Anesthesia For Craniotomy

Anesthesia for craniotomy - UpToDate 14/12/21 9'28
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Anesthesia for craniotomy

Authors: Chanannait Paisansathan, MD, Mehmet S Ozcan, MD, FCCP
Section Editor: Jeffrey J Pasternak, MD
Deputy Editor: Marianna Crowley, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Nov 2021. | This topic last updated: Aug 11, 2021.
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
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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 after 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
2
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
2 2
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 g/dL, and treat values above 180
g/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 critical illness".)
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
● Anesthetic management for craniotomy should be designed to maintain optimal

cerebral physiology. General endotracheal anesthesia is the preferred technique,
though for specific indications, the craniotomy can be performed awake.
● The optimal anesthetic regimen (ie, total intravenous anesthesia [TIVA] versus
inhalation anesthesia) for elective craniotomy is controversial. In many cases, we use
a balanced anesthetic including relatively 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.)
● Anesthetics have a variety of effects on cerebral physiology ( table 1).
• In general, 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.)
• The potent, halogenated inhalation anesthetics (ie, isoflurane, sevoflurane,

desflurane, halothane) are all 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 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.)
• IV agents may be used for maintenance of anesthesia along with inhalation

agents, or as TIVA. Most commonly, propofol is administered as an infusion,
along with opioids. Propofol infusion causes reduction in CMR, CBF, and ICP, while
CO2 responsiveness is maintained. When administered with controlled
ventilation, opioids have minimal effects on cerebral physiology. (See
'Intravenous anesthesia' above.)
● The anesthesiologist and surgeon should have a preoperative discussion regarding

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.)
● 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.)
● 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.)
● 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.)
● 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 may be part of the surgical plan, or it may be required in response
to unexpected brain swelling. (See 'Brain relaxation' above.)
● 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.)
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Topic 93391 Version 27.0
GRAPHICS
The effects of anesthetic agents on cerebral physiology
Anesthetic Cerebral
CMRO 2 CBF ICP
agents autoregulation
Nitrous oxide ↑↑ ↑↑↑ ↑↑ No change
Sevoflurane ↓ ↑↑ ↑ No change
Isoflurane ↓↓ ↑ ↑ No change
Desflurane ↓ ↑↑↑ ↑↑ No change
Propofol, ↓↓↓ ↓↓↓ ↓↓ No change

thiopental, and
etomidate
Benzodiazepines ↓ ↓↓ ↓ No change
Ketamine ↑↑ Unknown Unknown No change
Dexmedetomidine ↓↓ ↓ No change ↓
Opioids ↑ ↓↓ ↓ No change
For further details, refer to the UpToDate topic on anesthesia for craniotomy.
CMRO 2 : cerebral metabolic rate of oxygen; CBF: cerebral blood flow; ICP: intracranial pressure.
Graphic 105673 Version 3.0
Contributor Disclosures
Chanannait Paisansathan, MD No relevant financial relationship(s) with ineligible companies to
disclose. Mehmet S Ozcan, MD, FCCP No relevant financial relationship(s) with ineligible companies to
disclose. Jeffrey J Pasternak, MD No relevant financial relationship(s) with ineligible companies to
disclose. Marianna Crowley, MD No relevant financial relationship(s) with ineligible companies to
disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

Anesthesia For Craniotomy - UpToDate

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Anesthesia for craniotomy - UpToDate 14/12/21 9'28

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Craniotomy is performed for a variety of indications, including tumor resection,

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

reappearance of prior deficits may represent differential emergence, and may

Alternatively, transesophageal echocardiography (TEE) can be performed after

Medications — As usual, the patient's medications should be reviewed; considerations in

● Anticonvulsants – Many patients who undergo craniotomy are taking

● Glucocorticoids – Patients with intracranial masses may be taking glucocorticoids.

● Anticoagulants – In most cases, aspirin, nonsteroidal antiinflammatory drugs, and

preoperative blood tests, chest radiograph, and electrocardiogram (ECG) should be

PLANNING THE ANESTHETIC

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

● What is the expected blood loss?

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

● Will neurophysiologic monitoring (ie, evoked potentials, electroencephalography,

Pinning is a brief, sudden, and painful stimulus comparable to incision or

● Preincision preparation – After skull pinning, a light level of anesthesia is required

● Intracranial procedure – Depending on the indication and location of the

● Wound closure – After completion of the intracranial procedure, hemostasis is

Monitoring — Standard American Society of Anesthesiologists (ASA) monitors (ie,

Arterial catheterization — Continuous BP monitoring with an intra-arterial catheter is

Neurophysiologic monitoring — Intraoperative electroencephalography (EEG) and

Intracranial pressure monitoring — Patients may have an extraventricular drain (EVD)

Processed electroencephalography — When total IV anesthesia (TIVA) is used, we use a

Intravenous access — We place two IV catheters for most routine craniotomies.

Central venous catheterization — A CVC may be placed for central administration of

Premedication — Premedication for craniotomy should be individualized based on the

Induction of anesthesia — Similar to anesthesia for most other procedures, IV induction

● Hemodynamic stability – Drugs and doses should be selected to maintain CPP

● Avoidance of increase in ICP – Medication and ventilation should be managed to

Anesthesia induction agents — In general, with the exception of ketamine, IV induction

● Barbiturates – Barbiturates for induction of anesthesia include thiopental (3 to 6

The effects of etomidate on cerebral vasculature are complex. In animal models,

Etomidate is associated with a higher rate of postoperative nausea and vomiting

● Ketamine – The effects of ketamine on cerebral physiology are controversial. Data

Opioids — An opioid is usually administered as part of induction of anesthesia to reduce

Lidocaine — Lidocaine (1 to 1.5 mg/kg IV) may be administered during induction of

Neuromuscular blocking agents — In most cases, a neuromuscular blocking agent

Nondepolarizing NMBAs have no direct effects on cerebral physiology. Less commonly

For RSII in patients in whom ICP is a concern, we administer a defasciculating dose of

Positioning — Positioning for craniotomy requires meticulous attention to detail. These

General concerns related to positioning include the following:

● VAE – The incidence of VAE in sitting craniotomy is reported to be between 18 and 76

● Cardiovascular effects – The vasodilation and myocardial depression that can

positioning for surgery and anesthesia in adults", section on 'Physiologic effects of

Hemodynamic changes can be mitigated by IV fluid administration, positioning with

● Pneumocephalus – Supratentorial pneumocephalus (STP) can develop during

If symptomatic or associated with loss of intraoperative SSEP signals, STP is usually

Maintenance of anesthesia — The optimal choice of medications for maintenance of

craniotomy is debated among neuroanesthesiologists, without a clear consensus. A meta-

Potent inhalation agents — The potent, halogenated inhalation anesthetics (ie,

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

● N2O with IV anesthetics – Concomitant administration of IV anesthetic medications

● N2O with hyperventilation – Since autoregulation is preserved, hyperventilation

Intravenous anesthesia — IV anesthetics can be administered for maintenance of

● Opioids – When administered as part of IV anesthesia with controlled ventilation,

● Dexmedetomidine – Dexmedetomidine is a highly selective alpha2 agonist with

The vasoconstrictive property of dexmedetomidine may be of theoretical concern in

Neuromuscular blocking agents — Patients are typically paralyzed during anesthesia

Goal for intraoperative blood pressure — BP should be controlled during

autoregulation, with a margin for error.