Perioperative Care of the Pediatric Neurosurgical Patient

Abstract

The management of infants and children with conditions of the brain and spinal cord can be challenging, and optimal management requires a thorough understanding of the developmental stages, age related physiological changes, and the pathophysiological processes that occur with these conditions. Patients with neurological conditions often undergo neurosurgical procedures and encounter clinicians from a variety of specialties. The perioperative period, is therefore, an important therapeutic window and clinicians who manage these patients during this period can provide patients with the opportunity to achieve full neurological recovery before, during, and after neurosurgery. For the preoperative period, pediatricians and emergency physicians are able to diagnose urgent/emergent neurosurgical conditions, prepare patients neurosurgery and prevent clinical deterioration from neurological conditions until definitive therapy such as neurosurgery can be provided. During surgery, anesthesiologists aim to provide optimal brain physiological conditions and optimal anesthetic and hemodynamic care during complex neurosurgical procedures. During the postoperative period, intensivists are responsible for anticipating and preventing postoperative consequences, and for helping patients achieve full neurological recovery. This chapter provides information on the neurological issues that should be considered during the perioperative period in the care of children undergoing neurosurgery.

Introduction

The perioperative management of pediatric neurosurgical patients presents challenges to physicians from many disciplines including pediatricians, emergency medicine physicians, neurosurgeons, anesthesiologists, and intensivists. A basic understanding of age-dependent variables and the interaction between preoperative, anesthetic, and surgical conditions and needs are essential to minimizing perioperative morbidity and mortality and to optimizing outcomes after neurosurgery. This chapter will highlight these age-dependent physiological and pathophysiological changes relevant to the perioperative (preoperative, intraoperative and postoperative) management of the pediatric neurosurgical patient.

Developmental Physiology of the Nervous System

Intracranial Pressure (ICP)

Under normal physiological conditions, ICP is 2–6 mmHg in full term infants and higher in children and adults (0–15 mmHg). Intracranial compliance is defined as the change in intracranial pressure relative to the intracranial volume. As intracranial volume acutely rises, the ability to compensate due to lack of compliance reduces and ICP increases. Acute increases in cranial volume due to massive hemorrhage or obstructed cerebro-spinal fluid (CSF) flow cannot be attenuated by expansion of the cranial vault and frequently result in life-threatening intracranial hypertension in infants [1]. Once the fontanelles and sutures have closed, children have a relatively smaller cranial volume and lower intracranial compliance than adults. Contributory factors to increases in ICP include a higher ratio of brain water content, less CSF volume, and a higher ratio of brain content to intracranial capacity [2]. Intracranial hemorrhage, inflammation/infection, tumors or congenital malformations can lead to decreased CSF absorption with possible elevations in ICP. Pediatric neurosurgical patients may have elevated ICP during the perioperative period due to any of these processes described above from preoperative or post surgical hemorrhage of any space occupying lesion.

Cerebral Blood Flow (CBF)

Complex homeostatic mechanisms regulate the cerebral circulation during the perioperative period and these must be considered when managing systemic and cerebral hemodynamics. Factors influencing CBF are: (1) cerebral metabolism, (2) partial pressure of arterial carbon dioxide (PaCO₂) (Fig. 10.1) (3) partial pressure of oxygen in arterial blood (PaO₂) (Fig. 10.2) (4) blood viscosity and (5) cerebral autoregulation (Fig. 10.3). Flow-metabolism coupling is the most significant regulator of the cerebral circulation and is typically preserved [3–5]. However, during periods of central nervous system (CNS) activation, CBF increases more than CMRO₂, resulting in a decrease in the cerebral oxygen extraction fraction [6] During development, CBF changes with age, mirroring changes in neural development and synaptogenesis. The healthy brain receives about 15 % of cardiac output and normal adult CBF is approximately 50 mL/100 g/min. There are relatively few data on CBF available from healthy children. In one older study, Kennedy and Sokoloff found CBF to be much higher, on the order of 100 mL/100 g/min, in conscious healthy children [7]. A recent study using arterial spin labeling found similar values in young children [8], which then decrease and approach adult values during the adolescent years, suggesting that CBF increases during early childhood, peaks during early-mid childhood and plateaus during late childhood at approximately 7–8 years [9].

Fig. 10.1

Relationship between PaCO₂ and cerebral blood flow

Fig. 10.2

Relationship between PaO₂ and cerebral blood flow

Fig. 10.3

Relationship between mean arterial pressure and cerebral blood flow (normal cerebral autoregulation)

Compared to 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 above 50 mmHg below a threshold of PaO₂ of 50 mmHg, CBF increases to maintain adequate cerebral oxygen delivery. Cerebral blood flow may be excessive (hyperemia) or inadequate (ischemia) relative to cerebral metabolism during the perioperative period, these changes may be focal, regional and or global, and advanced neuromonitoring techniques may aid in increasing our understanding of the pathophysiological processes involved.

Cerebral Metabolic Rate (CMR)

Global CMR for oxygen and glucose is generally higher in children than in adults (oxygen 5.8 vs. 3.5 mL/100 g brain tissue/min and glucose 6.8 vs. 5.5 mL/100 g brain tissue/min respectively [7]). Similar to age related changes in CBF, studies of healthy anesthetized children also suggest age-related increases in CMRO₂, which are 104 μmol/100 g/min in infants and 135 μmol/100 g/min in children ages 3 weeks–14 years [8]. Similar to CMRO₂, cerebral metabolic rate for glucose (CMRglu) is lower at birth (13–25 μmol/100 g/min), increases during childhood, peaks by 3–4 years (49–65 μmol/100 g/min), and remains high until 9 years of age. Thereafter CMRglu decreases, and approaches adult rates (19–33 μmol/100 g/min) [10]; changes in CRMO₂ and CRMGlu mirror age-related changes in CBF (Fig. 10.4). Cerebral metabolic rate of oxygen and glucose may be altered in children with neurosurgical conditions during the perioperative period, especially while receiving sedation, and or while recovering from general anesthesia.

Fig. 10.4

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). Corresponding Adult Values: VMCA 50 cm/s, CBF 50 mL/100 g/min, CMRglu 19–33 mol/100 g/min

CO₂ Reactivity

PaCO₂ is the most powerful modulator of the cerebral circulation and the cerebral circulation is exquisitely sensitive to changes in PaCO₂ [11, 12]. Yet, much of our therapy aimed to modulate changes in CBF via changes in PaCO₂ is empiric, and without knowledge of individual patients CO₂ reactivity or CBF response to the intervention made. Similar to CBF and metabolism, carbon dioxide (CO₂₎ reactivity may be higher in healthy children than in adults [13–15]. Studies suggest that reactivity to CO₂ is well developed even in healthy preterm infants [16] and that CO₂ reactivity in newborns correlates with the lowest pH and may reflect the severity of perinatal asphyxia [17]. One recent study suggests that CO₂ reactivity and cerebral autoregulation may be altered in patients undergoing tumor resections (Fig. 10.5). While these data are from adults, it is possible that the same pathophysiological processes occur in children.

Fig. 10.5

Intact (a) and impaired (b) Cerebral autoregulation

Viscosity and CBF

Compared to PaCO₂, the influence of viscosity on the cerebral circulation is less. There are minimal changes in CBF with changes in PaO₂ above 50 mmHg below a threshold of PaO₂ of 50 mmHg, CBF increases to maintain adequate cerebral oxygen delivery. Unlike CO₂R, the equilibration of CBF is longer and takes approximately 6 min after the establishment of hypoxemia [18]. The influence of oxygen, on the cerebral circulation is less so than exerted by PaCO₂. Variability in Hct in children undergoing neurosurgery may lead to variability in CBF, CBV and ICP.

Cerebral Autoregulation

Cerebral autoregulation is an important homeostatfic regulator of CBF where 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 mmHg results in little or no change in CBF [19, 20]. This adaptive mechanism maintains constant (adequate) CBF by vasodilation or decreasing cerebrovascular resistance. Under normal conditions, beyond these limits of autoregulation, hypotension may result in cerebral ischemia, and hypertension may cause cerebral hyperemia.

Healthy infants appear to autoregulate CBF as well as older children, but the long held assumption that the lower limit of autoregulation (LLA) is lower in younger compared to older children may not be valid (same LLA range for younger and older children 46–76 mmHg) [21]. There are no data on the LLA in healthy neonates. However, estimates of the lower limit of autoregulation derived from the cerebral oximetry index in pediatric patients undergoing cardiopulmonary bypass were at 42 ± 7 mmHg [22]. Since blood pressure increases with age, neonates and young children may be at increased risk of cerebral ischemia due to lower blood pressure reserve (mean arterial pressure – LLA) and narrow autoregulatory range [23] and during critical illness, CBF may be completely pressure passive [24]. 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. There may also be age-related differences in the time to return of normal autoregulation in young children [25] but there are no data on this in neonates. Animal data suggest that while CBF pressure autoregulation and reactivity to CO₂ operate in the newborn rat, hypercapnia abolishes cerebral autoregulation [23] and that abolished autoregulation is associated with cerebral damage in asphyxiated infants. Moreover, the combination of isoelectric electroencephalograms and cerebral hyperperfusion is an early indicator of very severe brain damage [16]. Despite these clinical observations, mechanisms of normal cerebral autoregulation in healthy children and adaptations in acute disease are not completely understood and like changes in CBF, both anatomic and physiological maturation might play a role in the development of a fully developed autoregulatory response. Children with neurosurgical conditions such as traumatic brain injury (TBI) or tumors may have impaired cerebral autoregulation during the peri-operative period, requiring clinicians to actively provide tight control of systemic and cerebral hemodynamics [26].

Pharmacology of the Nervous System

Intravenous sedative and anesthetic drugs affect cerebral hemodynamics and have varying cerebral hemodynamic profiles. Different classes of sedatives differentially impact cerebrovascular resistance, cerebral autoregulation, CBF, and CMR. Preoperative sedation and analgesia choice may impact intraoperative cerebral hemodynamics, and intraoperative use of volatile anesthetic agents may affect post operative recovery and outcomes. Post operative choice of sedation and analgesia may influence the clinician’s ability to perform an adequate neurological examination and prevent timely tracheal extubation.

Propofol

It has been reported that propofol maintains cerebral autoregulation and cerebrovascular reactivity to carbon dioxide above 30 mmHg end-tidal carbon dioxide levels in children [27]. Furthermore, propofol, at high doses, lowers CBF and mean arterial pressure values in children, which may be mediated by its cerebral vasoconstrictive properties [28]. Propofol may depress systemic blood pressure but both potently decrease CMRO₂, CBF, and ICP [29]. Propofol has been purported to have neuroprotective properties, especially in preclinical studies, but its clinical efficacy in neurologically compromised pediatric patients has not been tested. Etomidate and ketamine are less likely to cause hypotension than propofol. However, CNS excitation and increased ICP have been associated with these drugs respectively, and they may not be appropriate for many neurosurgical patients. Finally, propofol infusion syndrome which characterized by the lactic acidosis, rhabdomyolysis, and circulatory collapse after prolonged administration of propofol, in children, precludes its use for sedation beyond 48 h in the PICU setting [30].

Barbiturates

Barbiturates decrease CBF, CBV, and CMRO₂ in a dose dependent manner [31–33] and therefore reduce ICP. Neither CBF nor cerebral metabolism is significantly altered by subanesthetic doses of barbiturates. When the electroencephalogram (EEG) becomes isoelectric, CBF and CMRO₂ decrease to about 50 % of normal, and additional doses of barbiturates have little further effect. Barbiturates may also be used to prevent increases in ICP that can occur with laryngoscopy and tracheal intubation. Autoregulation and the cerebrovascular response to changes in PaCO₂ remain intact during barbiturate anesthesia. The rate of CSF formation and the resistance to reabsorption of CSF are not altered by barbiturates [34]. In doses that suppress the EEG, barbiturates reduce cerebral damage in animal and human models of focal cerebral ischemia [35, 36]. In animals, barbiturates also reduce the extent of cerebral edema after a cortical freeze injury. This decrease in edema is in contrast to the response observed with the volatile anesthetics [37].

Opioids

Opioids are commonly used as a part of a sedation plan during the perioperative period in neurosurgical patients. In general, opioids have little effect on CBF, CBV, or ICP unless respiration is depressed and PaCO₂ is increased [38–41]. Fentanyl, for example, is generally considered safe in pediatric neurosurgical patients and does not alter the rate of CSF formation, though it does reduce the resistance to CSF reabsorption by 50 % [42, 43]. The neonatal cerebral circulation is unaffected by fentanyl [44]. At conventional doses, sufentanil [45, 46] and alfentanil [47] do not appear to have adverse effects on the cerebral vasculature or upon ICP in most patients. In a subset of patients with severe head injuries and very poor intracranial compliance, sufentanil may cause a small (e.g., 10 mmHg) and transient increase in ICP that may be clinically significant in some settings [48–50]. Remifentanil is an ultra–short-acting opioid that is rapidly metabolized by plasma cholinesterases and has gained in popularity for use as part of the general anesthetic technique. The very short clinical duration of effect of remifentanil and its context-sensitive half life that is independent of the duration of infusion [51, 52] make it an appealing opioid for lengthy neurosurgical procedures, after which rapid return of consciousness is desirable. As is the case with other opioids that have been studied, remifentanil does not increase CBF or ICP [53, 54]. Remifentanil, like other opioids, preserves cerebral autoregulation and CO₂ reactivity [55–58]. Return of consciousness is very rapid after remifentanil is discontinued, and the frequency of administration of naloxone to permit neurologic assessment is decreased [59]. However, because remifentanil analgesia is very brief after its discontinuation, a long-acting opioid analgesic must be administered to prevent severe pain and rebound hypertension before or soon after remifentanil is discontinued [60, 61].

Etomidate

Etomidate reduces ICP by decreasing CBF and CMRO₂ by 34 and 45 %, respectively. It, too, preserves the CO₂ responsiveness of the cerebral circulation [62, 63]. A side effect of etomidate administration is myoclonus. Myoclonus has been reported after prolonged continuous infusion of etomidate [64].

Lidocaine

Lidocaine in clinical doses decreases CBF and reduces the increase in ICP associated with endotracheal intubation [65, 66]. The benzodiazepines (diazepam, lorazepam, and midazolam) decrease CBF and CMRO₂ approximately 25 % [67–72]. Adrenal suppression remains a concern.

Ketamine

In contrast to the other intravenous anesthetic agents, ketamine is a potent cerebrovasodilator. Ketamine increases CBF by 60 % with little change in CMRO₂ [73–75]. The cerebrovascular response to administration of ketamine is thought to be the result of regional cerebral activation induced by the drug [76]. Ketamine produces a marked increase in ICP, which can be reduced, but not prevented, by hyperventilation [74, 77, 78]. The increase in CBF, and presumably in ICP, can be blocked by previous administration of thiopental [73]. Ketamine has been associated with sudden elevation of ICP and clinical deterioration when used in patients with hydrocephalus and other intracranial pathology [78–80]. While ketamine is currently not routinely used as a general anesthetic in patients with reduced intracranial compliance, one recent study in critically ill children reported decreases in ICP following ketamine [81], thereby questioning the notion that ketamine increases ICP.

Dexmedetomidine

Dexmedetomidine is a selective alpha 2 agonist sedative hypnotic agent with a short half life that reduces sympathetic tone and is associated with decreasing opioid needs, benzodiazepines, propofol, and other sedative medication needs. Short-term sedation has been shown to be safe in studies, although hypotension and bradycardia are the most significant side effects with rebound hypertension occurring after abrupt cessation [82–86]. These side effects can be ameliorated by a low dose infusion without bolus (generally ≤0.5 μg/kg/h). In adults, dexmedetomidine decreases CBF in a dose related manner, decreases CMR, and preserves flow metabolism coupling, though it may decrease dynamic autoregulation [87, 88]. One small series found no adverse effect on brain PbO₂ with dexmedetomidine. Dexmedetomidine has been used as a sedative to facilitate awake craniotomy [89]. Overall, dexmedetomidine is emerging as an effective therapeutic agent in the management with a favorable cerebrovascular profile [90].

Neuromuscular Blocking Agents

Succinylcholine is a depolarizing neuromuscular blocking agent and is associated with life-threatening hyperkalemia and cardiac arrest in children with undiagnosed myopathies and has a U.S. Food and Drug Administration “black box warning”. Life-threatening hyperkalemia has been associated with succinylcholine administration in many types of central nervous system disorders, including TBI [90–93], near-drowning [94] subarachnoid hemorrhage [95], encephalitis [96], cerebrovascular accidents [97], and paraplegia [98, 99]. The onset of the period of vulnerability may begin as early as 24–48 h after injury and may last up to 1–2 years after injury [98]. Because the period of risk for succinylcholine-induced hyperkalemia after cerebral injury is undefined, succinylcholine should be avoided in these patients, except in the period immediately after injury. Succinylcholine can increase CBF and ICP in patients with reduced intracranial compliance [100–103] probably because of cerebral stimulation from succinylcholine-induced increases in afferent muscle spindle activity [104]. In contrast, most nondepolarizing relaxants have little effect on CBV and ICP [105–108] unless associated with histamine release (d-tubocurarine, atracurium), which causes transient cerebrovasodilation and increased ICP [109]. Succinylcholine use in critically ill children, especially in those who have not been ambulatory for 48 h is not recommended. 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 [110–112] Excessive doses of muscle relaxants may be given if 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) [113]. Acute administration of several anticonvulsants, including phenytoin and phenobarbital, enhances nondepolarizing neuromuscular blockade or delays its reversal [114, 115]. Importantly, many patients who have been receiving chronic phenytoin or carbamazepine therapy are relatively resistant to the effects of nondepolarizing relaxants [116–119], including rocuronium [115, 120], due to enhanced metabolism [121, 122].

Cerebral Vasodilators

Direct-acting vasodilators, including sodium nitroprusside, adenosine, nitroglycerin, diazoxide, and hydralazine, which may be used intraoperatively and into the postoperative period, impact cerebral physiology. These agents are cerebrovasodilators and may increase CBF and ICP [123–126]. The calcium channel blockers also raise CBF and ICP [127, 128]. These drugs should therefore be avoided in patients with reduced intracranial compliance, unless the dura is open or ICP is being monitored. Sodium nitroprusside lowers the range of cerebral autoregulation. Brain-surface oxygen tension is greater [129] and metabolic disturbances in brain biochemistry (e.g., lactate, pyruvate, and phosphocreatine levels) are less during nitroprusside-induced hypotension than with trimethaphan-induced or hemorrhage-induced hypotension [130].

Fluids, Blood Products, and Electrolytes

Meticulous fluid management is critical in the care of neurosurgical patients in children. Small patient size and immature renal function result in fluid and electrolyte imbalances. Water freely diffuses through the blood brain barrier 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 blood brain barrier into the brain, resulting in increased ICP. Osmolar gradients are maintained only when the blood brain barrier is intact, otherwise large molecules that are typically excluded such as albumin enter the brain and can worsen edema.

There is no definitive formula for volume replacement for the pediatric neurosurgical patient. Hemodynamic stability during the perioperative period requires careful maintenance of intravascular volume where pre-operative fluid restriction and/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 perioperative period. Estimation of the patient’s blood volume is essential in determining the amount of allowable blood loss and when to transfuse blood.

Isotonic crystalloid solutions (Plasmalyte) are commonly used during general anesthetic and for cerebral resuscitation. Rapid infusion of large quantities of normal saline (>60 mL/kg) can be associated with hyperchloremic acidosis [131]. The calculated maintenance rate of fluid administration depends on the weight of the patient [132]. 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 anti-diuretic hormone excretion, as noted below should be considered when determining the proper amount of fluid administration. Depending on the extent and length of the surgical procedure and exposure of vascular beds, additional fluid administration 3–10 mL/kg/h may be necessary during the intraoperative period. Unlike adults, children can become hypovolemic from scalp injuries and isolated TBI. Hypotonic crystalloids should be avoided during the perioperative period. The role of colloids is controversial. In 2007, the SAFE study reported that adult patients with TBI who received fluid resuscitation with albumin had higher mortality rates compared to those who received fluids with crystalloids [133]. The use of hydroxyethyl starch is discouraged during the perioperative period for resuscitation because of its role in exacerbating coagulopathy. Hypertonic saline 0.1–1.0 mL/kg may be used to increase CPP, but in this setting, studies show that there is no advantage to hypertonic saline compared to conventional pre-hospital fluid protocols [134].

Since 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 and a type and cross should be available prior to surgery and during the postoperative period. There are no guidelines regarding an appropriate threshold for transfusing blood in the neurosurgical patient since it is unclear what hematocrit is needed for optimum 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 intra- and postoperatively. In general, hematocrits of 17–25 % may warrant blood transfusion. Packed red blood cells (10 mL/kg) will raise the hematocrit by 10 %. Blood losses during surgery may be replaced with 3 mL of normal saline for 1 mL of estimated blood loss or a colloid solution such as 5 % albumin of an equal volume to the 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 as well as having “hidden” blood loss 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 5–6 mg/kg/min in order 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 [135, 136] and poor outcomes in adults [137]. However, it is unclear if tight glycemic control offers significant benefits to children [138, 139]. Limited evidence now suggests that tight control may carry undue risk of hypoglycemia and newer data are less supportive of very tight glycemic control [140]. Retrospective studies from children suggest that both hyperglycemia (glucose 200–250 mg/100 mL) and hypoglycemia occur after TBI [141] and that hyperglycemia is associated with poor outcome.

Cerebral edema can be occur during the perioperative period and may result in devastating consequences. Aggressive hyperventilation should be reserved for situations where herniation is impending and immediate life-saving maneuvers are required and data from patients with TBI suggest that even mild hyperventilation leads to hypoperfusion [142]. Elevation of the head above the heart and the use of hyperosmolar therapy (i.e., mannitol/hypertonic saline) are also methods to reduce ICP. Mannitol may be used in doses of 0.25–0.5 g/kg intravenously. This will transiently alter cerebral hemodynamics and raise serum osmolality by 10–20 mOsm/kg [143]. 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 [144]. Standard administration at our institution is typically 3 mL/kg as a 3 % via a central line (to avoid phlebitis and tissue necrosis) targeted to a serum sodium rate change of 0.05 meq/h with endpoints depending on initial serum sodium and degree of brain edema (typically 155–160 meq/L). 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, can reduce CSF formation, and decrease acute cerebral edema as well as preventing rebound swelling due to mannitol [145, 146].

Electrolyte Disorders

Non-osmotic 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 may be treated with hypertonic saline, fluid restriction, and administration of diuretics [147]. Cerebral salt wasting (CSW) occurs in approximately 11.3/1,000 procedures [148] with a duration of 6 days [149] in children and can be seen following TBI and other neurosurgical procedures and disease states such as meningitis [150], calvarial remodeling [151, 152], tumor resection [149], and even hydrocephalus [153]. Cerebral salt wasting, the result of excessively high atrial or brain natriuretic peptide levels [154], 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 fludocortisone [155].

Diabetes insipidus (DI) is a well-known complication of neurosurgical procedures involving or adjacent to the pituitary and hypothalamus, in association with craniopharyngioma, where it can be a presenting symptom in 40 % of cases. Diabetes insipidus is recognized by a rising serum sodium (>145 mg/dL) accompanied by copious (>4 mL/kg/h) output of dilute urine. Severe dehydration and hypovolemia may develop. One effective protocol employs maximal antidiuresis with intravenous vasopressin and strict limitation of intravenous fluids [156]. This strategy avoids the pitfalls of titrating drug to urine output and recognizes that renal blood flow remains normal in the normovolemic, but maximally antidiurese, child. Since urine output can be minimal (0.5 mL/kg/min), other clinical markers of volume status must be assessed.

Preoperative Evaluation and Preparation

Given the urgent nature of many pediatric neurosurgical procedures, a thorough preoperative evaluation may be difficult. However, it is important to obtain a relevant patient history which can reveal conditions that may increase the risk of adverse reactions to anesthesia and perioperative morbidity and identify patients who need more extensive evaluation or whose medical condition needs to be optimized before surgery. The chronicity and severity of the patient’s neurological condition will vary greatly and should dictate perioperative management. Special attention should be given to symptoms of allergy to latex products (e.g., meningomyeloceles) [157]. Severe dehydration and electrolyte abnormalities can be the result of protracted vomiting from intracranial hypertension. Patients with diabetes insipidus can develop hypovolemia due to polyuria. During the perioperative period, steroids are frequently initiated to palliate cerebral swelling in patients with intracranial tumors and therapeutic levels of anticonvulsants should be verified preoperatively and maintained. Patients on long-term anticonvulsants may develop toxicity, especially if seizures are difficult to control. This reaction frequently manifests with abnormalities in either the hematologic, hepatic function, or both.

Physical Examination

The preoperative physical examination should, at a minimum, include a brief but serial neurologic evaluation, that includes; (1) level of consciousness, (2) motor and sensory function, (3) normal and pathologic reflexes, (4) integrity of the cranial nerves, and (5) signs and symptoms of intracranial hypertension. Preoperative diagnoses predispose patients to complications such as those listed in Table 10.1. The modified Glasgow Coma Scale for infants and children is useful for assessing the mental status of the patient (Table 10.2). Lesions of the brainstem can manifest with cranial nerve dysfunction such as respiratory distress, impaired gag and swallowing, and pulmonary aspiration. Evidence of muscle atrophy and weakness should be noted, particularly if the patient is hemiparetic, hemiplegic or bedridden, since up-regulation of acetylcholine receptors may precipitate sudden hyperkalemia following 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 received osmotic or diuretic agents.

Table 10.1 Perioperative clinical implications for infants and children with neurological conditions

Table 10.2 Modification of the Glasgow Coma Scale Score for young children

Radiologic and Laboratory Evaluation

Most neurosurgical patients will have a brain magnetic resonance imaging (MRI) or CT scan as part of the preoperative assessment regardless of whether the preoperative period includes the emergency department or the ICU. These scans should be reviewed with the neurosurgeon in order to confirm the primary lesion and the presence of evolving neurological conditions (hydrocephalus, compressed cisterns, and midline shifts). For elective patients undergoing neurosurgery and who otherwise have no reason to have anemia, coagulopathy or electrolyte disturbances, no preoperative laboratory data may be required, as blood samples can be frequently obtained after induction of general anesthesia. In emergent cases, critically ill children, and trauma, the risk of significant blood loss associated with neurosurgery makes it desirable to have a preoperative hematocrit, electrolytes, and coagulation studies (e.g., prothrombin time and partial thromboplastin time). Patients with suprasellar pathology who undergo elective or semi-elective neurosurgery should have a preoperative endocrinology evaluation for ensuring optimized endocrine status (i.e., thyroid function). Type and cross matched blood should be order prior to all craniotomies and this may be facilitated either preoperatively or immediately after induction of anesthesia depending on local blood availability.

Premedication

Patients are typically admitted to the operating room for neurosurgery from the emergency department or ICU. Perioperative anxiety plays a significant role in the care of the pediatric neurosurgical patient for patients, providers and parents, often related to the cognitive development and age of the child. Preoperative sedatives given prior to the induction of anesthesia can ease the transition from the preoperative holding or ICU area to the operating room [158]. Sedatives are administered in the parents’ presence to facilitate a smooth separation and induction whether patients are coming to the OR from the ED or ICU. Midazolam (0.5–1.0 mg/kg) may be given orally or intravenously with adequate nurse supervision and in the absence of respiratory symptoms. Heavy premedication may be warranted to avoid agitation in patients with Moyamoya Syndrome or an intracranial aneurysm/arteriovenous malformation that has recently hemorrhaged. Opioids may be withheld preoperatively, since they may cause nausea or respiratory depression, especially in patients with increased ICP. Any administration of sedatives or analgesics that depress mental status merits close clinical observation and pulse oximetry in the child who will undergo neurosurgery.

General Principles of Intraoperative Management

General anesthesia is typically described to have three phases: induction, maintenance, and emergence. Typically, the patient’s preoperative status will dictate the appropriate technique and medication choices for all phases of general anesthesia.

Induction Phase of Anesthesia

In the presence of intracranial hypertension, the primary goal during induction is to minimize severe increases in ICP. In general, most intravenous drugs decrease CBF and metabolism and ICP. Thiopental (4–8 mg/kg) or propofol (2–5 mg/kg) have similar effects on cerebral hemodynamics and maintain tight coupling of CBF and CMR. Patients at risk for aspiration pneumonitis (including certain patients with high ICP) should have a rapid-sequence induction of anesthesia using cricoid pressure. An intravenous hypnotic drug such as thiopental or propofol is given and then immediately followed 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 pre-existing neurologic injury such as 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, since 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 may be avoided because of its known ability to increase cerebral metabolism, CBF, and ICP in patients with increased ICP. Mask induction can be induced in certain situations when patients are neurologically stable. ICP can be lowered during induction with controlled hyperventilation and administration of an opioid and/or barbiturates before laryngoscopy and intubation. A non-depolarizing muscle relaxant may then be administered after intravenous (IV) access has been established to facilitate intubation of the trachea. As discussed above, succinylcholine should be avoided in patients with denervating processes such stroke, or spinal cord injury, since it can result in life-threatening hyperkalemia.

Airway Management

Developmental changes and the presence of genetic disorders/syndromes in airway anatomy have a significant impact on management of the pediatric airway. Nasotracheal tubes may be preferred for situations when there is no concern for basilar skull fractures and when the patient will be prone since 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 following neurosurgical procedures. Infants, particularly those with the Chiari malformation [158] or myelomeningocoele [159] or children after procedures in the posterior fossa [160] 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 improves airway edema within 24 h. The presence of airway edema post operatively may be impacted by intraoperative patient positioning (e.g., prone positioning for posterior fossa and spinal cord surgery). In addition to the physiological sequelae of the sitting position, a whole spectrum of neurovascular compression and stretch injuries can occur. . Postoperative visual loss has been linked to spine surgery. The etiology is unclear but, in adults, may be linked to prone positioning, surgical duration, surgical blood loss, anemia or hypotension. Challenges with intraoperative positioning include prevention of excessive neck rotation to prevent venous flow, and prevention of venous air emboli (VAE) [161, 162].

Vascular Access

The routine use of central venous catheters in pediatric neurosurgical patients is controversial. At a minimum, the anesthesiologist will use two large peripheral venous cannulae for most craniotomies. Should peripheral intravenous be difficult to secure, central venous access may be needed. Since 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 Phase of Anesthesia

Specific drugs utilized for the maintenance of anesthesia have not been shown to affect the outcome of neurosurgical procedures when properly administered [163]. The most frequently utilized technique during neurosurgery consists of an opioid (i.e., fentanyl, sufentanil or remifentanil) and low dose (0.2–0.5 %) isoflurane or sevofurane (<1 MAC). Administration of a preoperative benzodiazepine such as midazolam (0.5 mg/kg p.o., 0.1 mg/kg I.V.) in select patients 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, due to enhance activity of the hepatic P450 enzymes [122]. Patients receiving chronic anticonvulsant therapy will require larger doses of muscle relaxants and opioids because of induced enzymatic metabolism of these agents [164]. Muscle relaxants should be withheld or permitted to wear off when assessment of motor function during neurosurgery is planned, either intraoperatively or post operatively.

Monitoring

Intraoperatively, patients undergoing major craniotomies are at risk of sudden hemodynamic instability due to hemorrhage, venous air emboli (VAE), herniation syndromes, and/or manipulation of cranial nerves. Postoperative opening of central venous line ports may also place patients at risk for VAE. In addition to standard monitoring of electrocardiography, pulse oximetry, and noninvasive blood pressure monitoring, the potential massive blood loss warrants placement of an arterial cannula for continuous invasive blood pressure monitoring as well as for sampling serial blood gases, electrolytes, glucose levels and hematocrit, in both the operating room and ICU. The utility of central venous catheterization remains controversial and there is no clear cut evidence suggesting the superiority of one location over the other. Concerns over the lack of adequate venous drainage with indwelling internal jugular lines sometimes leads clinicians to place lines in either the subclavian and or femoral vein, but these alternate sites are associated with complications such as pneumothorax and infection, respectively. Moreover, the diameter of the internal jugular vein is large enough to typically accommodate a central line and facilitate adequate venous drainage [165].

Advanced Neurophysiological Monitoring

Neurophysiological monitoring is commonly used in the intraoperative setting but is an emerging area of investigation in the ICU setting for diagnosis and prognostication. Recent advances in neurophysiological monitoring have enhanced the ability to safely perform neurosurgical procedures in functional areas of the brain and spinal cord. In general, electrocorticography (ECoG), electroencephalography (EEG), and somatosensory evoked potentials (SSEP) can be utilized with low levels of volatile anesthetics or ICU sedation. An anesthetic technique using high dose opioids and minimal inhaled agents (<1 MAC) is the most appropriate agent for this type of monitoring in the OR. Moreover, the use of sedatives should not be prohibitive to neuromonitoring in the ICU setting. Spinal cord and peripheral nerve surgery may require electromyography (EMG) and detection of muscle movement as an end-point, but muscle relaxation should be avoided or discontinued after tracheal intubation to facilitate monitoring. Motor evoked potentials (MEP) monitors 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. Volatile anesthetic agents, including nitrous oxide, have a dose-dependent depressant effect on the MEPs, while intravenous anesthetic drugs (propofol, opioids, ketamine, and dexmedetomidine) typically preserve MEPs.

Somatosensory evoked potentials, electroencephalograms, and bispectral index are examples of neurophysiological monitors which have been used in the OR and ICU in critically ill children [166]. Of these, EEG is the most commonly used monitor for seizures and cerebral ischemia and has been intensively investigated. Electroencephalographic waveforms are the summation of excitatory and inhibitory postsynaptic potentials from the superficial layers of the cerebral cortex. Both regional and global ischemia results in profound depression of EEG activity, characterized by an attenuation of high-frequency activity and appearance of slow waves in the corresponding area. This feature makes EEG monitoring the most reliable intraoperative monitor for focal cerebral ischemia. Direct analysis of the raw EEG by an electrophysiologist remains 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 electrocorticography 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 pharmacological interventions of improved cerebral perfusion.

Cerebral Oxygenation Monitors

The primary cause of cerebral ischemia in infants and children is cerebral hypoperfusion secondary to systemic arterial hypotension or sustained intracranial hypertension. The major perioperative modalities for monitoring cerebral ischemia are: (1) jugular venous oximetry, (2) cerebral oximetry and, (3) brain tissue oxygenation.

Jugular Oximetry

Jugular bulb catheters may be inserted retrograde into the internal jugular using angiocaths for intermittent sampling or fiberoptic catheters for continuous readings and are a useful tool for determining cerebral oxygenation (jugular venous oxygen saturation, SjvO₂). Normal SjVO₂ ranges from 50–75 %; values at either extreme reflect global ischemia or hyperemia, respectively. SjvO₂ monitoring can provide early diagnosis of global ischemia and is useful to guide decisions for guiding and optimizing hyperventilation therapy, perfusion pressure, fluid management, and oxygenation in head injured patients [167, 168]. While SjvO₂ monitoring is not ubiquitous during craniotomies, it is routinely performed for most craniotomies at some institutions. Matta et al. [169] have demonstrated in adults that SjvO₂ monitoring detects critical intraoperative cerebral desaturation that would otherwise have been untreated, and Moss et al. [170] have used SjvO₂ monitoring to determine the minimum blood pressure that should be maintained to avoid hypoperfusion during aneurysm surgery [171].

Cerebral Oximetry

Near infrared spectroscopy (NIRS) provides a noninvasive assessment of cerebral intravascular oxyhemoglobin and deoxyhemoglobin (oxy-Hb and deoxy-Hb) and mitochondrial cytochrome oxygenation by measuring the abilities of these two chromophores to absorb near infrared light. Quantitative measurement of changes in cerebral chromophore oxygen concentration is related to the overall optical attenuation of NIR light, and has been used to assess oxygen delivery and extraction, cerebral blood volume, CBF (indicator dye technique), and the redox state of the brain. The NIRS correlated with mean arterial pressure and is effective in identifying premature infants with impaired cerebrovascular autoregulation [172]. The equipment used in these studies is primarily research prototype and is not commercially produced. Therefore, this technique has yet to find a niche in routine intraoperative monitoring. Regional cerebral oximetry (rSO~INVOS, Somanetics Corporation, Troy, MI) is a simpler NIRS modality that measures relative changes in oxygen extraction in the total blood volume of a small brain area. This technique uses two wavelengths to determine oxy-Hb and total cerebral hemoglobin concentration. Because approximately 75 % of the blood volume within the brain is venous, the cerebral oximeter measurement reflects venous oxy-Hb saturation and has been reported to correlate with jugular bulb saturation.

Brain Tissue Oxygenation (PbO₂)

Brain tissue oxygenation is best studied in children in the TBI population. Measuring oxygen tension in the brain, it provides a measure of brain ischemia. A PbO₂ <10 mmHg in severe pediatric TBI reflects cerebral ischemia and this technology has been used to guide blood transfusion and prognosticate outcome in pediatric TBI [173]. Increasing normobaric oxygenation increases PbO₂ values in children with severe TBI but the response is variable. Currently, PbO₂ monitoring is an emerging advanced neruomonitor.

Anatomic Imaging and Cerebral Perfusion

Computed tomography (CT) is the mainstay of imaging during the preoperative and immediate postoperative periods. Indications for CT scans include timely diagnosis of lesions that cause increased ICP, detection of blood and the need for neurosurgery. Postoperative head CT scans are typically performed to exclude new onset hemorrhage post procedure. Intraoperative CT scans are available in some centers which obviates the need for transporting neurosurgical patient during the immediate postoperative period. Neurosurgical patients may be exposed to a large number of head CT scans during the perioperative period, which causes unwanted exposure to radiation. Concerns over the lifetime attributable risk of cancer from medical imaging, especially in the developing brain, from head CT scans have been raised by individual investigators [174] as well as national organizations which have campaigned to reduce unnecessary radiation exposure to children [175]. Early MRI scanning has been suggested as an alternative to head CT scans, especially in cases of suspected inflicted injury [176]. Advanced CT based techniques to examine cerebral perfusion are available but at present are constrained by radiation dose concerns. Arterial spin labeling and advanced MRI techniques provide estimates of changes in CBF and CBV and bedside transcranial Doppler technology measures cerebral blood flow velocity and is an appealing modality of evaluating cerebrovascular hemodynamics at the patient’s bedside and with no radiation risk.

Emergence Phase of Anesthesia

In critically ill children, when patients are taken from the operating room to the ICU with residual anesthesia or sedation and an indwelling tracheal tube, there is no emergence phase of anesthesia.

Special Considerations for Perioperative Management of Select Neurosurgical Diseases

Congenital Anomalies

Congenital anomalies of the central nervous system generally occur as midline defects. This dysraphism may occur anywhere along the neural axis, involving the head (encephalocele) or spine (meningomyelocele). The defect may be relatively minor and affect only superficial bony and membranous structures or may include a large segment of malformed neural tissue.

Encephalocele

Encephaloceles are neural tube defects that present as protrusions of brain and CSF arising from the occiput to the frontal area. They can even appear as nasal “polyps” if they protrude through the cribriform plate. Large defects may present challenges to tracheal intubation. Significant blood loss can develop during surgical excision of these anomalies, especially if venous sinuses are entered. Adequate intravenous access should be ensured and blood products should be available.

Myelodysplasia and Spinal Cord Defects

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 within 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. Airway management, mask fit, and intubation may be difficult in 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 [157]. 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 co-exists [177].

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 may include the musculoskeletal system, genitourinary system and immune system in addition to the central nervous system. As mentioned above, these patients are at high risk of latex allergy. 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. EMG monitoring can be helpful for identifying functional nerve roots as described above.

Cerebral Palsy results in spasticity and severe spasticity can be surgically alleviated by a selective dorsal rhizotomy (SDR). SDR 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 in order to decrease afferent nerve conduction. However, these rootlets can potentially contain sensory and proprioceptive fibers. Spinal cord reflexes can be quantified by measuring the Hoffman reflex as noted above. The postoperative care of these patients is completed by severe somatic incisional pain, dysasthesia and hyperesthesia of the affected limb and muscle spasms. A variety of post operative pain management techniques have been advocated in these patients. These include intravenous morphine and midazolam/diazepam infusions and epidural opioids [178].

Chiari Malformations

Chiari malformations are generally defined as an anatomical abnormality of the posterior fossa leading to cephalad displacement of the cerebellar vermis through the foramen magnum. There are four types of Chiari malformations. Type I occur in healthy children without myelodysplasia. These patients generally have much milder symptoms, sometimes presenting only with headache or neck pain, usually during adolescence. The Arnold-Chiari malformation (type II) almost always co-exists 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 present during infancy. Patients of any age may have abnormal responses to hypoxia and hypercarbia because of cranial nerve and brainstem dysfunction [179]. 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 Chiari malformations are associated with absent cerebellum, and large posterior fossa cerebrospinal fluid spaces.

Tumors

Since the majority of intracranial tumors in children occur in the posterior fossa, CSF flow is often obstructed and intracranial hypertension and hydrocephalus is often present. The intraoperative period includes elevation of the bone flap which can result in sinus tears, massive blood loss, and/or VAE. Surgical resection of tumors in the posterior fossa can also lead to brainstem and/or cranial nerve damage. Damage to the respiratory centers and cranial nerves can lead to apnea and airway obstruction after extubation of the patient’s trachea.

Brain tumors are the most common solid tumors in children [180]. Supratentorial tumors account for about 25–40 % of brain tumors in children, and supratentorial resection usually requires invasive monitoring and techniques to control elevated ICP. The majority of brain tumors in children are infratentorial, and include medulloblastomas, cerebellar astrocytomas, brainstem gliomas, and ependymomas of the fourth ventricle. Because posterior fossa tumors usually obstruct CSF flow, increased ICP occurs early. Presenting signs and symptoms include early morning vomiting and irritability or lethargy. Cranial nerve palsies and ataxia are also common findings with respiratory and cardiac irregularities, usually occurring late. Sedation or general anesthesia may be required for radiologic evaluation or radiation therapy and surgical resection poses a number of anesthetic challenges including positioning, arrhythmias and acute blood pressure changes, depressed respiration, as well as VAE and increased ICP.

Tumors in the midbrain include craniopharyngiomas, optic gliomas, pituitary adenomas, and hypothalamic tumors and account for approximately 15 % of all intracranial tumors. Hypothalamic tumors (hamartomas, gliomas, and teratomas) frequently present 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 since 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 since 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 due to the adequate reserve of antidiuretic hormone in the posterior pituitary gland capable of functioning for many hours even when the hypothalamic-pituitary stalk is damaged intraoperatively. Postoperative diabetes insipidus is marked by a sudden large increase in dilute urine output associated with 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/h in an adult) that an infusion of aqueous vasopressin (1–10 mU/kg/h) is best utilized 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 intravenous pitressin, since 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. Transsphenoidal surgery is generally only performed in adolescents and older children with pituitary adenomas. Since nasal packs are inserted at the end of surgery, patients should be fully awake prior to tracheal extubation and transported to the recovery room.

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 since 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 of age. They usually arise from the choroid plexus of the lateral ventricle and produce early hydrocephalus as a result of increased production of CSF and obstruction of CSF flow. Hydrocephalus usually resolves with surgical resection. When lesions lie near the motor or sensory strip, a special type of somatosensory evoked potential monitoring called “phase reversal” may also be used to delineate these locations [181]. 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 is the most common pediatric neurosurgical condition. It is a condition involving a mismatch of CSF production and absorption leading to increased intracranial CSF volume. The majority of cases of hydrocephalus are due to 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.

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 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 due to problems with the ability of the peritoneal cavity to absorb CSF as in peritonitis. VAE can 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 [182]. 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. 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 when they occur, and the anesthesiologist should be prepared for an emergency craniotomy during these procedures. Bradycardia and other arrhythmias have been also reported in conjunction with irrigation fluids and/or manipulation of the floor of the third ventricle [183].

There are a few special situations involving shunts that critical care physicians and anesthesiologists should be familiar with. 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, one must be careful not to dislodge the ventricular tubing. In addition, the height of the drainage bag should not be changed in relationship to the patient’s head to avoid sudden changes in ICP. 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, it is best to temporarily close the ventriculostomy tubing during these brief periods.

Slit ventricle syndrome develops in approximately 5–10 % of patients with CSF shunts and is associated with overdrainage of CSF and small, “slit-like” 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 intravenous solutions should be avoided in order to minimize brain swelling, because postoperative cerebral herniation have been reported after uneventful surgical procedures in these children [184]. 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 2,000 births, with males affected more frequently than females. The craniosynostosis 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 brain, with potential neurologic sequelae [185]. Surgical correction is usually performed within the first months of life to achieve the best cosmetic results. This is because brain growth is very rapid during infancy, “pushing” the skull into a normal shape. Repair of cranio-synostosis may involve removal of one small strip of bone from the skull, or it may entail a complete reconstruction of the calvarium. Although these operations are extradural procedures, significant blood loss from the scalp and cranium make these challenging anesthetic procedures. It is essential that adequate venous access for rapid blood administration is secured, especially if multiple sutures are involved during surgery and postoperatively. Antifibrinolytic drugs (tranexemic acid) may have some utility in these procedures [186]. However, seizures have been reported after the use of high doses in cardiac surgery, which may be due to the intrinsic ability of TXA to inhibit glycine receptors [187]. The incidence of VAE is also significant during these procedures [188]. Endoscopic strip craniectomies are associated with decreased blood loss, decreased surgical time, and improved postoperative recovery time during endoscopic strip craniectomy in neonates and infants [189, 190]. Tobias and colleagues reported a significant decrease in the incidence of VAE during this procedure [191].

Epilepsy

Epilepsy remains one of the most common neurologic disorders in children. Although a number of new pharmacologic interventions have shown promise in the medical management of childhood epilepsy, a large number of children continue to have intractable seizures and 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 upregulating hepatic P450 enzymes [122]. Intraoperative neurophysiologic monitors can be used to guide the actual resection of the epileptogenic focus and general anesthetics can compromise the sensitivity of these devices [192]. If cortical stimulation is utilized to mimic the seizure pattern or identify areas on the motor strip, neuromuscular blockade should be antagonized.

A variety of techniques are utilized during the entire perioperative period to aid in localization of seizure foci. A major part of preoperative planning should include a through discussion of the modality and type of neurophysiological monitoring to be used during the surgical procedure. 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 intracranial grid and strip electrodes. EEG grids and/or strips and placed on the exposed cortical surface in order to accurately create a map that will to localize the seizure focus. The patient is then observed in an electrophysiology unit in order 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 via an awake craniotomy technique. 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.

Intraoperative and 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. While phenytoin is the agent used most commonly for prophylaxis, maintaining therapeutic serum levels can be challenging [193]. Levetiracetam is becoming increasingly common and in many instances supplanting phenytoin as the choice for postoperative seizure prophylaxis. Both drugs can 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 with, lorezepam 0.1 mg/kg IV push over 2 min or diazepam 0.5 mg/kg PR are effective agents. Lorezapam may be repeated after 10 min 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 of these conditions are congenital lesions that present early in life. Large arteriovenous malformations (AVM) 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 [194]. Operative management is commonly associated with massive blood loss. Ligation of an AVM can lead to sudden hypertension with hyperemic cerebral edema [195] and should be treated with vasodilators such as labetalol or nitroprusside. Postoperative angiography may be indicated in order to rule out any residual AVMs or vascular leaks. Since re-hemorrhage or stroke can occur during the postoperative period, strict blood pressure parameters should be set to avoid hypo- and hypertension.

Moyamoya syndrome is a rare chronic vaso-occlusive disorder of the internal carotid arteries that presents as transient ischemic attacks and/or recurrent strokes in childhood. The etiology is unknown, but the syndrome can be associated with prior intracranial radiation, neurofibromatosis, Down’s syndrome, and a variety of hematological disorders including sickle cell disease. Medical management consists of antiplatelet medications, e.g., aspirin or calcium channel blockers. Surgical management is aimed at improving 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 [196]. This includes assuring generous preoperative hydration and maintaining the blood pressure within the patient’s preoperative levels. Maintenance of normocapnia is essential as well because both hyper- and hypocapnia can lead to steal phenomenon from the ischemic region and further aggravate cerebral ischemia [197]. Once the patient emerges from anesthesia, the same maneuvers that optimize cerebral perfusion should be extended into the postoperative period. Postoperative agitiation and pain should be aggressively treated to minimize hyperventilation and increases in cerebral metabolic demand.

Neurotrauma

The fundamentals of pediatric neurotrauma, including TBI, spinal cord injury, multiple trauma and inflicted injury are discussed elsewhere in this textbook. In brief, the perioperative management of pediatric neurotrauma consists of adhereing to published national guidelines. For severe TBI, recommendations of care are well described in the recently published 2012 Guidelines for Acute Care Management of Infants and Children with Severe TBI [198]. Neurotrauma and prevention of secondary insults after neurotrauma remains the mainstay of anesthetic and intensive care medicine except for when surgical decompression is needed. There are documented changes in cerebral hemodynamics that occur after TBI where systemic hypotension, cerebral hypoperfusion, impaired cerebral autoregulation may ensue. These secondary insults may lead to cerebral ischemia, cerebral hyperemia and poor outcomes [7, 26, 123, 167, 199–210]. It is important to note that the Pediatric Guidelines for Severe TBI do not contain data from the intraoperative period and hence the specific hemodynamic thresholds for treatment may or may not apply. However, at present, given the paucity of data, a target cerebral perfusion pressure of at least 40 mmHg should be targeted [211–214]. The choice of vasopressors to increase blood pressure and CPP may vary. One single center study suggests that norepinephrine might lead to a higher increase in CPP than phenylephrine or dopamine in children with severe TBI [215]. The management of increased ICP, including hyperventilation for severe TBI in children is also described elsewhere in this text and in the Pediatric Guidelines [198, 211, 216, 217]. Patients who have refractory high ICP may undergo decompressive craniectomy and or receive hypothermia. It is important to note, however, that hypothermia is associated with increased mortality in these patients [218].

Additional Considerations

Neuroendoscopy

Technological advances in minimally invasive endoscopic surgery have entered the neurosurgical arena. Since neuroendoscopic techniques are designed to minimize surgical incision, dissection, and blood loss, less aggressive fluid replacement and invasive hemodynamic monitoring is becoming the norm. Endoscopic strip craniectomies are associated with decreased blood loss, decreased surgical time, and improved postoperative recovery time during endoscopic strip craniectomy in neonates and infants [189, 190, 219]. Tobias and colleagues reported a significant decrease in the incidence of VAE during this procedure [191]. Endoscopic third ventriculostomy is another approach for the treatment of obstructive hydrocephalus in infants and children [220]. A flexible fiberoptic scope is inserted through a trocar and provides a working channel that allows the neurosurgeon to insert a ventricular catheter or make frenestrations. Despite the relative safety of this procedure, bradycardia and other arrhythmias have been reported in conjunction with lack of egress of irrigation fluids and/or manipulation of the floor of the third ventricle [183, 221]. Neurogenic pulmonary edema due to acute intracranial hypertension has also been reported with this procedure [222].

Pain Management

Physicians are typically taught that the brain feels no pain and that this is due to the fact that only the dura has pain receptors. Traditionally, concerns over opioid related respiratory depression have resulted in conservative pain control strategies, such as avoiding opioids and or the use of suboccipital nerve blockers or as needed opioids. The use of sedation may also decrease the ability to assess and accurately record pain and patients with extracranial disease states or conditions might have pain from those conditions. Yet, pain after craniotomy may be more common that previously recognized. Optimal perioperative pain control in neurosurgical patients may aid with lowering ICP, assure a favorable neurovascular milieu, and facilitate timely diagnosis of the neurological problem. In one meta analysis of RCTs data from a total of 519 adults, who received four treatment strategies (scalp infiltration [five RCTs], nerve scalp block [two RCTs], parecoxib [one RCT] and patient-controlled analgesia with morphine [one RCT]), the authors reported that scalp infiltration with local anaesthetic may provide adequate analgesia in the first few postoperative hours, and nerve scalp block may provide longer lasting analgesia for 6 h. Morphine was found to reduce total analgesic rescue doses with no significant effect on nausea and no other side-effects and there was no significant evidence was found to support the use of parecoxib in the treatment of postcraniotomy pain [223]. In the only pediatric study on postcraniotomy pain in children, Teo et al. reported that while most patients do not have pain during the first 72 h after surgery, many patients have at least one episode of a pain score ≥3 and predicted by duration of procedure. Perioperative pain regimens vary and include parenteral morphine, paracetamol, oxycodone, codeine, tramadol and ibuprofen [224]. No firm recommendations on analgesic therapy following craniotomy can be made because the number of well performed RCTs is limited and the study populations are very small. However, evidence on scalp infiltration suggests an analgesic effect in the first few postoperative hours.

OR to ICU Handoffs and ICU Handoffs to OR

Communication between the preoperative, intraoperative, and postoperative teams is essential for optimizing outcomes of pediatric neurosurgical patients. Creating specified checklists that facilitate transfer of critical and anticipatory events between members of the health care team including nurses and physicians is essential to preventing adverse events and to capturing near misses in these patients. One study by Brannen and colleagues showed that three-fourths of the handoffs had agreement about the severity of the patient’s illness but that there was low agreement about the most severe problem and the total problem lists between residents involved in the handoff communication. Attending physicians were able to identify more patient problems [225].

Conclusion

The perioperative management of the neurosurgical patient is complex and challenging, requiring a solid understanding of the patient, preoperative conditions, surgical procedure, anesthetic events and potential postoperative complications. Developmental age and gender related differences between patients add to the complexity and may impact the course and outcome of neurosurgical patients. Finally, tremendous coordination between the clinical care teams is critical to preventing adverse events in this vulnerable patient population.