The pediatric intensive care unit (PICU) is a multidisciplinary region of the hospital designed to care for patients with impending and current single or multiorgan failure. Pediatric patients with central nervous system (CNS) tumors are cared for in the PICU preoperatively, postoperatively, and potentially during outpatient management when complications arise, to treat both neurologic/neurosurgical and nonneurologic/neurosurgical conditions. The PICU is staffed with a team of doctors, pediatric intensivists, who work along with the primary team of neurosurgeons and oncologists, along with PICU nurses, pharmacists, respiratory therapists, and nutritionists—all dedicated to the complex management of critically ill patients.
An advantage of the intensive care unit is the ability to closely monitor patients with state-of-the-art technology. Vital signs can be monitored continuously via telemetry and invasively via arterial access, central venous access, and intracranial pressure monitoring devices. Frequent neurologic evaluations are done to ensure rapid diagnosis of potential complications. Practitioners of pediatric critical care medicine are required to be knowledgeable about common complications and familiar with the anatomic and physiological characteristics of the pediatric CNS. The combination of knowledge and technology allows for supportive care of the entire patient (neurologic, respiratory, cardiovascular, nutritional, infectious, and hematologic systems), and has contributed to an improved progression-free and overall survival rate of nearly 80% in certain pediatric brain tumors.1,2
Anatomy and Physiology of the Intracranial Space
To understand many of the postoperative and critical problems seen in pediatric patients with CNS tumors, the reader should be familiar with some of the basic neuroanatomic and neurophysiological principles outlined below.
The Monro-Kellie hypothesis states that the cranial vault contains a fixed volume and consists of three basic components—brain (80%), blood (10%), and cerebrospinal fluid (CSF) (10%)—that are encased by the thick inelastic dura mater and the semirigid cranium. These components exist in a state of volume-pressure equilibrium, and the expansion of one component must be compensated for a reduction in the volume of one or both other components.3 Figure 10.1 represents a graphic representation of intracranial compliance. The volume-pressure graph demonstrates that a mechanism exists for the cranial vault to remain at a constant pressure after an initial increase in intracranial volume (i.e., by tumor, edema, or hemorrhage). This is accomplished by the displacement of CSF and venous cerebral blood into the spinal space. The compensated bar on the curve represents an area where, despite the intracranial pressure (ICP) being normal, any further increases in volume (such as may be seen with continued tumor growth, edema, obstructive hydrocephalus, or hemorrhage into the tumor) will produce an exponential rise in ICP that may be life threatening. Further increases in intracranial volume will lead to an uncompensated state and a neurosurgical emergency with dangerously high ICP. There is a common misconception that the infant is protected from an increase in ICP by virtue of the open fontanel; however, it must be remembered that the brain is encased by inelastic dura mater, which limits the infant′s compensatory mechanisms. The infant has a shorter craniospinal axis (measured from the cranial dura down the length of the spinal canal to the lumbosacral area) than does the adult. It is evident that less potential space is available to allow for the displacement of CSF or cerebral blood in the pediatric patient. However, certain slow-growing brain tumors or other CNS lesions may be better tolerated by the infant because the slow growth allows eventual splitting and widening of the cranial sutures. This usually occurs over a period of weeks to months. It is the interaction of these three compartments and the physiological mechanism controlling each of them that underlies the framework of neuro-intensive care.4
The largest component (80%) of the intracranial vault is the brain. The brain parenchyma is composed of neurons (50%), and glial and vascular elements. There are three types of glial tissue: astroglia, which provides a supporting structure and plays a role in neuronal metabolism; oligodendroglia, which produces myelin around axons; and microglia, which serves as immune cells. Neurons are the basic processing units of the CNS, responsible for the production of neurotransmitters and the conduction of impulses. The energy supplied to the brain is utilized to maintain the neuronal transmembrane potential and support of the membrane (to keep K+ intracellular and Na+ extracellular), driving of axonal flow, production of neurotransmitters, and propagation of neural impulses.5 The brain′s need for energy is substantial; paradoxically, its store of energy-generating substrates is small, making it exclusively dependent on an adequate cerebral blood flow (CBF) for delivery of substrate.
The cerebral blood, including veins, arteries, and capillaries, accounts for approximately 10% of the volume of the intracranial vault. CBF is regulated by brain metabolism, blood pressure, and arterial partial pressure of carbon dioxide (PCO2) and of oxygen (PO2).
Cerebral perfusion pressure (CPP) is defined as the difference between the mean arterial pressure (MAP) and the ICP and is represented by the equation CPP = MAP – ICP. CPP is thus the driving pressure that provides substrate (oxygen and glucose) to the brain. The brain has a pressure autoregulatory ability that enables it to maintain a stable CBF over a wide range of CPP values by varying the diameter of its arterioles and precapillary vessels. There is also a metabolic autoregulatory mechanism that modulates the diameter of these vessels in response to the cellular metabolic environment. An increase in MAP produces vasoconstriction to maintain a stable CBF, whereas ischemia, hypoxia, or hypercarbia produces vasodilation to increase CBF ( Fig. 10.2 ).6 The normal CPP in adult is approximately 75 to 100 mm Hg, and the accepted lower limit needed to provide adequate CNS perfusion is 50 mm Hg.7 At a CPP below 20 mm Hg, irreversible neuronal damage occurs. In the neonate and infants, the accepted CPP is lower secondary to the lower age-related blood pressure.
Cerebrospinal fluid is the third component of the intracranial vault and represents approximately 10% of the cranial volume. CSF is a clear, aqueous solution that is an ultrafiltrate of plasma, which bathes the brain and spinal cord. The low specific gravity of CSF in relation to the brain reduces the mass effect of the brain to a minimum and serves as a protective cushion that prevents the brain′s full weight from producing traction on nerve roots, blood vessels, and delicate membranes. CSF also provides a chemically appropriate environment that is necessary for neurotransmission and the removal of metabolic by-products. It is important to realize that displacement of CSF into the spinal canal is one of the compensatory mechanisms for an increasing cerebral vault volume and that any obstruction to the egress of CSF may lead to an increase in ICP. Approximately 50 to 60% of all pediatric brain tumors arise in the posterior fossa, which is the area located under the tentorium cerebelli and includes the cerebellum, pons, and medulla oblongata.8 Tumors in this area can easily compromise CSF outflow, leading to acute hydrocephalus and increased ICP.
Critical Illness of Patients with CNS Tumors
Pediatric patients with brain tumors can be admitted to the intensive care unit to manage complex problems arising pre-surgically, postoperatively, and in the outpatient setting. The vast majority of these problems present with altered mentation, which can be identified by frequent neurologic examinations. Patients with brain tumors will experience illness involving neurologic, respiratory, cardiovascular, fluid/electrolyte, gastrointestinal, hematologic, and infectious systems requiring complex management in the intensive care unit.
A majority of complications seen in patients with brain tumors involve the CNS and present with a depressed mental status. When these complications are encountered postoperatively, one must consider delayed emergence from anesthesia, cerebral edema, hydrocephalus/shunt malfunction, pneumocephalus, electrolyte disturbances, intracranial hemorrhage, seizures, stroke/ischemia, hypoventilation, and posterior fossa mutism ( Table 10.1 ). Hydrocephalus, seizures, and cerebral edema are common neurologic complications in patients presenting with undiagnosed CNS tumors.
The CNS effects of anesthetics are complex and may include pupillary changes, sustained clonus, hyperreactive quadriceps reflexes, Babinski′s sign (up-going toes), shivering, and occasional transient worsening of preexisting neurologic deficits.9,10 These effects are usually seen with the use of inhalational anesthetics (enflurane and halothane) and resolve in less than an hour following the discontinuance of the anesthetic. Slow awakening or persistent somnolence may be seen following the use of narcotics (morphine, fentanyl). Patients undergoing craniotomy for large intracranial mass lesions awaken more slowly than do patients who have undergone spinal surgery or craniotomy for small brain tumors.11
The postoperative neurosurgical patient in the PICU should have neurologic assessments done approximately every 15 minutes for the first 4 hours, then every 30 minutes for the next 8 to 12 hours, and then hourly for the subsequent 12 hours. The most important clinical sign is the patient′s mental status. The most accepted and reliable tool for evaluating mental status is the Glasgow Coma Scale (GCS) ( Table 10.2 ). Patients with a rapidly increasing headache with vomiting, increasing drowsiness, new hemiparesis or paresthesias, pupillary changes, or drop in GCS score of 2 or more points in previously awake patients are usually manifesting a neurologic complication.
It is important to rule out other etiologies for altered mental status before settling upon the diagnosis of delayed emergence from anesthesia ( Table 10.1 ). Goals in the immediate postoperative period are to allow for rapid early emergence, document neurologic improvement, extubate as early as possible, and control pain without causing obtundation of the patient.
Cerebral edema is an increase in water content of the brain and may be classified as either cytotoxic or vasogenic. Cytotoxic edema is the accumulation of primarily intracellular water. This leads to an increase in the size of the brain cell and little change in the extracellular compartment.12,13 Vasogenic edema occurs as a result of plasma leak from the vasculature into the brain parenchyma. There is a little change in cell volume, and swelling occurs in the extracellular space. Vasogenic edema is associated with brain tumors both pre- and postoperatively, and may account for more neurologic findings than the tumor itself.14 Post-operative cerebral edema peaks at 36 to 72 hours; however, it can be encountered in the first 6 to 12 hours after surgery.
Glucocorticoids have been shown to decrease the edema associated with brain tumors. Mechanisms include reduced blood–brain barrier permeability; increased sodium, potassium, and water flux across the capillary/tissue interface; and direct inhibition of tumor growth.15–17 Dexamethasone is the drug of choice for treating edema with 25 times the glucocorticoid strength of cortisol and negligible mineralocorticoid activity. It is a potent anti-inflammatory agent that does not cause sodium or fluid retention. Preoperatively, symptoms from cerebral edema will improve with dexamethasone 4 mg once or twice a day. Postoperatively, the frequency of dosing is often increased to three or four times a day. Side effects of steroids include hyperglycemia, gastric ulceration and hemorrhage, myopathy, psychosis/mood disturbance, impaired wound healing, and impaired immune function, predisposing the patient to infections.18,19 Careful attention must be taken with discontinuation of steroid courses longer than 5 to 7 days, as it may result in adrenal insufficiency, which is manifested by fatigue, weakness, arthralgias, headaches, nausea, and hypotension.
Stress coverage to prevent intraoperative or postoperative adrenal crisis should be considered in patients who have been receiving high doses of glucocorticoids (more than 50 mg/m2 of cortisol daily) for a prolonged period (more than 10 to 14 days).20 The decision to administer stress coverage of steroids should be discussed with the anesthesiologist. Patients with adrenal crisis usually become hypotensive, hypoglycemic, hyponatremic, and hyperkalemic. Treatment includes prompt recognition and administration of isotonic fluids and hydrocortisone.21
Normal ICP rages from 5 to 15 mm Hg. Intracranial hypertension (ICH) occurs if the ICP remains elevated above that point for a sustained period of time. Daily fluctuations occur with sneezing, coughing, changes in position, and Valsalva maneuvers, but do not result in neurologic deterioration. ICH is a neurologic emergency in the postoperative patient. ICH should always be considered in the postoperative patient who suddenly has a change in the neurologic exam, a decrease in the GCS score of 2 or more points, unilateral papillary dilation, or posturing. ICH results from an increase in brain (cerebral edema), blood (postoperative hemorrhage, hypercarbia), or CSF (hydrocephalus), overcoming the brain′s ability to compensate.
Management of ICH is categorized into three tiers. Tier 1 interventions involve basic patient care techniques: elevation of the head of bed to 30 degrees; keeping the head midline; ensuring proper oxygenation; ruling out seizures; controlling fever; and maintaining normal blood pressure and cerebral perfusion pressure. Tier 2 interventions involve medical management with an increased risk of side effects: removal of CSF if an externalized ventricular drain is present; providing adequate sedation; neuromuscular blockade; and hyperosmolar therapy with either hypertonic saline or mannitol. Tier 3 interventions are those with a higher risk of complications and less well proven benefits: transient mild hyperventilation to a partial pressure of carbon dioxide in arterial gas (PaCO2) of 30 to 35 mm Hg; barbiturate coma; and decompressive craniotomy.22
Mannitol and hypertonic saline are thought to dehydrate the brain and improve brain rheology in the CNS microcirculation. Side effects of mannitol include dehydration and electrolyte depletion from diuretic effect and possible renal toxicity. Traditionally, mannitol dosing has been limited when serum osmolality reaches 320 mOsm/kg. More recently, calculation of the osmolar gap (the difference between directly measured serum osmolality and calculated osmolarity from the serum sodium, blood urea nitrogen [BUN], and glucose levels), and adjusting mannitol dosing to maintain an osmolar gap below 20 has become a technique to minimize mannitol nephrotoxity.23–25 Hypertonic saline is as effective as mannitol in lowering ICP. It can be administered either in bolus dosing of 5 mL/kg/dose or as a continuous infusion to maintain serum sodium at between 150 and 160 mmol/L and a serum osmolality < 360 mOsm/kg.26,27
Hyperventilation will reduce CBF to lower ICP, but carries the risk of producing tissue hypoxia. Additionally, if prolonged, the brain will reequilibrate and CBF will be increased at the lower PaCO2 value. If continued, tissue perfusion must be monitored by brain oxygen tissue (PbtO2) monitors, near-infrared spectroscopy (NIRS) of the brain, or jugular venous saturation (SjVO2) sampling.28 The goal of pentobarbital coma is to reduce the cerebral metabolic rate of injured brain by achieving 5 to 7 seconds of burst suppression during continuous electroencephalogram (EEG) monitoring.29 Side effects include hypotension and myocardial depression, and many patients receiving pentobarbital coma require catecholamine infusions to maintain an adequate blood pressure and CPP.
The initial step leading to brain ischemia is a reduction in CBF. Postoperative cerebral ischemia and infarction are rare in pediatric patients, occurring either as the result of intraoperative vessel ligation during tumor resection or as the result of excessive retraction leading to postoperative vasospasm. Affected areas will develop cytotoxic cerebral edema, leading to mass effect changes, vascular compression, and possible herniation syndromes.30 Vessels in the midbrain and diencephalon located at the base of the brain are tethered to the relatively immobile dura and are particularly susceptible.
Any increase in the metabolic rate (shivering, fever, hypoxia, seizures, etc.) will increase the risk of ischemic damage. Patients should be aggressively hydrated with isotonic fluids, and the blood pressure should be kept in the upper limit of normal for age range. Hypovolemia from diuresis and fluid restriction should be avoided. Placement of a central venous catheter to help assess a patient′s hydration status should be considered. CPP should be optimized with administration of catecholamines once an adequate fluid status is obtained.
Approximately 50 to 60% of pediatric brain tumors arise in the posterior fossa, and presenting signs and symptoms of obstructive hydrocephalus and elevated ICP are common. Patients with symptoms of obstructive hydrocephalus (altered mental status, severe headache, nausea/vomiting, focal neurologic deficits) are candidates for placement of an externalized ventricular drain (EVD). Additionally, following tumor resection, an EVD may be placed empirically as blood introduced into the subarachnoid space during surgery may interfere with CSF resorption. Many patients requiring preoperative ventriculostomy will see resolution following tumor resection and will tolerate removal of the EVD several days after surgery.31 Because many EVDs are only temporary, a recent trend toward endoscopic third ventriculostomy with avoidance of shunt hardware has begun to gain acceptance and has demonstrated fewer complications than EVD placement.32,33
Ventriculostomy may be complicated by parenchymal injury, hemorrhage (1.4%) infection, and shunt failure.34 Ventriculitis is a localized infection that appears to be most directly related to the length of time for which the catheter was left in place, with an incidence of 5 to 20%.35 Risk factors for infection are non-adherence to rigid insertion and maintenance protocols, CSF leakage, catheter irritation, and frequent EVD manipulation.36 Antistaphylococcal antibiotics are typically ordered prophylactically when an EVD is in place. Diagnosis of infection can be difficult due to inflammation caused by the presence of tumor or recent operation. CSF cultures every 48 to 72 hours are recommended.
Cerebrospinal fluid shunt failure and hydrocephalus is a complication seen in brain tumor patients both perioperatively and outside the operative period. The risk of shunt failure is greatest in the first several months following placement. Shunt failure can be mechanical (proximal or distal obstruction) or due to infection. Common signs and symptoms include headache, vomiting, nausea, altered mental status, lethargy, and general malaise.37
Obstruction is the most common cause of malfunction, with proximal obstructions occurring more frequently. The proximal shunt can be occluded with choroid plexus, ependymal cells, glial tissue, brain debris, fibrin, or blood, or the tip of the catheter may migrate into the brain parenchyma. Distal obstruction may occur with kinking of the tubing, disconnection of the tubing, intra-abdominal infection, or pseudocyst formation.
Infections may involve the shunt equipment, the wound, the CSF, or the distal site at which the shunt drains. Infections occur in about 11% of patients by 24 months.38 Clinical signs of infection depend on the site of infection. Wound infections manifest with fever, reddening of the incision or shunt tract, and discharge of pus along the incision in advanced cases. Patients with ventriculitis and meningitis have fever, headache, irritability, and neck stiffness. Treatment of choice is removal of the shunt hardware, placement of EVD, and parenteral antibiotics.
Seizures may be the first manifestation of brain tumors in 15 to 25% of children.39,40 Seizures occur more commonly in supratentorial tumors rather than in infratentorial tumors, and are more common in cortical and superficial lesions than in those arising in deeper structures. Seizures result from tumoral hemorrhage, necrosis, inflammation, and ischemia of surrounding neural tissues. New-onset seizures or increasing frequency of seizures in known brain tumor patients can be a marker of tumor progression or tumor recurrence.
Seizures in the postoperative period can lead to hypertension, hyperglycemia, hyperthermia, hypocapnia, and hypoxia, which in turn can lead to worsening cerebral edema and increased ICH. Patients with preoperative seizures, stroke, ICH associated with tumor or resection, subtotal resection, cortical-based tumors, or temporal lobe tumors are at a greater risk for postoperative seizures and likely warrant prophylaxis.41 However, this topic is poorly studied, and adult data suggest no benefit of prophylactic anticonvulsant use beyond 7 days postoperatively.42 A prolonged seizure (> 30 minutes) can result in lactic acidosis, hyperkalemia, renal failure, myoglobinuria, arrhythmias, pulmonary aspiration, leukocytosis, and CSF pleocytosis, and is a medical emergency.43 When a seizure does occur postoperatively, studies to rule out metabolic causes (hyponatremia, hypocalcemia, hypomagnesemia, or hypoglycemia) should be conducted. A computed tomography (CT) scan to evaluate for postoperative hematoma, pneumocephalus, and cerebral edema is recommended if a metabolic explanation cannot be found.
Posterior Fossa Syndrome
Posterior fossa syndrome, also known as posterior fossa mutism or cerebellar mutism, occurs postoperatively in 15 to 25% of patients with cerebellar tumors.44 Patients with medulloblastoma or tumors with brainstem invasion are at greatest risk to develop posterior fossa syndrome.45 It typically occurs 12 to 48 hours after surgery and is characterized by loss of verbal expression, pseudobulbar dysfunction, irritability, and ataxia. Speech recovery ranges from days to months, but a significant number of patients with severe symptoms will have persistent symptoms beyond a year. The exact cause is unknown.
Pain and Sedation
Pain is a noxious stimulus and may lead to tachycardia, hypertension, anxiety, nausea, and vomiting, which may all produce an elevation in ICP. Failure to provide adequate anesthesia will cause a neuroendocrine response as the result of the aforementioned sympathetic response. Epinephrine, norepinephrine, catecholamines, cortisol, glucagon, growth hormone, vasopressin, and interleukins are released, leading to a catabolic state, altered gas exchange, fever, immobility, immunosuppression, and psychological changes. It must be remembered that many children are unable or unwilling to complain of pain, and therefore the practitioner must have a high index of suspicion.
Pain assessment tools are divided into three categories: self-reported, behavioral, and physiological.46 Visual analog scales used by adults can be used reliably in children 8 years of age and older. Children between the ages of 3 and 7 years have been shown reliably to use pain scales containing faces showing increasing levels of stress to identify pain. Under the age of 2 years, self-report scales are less reliable, and physiological (heart rate, blood pressure, respiratory rate) and behavioral (screaming, grimacing, thrashing of limbs) markers must be used.47
Practitioners have a wide assortment of agents to treat postoperative pain. It is important that the pain and sedation regimen chosen for the agitated pediatric neurosurgical patient must either preserve the neurologic examination for clinical monitoring or have the potential to be discontinued with rapid return of an uncompromised examination.48 Common agents used in the PICU include opioids, benzodiazepines, acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), barbiturates, anesthetic agents (propofol, ketamine), and dexmedetomidine.49 Common side effects of sedative agents include altered mental status, respiratory depression, myocardial and cardiovascular depression, and motor incoordination. A summary of their mechanisms of action, advantages and side effects can be seen in Table 10.3 .50
Patients with brain tumors are at risk for multiple complications related to their respiratory system, and thus they require vigilant attentiveness. Respiratory insufficiency or failure can be due to apnea, upper airway obstruction, or lower airway disease. Once respiratory distress is localized, a cause can be identified and proper treatment administered.
Apnea results in hypoventilation and retention of carbon dioxide and hypoxemia ( Table 10.4 ).51 Complete cessation of gas exchange allows the PaCO2 to rise by 10 to 12 mm Hg in the first minute, 7 to 10 mm Hg in the second minute, and 3 to 6 mm Hg in the third minute.52 The retention of carbon dioxide can lead to altered mental status ranging from confusion to coma. Furthermore, hypercarbia leads to cerebral vasodilation and increased ICP. Prompt identification of a cause and either reversal or mechanical ventilation is highly important. Administration of supplemental oxygen should quickly reverse hypoxemia in patients without significant lower airway disease
Hypoventilation results from residual anesthetic agents or inadequate reversal of neuromuscular blockade. Administration of narcotics can lead to hypoventilation, and thus judicious titration of medication along with use of acetaminophen is indicated. Finally, patients with Cushing′s triad from increased ICP can develop irregular respirations with intermittent apnea. It should be considered when hypoventilation is associated with bradycardia and hypertension, and a prompt diagnosis should be made and treatment initiated.
Upper Airway Obstruction
Upper airway obstruction results in hypoventilation and retention of carbon dioxide and hypoxemia ( Table 10.5 ). Clinical findings include retractions (suprasternal, intercostal, and subcostal), nasal flaring, inspiratory stridor, paradoxical breathing, and decreased or absent air entry. Laryngospasm, airway edema, poor airway tone, and vocal cord paralysis can all result in upper airway obstruction.
Laryngospasm may occur due to secretions or during extubation.53 The incidence is highest in patients under 9 years of age and is highest in the 1- to 3-month-old age group. Patients with intercurrent upper respiratory tract infections are also at a greater risk. Lack of chest wall rise and severe suprasternal retractions during emergence from anesthesia are highly suggestive of laryngospasm. Therapy includes bag-mask ventilation with 100% oxygen and administration of a short-acting neuro-muscular blocking agent. Typically the neuromuscular blockade will resolve the laryngospasm, and the patient can be bag-mask ventilated until the blockade clears. The patient may require reintubation, although this is uncommon.
Glottic or laryngeal edema and postoperative croup occurs in 1 to 4% of intubated pediatric patients. The pediatric patient has a smaller larynx, and whereas in the adult patient 1 mm of edema produces only slight hoarseness, in the pediatric patient the airway is reduced by 75% and serious obstruction occurs.54 Symptoms include stridor, hoarseness, croupy cough, and thoracic retractions. Symptoms typically occur 30 to 60 minutes after extubation. Treatment includes positioning the patient upright, administering cool mist, inhaled racemic epinephrine, and steroids if the patient is not already receiving them for edema. Heliox, a mixture of helium and oxygen, can also be used to decrease turbulent blood flow and ease symptoms of distress in patients with swollen airways.55
The tongue is large relative to the size of the oral cavity in young children. Upper airway obstruction may occur as the tongue falls back into the pharynx and the negative pressure of inspiration causes the airway to collapse. This is usually correctable by a simple jaw thrust. If this maneuver is successful, a nasopharyngeal tube can be placed. The tube stents the tongue forward and allows the airway to remain patent. Oral airways should be avoided as they may stimulate gagging, vomiting, or laryngospasm.