Dexmedetomidine for Prevention of Postoperative Delirium After Intracranial Operation for Brain Tumor

Study Overview
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Brief Summary
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Postoperative delirium is common after major surgery, and is associated with adverse outcomes. Systematic reviews and meta-analyses of randomized controlled trials have shown that perioperative administration of dexmedetomidine may decrease the incidence of postoperative delirium in patients after either cardiac or non-cardiac surgery. However, neurosurgical patients are often excluded in clinical trials of postoperative delirium. In this prospective, multicenter, randomized, double-blinded, and placebo-controlled trial with two parallel arms, ICU admitted adult patients after intracranial operation for brain tumor will be enrolled. Low-dose dexmedetomidine will be applied during the early postoperative phase. The investigators aim to evaluate the efficacy and safety of low-dose dexmedetomidine for prevention of postoperative delirium in this patient population. The primary hypothesis is that, compared to the placebo group, the prophylactic use of low-dose dexmedetomidine can decrease the incidence of postoperative delirium without significant adverse events in patients after intracranial operation for brain tumor.

Detailed Description
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Postoperative delirium is common after major surgery, and is associated with adverse outcomes. However, patients with neurological illness are usually excluded from previous researches. Recently, limited studies have shown that the incidence of postoperative delirium in neurosurgical patients is approximately 20%, which is comparable to the results in other major surgery. Potential associations between postoperative delirium and adverse outcomes have also been found in neurosurgical patients. These results indicate that early prevention of postoperative delirium should be employed in this population. As a highly selective α2-adrenergic receptor agonist, dexmedetomidine has been investigated as a preventive agent for postoperative delirium. Systematic reviews and meta-analyses of randomized controlled trials have shown that perioperative administration of dexmedetomidine may decrease the incidence of postoperative delirium in patients after either cardiac or non-cardiac surgery. However, neurosurgical patients are often excluded in clinical trials of postoperative delirium. In this prospective, multicenter, randomized, double-blinded, and placebo-controlled trial with two parallel arms, ICU admitted adult patients after intracranial operation for brain tumor will be enrolled. Low-dose dexmedetomidine will be applied during the early postoperative phase. The investigators aim to evaluate the efficacy and safety of low-dose dexmedetomidine for prevention of postoperative delirium in this patient population. The primary hypothesis is that, compared to the placebo group, the prophylactic use of low-dose dexmedetomidine can decrease the incidence of postoperative delirium without significant adverse events in patients after intracranial operation for brain tumor.

Official Title
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Dexmedetomidine for Prevention of Postoperative Delirium in Patients After Intracranial Operation for Brain Tumor: a Multicenter Randomized Controlled Trial

Conditions
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Central Nervous System Diseases

Intervention / Treatment
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* Drug: Dexmedetomidine
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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The inclusion criteria are 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. The exclusion criteria include: 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 sinus 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 (Child-Pugh class C); Severe renal dysfunction requiring renal replacement therapy before the surgery; Allergies to ingredients or components of 5-[(1S)-1-(2,3-dimethylphenyl)ethyl]-1H-imidazole (dexmedetomidine hydrochloride); American Society of Anesthesiologists (ASA) classification of IV to VI; Moribund condition with low likelihood of survival for more than 24 hours; Pregnancy or lactation women; Current enrolment in another clinical trial; Refuse to participate.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexmedetomidine group<br>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<br>* 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.<br>* Other names: Dexmedetomidine hydrochloride;|
| Placebo Comparator: Normal saline group<br>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<br>* 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.<br>* Other names: 0.9% Sodium Chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of postoperative delirium | Postoperative delirium is defined as delirium within 5 postoperative days, which is diagnosed by the Confusion Assessment Method for the ICU (CAM-ICU) evaluated twice daily (8:00-10:00 AM, and 18:00-20:00 PM). | From postoperative day 1 to day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of adverse events | 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 | 
| The incidence of 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 | 
| Length of stay in the ICU | Time of ICU discharge | From the start of study agent infusion to postoperative day 28 | 
| Length of stay in hospital | Time of hospital discharge | From the start of study agent infusion to postoperative day 28 | 
| The incidence of all-caused deaths after the operation | All of the deaths that occur after the study agent infusion | From the start of study agent infusion to postoperative day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dexmedetomidine, delirium, postoperative, intracranial operation, prevention