Central Nervous System Diseases
Conditions
Keywords
dexmedetomidine, delirium, postoperative, intracranial operation, prevention
Brief summary
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
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.
Interventions
DRUGDexmedetomidine
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.
DRUGNormal saline
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.
Sponsors
Capital Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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: 1. Admitted to the ICU after 22:00 PM; 2. Medical records documented preoperative history of mental or cognitive disorders including schizophrenia, epilepsy, Parkinsonism, or dementia; 3. Medical records documented inability to communicate in the preoperative period due to coma or language barrier; 4. History of drug abuse of psychoactive and anesthetic drugs; 5. 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%; 6. Serious hepatic dysfunction (Child-Pugh class C); 7. Severe renal dysfunction requiring renal replacement therapy before the surgery; 8. Allergies to ingredients or components of 5-\[(1S)-1-(2,3-dimethylphenyl)ethyl\]-1H-imidazole (dexmedetomidine hydrochloride); 9. American Society of Anesthesiologists (ASA) classification of IV to VI; 10. Moribund condition with low likelihood of survival for more than 24 hours; 11. Pregnancy or lactation women; 12. Current enrolment in another clinical trial; 13. Refuse to participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The incidence of postoperative delirium | From postoperative day 1 to day 5 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The incidence of all-caused deaths after the operation | From the start of study agent infusion to postoperative day 28 | All of the deaths that occur after the study agent infusion |
| The incidence of non-delirium complications | From the start of study agent infusion to postoperative day 28 | Include airway obstruction and apnea, respiratory failure, cardiac events, coma, epilepsy, cerebral hemorrhage or infarction, renal injury and infection |
| Length of stay in the ICU | From the start of study agent infusion to postoperative day 28 | Time of ICU discharge |
| Length of stay in hospital | From the start of study agent infusion to postoperative day 28 | Time of hospital discharge |
| The incidence of adverse events | From the start of study agent infusion to postoperative day 1 | 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%) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pain intensity | From the start of study agent infusion to postoperative day 1 | Assessed by the critical-care pain observation tool (CPOT) with a total score of 0-8. Higher scores mean a worsening of pain. |
| Subjective sleep quality | From the start of study agent infusion to postoperative day 1 | Assessed by numerical rating scale (NRS) with a total score of 0-10. Higher scores mean a better sleep. |
| The number of patients with the use of sedatives and analgesics | From the start of study agent infusion to postoperative day 1 | Include propofol, midazolam, opioids and nonsteroidal anti-inflammatory drugs |
Countries
China
Contacts
Primary ContactJian-Xin Zhou, MD
Backup ContactXuan He, MD
Outcome results
None listed