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