Introduction
The goal of modern surgery for glioblastoma is maximal safe resection. Neurosurgeons are keenly aware of the dramatic negative effects that postoperative neurologic deficits have on survival and quality of life. In contrast, achieving a complete or near-complete resection of enhancing tumor has been associated with improved survival in patients with glioblastoma. Tumor resection using the technique of awake craniotomy may allow oncologic surgeons to enhance the extent of resection while minimizing the risks of neurologic deficit. Nevertheless, like any other surgical techniques, a thorough understanding of its indication, application, limitations, and outcomes is necessary for the surgeon undertaking its use. This chapter reviews the surgical decision making and technical points, and discusses outcomes related to awake craniotomy in patients with glioblastoma.
Indications for awake craniotomy in glioblastoma
Glioblastoma is an invasive and rapidly growing primary brain tumor that can arise de novo or by transformation from a low-grade astrocytoma. In many cases, secondary glioblastoma arising from a preexisting low-grade astrocytoma occurs in eloquent regions. Those patients with long-standing preexisting tumors may show shift of critical eloquent brain function to different anatomic locations, thereby potentially rendering a greater extent of resection possible than that predicted based on preoperative imaging and knowledge of expected functional anatomy. De-novo tumors may be confined to a noneloquent gyrus and displace adjacent eloquent cortex by respecting the sulcal margin. Resection of the affected gyrus with preservation of adjacent eloquent cortex can be achieved with cortical mapping. Glioblastomas migrate via the white matter tracts and therefore subcortical stimulation to identify the location of corticospinal tract fibers can further assist in resection of tumors extending to the corona radiate and centrum semiovale and near corticospinal and speech/language fibers. In common practice, awake craniotomy has been used for tumors in or adjacent to the paracentral lobule, insula, posterior dominant frontal lobe, dominant temporal lobe, dominant perisylvian region, and dominant angular gyrus. Other surgeons have also reported the use of awake craniotomy for dominant parietal tumors, tumors near the optic radiations, and tumors near the visual cortex.
Patient selection and preoperative evaluation
Patients with preserved or partially preserved eloquent cortex function are ideal candidates for awake craniotomy because the goal is to maintain or improve on preoperative function with tumor resection. When considering age appropriateness, it is important to factor whether the patient has the age-appropriate cognitive capacity to understand the elements of the procedure and follow directions. Elderly patients with early dementia, prior stroke, or with multiple comorbidities that have affected their cognitive performance are often excluded from participation. Furthermore, patients with prior psychiatric comorbidities, such as severe anxiety or claustrophobia, may find it difficult to tolerate the procedure. Preoperative evaluation includes a detailed neuropsychiatric history to rule out claustrophobia, posttraumatic stress disorder, delusional thoughts, hallucinations, dissociative states, and severe anxiety. Furthermore, it is important to assess medical risk factors for altered response to anesthetic agents, such as alcoholism, drug abuse, polypharmacy, benzodiazepine or narcotic dependence, respiratory illness, obesity, obstructive sleep apnea, uncontrolled seizures, and prior lack of effect of local anesthetics.
The ideal patient is motivated, mature, and able to tolerate a strange and stressful environment for an extended period of time. General rules for patient preparation include providing honest information about the steps of the procedure without overuse of medical jargon as well as straightforward discussion of risks, complications, and outcomes. Some clinicians suggest proper counseling augmented with other forms of information, such as short films. Other centers perform a test run of patient positioning and language testing the day before surgery. In our center, an additional brief overview of the procedure and what the patient will experience is provided in the preoperative area on the day of surgery because the patient may have forgotten the information from the preoperative clinic visit. The patient is reminded to report any discomfort, even minor discomfort or pain, at any point during the procedure and is reassured that the team will be responsive. Regardless of the patient education strategy used, the most important factor in patient satisfaction seems to be the time spent preoperatively with members of the clinical team establishing a trusting alliance. The importance of this factor is understandable in that patients experience a sense of powerlessness and loss of control before the procedure and this can be reduced by open communication.
Anesthetic considerations
Although the awake craniotomy is generally a well-tolerated procedure, its success depends heavily on specialized anesthetic management. It requires extensive knowledge in local anesthesia for scalp block, advanced airway management, sedation sequences, management of hemodynamics, and patient coaching.
Premedication
Premedication is intended to relieve anxiety without oversedation, as well as preventing nausea, seizures, reflux, pain, or other adverse events. Midazolam or alprazolam are short-acting benzodiazepines, which can be used to provide anxiolysis and prevent nausea before positioning. Pretreatment with metoclopramide and ondansetron also helps to prevent nausea. Dexamethasone is routinely given to reduce brain edema and prevent nausea. Although mannitol can be given after urinary catheter placement to reduce intracranial pressure, the authors have found that patients often complain of excessive thirst, which may interfere with language evaluation. Therefore, we only administer mannitol in cases in which other methods to reduce intracranial pressure have not worked. To prevent seizures, patients are usually pretreated with anticonvulsants as well. The 2 anticonvulsants of choice are levetiracetam (Keppra) and phenytoin (Dilantin).
Local Anesthesia
Initially, awake neurosurgery was done with only local anesthesia to the scalp and dura. However, with the discovery of neuroleptics such as propofol, local anesthesia and general anesthesia are now used in combination for greater patient comfort and amnesia during awake craniotomies. Local anesthetic is injected to reversibly reduce pain sensation in either a regional field block or complete scalp block. The scalp block targets 6 nerves: the auriculotemporal nerve, zygomaticotemporal nerve, supraorbital nerve, supratrochlear nerve, greater occipital nerve, and lesser occipital nerve. Additional injection of the pin sites and surgical skin incision line is associated with improved pain scores and has minimal risks for systemic toxicity. Furthermore, there is evidence that local anesthesia also serves to blunt the hemodynamic response to cranial fixation and incision, such as increased heart rate and blood pressure, which in turn may prevent increased intracranial pressure. Bupivacaine, levobupivacaine, and ropivacaine are chosen for their long duration of action. They may be administered in combination with epinephrine in concentrations of 1:200,000 or 1:400,000.
Asleep-Awake-Asleep Technique
The asleep-awake-asleep monitored anesthesia technique entails general anesthesia with or without the use of an airway for deep sedation during the opening and closing portions of the surgery, with the awakening of the patients during the critical portion of tumor resection. The following drug regimens are used for intraoperative sedation and analgesia: propofol-fentanyl, propofol-remifentanil, dexmedetomidine-remifentanil. In intubated patients, some anesthesiologists add a volatile anesthetic such as nitrous oxide for craniotomy opening.
Propofol is widely used for awake craniotomy because of its rapid onset of action and rapid redistribution and metabolism, which allow easy sedation titration. Furthermore, propofol decreases cerebral oxygen consumption, reduces intracranial pressure, and has antiseizure properties and antiemetic effects. Typically, a propofol infusion is used during the asleep segment of the procedure and then turned off 15 minutes before the awake portion.
In recent years, many anesthesiologists have been combining propofol with an opioid analgesic such as fentanyl or remifentanil. Both fentanyl and remifentanil have favorable pharmacokinetics with very short half-lives, which facilitates the transition to wakefulness. Remifentanil seems to be associated with fewer intraoperative seizures than other opioid analgesics ; however, remifentanil may cause bradycardia, which is a concern in patients taking β-blockers.
Dexmedetomidine is a newer alternative to propofol. Dexmedetomidine is a highly selective alpha-2 adrenoreceptor agonist with dose-dependent sedative, anxiolytic, and analgesic effects without respiratory suppression. Multiple studies have shown that the sedative effect of dexmedetomidine causes somnolence that can be easily reversed without subsequent agitation or confusion, as well as analgesia that reduces the necessary amounts of other drugs. In general, a dexmedetomidine load of 0.5 to 1 μg/kg/h over 20 minutes is followed by infusion at rates of 0.1 to 0.7 μg/kg/h to 20 minutes before testing.
In the case series presented by Hervey-Jumper and Berger there was no correlation between the various drug regimens for sedation and tumor grade, tumor site, stimulation-induced seizures, laryngeal mask airway (LMA) use, patient body mass index, or aborted procedure. One study found fewer stimulated seizures with propofol versus dexmedetomidine ; however, no drug regimen has been shown to be superior.
In most patients undergoing awake craniotomy a secured airway is not necessary. A low threshold for placement of a nasal trumpet occurs if the patient shows signs of airway obstruction or snoring with sedation, and noninvasive supplemental oxygen can be delivered via a nasal cannula. Nevertheless, oversedation during the sleep portion of surgery can lead to apnea, oxygen desaturation, and carbon dioxide retention. An LMA is an airway device that can be used in this event because of its ease of insertion and removal without manipulating the head. It is generally well tolerated by awake patients while in place, and can be removed easily during the awake portion so that the patient can verbalize clearly. In one case series, LMA was only required in 1% of patients as a result of tumors with significant mass effect and the need for hyperventilation caused by tumor vascularity and venous engorgement secondary to hypercapnia. Endotracheal intubation is preferred to LMA in the rare patients with risk of pulmonary aspiration, because the LMA does not protect against aspiration from gastric contents. A fiberoptic bronchoscope should be used to emergently intubate patients in this situation in order to minimize head movement.
Monitored Anesthesia Care
Monitored anesthesia care (MAC) is a sedation protocol in which the patient is sedated but breathing spontaneously, and responsive to name-calling throughout the procedure. MAC uses similar medications in lower doses in order to achieve conscious sedation with spontaneous ventilation. Theoretically, the light sedation during the opening and closing portions of the surgery allow a shorter time to full alertness and smoother transitions, but require a more cooperative patient. Propofol doses are often between 30 and 180 μg/kg/min and remifentanil doses range from 0.03 to 0.09 μg/kg/min. Once the dura is open, a low-dose infusion of remifentanil 0 μg/kg/min to 0.01 μg/kg/min or dexmedetomidine 0 μg/kg/h to 0.5 μg/kg/h can be used to achieve relaxation.
Complications
Anesthetic complications vary depending on anesthetic technique. There is a risk for airway complications and desaturations during awake-asleep-awake craniotomy given the use of sedation with an unprotected airway. However proper patient selection, preoperative airway evaluation, patient positioning, close monitoring of end-tidal carbon dioxide, and a readily available nasal trumpet, LMA, and endotracheal tube can prevent adverse sequelae. In some cases, hypoventilation results in increased brain volume during an awake craniotomy. Mannitol can be used before dural opening to minimize cerebral edema and herniation during dural opening. However, emergent intubation and conversion to general anesthesia may be required for significant brain swelling.
Intraoperative seizure is a dangerous complication when a patient is fixed in pins without a secured airway, occurring in 3% to 20% of patients. In one of the largest reviews of awake craniotomies, Hervey-Jumper and colleagues noted that in 859 cases the overall perioperative complication rate was 10%, in which there were only 2 intraoperative seizures reported and in 0.5% of the cases the awake mapping was aborted. Seizures stimulated by cortical mapping can usually be aborted by stopping the stimulation or delivering ice-cold saline directly onto the cortical surface. Resistant seizures may require immediate dosing of benzodiazepine or propofol, which may interfere with subsequent neurocognitive testing. Having propofol loaded into a syringe and attached to within 15 cm (6 inches) of intravenous tubing to the patient can ensure a quick response to uncontrolled seizure activity.
Hemodynamic instability, including hypertension, hypotension, and tachycardia, can be encountered. An arterial line for close monitoring and prompt treatment with the appropriate medications may prevent associated adverse outcomes. Patient agitation and movement can be resolved by altering sedative medication and adjusting the patient’s environment, such as temperature, light source, and padding. However, some patients experience severe emergence delirium, which can result in serious injury to themselves and members of the operating room team. A practice wake-up before making the incision can be used to preemptively assess the patient’s transition from asleep to awake in order to optimize patient safety. If the patient cannot tolerate the procedure or agitation cannot be controlled, the procedure can then be converted to general anesthesia.
Surgical technique
Positioning and Pinning
Positioning of awake patients is a crucial step in a successful awake craniotomy surgery. In addition to the usual considerations of optimizing tumor access and minimizing brain retraction, bleeding, intracranial pressure, and venous obstruction, there must be adequate space for the neurologic examination and an emergency airway.
With the patient lying supine on the operative table and sedated, local anesthetic is infiltrated into the scalp in a complete ring block. Following administration of the local anesthetic the patient is moved into position and pinned into the head frame. The patient should be positioned supine on the operative table with or without the use of a soft shoulder roll and pillows under the knees. The ankles, wrists, and elbows are padded with soft egg-crate foam. The neck is placed in a position of comfort, avoiding excessive flexion or rotation (no more than 20° of flexion or 30° of rotation). For lateral lesions the authors find that using a large shoulder roll and bolstering the ipsilateral hip with pillows is sufficient and avoids placing the patient in a lateral position. The ipsilateral arm is placed in a crossed-arm position over the body and supported with tape so that the ipsilateral shoulder does not slump. The contralateral arm is free for patient assessment and supported on an arm board. Complete visualization of the contralateral arm and leg should be maintained to allow for observation of any motor stimulation during surgery. The patient is secured to the table with multiple Velcro belts and tape to allow for table rotation to bring the craniotomy site to the apex of the surgeon’s view. At least 15° of reverse Trendelenburg position is used. The authors place a foot rest for patients who require greater than 30° of reverse Trendelenburg or who are obese, to eliminate traction on the neck. Body temperature is maintained at 36°C to 37°C to prevent shivering and allow rapid metabolism of anesthetic agents.
Surgical Incision and Draping
After registering the neuronavigation system the borders of the tumor are mapped on the scalp surface. A linear incision is devised, preserving the scalp vascularization and allowing an appropriately sized craniotomy. The craniotomy is designed based on the margins of the tumor and not for exposure of eloquent areas. The goal is to minimize exposure of eloquent brain not involved with tumor. Safe resection with negative mapping has previously been shown so that exposure of eloquent noninvolved brain for positive mapping is not required. A hair-sparing incision technique is used in virgin cases and minimal strip shave with clippers is used for reoperative cases or patients with short (<2.5 cm [1 inch]) hair. A Layla bar is used to prop up the sterile towels and overdrape to allow face exposure. Access to the patient’s airway under the drapes is further provided by a flexible loop attached to the bed frame. The surgical drapes should be arranged in a wide-open geometry to minimize claustrophobia and allow eye contact with patient as well as a view of the patient’s face, arms, and legs for neurologic examination. A portable microphone is attached to the patient’s neck to allow the surgeon to hear the patient from under the drapes. In order to confirm that the patient will tolerate the head frame and desired surgical position during tumor resection a wake-up test is performed before sterile preparation of the incision. Adjustments are made if the patient reports any discomfort. If the patient arouses in an agitated state with inability to follow commands the procedure is performed under continuous sedation with only biopsy of tumors in eloquent perisylvian cortex or with direct cortical/subcortical stimulation and motor evoke potential monitoring for tumors in or near the rolandic cortex or extending toward the corticospinal tract.
Language Mapping
Expressive speech is tested by having the patient count serial numbers from 1 to 50, name objects, and read a word out loud while the cortex is stimulated for 4 seconds at the start of the task. Receptive speech is tested by having the patient repeat a complex sentence stated by the examiner. A bipolar stimulating electrode with 5-mm spacing is used with square-wave pulse at 60 Hz and pulse duration of 2 milliseconds. The current is initially set at 1.5 to 2 mA and increased by 1-mA steps up to a maximum of 6 mA. Afterdischarges recorded on a 4-contact or 6-contact strip electrode or a Montreal frame in adjacent cortex indicate the need to reduce the stimulating current by 0.5 to 1 mA. Stimulation sites are distributed 1 cm apart, tested 3 times, and identified with sterile labels. The patient’s speech is assessed for speech arrest, slowing, dysnomia, or paraphasias elicited by the cortical stimulation. Speech arrest is characterized by the loss of speech production in the absence of involuntary muscle contraction affecting speech. Between stimulation episodes the patient is tested to determine recovery before continuation of testing. Localization of speech areas may be affected by the stimulation procedure used, extent of language testing, and differences in functional distribution between individual patients and languages. These factors may account for the higher rate of negative speech mapping compared with motor mapping. Preoperative fMRI may allow identification of language areas for craniotomy and surgical approach planning; however, brain shift during tumor removal requires the use of awake mapping to ensure safety during resection ( Fig. 13.1 ).
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