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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University Health Network, Toronto
Sponsor:
Information provided by (Responsible Party):
Nicolai Goettel, University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01545297
First received: February 29, 2012
Last updated: January 24, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention
Brain Tumor
Drug: Dexmedetomidine
Drug: Propofol
Drug: Remifentanil

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Comparison of Dexmedetomidine and Propofol-Remifentanil Conscious Sedation for Awake Craniotomy for Tumor Surgery: a Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Ability to perform intra-operative mapping during awake craniotomy [ Time Frame: immediately, intra-operative ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of complications (respiratory depression, failure to provide adequate analgesia) [ Time Frame: intra-operatively, 2h post-operatively, 24h post-operatively ] [ Designated as safety issue: No ]
  • Patient and surgeon satisfaction to the corresponding anesthetic technique [ Time Frame: intra-opeartively, 2h post-operatively, 24h post-operatively ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: November 2012
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Drug: Propofol
The infusion begins at propofol 25-250 mcg/kg/min for 15 min, and then titrated to effect.
Other Name: Diprivan (TM)
Drug: Remifentanil
The infusion begins at remifentanil 0.01-0.1 mcg/kg/min for 15 min, and then titrated to effect.
Other Name: Ultiva (TM)
Experimental: 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.
Drug: 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.
Other Name: Precedex (TM)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01545297

Contacts
Contact: Nicolai Goettel, MD +41 61 556 52 28 nicolai.goettel@usb.ch

Locations
Canada, Ontario
UHN Toronto Western Hospital Recruiting
Toronto, Ontario, Canada, M5T 2S8
Contact: Nicolai Goettel, MD    +41 61 556 52 28    nicolai.goettel@usb.ch   
Principal Investigator: Pirjo Manninen, MD         
Sub-Investigator: Nicolai Goettel, MD         
Sponsors and Collaborators
Nicolai Goettel
Investigators
Principal Investigator: Pirjo Manninen, MD, FRCPC Head of Neuroanesthesia, Associate Professor, University Health Network, Department of Anesthesia, University of Toronto, Canada
Study Director: Nicolai Goettel, MD University Health Network, Department of Anesthesia, University of Toronto, Canada
  More Information

Publications:

Responsible Party: Nicolai Goettel, MD, University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01545297     History of Changes
Other Study ID Numbers: 11-0607-A
Study First Received: February 29, 2012
Last Updated: January 24, 2014
Health Authority: Canada: Health Canada

Keywords provided by University Health Network, Toronto:
dexmedetomidine
conscious sedation
awake craniotomy
brain mapping

Additional relevant MeSH terms:
Propofol
Remifentanil
Dexmedetomidine
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Analgesics, Opioid
Narcotics
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Analgesics, Non-Narcotic
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014