A Comparison of Remifentanil and Dexmedetomidine for Craniotomy Perioperative Hemodynamics and Postoperative Pain

Study Overview
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Brief Summary
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This will be a randomized blinded clinical trial. Patients will be randomized to receive either a remifentanil or dexmedetomidine infusion for general anesthesia. The anesthesia team will know the result of randomization at induction. Data will be gathered by research personnel who will be blinded to the anesthetic method used. Patients will be blinded to the anesthetic they receive till they are discharged from the PACU when they will have the option to be unblinded. The Data Safety and -Toxicity Committee will review all serious adverse events and toxicity reports as well as annual reviews.

Detailed Description
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Anesthesia for craniotomy presents a unique challenge to the anesthesiologist. Anesthesia for neurosurgical procedures should provide optimal surgical conditions while maintaining appropriate cerebral oxygen supply and stable systemic hemodynamics. (1) It is important to prevent patient response to noxious stimuli during the procedure like pinning, drilling of the bone, opening and manipulation of the dura etc., avoid coughing and bucking during surgery and during extubation thus necessitating a deeper level of anesthesia and analgesia. At the same time it is desirable to have the patient fully awake toward the end of the surgery in order to facilitate neurologic evaluation. Management of the above presents a challenge during induction, maintenance and extubation and also during multiple critical stages of surgery Fear of the side effects of analgesic drugs frequently leads to the under-treatment of post-craniotomy pain. (2) Nevertheless, this pain continues to be commonly observed, is frequently severe, and, if unrelieved, may cause distress for the neurosurgical patient and serious complications for the operative brain. (2) There is a need for larger trials to delineate safety and efficacy of analgesic therapies with a focus on short- and long-term outcomes.

Official Title
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A Comparison of Remifentanil and Dexmedetomidine for Craniotomy Perioperative Hemodynamics and Postoperative Pain

Conditions
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Adult Intracranial Tumor, Adult Solid Tumor

Intervention / Treatment
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* Drug: Remifentanil
* Drug: Dexmedetomidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who undergo general anesthesia for elective surgical excision of a brain tumor with following specifications: Age: Older than 18 Primary and redo cases will be included Duration of surgery not exceeding 6 hrs. Exclusion Criteria: Patient refusal Emergency craniotomy Morbid obesity Uncontrolled hypertension - DBP more than 110 Cardiac conduction defects Patients with chronic pain.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Remifentanil<br>Remifentanil 0.08-0.15MCG/KG/MIN INFUSION THROUGHOUT PROCEDURE BASED ON HEMODYNAMICS | Drug: Remifentanil<br>* Remifentanil 0.08-0.15MCG/KG/MIN INFUSION THROUGHOUT PROCEDURE BASED ON HEMODYNAMICS<br>* Other names: Ultiva, G187084B;|
| Active Comparator: Dexmedetomidine<br>a loading dose of dexmedetomidine was given at 0.5 to 1 micrograms/kg ideal body weight over 15 minutes, followed by an infusion at 0.2 to 0.7 micrograms/kg/hour. | Drug: Dexmedetomidine<br>* a loading dose of dexmedetomidine was given at 0.5 to 1 micrograms/kg ideal body weight over 15 minutes, followed by an infusion at 0.2 to 0.7 micrograms/kg/hour.<br>* Other names: Precedex, Dexmedetomidine Hydrochloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemodynamics | Hemodynamics were defined as mean arterial pressure (MAP), measured in milimeters of mercury (mmHg). This outcome was analyzed using a repeated measures ANOVA approach. In the outcome measure data table, mean ± standard deviation MAP was reported as the aggregate mean across time points. | 15, 30, 45, 60, and 90 minutes after extubation. | 
| Postoperative Pain | Pain was measured using the visual analogue scale (VAS), where 0 is defined as no pain and 10 is defined as worst pain imaginable. This outcome was analyzed using a repeated measures ANOVA approach. In the outcome measure data table, mean ± standard deviation pain was reported as the aggregate mean across time points. | 15, 30, 45, 60, and 90 minutes after extubation. | 
| Total Opioid Consumption | Total opioid consumption was defined as the sum of all opioid doses given within the first 90 minutes after surgery, converted to milligram morphine equivalents. | Initial 90 minutes of recover after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart Rate | Heart rate was determined from the arterial catheter and measured as beats per minute. This outcome was analyzed using a repeated measures ANOVA approach. | 15, 30, 45, 60, and 90 minutes after extubation. | 
| Modified Short Orientation Memory Concentration Test (SOMCT) | The Modified Short Orientation Memory Concentration Test (SOMCT) is a validated questionnaire that discriminates among mild, moderate, and severe cognitive deficits. SOMCT is based on 6 questions and produces a total score ranging from 0 (worst possible function) to 28 (best possible function). Scores > 20 are considered normal. This outcome was analyzed using a repeated measures ANOVA approach. | 15, 30, 45, 60, and 90 minutes after extubation. | 
| Aldrete Score | The Aldrete score measured level of sedation and fitness and is used to assess the appropriate departure time from the post anesthesia care unit. The score ranges from 0 to 10, where 0 indicates poor fitness (and such patients are transferred to the ICU), while 10 indicates good fitness. This outcome was analyzed using a repeated measures ANOVA approach. | 15, 30, 45, 60, and 90 minutes after extubation. | 
| Nursing Workload Comparison | To evaluate the nurses workload when either of the two drugs are given in terms Nursing Research Usage form's therapeutic index scoring system. This score ranges from 0 (minimal interventions and time spent by nurses on study patient) to 22 (maximum interventions and time spent by nurses on the study patient). | 90 minutes after extubation | 
| Drug Stop Time to Open Eyes | time until patient first opened their eyes, squeezed a hand, or wiggled their toes in response to verbal commands after surgery | Anesthesia drug stop time to open eyes. Time is measured continuously until patients eyes open, regardless of how long it takes. | 
| Drug Stop Time to Recall | Time between extubation until patients could say their names. | Time between extubation until patients could say their names. | 
| Drug Stop Time to Fitness to Discharge |  | Anesthesia drug stop time to fitness to discharge. Time is measured continuously until fitness for discharge is reached, regardless of how long it takes. | 
| End Case to Post Anesthesia Care Unit (PACU) Discharge | Post Anesthesia Care Unit (PACU) Discharge time is the timing at which patients are discharged from the PACU. This outcome is the amount of time (minutes) from end case to PACU discharge. | End case to post anesthesia care unit (PACU) discharge. Time is measured continuously until PACU discharge, regardless of how long it takes. | 
| Postoperative Nausea | Indicator of whether patients had nausea or not | Whether patients had nausea or not, from anesthesia stop time until hospital discharge. | 
| Postoperative Vomitting | Indicator of whether patients had postoperative vomiting. | Whether patients had vomiting or not, from anesthesia stop time until hospital discharge. | 
| Postoperative Shivering | Indicator of whether patients had postoperative shivering. | Whether patients had postoperative or not, from anesthesia stop time until hospital discharge. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Craniotomy, pain relief, Adult solid neoplasm