Anesthesia for craniotomy

INTRODUCTION — Craniotomy is performed for a variety of indications, including tumor resection, intracranial vascular procedures, evacuation of hematoma, and trauma.

This topic will discuss overall anesthetic management for craniotomy. Anesthetic management for some specific types of craniotomy is discussed separately.

●(See "Anesthesia for posterior fossa craniotomy".)

●(See "Anesthesia for intracranial neurovascular procedures in adults".)

●(See "Anesthesia for awake craniotomy".)

PREOPERATIVE EVALUATION

History and physical examination — Evaluation before craniotomy should include the usual preanesthesia history and physical examination. Additional concerns specific to craniotomy include the following:

●Neurologic status – The patient's baseline neurologic status, including current and prior specific deficits, signs and symptoms of increased intracranial pressure (ICP), and history of seizures should be assessed.

On emergence from anesthesia, new deficits may be cause for concern, while reappearance of prior deficits may represent differential emergence, and may resolve quickly. (See 'Differential emergence or awakening' below.)

●Cardiac status – When the risk of venous air embolism (VAE) is high (eg, sitting position, surgery near venous sinuses), we obtain an echocardiogram that includes a study to rule out a patent foramen ovale (PFO) or other intracardiac shunt (eg, atrial septal defect, ventricular septal defect) and assess cardiac function; we consider a PFO a relative contraindication to the use of the sitting position. In addition, patients with pulmonary hypertension or right ventricular dysfunction may decompensate with even small amounts of intravenous (IV) air. (See 'Sitting position' below.)

Alternatively, transesophageal echocardiography (TEE) can be performed after induction of anesthesia for cases with high risk of air embolism. In this setting, if intracardiac shunt is identified, the procedure can be performed in a position with less risk of air embolism.

Medications — As usual, the patient's medications should be reviewed; considerations in anticipation of craniotomy include the following:

●Anticonvulsants – Many patients who undergo craniotomy are taking anticonvulsants, which can affect metabolism of a variety of drugs. Patients should be instructed to take the usual dose of anticonvulsant the morning of surgery, unless the patient is to undergo seizure focus mapping and resection.

●Glucocorticoids – Patients with intracranial masses may be taking glucocorticoids. Stress-dose glucocorticoids may be required before induction of anesthesia, and blood glucose may be elevated in patients taking these medications.

●Anticoagulants – In most cases, aspirin, nonsteroidal antiinflammatory drugs, and other medications that affect coagulation should be discontinued in advance of craniotomy. (See "Perioperative medication management", section on 'Medications affecting hemostasis' and "Perioperative management of patients receiving anticoagulants", section on 'Estimating procedural bleeding risk'.)

Laboratory evaluation — Patients presenting for craniotomy may have fluid and electrolyte abnormalities because of poor oral intake, glucocorticoid or diuretic administration, and/or centrally mediated endocrine abnormalities. Measurement of blood glucose, electrolytes, and complete blood count should be performed. Other preoperative blood tests, chest radiograph, and electrocardiogram (ECG) should be performed when indicated, as for other major surgery. A blood type and screen should also be performed.

PLANNING THE ANESTHETIC

General concerns — The following issues that affect anesthetic management should be addressed before any craniotomy, in consultation with the surgeon:

●Does the patient have increased intracranial pressure (ICP)?

●Is brain relaxation required during surgery? Dose and timing of medications, and ventilatory parameters should be discussed, including (see 'Brain relaxation' below):

•Diuretic

•Osmotherapy (eg, mannitol)

•Glucocorticoid

•Goal partial pressure of carbon dioxide (PaCO₂)

•Anesthetic drug choices

•Cerebrospinal fluid (CSF) drainage

●What are the goals for blood pressure (BP) management? (See 'Hemodynamic management' below.)

●How will the patient be positioned for surgery? (See 'Positioning' below.)

●Is there potential for venous air embolism (VAE)? (See 'Sitting position' below and "Intraoperative venous air embolism during neurosurgery".)

●What is the expected blood loss?

●Are anticonvulsants required? (See 'Antiseizure drugs' below.)

●Will neurophysiologic monitoring (ie, evoked potentials, electroencephalography, electrocorticography) be performed during surgery? (See 'Neurophysiologic monitoring' below.)

Surgical steps — Regardless of the indication, most craniotomies follow standard steps that affect anesthetic management. Periods of intense, painful stimulus are separated by relatively long periods of low-level stimulation, requiring adjustment of anesthetic depth.

●Skull pinning – The head is usually immobilized with the Mayfield apparatus, which consists of skull pins fixed to a clamp that is firmly attached to the operating table. The pins are placed through the skin and scalp, and into the outer table of the skull.

Pinning is a brief, sudden, and painful stimulus comparable to incision or laryngoscopy that can result in hypertension and tachycardia. To attenuate this hemodynamic response, various medications can be administered in anticipation of pinning, including opioid (eg, fentanyl 50 to 100 mcg intravenously [IV] or remifentanil 25 to 50 mcg IV), propofol (eg, 20 to 50 mg IV), esmolol (0.25 to 0.5 mg/kg IV), and lidocaine (eg, 1 mg/kg IV) [1-4]. Administration of opioids at the higher doses in these ranges can result in hypotension after the stimulus of pinning is over, particularly if administered with propofol. Timing of pinning should be coordinated with the surgeon to allow effective pretreatment.

We usually administer esmolol (0.5 to 1 mg/kg IV) and opioid (eg, fentanyl 100 mcg IV or remifentanil 50 mcg IV) approximately one minute prior to pinning. A small dose of propofol (eg, 20 to 50 mg IV) may be added depending on the patient's hemodynamic status and risk factors for subsequent hypotension.

Local anesthetic infiltration at the pin sites or scalp block may be performed to prevent the hemodynamic response to skull pinning [5-7]. (See "Scalp block and cervical plexus block techniques", section on 'Scalp block'.)

●Preincision preparation – After skull pinning, a light level of anesthesia is required for a variable, potentially long period of time during supplementary line placement, patient positioning, registration of the stereotactic guidance system, sterile skin preparation, and draping.

●Incision, raising scalp and bone flaps – Before incision, the level of anesthesia should be increased. Blood loss can be significant while the scalp flap is raised and may be hidden on the drapes or in a collection bag. Brain relaxation may be required prior to dural opening. (See 'Brain relaxation' below.)

●Opening the dura – The parietal dura is rich in pain fibers; manipulation of the dura is intensely painful [8,9] and requires continuation of a relatively deep level of anesthesia.

●Intracranial procedure – Depending on the indication and location of the pathology, the procedure may be brief and superficial (eg, evacuation of subdural hematoma) or lengthy with microscopic dissection (eg, clipping of a cerebral aneurysm). A lighter level of anesthesia may be required during the intracranial portion of surgery because brain tissue has no pain receptors.

●Wound closure – After completion of the intracranial procedure, hemostasis is achieved, followed by dural closure, replacement of the bone, and scalp closure. For extensive craniotomies, closure can take an hour or more. Although not as stimulating as incision, wound closure is painful. Opioids, acetaminophen, and/or antihypertensive medication may be required as the anesthetic is lightened for emergence. (See 'Emergence from anesthesia' below.)

ANESTHETIC MANAGEMENT — General endotracheal anesthesia is the preferred technique for craniotomy, though for specific indications, the procedure can be performed awake. (See "Anesthesia for awake craniotomy".)

Monitoring — Standard American Society of Anesthesiologists (ASA) monitors (ie, electrocardiogram [ECG], blood pressure [BP], pulse oximetry, temperature, oxygen analyzer, continuous end-tidal carbon dioxide [ETCO₂] analyzer) may be sufficient in select, minimally invasive craniotomies (eg, burr holes for subdural hematoma evacuation). In most cases, additional monitoring is indicated. (See "Induction of general anesthesia: Overview", section on 'Preparation for anesthetic induction'.)

Arterial catheterization — Continuous BP monitoring with an intra-arterial catheter is indicated for all patients with increased intracranial pressure (ICP) and for patients who undergo cerebrovascular procedures. Arterial catheterization is helpful for most other craniotomies, allowing optimization of cerebral perfusion pressure (CPP) and assessment of volume status, and facilitating blood sampling for blood gases and electrolytes.

Monitoring for venous air embolism — Venous air embolism (VAE) can occur whenever the operative site is positioned above the level of heart, as it usually is for craniotomy. Monitors specific for VAE are precordial Doppler and, for patients who have general anesthesia, transesophageal echocardiography. Monitoring for VAE is discussed in detail separately. (See "Intraoperative venous air embolism during neurosurgery", section on 'Monitoring for venous air embolism'.)

Neurophysiologic monitoring — Intraoperative electroencephalography (EEG) and evoked potential monitoring during craniotomy have implications for the choice of anesthetic medication. These monitoring modalities are discussed separately. (See "Neuromonitoring in surgery and anesthesia".)

Intracranial pressure monitoring — Patients may have an extraventricular drain (EVD) placed prior to or during craniotomy. An EVD may be used to drain cerebrospinal fluid (CSF) and to monitor ICP. (See "Evaluation and management of elevated intracranial pressure in adults".)

In contrast with arterial or central venous monitoring transducers, the EVD should not be connected to a pressure bag; dangerous increase in ICP can occur. Management of the EVD should be discussed with the surgeon before and during surgery [10].

Processed electroencephalography — When total IV anesthesia (TIVA) is used, we use a processed EEG monitor (eg, bispectral index [BIS] or SedLine) to help guide the dose of anesthetic and to facilitate rapid emergence from anesthesia. EEG monitoring used for intraoperative neuromonitoring can be used as well to assess anesthetic depth, and to monitor intraoperative seizure activity. (See 'Intravenous anesthesia' below and "Accidental awareness during general anesthesia", section on 'Brain monitoring' and "Neuromonitoring in surgery and anesthesia", section on 'Electroencephalography'.)

Intravenous access — We place two IV catheters for most routine craniotomies. Additional IV access may be required for cases with potential for significant hemorrhage.

Central venous catheterization — A CVC may be placed for central administration of vasoactive or caustic medication, to provide venous access for volume resuscitation, and for air aspiration in cases with a high likelihood of VAE [11,12]. (See "Intraoperative venous air embolism during neurosurgery", section on 'Central venous catheter placement'.)

Premedication — Premedication for craniotomy should be individualized based on the patient's level of anxiety, baseline neurologic status, and comorbidities. Patients with intracranial pathology may be especially sensitive to sedatives and opioids; premedication should be titrated to effect using small doses of medication (eg, midazolam 1 to 2 mg IV, administered in 0.5-mg increments). For patients with increased ICP, we withhold sedation until the patient is fully monitored in a setting that would allow immediate airway management.

Induction of anesthesia — Similar to anesthesia for most other procedures, IV induction of anesthesia is usually performed for adult patients who undergo craniotomy. The goals for induction of anesthesia for these cases include the following:

●Hemodynamic stability – Drugs and doses should be selected to maintain CPP while avoiding hypertension and the risk of intracranial hemorrhage.

●Avoidance of increase in ICP – Medication and ventilation should be managed to avoid increase in ICP, especially for patients with preoperative increased ICP.

In most cases, several classes of medications are used for induction of anesthesia (see "Induction of general anesthesia: Overview", section on 'Intravenous anesthetic induction' and "General anesthesia: Intravenous induction agents"). The effects of anesthetic medications on cerebral physiology are shown in a table (table 1).

Anesthesia induction agents — In general, with the exception of ketamine, IV induction agents cause reductions in both cerebral metabolic rate (CMR) and cerebral blood flow (CBF), resulting in no change or decrease in ICP (table 1). Autoregulation and responsiveness to carbon dioxide (CO₂) are preserved. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'Physiology'.)

●Propofol – CMR, CBF, cerebral blood volume (CBV), and ICP are reduced with induction doses of propofol [13,14], and autoregulation and CO₂ responsiveness are preserved [15]. Propofol may be used to induce an isoelectric EEG. This drug can cause hypotension; the induction dose should be adjusted for patient factors. (See "General anesthesia: Intravenous induction agents", section on 'Propofol'.)

●Barbiturates – Barbiturates for induction of anesthesia include thiopental (3 to 6 mg/kg IV) (outside the United States) and methohexital (1 to 1.5 Mg/kg IV) (limited availability). Barbiturates cause a dose-dependent reduction in CMR, CBF, and ICP, while autoregulation and CO₂ responsiveness are maintained [16-18]. Thiopental can produce an isoelectric EEG; in contrast, methohexital activates seizure foci. Barbiturates can cause hypotension, though (at an equivalent dose) to a lesser extent than propofol. The induction dose should be decreased in older patients and in those at increased risk of hypotension. (See "General anesthesia: Intravenous induction agents", section on 'Methohexital'.)

●Etomidate – Etomidate (0.15 to 0.3 mg/kg IV) is an induction agent that does not decrease BP or cardiac output. Administration of an induction dose decreases CBF and CMR and reduces ICP without adversely impacting CPP [19-21], while preserving CO₂ responsiveness [19]. However, even with a single induction dose, etomidate inhibits corticosteroid production in the adrenal gland for up to 24 hours [22,23]. (See "General anesthesia: Intravenous induction agents", section on 'Etomidate'.)

The effects of etomidate on cerebral vasculature are complex. In animal models, etomidate is a cerebral vasoconstrictor, possibly mediated by mitochondrial dysfunction and inhibition of nitric oxide synthase [24-26]. A study of human brain tissue oxygenation during intracranial aneurysm surgery reported that administration of etomidate at a dose that produced EEG burst suppression resulted in a 30 percent reduction in tissue partial pressure of oxygen (PO₂), with a further 32 percent reduction of PO₂ during temporary artery clipping [27]. Because of these studies, we avoid administration of etomidate for induction of anesthesia for patients with cerebral vasospasm or other conditions associated with cerebral ischemia.

Etomidate is associated with a higher rate of postoperative nausea and vomiting (PONV) than other induction agents [28,29].

●Ketamine – The effects of ketamine on cerebral physiology are controversial. Data regarding the effect of ketamine on cerebral physiology are conflicting. Some human and animal studies have reported that ketamine increases CBF, CMR, and ICP [30-34]. In contrast, other studies have reported no change or a decrease in these parameters, particularly when ketamine is administered with other anesthetics [35-39]. Given the uncertainty, we believe that ketamine should be used with caution for craniotomy, especially for patients with increased ICP. (See "General anesthesia: Intravenous induction agents", section on 'Ketamine'.)

Based on small case series and case reports, ketamine has been administered along with other antiepileptic drugs to successfully treat refractory status epilepticus [40,41].

Opioids — An opioid is usually administered as part of induction of anesthesia to reduce the required dose of induction agent, to suppress airway reflexes, and to attenuate the hemodynamic response to laryngoscopy and intubation. In this setting, opioids cause minimal effects on cerebral physiologic parameters as long as mean arterial pressure (MAP) is maintained [42,43]. Fentanyl, sufentanil, and alfentanil are all used for rapid effect. Remifentanil, an ultrashort-acting opioid, can be used for induction but should be administered by infusion, with or without an initial bolus, to avoid abrupt offset and resultant hypertension and tachycardia [44]. (See "General anesthesia: Intravenous induction agents", section on 'Opioids'.)

Lidocaine — Lidocaine (1 to 1.5 mg/kg IV) may be administered during induction of anesthesia to suppress the cough reflex during laryngoscopy and to blunt, but not eliminate, the hemodynamic response to intubation [45,46]. (See "General anesthesia: Intravenous induction agents", section on 'Lidocaine'.)

Neuromuscular blocking agents — In most cases, a neuromuscular blocking agent (NMBA) is administered after induction of general anesthesia to facilitate endotracheal intubation. Nondepolarizing NMBAs (eg, rocuronium, cisatracurium, vecuronium, and mivacurium) are most commonly used unless rapid sequence induction and intubation (RSII) is required or difficult airway management is anticipated. (See "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Endotracheal intubation' and "Rapid sequence induction and intubation (RSII) for anesthesia", section on 'Neuromuscular blocking agents (NMBAs)'.)

Nondepolarizing NMBAs have no direct effects on cerebral physiology. Less commonly used NMBAs that are associated with histamine release at higher or rapid doses (ie, atracurium, mivacurium) can theoretically cause a reduction in CPP because of a decrease in MAP and cerebral vasodilation and an increase in ICP [47]. (See "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Atracurium' and "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Mivacurium'.)

Succinylcholine, a depolarizing NMBA, can produce a transient increase in ICP, possibly the result of an increase in CBF related to the arousal response to muscle fasciculations [48]. However, the increase in ICP with succinylcholine is of short duration and can be attenuated by administration of a defasciculating dose of a nondepolarizing NMBA [49]. Succinylcholine is used for RSII and when endotracheal intubation may be difficult.

For RSII in patients in whom ICP is a concern, we administer a defasciculating dose of nondepolarizing NMBA (eg, rocuronium 2 mg IV, cisatracurium 1.5 mg IV, or vecuronium 0.3 mg IV) followed by succinylcholine 1.5 to 2 mg/kg IV. For RSII when succinylcholine is contraindicated (eg, burns, denervation injury), we administer rocuronium 1 mg/kg IV or high-dose remifentanil (propofol 2 to 2.5 mg/kg IV followed by ephedrine 10 mg IV and remifentanil 3 to 5 mcg/kg IV). (See "Rapid sequence induction and intubation (RSII) for anesthesia", section on 'Neuromuscular blocking agents (NMBAs)'.)

Positioning — Positioning for craniotomy requires meticulous attention to detail. These procedures are often long and can be performed in a variety of positions, including supine, prone, lateral or semilateral, and sitting or semisitting. The head is usually held in skull pins attached to a head frame and is often turned to the side, sometimes with the neck flexed.

General concerns related to positioning include the following:

●Nerve damage – Peripheral nerve damage can result from compression, stretch, or compromised perfusion to nerves. (See "Overview of lower extremity peripheral nerve syndromes" and "Overview of upper extremity peripheral nerve syndromes".)

●Cervical spine injury – Flexion and rotation of the cervical spine can result in injury. The patient's range of motion of the cervical spine should be examined preoperatively.

●Skin pressure injuries – Pressure points should be padded, as should all plastic connectors and other parts of IV tubing and monitoring devices.

●Ocular injury – The patient's eyes should be covered immediately after induction of anesthesia. We cover the eyes with occlusive adhesive dressing to keep the lids closed and to prevent skin preparation solution from entering the eyes. After positioning and draping, and periodically during the case, the patient's eyes should be checked to make sure the eye covering is in place and that there is no pressure on the eyes. (See "Postoperative visual loss after anesthesia for nonocular surgery".)

●Airway compromise – Neck flexion can kink the endotracheal tube (ETT) during positioning and/or later during the case when the ETT warms or with minor head movement. A wire reinforced, or armored, ETT can be used if kinking is a particular concern.

With prone positioning, the ETT can become dislodged during the positioning process, from gravity during the procedure, or as the tape loosens with oral secretions. For these cases, we secure the ETT using tape and transparent adhesive dressings and attach the breathing circuit to the head frame after positioning to support the tube.

We advise patients that we may remove facial hair if necessary to safely secure the endotracheal tube. In addition, for prone positioning for patients who can tolerate tachycardia, we administer glycopyrrolate 0.2 mg IV to reduce oral secretions and prevent tape dislodgement.

●VAE – VAE is a risk whenever the operative site is above the level of the heart, and this risk is higher during surgery around venous sinuses. For craniotomy, most patients are positioned somewhat head-up to facilitate venous drainage and brain relaxation. (See "Intraoperative venous air embolism during neurosurgery".)

Prone position — The prone position is commonly used for suboccipital craniotomy and other neurosurgical procedures and is associated with a number of physiologic effects and risks, which are discussed separately. (See "Patient positioning for surgery and anesthesia in adults", section on 'Prone'.)

Sitting position — The sitting position is sometimes used for posterior fossa and other craniotomies because it offers improved access to the apex of the posterior fossa and better surgical exposure [50]. However, the sitting position is associated with a higher risk of VAE, hypotension, and pneumocephalus compared with other positions for craniotomy. The neck flexion used in the sitting position has been implicated in rare cases of tongue and oropharyngeal swelling [51] and quadriplegia [52,53].

●VAE – The incidence of VAE in sitting craniotomy is reported to be between 18 and 76 percent depending on the detection method used [54-57], though not all instances of air embolism impact hemodynamics or outcome. VAE during craniotomy is discussed in detail separately. (See "Intraoperative venous air embolism during neurosurgery".)

●Cardiovascular effects – The vasodilation and myocardial depression that can accompany general anesthesia, along with venous pooling in the sitting position, can produce a decrease in cardiac preload, stroke volume, and MAP. (See "Patient positioning for surgery and anesthesia in adults", section on 'Physiologic effects of sitting position'.)

Hemodynamic changes can be mitigated by IV fluid administration, positioning with the hips flexed and the legs elevated, compression stockings, and gradual, incremental head elevation. Vasoactive drugs may be required to maintain adequate MAP (eg, phenylephrine infusion titrated to effect).

●Pneumocephalus – Supratentorial pneumocephalus (STP) can develop during procedures performed in the sitting position as CSF drains out of the cranial cavity at the durotomy site. In a series of 106 consecutive patients that underwent sitting craniotomy, 42 percent had postoperative STP detected on a computed tomography (CT) scan, with volumes ranging from 6 to 280 mL [58]. Six patients in this series had intraoperative somatosensory-evoked potential (SSEP) changes (ie, reduction in signal amplitude) that were attributed to STP, all of which measured greater than 90 mL in volume on postoperative CT scan.

If symptomatic or associated with loss of intraoperative SSEP signals, STP is usually referred to as tension pneumocephalus. Tension pneumocephalus can result in delayed emergence from anesthesia, locked-in syndrome, and lateral rectus muscle palsy [59-64], and requires emergent evacuation.

Maintenance of anesthesia — The optimal choice of medications for maintenance of anesthesia for craniotomy depends on the degree of preexisting intracranial hypertension, the need for brain relaxation during surgery, the use of neuromonitoring, and the patient's medical issues.

Medications can affect cerebral physiology through changes in cerebral metabolism and blood flow either directly, or indirectly by changing ICP and CPP (table 1). In many cases, a balanced anesthetic including relatively low doses of the potent inhalation anesthetics (ie, isoflurane, sevoflurane, desflurane, and halothane [where available]), with or without nitrous oxide (N₂O), and opioids is appropriate; for patients with elevated ICP, a predominantly IV technique should be used. A strategy for anesthesia during neuromonitoring is discussed separately. (See "Neuromonitoring in surgery and anesthesia", section on 'Anesthetic strategy'.)

The ideal anesthetic regimen (ie, TIVA versus inhalation anesthesia) for elective craniotomy is debated among neuroanesthesiologists, without a clear consensus. A meta-analysis including 14 studies with over 1800 patients who underwent craniotomy reported various outcome measures for TIVA compared with inhalation anesthesia [65]. ICP was approximately 5 mmHg lower and CPP approximately 16 mmHg higher with TIVA than with inhalation anesthesia, with no difference in operative conditions after dural opening, recovery profiles, postoperative complications, or neurologic outcome.

Potent inhalation agents — The potent, halogenated inhalation anesthetics (ie, isoflurane, sevoflurane, desflurane, halothane [where available]) are all dose-dependent cerebral vasodilators. While they reduce CMR, they can blunt cerebral autoregulation by uncoupling CBF and metabolism, and increase CBF [66,67]. The degree to which the potent inhalation agents increase CBF and therefore ICP depends on the balance between these effects. Below 1 minimum alveolar concentration (MAC), the net effect, without other contributing factors, is a modest decrease in CBF, while above 1 MAC, CBF increases [68-70].

Responsiveness to CO₂ is maintained during administration of volatile anesthetics [71].

Nitrous oxide — N₂O can cause increases in CBF, CMR, and ICP. Autoregulation in response to changes in CO₂ appears to be preserved when N₂O is administered [72,73]. The magnitude of changes in cerebral physiology with N₂O is affected by the administration of other anesthetic drugs and by ventilation, as follows:

●N₂O alone – N₂O alone can cause substantial increases in ICP and CBF in normal patients [74] and in patients with intracranial tumors [75].

●N₂O with IV anesthetics – Concomitant administration of IV anesthetic medications can blunt the increase in CBF that occurs with N₂O alone. Studies of CBF when N₂O was added to anesthesia with barbiturates [76,77], opioids [78], benzodiazepines, and propofol [79] have reported minimal or no increase in CBF.

●N₂O with volatile anesthetics – When added to anesthesia with a volatile inhalation anesthetic (ie, isoflurane, sevoflurane, desflurane, or halothane), N₂O can result in a substantial increase in CBF. As an example, one study that compared CBF during 1.5 MAC isoflurane anesthesia with 0.75 MAC isoflurane and 65 percent N₂O reported 43 percent greater CBF with the anesthetic that included N₂O [73].

●N₂O with hyperventilation – Since autoregulation is preserved, hyperventilation can prevent an increase in CBF during N₂O anesthesia [73].

We discontinue nitrous oxide once the dura is closed at the conclusion of surgery, to avoid expansion of any residual subdural air, which could result in delayed emergence from anesthesia.

Intravenous anesthesia — IV anesthetics can be administered for maintenance of anesthesia as part of a balanced anesthetic that includes inhalation agents, or as TIVA. Most commonly, TIVA includes an infusion of propofol along with infusion of a short-acting opioid (eg, remifentanil, fentanyl, alfentanil, or sufentanil). (See "Maintenance of general anesthesia: Overview" and "Maintenance of general anesthesia: Overview", section on 'Total intravenous anesthesia'.)

●Propofol infusion – Propofol infusion causes reduction in CMR, CBF, CBV, and ICP [80-82], while CO₂ responsiveness and autoregulation are maintained [15,83].

●Opioids – When administered as part of IV anesthesia with controlled ventilation, opioids have minimal, clinically irrelevant effects on cerebral physiology [78,84,85]. Morphine may cause histamine release in some patients, which could increase CBF.

●Dexmedetomidine – Dexmedetomidine is a highly selective alpha₂ agonist with sedative, sympatholytic, and analgesic properties that may be administered as an adjuvant for general anesthesia or for conscious sedation for awake craniotomy and other neurosurgical procedures.

Both animal and human studies have shown that dexmedetomidine is a cerebral vasoconstrictor that causes a dose-dependent reduction in CBF [86-90]. The other effects of this drug on cerebral physiology are less clear and may be species-dependent. In dogs, dexmedetomidine has been consistently shown to have no effect on CMR; this, coupled with a reduction in CBF, could lead to cerebral ischemia. In humans, dexmedetomidine may reduce CMR along with CBF, similar to other IV anesthetics. A study in which normal human volunteers received dexmedetomidine sedation reported parallel reductions in CMR and CBF, unchanged during hyperventilation [87].

The vasoconstrictive property of dexmedetomidine may be of theoretical concern in patients at risk for regional cerebral ischemia or compromised flow metabolism coupling (eg, traumatic brain injury [TBI], subarachnoid hemorrhage, intracranial lesions). However, data regarding this issue are limited. A small, retrospective study of patients with acute neurologic injury related to vascular lesions reported no reduction in brain tissue PO₂ with dexmedetomidine administration during craniotomy [91].

Neuromuscular blocking agents — Patients are typically paralyzed during anesthesia for craniotomy unless neuromonitoring precludes the administration of NMBAs. If the anesthetic is lightened during less stimulating periods of surgery, maintenance of neuromuscular block can reduce the chance of coughing or movement. Severe cough can result in straining, increased ICP, and brain herniation through the craniotomy. Movement while skull pins are in place can lead to slipping at the pin site, bleeding, and possible cervical spine injury.

A train-of-four (TOF) peripheral nerve stimulator is used to guide the dose of NMBA and the depth of neuromuscular block. For patients with upper motor nerve lesions and weakness or paralysis, the twitch monitor should be placed on the unaffected side.

We maintain relatively deep neuromuscular block (ie, one to two twitches on TOF stimulation) until the head frame is released from the operating table. Cough and movement while the skull is still fixed in place can result in cervical spine injury. Neuromuscular block should be fully reversed (eg, with neostigmine and glycopyrrolate or sugammadex) prior to emergence. (See "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Reversal of neuromuscular block'.)

Hemodynamic management

Goal for intraoperative blood pressure — BP should be controlled during craniotomy to maintain acceptable CPP (ie, MAP – ICP, or MAP – central venous pressure [CVP] if CVP > ICP). We aim for a CPP of 65 to 80 mmHg. Assuming a normal ICP (or CVP) range of 5 to 10 mmHg, MAP of 75 to 90 mmHg is a reasonable target range for an uncomplicated patient.

With some individual variation, autoregulation of CBF typically occurs within a MAP range of 60 to 150 mmHg [92]. Outside of this range, the brain is unable to compensate for changes in perfusion pressure, and the CBF increases or decreases passively with corresponding changes in pressure, resulting in the risk of ischemia at low pressures and edema or hemorrhage at high pressures. We aim for a MAP above the lower limit of autoregulation, with a margin for error.

The following considerations should determine the goal BP during craniotomy:

●Patient factors – Patient comorbidities may require modification of the goal BP during craniotomy. Normal cerebral autoregulation may be disrupted in patients with ischemic stroke [93], TBI [94], and hypertension. A study of awake patients with drug-induced hypotension reported that the lower limit of cerebral autoregulation was increased in patients with chronic hypertension compared with normotensive controls (113 mmHg versus 73 mmHg) [95].

For patients with hypertension, we usually aim for a mean BP close to baseline.

●Intracranial pathology

•Cerebral autoregulation might be blunted or abolished in certain conditions, either regionally (eg, brain tumors) [96] or globally (eg, TBI) [97,98].

•Occlusive disease of the cerebral arteries may lead to reliance on collateral arterial blood flow; higher CPP would be required to perfuse the ipsilateral brain.

•In patients with elevated ICP, MAP should be increased to maintain adequate cerebral perfusion.

●Procedure-related factors – Surgical maneuvers (eg, application of a temporary clip on a major cerebral artery) may require a higher CPP to assure collateral circulation [99]. In contrast, a lower BP may be required during specific portions of intracranial vascular procedures.

●Anesthetic factors – Volatile anesthetics can blunt cerebral autoregulation. (See 'Potent inhalation agents' above.)

Our approach — Our approach to the maintenance of adequate mean BP is as follows:

●Optimize intravascular volume. (See 'Fluid management' below.)

●Titrate anesthetic agents to match the level of surgical stimulus in order to minimize hypotensive anesthetic effects and hypertensive responses to stimulation. (See 'Surgical steps' above.)

●Administer phenylephrine by infusion at the lowest dose necessary to achieve adequate CPP, titrated to effect.

●Treat hypertension by deepening the anesthetic and, if necessary, by administering titrated boluses of short-acting vasodilators (eg, labetalol 5 to 10 mg IV, esmolol 20 to 50 mg bolus) or, if necessary, by vasodilator infusion (eg, nitroglycerin 10 to 400 mcg/minute IV, or nicardipine 2.5 to 15 mg/hour).

Vasoactive drugs — Vasoactive drugs are commonly administered during anesthesia for craniotomy to achieve BP goals. The effects of these drugs on cerebral physiology are complex and reflect the baseline BP, the status of autoregulatory mechanisms, the mechanism of the drug effect, and the magnitude of BP change:

●Vasopressors – Vasoconstrictors are often administered to counteract the vasodilation that is typically caused by anesthetic agents. Small boluses of short-acting agents are often administered during induction of anesthesia (eg, ephedrine 5 to 10 mg IV, phenylephrine 40 to 80 mcg IV). The effects of phenylephrine and ephedrine on cerebral oxygenation may be different, even at the same blood pressure. In a randomized trial of patients with supratentorial brain tumors, ephedrine was associated with improved cerebral blood flow and regional cerebral oxygen saturation in the normal brain hemisphere but not in the diseased hemisphere, compared with phenylephrine [100]. In this study, ephedrine was administered as an infusion, which is not usual practice.

An infusion of a vasopressor may be required during maintenance of anesthesia, especially during periods of reduced surgical stimulation.

•Phenylephrine – Phenylephrine, a direct alpha₁ adrenergic agonist, is usually the first-choice agent in this setting. The effect of phenylephrine on CBF is controversial. Pure alpha agonists are thought to be systemic, but not cerebral, vasoconstrictors. Therefore, in most circumstances, when BP is increased with phenylephrine, CBF increases [101-103]. However, several studies in anesthetized patients [104,105], and others in awake volunteers [106,107], have suggested that under at least some circumstances, phenylephrine may be associated with a decrease in cerebral oxygenation. Methodologic concerns have been raised over the use of near-infrared spectroscopy for these studies [108], but the possibility of decreased cerebral perfusion with phenylephrine in patients at particular risk should be considered.

•Other vasopressors – Other vasopressors may be indicated, depending on the patient's cardiac function and other comorbidities. A beta₁-receptor agonist (eg, dobutamine) or an agent with both alpha and beta agonist properties (eg, norepinephrine, dopamine) may be required. Low dose vasopressin (eg, 0.01 to 0.04 units per minute) may be useful as a supplementary vasopressor for hypotension refractory to other treatment. Vasopressin at higher doses is usually avoided because it can cause cerebral vasoconstriction [109]. (See "Use of vasopressors and inotropes".)

Similar to phenylephrine, a study of awake volunteers reported a reduction in cerebral oxygenation when norepinephrine was administered [110].

●Vasodilators – Vasodilators or beta blockers may be required during maintenance and emergence from anesthesia. (See 'Emergence from anesthesia' below.)

Vasodilators (ie, nitroprusside, nitroglycerin, hydralazine, and calcium channel blockers) dilate the cerebral circulation and can increase CBF if adequate MAP is maintained. Therefore, vasodilators should be used with caution in patients with increased ICP, as these drugs may increase CBV and exacerbate intracranial hypertension.

●Beta blockers – Beta blockers either reduce or have no effect on CBF and CMR [111].

Antiseizure drugs — Seizure can occur in 15 to 20 percent of patients without history of epilepsy following a nontraumatic supratentorial craniotomy. We administer a single dose of levetiracetam prior to incision for supratentorial craniotomy. Levetiracetam, phenytoin, and fosphenytoin are equally efficacious for seizure prophylaxis. We administer levetiracetam because in contrast with the other two drugs, it is not associated with hypotension during administration, has more reliable pharmacokinetics, and does not require serum monitoring. Also, unlike phenytoin, there is no concern over tissue injury with extravasation of levetiracetam.

Options for antiepileptic drug (AED) administration in this setting include the following:

●Levetiracetam – 500 to 1000 mg IV

●Fosphenytoin – 10 to 20 mg phenytoin equivalents (PE)/kg over 30 minutes, maximum rate 150 mg PE/minute

●Phenytoin – 15 mg/kg IV, ≤50 mg/minute to avoid hypotension and bradycardia

Phenytoin is rarely administered where fosphenytoin is available. Extravasation during administration of IV phenytoin may cause severe tissue necrosis, and inadvertent intraarterial administration of phenytoin has been associated with gangrene.

Patients who are taking AEDs preoperatively should be maintained on their regular doses throughout the perioperative setting to avoid seizures.

Fluid management — Goals of fluid management for craniotomy include maintenance of normovolemia to achieve adequate cerebral perfusion, and avoidance of cerebral edema. Fluid should be administered at a rate and volume that achieves even fluid balance. The following general principles apply:

●Choice of crystalloid solution – Isotonic (eg, plasmalyte), slightly hypotonic (eg, Ringer's lactate), or slightly hypertonic (eg, 0.9% sodium chloride [NaCl]) crystalloid solutions can be administered as maintenance fluid during craniotomy.

•Hypotonic fluid – Hypotonic fluids can increase brain interstitial fluid even in healthy state [112,113]. When used in moderation, this effect is likely not clinically significant.

•Isotonic fluid – Isotonic crystalloid solutions do not increase the interstitial fluid content of the brain with an intact blood–brain barrier.

•Hypertonic fluid – Hypertonic solutions decrease the interstitial fluid content of the brain with an intact blood–brain barrier, pulling water across the cerebral capillary endothelium down its osmotic gradient. Hypertonic saline (HTS) can increase the volume of the brain with impaired blood–brain barrier function [114].

Large volumes of normal saline (0.9% NaCl) can cause hyperchloremic acidosis [115]. As an alternative, plasmalyte, or Ringer's lactate alternating with saline, can be used to avoid hyperchloremic acidosis.

●Colloid solutions – Colloid administration during craniotomy is controversial, especially for patients with TBI. A post-hoc analysis of resuscitation with albumin compared with saline in patients with severe TBI reported worse long-term outcome with albumin [116]. However, this finding may not apply to intraoperative fluid management with cerebral edema from other causes. In a hypovolemic and hypotensive patient, 5 or 25% albumin can be used to restore intravascular volume status quickly.

Starch solutions should be avoided for craniotomy because they can interfere with platelet function and the factor VII clotting complex [117] and could result in bleeding. (See "Intraoperative fluid management", section on 'Hydroxyethyl starches'.)

●Fluid balance – We aim for an even fluid balance during craniotomy. Positive fluid balance can create or worsen cerebral edema [112], while hypovolemia may reduce CPP.

Urine output can be large when mannitol and diuretics are administered for brain relaxation. In this setting, we match urine output with fluid administration, modified as required to replace blood loss. (See "Intraoperative fluid management", section on 'Monitoring intravascular volume status'.)

Ventilation — The goal partial pressure of CO₂ (PaCO₂) should be discussed with the surgeon preoperatively. Hyperventilation and the resulting reduction in CBF may be required to reduce ICP or to improve surgical exposure by relaxing the brain. (See "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis", section on 'Cerebral blood flow' and 'Planned brain relaxation' below.)

General considerations include the following:

●Hypercarbia should always be avoided during craniotomy. Elevations in PaCO₂ result in increased CBF and may increase ICP. Unless hyperventilation is required, we maintain PaCO₂ at 35 to 38 mmHg.

●Therapeutic hyperventilation should be guided by blood gases rather than by ETCO₂. While ETCO₂ generally correlates well with PaCO₂, a number of factors (eg, age, lung disease, surgical positioning) can result in significant discrepancy [118,119]. In our clinical experience, PaCO₂ is commonly 8 to 10 mmHg higher than ETCO₂ in patients with COPD though this difference is variable.

●The vasoconstriction that accompanies hyperventilation may result in ischemia, particularly for at-risk brain tissue (eg, after TBI, after subarachnoid hemorrhage, or under surgical retractors during craniotomy). Hyperventilation to a PaCO₂ of 25 to 30 mmHg can improve surgical conditions during supratentorial craniotomy [120]. However, multiple human and animal studies using a variety of methodologies have reported evidence of brain ischemia in injured brains with hyperventilation to a PaCO₂ of 25 to 30 mmHg [121].

Therefore, we believe that hyperventilation should be used only when indicated. As part of a multimodal approach to brain relaxation for surgical exposure, we hyperventilate as briefly as possible to achieve a PaCO₂ of 30 to 35 mmHg. Ventilation should be returned to normal gradually to avoid rebound cerebral vasodilation.

Hyperventilation for acute cerebral edema is discussed separately. (See 'Intraoperative cerebral edema' below.)

Brain relaxation — Brain relaxation, or brain shrinkage, may be part of the surgical plan or may be required in response to unexpected brain swelling or tightness during the procedure.

Brain relaxation or shrinkage may be required to improve surgical exposure and to avoid ischemia related to pressure from retractors placed during surgery. Techniques for this purpose include administration of diuretics to reduce intravascular volume, mannitol or 3% hypertonic saline for osmotherapy, glucocorticoids to reduce swelling, hyperventilation for vasoconstriction, and elevation of the patient's head to facilitate venous drainage. For some procedures, a lumbar cerebrospinal fluid (CSF) drain is placed preoperatively to reduce brain bulk.

Osmotherapy works by creating an osmotic gradient that draws water out of brain tissue to reduce brain bulk. Effective osmotherapy with mannitol or hypertonic saline requires an intact blood brain barrier; areas of brain with a disrupted blood–brain barrier may swell more with osmotherapy [114].

Planned brain relaxation — When brain relaxation is planned as part of the procedure, in consultation with the surgeon, we use the following regimen after induction of anesthesia:

●Furosemide 10 to 20 mg IV

●Dexamethasone 10 mg IV

●Osmotherapy with mannitol 0.5 to 1g/kg IV administered over 10 to 15 minutes to avoid hypotension, or 3% hypertonic saline 3 to 5 mL/kg [122] (see 'Intraoperative cerebral edema' below)

●Hyperventilation to ETCO₂ 27 to 32 mmHg (aiming for PaCO₂ of 30 to 35 mmHg) (see 'Ventilation' above)

Intraoperative cerebral edema — If the surgeon encounters cerebral edema (ie, the "tight brain"), management requires a quick review of the physiologic principles of ICP dynamics, and optimization. We use the following checklist to manage cerebral edema:

●Is cerebral venous drainage optimal?

•Patient position – Elevation of the head should be the first maneuver attempted to improve venous drainage from the brain. If possible, adjustment of head rotation may improve venous drainage as well.

•Intrathoracic pressure – Positive intrathoracic pressure impedes venous return to the right heart. If oxygenation permits, discontinuing positive end-expiratory pressure (PEEP) and adjusting the ventilator settings to decrease mean airway pressure may improve venous return.

•Right heart function – If there is a decrease in right heart contractility, this could lead to an elevation of CVP and decrease in venous return. Therefore, any myocardial dysfunction, especially right heart failure, should be treated appropriately.

●Is there cerebral vasodilation?

•Hypercapnia – Increase in minute ventilation may reduce cerebral vasodilation, depending on the starting ETCO₂ and PaCO₂. A sample should be sent for arterial blood gas measurement to guide therapy.

•Inhalation anesthetic agents – Volatile anesthetic and/or N₂O should be discontinued and the anesthetic converted to TIVA.

•Increased CMR – Temperature elevation and increased sympathetic activity (eg, seizures, light anesthesia) should be treated.

●Can CSF be drained? – If an EVD or lumbar drain is in place, evacuation of CSF can rapidly reduce ICP. CSF should be drained in increments (eg, 5 to 10 mL at a time) with ongoing assessment of brain conditions.

●Is osmotherapy indicated? – If the steps above are ineffective, osmotherapy is indicated. For osmotherapy to treat intraoperative cerebral edema, we administer 0.5 to 1 g/kg of mannitol, 3 to 5 mL/kg of 3% NaCl, or 0.4 mL/kg of 23.4% NaCl, over 15 to 20 minutes. For emergent therapy (eg, active brainstem herniation), we administer 23.4% NaCl, 30 mL over ≤3 minutes.

Mannitol (usually 20% solution) and various concentrations (3, 7.5, and 23.4%) of HTS have comparable efficacy in equiosmolar doses [123]; 20% mannitol and 3% NaCl are roughly equiosmolar. The following considerations apply during osmotherapy:

•Mannitol – Twenty percent mannitol can be administered via a peripheral IV, and should be infused over 15 to 20 minutes to avoid hypotension. Mannitol causes an initial increase in intravascular volume followed by osmotic diuresis and net negative fluid balance. Mannitol should be avoided in patients who may not tolerate the initial increase in intravascular volume (eg, patients with congestive heart failure) or who cannot eliminate mannitol (eg, patients with renal dysfunction).

•HTS – Three percent NaCl can be administered via a peripheral IV, while more concentrated solutions (ie, 7.5 and 23.4%) must be administered through a CVC; except for emergent situations, HTS should be infused over 15 to 20 minutes. HTS causes a sustained increase in plasma volume. Concerns related to HTS therapy include the following:

-Rapid administration of HTS can result in hypervolemia and hypertension due to rapid expansion of blood volume; this is rarely of clinical concern in the operating room (OR).

-Rapid administration of HTS can cause acute elevation of serum sodium. As an example, administration of approximately 5 mEq/kg of sodium (approximately 45 mL of 23.4% NaCl) over two minutes can increase plasma sodium from 140 to 152 mEq/L. While osmotic demyelination syndrome (ODS) has occurred with rapid elevation in patients with severe hyponatremia, there are no reports of ODS occurring in the setting of osmotherapy for brain relaxation in normonatremic patients. (See "Osmotic demyelination syndrome (ODS) and overly rapid correction of hyponatremia".)

-Rapid administration of concentrated HTS (ie, 30 mL of 23.4% NaCl over less than one minute) can cause osmotic disruption of the blood–brain barrier, which can result in seizures, cerebral edema, and intracranial hypertension.

●Is intracranial hypertension still refractory to treatment? — High dose barbiturate therapy (eg, pentobarbital 5 to 20 mg/kg IV bolus, followed by 1 to 4 mg/kg per hour, titrated to EEG burst suppression) may be used to control elevated ICP refractory to maximum standard medical treatment. It should be noted that pentobarbital, even after administration for a few hours at this dose range, will have a very long context-sensitive half-life. Vasopressor therapy may be required to maintain adequate cerebral perfusion pressure if high dose barbiturate causes hypotension.

Alternatively, propofol can be used to help control ICP, but caution is required as high dose propofol is associated with significant morbidity. (See "Management of acute moderate and severe traumatic brain injury", section on 'Sedation and analgesia'.)

Brain protection — Management of temperature and glucose is important for patients with brain injury and ischemia (eg, during aneurysm clipping). In addition, in these settings, medications are often administered for neuroprotection (eg, barbiturates, propofol). Neuroprotection during craniotomy is discussed separately. (See "Anesthesia for intracranial neurovascular procedures in adults" and "Anesthesia for patients with acute traumatic brain injury", section on 'Neuroprotection'.)

Glycemic control — We manage glucose and insulin administration (IV bolus or infusion of regular insulin) to achieve blood glucose of 110 to 150 mg/dL, and treat values above 180 mg/dL.

Hypoglycemia causes and exacerbates neuronal damage and should be avoided during craniotomy [124]. However, hyperglycemia is associated with increased morbidity and mortality after TBI [125-127] and decreased survival after brain tumor resection [128,129]. (See "Anesthesia for patients with acute traumatic brain injury", section on 'Glucose management'.)

Neither the glucose level above which neuronal damage occurs nor an ideal target plasma glucose concentration have been established, but tight glucose control (ie, target blood glucose of 80 to 110) is associated with increased risk of hypoglycemia. (See "Glycemic control in critically ill adult and pediatric patients".)

Emergence from anesthesia — Most patients are awoken and extubated in the OR after craniotomy. Extubation may be delayed for patients who undergo infratentorial surgery if there are concerns for lower cranial nerve dysfunction that might impact airway reflexes, and for patients who undergo long procedures in the prone position [130-132].

Management of emergence — The ideal emergence should be smooth, with avoidance of cough, straining, and hypertension, and with the patient awake enough for an adequate neurologic examination (eg, responding to commands, moving all extremities on command, adequate vision assessment). Goals for emergence include the following:

●Minimal residual anesthesia – Ideally, a neurologic exam is performed at the end of the craniotomy before leaving the OR. Neuromuscular block should be fully reversed, and anesthetic agents used for maintenance should be at effect-site concentrations compatible with return of consciousness (eg, inhalation agents less than 0.2 MAC-equivalent end tidal concentration, propofol titrated downward as surgery ends).

●Plan for postoperative pain control – In contrast with other surgical procedures, opioids should not be administered at a dose that is expected to prevent anticipated pain, but rather titrated as needed following extubation and neurologic exam.

As an example, after stopping a remifentanil infusion at the end of surgery, we usually perform a neurologic exam before administering a small dose of a short-acting opioid (eg, fentanyl 0.5 to 1 mcg/kg IV in the OR). We titrate further analgesics in the recovery room or intensive care unit (ICU). In our experience, more liberal opioid dosing based on anticipated pain or guided by hemodynamic endpoints (eg, to keep systolic BP below 160 mmHg) often results in somnolence, a delay in a satisfactory neurologic examination, and occasionally unnecessary head imaging.

We reserve long-acting opioids, such as hydromorphone (0.2 mg IV), for patients with no preoperative altered mental status and for those who have been taking preoperative or chronic opioids prior to the craniotomy.

●Hemodynamic management – Following a routine tumor resection for a patient without chronic hypertension or with controlled chronic hypertension, we aim to maintain a systolic blood pressure of <160 mmHg, as systolic pressures >160 mmHg are associated with increased risk of postoperative intracranial hemorrhage [133,134].

Hypertension is common on emergence from anesthesia for craniotomy and should be treated quickly. In addition to an association with intracranial hemorrhage [133], hypertension can also worsen cerebral edema in those areas where the blood–brain barrier is disrupted. Treatment should be titrated to avoid hypotension, cerebral hypoperfusion, and enlargement of an area of cerebral ischemia [135].

Medications commonly administered to control hypertension on emergence include the following:

•Labetalol – Labetalol is a combined alpha-adrenergic and beta-adrenergic blocker, with onset of IV administration within five minutes and duration of action of three to six hours. Unless beta block is contraindicated (eg, reactive airways disease), labetalol is our first-line treatment for emergence hypertension in this setting. We follow a stepwise titration, with initial dose of 0.2 mg/kg followed by subsequent doses of 0.4, 0.8, and 1.6 mg/kg every 10 minutes while monitoring BP continuously. The maximum dose can be repeated up to three total doses, not to exceed a cumulative dose of 300 mg.

•Esmolol – Esmolol is an ultrashort-acting beta₁ selective antagonist that can be administered by bolus (0.25 to 1 mg/kg IV) or infusion (0.1 to 0.25 mcg/kg/minute IV) [136,137]. Esmolol is useful when hypertension is likely to resolve quickly (eg, once postoperative pain is controlled). Without infusion or supplementation with a longer-acting antihypertensive medication, esmolol can lead to rebound hypertension.

•Nicardipine – Nicardipine is a short-acting calcium channel blocker with onset in <2 minutes and duration of action of approximately 60 minutes. For treatment of hypertension in this setting, nicardipine can be a useful alternative to labetalol. Because of its relatively short duration of action, it is usually either administered by infusion (2.5 to 15 mg/hour IV) or with a longer-acting antihypertensive medication. Nicardipine can also be administered as a bolus (0.5 to 2 mg IV). A prospective study of preemptive BP control in 42 craniotomy patients reported that when added to enalaprilat, nicardipine (2 mg boluses IV) was as effective as labetalol (5 mg boluses IV) at controlling postoperative BP [138].

●ICP control – Emergence should be managed to avoid coughing, straining, retching, and vomiting, all of which can increase CVP and ICP. Prophylactic antiemetics should be administered routinely, and airway suctioning should be performed before the depth of anesthesia is lightened.

Hypoventilation on emergence can result in increased PaCO₂ and can cause cerebral vasodilation and increased ICP; during emergence, ventilation should be assisted until the patient maintains adequate minute ventilation.

Delayed emergence — When the patient is slow to emerge from anesthesia, the cause may be related to surgical, anesthetic, preexisting, or physiologic factors. If the patient has a significant preoperative neurologic deficit, emergence may be delayed and extubation may need to be deferred. When there is a high likelihood that the surgical procedure may improve the patient's mental status (eg, evacuation of a large epidural hematoma), neurologic exam may be attempted and extubation considered.

●Delayed emergence checklist – As some potential causes require emergent action, assessment of the patient who fails to emerge from anesthesia should include the surgeon and should proceed in a systematic fashion. (See "Delayed emergence and emergence delirium in adults", section on 'Delayed emergence'.)

The following checklist can be used to evaluate the patient in this setting:

•Vital signs – BP, temperature, oxygen saturation, respiratory rate and ETCO₂ should be assessed and abnormalities corrected.

•Reversal of NMBAs – Reversal should be assessed with a TOF nerve stimulator.

•Residual anesthetic medication – End-tidal inhalation anesthetic should be noted; residual propofol and/or opioid effect should be considered. A processed EEG monitor for anesthetic effect may be useful.

If opioid effect is likely, reversal with naloxone (40 to 80 mcg IV every two to four minutes) may be attempted cautiously, as naloxone may reverse analgesia and cause sudden hypertension.

If benzodiazepine effect is likely, reversal with flumazenil can be attempted (flumazenil 0.2 mg IV over 15 seconds, repeated as necessary at one-minute intervals to maximum 1 mg IV). (See "Delayed emergence and emergence delirium in adults", section on 'Benzodiazepines'.)

•Metabolic status – Capillary blood glucose, arterial blood gases, and electrolytes should be measured.

•Surgical causes – Cerebral edema, intracerebral hematoma, and ischemia (total occlusion of an artery or hypoperfusion) are potential surgical causes for a delayed emergence. Pupils should be examined along with response to pain and reflexes.

When no cause for delayed emergence can be identified, an emergent CT scan should be performed to assess for intracranial hemorrhage, brain edema, pneumocephalus, or other pathology.

Differential emergence or awakening — Transient focal neurologic deficits can occur following sedation or general anesthesia in patients with a prior history of a neurologic deficit related to stroke, brain tumor, and carotid disease. In the context of anesthesia, this phenomenon has been called differential awakening; patients typically exhibit a focal motor deficit immediately upon emergence that improves over 30 minutes to several hours. The mechanism remains to be elucidated, but the time course suggests a pharmacologic cause.

Transient focal neurologic deficits have been elicited with administration of both sedatives and opioids to patients with a history of neurologic deficits [139-142], and in patients with brain mass lesions without known deficits [143,144]. Reversal of opioid-induced deficits with naloxone and of midazolam induced-deficits with flumazenil [144] have been reported.

When a focal neurologic deficit is evident on emergence from anesthesia, multidisciplinary evaluation should be performed, with differential emergence included among potential etiologies.

Postoperative care — Although debated, even an uneventful craniotomy remains an indication for admission to the ICU [145]. The primary indication for intensive care is to allow serial (usually hourly) neurologic exams and rapid response to abnormalities. In addition, postoperative intensive care allows continuous BP monitoring and control, ICP monitoring when required, and treatment of pain and PONV.

OUR ANESTHESIA STRATEGY — There are many ways to safely manage anesthesia for craniotomy. Our usual strategy for these procedures, which must be modified based on patient factors and the specific surgery, is as follows:

●Supratentorial nonvascular craniotomy without preexisting intracranial hypertension:

•Premedication – Individualized: Acceptable to use no premedication or midazolam 1 to 2 mg intravenously (IV) in divided doses, if needed

•Induction

-Fentanyl 2 to 4 mcg/kg IV or remifentanil 1 to 3 mcg/kg IV

-Lidocaine 1 to 1.5 mg/kg IV

-Propofol 1.5 to 2 mg/kg IV

-Rocuronium 0.6 mg/kg IV

•Maintenance

-Sevoflurane 0.6 to 0.8 minimum alveolar concentration (MAC) end-tidal concentration (titrate to bispectral index [BIS] of 50 to 60, if monitored)

-Fentanyl 1 to 2 mcg/kg every one to two hours or remifentanil 0.05 to 0.2 mcg/kg/minute

-Rocuronium titrated to one to two twitches in train-of-four (TOF) (if not contraindicated with motor evoked potential [MEP] monitoring)

•Fluids – 0.9% sodium chloride (NaCl) to match urine output

•Ventilation – Titrated to achieve partial pressure of carbon dioxide (PaCO₂) 35 to 40 mmHg

•Antiemetic – Ondansetron 4 mg IV one hour prior to emergence

•Pain control alternatives (see 'Emergence from anesthesia' above):

-If remifentanil infusion has been administered, prompt postoperative neurologic examination, followed by fentanyl 1 mcg/kg IV, further fentanyl or hydromorphone titrated to effect

Or

-If fentanyl administered intraoperatively, further fentanyl titrated to effect postoperatively

Or

-Morphine 3 to 5 mg IV or hydromorphone 0.5 mg IV 30 minutes prior to emergence, further opioid titrated to effect after postoperative neurologic examination

●Supratentorial nonvascular craniotomy with concerns for preexisting intracranial hypertension:

•Premedication – No premedication preferable

•Induction

-Fentanyl 2 to 4 mcg/kg IV or remifentanil 1 to 3 mcg/kg IV

-Lidocaine 1 to 1.5 mg/kg IV

-Propofol 1.5 to 2 mg/kg IV

-Rocuronium 0.6 mg/kg IV

•Maintenance: Total IV anesthesia (TIVA)

-Propofol 70 to 140 mcg/kg/minute (titrate to BIS of 50 to 60, if monitored)

-Remifentanil 0.05 to 0.3 mcg/kg/minute (higher in range if neuromuscular blocking agent [NMBA] is not used)

-Rocuronium titrated to one to two twitches in TOF (if not contraindicated by neuromonitoring)

•Fluids – 0.9% NaCl to match urine output

•Ventilation – Titrated to achieve PaCO₂ 30 to 35 mmHg

•Antiemetic – Ondansetron 4 mg IV one hour prior to emergence

•Pain control alternatives:

-If remifentanil infusion administered intraoperatively, prompt postoperative neurologic examination, followed by fentanyl 1 mcg/kg IV, further fentanyl or hydromorphone titrated to effect

Or

-If fentanyl administered intraoperatively, further fentanyl titrated to effect postoperatively

Or

-Morphine 3 to 5 mg IV or hydromorphone 0.5 mg IV 30 minutes prior to emergence, further opioid titrated to effect after postoperative neurologic examination

SUMMARY AND RECOMMENDATIONS

●Preoperative planning – The anesthesiologist and surgeon should discuss preexisting increased ICP, positioning for surgery, the risk of venous air embolism (VAE), goals for blood pressure (BP) and ventilation (goal partial pressure of CO₂ [PaCO₂]), and whether neurophysiologic monitoring will be used. (See 'General concerns' above.)

●Choice of anesthetic technique – General endotracheal anesthesia is the preferred technique, though for specific indications, the craniotomy can be performed awake. (See 'Anesthetic management' above.)

●Choice of anesthetic medications

•Total intravenous versus inhalation anesthesia – The optimal anesthetic regimen for elective craniotomy is controversial. In many cases, we use a balanced anesthetic including low doses of a potent inhalation anesthetic (ie, isoflurane, sevoflurane, desflurane, and halothane), with or without nitrous oxide (N₂O), and opioids; a predominantly intravenous (IV) technique is preferred for patients with elevated intracranial pressure (ICP). (See 'Maintenance of anesthesia' above and 'Our anesthesia strategy' above.)

•Effects on cerebral physiology – Anesthetics have a variety of effects on cerebral physiology (table 1).

-IV induction agents – With the exception of ketamine, IV induction agents (ie, propofol, barbiturates, etomidate) cause reductions in both cerebral metabolic rate (CMR) and cerebral blood flow (CBF), resulting in no change or a decrease in ICP, while responsiveness to carbon dioxide (CO₂) is maintained. (See 'Anesthesia induction agents' above.)

-Volatile anesthetics – Isoflurane, sevoflurane, desflurane, and halothane are dose-dependent cerebral vasodilators. While they reduce CMR, they can blunt cerebral autoregulation by uncoupling CBF and metabolism and increase CBF and ICP. Below 1 minimum alveolar concentration (MAC), there is a modest decrease in CBF. Above 1 MAC, CBF increases. Responsiveness to CO₂ is maintained. (See 'Potent inhalation agents' above.)

-N₂O – N₂O can increase CBF, CMR, and ICP, with preserved CO₂ responsiveness. The magnitude of changes in cerebral physiology with N₂O is affected by the administration of other anesthetic drugs and by ventilation. (See 'Nitrous oxide' above.)

-Propofol infusion – Propofol infusion causes reduction in CMR, CBF, and ICP, while CO₂ responsiveness is maintained. (See 'Intravenous anesthesia' above.)

-Opioids – When administered with controlled ventilation, opioids have minimal effects on cerebral physiology. (See 'Intravenous anesthesia' above.)

●Positioning – Positioning for craniotomy requires meticulous attention to detail to avoid nerve injury, skin pressure injuries, ocular injury, and airway compromise. Supine, prone, lateral, or sitting positions may be used. The sitting position is associated with a higher risk of VAE, hypotension, and pneumocephalus and is relatively contraindicated in those with a potential right-to-left intracardiac shunt. (See 'Positioning' above.)

●Blood pressure goal – BP should be controlled during craniotomy to maintain adequate cerebral perfusion pressure (CPP). We aim for a CPP of 65 to 80 mmHg. Assuming a normal ICP of 5 to 10 mmHg, mean arterial pressure (MAP) of 75 to 90 mmHg is a reasonable target range for an uncomplicated patient. (See 'Hemodynamic management' above.)

●Fluid management – IV fluid should be administered at a rate and volume that achieves even fluid balance to achieve adequate cerebral perfusion and avoidance of cerebral edema. We administer 0.9% saline to match urine output. (See 'Fluid management' above.)

●Ventilation – Hypercarbia should always be avoided during craniotomy. Hyperventilation reduces CBF and may be required to reduce ICP or to improve surgical exposure by relaxing the brain. Hyperventilation should not be used routinely, as the vasoconstriction that accompanies hyperventilation may result in brain ischemia. When indicated, hyperventilation should be guided by blood gases rather than by end-tidal CO₂ (ETCO₂), aiming for a PaCO₂ of 30 to 35 mmHg. (See 'Ventilation' above.)

●Brain relaxation – Brain relaxation may be part of the surgical plan, or it may be required in response to unexpected brain swelling. (See 'Brain relaxation' above.)

●Emergence – Emergence from anesthesia for craniotomy should be rapid and smooth to allow a postoperative neurologic examination. Opioids should be titrated as needed after emergence. Hypertension is common on emergence and should be treated rapidly. (See 'Emergence from anesthesia' above.)