Intracranial Pressure

Normal intracranial pressure (ICP) is relatively low in premature infants and slightly higher in full-term infants (2 to 6 mm Hg) and children and adults (0 to 15 mm Hg). Intracranial compliance is defined as change in intracranial pressure relative to the intracranial volume (Fig. 22-1). At normal intracranial volumes (point 1 in Fig. 22-1), ICP is low but compliance is high and remains so despite small increases in volume. As intracranial volume acutely rises, the ability to compensate is rapidly overwhelmed. This occurs even when the ICP is still within normal limits, but the compliance is low (point 2 in Fig. 22-1). When ICP is already high, a threshold is reached, after which further volume expansion leads to rapid ICP elevation (point 3 in Fig. 22-1). Point 4 (see Fig. 22-1) reflects maximal intracranial volume and high ICP. Clinically, intracranial compliance can be assessed by a variety of devices that measure intracranial pressure (Wiegand and Richards, 2007).

FIGURE 22-1 Intracranial compliance curve. At normal intracranial volumes (point 1), intracranial pressure (ICP) is low but compliance is high and remains so despite small increases in volume. As intracranial volume acutely rises, the ability to compensate is rapidly overwhelmed. This only occurs when the ICP is still within normal limits but compliance is low (point 2). When ICP is already high, a threshold is reached where further volume expansion leads to rapid ICP elevation (point 3). Point 4 reflects maximal intracranial volume and high ICP.

The neonatal cranial vault is unique in that it is in a state of flux. Open fontanelles and cranial sutures lead to a compliant intracranial space (Fig. 22-2). The mass effect of a slow-growing tumor or insidious hemorrhage is often masked by a compensatory increase in intracranial volume accompanied by head growth. When ICP increases occur slowly, open fontanelles and cranial sutures separate and enlarge the intracranial space, and thus the mass effect of a slow-growing tumor or insidious intracranial bleeding is often shrouded by a compensatory increase in intracranial volume (widening of the fontanelles and cranial sutures). However, acute increases in cranial volume caused by massive hemorrhage or obstructed cerebrospinal fluid (CSF) flow cannot be attenuated by expansion of the cranial vault and frequently result in life-threatening intracranial hypertension in infants (Shapiro et al., 1980). Once the fontanelles and sutures have closed, children have a smaller cranial volume and lower intracranial compliance than adults. The posterior fontanelle is usually closed by 2 months of age. The anterior fontanelle closes after the posterior fontanelle. By 3 months of age, the anterior fontanelle is closed in 1% of infants. By 1 year it is closed in about 40%, and by 2 years it is closed in 96%. Contributory factors include a higher ratio of brain water content, less CSF volume, and a higher ratio of brain content to intracranial capacity (Arieff et al., 1992). Thus, children are at higher risk of herniation than adults.

FIGURE 22-2 Effect of cranial sutures and fontanelle in neonates and infants. Initially the compliant skull of the neonate minimizes insidious increases in intracranial volume. However, acute increases in intracranial volume (hemorrhage and obstructed ventriculoperitoneal shunt) lead to rapid rises in intracranial pressure.

Cerebrospinal Fluid Dynamics

Cerebrospinal fluid is produced by the choroid plexus and absorbed through arachnoid villi and the ependymal lining of the ventricles. The ventricular system consists of paired lateral ventricles, which connect to the third ventricle via the foramen of Monro; the third ventricle connects to the fourth ventricle through the aqueduct of Silvius. The fourth ventricle communicates via the paired foramina of Luschka and the foramen of Magendie to a system of cisterns. The rate of reabsorption of CSF increases as ICP increases. Intracranial hemorrhage, inflammation or infection, tumors, or congenital malformations can lead to decreased CSF absorption with possible elevations in ICP. In the adult, the normal volume of CSF is approximately 150 mL, of which 25% is in the ventricular system. CSF is formed at approximately 20 mL/hr.

Cerebral Blood Flow

The cerebral circulation is tightly regulated by a number of homeostatic mechanisms. The major influences of the cerebral circulation are metabolism, partial pressure of arterial carbon dioxide (Paco₂), partial pressure of oxygen in arterial blood (Pao₂)_, blood viscosity, and cerebral autoregulation. Coupling of flow and metabolism is the most significant regulator of the cerebral circulation and is preserved even during sleep (Madsen and Vorstrup, 1991; Lenzi et al., 2000) and during general anesthesia (Lam et al., 1995). Under normal conditions, cerebral blood flow (CBF) is tightly coupled to cerebral metabolism and cerebral metabolic rate of oxygen consumption (CMRo₂) at global as well as regional levels. However, during periods of CNS activation, CBF increases more than CMRo₂, resulting in a decrease in the cerebral oxygen extraction fraction (Fox and Raichle, 1986)

During development, CBF changes with age, mirroring changes in neural development. CBF increases during early childhood, peaking during early-to-mid childhood and plateauing at 7 to 8 years (Wintermark et al., 2004). The healthy brain receives about 15% of cardiac output, and normal adult CBF is approximately 50 mL/100 g per minute (Vavilala et al., 2002a). There are few data available from healthy children. Kennedy and Sokoloff (1957) found CBF to be much higher, in the order of 100 mL/100 g per minute, in conscious healthy children, and a study using arterial spin labeling found similar values in young children (Biagi et al., 2007), which then decreased and approached adult values during the teenage years. Even during low-dosage sevoflurane anesthesia, values for CBF in children are higher than those for adults, whose CBF ranges between 50 and 100 mL/100 g per minute (Settergren et al., 1980).

Transcranial Doppler (TCD) ultrasonography can be used to estimate CBF, assuming that changes in CBF are proportional to changes in cerebral blood flow velocity (CBFV), and that mean flow velocities are used to represent mean CBF. Systolic and diastolic flow velocity parameters are often used to examine resistance of the cerebral vessels and also brain death. Studies using TCD show that in healthy newborns, CBFV is approximately 24 cm/sec, thereafter increasing with age until 6 to 9 years (97 cm/sec) (Bode and Wais, 1988) (Fig. 22-3). Beyond 10 years of age, CBFV decreases, approximating adult values of about 50 cm/sec (Aaslid et al., 1984; Vavilala et al., 2002a). Sex differences have also been observed and may result from differences in hematocrit, hormones, vessel size, or cerebral metabolism (Kennedy and Sokoloff, 1957; Tontisirin et al., 2007). The mean CBFV estimates for middle cerebral artery (V_MCA; anterior circulation) and basilar artery (V_BAS; posterior circulation) by age and sex are listed in Figure 22-3 and Table 22-1 (Bode and Wais, 1988; Wintermark et al., 2004; Vavilala et al., 2005).

FIGURE 22-3 Age-related changes in mean flow velocity of middle cerebral artery (VMCA) in both sexes. cerebral blood flow (CBF) and cerebral metabolic rate of glucose (CMRglu) [14,22,27,39,40]. Adult values: VMCA, 50 cm/sec [15,16], CBF, 50 mL/100 g per minute [13], CMRglu, 19 to 33 µmol/100 g per minute [27].

Cerebral Metabolic Rate

Global cerebral metabolic rate (CMR) for oxygen and glucose is higher in children than in adults (oxygen, 5.8 versus 3.5 mL/100 g brain tissue per minute, and glucose, 6.8 versus 5.5 mL/100 g brain tissue per minute, respectively) (Kennedy and Sokoloff, 1957). Like CMRo₂, cerebral metabolic rate for glucose (CMRglu) is lower at birth (13 to 25 µmol/100 g per minute), increases during childhood, peaks by 3 to 4 years (49 to 65 µmol/100 g per minute), and remains high until 9 years of age. CMRglu decreases thereafter, approaching adult rates (19 to 33 µmol/100 g per minute) (Chugani et al., 1987); changes in CMRo₂ and CRMglu mirror age-related changes in CBF (see Fig. 22-3).

Adenosine and nitric oxide (NO) are two purported mediators of flow–metabolism coupling and CBF increase with neuronal activation. Although the effect of adenosine on human CBF is controversial (Stange et al., 1997; Sollevi et al., 1987), up-regulation of NO production has been reported to increase CBF (Endres et al., 2004). Antagonists of both adenosine and NO attenuate the rise in CBF associated with neuronal activation, although neither mediator antagonist, alone or in combination, completely abolishes the CBF increase in response to neuronal activation (Gotoh et al., 2001). Therefore, other mediators, such as H⁺ ions, adenine nucleotides, potassium, prostaglandins, and vasoactive intestinal peptide, may also be involved in flow–metabolism coupling.

Hypothermia causes a reduction in CMRo₂, thereby decreasing CBF via flow–metabolism coupling. CBF decreases approximately 5% to 7% per degree Celsius, and reduction of the brain temperature to 15° C will reduce CMRo₂ to 10% of normothermic values (Vavilala et al., 2002). Hypothermia causes a reduction in both the basal metabolism required for maintenance of cellular integrity and the functional metabolism of the CNS.

Carbon Dioxide Vasoreactivity

Cerebral circulation is exquisitely sensitive to changes in Paco₂ (Harper and Glass, 1965; Padayachee et al., 1986). Like that of CBF and metabolism, the vasoreactivity of CO₂ may be higher in healthy children than in adults (13.8% and 10.3% change in mean CBFV per 1 mm Hg change in end-tidal CO₂) during propofol anesthesia (Leon and Bissonnette, 1991; Rowney et al., 2002; Karsli et al., 2003) The cerebrovascular response to changing CO₂ is attenuated at low blood pressure (Harper and Glass, 1965), increases in the presence of moderate hypoxia, decreases again during severe hypoxia (Quint et al., 1980), and may remain abnormally low after a hypoxic episode. Although there is an overall paucity of information regarding CO₂ reactivity in healthy children and in pediatric disease states, older studies suggest that reactivity to CO₂ is well developed even in healthy preterm infants (Pryds et al., 1990) and that CO₂ reactivity in newborns correlates with the lowest pH and may reflect the severity of perinatal asphyxia (Baenziger et al., 1999).

There are many potential control mechanisms involved in reactivity to carbon dioxide (CO₂R). Although neural regulation of CO₂R may be important (Meyer et al., 1971; Bates et al., 1977; Rovere et al., 1977), the most prominent proposed mechanism is the biochemical/metabolic control of cerebral vasoreactivity. The brisk response of the cerebral vasculature to CO₂ (the biochemical mechanism) is caused by the rapid diffusion of arterial CO₂ across the blood-brain barrier (BBB) into the perivascular fluid and cerebral vascular smooth muscle. Changes in extracellular fluid pH by both CO₂ and bicarbonate ions lead to cerebral vasodilation and increased CBF (Kontos et al., 1977). Although CO₂ is a potent cerebral vasodilator, the role of arterial H⁺ ions is more controversial. Although pH is not known to generally affect the cerebral vasculature, because arterial H⁺ ions do not readily diffuse across the intact BBB (Harper and Bell, 1963), severe metabolic acidosis may cause vasodilation and increase CBF (Westerlind et al., 1994). Therefore, severe metabolic acidosis and alkalosis may affect cerebral vascular tone, as do respiratory acidosis and alkalosis.

During chronic hypercapnia maintained for 6 hours, an adaptive increase in the pH of the CSF occurs with a decrease in CBF (Warner et al., 1987). A decrease in pH is accompanied by an increase in CSF bicarbonate. Similarly, during chronic hypocapnia, CSF bicarbonate concentration decreases, CSF pH gradually decreases, and CBF increases (Muizelaar et al., 1988).

The mechanism of CO₂R also appears to be regulated by local mediators rather than by chemoreceptors in the periphery. NO is partially responsible for CO₂-mediated cerebral vasodilation. Schmetterer and coworkers (1997) demonstrated a significant reduction in mean V_MCA to hypercapnia in healthy humans after administration of an NO synthase (NOS) inhibitor. However, NOS inhibitors do not completely ablate CO₂R, and NO may be more important in regional than in global regulation of vasoreactivity. The cerebral cortex in primates was the only site in which NOS inhibitor attenuated the CBF response to increasing arterial CO₂ concentration (McPherson et al., 1995). Another putative mediator of CO₂R is prostaglandin (PG) E₂. In contrast, indomethacin (a cyclooxygenase inhibitor) was shown to inhibit prostanoid synthesis and completely abolished CO₂-induced cerebral vasodilation (Wagerle and Degiulio, 1994).

Hypoxic and Hyperoxic Control of CBF

Compared with Paco₂, the influence of Pao₂ on the cerebral circulation is of much less clinical significance. There are minimal changes in CBF with changes in Pao₂ to greater than 50 mm Hg. Below that threshold of 50 mm Hg, CBF increases to maintain adequate cerebral oxygen delivery. Unlike CO₂R, the equilibration of CBF is longer and takes approximately 6 minutes after the establishment of hypoxemia (Ellingsen et al., 1987).

Hypoxemia may induce cerebral vasodilation via anaerobic glycolysis and lactic acid production, causing decreased extracellular pH and subsequent vasodilation. However, pH changes during hypoxemia are only partially responsible for the increased CBF (Koehler and Traystman, 1982). Adenosine has been shown to be necessary for the vasodilatory response to hypoxemia (Morii et al., 1987; Brian et al., 1996; DiGeronimo et al., 1998). NO has also been implicated as a mediator, because NOS inhibitors attenuate the increase in CBF that occurs during hypoxemia (Hudetz et al., 1998). Opioids such as methionine enkephalin and leucine enkephalin have been observed to contribute to hypoxic pial artery dilation in the piglet. Vasopressin-induced CSF methionine enkephalin and leucine enkephalin release are attenuated in the presence of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) antagonists. These data show that both cAMP and cGMP contribute to vasopressin-induced pial artery dilation and the release of the opioids methionine enkephalin and leucine enkephalin (Rossberg and Armstead, 1997).

Although hypoxemia produces cerebrovasodilation, the influence of increases in Pao₂ (hyperoxia) at normal atmospheric pressure is less well characterized and somewhat controversial (Armstead, 1998). Previous reports have documented both decrease in CBF (Kennedy et al., 1972) and no change in CBF (Busija et al., 1980) during hyperoxia. Animal studies demonstrate that hyperoxia elicits pial artery vasoconstriction during normocapnia, and that vasoconstrictor peptide endothelin-1 (ET-1) contributes to that vascular response (Armstead, 1999).

Effects of Viscosity on CBF

Viscosity of blood is primarily a function of hematocrit (Hct), and decrease in viscosity is usually secondary to hemodilution. During anemia, CBF increases as a result of improved rheology of the blood flow in the cerebral vessels and as a compensatory response to decreased oxygen delivery (Tomiyama et al., 1999). Although some data suggest that an Hct of less than 30% is associated with worse Glasgow Outcome Scale scores at discharge for adults with severe traumatic brain injury (TBI) (Carlson et al., 2006), neither the optimal duration for maintaining a specific hemoglobin (Hgb) level nor the relationship between target transfusion and neurologic outcome is fully known (Timmons, 2006). A recent study of critically ill children demonstrated that maintaining a Hgb of 7 g/dL rather than 9.5 g/dL can reduce requirements for blood transfusion, but none of these subjects had TBI (Lacroix et al., 2007).

Cerebral Autoregulation

Cerebral autoregulation is a homeostatic process: arterioles dilate and constrict to maintain CBF nearly constant over a range of blood pressures. In healthy adults, changes in mean arterial pressure (MAP) between 60 and 160 mm Hg result in little or no change in CBF (Fig. 22-4) (Lassen, 1959; Paulson et al., 1990). This adaptive mechanism maintains constant (adequate) CBF by vasodilation or decreasing cerebrovascular resistance. Beyond these limits of autoregulation, hypotension may result in cerebral ischemia, and hypertension may cause cerebral hyperemia.

FIGURE 22-4 Normal and absent autoregulation curves. The “absent” curve indicates a pressure-passive condition in which cerebral blood flow (CBF) varies in proportion to cerebral perfusion pressure. The curve is drawn to indicate subnormal CBF values during normotension, as have been shown to occur immediately after head injury and subarachnoid hemorrhage. The potential for modest hypotension to cause ischemia is apparent. MAP, mean arterial pressure.

(From Miller RD, Eriksson LI, Fleisher LA, et al., editors: Miller’s anesthesia, ed 7, Philadelphia, 2010, Churchill Livingstone.)

Healthy infants appear to autoregulate CBF as well as older children during low-dosage sevoflurane anesthesia, but the long-held assumption that the lower limit of autoregulation (LLA) is lower in young than in older children may not be valid (same LLA range for younger and older children, 46 to 76 mm Hg) (Vavilala et al., 2003). There are no data on the LLA in healthy neonates. Because blood pressure increases with age, young children may be at increased risk of cerebral ischemia as a result of lower blood pressure reserve (mean arterial pressure to LLA); however, neonates are especially vulnerable to cerebral ischemia and intraventricular hemorrhage because of this narrow autoregulatory range (Pryds et al., 2005) (Fig. 22-5). Sick premature neonates have CBF pressure-passivity, resulting in a linear correlation between CBF and systemic blood pressure (Boylan et al., 2000). Therefore, tight blood pressure control is essential in the management of neonates to minimize both cerebral ischemia during hypotension and intraventricular hemorrhage with increased blood pressure. Techniques such as deliberate hypotension in very young children or infants may not be desirable. Age-related increased latency may also occur in cerebral autoregulatory response in young children (Vavilala et al., 2002a), but no data exist in neonates. Animal data suggest that although CBF pressure autoregulation and reactivity to CO₂ operate in the newborn rat, hypercapnia abolishes cerebral autoregulation (Pryds et al., 2005), that abolished autoregulation is associated with cerebral damage in asphyxiated infants, and that the combination of isoelectric electroencephalograms (EEGs) and cerebral hyperperfusion is an early indicator of very severe brain damage (Pryds et al., 1990).

FIGURE 22-5 Autoregulation of cerebral circulation in neonates (curve B) and adults (curve A).

(Redrawn from Harris MM: Pediatric neuroanesthesia. In Berry FA, editor: Anesthetic management of difficult and routine pediatric patients, ed 2, New York, 1990, Churchill Livingstone, p 341. After data of Hernández MJ, Brennan RW, Vannucci RC, et al: Cerebral blood flow and oxygen consumption in the newborn dog, Am J Physiol 234:R209, 1978.)

Despite these clinical observations, the mechanisms of normal cerebral autoregulation in healthy children and adaptations in acute disease are not completely understood, and as occurs with changes in CBF, both anatomic and physiologic maturation might play a role in the development of a fully developed autoregulatory response. The mechanisms of cerebral autoregulation may involve a combination of myogenic, neurogenic, and metabolic processes. The metabolic mechanism stipulates that autoregulation is mediated by the release of a vasodilator substance that regulates the cerebrovascular resistance to maintain CBF constant. Although no specific substance fits all experimental observations, adenosine, a potent cerebral vasodilator, is formed from the breakdown of ATP when neuronal demand of oxygen exceeds supply (Winn et al., 1985). Adenosine can be found in increased concentration in cerebral tissue as systemic blood pressure falls toward the lower limit of autoregulation. In fact, brain adenosine concentration doubles within 5 seconds of decreasing blood pressure (Winn et al., 1980). Cortical activation via contralateral peripheral stimulation is also immediately followed by adenosine release and regional vasodilation (Ngai et al., 1998). It has been suggested that NO exerts an influence on basal and stimuli mediated cerebrovascular tone. The mechanism of NO-induced cerebral vasodilation probably involves cGMP and a decrease in intracellular calcium. It is unclear to what extent NO affects cerebral autoregulation in both healthy patients and in patients with TBI. Although earlier studies suggest that NO has no influence on cerebral autoregulation, Jones and coworkers (1999) described an increase in the lower limit of autoregulation with NOS inhibitors. Other transmitters or substances that have been proposed as mediators of autoregulation include protein kinase C (Jones et al., 1999), melatonin (Régrigny et al., 1999), prostacyclin, activated potassium channels, and intracellular second messengers (Faraci and Heistad, 1998).

Pressure-dependent myogenic tone in the systemic resistance vessels was first proposed by Bayliss in 1902 was not experimentally verified until approximately 50 years later. The myogenic theory states that the basal tone of the vascular smooth muscle is affected by change in perfusion or transmural pressure, and that muscle contracts with increased MAP and relaxes with decreased MAP. Studies suggest that there may be two myogenic mechanisms involved in cerebral autoregulation: a rapid reaction to pressure pulsations and a slower reaction to change in MAP. This adaptive process appears to be initiated within the first 400 msec (rapid and rate-dependent response) and is probably completed in a few minutes by the slower and rate-independent component of the autoregulatory process. The slower secondary component appears to be the dominant force in regulating CBF. Autoregulation might also be invoked by incremental increases in blood pressure. However, constant pressure elevation is probably not a sufficient stimulus to maintain sustained vascular contraction. Some investigators believe the myogenic mechanism sets the limits of autoregulation, whereas the metabolic mediators are responsible for cerebral autoregulation itself.

The Neurogenic Mechanism

Perivascular innervation of the cerebral resistance vessels and the specific neurotransmitter contained in the perivascular nerve fibers may also modulate vascular response to change in blood pressure. However, the specific mechanisms by which the CNS exerts control on the cerebral vasculature are poorly understood. Although acetylcholine is the most abundant perivascular neurotransmitter, the list of neurotransmitters involved in this neural response includes norepinephrine, neuropeptide Y, cholecystokinin, acetylcholine, vasoactive intestinal peptide, and calcitonin gene-related peptide (Yoon et al., 1997). Experimentally sympathetic stimulation can shift the autoregulatory curve to the right, thus protecting the brain against severe elevation of MAP.

Intravenous Anesthetics

Inhalational Anesthetics

Volatile anesthetic drugs are potent cerebrovasodilators and may produce uncoupling of CMRo₂ and CBF, and different volatile anesthetics may have varying uncoupling profiles (Hansen et al., 1989). Uncoupling may lead to increased CBV and can exacerbate intracranial hypertension. Children have increased sensitivity to the vasodilatory effects of volatile drugs. TCD measurements reveal that the following volatile agents increase CBFV in descending order: halothane, desflurane, isoflurane, and sevoflurane. Autoregulation is also blunted in the presence of volatile drugs in a dosage-dependent fashion. However, this perturbation is mitigated by hypocapnia. Nitrous oxide has vasodilatory effects alone and in combination with other anesthetics. Because isoflurane and sevoflurane significantly decrease CMRo₂ in children and maintain coupling, these two inhaled drugs are ideal anesthetics for the neurologically compromised patient. Sevoflurane does not significantly affect CBFV, and it preserves cerebral autoregulation in children anesthetized with up to a minimum alveolar concentration (MAC) of 1.5 (Fairgrieve et al., 2003; Wong et al., 2006).

Muscle Relaxants

Nondepolarizing Muscle Relaxants

The presence of motor deficits or the administration of anticonvulsants may affect the dosage of nondepolarizing muscle relaxant necessary in neurosurgical patients. Hemiplegia from an upper motor neuron lesion (such as a stroke or a brain tumor) is associated with resistance to nondepolarizing relaxants on the paretic side (Graham, 1980; Moorthy and Hilgenberg, 1980; Shayevitz and Matteo, 1985). Excessive dosages of muscle relaxants may be given if the dosage is guided by a nerve stimulator monitoring a hemiplegic extremity. In contrast, an increased response to nondepolarizing muscle relaxants is observed in paretic-muscle lower motor neuron lesions (e.g., paraplegia and quadriplegia) (Brown et al., 1975). Acute administration of several anticonvulsants, including phenytoin, phenobarbital, trimethadione, and ethosuximide, enhances nondepolarizing neuromuscular blockade or delays its reversal (Gandhi et al., 1976; Spacek et al., 1999). Patients receiving chronic phenytoin or carbamazepine therapy are resistant to the effects of nondepolarizing relaxants, including pancuronium, (Roth and Ebrahim, 1987), metocurine (Ornstein et al., 1985), vecuronium (Ornstein et al., 1987; Alloul et al., 1996), and rocuronium (Spacek et al., 1999; Hernández-Palazón et al., 2001) but, interestingly, not mivacurium or atracurium (Ornstein et al., 1987; Spacek et al., 1996). The cause of phenytoin-induced resistance to nondepolarizing muscle relaxants and the reason for the lack of the same effect with mivacurium or atracurium are unclear. Finally, no data have yet been published describing the interactions of anticonvulsants (felbamate, gabapentin, levetiracetam, tiagabine, topiramate, sodium valproate, or valproic acid) with nondepolarizing neuromuscular blocking drugs (Fig. 22-6).

FIGURE 22-6 Effect of chronic anticonvulsant therapy on the half-life of the muscle relaxant vecuronium. Vecuronium plasma concentrations are plotted against time after a single bolus dose of vecuronium (0.15 mg/kg). Mean ± SD is plotted for all three groups.

Vasodilators

The direct-acting vasodilators, including sodium nitroprusside, ATP, adenosine, nitroglycerin, diazoxide, and hydralazine, are cerebrovasodilators and may increase CBF and ICP (Stoyka and Schutz, 1975; Turner et al., 1977; Marsh et al., 1979; Cottrell et al., 1980; McDowall, 1985). The calcium channel blockers also raise CBF and ICP (Griffin et al., 1983; Mazzoni et al., 1985). These drugs should therefore be avoided in patients with reduced intracranial compliance, unless the dura is open or ICP is monitored. Indirect-acting antihypertensives, including trimethaphan (a ganglionic blocker), propranolol and esmolol (β-adrenergic blockers), and labetalol (a combined α- and β-blocker), do not increase CBF or ICP (Magness et al., 1973; Turner et al., 1977; McDowall, 1985). These agents are useful for the control of blood pressure in patients with elevated ICP. Trimethaphan may interfere with the neurologic examination by causing mydriasis, cycloplegia, or anisocoria. Sodium nitroprusside lowers the range of cerebral autoregulation. Brain-surface oxygen tension is greater (Maekawa et al., 1977) and metabolic disturbances in brain biochemistry (e.g., lactate, pyruvate, and phosphocreatine levels) are less during nitroprusside-induced hypotension than with trimethaphan- or hemorrhage-induced hypotension (Michenfelder and Theye, 1977). In addition, cortical blood flow and electrical activity are better preserved at lower MAP with sodium nitroprusside (Ishikawa and McDowall, 1981). Nitroprusside, however, induces more pronounced blood-brain barrier dysfunction than does trimethaphan (Ishikawa et al., 1983). Because CBF, brain oxygen tension, neuronal function, and brain metabolism are better maintained with sodium nitroprusside than with trimethaphan at a MAP of 50 mm Hg, sodium nitroprusside is the preferred agent for deliberate hypotension.

Central Nervous System Toxicity of Anesthetic Agents

Preclinical studies have demonstrated that prolonged exposure of fetal and neonatal laboratory animals to anesthetic drugs leads to accelerated neurodegeneration (Ikonomidou et al., 1999; Jevtovic-Todorovic et al., 2003; Slikker et al., 2007). The data generated in these reports have provoked a heated debate on its relevance to the practice of pediatric anesthesia (Anand and Soriano, 2004; Olney et al., 2004). There is no doubt that this phenomenon is valid in the experimental paradigms used in these laboratory investigations. The same model has also implicated dexamethasone and magnesium sulfate in accelerating neuroapoptosis in the development of rat brain (Noguchi et al., 2008; Dribben et al., 2009). However, a number of factors make the extrapolation of these findings to humans in the daily practice of clinical pediatric anesthesiology questionable. For example, these animal and in vitro studies have significant limitations in terms of agent dosage and duration of exposure (both absolute and in comparison with human studies) (Loepke and Soriano, 2008). Furthermore, no defined clinical markers or syndromes are associated with neonatal exposure to general anesthetics. Unlike general anesthetic agents, exposure to alcohol or anticonvulsant drugs during gestational development has clearly characterized clinical syndromes. Although histologic evidence of accelerated neurodegeneration has been verified by several investigational groups, discrepancies in neurocognitive outcomes exist (Loepke et al., 2009). Prospective clinical investigations are underway to verify these observations. Finally, the majority of neonatal and infant surgery is urgent or emergent, and anesthetic care is essential to proceed safely. It has been clearly demonstrated that inadequate anesthesia leads to poor postoperative outcomes in infants (Anand and Hickey, 1987; Anand and Soriano, 2004), and it is crucial to attenuate the stress response associated with surgical stimulation.

Several retrospective reports have positively linked exposure to general anesthesia before the age of 4 with an increased chance of developing learning deficits. Wilder and colleagues (2009) examined the extensive medical and school records of 5358 children in Rochester, Minnesota, and determined that there was an association between learning deficits in school and having more than two surgeries before age 4. A cross-sectional study done by Kalkman and colleagues (2009) in Utrecht, The Netherlands, surveyed a small number of parents of children who had had surgery at a young age and determined that there was a trend toward greater prevalence of learning deficits in children who had had early surgery. However, these reports need to be reconciled with a recent report demonstrating no causal relationship between anesthesia exposure and subsequent learning behavior in twin cohorts (Bartels et al., 2009). Clinicians should be aware of the rapid developments in the area of anesthetic-induced neurodegeneration and keep in mind the degree of necessity of infant surgical procedures and the more significant effects of the hypoxic and cardiovascular mechanisms of brain injury and death during anesthesia and surgery in these patients.

Physical Examination

The physical examination should include a brief neurologic evaluation that includes consciousness level, motor and sensory function, normal and pathologic reflexes, integrity of the cranial nerves, and signs and symptoms of intracranial hypertension (Fig. 22-7 and Table 22-4). It is essential to document these factors in the preoperative examination to be able to gauge postoperative neurologic function. Lesions of the brainstem can manifest with cranial nerve dysfunction such as respiratory distress, impaired gag reflex and swallowing, and pulmonary aspiration. Evidence of muscle atrophy and weakness should be noted, particularly if the patient is hemparetic, hemiplegic, or bedridden, because up-regulation of acetylcholine receptors may precipitate sudden hyperkalemia after succinylcholine administration and induce resistance to nondepolarizing muscle relaxants in the affected limbs. Body weight should be accurately measured to guide the administration of drugs, fluids, and blood products. Physical signs of dehydration should be noted, especially in patients who have been chronically ill or have received osmotic or diuretic agents.

FIGURE 22-7 An infant with hydrocephalus. Note enlarged head and the downward gaze (the setting-sun sign). The latter suggests the presence of intracranial hypertension.

TABLE 22-4 Signs of Intracranial Hypertension in Infants and Children

Radiologic and Laboratory Evaluation

Most neurosurgical patients have a magnetic resonance imaging (MRI) or CT scan of the head as part of the preoperative assessment. These scans should be reviewed with the neurosurgeon to confirm the primary lesion and the presence of evolving neurologic conditions (hydrocephalus, compressed cisterns, midline shifts) (Fig. 22-8). Preoperative laboratory tests should be tailored to the proposed neurosurgical procedure. Given the risk of significant blood loss associated with surgery, the hematocrit, prothrombin time, and partial thromboplastin time should be obtained to uncover any insidious hematologic disorder. Patients with suprasellar pathology should have an endocrinology evaluation. Type- and cross-matched blood should be ordered before all craniotomies. Endocrinologists may be needed to help optimize the patient’s condition before surgery and to assist in postoperative management. Liver function tests and a hematologic profile should be obtained if not recently reviewed for children taking long-term anticonvulsants.

FIGURE 22-8 A, CT scan depicting normal (left) and compressed (right) basal cisterns. The basal, or perimesencephalic, cerebrospinal fluid space consists of the interpeduncular cistern (anterior), the ambient cisterns (lateral), and the quadrigeminal cisterns (posterior). In the patient (right) with diffuse cerebral swelling (caused by sagittal sinus thrombosis), the cisterns have been obliterated. B, Hydranencephaly. CT scan demonstrates replacement of the cerebral hemispheres by a large, water-dense cavity with residual islands of brain tissue in regions of the occipital poles and right inferior temporal lobe.

(A, Courtesy Ivan Petrovitch, MD; B, courtesy Division Neuroradiology, University of Health Center of Pittsburgh.)

Premedication

Perioperative anxiety plays a significant role in the care of the pediatric neurosurgical patient. Anxiety issues are related to the cognitive development and age of the child (see Chapter 2, Behavioral Development). Preoperative sedatives given before the induction of anesthesia can ease the transition from the preoperative holding area to the operating room (Kain et al., 2004). Oral midazolam is particularly effective in relieving anxiety and producing amnesia. If an indwelling IV catheter is in place, midazolam can be slowly titrated to achieve sedation. Sedation is usually withheld from pediatric neurosurgical patients until they arrive in the preoperative area to avoid the problem of an oversedated, neurologically impaired patient with inadequate supervision; however, heavy premedication may be warranted to avoid agitation in patients with moyamoya disease or an intracranial aneurysm or arteriovenous malformation that has recently bled. Narcotics are best withheld preoperatively, as they may cause nausea or respiratory depression, especially in patients with increased ICP.

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 5 to 20 minutes to take effect. Alternatively, after application of EMLA (eutectic mixture of local anesthetics, 2.5% lidocaine, and 2.5% prilocaine) cream, an IV catheter can be inserted, into which incremental dosages of IV midazolam may then be carefully titrated.

Induction of Anesthesia

The patient’s preoperative status dictates the appropriate technique and drugs for induction of anesthesia. A modified Glasgow Coma Scale for infants and children is useful for assessing the mental status of the patient before the administration of anesthesia (Table 22-5). Somnolent patients with intracranial hypertension are at risk for aspiration pneumonitis and require a rapid-sequence induction of anesthesia.

In the presence of intracranial hypertension, the primary goal during induction is to minimize severe increases in ICP. The effects of anesthetic drugs on cerebral hemodynamics were discussed extensively earlier in this chapter and are summarized in Table 22-2. In general, most IV drugs decrease CBF, metabolism, and ICP. Thiopental (4 to 8 mg/kg) and propofol (2 to 5 mg/kg) have similar effects on cerebral hemodynamics and maintain tight coupling of CBF and cerebral metabolic rate. Patients at risk for aspiration pneumonitis (including certain patients with intracranial hypertension) should have rapid-sequence induction of anesthesia using cricoid pressure. An IV hypnotic drug, such as thiopental or propofol, is administered and followed immediately by a rapid-acting muscle relaxant. Rocuronium can be used when succinylcholine is contraindicated, such as for patients with spinal cord injuries or paretic extremities. In instances of preexisting neurologic injury (e.g., in a patient with a history of a stroke resulting in a weak extremity), succinylcholine can result in sudden, catastrophic hyperkalemia. Etomidate and ketamine are frequently used to induce anesthesia in hemodynamically compromised patients, because these drugs are less likely to cause hypotension than thiopental or propofol. However, CNS excitation and increased ICP have been associated with these drugs, respectively, and they may not be appropriate for many neurosurgical patients. Ketamine should be avoided because of its known ability to increase cerebral metabolism, CBF, and ICP.

General anesthesia can be induced with sevoflurane and nitrous oxide in patients who are neurologically stable. Although volatile anesthetic drugs are potent cerebrovasodilators and may produce uncoupling of cerebral metabolic requirement of oxygen, its use for induction of anesthesia is relatively brief. ICP can be lowered during induction by initiating controlled hyperventilation and administering opioid and barbiturate supplements before laryngoscopy and intubation. A nondepolarizing muscle relaxant may then be administered after IV access has been established to facilitate intubation of the trachea. Pancuronium is an ideal muscle relaxant for neonates and infants because it produces tachycardia that counters the parasympathetic effect of laryngoscopy.

A common problem is an uncooperative toddler who has an intracranial tumor, has moderately decreased intracranial compliance, and is agitated and resistant to parental separation. Some clinicians advocate the use of rectal barbiturates with meticulous attention to airway maintenance to avoid obstruction and resultant hypercarbia and hypoxemia. However, others argue that a crying, agitated child has demonstrated a tolerance to increased ICP and that IV induction is safer. Fortunately (for the anesthesiologist), patients who have severe intracranial hypertension generally have a decreased level of consciousness, and it becomes easier to insert an IV catheter when it is most necessary.

Succinylcholine should be avoided in patients with denervating processes such stroke, or spinal cord injury, because it can result in life-threatening hyperkalemia.

Airway Management

Developmental changes in airway anatomy have a significant impact on management of the pediatric airway. Nasotracheal tubes may be best suited for situations when the patient will be prone, because orotracheal tubes can kink at the base of the tongue when the head is a flexed and result in airway obstruction. The timing of tracheal extubation may be challenging after neurosurgical procedures. Infants, particularly those with Chiari malformation (Cochrane et al., 1990) or older children after procedures in the posterior fossa (Cochrane et al., 1994), may exhibit intermittent apnea, vocal cord paralysis, or other irregularities before resuming a stable respiratory pattern. Significant airway edema and postoperative obstruction can complicate prone procedures or those involving significant blood losses and large volume replacement. Lingual or supraglottic swelling may require direct laryngoscopy to assess the airway. Head-up positioning and gentle forced diuresis usually improve airway edema within 24 hours.

Positioning

Patient positioning for surgery requires careful preoperative planning to allow adequate access to the patient for both the neurosurgeon and anesthesiologist. For the patient with altered physiologic states, various surgical positions can predispose to injury (Fig. 22-9 and Table 22-6). The prone position is commonly used for posterior fossa and spinal cord surgery. The sitting position may be more appropriate for obese patients, who may be difficult to ventilate in the prone position because of increased intrathoracic pressure. In addition to the physiologic sequelae of the sitting position, a spectrum of neurovascular compression and stretch injuries can occur. It is important to ensure free abdominal wall motion. Increased intraabdominal pressure can impair ventilation, cause venocaval compression, and increase epidural venous pressure and bleeding. Postoperative visual loss has been linked to surgery in the prone position. Therefore, the eyes must be free of any direct contact with the horseshoe or Mayfield head holder (Lee et al., 2006). Many neurosurgical procedures are performed with the head slightly elevated to facilitate venous and CSF drainage from the surgical site; however, superior sagittal sinus pressure decreases with increasing head elevation, and this increases the likelihood of VAE (Grady et al., 1986). Excessive rotation of the head can impede venous return via compression of the jugular veins and can lead to impaired cerebral perfusion, increased ICP, and venous bleeding. Flexion of the head can cause the tracheal tube to migrate into a main stem bronchus. Extreme head flexion can cause brainstem compression in patients with posterior fossa pathology, such as mass lesions or an Arnold-Chiari malformation and high cervical spinal cord ischemia. Likewise, extreme head extension may result in inadvertent tracheal extubation. Finally, all pressure points should be padded and peripheral pulses checked to prevent peripheral nerve and vascular compression and pressure injury.

FIGURE 22-9 Positioning patients and padding them to prevent injuries is essential, especially for prolonged procedures with the patient in the prone position.

TABLE 22-6 Physiologic Effects of Patient Positioning

Vascular Access

The routine use of central venous catheters in pediatric neurosurgical patients is controversial. The small bore and relatively long length of pediatric central catheters may produce too much resistance to high flow rates. Typically, two large peripheral venous cannulae are sufficient for most craniotomies. Should peripheral IV be difficult to secure, a cannulation of the femoral vein avoids the risk of pneumothorax associated with subclavian catheters, and it does not interfere with cerebral venous return as may be the case with jugular catheters. Because significant blood loss and hemodynamic instability can occur during craniotomies, an arterial catheter provides direct blood pressure monitoring and sampling for blood-gas analysis.

Maintenance of Anesthesia

Specific drugs used for the maintenance of anesthesia have not been shown to affect the outcome of neurosurgical procedures when properly administered (Todd et al., 1993). The most frequently used technique during neurosurgery consists of an opioid (i.e., fentanyl, sufentanil, or remifentanil) along with inhaled nitrous oxide (70%) and low-dosage (0.2% to 0.5%) isoflurane. Routine administration of a preoperative benzodiazepine such as midazolam (0.5 mg/kg orally, or 0.1 mg/kg intravenously) should provide some degree of amnesia of perioperative events as well as minimize anxiety.

Chronic administration of anticonvulsant drugs, such as phenytoin and carbamazepine, induces rapid metabolism and clearance of neuromuscular blockers and opioids because of the enhanced activity of the hepatic P450 enzymes (Soriano and Martyn, 2004). Patients receiving chronic anticonvulsant therapy require larger dosages of muscle relaxants and narcotics because of the induced enzymatic metabolism of these agents (see Fig. 22-6) (Soriano et al., 2001). Muscle relaxants should be withheld or permitted to wear off when assessment of motor function during neurosurgery is planned.

Fluid and Electrolyte Management

Meticulous fluid management is critical in the care of neurosurgical patients who are children. Diminutive size and immature renal function make fluid and electrolyte imbalances common. Water freely diffuses through the BBB and disruptions in tight junctions, and inequality of pressure gradients in osmolality, hydrostatic pressure, and colloid oncotic pressure facilitate the net movement of fluid across the BBB into the brain, resulting in increased ICP. Osmolar gradients are maintained only when the BBB is intact; when it is disrupted, large molecules that are typically excluded, such as albumin, enter the brain and can worsen edema.

There is no absolute formula for volume replacement in pediatric neuroanesthesia. Hemodynamic stability during intracranial surgery requires careful maintenance of intravascular volume, but preoperative fluid restriction or diuretic therapy may lead to blood pressure instability and even cardiovascular collapse if sudden blood loss occurs during surgery. Therefore, normovolemia should be maintained throughout the procedure. Estimation of the patient’s blood volume is essential in determining the amount of allowable blood loss and when to transfuse blood. Blood volume depends on the age and size of the patient.

Normal saline is commonly used as the maintenance fluid during neurosurgery because it is mildly hyperosmolar (308 mOsm/kg) and should minimize cerebral edema. Isotonic crystalloid solutions are commonly used during anesthesia and for cerebral resuscitation. However, rapid infusion of large quantities of normal saline (>60 mL/kg) can be associated with hyperchloremic acidosis (Scheingraber et al., 1999). The calculated maintenance rate of fluid administration depends on the weight of the patient (Holliday and Segar, 1957). These rates are based on normal physiologic conditions. Increases in insensible losses, blood loss, or other conditions such as diabetes insipidus or the syndrome of inappropriate antidiuretic hormone excretion, as noted later, should be considered when determining the proper amount of fluid administration. Depending on the extent and length of the surgical procedure and the exposure of vascular beds, additional fluid administration (3 to 10 mL/kg per hour) may be necessary. Unlike adults, children can become hypovolemic from scalp injuries and isolated traumatic brain injury. Hypotonic crystalloids should be avoided, and the role of colloids is controversial. In 2007, the SAFE study reported that patients with TBI who received fluid resuscitation with albumin had higher mortality rates than those who received fluids with crystalloids (Myburgh et al., 2007). The use of hydroxyethyl starch is discouraged because of its role in exacerbating coagulopathy. Hypertonic saline (0.1 to 1.0 mL/kg) may be used to increase CPP, but, in this setting, well-conducted studies show that there is no advantage to hypertonic saline compared with conventional prehospital fluid protocols (Cooper et al., 2004), and the very large, randomized SAFE trial found that there was no difference in 28-day survival between albumin and saline resuscitation for intensive care patients. However, in a subgroup of patients with TBI, fluid resuscitation with albumin was noted to have higher mortality rates than resuscitation with crystalloid (Myburgh et al., 2007).

Because the potential for significant blood loss is likely in most craniotomies in infants and children, the maximum allowable blood loss should be determined in advance to know when blood should be transfused to the patient. However, there are no guidelines regarding an appropriate threshold for transfusing blood, as it is unclear what hematocrit is needed for optimal oxygen delivery for the pediatric brain and in different disease states. Thus, the decision to transfuse should be dictated by the type of surgery, underlying medical condition of the patient, and potential for additional blood loss both intraoperatively and postoperatively. Hematocrits of 17% to 25 % may warrant blood transfusion. Packed red blood cells (10 mL/kg) raise the hematocrit by 10%. Blood losses may be replaced with 3 mL of normal saline per 1 mL of loss blood, or a colloid solution such as 5% albumin equal to the volume of blood loss. It can be difficult to accurately estimate blood loss during intracranial procedures, as the anesthesiologist may have a compromised view of the surgical field, and blood loss may be hidden in the drapes or elsewhere.

Infants are at particular risk for perioperative hypoglycemia. Small premature neonates, with limited reserves of glycogen and limited gluconeogenesis, require continuous infusions of glucose at 5 to 6 mg/kg per minute to maintain serum levels. At the same time, the stress of critical illness and resulting insulin resistance can produce hyperglycemia that, in turn, is associated with neurologic injury (Jeremitsky et al., 2005; Van den Berghe et al., 2005) and poor outcomes in adults (Van den Berghe et al., 2001). However, it is unclear if tight glycemic control offers significant benefits to children (Branco and Tasker, 2007; Klein et al., 2007). Limited evidence now suggests that tight control may carry undue risk of hypoglycemia, and newer data are less supportive of very tight glycemic control (Van den Berghe et al., 2006). Retrospective studies from children suggest that both hyperglycemia (glucose level at 200 to 250 mg/100 mL) and hypoglycemia occur after TBI (Sharma et al., 2009), and that hyperglycemia is associated with poor outcome. Continuous intraoperative monitoring is not yet the standard of care. Hourly glucose checks are recommended.

Brain swelling can occur during neurosurgical procedures, with devastating consequences. Aggressive hyperventilation should be reserved for when herniation is impending and immediate life-saving maneuvers are required. However, a study in adults demonstrated that moderate hyperventilation may improve surgical conditions (Gelb et al., 2008). There is considerable evidence in patients with TBI that even mild hyperventilation leads to hypoperfusion (Coles et al., 2002). Although there are no data suggesting such a phenomenon in other neurosurgical patient populations, other methods of reducing intracranial pressure can be used. Elevation of the head above the heart and the use of hyperosmolar therapy (e.g., mannitol or hypertonic saline) are generally used initially.

Mannitol (0.25 to 0.5 g/kg) transiently alters cerebral hemodynamics and raises serum osmolality by 10 to 20 mOsm/kg (Soriano et al., 1996). However, repeated dosing can lead to extreme hyperosmolality, renal failure, and further brain edema. Hypertonic saline increases serum sodium, decreases ICP, and increases CPP titrated to a serum sodium rate change and brain edema (Khanna et al., 2000). Administration is typically 3 mL/kg of 3% (hypertonic) saline targeted to a serum sodium rate change of 0.05 mEq/hr and serum sodium levels of 155 to 160 mEq/L. However, the endpoints depend on the initial serum sodium and the degree of brain edema (typically 155 to 160 mEq/L). Three percent normal saline is generally administered centrally to avoid phlebitis and tissue necrosis, but hypertonic saline concentrations of 2% may be administrated peripherally. Theoretical risks include central pontine myelinolysis and renal failure. Furosemide is a useful adjunct to mannitol for decreasing acute cerebral edema and has been shown in vitro to prevent rebound swelling caused by mannitol (McManus and Soriano, 1998; Thenuwara et al., 2002).

Nonosmotic secretion of antidiuretic hormone (ADH) makes hyponatremia common after neurosurgery. Elevated ADH levels can result from a variety of stimuli, ranging from pain and nausea to fluid shifts and intravascular hypovolemia. Acute hyponatremia can provoke seizures and can be treated with hypertonic saline, fluid restriction, and diuretics (Porzio et al., 2000). The syndrome of cerebral salt wasting is also common in children and can be seen after head trauma and all manner of neurosurgical procedures. The syndrome has been diagnosed with increasing frequency and reported in association with meningitis (Celik et al., 2005), calvarial remodeling (Levine et al., 2001; Byeon and Yoo, 2005), tumor resection (Jimenez et al., 2006), and even hydrocephalus (Table 22-7). Although it is easily confused with other entities (Singh et al., 2002), a recent retrospective review put its incidence at 11.3 per 1000 procedures (Jimenez et al., 2006). In these patients, the mean duration of symptoms was 6 days, with a range of 1 to 5. Cerebral salt wasting, the result of excessively high atrial or brain natriuretic peptide levels (Berger et al., 2002), is marked by hyponatremia, hypovolemia, and excessive urinary excretion of sodium. Although the classic treatment involves saline administration, more rapid resolution has been achieved with fludrocortisone (Papadimitriou et al., 2007).

Diabetes insipidus is a well-known complication of surgical procedures involving or adjacent to the pituitary and hypothalamus. It is most frequently seen in association with craniopharyngioma, where it can be a manifesting symptom in 40% of cases (Ghirardello et al., 2006). Diabetes insipidus is recognized by a rising serum sodium (>145 mg/dL) accompanied by copious (>4 mL/kg per hour) output of dilute urine. Severe dehydration and hypovolemia may develop. One effective protocol employs maximal antidiuresis with IV vasopressin and strict limitation of IV fluids (Wise-Faberowski et al., 2004). This strategy avoids the pitfalls of titrating drug to urine output and recognizes that renal blood flow remains normal in the normovolemic, but maximally antidiuresed, child. Because urine output can be minimal (0.5 mL/kg per minute), other clinical markers of volume status must be used.

Venous Air Embolus

Venous air embolus can occur during craniotomies in infants and children, primarily because the head of a small child is large in relation to the rest of the body, and it rests above the heart in either the prone or the supine position. Venous sinuses have dural attachments that impede their ability to collapse. Other conduits for VAE include bone, bridging veins, and spinal epidural veins. When air enters the central circulation, right ventricular output is impeded, leading to pulmonary edema and bronchoconstriction and cor pulmonale, cardiovascular collapse, and death in the most severe cases. Air may gain access to the systemic circulation through right-to-left intracardiac shunts. Potential cardiac shunts exist in many healthy infants and children and may become clinically significant if pulmonary hypertension develops acutely after a large air embolism. Paradoxical air emboli may cause cerebral or coronary artery obstruction, with subsequent cerebral infarction or ventricular fibrillation. Although the incidence of VAE is greatest in the sitting position, it has been reported in the lateral, supine, and prone positions. 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 higher incidence of hypotension and a lower likelihood of successful aspiration of central (intravascular) air (Cucchiara and Bowers, 1982).

Venous air emboli pose a risk during craniotomies in infants and children, primarily because the head of a small child is large in relation to the rest of body and rests above the heart in both the prone and supine positions (Harris et al., 1987; Faberowski et al., 2000). Standard neurosurgical techniques may elevate the patient’s head even further by elevating the head of the table to improve cerebral venous drainage, which can increase the risk for air entrainment into the venous system through open venous channels in bone and sinuses (Grady et al., 1986). Patients with cardiac defects with potential for right-to-left shunting, such as patent foramen ovale or a patent ductus arteriosus, are at high risk for paradoxical air emboli leading to cerebral or myocardial infarction.

Prompt recognition of VAE is crucial to successful management (Fig. 22-10). Precordial Doppler ultrasonography has been demonstrated to be the earliest and most sensitive indicator of intracranial air. It enables diagnosis before the pathologic consequences occur. The Doppler probe is best positioned on the anterior chest, usually just over or to the right of the sternum at the fourth intercostal space (i.e., the nipple line). An alternative site between the scapulae on the posterior thorax can be used in infants in the prone position weighing approximately 6 kg or less (Soriano et al., 1994). Doppler positioning can be confirmed by listening for the characteristic change in sounds after rapid administration of a few milliliters of saline into a central or peripheral venous catheter. When VAE occurs, there is reflex pulmonary vasoconstriction and ventilation/perfusion mismatch caused by the air blocking passage of blood. This reflex results in increased dead-space ventilation and causes a sudden decrease in end-tidal CO₂ concentration. Monitoring the end-tidal CO₂ concentration is very useful in making the diagnosis and can be used to monitor the severity and duration of air emboli. An increase in end-tidal nitrogen concentration during continuous monitoring is a specific sign of air emboli, but it is usually of such small magnitude that it is difficult to detect with devices currently available in clinical practice. Increases in right atrial and pulmonary artery pressures correlate with the size of emboli, but these delayed findings alone should not be relied on for monitoring and diagnosis. Echocardiography (transthoracic or transesophageal) may be the most specific method for detecting small air emboli but is not easily used intraoperatively, especially in small infants and children. In addition to the characteristic changes in Doppler sounds, sudden decreases in end-tidal CO₂, dysrhythmias, and ischemic changes in the electrocardiogram can occur with VAE.

FIGURE 22-10 The relative sensitivities of various monitoring techniques to the occurrence of venous air embolism (VAE). BP, Blood pressure; CO, cardiac output; CVP, central venous pressure; ECG, electrocardiogram; ET-CO₂, end-tidal CO₂; PAP, pulmonary arterial pressure; physiol, physiologic; T-echo, transesophageal echo.

(From Miller RD, Eriksson LI, Fleisher LA, et al., editors: Miller’s anesthesia, ed 7, Philadelphia, 2010, Churchill Livingstone.)

Aspiration of air from a central venous catheter is rarely successful unless massive amounts have been entrained. If small venous air emboli are detected by other devices (e.g., Doppler, end-tidal CO₂), the value of central venous catheter aspiration for air is quite limited. As soon as a change in Doppler sounds is noted during surgery (and not believed to be caused by administration of IV medications), the surgeon should be informed and nitrous oxide and inhalation agents discontinued. Attempts should immediately be made to identify and occlude the site of air entry, either by flooding the operative field with saline when appropriate (such as during a posterior fossa craniotomy) or by applying bone wax to bone edges. The head of the table can be lowered if necessary, which will have the effect of increasing cerebral venous pressure and stopping entrainment of air as well as augmenting the patient’s peripheral venous return and increasing systemic blood pressure. Jugular veins can be compressed manually, although great care must be taken to avoid simultaneous compression of the carotid arteries. Attempts can be made to aspirate air through a central venous catheter if one is in place. The application of positive end-expiratory pressure increases central venous pressure but also decreases cardiac filling pressure, cardiac output, and blood pressure; extreme increases in positive end-expiratory pressure are usually unwarranted. One must be prepared to provide vasopressor support and fluid resuscitation.

Once the patient has been stabilized, the procedure is resumed and a revised anesthesia plan is instituted. The decision to administer nitrous oxide after successful treatment of VAE is controversial. If reinstitution of nitrous oxide is associated with another decrease in end-tidal CO₂ concentration or clinical deterioration, then residual air bubbles are probably present and nitrous oxide should be discontinued. If no changes occur, many clinicians reinstitute nitrous oxide unless repeated episodes of VAE occur. Hemodynamic support may be necessary to avoid hypotension, maintain adequate cerebral perfusion pressure, and minimize ischemic injury. Therefore, dopamine and epinephrine are effective in supporting systemic pressure and restoring cerebral blood flow, even in very low birth weight infants (Munro et al., 2004).

Neurophysiologic Monitoring

Recent advances in neurophysiologic monitoring have enhanced the ability to safely perform neurosurgical procedures in functional areas of the brain and spinal cord. However, the neurodepressant effects of many commonly used anesthetic agents limit the usefulness of these monitors. In general, electrocorticography (ECoG) and EEG can be used with low levels of volatile anesthetics. Somatosensory evoked potentials used during spinal and brainstem surgery can also be depressed by high levels of volatile agents and, to a lesser extent, nitrous oxide. An anesthetic technique using high-dosage opioids and minimal inhaled agents (<1 MAC) is the most appropriate type of monitoring. Alternatively, total IV anesthesia (TIVA) techniques can be used. Spinal cord and peripheral nerve surgery may require electromyography (EMG) and detection of muscle movement as an endpoint. Therefore, muscle relaxation should be avoided or discontinued after tracheal intubation to facilitate monitoring. Table 22-2 lists common anesthetics and their effects on various neurophysiologic monitors. Motor evoked potential (MEP) can be used to monitor the integrity of the motor tracts of the spinal cord by stimulating the motor cortex and detecting the action potentials in the corresponding muscle groups (Table 22-8). Volatile anesthetic agents, including nitrous oxide, have a dosage-dependent depressant effect on the MEP. IV anesthetics (propofol, opioids, ketamine, and dexmedetomidine) preserve the MEP.

TABLE 22-8 Effect of Surgical Brainstem Manipulation

CN, Cranial nerve; ECG, electrocardiogram; EMG, electromyogram.

Monitors of Cerebral Oxygenation

The primary cause of cerebral ischemia in infants and children is cerebral hypoperfusion secondary to systemic arterial hypotension or sustained intracranial hypertension. The four major intraoperative modalities for monitoring cerebral ischemia are EEG, TCD, cerebral oximetry, and jugular bulb catheters.

Electroencephalography

The EEG is the most commonly used monitor for cerebral ischemia and has been intensively investigated during anesthesia. Electroencephalographic waveforms are the summation of excitatory and inhibitory postsynaptic potentials from the superficial layers of the cerebral cortex. Both regional and global ischemias result in profound depression of EEG activity, characterized by an attenuation of high-frequency activity and the appearance of slow waves in the corresponding area (Fig. 22-11). This feature makes the EEG the most reliable intraoperative monitor for focal cerebral ischemia. Direct analysis of the raw EEG by an electrophysiologist is the gold standard for monitoring cerebral ischemia. Conditions in which cerebral perfusion may be compromised can be monitored with scalp EEG electrodes or direct ECoG with subdural strip electrodes. Cerebrovascular disease is rare in infants and children, but two conditions in which EEG monitoring may be beneficial are temporary clipping of cerebral aneurysms and moyamoya disease. Cerebral aneurysm clipping can result in ischemia in the cerebral regions supplied by adjacent arteries. Direct ECoG in the region at risk can detect cerebral ischemic during test occlusion of the aneurysm and can serve as a guide for proper positioning of the aneurysm clip and institution of pharmacologic interventions to improve cerebral perfusion.

FIGURE 22-11 Slowing on the electroencephalogram (EEG). An intraoperative EEG of a child with impaired perfusion of the left hemisphere reveals characteristic waves with slow frequencies and high amplitudes (arrows) in the left-side leads.

Nerve Root Monitoring

Neurosurgical procedures for tethered spinal cord syndrome and spasticity often use EMG monitoring to aid in identification and dissection of the nerve roots. The tethered spinal cord syndrome from spinal dysraphism is associated with conditions such as myelomeningocele, lipoma of the filum terminalis, spina bifida occulta, and adhesions from prior spinal surgery. Identification of functional nerve roots may be difficult and can result in an inadvertent injury during the surgical dissection. EMG monitoring can be helpful for identifying functional nerve roots. Placement of the EMG electrodes in the external anal and urethral (in females) sphincter allows continuous monitoring of the nerve roots supplying the pudendal nerves (S2 to S4). Movement and evoked action potentials of the anterior tibialis and sural muscles can also be detected both visually and by EMG, respectively. Muscle contractions can be readily observed by using clear sterile plastic drapes. Inserting a balloon manometer into the bladder and recording changes in pressure during stimulation can assess detrusor muscle function. Muscle relaxation must be discontinued before stimulation to accurately detect motor activity. The patient should be deeply anesthetized, because direct nerve root stimulation often elicits a significant sympathetic response and pain.

A specific modality for monitoring spinal cord reflexes is the Hoffman reflex (HR), which is a measure of motor neuron excitability and is significantly increased in children with spastic diplegia. This response can be evoked by directly stimulating the nerve root and recording the direct efferent muscle response and the HR (Fig. 22-12). The HR represents the reflex potential emanating from the motor neurons of the spinal cord (Logigian et al., 1994). An abnormal reflex would have an exaggerated HR amplitude. Inhalational agents, nitrous oxide, barbiturates, and benzodiazepines all depress the HR (Soriano et al., 1995). An opioid-based anesthetic with intermittent doses of ketamine or propofol does not appear to suppress the HR. Because the EMG is the observed endpoint of HR, muscle relaxation should be avoided.

FIGURE 22-12 The Hoffman reflex (HR). The initial biphasic wave represents the muscle response (MR) and is followed by the HR.

Encephaloceles

Encephaloceles are neural tube defects that are protrusions of brain and CSF arising from the occiput to the frontal area (Fig. 22-13). They can even look like nasal polyps if they protrude through the cribriform plate. Large defects may present challenges to endotracheal intubation. Much blood loss can occur, especially if venous sinuses are entered. Adequate IV access should be ensured, and blood products should be available.

FIGURE 22-13 A newborn infant with an occipital encephalocele. Neurologic function was intact. The anesthesiologist’s primary challenge is to control and intubate the airway in the lateral position to avoid traumatizing the lesion.

Myelodysplasia

Defects in the spine are known as spina bifida. If a bulge containing CSF without spinal tissue exists, it is called a meningocele. When neural tissue is also present in the lesion, the defect is called a meningomyelocele. Open neural tissue is known as rachischisis. Hydrocephalus is usually present when paralysis occurs below the lesion and is usually associated with an Arnold-Chiari malformation (see later) (Figs. 22-14 and 22-15).

FIGURE 22-14 A, Newborn infant with a lumbosacral meningomyelocele. Note the partial epithelialization of the neural tissue, which is exposed to air centrally. Neurologic function was severely impaired distal to the defect. B, Schematic of meningomyelocele.

(B, From Carter S, Gold AP: Nervous system. In Rudolph AM, Barnett HL, Einhorn AH, editors: Pediatrics, ed 16, Norwalk, Conn, 1977, Appleton-Century-Crofts.

FIGURE 22-15 A, Newborn infant with a lumbar meningocele. No neural elements were in the sac, and neurologic function was normal distal to the lesion. B, Schematic of meningocele.

(B, From Carter S, Gold AP: Nervous system. In Rudolph AM, Barnett HL, Einhorn AH, editors: Pediatrics, ed 16, Norwalk, Conn, 1977, Appleton-Century-Crofts.

Most patients with a meningomyelocele present for primary closure within the first day or two of life to minimize the risk of infection. Many are now scheduled electively before birth for repair, because the defect is usually apparent on prenatal ultrasonography. Many neurosurgeons prefer to insert a ventriculoperitoneal shunt at the time of initial surgery. Alternatively, a shunt may be inserted a few days later or even occasionally deferred if there is no evidence of hydrocephalus at birth. A major anesthetic consideration is positioning the neonate for induction at surgery. In most cases, tracheal intubation can be performed with the infant in the supine position and the uninvolved portion of the patient’s back supported with towels (or a “donut” ring), so that there is no direct pressure on the meningomyelocele. For very large defects, it is occasionally necessary to place the infant in the lateral position for induction and intubation. Succinylcholine is rarely necessary in these situations, yet it does not appear to cause problems with hyperkalemia because the defect develops early in gestation (Dierdorf et al., 1986).

Airway management, mask fit, and intubation may be difficult for infants with massive hydrocephalus or very large defects. Blood loss may be considerable during repair of a meningomyelocele when large amounts of skin are to be undermined to cover the defect.

Patients with myelodysplasia are at high risk of developing allergic reactions to latex (Holzman, 1997). This is probably a result of repeated exposures to latex products encountered during surgery, including nonneurosurgical procedures required to correct coexisting orthopedic and urologic problems, or repeated bladder catheterizations. Patients who develop latex allergy appear to have an increased incidence of allergic reactions to other substances, including some antibiotics and foods, so anaphylaxis should always be anticipated in these situations. Postoperatively, respiratory status should be carefully assessed. Pulse oximetry is valuable during recovery from anesthesia because of difficulty with breathing after a tight closure, and because ventilatory responses to hypoxia are often diminished or absent in these patients when a Chiari malformation coexists (Waters et al., 1998).

Spinal dysraphism is the primary indication for laminectomies in pediatric patients. Patients with myelomeningocele suffer from multisystem diseases that result from a severe injury to the developing CNS early in gestation. The systems involved can include the musculoskeletal system, genitourinary system, and immune system in addition to the CNS. These patients suffer frequent exposures to latex products and are at high risk for developing a hypersensitivity to latex. All these patients should be treated with a latex alert, and a true anaphylaxis to latex must be considered when appropriate. Latex allergy can manifest itself by a severe anaphylactic reaction heralded by hypotension and wheezing with or without a rash and should be rapidly treated by removal of the source of latex and administration of IV fluid and vasopressors (Holzman, 1997). Insertion of an epidural catheter by the surgeon under direct vision can provide a conduit for the administration of local anesthetics and opioids for the management of postoperative pain.

Other spinal anomalies (lipomeningoceles, lipomyelomeningoceles, diastematomyelias, and dermoid tracts) may manifest themselves as tethered cords. Children who have had a meningomyelocele repaired after birth may also develop an ascending neurologic deficit from a tethered spinal cord as growth occurs.

The tethered spinal cord syndrome from spinal dysraphism is associated with conditions such as myelomeningocele, lipoma of the filum terminalis, spina bifida occulta, and adhesions from prior spinal surgery. Persistence of this anatomic anomaly can lead to cord or nerve root distortion and impaired perfusion of the spinal cord, resulting in progressive neurologic deficits and chronic pain. Early detection of a tethered cord is now more common with MRI. Visualization and identification of functional nerve roots may be difficult and may result in an inadvertent injury during the surgical dissection. This can lead to fecal and urinary incontinence and exacerbation of lower extremity neurologic dysfunction. EMG monitoring can be helpful for identifying functional nerve roots, as described earlier.

Severe spasticity associated with cerebral palsy can be surgically alleviated by a selective dorsal rhizotomy, which reduces spasticity by surgically dividing dorsal rootlets to diminish the afferent input to motor neurons in the spinal cord, thus decreasing the hyperactive active reflexes associated with spastic diplegia. Pathologic rootlets are identified by direct stimulation and noting the corresponding muscle action potential with EMG. Exaggerated action potentials can be elicited in innervated as well as other distal muscle groups. These abnormal rootlets are partially sectioned to decrease afferent nerve conduction. However, these rootlets may contain sensory and proprioceptive fibers. Spinal cord reflexes can be quantified by measuring the HR (as noted earlier). The postoperative care of these patients is completed by severe somatic incisional pain, dysesthesia, and hyperesthesia of the affected limb and muscle spasms. A variety of postoperative pain management techniques have been advocated in these patients. These include IV morphine, midazolam/diazepam infusions, and epidural opioids (Geiduschek et al., 1997).

Chiari Malformations

Chiari malformations are generally anatomic abnormalities of the posterior fossa leading to cephalad displacement of the cerebellar vermis through the foramen magnum. There are four types of Chiari malformations (Fig. 22-16 and Box 22-1). Type I occurs in healthy children without myelodysplasia. These patients, most of them adolescents, generally have much milder symptoms, sometimes presenting with only headache or neck pain. The Arnold-Chiari malformation (type II) almost always 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 and lower brainstem below the plane of the foramen magnum. Medullary cervical cord compression can occur. 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 appear during infancy. Patients of any age may have abnormal responses to hypoxia and hypercarbia because of cranial nerve and brainstem dysfunction (Ward et al., 1986). Extreme head flexion may cause brainstem compression in otherwise asymptomatic patients. Type III Chiari malformations are associated with encephaloceles and have the most severe symptoms and long-term disability. Type IV is associated with absent cerebellum, and large posterior fossa CSF spaces.

FIGURE 22-16 Sagittal and coronal MR images of Chiari type I malformation. Note descent of cerebellar tonsils (T) below the level of the foramen magnum (white line) to the level of the posterior arch (*).

Tumors

Brain tumors are the most common solid tumors in children, which are exceeded only by the leukemias as the most common pediatric malignancy (Pollack, 1994). Supratentorial tumors account for about 25% to 40% of brain tumors in children. Supratentorial resection usually requires invasive monitoring and techniques to control elevated ICP (Fig. 22-17). The majority of brain tumors in children are infratentorial, in the posterior fossa. These include medulloblastomas, cerebellar astrocytomas, brainstem gliomas, and ependymomas of the fourth ventricle (Fig. 22-18). 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.

FIGURE 22-17 MR image of supratentorial tumor. High-grade gliomas are generally less well circumscribed, with irregular enhancement.

FIGURE 22-18 MR image of infratentorial tumors. A, Brainstem glioma. B, Ependymoma displacing the pons and medulla.

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 will be flexed, and the position and patency of the endotracheal tube must be meticulously ensured. A nasotracheal tube is preferred when the patient is prone, as it is easier to secure and less likely to be dislodged. Proper positioning of the endotracheal tube is initially done by confirmation of clear bilateral breath sounds with the head flexed as much as possible while the patient is still supine after intubation is performed. Care should be taken to ensure that all other nasal and oral tubes (e.g., gastric, esophageal) do not cause pressure on the nares or lips, which can lead to edema or erosion after lengthy procedures.

Arrhythmias and acute blood pressure changes may occur during surgical exploration, especially when the brainstem is manipulated, so careful observation of the electrocardiogram and arterial waveform tracing is important. Altered respiratory control is generally masked by muscle relaxants and mechanical ventilation. Intracranial compliance is presumed to decrease even when ICP is only marginally elevated, thus precautions to minimize increases in ICP should be taken. If ICP is markedly elevated or acutely worsens, a ventricular catheter may be inserted by the neurosurgeon prior to tumor resection to permit emergent drainage of CSF. Fixation pins used in small children can cause skull fractures, dural tears, and intracranial hematomas. Elevation of the bone flap can result in sinus tears, massive blood loss, or VAE. Surgical resection of tumors in the posterior fossa can also lead to brainstem and cranial nerve damage. Table 22-8 lists some of the signs of encroachment on these structures. VAE is a potentially serious complication that is not eliminated by the use of 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. Damage to the respiratory centers and cranial nerves can lead to apnea and airway obstruction after extubation of the patient’s trachea.

Tumors in the midbrain include craniopharyngiomas, optic gliomas, pituitary adenomas, and hypothalamic tumors and account for approximately 15% of intracranial tumors (Fig. 22-19). Hypothalamic tumors (hamartomas, gliomas, and teratomas) frequently appear with precocious puberty in children who are large for their chronological age. Craniopharyngiomas are the most common perisellar 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 tests measured. Steroid replacement (dexamethasone or hydrocortisone) is generally administered because the integrity of the hypothalamic-pituitary-adrenal axis may be uncertain. In addition, diabetes insipidus occurs preoperatively in some patients and is a common postoperative problem. A careful 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. This occurs because the reserve of antidiuretic hormone in the posterior pituitary gland is enough to allow 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 a rising serum sodium concentration and osmolality. Treatment can initially be with dilute crystalloid solutions to replace the urine output, with careful attention to electrolyte measurements. However, urine output is usually so prodigious (up to 1 L/hr in an adult) that an infusion of aqueous vasopressin (1 to 10 mU/kg per hour) is best used, with fluid input then carefully restricted to match urine replacement and estimates of insensible losses. If diabetes insipidus persists, intranasal desmopressin can be used to replace IV pitressin, because desmopressin generally needs to be administered only twice daily. Return of antidiuretic hormone activity a few days postoperatively may cause a marked decrease in urinary output, water intoxication, seizures, and cerebral edema if desmopressin is not discontinued and fluid administration not adjusted appropriately.

FIGURE 22-19 MR image of craniopharyngiomas, demonstrating both cystic and solid components.

Transsphenoidal surgery is generally performed only in adolescents and older children with pituitary adenomas. However, this procedure should be treated like other midbrain tumors in terms of monitoring and vascular access. Patients 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, patients should be fully awake prior to tracheal extubation.

Approximately 25% of intracranial tumors in children involve the cerebral hemispheres. These 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, as it can cause sudden massive hyperkalemia. Nondepolarizing muscle relaxants and narcotics may be metabolized more rapidly than usual in patients receiving chronic anticonvulsants. Choroid plexus papillomas are rare but occur most often in children younger than 3 years. 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 also be used to delineate these important eloquent locations (Hatipoğlu et al., 2009). If cortical stimulation is planned to help identify motor areas, muscle relaxants must be permitted to wear off. Nitrous oxide and narcotics are usually sufficient to prevent patient movement during these periods.

Hydrocephalus

Hydrocephalus, the most common pediatric neurosurgical condition, involves a mismatch of CSF production and absorption, leading to increased intracranial CSF volume (Fig. 22-20). The majority of cases of hydrocephalus result from obstruction of CSF flow or inability to absorb CSF appropriately. Hemorrhage (neonatal intraventricular or subarachnoid), congenital problems (aqueductal stenosis), trauma, infection, or tumors (especially in the posterior fossa) can cause hydrocephalus. Hydrocephalus is classified as nonobstructive/communicating or obstructive/noncommunicating based on the ability of CSF to flow around the spinal cord in its usual manner. Unless the etiology of the hydrocephalus can be definitively treated, treatment entails surgical placement of a ventricular drain or ventriculoperitoneal shunt.

FIGURE 22-20 Infantile hydrocephalus. CT scan demonstrates a dilated ventricular system and thinning of the cortical mantle.

(Courtesy Division of Neuroradiology, University Health Center of Pittsburgh.)

Intracranial hypertension or a decrease in intracranial compliance almost always accompanies untreated hydrocephalus in children. How much intracranial compliance exists and how acutely hydrocephalus develops are both instrumental in how severe the signs and symptoms of hydrocephalus will be. In the young infant, if hydrocephalus develops slowly, the skull will insidiously expand and the cerebral vault will expand. However, in older children, the cranial bones are fused or the cranium cannot expand fast enough, and signs of impending herniation rapidly become apparent. The patient may become progressively more lethargic and develop vomiting, cranial nerve dysfunction, bradycardia, and ultimately death.

The approach to patients with symptomatic hydrocephalus should be directed at controlling ICP and rapidly relieving the obstruction. These patients may be vomiting and at risk for pulmonary aspiration. A rapid-sequence induction of anesthesia with thiopental or propofol followed by a succinylcholine or rocuronium is indicated in these situations. Hyperventilation should be instituted as soon as the trachea is intubated.

Unless the etiology of the hydrocephalus can be definitively treated, treatment entails surgical placement of a ventricular shunt. Most shunts transport CSF from the lateral ventricles to the peritoneal cavity (ventriculoperitoneal shunts). Occasionally the distal end of the shunt must be placed in the right atrium or pleural cavity, usually because of problems with the ability of the peritoneal cavity to absorb CSF, as in peritonitis. VAE may occur during placement of the distal end of a ventriculoatrial shunt.

Endoscopic third ventriculoscopy by way of a percutaneous flexible neuroendoscope is an alternative to extracranial shunt placement (Goumnerova and Frim, 1997). During these procedures, a ventriculostomy may be made to bypass an obstruction (such as aqueductal stenosis) by forming a communicating hole from one area of CSF flow to another using a blunt probe inserted through the neuroendoscope (Fig. 22-21). Common locations for a ventriculostomy are through the septum pellucidum (so the lateral ventricles can 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, and the anesthesiologist should be prepared for an emergency craniotomy during these procedures. Bradycardia and other arrhythmias have also been reported in conjunction with irrigation fluids and manipulation of the floor of the third ventricle (El-Dawlatly et al., 2000).

FIGURE 22-21 Ventriculoscopy. A, The foramen of Monro viewed from the left. B, The floor of the third ventricle, with the infundibular recess anterior and the mamillary bodies posterior. C, Wire used to make the hole. D, Two small holes. E, Fogarty catheter used to expand the holes. F, The hole (close-up view). G, The hole in relationship to the mamillary bodies and the infundibular recess. H, The foramen as the surgeon exits.

There are a few special situations involving shunts that anesthesiologists should be familiar with. For example, children who develop a shunt infection usually have their entire shunt system removed and external ventricular drainage established. They return to the operating room for placement of a new system several days later after their infection has been treated with antibiotics. While an external drain is in place, care must be taken not to dislodge the ventricular tubing. In addition, to avoid sudden changes in ICP, the height of the drainage bag should not be changed in relationship to the patient’s head. For example, suddenly lowering an open drainage bag can siphon CSF rapidly from the patient, resulting in collapse of the ventricles and rupture of cortical veins. When transporting patients 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.

Slit ventricle syndrome develops in approximately 5% to 10% of patients with CSF shunts and is associated with overdrainage of CSF and small, slitlike lateral ventricular spaces. Patients with this condition do not have the usual amount of intracranial CSF to compensate for alterations in brain or intracranial blood volume. Administration of excess or hypotonic IV solutions should be avoided to minimize brain swelling, because postoperative cerebral herniation has been reported after uneventful surgical procedures in these children (Eldredge et al., 1997).

Postoperatively, the patient’s mental status should be monitored because of the possibility of the reobstruction of the shunt, leading to life-threatening hydrocephalus.

Craniosynostosis

Craniosynostosis is a congenital anomaly in which one or more cranial sutures close prematurely. It occurs in approximately one of every 2000 births, with males affected more frequently than females. It can involve one suture, or it may be very complex and be associated with a variety of syndromes. If left uncorrected, the deformed cranium can result in increased ICP and compression of the brain, with potential neurologic consequences (Inagaki et al., 2007). Surgical correction is usually performed within the first months of life to achieve the best cosmetic results, because brain growth is very rapid during infancy, “pushing” the skull into a normal shape. Repair of craniosynostosis may involve removal of one small strip of bone from the skull, or it may entail a complete reconstruction of the calvarium (see Chapter 25, Anesthesia for Plastic Surgery).

Although these operations are extradural procedures, significant blood loss from the scalp and cranium make them challenging. It is essential that adequate venous access for rapid blood administration be secured, especially if multiple sutures are involved. Antifibrinolytic drugs (tranexamic acid) may have some usefulness in these procedures. The incidence of VAE is also significant during these procedures (Faberowski et al., 2000). Precordial Doppler ultrasonography and end-tidal CO₂ monitoring are useful for early detection of VAE. Because neuroendoscopic techniques are designed to minimize surgical incision, dissection, and blood loss, less aggressive fluid replacement and invasive hemodynamic monitoring is becoming the norm. The application of endoscopic techniques for craniosynostosis repair has resulted in significantly less morbidity. Endoscopic strip craniectomies are associated with decreased blood loss, decreased surgical time, and improved postoperative recovery time for neonates and infants (Jimenez and Barone, 1998; Jimenez et al., 2002). Tobias and colleagues (2001) reported a significant decrease in the incidence of VAE during this procedure.

Epilepsy

Epilepsy remains one of the most common neurologic disorders in children. Although new pharmacologic interventions have shown promise in the medical management of childhood epilepsy, a large number of children continue to have intractable seizures, and physicians resort to surgical interventions in such situations. Chronic administration of anticonvulsant drugs, such as phenytoin and carbamazepine, induces rapid metabolism and clearance of neuromuscular blockers and opioids by up-regulating hepatic P450 enzymes (Soriano and Martyn, 2004). General anesthetics can compromise the sensitivity of intraoperative neurophysiologic monitors that are used to guide the actual resection of the epileptogenic focus (Eldredge et al., 1995). If cortical stimulation is used to mimic the seizure pattern or identify areas on the motor strip, neuromuscular blockade should be antagonized.

Advances in neurophysiologic monitoring have enhanced the ability to safely perform more definitive neurosurgical resections in functional areas of the brain. A variety of techniques are used during the entire perioperative period to aid in localization of seizure foci. A major part of preoperative planning should include a thorough discussion of the modality and type of neurophysiologic monitoring to be used during the surgical procedure. In general, ECoG and an EEG can be used when the patient is on low levels of volatile anesthetics. Cortical stimulation of the motor cortex necessitates observation of motor movement of the specific area of the homunculus. Therefore, muscle relaxation should be avoided, or permitted to dissipate, during the monitoring period. ECoG is typically recorded continuously on a polygraph via a grid and strip electrodes placed on the surface of the brain after dural opening. Because some epileptogenic foci are in close proximity to cortical areas controlling speech, memory, and motor or sensory function, monitoring of patient and electrophysiologic responses is frequently used to minimize iatrogenic injury to these areas (Adelson et al., 1995; Ojemann et al., 2003). Cortical stimulation of the motor strip in a child under general anesthesia will require either EMG or direct visualization of muscle movement. Neuromuscular blockade should not be used in this situation. Cortical stimulation is possible using a dual channel stimulator. Epileptogenic activity may be evident by either clearly documented electrographic seizures or EEG spike activity, which consists of either interictal spikes of 50 to 80 msec or sharp waves of 80 to 200 msec. During anesthesia, the use of low concentrations of volatile anesthetics or nitrous oxide and opioids alone should avoid attenuating ECoG and EEG recordings.

In patients with generalized seizures, precise localization of the seizure focus is essential to minimize postoperative functional deficits. This involves serial craniotomies. The first is insertion of an intracranial grid and strip electrodes. EEG grids or strips are placed on the exposed cortical surface to accurately create a map that will localize the seizure focus. The patient is then observed in an electrophysiology unit to map the location of the seizure foci and provide a road map for the neurosurgeon for the resection. In some cases, the patient is monitored over several days. Once a seizure map is generated, the patient returns to the operating room for definitive resection. Depending on the location of seizure foci, age, and development of the patient, the resection is performed under general anesthesia or by an awake craniotomy technique. It is important to avoid administration of nitrous oxide until the dura is opened, because intracranial air can persist up to 3 weeks after a craniotomy, and nitrous oxide in these situations can cause rapid expansion of air cavities and result in tension pneumocephalus (Reasoner et al., 1994).

Neural function is best assessed in an awake and cooperative patient (Penfield, 1954). Positioning of the patient is critical for the success of this technique, as the patient must remain still for an extended period of time. The patient should be in a semilateral position to allow patient comfort as well as surgical and airway access to the patient. Motor and sensory cortices are localized by inducing motor movements or sensory changes with cortical stimulation. Language function is tested by eliciting speech arrest with cortical stimulation. Verbal memory is tested by stimulating the hippocampus or lateral temporal cortex. A variety of techniques have been advocated to facilitate intraoperative assessment of motor-sensory function and speech. These range from no sedation with local anesthesia, to asleep-awake-asleep techniques involving general anesthesia induced before and after functional testing (Sarang and Dinsmore, 2003; Brunson and Mayhew, 2005). The asleep-awake-asleep technique entails induction of general anesthesia. The airway is secured either by tracheal intubation or by placement of a laryngeal mask airway. General anesthesia is maintained during the craniotomy. The anesthetic is discontinued to permit functional neurophysiologic testing. Once the testing is completed, general anesthesia is reinstituted and the airway is secured. The advantage of this technique is that the patient is completely anesthetized during the most painful segments of the surgery. However, a major drawback is the depressant effects of residual anesthetics and the inability to predict the patient’s response to emerging from anesthesia under the surgical drapes. Therefore, monitored conscious sedation is the most frequently used technique in pediatric patients. Deep levels of sedation with a variety of IV anesthetic and sedative drugs (propofol and dexmedetomidine) combined with an opioid (fentanyl or remifentanil) have been shown to be efficient in several clinical reports (Ard et al., 2003; Keifer et al., 2005; Everett et al., 2006). An important factor in the choice of anesthetic drugs is its effect on the intraoperative ECoG. Therapeutic levels of propofol can potentially depress the ECoG. Propofol, when discontinued 20 minutes before monitoring, did not interfere with the ECoG, in awake cooperative children older than 10 years (Soriano et al., 2000a). However, it is imperative that candidates for an awake craniotomy be mature and psychologically prepared to participate in this procedure. Therefore, patients who are developmentally delayed or have a history of severe anxiety or psychiatric disorders should not be considered appropriate for an awake craniotomy.

Postoperative seizures are an uncommon but devastating complication. Prophylaxis in the perioperative period and aggressive treatment of new convulsions are well-recognized mainstays of care. Phenytoin is the agent used most commonly for prophylaxis, but maintaining therapeutic serum levels can be a challenge (Wolf et al., 2006). Levetiracetam (Keppra) is becoming increasingly common and in many instances supplants phenytoin as the choice for prophylaxis. Both drugs can be administered intravenously, but unlike phenytoin, administration of levetiracetam does not require following serum drug levels to monitor for toxicity. Alternative agents frequently used in pediatrics include phenobarbital, carbamazepine, and valproic acid. Status epilepticus can be treated effectively with lorezepam (0.1 mg/kg IV bolus over 2 minutes) or diazepam (0.5 mg/kg rectally). Lorezepam may be repeated after 10 minutes and accompanied by fosphenytoin (20 mg/kg IV or IM) if initial doses are ineffective. Phenobarbital (20 mg/kg) is also an effective first-line antiepileptic drug.

Vascular Malformations

Vascular anomalies are rare in infants and children. Most are congenital lesions that appear early in life. Large arteriovenous malformations (AVMs) in neonates may be associated with high-output congestive heart failure and require vasoactive support. Initial treatment of large AVMs often consists of several treatments involving intravascular embolization in the interventional radiology suite (Burrows and Robertson, 1998). Operative management is commonly associated with massive blood loss. Ligation of an AVM can lead to sudden hypertension with hyperemic cerebral edema (Morgan et al., 1999) and should be treated with vasodilators such as labetalol or nitroprusside.

Moyamoya syndrome is a rare chronic vasoocclusive disorder of the internal carotid arteries that appears as transient ischemic attacks or recurrent strokes (or both) in childhood. The etiology is unknown, but the syndrome can be associated with prior intracranial radiation, neurofibromatosis, Down syndrome, and a variety of hematologic disorders including sickle cell disease. Medical management consists of antiplatelet medications (e.g., aspirin or calcium channel blockers) and surgical management aims to improve blood flow to the ischemic area. The operation involves suturing a scalp artery onto the pial surface of the brain (pial synangiosis). The anesthetic management of these patients is directed at optimizing cerebral perfusion (Soriano et al., 1993); this includes ensuring generous preoperative hydration and maintaining the blood pressure close to the patient’s preoperative levels. Maintenance of normocapnia is essential as well, because both hypercapnia and hypocapnia can lead to steal from the ischemic region and further aggravate cerebral ischemia (Kuwabara et al., 1997). A nitrous oxide and narcotic-based anesthetic provides a stable level of anesthesia for these patients and is compatible with intraoperative EEG monitoring. Once the patient emerges from anesthesia, the same maneuvers that optimize cerebral perfusion should be extended into the postoperative period.

Neurotrauma

Neurotrauma primarily includes TBI and spinal cord injury (SCI). TBI is the leading cause of death and disability in children over 1 year of age. Approximately half of children with cervical spine injury have concomitant TBI, and the presence of TBI increases the risk of spine injury. After TBI, mortality is lower for children than for adults (10.4% versus 2.5%), but certain factors predict worse outcomes (Box 22-2). Because secondary injuries can progressively worsen outcome, basic life support algorithms, such as Pediatric Advanced Life Support (PALS) and Advanced Trauma Life Support (ATLS), and the principles of ATLS, including primary and secondary surveys, should be immediately applied. The spine cannot be “cleared” by radiographic examination alone; a child with normal cervical spine radiographs should be maintained with cervical spine immobilization until a thorough examination can be performed. In children, cervical spine fractures can occur without neurologic deficit, and neurologic deficit can occur without fracture. Neurologic deficit without fracture has been termed SCIWORA (SCI without radiologic abnormalities). Most children undergo an MRI evaluation. Blunt abdominal trauma and long-bone fractures may occur with TBI/SCI and can be major sources of blood loss. Craniotomies for the evacuation of either epidural or subdural hematomas are at high risk for massive blood loss and VAE. Infants with inflicted trauma often present with a myriad of chronic and acute subdural hematomas (Duhaime et al., 1998). Most inflicted injuries involving death involve TBI. Children with inflicted TBI (iTBI) commonly present with altered consciousness, coma, seizures, vomiting, or irritability, and either injuries out of proportion to history or developmental milestones or incomplete histories. Types of injuries include subdural hematoma, subarachnoid hemorrhage, skull fractures, and diffuse axonal injury with or without cerebral edema. Outcome is poor after iTBI.

Cerebral Hemodynamics after TBI

Cerebral Metabolic Rate, Blood Flow, Autoregulation, and CO₂ Reactivity

During the first 6 to 12 hours after TBI, the brain may suffer poor perfusion and cerebral ischemia. This may be followed by hyperemia and ICP. Finally, vasospasm occurs in up to 19% of patients with TBI, and poor perfusion may occur (White et al., 2001). Compared with children without TBI, children with TBI have a lower V_MCA, and cerebral hypoperfusion (CBF < 25 mL/100 g per minute) is associated with cerebral ischemia and poor outcome (Adelson et al., 1997; Skippen et al., 1997). However, after TBI, CBF and CMRo₂ may not be matched, resulting in either cerebral ischemia or hyperemia. As noted before, there are age-related changes in V_MCA, CBF, and CMRglu (see Fig. 22-3) (Kennedy and Sokoloff, 1957; Ogawa et al., 1987; Bode and Wais, 1988; Vink et al., 1988). One study of 30 children showed CO₂ vasoreactivity changes of less than 2% to be associated with poor outcome (Adelson et al., 1997). Cerebral autoregulation is impaired more often after severe (42%) than after mild (17%) pediatric TBI (Stoyka and Schutz, 1975; Bouma et al., 1998; Vavilala et al., 2004, 2007), and autoregulation may be more impaired in children with iTBI (Vavilala et al., 2007). Hemispheric differences in cerebral autoregulation are common (40%) after focal TBI (Vavilala et al., 2008). If cerebral autoregulation is impaired, lower blood pressure may passively result in diminished CPP and CBF (Fig. 22-22). Autoregulation is not a static condition and may deteriorate in patients with initially intact autoregulatory capacity. Empirically increasing MAP to prevent cerebral ischemia in the presence of unilaterally impaired cerebral autoregulation in the presence of hyperemia could result in cerebral hemorrhage (Bruce et al., 1981; Aldrich et al., 1992; Mandera et al., 2002). Impaired cerebral autoregulation has been associated with poor outcome after pediatric TBI (Vavilala et al., 2006, 2007).

FIGURE 22-22 A, Intact cerebral autoregulation. There is relatively little change in cerebral blood flow velocity (CBFV) with increase in mean arterial pressure (MAP). B, Impaired cerebral autoregulation. There is a linear increase in CBFV with increase in MAP.

Cerebral Perfusion Pressure

In 2003, pediatric guidelines issued by a number of organizations recommended that a CPP of less than 40 mm Hg be avoided after severe TBI to prevent cerebral hypoperfusion leading to cerebral ischemia (Adelson et al., 2003). However, although it is not well understood, there is probably an age-dependent CPP threshold, with older children with TBI requiring higher CPP (Chambers et al., 2005, 2006). Furthermore, there may be variability (low and high) in CBFV, despite a CPP of greater than 40 mm Hg (Philip et al., 2009). These data suggest that empirical CPP management may not have predictable effects on CBF. However, today, either systolic blood pressure or CPP is used clinically to estimate cerebral perfusion. The presence of Cushing’s reflex and autonomic dysfunction might be the only indicators of increased ICP. Although hypotension is defined by a systolic blood pressure below the fifth percentile, in the absence of ICP monitoring and suspected increased ICP, supranormal systolic blood pressure may be needed to maintain CPP. At a minimum, MAP should not be allowed to decrease below values normal for age by using vasopressors. IV phenylephrine infusion is often used to maintain CPP above 50 mm Hg.

Intracranial Pressure and Intracranial Pressure Monitoring

The management of increased ICP in children is similar to that in adults (Fig. 22-23). The indications for ICP monitoring and the treatment threshold for increased ICP are given in the 2003 pediatric guidelines (Adelson et al., 2003). The use of ICP monitoring for infants and children with severe TBI and a Glasgow Coma Scale of 8 or less varies, but it is supported by several clinical studies (Adelson et al., 2003). Symptoms of increased ICP (>20 mm Hg) are nonspecific in children, and intermittent apnea may be its first sign in infancy (Sharples et al., 1995). ICP measurements from ventricular catheters and fiberoptic intraparenchymal transducers have a good correlation (Gambardella et al., 1993). Ventricular catheters also provide a conduit for withdrawing CSF.

FIGURE 22-23 Algorithm for intracranial pressure management.

(Adapted from Adelson PD, Bratton SL, Carney NA, et al: Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents: critical pathway for the treatment of established intracranial hypertension in pediatric traumatic brain injury, Pediatr Crit Care Med 4[3 Suppl]:S65, 2003.)

Intracranial hypertension can be initially managed through elevation of the head, neuromuscular blockade, and hyperosmolar therapy. Mannitol can be given at a dosage of 0.25 to 1.0 g/kg intravenously. All diuretics interfere with the use of urine output as a guide to intravascular volume status. Hypertonic saline (3% NaCl) decreases ICP and increases CPP (Khanna et al., 2000). High-dosage barbiturate therapy can be titrated to produce a burst suppression pattern on the EEG, which results in a reduction in CMR. Refractory ICP can be treated with thiopental infusions, but volume loading and inotropic support may be needed to counter myocardial depression and hypotension (Adelson et al., 2003). If these maneuvers fail to control elevated ICP, decompressive craniectomy should be considered. Careful monitoring of blood gasses, minute ventilation, and end-tidal CO₂ tensions are recommended. Current guidelines recommend maintaining normocapnia (Paco₂, 35 to 40 mm Hg) except in the presence of impending herniation.