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Cancer of the central nervous system is the 10th leading cause of death in the United States. An estimated 23,820 adults and 3720 children under the age of 15 years will be diagnosed with a primary tumor of the brain or spine in 2019. Primary tumors from the lung, breast, kidney, and bladder, and melanoma, leukemia, and lymphoma frequently metastasize to the brain, creating a secondary tumor. The treatment for both primary and metastatic brain tumors includes chemotherapy, radiation therapy, and surgery.
There are many anesthetic challenges for patients undergoing craniotomy for tumor resection. Depending on the size and location of the tumor, these patients can present with baseline motor or sensory neurologic deficits as well as seizures that may be poorly controlled. Intraoperatively, craniotomy patients require tight blood pressure control and hemodynamic stability to optimize surgical exposure and minimize blood loss. At the conclusion of surgery, a smooth and rapid emergence is desirable to decrease the risk of intracranial hemorrhage and allow for an immediate assessment of the patient’s neurologic status. Postoperatively, judicious use of pain medication must be undertaken to achieve adequate pain control while minimizing associated side effects, which may mask or mimic the signs and symptoms of postoperative surgical complications.
Preoperative assessment of the patient scheduled for craniotomy should include a complete history and physical examination with meticulous documentation of current neurologic status and evaluation for the presence of elevated intracranial pressure (ICP). Accurate documentation of the patient’s baseline neurologic status serves as a benchmark against which postoperative neurologic status can be measured. A significant number of these patients have neurologic findings, including seizure, vision changes, focal motor or sensory deficits, speech difficulties, balance disturbances, confusion, memory lapses, and headache. Tumors involving the pituitary gland can cause endocrine disturbances including muscle weakness, cold intolerance, excessive sweating, irritability, amenorrhea, sexual dysfunction, polyuria, unintended weight change, hypertension, hyperglycemia, easy bruisability, striae, mood change, moon facies, coarsened facial features, enlargement of hands and feet, and increased body hair. A detailed description of the seizure history, including seizure type, associated symptoms, frequency, most recent occurrence, medications tried, successful medications, and recently taken antiepileptics prepares clinicians to diagnose and treat perioperative seizures. Unilateral pupillary dilatation, double or blurred vision, photophobia, oculomotor or abducens palsy, headache, altered mental status, nausea or vomiting, or papilledema on fundoscopic examination should raise concerns for elevated ICP. Patients with severely elevated ICP can present with somnolence and irregular respiration. The appearance of Cushing’s triad consisting of systemic hypertension, bradycardia, and irregular respiration heralds impending brain herniation and death ( Fig. 19.1 , Table 19.1 ). Nausea and, less frequently, vomiting are common in patients with brain tumors, and many patients are on antiemetics during the preoperative period. Multimodal prophylaxis for postoperative nausea and vomiting (PONV; described later) is indicated for all patients undergoing a craniotomy, as the procedure itself is associated with a high incidence of PONV even if preprocedure symptoms are not present.
General | Tentorial Herniation (Lateral) | Tentorial Herniation (Central) | Tonsillar Herniation |
Headache Vomiting Visual disturbances Diplopia Cushing’s triad: Increased systolic pressure Widened pulse pressure Bradycardia Irregular breathing Depressed consciousness |
Third nerve palsy False localizing Ipsilateral hemiparesis (Kernohan’s notch) Depressed consciousness Homonymous hemianopia |
Upward gaze palsy Deteriorating level of consciousness Diabetes insipidus |
Neck stiffness Elevated blood pressure Slowed pulse rate Transient losses of vision Retinal venous pulsation Papilledema Unilateral pupillary dilatation Kernohans’s notch syndrome |
Previous cancer diagnoses and treatments, including surgery, chemotherapy, and radiation therapy, are important details of the patient’s history. For patients with a primary brain tumor, a prior craniotomy, especially if recent, may make a scalp block (discussed later) unwise. If the brain tumor is metastatic from a melanoma or renal cell primary, blood loss during craniotomy can be significantly higher. Radiation to the neck can create fibrosis and scarring of the soft tissues, making both mask ventilation and direct laryngoscopy extremely difficult or impossible. Radiation to the chest can impair both cardiac and pulmonary function. Chemotherapy agents can affect cardiac, pulmonary, hematopoietic, renal, and hepatic functions. A thorough understanding of the impact of each patient’s prior chemotherapy regimen on organ function is imperative. Patients frequently use antiepileptics, antiemetics, steroids, and hypoglycemic agents. Antiepileptics should, at a minimum, be continued in the perioperative period, and often an additional dose is administered in the early intraoperative period. A multimodal prophylactic approach to PONV is advised and often includes agents from at least three different drug classes: steroids, 5-HT 3 receptor antagonists, NK-1 receptor antagonists, antihistamines, phenothiazines, and 5-HT 4 receptor agonists. The most common combination used at our institution is a steroid, a 5-HT 3 receptor antagonist, and an NK-1 receptor antagonist. Hyperglycemia secondary to steroid administration and preexisting diabetes is common and should be managed in a systematic manner using an insulin sliding scale with either subcutaneous administration or intravenous infusion of insulin. NK-1 inhibitors interfere with birth control, and alternative means of contraception are advised for 30 days following the last dose of a medication from this drug class.
The mass effect from the brain tumor and the surrounding edema is best quantified with a computed tomography (CT) scan or magnetic resonance imaging (MRI). Findings of flattened gyri, narrowed sulci, or compression of the intracranial ventricles indicate elevated ICP. Preexisting anemia (from chemotherapy) and hyperglycemia (from steroid use) are common laboratory findings. We obtain blood typing and an antibody screen on all craniotomy patients and adhere to a protocol for perioperative glucose management, with treatment indicated for glucose above 180 mg/dL.
When formulating an intraoperative plan of care, the anesthesiologist should consider the tumor location, surgical positioning, neuromonitoring plans, and bleeding risk. Tumors are classified as either supratentorial or infratentorial, depending on whether they lie above or below the tentorium cerebelli, respectively. In adults primary supratentorial tumors predominate and may involve eloquent areas of the brain responsible for speech generation and comprehension, or motor function. By contrast, infratentorial tumors are more common in pediatric patients and may involve the cerebellum, fourth ventricle, cerebellopontine angle, and brainstem. Due to their locations, supratentorial and infratentorial tumors may present differently.
Positioning surgical patients is often a compromise between optimal surgical exposure and what can actually be physiologically tolerated by the patient. Most craniotomies are performed with the patient in the supine, lateral, or prone positions, with the patient’s head elevated by 10–30 degrees. The semisitting or semi-Fowler’s position can offer an advantageous surgical exposure for posterior fossa tumors, although the risk of vascular air embolism (VAE) is increased. The risk of VAE and a treatment plan should be discussed with the surgeon for every patient undergoing craniotomy. Transesophageal echocardiography is the most sensitive method for detection of VAE, but it is rarely employed in craniotomies because of its expense and invasiveness, and the need for special expertise in interpreting images. Precordial Doppler is the most sensitive noninvasive method for detecting VAE and can be placed on the 2nd, 3rd, or 4th intercostal space to the right or left of the sternum, or between the right scapula and spine in prone patients. Other methods of VAE detection that are considered to be highly sensitive include a pulmonary artery catheter and transcranial Doppler, neither of which is routinely used during craniotomies. Treatment for VAE should be readily available during every craniotomy and includes bone wax to seal air entry sites at the cut bone surfaces, normal saline to flood the surgical field, the ability to place the patient in the Trendelenburg position, the application of positive end-expiratory pressure, and manual compression of the jugular veins. Special attention must be paid to the protection of the eyes from both the preoperative skin preparation solution and inadvertent pressure from personnel and equipment. Liberal application of sterile eye ointment followed by eye pads and an occlusive, waterproof cover provides corneal protection, and provider vigilance is necessary to prevent pressure injury to the eyes.
Intraoperative neuromonitoring modalities include somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs), electroencephalography (EEG), electromyography (EMG), auditory brainstem response (ABR), Hoffmann’s reflex testing (H-reflex), and cranial nerve testing, most commonly the facial nerve (CNVII). The selection of which modalities to use is determined by the neurologic pathways at risk of injury during surgery. A detailed description of neuromonitoring modalities is beyond the scope of this chapter. SSEPs and MEPs are the most common neuromonitoring modalities used during craniotomies. SSEPs monitor the integrity of the sensory pathways from the periphery to the brain by measuring both the speed and amplitude of electrical signals traveling from a peripheral sensory nerve through the dorsal root ganglia, along the posterior column of the spinal cord to the brain. MEPs monitor the integrity of the motor pathways from the brain to the periphery by measuring both the speed and amplitude of electrical signals traveling from the motor cortex through the corticospinal tracts through the anterior horn to the peripheral muscle. Both SSEPs and MEPS are commonly used in posterior spine surgery, supratentorial craniotomies, neurovascular surgery, and skull base surgery.
Inhalational anesthetics and intravenous agents may be used alone or in combination to provide general endotracheal anesthesia for craniotomy surgery. Although the use of inhalational agents alone offers a simple anesthetic approach, may minimize the risk of side effects from polypharmacy, and provide a reliable measure of anesthetic depth, inhalational agents can adversely affect central nervous system physiology. All volatile anesthetics to varying degrees increase cerebral blood flow (CBF), decrease cerebral metabolic rate (CMR), and inhibit or even abolish cerebral autoregulation. Cerebral vasodilation that results from the uncoupling of CBF from CMR can increase ICP in the closed cranium or compromise surgical exposure in an open cranium. While the vasodilatory and ICP effects can be mitigated or even reversed with hypocapnia in a normal brain, eliminating this response may not be possible when intracranial pathology is present. , Volatile anesthetics also adversely affect intraoperative neuromonitoring of SSEPs, visual evoked potentials (VEPs), and MEPs by increasing cortical latency and decreasing cortical amplitude in a dose-dependent manner. However, volatiles have minimal effects on brainstem potentials, and thus the use of inhalational agents during brainstem monitoring is acceptable.
Total intravenous anesthesia (TIVA) may be clinically indicated for specific craniotomy cases. Given the extreme sensitivity of MEPs to volatile anesthetics, TIVA should be used when neuromonitoring involves MEPs. Additionally, when elevated ICP is of particular concern, TIVA is preferred because inhalational agents can adversely affect ICP. Although ICP may not be an issue in an open cranium, the vasodilatory effects of volatile anesthetics may compromise surgical exposure; therefore if the surgical field is suboptimal, TIVA should be considered.
A combined technique that utilizes both inhalational and intravenous anesthetics offers significant advantages. Although the vasodilatory effects of volatile anesthetics can adversely affect ICP, surgical exposure, and neuromonitoring signals, these effects are usually dose-dependent. For most craniotomy cases, the use of volatile anesthetics at doses of 0.5 MAC or less supplemented with intravenous anesthetics may be acceptable.
Intravenous anesthetics and adjuncts have advantages and disadvantages when used in craniotomy. Propofol is the most commonly used intravenous anesthetic in the setting of a combined general anesthetic technique and is the primary anesthetic for TIVA. Unlike volatile anesthetics, propofol decreases both CBF and CMR without inducing cerebral vasodilation; the result is overall ICP reduction. However, propofol may lower mean arterial pressure (MAP), potentially compromising cerebral perfusion pressure (CPP) and increasing the risk of ischemic injury during craniotomy. Studies have shown that propofol anesthesia, regardless of dose, causes lower jugular bulb oxygen saturation when compared to sevoflurane-nitrous oxide or isoflurane-nitrous oxide anesthesia. Improper titration of propofol intraoperatively may contribute to prolonged emergence and postoperative sedation.
Intravenous opioid infusions are commonly used during craniotomy. While administration of opioids provides intraoperative and postoperative analgesia that may facilitate a smooth emergence, their use can delay wake-up, contribute to postoperative sedation, and interfere with an accurate and timely neurologic assessment. To avoid these side effects of longer-acting opioids, remifentanil, an ultrashort-acting opioid, is advantageous for use during craniotomy. Remifentanil does not provide any postoperative analgesia and may cause postoperative rebound hyperalgesia. According to a literature review that included 21 studies assessing intraoperative remifentanil use and acute or chronic postoperative pain, less than half of the studies found a higher postoperative analgesic requirement in patients who received remifentanil, and only four studies showed a potential association between remifentanil and chronic pain. Remifentanil use with volatile agents was associated with increased pain levels postoperatively compared to its use with TIVA or in a combined inhalation and intravenous technique. The incidence of hyperalgesia with intraoperative remifentanil use may be a function of dose, with higher infusion rates and cumulative doses posing a greater risk.
Lidocaine infusions have been shown to be beneficial in enhanced recovery protocols as adjunct medications. Lidocaine is potentially neuroprotective since it prevents sodium influx, which is the first step in the ischemic cascade, and blocks specific apoptotic cell death pathways to reduce postnecrotic injury. However, local anesthetic toxicity that can induce seizures is a potential risk, while the sedative effects of lidocaine may delay emergence and hinder rapid neurologic assessment postoperatively.
Dexmedetomidine is a selective α 2 -adrenergic agonist with anesthetic and analgesic properties. Dexmedetomidine-induced sedation results from indirect upregulation of gamma-aminobutyric acid (GABA) activity in the central nervous system through decreased noradrenergic neuron activity, while its pain-relieving properties are a result of its effects at the spinal cord level and supraspinal sites. Unlike most other sedatives and opioids, dexmedetomidine does not cause respiratory depression. It also does not reduce the latency or amplitude of the intraoperative neuromonitoring signals. Given these advantages and the synergistic effect of dexmedetomidine with various anesthetics, dexmedetomidine may be used as an adjuvant to standard general anesthesia, thereby decreasing the dose requirements of other anesthetics and analgesics that adversely affect intraoperative neuromonitoring. The side effects of dexmedetomidine include hypotension and bradycardia; therefore its use may not be appropriate in patients with significant cardiac disease or hemodynamic compromise.
Ketamine is an N -methyl-d-aspartate (NMDA) antagonist that is effective in reducing pain both intraoperatively and postoperatively. For craniotomy utilizing neuromonitoring, ketamine enhances SSEPs by increasing the amplitude, but not latency, of these recordings while minimally affecting MEPs. Because ketamine also activates certain cortical areas of the brain, the frequency on EEG is increased, resulting in a higher reading on Bispectral Index (BIS) monitoring. This cerebral stimulatory effect activates subcortical seizure activity in patients with seizure disorders. Furthermore, ketamine increases CBF and CMR, thereby negatively impacting ICP and potentially compromising the surgical exposure. For these reasons, ketamine should be avoided in patients with uncontrolled seizures or elevated ICP. Although ketamine can have psychogenic side effects, the use of subanesthetic doses will mitigate this risk while still providing effective postoperative analgesia. ,
Tumor resection is a balance between extensive tumor removal and the preservation of brain function. The use of preoperative functional MRI, neuronavigation, fluorescent dyes, intraoperative magnetic resonance imaging (iMRI), and intraoperative stimulation mapping (ISM) helps delineate tumors from the functional brain. In awake craniotomy, the patient participates in ISM and neuropsychologic testing during tumor resection. Some centers use both iMRI and ISM to improve resection and minimize functional impairment.
The awake technique is the gold standard for tumor resection near “eloquent areas” of the brain. , “Eloquent areas” of the brain if injured lead to motor, sensory, vision, hearing, speech, or language processing deficits. Anatomically, “eloquent areas” of the brain include the primary motor cortex (precentral gyrus), primary sensory cortex (postcentral gyrus), primary visual cortex, primary auditory cortex, left posterior inferior frontal gyrus (Broca’s area), and left posterior superior temporal gyrus (Wernicke’s area). Tumors in or near the primary motor cortex, primary sensory cortex, or speech areas are often resected under awake conditions. Tumor location is the primary driver for choosing an awake craniotomy technique. During the awake portion of the craniotomy, patient participation in neurocognitive testing assists the surgeon in identifying functional areas of the brain, facilitating a more complete resection of the tumor while preserving brain function. A meta-analysis of 90 published reports of glioma resection with and without ISM concluded that glioma resections using ISM are associated with fewer late severe neurologic deficits and more extensive resection, and they involve eloquent locations more frequently.
Preoperative assessment by an anesthesiologist should occur at least 1 day prior to the planned surgery. A thorough preoperative evaluation and discussion between the anesthesiologist assigned to the case and the patient is strongly recommended to build rapport and trust, document preexisting neurologic deficits, prepare the patient for the surgical events, and appropriately set patient expectations. The discussion must include expected intraoperative body positioning, the possibility of unpleasant sensations (e.g., hip or shoulder pain, dry mouth, headache during resection, nausea, unfamiliar noises from surgical equipment), the tunnel-like view the patient will have due to surgical draping, strategies used to keep the patient as comfortable as possible, and the possibility that an awake technique may be abandoned if safety becomes compromised. The anesthesiologist must assess patient motivation, temperament, ability to cooperate and communicate, and preexisting comorbidities when considering the awake technique. Patients who are claustrophobic, severely anxious, or diagnosed with a psychiatric illness may not be able to stay calm and cooperate during the awake portion of the case. Patients with substantial speech impairment or expressive aphasia may not have a consistent baseline during preoperative testing, making intraoperative testing less reliable. A patient with a difficult airway or sleep apnea poses significant challenges for adequate oxygenation and ventilation.
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