Intracranial Compartments

The skull can be compared to a rigid container with almost incompressible contents. Under normal conditions, the intracranial space is occupied by the brain and its interstitial fluid (80%), cerebrospinal fluid (CSF, 10%), and blood (10%). In pathologic states, space-occupying lesions such as edema, tumors, hematomas, or abscesses alter these proportions. The Monro-Kellie hypothesis, elaborated in the 19th century, states that the sum of all intracranial volumes is constant. An increase in volume of one compartment must be accompanied by an approximately equal decrease in volume of the other compartments, except when the cranium can expand to accommodate a larger volume. Gradual increases in intracranial volumes, such as a slow-growing tumor or hydrocephalus, can be compensated by the compliant nature of open fontanelles and sutures in young children; increasing head circumference can result.¹ However, herniation can occur in children with open fontanelles if large increases in intracranial pressure (ICP) develop acutely. In the nonacute situation, the brain can compensate for pathologic increases in intracranial volume by intracellular dehydration and reduction of interstitial fluid.^2–4

Under normal conditions, CSF exists in dynamic equilibrium, with absorption balancing production. The rate of CSF production in adults is approximately 0.35 mL/min or 500 mL/day.⁵ The average adult has 100 to 150 mL of CSF distributed throughout the brain and subarachnoid space. Children have correspondingly smaller volumes of CSF, but the rate of CSF production is similar to that of adults.^5,6

Production of CSF is only slightly affected by alterations of ICP and is usually unchanged in children with hydrocephalus.⁶ Some drugs, including acetazolamide, furosemide, and corticosteroids, are mildly effective in transiently decreasing CSF production.^1,7,8 There is an inverse relationship between the rate of CSF production and serum osmolality; an increase in serum osmolality causes a decrease in CSF production. Choroid plexus papillomas causing overproduction of CSF are rare but are more likely to occur during childhood.

Absorption of CSF is not well understood, but the arachnoid villi appear to be important sites for reabsorption of CSF into the venous system. One-way valves between the subarachnoid space and the sagittal sinus appear to open at a gradient of about 5 mm Hg. Some resorption may occur from the spinal subarachnoid space and from the ependymal lining of the ventricles. Resorption increases with an increase in ICP. However, CSF absorption is decreased by pathologic processes that obstruct arachnoid villi or interfere with CSF flow, such as intracranial hemorrhage, infection, tumor, and congenital malformations.⁹

Intracranial Pressure

Increased ICP causes secondary brain injury by producing cerebral ischemia and ultimately causing herniation. Ischemia occurs when ICP increases and cerebral perfusion pressure (CPP) decreases. As cerebral blood flow (CBF) and the supply of nutrients are curtailed, cell damage and death occur, leading to increased intracellular and extracellular water and further increases in ICP. When ICP increases, CPP can decrease, the brain can become ischemic, and cell death can ensue (Fig. 24-1).¹⁰

FIGURE 24-1 Cerebral blood flow (CBF), cerebral perfusion pressure (CPP), and brain ischemia. Changes in CBF and CPP affect neuronal synaptic function and cellular integrity. When CBF decreases to 15 to 20 mL/100 g/min, there is distinct neuronal dysfunction on the electroencephalogram (EEG). At 15 mL/100 g/min, the EEG is essentially flat, and electrical activity ceases to function. At 6 to 15 mL/100 g/min, a penumbral state occurs in which there is energy for cellular integrity but insufficient energy for synaptic function. Neuronal survival is unlikely if this low CBF is allowed to persist for more than an ill-defined but critical period. At less than 6 mL/100 g/min, there is no energy for cellular membrane integrity. Infarction occurs at this stage unless reperfusion is accomplished immediately.

Intracranial Compliance

The absolute value of ICP does not indicate how much compensation is possible. If the ICP increases significantly, compensatory mechanisms have failed. However, pathologic states may be present despite an ICP within the normal range. Intracranial compliance (i.e., the change in pressure relative to a change in volume) is a valuable concept. Figure 24-2 is a schematic diagram of the relationship between the addition of volume to intracranial compartments and ICP. The shape of the curve depends on the time over which the volume increases and the relative size of the compartments. At normal intracranial volumes (point 1), ICP is low, but compliance is high and remains so despite small increases in volume. If volume increases rapidly, compensatory abilities are surpassed, and further increases in volume are reflected as increases in pressure. This can occur when the ICP is still within normal limits but the compliance is low (point 2). If the ICP is already increased further volume expansion causes a rapid increase in ICP (point 3). In clinical practice, compliance can be evaluated with a ventriculostomy catheter or by observing the response of ICP to external stimulation (e.g., tracheal suction, coughing, agitation).

FIGURE 24-2 Idealized intracranial compliance curve for intracranial pressure (ICP) plotted against intracranial volume.

Several physiologic and mechanical factors such as a greater percentage of brain water content, less CSF volume, and greater percentage of brain content to intracranial capacity contribute to a relatively decreased intracranial compliance in children compared with adults.² Children may be at increased risk for herniation compared with adults when similar relative increases in ICP have occurred. However, infants faced with a slowly increasing ICP may have a greater compliance due to their open fontanelles and sutures.

Cerebral Blood Volume and Cerebral Blood Flow

In addition to CSF, cerebral blood volume (CBV) represents another compartment in which compensatory mechanisms influence ICP. Although the CBV occupies only 10% of the intracranial space, changes related to dynamic blood volume occur, often initiated by anesthesia or intensive care procedures. As with other vascular beds, most intracranial blood is contained in the low-pressure, high-capacitance venous system. Increases in intracranial volume are initially met by decreases in CBV. This response is apparent in hydrocephalic infants, in whom venous blood shifts from intracranial to extracranial vessels, producing distended scalp veins.¹⁹

In the normal adult, CBF is approximately 55 mL/100 g of brain tissue per minute.^20–22 This represents almost 15% of the cardiac output for an organ that accounts for only 2% of body weight. Estimates of CBF are less uniform for children. Normal CBF in healthy awake children is approximately 100 mL per 100 g of brain tissue per minute, which represents up to 25% of cardiac output.^23,24 CBF in neonates and preterm infants (approximately 40 mL/100 g/min) is less than in children and adults.^25,26 In infants, CBF is subject to modification by sleep states and feeding.²⁷

CBF is regulated to meet the metabolic demands of the brain. In adults, the cerebral metabolic rate for oxygen consumption (CMRo₂) is 3.5 to 4.5 mL O₂/100 g/min; in children, it is greater.²³ General anesthesia reduces CMRo₂ by as much as 50%.²⁸ Coupling of CBF and CMRo₂ is probably mediated by the effect of local hydrogen ion concentration on cerebral vessels. Conditions that cause acidosis (e.g., hypoxemia, hypercarbia, ischemia) dilate the cerebral vasculature, which augments CBF and CBV. A reduction in brain metabolism (i.e., CMRo₂) similarly reduces CBF and CBV. When autoregulation is impaired, CBF is determined by factors other than metabolic demand. If the CBF exceeds metabolic requirements, luxury perfusion or hyperemia exists. Many pharmacologic agents act directly on the cerebral vasculature to alter CBF and CBV.

Cerebral Perfusion Pressure

CPP is a useful and practical estimate of the adequacy of the cerebral circulation, because CBF is neither easily nor widely measured. Defined as the pressure gradient across the brain, CPP is the difference between the systemic mean arterial pressure (MAP) at the entrance to the brain and the mean exit pressure (i.e., central venous pressure [CVP]). When ICP is increased, it replaces CVP in the calculation of CPP. In supine children, the mean CPP is the difference between the MAP and the mean ICP (CPP = MAP − ICP). If the brain and heart are positioned at different heights, all pressures should be referenced at the level of the head (e.g., external auditory meatus).

Cerebrovascular Autoregulation

Effects of Blood Pressure

In adults, CBF remains relatively constant within a MAP range of 50 to 150 mm Hg (Fig. 24-3). Autoregulation enables brain perfusion to remain stable despite moderate changes in MAP or ICP. Autoregulation is partially mediated by myogenic control of arteriolar resistance. When CPP decreases, cerebral vessels dilate to maintain CBF, thereby increasing CBV. When CPP increases, cerebral vasoconstriction occurs, maintaining the CBF with a reduced CBV. When ICP and CVP are low, MAP normally approximates CPP. Beyond the range of autoregulation, CBF becomes pressure dependent. In children with chronic hypertension, the upper and lower limits of autoregulation are increased. Cerebral autoregulation can be abolished by acidosis, medications, tumor, cerebral edema, and vascular malformations, even at sites far removed from a discrete lesion.²⁰

FIGURE 24-3 The effects of increasing mean blood pressure (BP), arterial partial pressure of oxygen (Pao₂), and arterial partial pressure of carbon dioxide (Paco₂) on cerebral blood flow (CBF) in the normal brain.

(From Shapiro HM. Intracranial hypertension: therapeutic and anesthetic considerations. Anesthesiology 1975;43:447.)

The limits of autoregulation are not known for normal infants and children, but autoregulation probably occurs at lower absolute values than in adults.²⁹ Although the lower limit of autoregulation in adults is approximately 50 mm Hg, this blood pressure may be beyond that of the neonate. Intact autoregulatory mechanisms have been demonstrated within lower blood pressure ranges in newborn animals compared with mature animals.³⁰ Cerebral autoregulation may also be abolished in critically ill humans.³¹

Preoperative Evaluation

Premedication

Sedation is usually withheld from pediatric neurosurgical patients until they arrive in the preoperative area to allow titration of drug to desired effect while under direct supervision. Opioids are usually withheld preoperatively because they may cause nausea or respiratory depression, especially in children with increased ICP, and sedatives alone usually are adequate to relieve anxiety.

Sedatives are administered in the parents’ presence to facilitate a smooth separation and induction. Midazolam (0.5 to 1.0 mg/kg) may be given orally; it usually requires 10 to 20 minutes to take effect. Incremental doses of intravenous midazolam (0.05 mg/kg) may also be useful in children who tolerate intravenous placement.

Monitoring

Minimal monitoring for pediatric neuroanesthesia requires a stethoscope (precordial or esophageal), electrocardiograph, pulse oximeter, sphygmomanometer, capnograph, and thermometer. Neuromuscular blockade monitoring is also important, but nerve stimulators may give misleading information about the extent of relaxation if applied to a denervated extremity. If the child has paresis, nerve stimulation should be at a site of normal neurologic function. Precordial Doppler ultrasound is recommended in children undergoing craniotomy, especially in the head-up position, because the relatively large head size of children places them at increased risk for air emboli. Monitoring devices for ICP are used for the same indications as in adults. Intraoperative EEG and electrophysiologic monitoring require advanced coordination among the neurosurgeon, anesthesiologist, and neurophysiologist. Urinary output should be measured during prolonged procedures, in cases with anticipated large blood loss, and when diuretics or osmotic agents are administered.

An arterial catheter is placed for craniotomies in which there is a potential for sudden and severe hemodynamic changes. Small child size should not preclude the use of invasive monitoring and may actually be an indication for a more aggressive approach. An increase in the paradoxical arterial pressure waveform with positive-pressure ventilation is often an excellent indication of intravascular volume deficiency and the need for fluid replacement (see Fig. 10-10). Intraarterial catheters can be placed percutaneously in the radial, dorsalis pedis, or posterior tibial arteries even in small infants, and it is rarely necessary to resort to surgical cutdown. The arterial transducer should be zeroed at the level of the head if the head and heart positions are different so that CPP can be accurately assessed. The lateral corner of the eye or the external auditory meatus approximate the level of the foramen of Monro, and either is a convenient landmark. In the first days of life, the umbilical artery and the umbilical vein can be cannulated. These catheters should be discontinued as soon as alternative access is established because of the potential for serious complications.

Percutaneous central venous cannulation (i.e., external or internal jugular, femoral, or subclavian veins) using the Seldinger technique is possible even in the smallest infants (see Chapter 48). However, in children undergoing neurosurgical resections, consideration should be given to sites other than neck veins, such as the femoral vein, thereby avoiding the Trendelenburg position during catheter insertion and the risk of accidental carotid artery puncture and hematoma formation, which may compromise CBF and intracranial venous drainage. If there is no issue with ICP, the subclavian vein is a reasonable alternative. Cannulation of antecubital veins may provide central venous access, but threading the catheter into the inlet of the right atrium may be technically difficult in small children. When rapid blood loss is a consideration in a small child in whom adequate peripheral venous access is difficult to obtain, a single-lumen, large-bore catheter is most commonly inserted in a femoral vein. Catheters inserted into the femoral veins usually are accessible to the anesthesiologist during most neurosurgical procedures. Multiple-lumen central venous catheters are inadequate for rapid blood transfusion. All central catheters should be removed as soon as possible after the procedure to minimize the risk of venous thrombosis.

Induction

For children with intracranial hypertension, the primary goals during induction are to minimize severe increases in ICP and decreases in blood pressure. Most intravenous drugs decrease CMRo₂ and CBF, which consequently decreases ICP.⁴⁶ Historically, sodium thiopental (4 to 8 mg/kg) was the default induction agent for neurosurgical cases. However, sodium thiopental is no longer available in the United States, although it remains available in other countries. In the United States, propofol has become the intravenous induction agent of choice for most children. Propofol (2 to 4 mg/kg) appears to have similar cerebral properties and an antiemetic effect; however, its antiemetic effect is usually not relevant for lengthy procedures. Etomidate, a possible neuroprotective agent, can be used if hemodynamic stability is a concern.^47–49 Ketamine should be avoided because of its known ability to increase cerebral metabolism, CBF, and ICP. Sudden increases in ICP have been reported after ketamine administration, especially in infants and children with hydrocephalus.^50,51

Other measures to reduce ICP during induction include controlled hyperventilation and administration of fentanyl and supplemental hypnotics before laryngoscopy and intubation. Lidocaine (1.5 mg/kg) limits the increase in ICP when administered intravenously just before laryngoscopy.⁵²

Sevoflurane has replaced halothane for inhaled inductions because of its more rapid onset, acceptability for pediatric patients, and hemodynamic stability. Similar to isoflurane in its cerebral physiologic effects, sevoflurane with hyperventilation appears to blunt the increase in ICP due to cerebral vasodilatation from inhalational anesthetic agents alone.^53–55 Sevoflurane offers an additional advantage because it causes less myocardial depression compared with halothane.⁵⁶ However, sevoflurane when combined with hyperventilation produces epileptiform activity as measured by EEG. This may occur even in children with no history of clinical seizure activity (see Chapter 6).⁵⁷

A common presentation is an uncooperative toddler who has an intracranial tumor and moderately decreased intracranial compliance and is agitated and resistant to separation from parents. Some clinicians would argue that a crying, agitated child has demonstrated a tolerance to increased ICP and that an intravenous induction is safer. Fortunately (for the anesthesiologist, although not for the child), children who have severe intracranial hypertension typically have a decreased level of consciousness, and it becomes easier to insert an intravenous catheter in those situations when it is most necessary.

Airway Management and Intubation

Airway management must be effective and smooth to avoid the ICP-increasing effects of hypoxemia, hypercarbia, and coughing. Opioid administration and supplemental hypnotics before intubation improve cerebral compliance and minimize increases in ICP caused by laryngoscopy and intubation.

Either oral or nasal intubation may be appropriate. Nasotracheal intubation offers the advantage of increased stability and increased comfort for children when postoperative intubation is necessary. Nasotracheal tubes are often used for children who will be in the prone position (e.g., for a posterior fossa craniotomy), children whose airway will be inaccessible during the surgical procedure, and for smaller children.

Contraindications to nasal intubation include choanal stenosis, possible basilar skull fracture, transsphenoidal procedures, and sinusitis. If nasotracheal intubation is planned, it is advantageous to prepare the nares with topical vasoconstrictors, recognizing that systemic hypertension can occur in response to nasally administered vasoconstrictors. Placing a few drops of 0.25% phenylephrine (Neo-Synephrine) or oxymetazoline on cotton-tipped applicators and positioning them in the nares against the nasal mucosa can prevent overdosage and help to gauge the patency of the nasal passage when anesthesia has been induced. It may also be useful to use a red rubber catheter or a nonlatex nasal trumpet to gently dilate the nares and minimize the risk of bleeding.⁵⁸ Whichever route is chosen for intubation, it is important to secure the tracheal tube with care because loss of airway intraoperatively in a prone child in pins or a child with limited airway access can result in disaster.

In prolonged, combined neurosurgical and craniofacial reconstructions, the tracheal tube may be sutured to the nasal septum or wired to the teeth. A nasogastric or orogastric tube is inserted after intubation to decompress the stomach and evacuate gastric contents; leaving it open to gravity drainage during the case can prevent positive pressure from building up in the stomach if air leaks around an uncuffed tracheal tube. The child’s eyes should be closed and covered with a large, clear, waterproof dressing.

Neuromuscular Blocking Drugs

Because of its rapid onset and brief duration of action, succinylcholine is frequently used to facilitate intubation in children with a full stomach. The intubating dose is 1 to 2 mg/kg given intravenously or 4 to 5 mg/kg given intramuscularly.⁵⁹ In children, it may be safest to precede this with atropine (0.01 to 0.02 mg/kg) to prevent bradycardia. Succinylcholine does not significantly increase ICP in humans,⁶⁰ and any effect may be minimized by pretreatment with a nondepolarizing muscle relaxant.⁶¹ However, this may make succinylcholine less effective, even when the dose of succinylcholine is increased. Succinylcholine is contraindicated when it may induce life-threatening hyperkalemia in the presence of denervation injuries due to various causes, including severe head trauma, crush injury, burns, spinal cord dysfunction, encephalitis, multiple sclerosis, muscular dystrophies, stroke, or tetanus.⁶²

Alternatively, nondepolarizing muscle relaxants such as rocuronium, pancuronium, cisatracurium, or vecuronium may be used, but all have a slower onset of action than succinylcholine. However, when rocuronium is administered in sufficiently large doses (1.2 mg/kg), the onset of action is comparable with that of succinylcholine, with equivalent intubating conditions achieved in less than 1 minute.⁶³

Positioning

Positioning is an especially important consideration in pediatric neuroanesthesia. Children with increased ICP should be transported to the preoperative holding area and operating room with the head elevated in the midline position to maximize cerebral venous drainage.

After the child is in the operating room, the neurosurgeons and anesthesiologists must have adequate access to the child. In infants and small children, slight displacement of the tracheal tube can result in extubation or endobronchial intubation. During prolonged procedures, it is important for the anesthesiologist to be able to visually inspect the tracheal tube and circuit connections and to suction the tracheal tube when necessary. Using proper draping and a flashlight, the operator can usually create a “tunnel” to ensure access to the airway. All but very small children are placed in pins in a Mayfield head holder. The direction of the tube exiting the nares should be adjusted to remove pressure and avoid the risk of ischemia, particularly for cases that will continue for several hours. Neonates and small infants have thin calvaria, so head-pinning systems are often avoided. Instead, there are a variety of non–pin-based headrests available for these children. Adequate padding should be used in such situations (Figs. 24-4 and 24-5). Extreme head flexion can cause brainstem compression in children with posterior fossa pathology, such as a mass lesion or Arnold-Chiari malformation. Extreme flexion can also cause high cervical spinal cord ischemia and tracheal tube kinking and obstruction.⁶⁴

FIGURE 24-4 A, The child is positioned prone before surgery. Extreme head extension was needed for correction of craniosynostosis, but the equipment for securing the head was the same as that used for a prone craniotomy. B, This particular frame uses gel pads to support the chin, ears, and forehead.

FIGURE 24-5 Resuscitation from the modified standard sitting position. The normal operative position (A and B) is compared with the resuscitation position (C). The position can be expeditiously changed by one control of the operating table.

Extremities should be well padded and secured in a neutral position (i.e., palm supinated or neutral to avoid ulnar nerve compression). It is important to avoid stretching peripheral nerves and to prevent skin and soft tissue pressure injury because of direct contact with surgical accessories such as instrument stands and grounding wires (see Fig. 24-5). It is also important to ensure that extremities that are not directly visible to the anesthesiologist (e.g., those on the opposite side of the operating room table) cannot fall off the table during surgery, even if the table is rotated. In older children and adolescents undergoing prolonged procedures, deep vein thrombosis prophylaxis should be considered using compression or pneumatic stockings.^65,66

Local Anesthesia

Local anesthetic should be injected subcutaneously before a skin incision to provide analgesia, and epinephrine is included in the local anesthetic to reduce cutaneous blood loss. If 0.25% bupivacaine with 1 : 200,000 epinephrine is used, the dose should be limited to 0.5 mL/kg. When greater volumes are required, the solution can be diluted with normal saline. This dilute solution is still effective for vasoconstriction and provides a prolonged sensory block postoperatively. Specific blocks of supraorbital and supratrochlear nerves can provide analgesia from the frontal area to the midcoronal portion of the occiput.⁷⁰ Blockade of the great occipital nerve provides analgesia from the posterior of the occiput to the midcoronal area of the occiput, whereas block of the supraorbital nerve provides analgesia to the front of the occiput (see Figs. 41-9 and 41-10).^71,72

Maintenance of General Anesthesia

General anesthesia is required for most therapeutic and many diagnostic procedures in pediatric neurosurgery. Ventilation is controlled if intracranial hypertension is a concern. Although spontaneous ventilation provides another indication of brainstem function, its disadvantages (eg., hypoventilation, increased potential for air embolism) are usually outweighed by the safety of controlled ventilation.

Maintenance of general anesthesia can be accomplished using inhalational anesthetics, intravenous infusions, or a combination of these drugs. Anesthetics that decrease ICP and CMRo₂ and maintain CPP are most desirable (Table 24-1). The commonly used inhalational agents uncouple CBF and CMRo₂ such that CBF increases while CMRo₂ decreases. All potent inhalational agents are cerebral vasodilators, which increase the CBF and ICP. Low concentrations of isoflurane, sevoflurane, or desflurane, combined with ventilation to maintain normocarbia, minimally affect CBF and ICP.^53,54,73 Isoflurane is often the inhalational agent of choice for maintenance of neuroanesthesia. At two times the minimal alveolar concentration (MAC), this dose of isoflurane induces a level of anesthesia that is associated with an isoelectric EEG while, unlike several other inhalational agents, maintaining hemodynamic stability. Enflurane is no longer used and may be epileptogenic, especially when combined with hyperventilation.⁷⁴ Other studies have demonstrated a similar effect with sevoflurane and hyperventilation, but the clinical implications of this are yet to be defined.⁷⁵

Practitioners debate the routine use of nitrous oxide for intracranial neurosurgical procedures. Opponents cite the increased risk of postoperative nausea and vomiting (PONV) with nitrous oxide in a surgical population already at greater risk for PONV.⁷⁶ Proponents cite studies that failed to demonstrate an increased risk of PONV.⁷⁷ Nitrous oxide can increase CBF in humans in a dose-dependent fashion through cerebral vasodilatation.^78,79 This increase in CBF can lead to an increase in ICP, which can be deleterious if the child already has reduced intracranial compliance.⁸⁰ Nitrous oxide can also affect somatosensory and motor evoked potentials, especially when concentrations in excess of 50% are used.^81–83 Animal data have shown that nitrous oxide can counteract the protective effects of thiopental in a model of cerebral ischemia.⁸⁴

Proponents of the use of nitrous oxide for intracranial procedures cite the long track record of safety. There are no outcome studies in humans showing a difference between using nitrous oxide or not. It is often of great clinical interest to obtain a neurologic assessment immediately after the conclusion of an intracranial procedure, and some practitioners prefer the use of nitrous oxide to aid in achieving this goal. Studies have demonstrated the safety of using nitrous oxide in a variety of combinations with other agents during intracranial procedures.⁸⁵ Nitrous oxide is relatively contraindicated, however, if the child has undergone a craniotomy within the past few weeks because air can remain in the head for prolonged periods after previous neurosurgery.⁸⁶

Fentanyl is often administered as part of an opioid-based technique because it is easily titratable with minimal adverse effects. A common loading dose is 5 to 10 µg/kg, with a dose of 2 to 5 µg/kg/hr usually adequate for maintenance. Adverse effects, including hypotension, can be avoided by giving the loading dose incrementally. Practitioners commonly use other opioids such as remifentanil and sufentanil. Dexmedetomidine, an α₂-agonist sedative, has also been used in children for neurophysiologic monitoring, for awake craniotomies, to facilitate smooth wake-ups after neurosurgical procedures, and for neuroprotection.^87–90

Apoptotic Neurodegeneration

Several investigators have demonstrated that commonly used anesthesia drugs accelerate programmed cell death (i.e., apoptosis) in the CNS of immature rodents and rhesus monkeys.^91–93 This laboratory observation has provoked a heated debate about its relevance to anesthetizing neonates,^94–97 which has been extended to the lay press.⁹⁸ Although these experimental paradigms have yielded some surprising findings, extrapolating these data to the practice of anesthetizing human neonates is questionable (see Chapter 23).

The animal and in vitro studies have significant limitations with respect to the experimental model, agent dosage or concentration, duration of exposure (absolute and compared with human exposures), lack of surgical stimulation, and developmental age and stage. No detectable clinical marker or syndrome is associated with early anesthesia exposure in former neonates who have undergone surgery and anesthesia at birth or in the first several years of life during rapid brain growth (i.e., synaptogenesis). In the only primate study, the degree of apoptosis after 3 hours of a ketamine infusion was similar to that of the control but significantly less than after a 24-hour infusion.⁹³ This occurred in the presence of blood concentrations of ketamine that were 10-fold to several hundred-fold greater than those reported after a single dose of ketamine in infants. These findings suggest that in this model, ketamine-associated neurodegeneration is a time-dependent, dose-dependent phenomenon whose limits have not been established.

Despite the confounding effects of prematurity and coexisting congenital anomalies, clearly characterized syndromes have been associated with maternal consumption of alcohol and anticonvulsant drugs. Discrepancies in neurocognitive outcomes exist.^92,99 Most neonatal and infant surgery is urgent, and anesthesia care is essential to proceed safely. Several retrospective database studies suggest that multiple anesthesia episodes are associated with learning disabilities and cognitive dysfunction, but most of these children were anesthetized before pulse oximetry and capnography were a standard of care. Unrecognized episodes of hypoxemia or excessive ventilation with reduced CBF might have contributed. It is also unclear whether children who required more than one surgical procedure when younger than 4 years of age might have had neurocognitive developmental issues that were associated with the pathology requiring surgery and were totally separate from exposure to anesthetic agents.^100–102 One retrospective study demonstrated that identical twins who were discordant for general anesthesia and surgery showed no evidence of cognitive dysfunction in follow-up assessments.¹⁰³

In summary, a growing body of evidence supports the idea that some anesthetic agents are harmful to the developing brain in various species of neonatal animals. There is neither adequate evidence nor a consensus among practitioners that this phenomenon occurs in very young humans, but this remains an area of great interest and research.

Blood and Fluid Management

Blood loss is difficult to estimate accurately during neurosurgery because most of the losses are absorbed by the operative drapes and the surgical field is difficult for the anesthesiologist to visualize. Accuracy can be improved if all suctioned blood is collected in calibrated containers visible to the anesthesiologist and an overhead camera provides a view of the operative field at all times. Blood loss is usually greatest at the beginning of surgery, when the scalp is incised, and when a large bone flap is removed.

Fluid and blood product management is discussed in Chapters 8 and 10. Disruption of the blood-brain barrier by underlying pathologic processes, trauma, or surgery predisposes neurosurgical patients to cerebral edema, which may be exacerbated by excessive administration of intravenous fluids. Intravenous fluid management during neurosurgical anesthesia involves cerebral perfusion, cerebral edema, water and sodium homeostasis, and serum glucose concentration.

In most cases, blood transfusions are not planned and attempts are made to avoid administration of blood products with their associated risks. Crystalloid solutions are commonly administered. Lactated Ringer solution is not considered a truly isotonic solution because its osmolality is 273 mOsm/L (normal: 285 to 290 mOsm/L). Normal saline, which is slightly hypertonic (308 mOsm/L), is the fluid of choice because reduction of serum osmolality is not desirable. However, rapid infusion of large volumes of normal saline has been associated with a hyperchloremic non-anion gap metabolic acidosis.¹⁰⁴ The clinical significance of this acidosis is not clear. If there are large fluid requirements during surgery, alternating bags of lactated Ringer solution with normal saline can minimize the risk of hypernatremia and acidosis and avoid hypoosmolality.

Inducing dehydration with osmotic and loop diuretics is a useful strategy to minimize cerebral edema and provide an optimal surgical field. However, hypotension and rebound effects may be associated with their use. Rapid administration of hypertonic solutions can cause profound but transient hypotension due to peripheral vasodilation.¹⁰⁵ Glucose-containing solutions usually are unnecessary during neurosurgical procedures because blood glucose concentrations are well-maintained even in small children in the absence of intravenous glucose administration during typical (balanced) neurosurgical anesthetics. However, glucose may be indicated when hypoglycemia is a concern, such as in diabetic children, children receiving hyperalimentation, preterm and full-term neonates, and malnourished or debilitated children. In these situations, glucose solutions should be administered at or slightly below maintenance rates (by constant infusion pump) and serum glucose concentrations should be monitored periodically throughout surgery. The potential association of larger cerebral infarct size with hyperglycemia (i.e., blood glucose values in excess of 250 mg/dL) during ischemia is of particular concern.¹⁰⁶

Meticulous management of fluids and blood products to minimize cerebral edema is a cornerstone of pediatric neuroanesthesia. Although cerebral hemorrhage is fortunately a rare event, when it does occur, it can be sudden and catastrophic. All children should have secure, large-bore intravenous access, and blood products should be available along with the means for warming the blood.

Temperature Control

Because the head accounts for a large proportion of an infant’s body surface area, infants are particularly susceptible to heat loss during neurosurgical procedures. Attention should be focused on maintaining normal temperature from the time the child is brought into the operating room, although moderate hypothermia during neurosurgery may be useful to decrease the CMRo₂. Ambient room temperature should be increased during positioning, preparation, and draping. Infrared warming lights may be helpful for infants, and warming blankets may be useful for infants weighing less than 10 kg. Forced-air warming remains the most effective means of maintaining body temperature.¹⁰⁷

Venous Air Emboli

Venous air embolism (VAE) is a potential danger during intracranial procedures. The larger the pressure gradient between the operative site and the heart, the greater the potential for clinically significant entrainment of air into the central circulation.¹⁰⁸ For example, when the operative site is far above the heart (e.g., in a seated craniotomy) or when the CVP is low (e.g., acute blood loss during craniofacial procedures), it creates an environment for a VAE. Intracranial procedures are a particular concern because intracranial venous sinuses have dural attachments that impede their ability to collapse. Other potential air entry sites during neurosurgical procedures include bone, bridging veins, and spinal epidural veins. The sequence of events that should be followed when a VAE occurs is to identify the problem, stop further air entrainment, and support the circulation. Understanding the cause, prevention, and treatment of VAE is crucial because the consequences can be life-threatening.

When air enters the central circulation, it can accumulate in the right atrium or the right ventricular outflow tract. Cardiac output may be reduced, depending on the size of the air lock. If enough air is entrained into the circulation, the preload to the right ventricle decreases, or the right-sided heart afterload increases acutely, which can lead to cor pulmonale, acutely decreasing left ventricular preload and ultimately causing cardiovascular collapse. One study in dogs demonstrated that as little as 1 mL/kg of air could increase pulmonary artery pressure 200% to 300%.¹⁰⁹ Intracardiac shunts such as a patent foramen ovale, atrial or ventricular septal defects, and other congenital cardiac defects may allow air to access the systemic circulation, including the coronaries and brain. The risk of VAE is even greater in infants and children because potential intracardiac shunts exist in many otherwise healthy infants and children. They may become clinically important if pulmonary hypertension develops acutely after a large air embolism. Some clinicians recommend preoperative echocardiographic screening for patent foramen ovale in any child being considered for a sitting craniotomy; others regard a patent foramen ovale to be an absolute contraindication to the sitting position.^110,111

Although the incidence of VAE is greatest in the sitting position, the lateral, supine, and prone positions are not free of risk. VAE have also been observed during craniotomy for craniosynostosis, even when the operating room table is flat and rarely when the surgery involved endoscopic strip craniectomy, although most occur without clinical sequelae.^112,113 The incidence of VAE in children undergoing suboccipital craniotomy in the sitting position is not significantly different from that in adults, but children appear to have a greater incidence of hypotension and a smaller likelihood of successful aspiration of central (intravascular) air.¹¹⁴

Several techniques may be used to detect VAE. Depending on the study design, the usual order of sensitivity of detecting air in the heart is transvenous intracardiac echocardiography (0.15 mL/kg) > transesophageal echocardiography (0.19 mL/kg) = precordial Doppler probe (0.24 mL/kg) > pulmonary artery pressure (0.61 mL/kg) = end-tidal CO₂ tension (0.63 mL/kg) = arterial O₂ tension > mean arterial pressure (1.16 mL/kg) = arterial CO₂ tension.^115,116 Transvenous intracardiac echocardiography is commonly used to guide catheters in cardiac ablation procedures or insertion of foramen ovale occlusion devices, but it is invasive and infrequently used in pediatric anesthesia. A precordial Doppler probe has been traditionally placed over the fourth or fifth intercostal space at the right sternal border to best monitor right heart sounds, although evidence suggests that placing the Doppler probe at the left parasternal border may be at least as sensitive (Fig. 24-6).^117,118 Appropriate Doppler positioning can be confirmed by listening for the characteristic change in sounds after rapid administration of a few milliliters of saline into a venous catheter. The precordial Doppler probe is particularly valuable because it is inexpensive, easy to use, benign, and noninvasive. Although transthoracic or transesophageal echocardiography is the most specific method for detecting small air emboli, it is not easily used intraoperatively, especially in children during neurosurgical procedures.^110,119,120

FIGURE 24-6 Relative sensitivities of air embolism–monitoring modalities. ECG, Electrocardiogram.

Monitoring end-tidal gas tensions is important during neurosurgical procedures. When VAE occurs, there is a ventilation/perfusion mismatch caused by the air blocking passage of blood through the pulmonary circulation, increasing dead space ventilation with a sudden decrease in end-tidal CO₂ partial pressure and activation of complement resulting in pulmonary interstitial edema, neutrophil infiltration, and lung injury (Fig. 24-7).¹¹⁵ The end-tidal CO₂ partial pressure remains a useful and cost-effective strategy in diagnosing massive VAE, although its sensitivity has been surpassed by other approaches (see Fig. 24-6). An increase in end-tidal nitrogen partial pressure during continuous monitoring is a specific sign of air emboli. Although slightly more sensitive than a decrease in end-tidal CO₂, an increase in end-tidal nitrogen is not detected by most infrared analyzers in practice and is usually of such small magnitude that it may be difficult to detect.

FIGURE 24-7 Mechanism of decreased end-tidal carbon dioxide (etco₂) after an air embolus.

(Courtesy J. Drummond, MD.)

Less sensitive or more invasive methods to detect VAE include ECG changes, changes in heart rate, decreases in systemic blood pressure, and increases in right atrial and pulmonary arterial pressures. Right atrial and pulmonary artery pressures increase quickly after the emboli (within 30 seconds). The magnitude of these increases correlates with the size of emboli, although these findings should not be relied on alone for monitoring and diagnosis.

On suspicion or diagnosis of VAE, immediate measures must be taken by the surgeons and anesthesiologists to prevent continued entrainment of air and consequent hemodynamic deterioration. The surgeon should immediately flood the field with saline and apply bone wax to exposed bone edges. The anesthesiologist should discontinue nitrous oxide and place the child in the Trendelenburg position, which has the effect of increasing cerebral venous pressure, stopping entrainment of air, augmenting the child’s peripheral venous return, and increasing systemic blood pressure. Occlusion of the internal jugular veins in an attempt to increase cerebral venous pressure should be done with great care because occlusion of the carotid arteries can lead to cerebral ischemia. The application of positive end-expiratory pressure increases CVP but also decreases cardiac filling pressure, cardiac output, and blood pressure; extreme increases in positive end-expiratory pressure are usually unwarranted. Chest compressions, vasopressors, and aggressive fluid resuscitation may be required.

Aspiration of air from a central venous catheter is rarely successful unless massive amounts have been entrained. When central venous catheters are necessary, such as for a child in the sitting position or when massive blood loss is anticipated, an attempt should be made to place the tip at the junction of the superior vena cava and right atrium to provide the optimal location for aspiration of entrained air. More importantly, a central venous catheter is useful to estimate maintenance of circulating blood volume and to rapidly administer fluids and resuscitative medications when necessary. The position of a central venous catheter near the heart should be confirmed by radiograph, by transducing CVPs, or with the aid of ECG monitoring (i.e., biphasic P waves develop in a lead at the tip of the catheter). The threshold for aspirating air may be increased by properly positioning a multiple-orifice central venous catheter using a transvenous intracardiac echocardiography probe.¹¹⁵ Because erosion of the catheter tip through the heart causing fatal pericardial tamponade has occurred after surgery in small children, soft silicone catheters are recommended.^121,122

Emergence

Protecting the brain is a major concern during neurosurgical procedures (Table 24-2). Emergence and extubation should be smooth and controlled to prevent fluctuations in ICP and in venous and arterial pressures.¹²³ To avoid vomiting during emergence, a multimodal antiemetic approach is advised.¹²⁴ Despite this approach, the incidence of PONV is high, which may be attributed to several factors: blood in the CSF is a potent emetic, opioids are often used to treat postoperative pain, and headache itself can precipitate emesis.

TABLE 24-2 Maneuvers of Neuroprotection

CBF, Cerebral blood flow; CMRglu, cerebral metabolic rate for glucose; CMRo₂, cerebral metabolic rate for oxygen; CPP, cerebral perfusion pressure; ICP, intracranial pressure; Paco₂, partial pressure of arterial carbon dioxide.

Intravenous lidocaine (1.0 to 1.5 mg/kg) given before extubation may help to suppress coughing and straining on the tracheal tube, although fentanyl appears to be equally effective and may be less sedating. Labetalol, an α- and β-adrenergic blocking agent, can be administered incrementally for the control of blood pressure during the acute period of emergence, but this is rarely necessary in children who have received adequate doses of opioids during surgery. For adolescents, intravenous labetalol (0.1 to 0.4 mg/kg given every 5 to 10 minutes until desired effect is achieved) may be necessary, but this usually does not have to be repeated in the postoperative period. Esmolol is used by some practitioners and has been as effective as labetalol in controlling hypertension after intracranial surgery in adults.¹²⁵ However, esmolol should be used with caution in infants and smaller children because their cardiac output depends on heart rate. There are no studies evaluating the use of esmolol in children for such an application. Dexmedetomidine may be useful in facilitating a smooth emergence while still allowing evaluation of the child’s neurologic status.

Neuromuscular blockade should be pharmacologically reversed because even the slightest residual weakness is poorly tolerated and may interfere with the neurologic examination. Adequate spontaneous ventilation and oxygenation and an awake mental status are required before extubation. If postoperative intracranial hypertension is possible or if the child does not meet respiratory or neurologic criteria for extubation, the tracheal tube should be left in place, sedation should be administered, and the child should be transported to an intensive care unit.

The child should be as fully alert as possible immediately after the operation to permit repeated neurologic examinations to assess recovery and to detect a deteriorating status. In unconscious children, ICP can be monitored invasively. CT scans can help to evaluate the cause of an increased ICP or deteriorating mental status.

Pain is usually not severe after a craniotomy, but it can be treated with incremental doses of opioids. Ketorolac is best avoided in the early postoperative period because of its effects on platelet function. Acetaminophen may be administered orally, rectally, or intravenously for mild pain.¹²⁶

Diabetes insipidus or inappropriate secretion of antidiuretic hormone may complicate postoperative fluid and electrolyte management, particularly when surgery is in the region of the hypothalamus and pituitary gland. Careful observation of fluid status and repeated laboratory evaluation of blood and urine osmolality and sodium levels are important in this situation. When diabetes insipidus occurs, it can be managed with a continuous infusion of dilute aqueous vasopressin (1 to 10 mU/kg/hr).¹²⁷ In such circumstances, large volumes of hypotonic intravenous solutions must be avoided because they may rapidly decrease the serum sodium level and osmolality. If normal saline is administered in strictly limited volumes, aqueous vasopressin can control the electrolyte and fluid balances of children with diabetes insipidus until they resume oral fluids. At that time, intranasal or oral desmopressin (DDAVP) can be substituted. When diabetes insipidus develops after surgery in the pituitary region (e.g., during resection of a craniopharyngioma), it may only be transient, and it is important to repeatedly assess the need for vasopressin.

Portable EEGs and evoked auditory, somatosensory, and less commonly, visual potentials may be helpful in assessing children who are deeply sedated or paralyzed. Observation in an intensive care unit capable of managing children is essential for the prevention or early detection and treatment of postoperative complications. CT and MRI are often performed 1 or 2 days after a craniotomy or earlier if neurologic deterioration develops.

Trauma

Skull Fractures

Skull fractures are a common manifestation of head trauma in children. Most are linear and do not require surgical treatment. These fractures are of concern primarily because the force required to produce them may damage the underlying brain and vasculature. A linear fracture over a major blood vessel (e.g., middle meningeal artery) or a large dural sinus may result in intracranial hemorrhage. Most children have an uneventful course after sustaining a simple skull fracture. A few develop a leptomeningeal cyst or growing fracture that eventually requires surgical treatment. Multiple skull fractures in the absence of documented major trauma should always raise the suspicion of child abuse (See Fig. 38-2), which is also referred to as nonaccidental trauma.

Depressed skull fractures often require surgical repair. They may occur even in the absence of a scalp laceration. However, displacement of the inner table of the skull requires greater force than that needed to produce a simple linear fracture and has greater potential to damage underlying tissues. Approximately one third of all depressed fractures are uncomplicated, another third are associated with dural lacerations, and the remaining third are associated with cortical lacerations. The extent of cortical injury is the primary determinant of morbidity and mortality. Surgical débridement and elevation of the depressed bone are usually performed as soon as possible after the injury (Fig. 24-8, A).

FIGURE 24-8 A, This depressed skull fracture required surgical intervention. B, Children with severe head trauma (in this case, a shaken baby) may present with marked increases in intracranial pressure.

Basilar skull fractures are less common in children. Despite the force needed to produce these fractures, they typically have an excellent prognosis and rarely require surgical intervention. However, the possibility of a basilar skull fracture should be considered when caring for children with altered mental status, seizures, or associated trauma requiring surgery. Findings include periorbital ecchymoses (“raccoon eyes”), retroauricular ecchymosis (i.e., the Battle sign) (see Fig. 38-2, B), hemotympanum, clear rhinorrhea, or otorrhea. Unless absolutely necessary (e.g., mandibular wiring), nasotracheal intubation or passage of a nasogastric tube is best avoided because these tubes have inadvertently traversed these skull fractures and entered the cranium.^132–134 Complications of basilar skull fracture include meningitis from a CSF leak, cranial nerve damage, and anosmia.

Craniotomy

Tumors

Brain tumors are the most common solid tumors in children, exceeded only by the leukemias as the most common pediatric malignancy.¹⁶³ Between 1500 and 2000 new brain tumors are diagnosed annually in children in the United States. Unlike those in adults, most brain tumors in children are infratentorial in the posterior fossa. They include medulloblastomas, cerebellar astrocytomas, brainstem gliomas, and ependymomas of the fourth ventricle. Because posterior fossa tumors usually obstruct CSF flow, increased ICP occurs early. Presenting signs and symptoms include early morning vomiting and irritability or lethargy. Cranial nerve palsies and ataxia are also common findings, with respiratory and cardiac irregularities usually occurring late. Sedation or general anesthesia may be required for radiologic evaluation or radiation therapy.

Surgical resection of a posterior fossa tumor presents a number of anesthetic challenges. Children are usually positioned prone, although the lateral or sitting positions are used by some neurosurgeons. In any case, the head is flexed, and the position and patency of the tracheal tube must be meticulously ensured. In the event that the tracheal tube does become dislodged when the child is in a head holder and prone, successful emergent airway management has been described using a laryngeal mask airway.¹⁶⁴

Arrhythmias and acute blood pressure changes may occur during surgical exploration, especially when the brainstem is manipulated. The electrocardiogram and arterial waveform should be closely monitored. Altered respiratory control may be masked by neuromuscular blocking drugs (NMBDs) and mechanical ventilation. Even when ICP is only marginally increased, intracranial compliance is presumed to have decreased. This warrants precautions against further increases in ICP. If ICP is markedly increased or acutely worsens, a ventricular catheter may be inserted before the tumor is resected. VAE is a potentially serious complication that is not eliminated by the prone or lateral position because head-up gradients of 10 to 20 degrees are frequently used to improve cerebral venous drainage. In infants and toddlers, large head size relative to body size accentuates this problem.

Supratentorial tumors in the midbrain include craniopharyngiomas, optic gliomas, pituitary adenomas, and hypothalamic tumors and account for approximately 15% of intracranial tumors. Hypothalamic tumors (i.e., hamartomas, gliomas, and teratomas) frequently manifest with precocious puberty in children who are large for their chronologic age. Craniopharyngiomas are the most common parasellar tumors in children and adolescents and may be associated with hypothalamic and pituitary dysfunction. Symptoms often include growth failure, visual impairment, and endocrine abnormalities.

Signs and symptoms of hypothyroidism should be sought and thyroid function measured. Corticosteroid replacement (i.e., dexamethasone or hydrocortisone) usually is administered because the integrity of the hypothalamic-pituitary-adrenal axis may be uncertain. Diabetes insipidus can occur preoperatively and is a common postoperative problem. The history usually reveals this condition preoperatively, especially if attention is focused on nocturnal drinking and enuresis. Evaluation of serum electrolytes and osmolality, urine specific gravity, and urine output is helpful because hypernatremia and hyperosmolality, along with dilute urine, are typical findings. If diabetes insipidus does not exist preoperatively, it usually does not develop until the postoperative period because there is an adequate reserve of antidiuretic hormone in the posterior pituitary gland capable of functioning for many hours, even when the hypothalamic-pituitary stalk is damaged intraoperatively.

Postoperative diabetes insipidus is marked by a sudden large increase in dilute urine output associated with an increasing serum sodium concentration and osmolality. Protocols have been developed to guide intraoperative and postoperative management of diabetes insipidus (see Chapter 8).¹²⁷ Return of antidiuretic hormone activity a few days postoperatively may cause a marked decrease in urinary output, water intoxication, seizures, and cerebral edema if it is not recognized and fluid administration is not adjusted appropriately.

Transsphenoidal surgery typically is performed only in adolescents and older children with pituitary adenomas. However, it should be treated like other midbrain tumors in terms of monitoring and vascular access. Children are usually intubated orally to give the surgeon optimal access to the nasopharynx, and preparations for an emergent craniotomy should be anticipated in case unexpected massive bleeding develops. Because nasal packs are inserted at the end of surgery, the child should be fully awake before tracheal extubation.

Gliomas of the optic pathways occur with increased frequency in children with neurofibromatosis. Presenting symptoms include visual changes and proptosis; increased ICP and hypothalamic dysfunction are usually late findings. Neurofibromas tend to be highly vascular, and the anesthesiologist should be prepared for significant blood loss.

Approximately 25% of intracranial tumors in children involve the cerebral hemispheres. They are primarily astrocytomas, oligodendrogliomas, ependymomas, and glioblastomas. Neurologic symptoms are more likely to include a seizure disorder or focal deficits. Succinylcholine should be avoided if motor weakness is present because it can cause sudden severe hyperkalemia. Nondepolarizing NMBDs and opioids may be metabolized more rapidly than usual in children who are receiving chronic anticonvulsants. Choroid plexus papillomas are rare but occur most often in children younger than 3 years of age. They usually arise from the choroid plexus of the lateral ventricle and produce early hydrocephalus as a result of increased production of CSF and obstruction of CSF flow. Hydrocephalus usually resolves with surgical resection. When lesions lie near the motor or sensory strip, a special type of somatosensory evoked potential monitoring called phase reversal may be used to delineate the locations.¹⁶⁵ If cortical stimulation is planned to help identify motor areas, NMBDs must be permitted to wear off and the anesthetic technique adjusted to achieve immobilization without paralysis.

Stereotactic biopsies or craniotomies present special concerns regarding airway accessibility. Newer head frames have adjustable anterior positions so that the airway is readily accessible (E-Fig. 24-1). They are especially useful for stereotactic neurosurgery. It is more comfortable and less distressing for the child to be anesthetized before the head frame is applied, even though this means the anesthesiologist must induce anesthesia in the radiology suite and then transport the child from the CT scanner to the operating room. The wrench that is used to apply and remove the head frame should be taped to the frame at all times so that it is always readily available if emergent removal of the head frame becomes necessary (e.g., during transport).

E-FIGURE 24-1 The modified Brown-Roberts-Wells stereotactic head frame has an adjustable face piece that provides enhanced access to the airway.

(From Stokes MA, Soriano SG, Tarbell NJ, et al. Anesthesia for stereotactic radiosurgery in children. J Neurosurg Anesthesiol 1995;7:100-8.)

Vascular Anomalies

Arteriovenous Malformations

Arteriovenous malformations consist of large arterial feeding vessels, dilated communicating vessels, and large draining veins carrying arterialized blood. Large malformations, especially those involving the posterior cerebral artery and vein of Galen, may manifest as congestive heart failure (i.e., high-output heart failure, often with pulmonary hypertension) in the neonate. The prognosis for these types of arteriovenous malformations is quite poor. Saccular dilation of the vein of Galen may manifest later in infancy or childhood as hydrocephalus due to obstruction of the aqueduct of Sylvius. Malformations not large enough to produce congestive heart failure usually remain clinically silent unless they cause seizures or a stroke or until the acute rupture of a communicating vessel results in subarachnoid or intracerebral hemorrhage.¹⁶⁶ Intracranial hemorrhages are the most common presentation in this population, with an associated mortality rate of 25%.

Treatment usually consists of embolization or irradiation of deep malformations, surgical excision (usually of the more superficial ones), or a combination of these modalities. Management for elective embolic procedures involves general anesthesia. Moderate hyperventilation may enhance visualization of abnormal blood vessels that do not respond with vasoconstriction. The anesthesiologist should be knowledgeable about the types of embolic agents that can be used and their potential complications. Anticonvulsant therapy is routine. Neonates in cardiac failure may be receiving inotropic agents. Bleeding, especially from the femoral arterial puncture site (which cannot always be visualized), should always be a consideration. Fluid overload result from the large amount of contrast agents administered, especially in a young infant who may already be in high-output cardiac failure. The anesthesiologist should be prepared for the possibility of an emergency craniotomy if a vessel ruptures.

Aneurysms

Intracranial aneurysms most often result from a congenital malformation in an arterial wall. Children with coarctation of the aorta or polycystic kidney disease have an increased incidence of these aneurysms. They usually remain asymptomatic during childhood; most ruptures that occur in childhood are fatal. Symptoms of subarachnoid or intracerebral hemorrhage frequently appear suddenly in a previously healthy young adult. When technically feasible, surgical ligation or clipping constitutes the treatment of choice.¹⁶⁷

Anesthesia for surgical resection of vascular malformations and aneurysms in children presents unique challenges, especially if the diagnosis has been preceded by an intracranial hemorrhage. Blood products should be in the operating room and verified before the start of the procedure. An adequate depth of anesthesia should be ensured before any invasive maneuver to prevent precipitous hypertension. Adequate venous access to respond to sudden and massive blood loss is crucial but can wait until after induction of anesthesia. A blood-warming device, such as a rapid transfusion device, should be immediately available.

Controlled hypotension may be valuable in some situations for brief periods to reduce tension in the abnormal blood vessels and improve the safety of surgical manipulation.¹⁶⁸ It is not clear, however, whether the benefits of controlled hypotension are worth the risks, especially in small children (see Chapter 10). Controlled hypotension should not be used in children with increased ICP because of the risk of decreasing CPP, with resulting ischemia and further increased ICP. Although the absolute limits of acceptable hypotension are unknown, a mean blood pressure greater than 40 mm Hg for infants or 50 mm Hg for older children appears to be safe; teenagers should have a target mean arterial pressure no less than 55 mm Hg. At the conclusion of the procedure, the blood pressure is returned to normal, but before closing the dura, the operative site should be inspected for bleeding.

Hemodynamic stability is important during emergence to avoid bucking, coughing, straining, and hypertension during extubation. Excessive hypertension can result in postoperative bleeding, although in most cases of aneurysm clipping, a slightly increased blood pressure may be desirable postoperatively to minimize the risk of vasospasm. After resection of an arteriovenous malformation, there can be serious postoperative complications due to cerebral edema with increased ICP or hemorrhage. This normal perfusion pressure breakthrough is probably caused by hyperemia of the areas surrounding the previous arteriovenous malformation site, where vessels suffer from continued vasomotor paralysis and cannot vasoconstrict. Treatment is controversial but usually involves therapy for increased ICP (e.g., diuretics, moderate hyperventilation, head elevation) in addition to judicious use of moderate hypotension (while maintaining CPP) and moderate hypothermia. When surgery is completed, it is important that children are able to cooperate with a neurologic examination and that there is careful control of blood pressure in the intensive care unit.

Moyamoya Disease

Moyamoya disease is an anomaly that results in progressive and life-threatening occlusion of intracranial vessels, primarily the internal carotid arteries near the circle of Willis.¹⁶⁹ An abnormal vascular network of collaterals develops at the base of the brain, and the appearance of these many, small vessels on angiography was originally described by the Japanese name moyamoya, which roughly translates as “puff of smoke.” The congenital form of the disease can involve the systemic vasculature, including pulmonary, coronary, and renal vessels; affected renal arteries are the most commonly identified angiographic lesion. The acquired variety (i.e., moyamoya syndrome) may be associated with meningitis, neurofibromatosis, chronic inflammation, connective tissue diseases, certain hematologic disorders, Down syndrome, or prior intracranial radiation. Some children with neurologic symptoms from sickle cell disease may also have moyamoya.¹⁷⁰ Moyamoya disease appears to be more common among children of Japanese ancestry. Associated intracranial aneurysms are rare in children but may occur in more than 10% of affected adult patients. Abnormal electrocardiographic findings have been described with the syndrome in adults.

Moyamoya disease usually manifests as transient ischemic attacks progressing to strokes and fixed neurologic deficits in children. The attacks may be precipitated by hyperventilation.¹⁷¹ The morbidity and mortality rates are high if the condition is left untreated. Medical management consists of antiplatelet therapy, such as aspirin, or calcium channel blockers. The most common surgical operation for correction in children is pial synangiosis, which involves suturing a scalp artery (usually the superficial temporal artery) directly onto the pial surface of the brain to enhance angiogenesis (Fig. 24-9).¹⁷²

FIGURE 24-9 Moyamoya disease. A, The top angiogram shows the pattern of arterial filling after injection of the internal carotid artery in a child with moyamoya disease before pial synangiosis. Area A shows poor filling from the middle cerebral artery as a result of the disease process. Area B shows the characteristic hazy collaterals, or moyamoya vessels. The bottom angiogram is from the same child after pial synangiosis. The angiogram was obtained after injection of the superficial temporal artery, and it shows good filling in the middle cerebral artery distribution in area A. Area B does not fill from the middle cerebral artery. B, Pial synangiosis. The superficial temporal artery is prepared to be sutured to the pia of the cerebral cortex. After the craniotomy is completed, this artery can be sewn directly onto the underlying pia mater. The result of this procedure is improvement of blood flow to ischemic areas of the cerebral cortex.

Careful and continuous monitoring of end-tidal CO₂ partial pressure is essential in anesthesia management.¹⁷³ Children with moyamoya disease have reduced hemispheric blood flow bilaterally, and hyperventilation may further reduce regional blood flow and cause significant EEG and neurologic changes.¹⁷⁴ Normocapnia must be maintained throughout all phases of the procedure, including induction of anesthesia. Adequate hydration and maintenance of baseline blood pressure are indispensable. Most of these children have an intravenous catheter inserted the night before surgery and are given 1.5 times the amount of maintenance fluids to avoid dehydration during the perioperative period. EEG monitoring during these procedures can detect and help to treat ischemia that appears to be a result of cerebral vasoconstriction in response to direct surgical manipulation of the brain.¹⁷⁵ Normothermia is maintained, particularly at the end of the procedure, to avoid postoperative shivering and an exaggerated stress response. As with most neurosurgical procedures, a smooth extubation without hypertension or crying is desirable. Although scant literature exists regarding intraoperative and postoperative complications during moyamoya surgery, it appears that most complications (e.g., strokes) occur postoperatively and are associated with dehydration and crying (i.e., hyperventilation) episodes.¹⁷⁶

Seizure Surgery

Epilepsy is one of the most common neurologic disorders of childhood. Despite the development of new drugs and regimens, the prevalence of pharmacologically intractable seizures remains high. Advances in neuroimaging and EEG monitoring provide epileptologists anatomic targets that mediate some medically intractable seizure disorders. Advances in pediatric neurosurgery have exploited these technologies and dramatically improved the outcomes for infants and children.¹⁷⁷

Children presenting for surgical management of seizures take anticonvulsant medications, which can have serious side effects, including abnormalities of hematologic function such as abnormal coagulation, depression of red or white blood cell production, and decreased platelet counts. Other problems may arise from altered hepatic function. Specific anticonvulsant concentrations should be determined preoperatively to detect subtherapeutic or toxic concentrations. Many anticonvulsants enhance metabolism of nondepolarizing NMBDs and opioids, increasing (up to 50%) the amount of these drugs needed during a surgical procedure. The preoperative evaluation should detect underlying conditions that are causing the seizures and the disabilities that can result from progressive neurologic dysfunction.

A major concern during resection of seizure foci is avoiding harming brain tissue that controls vital functions, such as motion, sensation, speech, and memory (so-called eloquent cortex), especially if a seizure focus is adjacent to cortical areas controlling these functions. Cooperative adolescents and adults can assist in determination of the limits of safe cortical resection if they can be continually assessed during the surgical procedure. The technique of awake craniotomy is often performed in carefully selected adolescents. An awake craniotomy encompasses a wide variety of techniques whose common goal is to allow intraoperative assessment and feedback to determine if the eloquent cortex is at risk during resection.

Children are selected for this procedure on an individual basis. Most children younger than 12 years old and many teenagers cannot tolerate an awake craniotomy. However, selected individuals may do well. The anesthesiologist should have detailed conversations with the child and parents to determine appropriateness before initiating such a procedure.

Some practitioners perform the entire procedure, including line placement, infiltration of local anesthetic, skull and dural opening, and resection, with the child completely awake or with minimal sedation. This particular approach requires an extremely motivated child. A variation on this technique uses short-acting sedatives and analgesics, such as propofol and fentanyl, titrated to induce unconsciousness but maintain spontaneous ventilation for instillation of local anesthetics, insertion of monitoring catheters, placement of head pins, and skull opening.¹⁷⁸ Subsequently, children can be allowed to awaken during surgical resection. They can then have sedatives and opioids reinstituted for the craniotomy closure.

Alternatively, some anesthesiologists use the asleep-awake-asleep technique. It consists of inducing general anesthesia and maintaining airway control with a supraglottic device (i.e., laryngeal mask airway). General anesthesia is maintained for line placement, placement of head pins, and skull and dural opening. The child is then awakened, the supraglottic airway is removed, and the surgeons proceed with resection. At the conclusion of the resection, general anesthesia is again induced and the supraglottic airway reinserted for closure of the dura, skull, and skin. There are several disadvantages to the asleep-awake-asleep approach. One of the major concerns when employing this approach is airway management during emergence and induction while the child is in head pins. If the child coughs or bucks while immobilized, cervical spine injuries or scalp lacerations can occur. Brain swelling is also a concern in a child who is breathing spontaneously under general anesthesia with an inhalational anesthetic and possibly with nitrous oxide.

Regardless of the technique chosen, the anesthesiologist must have an in-depth discussion with the child or adolescent about intraoperative needs and expectations. The preoperative period is the time to decide whether the child is a candidate for an awake craniotomy. There are no randomized, controlled trials comparing the safety or effectiveness of the techniques described.

Younger children (up to 12 years of age) or uncooperative children of any age do not tolerate this approach and require general anesthesia throughout. In these circumstances, intraoperative electrophysiologic studies, such as somatosensory evoked potentials, EEG, and motor stimulation, may be used to help localize and determine the function of the site of planned resection. If EEG studies are to be performed, the anesthetic technique should be adjusted to maximize EEG signals. If direct cortical motor stimulation is planned, NMBDs must be permitted to wear off. Occasionally, a seizure focus is difficult to identify intraoperatively. In these situations, hyperventilation or methohexital (in small doses, 0.25 to 0.5 mg/kg) may be helpful in lowering the seizure threshold and producing EEG seizure activity.^179,180

In some children, the site of origin of generalized seizures is difficult to determine. When this occurs, evaluation with intracranial EEG monitoring (“grids and strips”) may be accomplished with direct electrocorticography (E-Fig. 24-2). The leads are placed on the surface of the cortex after a craniotomy performed under general anesthesia. Intraoperative EEG monitoring is limited during these procedures to ensuring that all leads are functional; monitoring for seizures takes place over the next several days to identify a focus that is amenable to resection. These children need to be observed carefully in the postoperative period because complications can develop from having intracranial electrodes in place. Because air frequently persists in the skull for up to 3 weeks after a craniotomy,⁸⁶ these children should not have nitrous oxide administered for a subsequent procedure (e.g., to resect a seizure focus, to remove the electrocorticography leads) until their dura has been opened to prevent the development of tension pneumocephalus.

E-FIGURE 24-2 Skull radiograph of a child with intracranial electrocorticography grids in place.

When a focal resection is not possible, a lobectomy or corpus callosotomy may be attempted. However, children undergoing the latter procedure are often somnolent for the first few postoperative days, especially if a complete callosotomy is performed. This also occurs in children who have undergone insertion of multiple subdural grids and strips. Occasionally, small children undergo a hemispherectomy because their seizures are attributed to an abnormal hemisphere that is already severely dysfunctional, as when affected by hemiparesis. These can be challenging cases for the anesthesiologist because much blood can be lost (from one half to multiples of the estimated blood volume).¹⁸¹ This procedure is usually performed when children are very young to permit the other hemisphere to take over the function of both sides. Large-bore intravenous access is necessary in these cases to facilitate rapid replacement of blood, crystalloid solutions, and medications. Arterial pressure monitoring is routine, and many practitioners also use CVP monitoring.

An advance in the treatment of epilepsy has been the development of the vagal nerve stimulator. Although its exact mechanism of action is not well understood, it appears to inhibit seizure activity at brainstem or cortical levels.^182,183 It is becoming a popular form of treatment because it has shown benefit with minimal side effects in many children who are disabled by intractable seizures. Large, randomized trials are being conducted to determine the overall efficacy of this treatment. There are few published series of vagal nerve stimulation in children, but it is estimated that there is a 60% to 70% improvement in seizure control, with the best results achieved in those with drop attacks.^184,185

The vagal nerve stimulator is a programmable device that is similar to a cardiac pacemaker placed subcutaneously under the left anterior chest wall. Bipolar platinum stimulating electrode coils, which are implanted around the left vagus nerve, are connected to the generator by subcutaneously tunneled wires. The device automatically activates for up to 30 seconds every 5 minutes. Although stimulation of the vagal nerve in this manner may affect vocal cord function, sudden bradycardia or other side effects are uncommon.¹⁸⁶ When children with vagal nerve stimulators return for subsequent operations, it may be appropriate to deactivate the stimulator while the child is under general anesthesia to prevent repetitive vocal cord motion.

Hydrocephalus

Hydrocephalus is a condition involving a mismatch of CSF production and absorption, resulting in an increased intracranial CSF volume. It can be caused by a variety of pathologic processes, including arachnoid cysts (E-Fig. 24-3). Except for rare instances of excess CSF production, such as in choroid plexus papillomas, most cases of hydrocephalus result from some type of obstruction or an inability to absorb CSF appropriately. Commonly, this is a result of neonatal intraventricular or subarachnoid hemorrhage, congenital problems (e.g., aqueductal stenosis), trauma, infection, or tumors, especially those in the posterior fossa. Hydrocephalus can be classified as nonobstructive/communicating or obstructive/noncommunicating based on the ability of CSF to flow around the spinal cord in its usual manner.

E-FIGURE 24-3 Arachnoid cysts can cause hydrocephalus in children. A, Before decompression, the mass effect is obvious. B, After fenestration of the cyst, cerebrospinal fluid has a path of egress from inside of the cyst to the normal cerebrospinal fluid circulation. The mass effect is resolved.

Intracranial hypertension or decreased intracranial compliance typically accompanies untreated hydrocephalus in children. How much intracranial compliance exists and how acutely hydrocephalus develops are both factors in how severe the signs and symptoms of hydrocephalus become. If hydrocephalus develops slowly in the young infant, the skull will expand and the cerebral cortical mantle will stretch until massive craniomegaly (often with irreversible neurologic damage) occurs. However, if the cranial bones are fused or the cranium cannot expand fast enough, neurologic signs and symptoms rapidly become apparent. The child may become progressively more lethargic and develop vomiting, cranial nerve dysfunction (i.e., setting sun sign), bradycardia, brain herniation, and death.

Unless the cause of the hydrocephalus can be definitively treated, treatment usually involves surgical placement of an extracranial shunt. Most shunts transport CSF from the lateral ventricles to the peritoneal cavity (i.e., ventriculoperitoneal shunts). The distal end of the shunt occasionally must be placed in the right atrium or pleural cavity, usually because of problems with the ability of the peritoneal cavity to absorb CSF. Newer shunt systems with programmable valves are being tried to reduce the need for shunt revisions.¹⁸⁷

The use of a percutaneous flexible neuroendoscope through a burrhole in the skull has provided an alternative to extracranial shunt placement.^188,189 During these procedures, a ventriculostomy may be made to bypass an obstruction (e.g., aqueductal stenosis) by forming a communicating hole from one area of CSF flow to another using a blunt probe inserted through the neuroendoscope (Video 24-1). Common locations for a ventriculostomy are through the septum pellucidum (allowing lateral ventricles to communicate) or through the floor of the third ventricle into the adjacent CSF cisterns. Complications such as damage to the basilar artery or its branches or neural injuries can be life-threatening when they occur, and the anesthesiologist should be prepared for an emergency craniotomy during these procedures. Hemodynamic instability may occur intraoperatively if excessive cold irrigating solutions or large volumes are infused through the endoscope.

The anesthetic plan for a child with hydrocephalus should be directed at controlling ICP and relieving the obstruction as soon as possible. Children with an increased ICP are at risk for vomiting and pulmonary aspiration. Rapid-sequence induction and tracheal intubation should be performed. Ketamine is avoided in these children because of its potential to cause sudden massive intracranial hypertension.¹⁹⁰ Despite this concern, there is some evidence that ketamine may ameliorate the increased intracranial pressure in children.^191,192 In infants, hydrocephalus often produces large, dilated scalp veins, and they can be used for induction of anesthesia if necessary. If intravenous access cannot be established, induction with sevoflurane and gentle cricoid pressure may be an alternative, although less desirable, method of induction.¹⁹³ This method results in venodilation and usually facilitates establishment of intravenous access. After an intravenous catheter is inserted, the child may be paralyzed, the lungs ventilated, the trachea intubated, and the inhalational agent decreased or discontinued. The possibility of VAE during placement of the distal end of a ventriculoatrial shunt should always be considered. Postoperatively, children should be observed carefully because an altered mental status and recent peritoneal incision place them at increased risk for pulmonary aspiration after feeding begins. Analgesia may be provided with a variety of easily performed blocks of the head (see Figs. 41-15 and 41-16).

Anesthesiologists should be familiar with a few special situations involving shunts. Children who develop a shunt infection usually have the entire shunt system removed and external ventricular drainage established. They return to the operating room for insertion of a new shunt several days after the infection has been treated with antibiotics. While an external drain is in place, the operator must be careful not to dislodge the ventricular tubing. The height of the drainage bag should not be significantly changed in relation to the child’s head to avoid sudden alterations in ICP. For example, suddenly lowering an open drainage bag can siphon CSF rapidly from the head, resulting in collapse of the ventricles and rupture of cortical veins. When transporting children with CSF drainage or when moving them from a stretcher to an operating room table, it is best to close off the ventriculostomy tubing during these brief periods.

Anesthesiologists should be aware of the condition known as slit ventricle syndrome (Fig. 24-10). This situation develops in 5% to 10% of children with CSF shunts and is associated with overdrainage of CSF and small, slitlike, lateral ventricular spaces. Children with this condition do not have the usual amount of intracranial CSF to compensate for alterations in brain or intracranial blood volume. Special attention should be paid when CT scans identify this condition. It is probably safest to avoid the administration of excess or hypotonic intravenous solutions in these situations in the intraoperative and postoperative periods to minimize the potential for brain swelling. Some of these children cannot accommodate to situations that otherwise healthy children can easily tolerate. Episodes of postoperative cerebral herniation have been reported after uneventful surgical procedures.⁴⁵

FIGURE 24-10 Computed tonographic scans of children with normal-sized ventricles (A), untreated hydrocephalus (B), hydrocephalus treated with a ventricular shunt (C), and hydrocephalus treated with a ventricular shunt, resulting in slit ventricles (D).

(Courtesy Ellen Grant, MD.)

Congenital Anomalies

Congenital CNS anomalies typically occur as midline defects. This dysraphism may occur anywhere along the neural axis, involving the head (i.e., encephalocele) or spine (i.e., meningomyelocele) (Fig. 24-11, A). The defect may be relatively minor and affect only superficial bony and membranous structures, or it may include a large segment of malformed neural tissue.

FIGURE 24-11 A, An infant with an anterior encephalocele. B, An infant with a posterior encephalocele and myelomeningocele defects. Notice the large exposed surface areas that make this child prone to dehydration. Difficulty may be encountered in positioning for induction of anesthesia, and significant loss of blood and cerebrospinal fluid during surgical correction should be anticipated.

Chiari Malformations

There are several types of Chiari malformations (Table 24-3). The Arnold-Chiari malformation (type II) usually coexists in children with myelodysplasia. This defect consists of a bony abnormality in the posterior fossa and upper cervical spine with caudal displacement of the cerebellar vermis, fourth ventricle, and lower brainstem below the plane of the foramen magnum. Medullary cervical cord compression can occur (Figs. 24-12 and 24-13). Vocal cord paralysis with stridor and respiratory distress, apnea, abnormal swallowing and pulmonary aspiration, opisthotonos, and cranial nerve deficits may be associated with the Arnold-Chiari malformation and usually manifests during infancy. Children with vocal cord paralysis or a diminished gag reflex may require tracheostomy and gastrostomy to secure the airway and to minimize chronic aspiration. Children of any age may have abnormal responses to hypoxia and hypercarbia because of cranial nerve and brainstem dysfunction.^199,203 Extreme head flexion may cause brainstem compression in otherwise asymptomatic children.

TABLE 24-3 Types of Chiari Malformation

Type I	Caudal displacement of cerebellar tonsils below the plane of the foramen magnum
Type II (Arnold-Chiari; associated with myelomeningocele)	Caudal displacement of the cerebellar vermis, fourth ventricle, and lower brainstem below the plane of the foramen magnum Dysplastic brainstem with characteristic kink, elongation of the fourth ventricle, beaking of the quadrigeminal plate, hypoplastic tentorium with small posterior fossa, polymicrogyria, enlargement of the massa intermedia
Type III	Caudal displacement of the cerebellum and brainstem into a high cervical meningocele
Type IV	Cerebellar hypoplasia

FIGURE 24-12 A, Sagittal, T1-weighted magnetic resonance imaging (MRI) of a normal child. B, Sagittal, T1-weighted MRI of a child with a Chiari I malformation, which consists of caudal displacement of the cerebellar tonsils at least 5 mm into the upper cervical spinal canal, often with no clinical symptoms. C, Sagittal, T1-weighted MRI of a child with a type II Chiari malformation, which is characterized by caudal displacement of the cerebellar tonsils, additional brain anomalies, and a meningomyelocele deformity.

(Courtesy Ellen Grant, MD.)

FIGURE 24-13 The images show the posterior fossa in a child with a Chiari II malformation before and after posterior fossa decompression. A, Notice the downward herniation of the cerebellar tonsils. B, Resolution of cerebellar tonsillar herniation after posterior fossa decompression.

Type I Chiari malformations can occur in healthy children without myelodysplasia. These defects also involve caudal displacement of the cerebellar tonsils below the foramen magnum, but children usually have much milder symptoms, sometimes manifesting only as headache or neck pain.²⁰⁴ Surgical treatment usually involves a decompressive suboccipital craniectomy with cervical laminectomies.

Neuroradiologic Procedures

Many neuroradiologic procedures are performed in children. Anesthetic considerations for neurodiagnostic procedures (e.g., CT, MRI) are discussed elsewhere in this book (see Chapters 45 and 47), but certain therapeutic neuroradiologic procedures are addressed here.

To improve intraoperative navigation during intracranial procedures, the concept of intraoperative MRI was introduced in the mid-1990s. The technology has advanced to include a variety of operating room suite designs that encompass MRI machines (E-Fig. 24-4). These procedures present special challenges for neurosurgeons and anesthesiologists.^205–209 As with anesthesia for diagnostic MRI scans, special monitors, infusion pumps, and an MRI-safe or MRI-conditional anesthesia machine are required. It is challenging to do surgical procedures in this environment, especially because these procedures may take many hours, they may be associated with significant blood loss, and access to the child is severely limited. Some monitoring equipment found in conventional operating rooms (e.g., precordial Doppler ultrasonography, core temperature probes, fluid warmers) is not MRI safe or conditional. Nevertheless, numerous neurosurgical procedures have been safely performed in children in these MRI operating rooms, and the equipment for these procedures is rapidly evolving.

E-FIGURE 24-4 Intraoperative magnetic resonance imaging (MRI) unit. A child undergoing a craniotomy for tumor resection is being prepared to undergo an intraoperative MRI to assess the extent of resection needed. The child currently has an open craniotomy. The surgical field is kept sterile under the clear plastic drape. The mobile, 1.5-T MRI unit is moving out over the child and will be completely over the child’s head during imaging. The information provided by the intraoperative scan helps to guide intraoperative decision-making, such as the need for continued resection if residual tumor is found. Although this technology represents an advance in intraoperative navigation, the technical difficulties of anesthetizing a child for a major surgical procedure in a high-strength magnetic field environment are significant.

Acknowledgments

The authors wish to thank Veronica Miller, MD, and Elizabeth A. Eldredge, MD, for their prior contributions to this chapter.