in the clinical guidelines and consensus statements. Dexmedetomidine, a highly selective α2-adrenergic receptor agonist, has been investigated as a pharmacological intervention to prevent postoperative delirium. Several randomized controlled trials have shown that prophylactic use of low-dose dexmedetomidine (0.1 ug/kg/hour without loading infusion) may decrease the incidence of postoperative delirium in patients after cardiac and non-cardiac operations. However, neurosurgical patients are often excluded from previous studies due to potential consciousness and cognition impairment. The investigators design this pilot randomized controlled trial aiming to clarify the feasibility and safety of use of low-dose dexmedetomidine for prevention of postoperative delirium in patients after intracranial operation for brain tumor.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • ICU, Beijing Tiantan Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients after elective intracranial operation for brain tumor under general anesthesia and who are admitted to the ICU directly from the operating room or postoperative care unit.

Exclusion Criteria:

• age under 18 years;
• admitted to the ICU after 22:00 PM;
• medical records documented preoperative history of mental or cognitive disorders including schizophrenia, epilepsy, Parkinsonism, or dementia;
• medical records documented inability to communicate in the preoperative period due to coma or language barrier;
• history of drug abuse of psychoactive and anesthetic drugs;
• known preoperative severe bradycardia (lower than 50 beats/min), sick sinus syndrome, second- or third-degree atrioventricular block, or left ventricular ejection fraction lower than 30%;
• serious hepatic dysfunction defined as Child-Pugh class C;
• severe renal dysfunction requiring renal replacement therapy before the surgery;
• allergies to ingredients or components of dexmedetomidine hydrochloride;
• American Society of Anesthesiologists classification of IV to VI;
• moribund condition with low likelihood of survival for more than 24 hours;
• pregnancy or lactation women;
• current enrollment in another clinical trial;
• refusal to participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Normal saline group; Continuously intravenous infusion of normal saline at a rate of 0.025 ml/kg/hour started immediately after enrollment until 08:00 AM on the postoperative day one.	Drug: Normal saline group; Normal saline is also diluted with normal saline to 50 ml and is continuously intravenous infused at a rate of 0.025 ml/kg/hour, which is the same with the dexmedetomidine group. The intravenous infusion begins immediately after enrollment until 08:00 AM on the postoperative day one.; Other Names: 0.9% Sodium Chloride
Experimental: Dexmedetomidine group; Continuously intravenous infusion of dexmedetomidine hydrochloride at a rate of 0.1 μg/ kg/hour (0.025 ml/kg/hour) started immediately after enrollment until 08:00 AM on the postoperative day one.	Drug: Dexmedetomidine; Dexmedetomidine hydrochloride (200 μg/2 ml) is diluted with normal saline to 50 ml and is continuously intravenous infused at a rate of 0.025 ml/kg/hour (dexmedetomidine 0.1 μg/kg/hour). The intravenous infusion begins immediately after enrollment until 08:00 AM on the postoperative day one.; Other Names: Dexmedetomidine hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of study agent interruption during the study	Predicted adverse events in the present study included bradycardia (defined as heart rate lower than 50 beats/min), hypotension (defined as systolic blood pressure lower than 90 mmHg), tachycardia (defined as heart rate greater than 100 beats/min), hypertension (defined as systolic blood pressure greater than 160 mmHg) and hypoxemia (defined as pulse oxygen saturation lower than 90%). The treatment of adverse events was determined by the responsible attending ICU physicians, who could stop the study agent infusion when the treatment failure or other conditions deemed necessary.	From the start of study agent infusion to postoperative day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from the end of operation to randomization	Time from the end of operation to randomization	From the end of operation until the randomization, assessed up to 24 hours
Duration of study agent infusion	Duration of study agent infusion	From the start of study agent infusion to postoperative day 1
Incidence of adverse events from the start of study agent infusion until 24 hours or until ICU discharge	Include bradycardia (defined as heart rate lower than 55 beats/min), hypotension (defined as systolic blood pressure lower than 90 mmHg), and hypoxemia (defined as pulse oxygen saturation lower than 90%)	From the start of study agent infusion to postoperative day 1
Non-delirium complications	Include airway obstruction and apnea, respiratory failure, cardiac events, coma, epilepsy, cerebral hemorrhage or infarction, renal injury and infection	From the start of study agent infusion to postoperative day 28

Collaborators and Investigators

• Sponsor: Capital Medical University
• Investigators: Study Chair: Jian-Xin Zhou, MD, Capital Medical University

Publications and helpful links

General Publications

• He X, Cheng KM, Duan YQ, Xu SS, Gao HR, Miao MY, Li HL, Chen K, Yang YL, Zhang L, Gu HQ, Zhou JX. Feasibility of low-dose dexmedetomidine for prevention of postoperative delirium after intracranial operations: a pilot randomized controlled trial. BMC Neurol. 2021 Dec 4;21(1):472. doi: 10.1186/s12883-021-02506-z.

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2020
• Primary Completion (Actual): December 12, 2020
• Study Completion (Actual): December 21, 2020

Study Registration Dates

• First Submitted: July 28, 2020
• First Submitted That Met QC Criteria: July 29, 2020
• First Posted (Actual): July 31, 2020

Study Record Updates

• Last Update Posted (Actual): January 12, 2021
• Last Update Submitted That Met QC Criteria: January 10, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: delirium; prevention; dexmedetomidine; postoperative; intracranial operation
• Additional Relevant MeSH Terms: Mental Disorders; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Nervous System Diseases; Central Nervous System Diseases; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: KY2019-091-02A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No