Even with appropriate patient selection, awake craniotomy poses multiple challenges for all persons involved. Close communication between the neurosurgeon and anesthesiologist is critical. A well-planned and executed anesthetic allows for maximum patient comfort, while maintaining a responsive patient for cortical mapping or cognitive testing for language localization (1).
In this report, we discuss the use of dexmedetomidine as a rescue drug during an awake craniotomy for cortical motor mapping and tumor resection. IRB approval and a Health Insurance Portability and Accountability waiver have been obtained for this report.
A 57-yr-old female presented for left parietal craniotomy requiring cortical motor mapping and tumor resection. Her medical history was significant for a left frontal parietal glioblastoma mutiforme initially diagnosed approximately 2 yr earlier. She initially responded well to external beam radiation therapy and temozolomide, a cytotoxic drug used for the treatment of adult patients with refractory malignant glioma. Before surgery, the patient evidenced progression of the tumor by magnetic resonance imaging and a worsening right hemiparesis. She therefore qualified as a candidate for participation in a surgical protocol for patients with recurrent malignant glioma. Two days before the awake craniotomy, she underwent a stereotactic brain biopsy, which demonstrated malignant glioma, and inoculation of an experimental drug (blinded to us at this time) under the protocol guidelines. She tolerated this procedure without problems. When the unpremedicated patient arrived in the operating room standard noninvasive monitors (pulse oximeter, arterial blood pressure cuff, and electrocardiogram electrodes) were placed. Oxygen was provided via a gas-monitoring nasal cannula (Salter Labs, Arvin, CA) at 2 L/min. Anesthesia was induced with a combination of IV infusions of propofol (75 μg · kg–1 · min–1) and remifentanil (0.1 μg · kg-1 · min–1) along with intermittent boluses of propofol (10–20 mg) as needed until loss of lid reflex. Spontaneous ventilation was maintained throughout the procedure. At this point, a right radial arterial line and a Foley catheter were placed. The Mayfield pin headholder was applied after anesthetizing the pin sites with a local anesthetic consisting of equal volumes of 1% lidocaine with epinephrine 1:100000 and 0.25% bupivacaine with epinephrine 1:200000. A six-point scalp block was placed using the same local anesthetic. A total of 20 mL were used for both procedures. The patient was turned to the right decubitus position and held in place with a deflatable beanbag.
Incision, bone flap removal, and dural opening proceeded without incident. The propofol infusion was stopped with bone flap removal, and the patient was awake and cooperative by the end of dural tack-up suture placement. Direct cortical electrical stimulation was performed for mapping of functional primary motor cortex. A constant current biphasic stimulator (Model 512C; Grass Instruments, Quincy, MA) was used with a hand-held bipolar wand freely moved to different locations on the cortex at the surgeon’s discretion. Stimulation variables were 2–5 s duration, frequency of 50 Hz, and pulse width of 200 ms. Currents eliciting motor responses ranged from 4–6 milliamps.
Initial mapping proceeded for approximately 45 min. At this time, the patient began complaining of discomfort in her right side and with her positioning in general. Attempts to alleviate these complaints by increasing the remifentanil infusion rate resulted in decreased respiratory rate, increased end-tidal CO2 partial pressure (ETco2), and increased brain tension as assessed by surgical palpation, which resolved when the patient was asked to take several deep rapid breaths. Arterial blood gas measurements were not obtained during this episode. ETco2 recorded by the gas-monitoring nasal cannula demonstrated a change from 17.7 mm Hg to 19.1 mm Hg. Pulse oximetry remained at 100% throughout this episode. Resumption of the propofol infusion resulted in oversedation and the patient’s inability to participate in the mapping process.
To continue patient participation in the mapping procedure, and to avoid conversion to a general anesthetic, dexmedetomidine was delivered at an infusion rate of 0.20 μg · kg–1 · h–1 IV without bolus loading. Within 5 min, the patient was sedated but able to answer questions and was comfortable. Dexmedetomidine infusion was decreased to 0.15 μg · kg–1 · h–1 and maintained at this rate throughout the remaining cortical mapping. The propofol and the remifentanil infusions were discontinued and never restarted.
Total cortical motor mapping time was 89 min. Tumor resection proceeded without further incident. On several occasions throughout the resection, various areas of the cortex and tumor bed were stimulated. The patient was able to cooperate fully with localization of movement or sensations. After tumor resection, dexmedetomidine infusion was increased to 0.2 μg·kg–1·h–1 and was stopped when the bone flap was replaced. The patient tolerated the procedure well and was awake when leaving the operating room. The next day, she recalled being uncomfortable in the right decubitus position but had no recall of continuing discomfort during the case.
Anesthetic techniques for awake craniotomy vary greatly (2). Propofol and remifentanil infusions during awake craniotomies have been used for cortical mapping during brain tumor resections (3,4). The patients in these two studies experienced excessive sedation, respiratory depression, desaturation, and airway obstruction. Our patient also experienced some of these side effects while receiving propofol and remifentanil infusions.
In 2001 Bekker et al. (5) reported the first use of dexmedetomidine as an adjunct to an asleep-awake technique for craniotomy. As part of a general anesthetic consisting of 70% nitrous oxide/oxygen/sevoflurane (0.3%–0.7%) delivered via a laryngeal mask airway, an initial loading dose of 1 μg/kg was administered over 30 min, followed by an infusion at 0.4 μg·kg–1·h–1. In preparation for awakening, sevoflurane and nitrous oxide were discontinued, the laryngeal mask airway was removed and the dexmedetomidine infusion rate decreased to 0.2 μg·kg–1 ·h–1. Though the dosage required adjustment (decreased to 0.1 μg·kg–1·h–1) secondary to excessive sedation, the technique resulted in a cooperative patient who underwent 2 hours of language localization and subsequent tumor resection with continued testing to assess language.
Bustillo et al. (6) reported a series of five patients sedated with dexmedetomidine for superselective Wada testing for arteriovenous malformation embolization. Two patients received an initial loading dose (1 μg/kg) and continuous infusion (0.2–0.6 μg·kg–1 · h–1), while 3 received only a continuous infusion (0.2–0.7 μg·kg–1·h–1). All patients received fentanyl (160.0 ± 85.2 μg) and midazolam (2.8 ± 1.9 mg) at the start of the case. Because of an inability to undergo cognitive testing, all cases were cancelled.
Mack et al. (7) reported 10 patients who underwent awake craniotomy for neurocognitive testing while receiving varying dosages of dexmedetomidine infusions. Group 1 patients received a general anesthetic and were awakened at the appropriate time. Group 2 patients were sedated with an anesthetic composed of midazolam, fentanyl bolus, and remifentanil infusion. Each group received an initial loading dose (0.5–1.0 μg/kg over 20 min) and a continuous infusion (0.01–1.0 μg·kg–1·h–1) of dexmedetomidine. Testing was successful in all 10 patients.
As demonstrated by these reports, there is no consistent use pattern for dexmedetomidine. Nor does there appear to be an easy explanation for the widely varying clinical outcomes.
Significant sedative synergism has been reported between midazolam and dexmedetomidine when administered together (8). Khan et al. (9), in addition to reporting a dose-related decrease in the minimum alveolar concentration of isoflurane associated with dexmedetomidine infusions, also experienced significant increased degrees of sedation in healthy volunteers who received dexmedetomidine versus placebo (P < 0.0001). Ebert et al. (10) described a decrease in recall with a blood level dosage of dexmedetomidine of 0.7 ng/mL. Hall et al. (11) using an initial dose of 6 μg·kg–1·h–1 of dexmedetomidine over 10 min followed by a 50-min infusion of dexmedetomidine at 0.2 μg·kg–1·h–1, 0.6 μg·kg–1 ·h–1, or saline (placebo group), demonstrated a 37% and 47% reduction in word recall respectively compared with 6% in the placebo group.
Not all combinations of potent inhaled anesthetics, propofol, remifentanil, fentanyl, midazolam, and dexmedetomidine, administered as an infusion with or without an initial dose, or with some administered in bolus dose fashion (midazolam and fentanyl) with dexmedetomidine infusions have undergone pharmacokinetic studies. A study by Khan et al. (9) demonstrated that isoflurane did not affect the pharmacokinetics of dexmedetomidine.
Individually, the pharmacokinetics of the various drugs used in these studies do not point toward an answer to the widely varying clinical outcomes. Remifentanil has a context-sensitive half-time of 3–5 minutes independent of the duration of infusion (12). Propofol has a context-sensitive half-time of <25 minutes after infusions lasting up to 3 hours.(13) The context-sensitive half-time of dexmedetomidine ranges from 4 minutes after a 10-minute infusion to 250 minutes after an 8-hour infusion (14). All of these case studies or reports have been well within these time frames.
In summary, we report the use of dexmedetomidine as a rescue drug during an awake craniotomy for cortical mapping and tumor resection. It provided sedation and analgesia, allowing the surgeon and neurologist to continue sensory and motor mapping without having to convert to a general anesthetic. The patient presented with worsening hemiparesis. Conversion to a general anesthetic with loss of patient input during cortical stimulation could have resulted in additional resection of cortex causing hemiplegia.
1. Matz PG, Cobbs C, Berger MS. Intraoperative cortical mapping as a guide to the surgical resection of gliomas. J Neuro Oncol 1999;42:233–45.
2. Manninen P, Contreras J. Anesthetic considerations for craniotomy in awake patients. Int Anesthesiol Clin 1986;24:157–74.
3. Johnson KB, Egan TD. Remifentanil and propofol combination for awake craniotomy: case report with pharmacokinetic simulations. J Neurosurg Anesthesiol 1998;10:25–9.
4. Hans P, Bonhomme V, Born JD, et al. Target-controlled infusion of propofol and remifentanil combined with bispectral index monitoring for awake craniotomy. Anaesthesia 2000;55:255–9.
5. Bekker AY, Kaufman B, Samir H. The use of dexmedetomidine infusion for awake craniotomy. Anesth Analg 2001;92:1251–3.
6. Bustillo MA, Lazar RM, Finck AD, et al. Dexmedetomidine may impair cognitive testing during endovascular embolization of cerebral arteriovenous malformations: a retrospective case report series. J Neurosurg Anesthesiol 2002;14:209–12.
7. Mack PF, Perrine K, Kobylarz G, et al. Dexmedetomidine and neurocognitive testing in awake craniotomy. J Neurosurgical Anesthesiol 2004;16:20–5.
8. Salonen M, Reid K, Maze M. Synergistic interaction between α2–adrenergic agonists and benzodiazepines in rats. Anesthesiology 1992;76:1004–11.
9. Khan ZP, Munday IT, Jones RM, et al. Effects of dexmedetomidine on isoflurane requirements in healthy volunteers. 1: Pharmacodynamic and pharmacokinetic interactions. Br J Anaesth 1999;83:372–80.
10. Ebert TJ, Hall JE, Barney JA, Uhrich TB. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology 2000;93:382–94.
11. Hall JE, Uhrich TD, Barney JA, et al. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg 2000;90:699–705.
12. Westmoreland CL, Hoke JF, Sebel PS, et al. Pharmacokinetics of remifentanil (G187084B) and its major metabolite (G19029) in patients undergoing elective inpatient surgery. Anesthesiology 1993;79:893–903.
13. White PF, Smith I. Propofol. In: White PF, ed. Intravenous anesthesia. Baltimore: Williams and Wilkins, 1997;111–52.
14. Reeves JG, Glass SA, Lubarsky DA. Intravenous nonopioid anesthetics. In: Miller RD, ed. Miller’s Anesthesia, 6th ed. Philadelphia: Elsevier Churchill Livingstone, 2005;317–78.