Comparison of Dexmedetomidine and Propofol-Remifentanil Conscious Sedation for Awake Craniotomy for Tumor Surgery
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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N/A |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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 Names:
Drug: Remifentanil
The infusion begins at remifentanil 0.01-0.1 mcg/kg/min for 15 min, and then titrated to effect.
Other Names:
|
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 Names:
|
Outcome Measures
Primary Outcome Measures
- Ability to perform intra-operative mapping during awake craniotomy [immediately, intra-operative]
Secondary Outcome Measures
- Incidence of complications (respiratory depression, failure to provide adequate analgesia) [intra-operatively, 2h post-operatively, 24h post-operatively]
- Patient and surgeon satisfaction to the corresponding anesthetic technique [intra-opeartively, 2h post-operatively, 24h post-operatively]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Adult patients more than 18 years of age.
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ASA score I, II and III.
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Patients scheduled to undergo awake craniotomy for elective tumor resection.
Exclusion Criteria:
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Patients with allergies to the drugs being used.
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Patients who are pregnant.
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Patients with alcohol or substance abuse.
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Patients who are not able to understand the instructions for an awake craniotomy and questions regarding intra-operative pain, and post-operative satisfaction.
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Lack of informed consent.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | UHN Toronto Western Hospital | Toronto | Ontario | Canada | M5T 2S8 |
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
Study Documents (Full-Text)
None provided.More Information
Publications
- Bamgbade OA, Alfa JA. Dexmedetomidine anaesthesia for patients with obstructive sleep apnoea undergoing bariatric surgery. Eur J Anaesthesiol. 2009 Feb;26(2):176-7. doi: 10.1097/EJA.0b013e32831a47cb.
- Bekker AY, Kaufman B, Samir H, Doyle W. The use of dexmedetomidine infusion for awake craniotomy. Anesth Analg. 2001 May;92(5):1251-3.
- Berkenstadt H, Perel A, Hadani M, Unofrievich I, Ram Z. Monitored anesthesia care using remifentanil and propofol for awake craniotomy. J Neurosurg Anesthesiol. 2001 Jul;13(3):246-9.
- Bhana N, Goa KL, McClellan KJ. Dexmedetomidine. Drugs. 2000 Feb;59(2):263-8; discussion 269-70.
- Blanshard HJ, Chung F, Manninen PH, Taylor MD, Bernstein M. Awake craniotomy for removal of intracranial tumor: considerations for early discharge. Anesth Analg. 2001 Jan;92(1):89-94.
- Chawla S, Robinson S, Norton A, Esterman A, Taneerananon T. Peri-operative use of dexmedetomidine in airway reconstruction surgery for obstructive sleep apnoea. J Laryngol Otol. 2010 Jan;124(1):67-72. doi: 10.1017/S002221510999123X. Epub 2009 Oct 26.
- Chernik DA, Gillings D, Laine H, Hendler J, Silver JM, Davidson AB, Schwam EM, Siegel JL. Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol. 1990 Aug;10(4):244-51.
- Cheung CW, Ying CL, Chiu WK, Wong GT, Ng KF, Irwin MG. A comparison of dexmedetomidine and midazolam for sedation in third molar surgery. Anaesthesia. 2007 Nov;62(11):1132-8.
- Coles JP, Leary TS, Monteiro JN, Brazier P, Summors A, Doyle P, Matta BF, Gupta AK. Propofol anesthesia for craniotomy: a double-blind comparison of remifentanil, alfentanil, and fentanyl. J Neurosurg Anesthesiol. 2000 Jan;12(1):15-20.
- Conte V, Magni L, Songa V, Tomaselli P, Ghisoni L, Magnoni S, Bello L, Stocchetti N. Analysis of propofol/remifentanil infusion protocol for tumor surgery with intraoperative brain mapping. J Neurosurg Anesthesiol. 2010 Apr;22(2):119-27. doi: 10.1097/ANA.0b013e3181c959f4.
- Coursin DB, Coursin DB, Maccioli GA. Dexmedetomidine. Curr Opin Crit Care. 2001 Aug;7(4):221-6. Review.
- From RP, Warner DS, Todd MM, Sokoll MD. Anesthesia for craniotomy: a double-blind comparison of alfentanil, fentanyl, and sufentanil. Anesthesiology. 1990 Nov;73(5):896-904.
- Johnson KB, Egan TD. Remifentanil and propofol combination for awake craniotomy: case report with pharmacokinetic simulations. J Neurosurg Anesthesiol. 1998 Jan;10(1):25-9. Erratum in: J Neurosurg Anesthesiol 1998 Apr;10(2):69.
- Kamibayashi T, Maze M. Clinical uses of alpha2 -adrenergic agonists. Anesthesiology. 2000 Nov;93(5):1345-9. Review.
- Mack PF, Perrine K, Kobylarz E, Schwartz TH, Lien CA. Dexmedetomidine and neurocognitive testing in awake craniotomy. J Neurosurg Anesthesiol. 2004 Jan;16(1):20-5.
- Manninen PH, Balki M, Lukitto K, Bernstein M. Patient satisfaction with awake craniotomy for tumor surgery: a comparison of remifentanil and fentanyl in conjunction with propofol. Anesth Analg. 2006 Jan;102(1):237-42.
- Nelson LE, Lu J, Guo T, Saper CB, Franks NP, Maze M. The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology. 2003 Feb;98(2):428-36.
- Oda Y, Toriyama S, Tanaka K, Matsuura T, Hamaoka N, Morino M, Asada A. The effect of dexmedetomidine on electrocorticography in patients with temporal lobe epilepsy under sevoflurane anesthesia. Anesth Analg. 2007 Nov;105(5):1272-7, table of contents.
- Ramsay MA, Saha D, Hebeler RF. Tracheal resection in the morbidly obese patient: the role of dexmedetomidine. J Clin Anesth. 2006 Sep;18(6):452-4.
- Sarang A, Dinsmore J. Anaesthesia for awake craniotomy--evolution of a technique that facilitates awake neurological testing. Br J Anaesth. 2003 Feb;90(2):161-5.
- Serletis D, Bernstein M. Prospective study of awake craniotomy used routinely and nonselectively for supratentorial tumors. J Neurosurg. 2007 Jul;107(1):1-6.
- Silbergeld DL, Mueller WM, Colley PS, Ojemann GA, Lettich E. Use of propofol (Diprivan) for awake craniotomies: technical note. Surg Neurol. 1992 Oct;38(4):271-2.
- Souter MJ, Rozet I, Ojemann JG, Souter KJ, Holmes MD, Lee L, Lam AM. Dexmedetomidine sedation during awake craniotomy for seizure resection: effects on electrocorticography. J Neurosurg Anesthesiol. 2007 Jan;19(1):38-44.
- Venn RM, Bradshaw CJ, Spencer R, Brealey D, Caudwell E, Naughton C, Vedio A, Singer M, Feneck R, Treacher D, Willatts SM, Grounds RM. Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia. 1999 Dec;54(12):1136-42.
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