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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dexmedetomidine group | Experimental | 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. |
|
| Normal saline group | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexmedetomidine | Drug | 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. |
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| The number of patients with the use of sedatives and analgesics | Include propofol, midazolam, opioids and nonsteroidal anti-inflammatory drugs | From the start of study agent infusion to postoperative day 1 |
| Pain intensity |
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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jian-Xin Zhou, MD | Contact | 8610 59978019 | zhoujx.cn@gmail.com | |
| Xuan He, MD | Contact | hexuan1204@icloud.com |
| Name | Affiliation | Role |
|---|---|---|
| Jian-Xin Zhou, MD | Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University | Beijing | Beijing Municipality | 100070 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33234648 | Derived | He X, Cheng KM, Zhang L, Gu H, Qu X, Xu Y, Ma P, Zhou JX. Dexmedetomidine for the prevention of postoperative delirium in patients after intracranial operation for brain tumours (DEPOD study): a study protocol and statistical plan for a multicentre randomised controlled trial. BMJ Open. 2020 Nov 23;10(11):e040939. doi: 10.1136/bmjopen-2020-040939. |
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| ID | Term |
|---|---|
| D002493 | Central Nervous System Diseases |
| D003693 | Delirium |
| ID | Term |
|---|---|
| D009422 | Nervous System Diseases |
| D003221 | Confusion |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
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| ID | Term |
|---|---|
| D020927 | Dexmedetomidine |
| D000077330 | Saline Solution |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
|
| Normal saline | Drug | 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. |
|
|
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 |
Assessed by the critical-care pain observation tool (CPOT) with a total score of 0-8. Higher scores mean a worsening of pain.
| From the start of study agent infusion to postoperative day 1 |
| Subjective sleep quality | Assessed by numerical rating scale (NRS) with a total score of 0-10. Higher scores mean a better sleep. | From the start of study agent infusion to postoperative day 1 |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D000077324 |
| Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |