Comparison of Dexmedetomidine and Propofol-Remifentanil Conscious Sedation for Awake Craniotomy for Tumor Surgery

NCT ID: NCT01545297

Last Updated: 2016-07-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2014-12-31

Brief Summary

Awake craniotomy for resection of brain tumor located in close proximity to areas of eloquent brain function, such as speech, motor and sensory, is an accepted procedure used to minimize neurological injury during resection. During awake craniotomy, anesthesia is usually provided using a combination of local anesthesia (regional scalp block and/or local infiltration) and intravenous (IV) agents to provide sedation, anxiolysis and analgesia. Propofol sedation, commonly in combination with a shorter acting opioid such as fentanyl, or remifentanil, is an effective and popular technique during awake craniotomy, achieving a high degree of patient satisfaction and acceptance. Most of the anesthetic agents are associated with some respiratory depression.

The anesthetic agent called dexmedetomidine is a potent, highly selective α2-adrenoceptor agonist. The effects of dexmedetomidine are anxiolysis, analgesia, sedation and sympatholysis, and it is not associated with respiratory depressive effect. Bekker et al. first reported the successful use of dexmedetomidine in awake craniotomy in 2001.

The purpose of this blinded, prospective, randomized study is to compare the efficacy of dexmedetomidine versus propofol-remifentanil based sedation in patients undergoing awake craniotomy for resection of tumors. The study hypothesis is that the efficacy of performing intra-operative brain mapping is identical between dexmedetomidine and the propofol-remifentanil based sedation. The primary end-points are to assess the ability to perform intraoperative mapping during awake craniotomy. Secondary end-points will assess the incidence of complications (respiratory depression, failure to provide adequate analgesia), as well as patient and surgeon satisfaction to the corresponding anesthetic technique.

Detailed Description

Awake craniotomy for resection of brain tumor located in close proximity to areas of eloquent brain function, such as speech, motor and sensory, is an accepted procedure used to minimize neurological injury during resection. The level of sedation and analgesia during the different stages of surgery varies, but importantly, the patient needs to be awake and alert during brain mapping. During awake craniotomy, anesthesia is usually provided using a combination of local anesthesia (regional scalp block and/or local infiltration) and intravenous (IV) agents to provide sedation, anxiolysis and analgesia. There is considerable variation in the anesthetic management of the awake craniotomy in different institutions. Propofol sedation, commonly in combination with a shorter acting opioid such as fentanyl, or remifentanil, is an effective and popular technique during awake craniotomy, achieving a high degree of patient satisfaction and acceptance. However, the awake craniotomy remains one of the most challenging techniques of anesthesia care in terms of balancing an adequate depth of sedation and analgesia to combat the rapid changes of surgical stimulation yet having an alert patient for brain mapping. Furthermore, most of the anesthetic agents are associated with some respiratory depression.

A newer anesthetic agent called dexmedetomidine (Precedex (TM), Hospira Healthcare Corporation, Saint Laurent, Québec, Canada) is a potent, highly selective α2-adrenoceptor agonist with an α2:α1 selectivity ratio of 1600:1. It has been available in the Canada since 2009 as a short-term sedative agent, and is available in the UHN. The use of dexmedetomidine has been in mechanically ventilated patients in ICU and for intra-operative sedation. The well-documented beneficial effects of dexmedetomidine are anxiolysis, analgesia, sedation and sympatholysis, and it is not associated with respiratory depressive effect.

Dexmedetomidine has been successfully used to provide sedation in dental procedures, awake fibreoptic intubation, bariatric surgery and morbidly obese patients, as well as obstructive sleep apnea patients. The pharmacokinetic properties of dexmedetomidine is very predictable and titratable, with a rapid distribution half-life (t1/2α) being approximately 5-6min and an elimination half-life (t1/2β) of approximately 2h. Bekker et al. first reported the successful use of dexmedetomidine in awake craniotomy in 2001. Subsequent case series published by Souter et al. demonstrated that dexmedetomidine can be used either as a sole agent or in combination with other agents such as fentanyl during seizure foci resection with accurate intraoperative brain mapping.

The hypnotic effect of dexmedetomidine is mediated by the hyperpolarization of noradrenergic neurons in the locus ceruleus, which proposed that dexmedetomidine converges on a natural sleep pathway to exert its sedative effect. Venn and co-workers, as part of a large European multicentre trial investigating dexmedetomidine for postoperative sedation in the ICU, reported that: "Patients are calmly and easily roused from sleep to allow excellent communication and cooperation while intubated and ventilated, and then similarly quickly return to sleep". This unique sedation state is very useful for awake craniotomy, which requires deep level of sedation during painful operative procedures, as well as easily rousable state during mapping of eloquent function.

The purpose of this blinded, prospective, randomized study is to compare the efficacy of dexmedetomidine versus propofol-remifentanil based sedation in patients undergoing awake craniotomy for resection of tumors. The study hypothesis is that the efficacy of performing intra-operative brain mapping is identical between dexmedetomidine and the propofol-remifentanil based sedation. The primary end-points are to assess the ability to perform intraoperative mapping during awake craniotomy. Secondary end-points will assess the incidence of complications (respiratory depression, failure to provide adequate analgesia), as well as patient and surgeon satisfaction to the corresponding anesthetic technique.

Conditions

Brain Tumor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Propofol-Remifentanil

Group I. (propofol/remifentanil): Infusions begin at remifentanil (0.01-0.1 mcg/kg/min) and propofol (25-250 mcg/kg/min) for 15 min, and then titrated to effect.

Group Type: ACTIVE_COMPARATOR

Propofol

Intervention Type: DRUG

The infusion begins at propofol 25-250 mcg/kg/min for 15 min, and then titrated to effect.

Remifentanil

Intervention Type: DRUG

The infusion begins at remifentanil 0.01-0.1 mcg/kg/min for 15 min, and then titrated to effect.

Dexmedetomidine

Group II. (dexmedetomidine): The infusion begins at 0.3-0.4 mcg/kg/hr for 15 min, and then titrated down to 0.1-0.2 mcg/kg/hr.

Group Type: EXPERIMENTAL

Dexmedetomidine

Intervention Type: DRUG

The infusion begins at dexmedetomidine 0.3-0.4 mcg/kg/hr for 15 min, and then titrated down to 0.1-0.2 mcg/kg/hr.

Interventions

Dexmedetomidine

The infusion begins at dexmedetomidine 0.3-0.4 mcg/kg/hr for 15 min, and then titrated down to 0.1-0.2 mcg/kg/hr.

Intervention Type: DRUG

Propofol

The infusion begins at propofol 25-250 mcg/kg/min for 15 min, and then titrated to effect.

Intervention Type: DRUG

Remifentanil

The infusion begins at remifentanil 0.01-0.1 mcg/kg/min for 15 min, and then titrated to effect.

Intervention Type: DRUG

Other Intervention Names

Precedex (TM); Diprivan (TM); Ultiva (TM)

Eligibility Criteria

Inclusion Criteria

• Adult patients more than 18 years of age.
• ASA score I, II and III.
• Patients scheduled to undergo awake craniotomy for elective tumor resection.

Exclusion Criteria

• Patients with allergies to the drugs being used.
• Patients who are pregnant.
• Patients with alcohol or substance abuse.
• Patients who are not able to understand the instructions for an awake craniotomy and questions regarding intra-operative pain, and post-operative satisfaction.
• Lack of informed consent.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nicolai Goettel

OTHER

Sponsor Role: lead

Responsible Party

Nicolai Goettel

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Pirjo Manninen, MD, FRCPC

Role: PRINCIPAL_INVESTIGATOR

Head of Neuroanesthesia, Associate Professor, University Health Network, Department of Anesthesia, University of Toronto, Canada

Nicolai Goettel, MD

Role: STUDY_DIRECTOR

University Health Network, Department of Anesthesia, University of Toronto, Canada

Locations

UHN Toronto Western Hospital

Toronto, Ontario, Canada

Countries

Canada

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Other Identifiers

11-0607-A

Identifier Type: -

Identifier Source: org_study_id