Chapter 8: Intensive Care Unit (ICU) Management of Brain Tumors

This patient is clearly demonstrating clinical signs of herniation. The comatose examination with loss of airway protection requiring mechanical ventilation as well as the neurologic signs such as dilation and loss of reactivity of the right pupil and flexor posturing of the left arm/leg are strong indicators that the patient is suffering from right-sided brainstem compression. This constellation of neurologic signs is the most concerning issue in this patient's presentation and, as such, requires the most immediate attention from the treating physician.

A stat CT of the head (Figure 8-1) will demonstrate location of the mass, extent of midline shift, edema, hydrocephalus, lesional (with possible intraventricular) hemorrhage, and type of herniation. In this case, a large (5.5 × 5.6 × 5.7 cm), calcified, hyperdense mass is noted along the superior anterior falx associated with moderate surrounding edema and causing mass effect upon the right greater than left frontal horns. There is no associated hemorrhage or hydrocephalus. There is loss of sulcation indicative of elevated intracranial pressure (ICP), as well as acute infarcts in the bilateral occipital lobes, right greater than left, suggesting an ongoing process of transtentorial (uncal) herniation.

The immediate medical interventions are directed toward lowering the patient's elevated ICP. First, raising the head of the bed to at least 30 degrees will prevent cerebral venous outflow obstruction. Second, hyperventilating the patient to a goal Paco₂ of 25 to 30 mm Hg will provide transient lowering of ICP by inducing vasoconstriction of cerebral arteries and arterioles, which will lower cerebral blood volume (CBV). Third, administration of sedatives, analgesics, and potentially paralytic agents helps to control agitation and in particular cases, such as propofol (beginning at 10 mg/kg per minute), reduces CBV and slows cerebral metabolism, actions that contribute to lowering ICP.¹

The next major intervention is the use of hyperosmolar therapy, typically with continuous infusion of 3% hypertonic saline coupled with boluses of 23.4% hypertonic saline (in 30-mL pushes), along with standard mannitol administration (25% solution given at 0.25 to 1 g/kg). Such agents work by increasing serum osmolality, which brings water from the extracellular space into the serum, thereby reducing brain swelling. The goal serum osmolality is typically greater than 320 mOsm/L and the goal plasma sodium level in such a patient is typically 150 to 155 with sodium checks every 4 to 6 hours, as a sodium level above 155 has not been shown to be of proven clinical benefit.² The side effects of hyperosmolar therapy include electrolyte imbalances (eg, hypokalemia), pulmonary edema (resulting from rapid intravascular volume expansion), coagulopathy, and intravascular hemolysis.³ Despite the radiographic features of this lesion, which point to it being an extra-axial mass such as a meningioma, it is still causing significant vasogenic edema that should be treated with intravenous steroids. An immediate bolus of 10 mg IV dexamethasone (Decadron), followed by a maintenance dose of 8 to 32 mg/day, should be implemented.⁴ Dexamethasone works by reducing the permeability of the cerebral capillaries.

Given the recent seizure, which likely precipitated the herniation event (seizures transiently elevate ICP, likely from increasing cerebral blood flow [CBF]), the patient should be maintained on antiepileptic medication, either phenytoin (Dilantin) (following a 20-mg/kg loading dose) or Keppra (following a 1-g loading dose).

There is also a discussion to be had regarding insertion of an ICP monitor in this patient. Typically, for patients with clinical signs of elevated ICP and a Glasgow Coma Scale (GCS) score less than 8 warrant direct, invasive monitoring of ICP.⁵ Since this patient presented with a known intracranial mass causing elevated ICP, the indication for an ICP monitor is less cogent given that imminent surgery will remove the source of the elevated ICP. If the patient were to be stabilized and supported for an extended period of time, for example, in the case of an unresectable lesion or in the obvious case of traumatic brain injury, then the utility of an ICP monitor becomes clear. In this case, therefore, an ICP monitor was not inserted immediately given the plan for urgent operative decompression.

The initial interventions in this patient are directed at lowering ICP. But these interventions only solve part of the problem: edema and seizures as contributors to the herniation syndrome. Clearly, the next step needs to be aimed at expeditious resection of the intracranial mass lesion. Once the patient is stabilized, magnetic resonance imaging (MRI) of the brain with and without contrast must be performed to better characterize the lesion in terms of location, type, and precise anatomic relationships to surrounding structures including associated vasculature. This study will also aid in the decision of whether preoperative embolization is necessary, since this is likely a well-vascularized meningioma.

MRI of the brain was performed with magnetic resonance angiography (MRA) of the head and neck (Figure 8-2), revealing a 5.6 cm × 7.1 cm × 4.9 cm heterogeneously enhancing anterior falcine mass with evidence of internal necrosis and significant surrounding vasogenic edema and mass effect, which is consistent with a large parafalcine meningioma. The effacement of right greater than left frontal horns is again demonstrated. There is also diffusion-weighted imaging (DWI) restriction in bilateral medial temporal and occipital lobes suggestive of an acute infarct from bilateral posterior cerebral artery (PCA) compression during the recent herniation event (Figure 8-3).

At this point, the decision of preoperative embolization must be addressed. The major risk of embolization in a tumor of this size (which has very recently caused significant herniation) is causing a hemorrhagic or ischemic insult; both hemorrhage and ischemia may occur in the intratumoral or peritumoral region, either of which could precipitate another herniation event.^6,7 There are no strict guidelines for making this decision, and therefore it is left to the cerebral angiographer and the neurosurgeon to decide on its safety and utility. The benefit of embolization is to minimize blood loss during the operation by injecting small particles (typically polyvinyl alcohol [PVA]) into major extracranial feeding vessels. In this case, the decision was made to forego embolization in favor of urgent open resection in the operating room.

The patient underwent a bicoronal craniotomy for resection of a parafalcine meningioma. The operation proceeded uneventfully; of note, the superior sagittal sinus was sacrificed as it was invaded with tumor and did not appear to be patent. A gross total resection was achieved, and the patient returned to the ICU for postoperative management.

The patient returned to the ICU ventilated, maintained on 3% hypertonic saline infusion, IV Decadron, and IV Dilantin. A postoperative CT scan was performed that showed complete removal of the meningioma but relatively significant residual edema. Now that the main source of the patient's elevated ICP has been removed, it is appropriate to begin weaning the hypertonic saline while keeping in mind that there is moderate to severe remaining edema. This must be done in slow, stepwise fashion to avoid rebound cerebral edema that could potentially incite another herniation event and with regular every 4- to 6-hour sodium checks.⁸ Begin with decreasing the rate of the 3% hypertonic saline with the goal of keeping the sodium within 10 mEq of the plateau level within the first 24 hours. The following step is to switch from the 3% to 2% hypertonic saline, again with the goal of keeping the patient's sodium level above 140 over the next 24-hour window. After a minimum of 48 hours' postsurgery, it becomes possible to switch the patient to a normal saline infusion with the goal sodium in the normal range (135 to 145) for the remainder of the ICU stay.

The Decadron can be tapered off over a 2-week period, given the severity of the edema and the fact that this is a benign extra-axial lesion, while the patient should be maintained on a steady level of Dilantin for a minimum of 1 month and potentially for 3 to 6 months given that she presented with seizures.⁹ There is also the option of transitioning the patient to Keppra from Dilantin in favor of a more benign side-effect profile at the discretion of the treating neurologist.¹⁰ Ventilatory weaning and other intensive care interventions are left to the judgment of the critical care neurologist.

Given the size and location of this malignant-appearing mass lesion, it comes as no surprise that this patient presented with a clinical herniation syndrome. Moreover, as is clear on the CT scan, another alarming radiographic feature of this lesion is its associated edema. In fact, the herniation event was most likely due to the edema and not to the mass itself, as evidenced by the patient's neurologic improvement from hyperosmolar therapy and the large IV corticosteroid bolus. There is also the possibility that the mass induced a seizure that transiently elevated her ICP, thereby precipitating the herniation episode.

So the question is whether this patient needs to undergo emergent operative decompression of this lesion or whether a delay is permissible in order to allow the steroids to take effect in terms of treating the edema. Such a brief delay would also allow for other interventions and studies to be pursued. With the observed neurologic improvement, the decision made in this case was to delay surgery. This was done at the risk of having the patient seize and perhaps transiently herniate again, as well as at the risk of developing intratumoral hemorrhage that could replicate the cascade of events that brought the patient to the ER in the first place. By delaying the surgery for 24 to 48 hours, important interventions were either initiated or continued: an MRI with gadolinium contrast was obtained; continuous electroencephalographic (cEEG) monitoring was begun to determine if the patient required more maintenance Dilantin or a second antiepileptic agent based on the presence or absence of seizure activity; hypertonic therapy in the form of 3% saline was infused with a goal sodium level of at least 145; and IV Decadron was continued at a dose of 10 mg every 4 hours. With the more reliable neurologic examination to follow, it was considered unnecessary at this point to insert an ICP monitor.

The contrast MRI allowed for better operative planning, especially because the noncontrast CT scan was somewhat difficult to interpret in this patient in terms of tumor origin. The MRI revealed that the tumor likely arose from the inferior left parietal lobe (Figure 8-5); there was also a better quantification of the edema along with a more detailed assessment of the degree of necrosis and proximity to important vasculature. All of this pointed to this tumor being a high-grade malignant lesion, likely a glioblastoma multiforme (GBM). In addition to the MRI, the cEEG did not reveal any epileptiform activity, while the patient's sodium level rose in response to the hypertonic saline infusion.

It is also important to note the surgical delay theoretically reduces the risk of intraoperative bleeding complications since the edema is given a chance to resolve with steroid therapy. An emergent operation on a very swollen brain that is actively herniating carries with it the risk of inducing significant bleeding as well as making the surgical resection of such a lesion more technically challenging when faced with such friable tissue. Therefore, surgery was performed in a 24- to 48-hour window following the acute herniation event, and in this case proceeded uneventfully. This delay is weighed against the risk of an intratumoral hemorrhage developing that could precipitate another, perhaps more devastating, herniation event. Such an intratumoral hemorrhage would need to be treated with urgent surgical decompression once the patient is medically stable. For this patient, the postoperative concerns and goals were essentially identical to those described in the aforementioned first case.

Hydrocephalus is the most concerning issue in this patient. Intracranial mass lesions located in the posterior fossa as well as in the pineal region and third ventricle are prone to causing hydrocephalus due to obstruction of cerebrospinal fluid (CSF) outflow. In cases of hydrocephalus, there is a spectrum of clinical severity, ranging from mild headache to more severe headache with vomiting (as in this patient) to significant obtundation, loss of airway protection, and other signs of impending herniation. In this latter, more emergent scenario, the hydrocephalus must be treated immediately and can nearly always be controlled through placement of an external ventricular drain. This allows for external drainage of CSF prior to addressing the obstructive mass lesion.

In this case, ventricular drainage was considered unnecessary in light of the patient's clinical status (awake, interactive, orienting). Even in patients who demonstrate long-standing symptoms consistent with chronic hydrocephalus, they can present with an acute decline that may need to be treated with ventricular drainage.

MRI with and without contrast is the standard imaging study for all mass lesions of the posterior fossa. The MRI characteristics of the lesion in this case were most consistent with hemangioblastoma, a benign well-vascularized central nervous system (CNS) tumor arising from stromal cells of small blood vessels and typically located in the cerebellum, brainstem, and spinal cord. In fact, 8% to 12% of all posterior fossa tumors are hemangioblastomas, although it accounts for only 1.0% to 2.5% of all intracranial mass lesions. It is commonly associated with Von Hippel–Lindau (VHL) disease (approximately 25% of all hemangioblastomas). As seen in the MRI here (Figure 8-7), the mass is avidly contrast enhancing with a characteristic mural nodule and a cystic core. There is also associated edema, and along with the hydrocephalus and headaches, it was considered prudent to start Decadron.

Since the MRI characteristics of this mass were very suggestive of hemangioblastoma, additional workup was conducted including ophthalmologic evaluation for retinal lesions (commonly found in VHL patients), a total spine MRI with and without contrast to search for spinal cord hemangioblastomas (may be performed postsurgery), and vanillylmandelic acid (VMA) and metanephrine levels (elevated with pheochromocytoma, which is also associated with VHL). Determining the presence of a pheochromocytoma preoperatively is a critical step given the anesthetic risks associated with this tumor; for example, hypertensive crisis and tachycardia from catecholamine release during anesthesia induction.¹¹ This patient had no retinal lesions, but was ultimately diagnosed with VHL; he also had a pheochromocytoma (elevated urine and plasma metanephrines coupled with an adrenal mass diagnosed on abdominal CT) and a T12-enhancing lesion suspicious for a spinal cord hemangioblastoma. In this circumstance, it is prudent to have an endocrinologist formally evaluate the patient and advise on preoperative and postoperative blood pressure management as well as alerting the anesthesia team to the presence of a pheochromocytoma. The endocrinologist is then in a position to follow the patient long-term once the surgery is finished.

There is also the question of preoperative angiography and embolization. Cerebellar hemangioblastomas are well-vascularized lesions that are occasionally embolized preoperatively in an effort to control intraoperative blood loss. Reports vary in terms of preoperative embolization success—more recent studies point to a high enough postembolization risk of hemorrhage such that embolization is not routinely recommended.¹²

As noted earlier, there is no need to manage the hydrocephalus in this case in an urgent fashion. Therefore, the issue is how to manage the hydrocephalus both during and following the operation. In this case, the goal is obtain control of CSF drainage prior to operative decompression via a retrosigmoid suboccipital craniotomy approach. This will prevent cerebellar herniation through the dural opening made by the neurosurgeon while approaching the mass. Two interventions were made prior to the planned craniotomy: (1) an endoscopic third ventriculostomy (ETV) and (2) placement of a right frontal external ventricular drain (EVD). The ETV provides both short- and long-term control of hydrocephalus—by creating a new passage through the floor of the third ventricle into the prepontine cistern, the level of the obstruction caused by the hemangioblastoma (at the fourth ventricle) is essentially bypassed, allowing for CSF outflow and absorption to approach normal parameters (Figure 8-8). The EVD will provide continuous intraoperative control of CSF outflow and then will remain in place postoperatively to control the hydrocephalus while the patient recovers from the resection.

The hydrocephalus is expected to resolve following resection of the obstructive mass lesion, but it will not improve rapidly. Postoperative swelling will slow resolution of hydrocephalus, thus the EVD serves three functions in the recovery period: (1) ICP monitoring, (2) CSF drainage for control of hydrocephalus, and (3) CSF drainage to prevent leakage through the incision site and, therefore, to promote wound healing. The level at which the EVD is set is determined by the neurosurgeon; in this situation, the typical level is 10 cm H₂O above the external auditory meatus. Over the next few days, the EVD should be progressively raised above the 10–cm H₂O level, while the patient's symptoms (mainly headache, but also level of arousal), ICP readings, and wound must be assessed to determine whether the EVD wean is being tolerated. Exacerbation of headache, persistently elevated ICPs (typically above 20 is cause for concern), and leakage from the incision are indications that the drain wean is not being tolerated and that the patient still requires additional CSF drainage.

Noncontrast head CT scans should also be intermittently performed to evaluate the patency of the fourth ventricle and the overall radiographic picture of hydrocephalus prior to planned bedside removal of the EVD. Although it is preferable to remove the EVD when the fourth ventricle appears patent on noncontrast head CT scan, the fact that an ETV was also performed here does not make a patent fourth ventricle an absolute requirement for drain removal. In those cases where an ETV is not performed, radiographic patency of the fourth ventricle is advisable prior to EVD removal (Figure 8-9). Once the EVD is removed, the patient is ready for discharge from the NICU to a floor bed.

As is customary with lesions of the posterior fossa, a 2-week Decadron taper is prescribed immediately following the operation. There is no indication for antiepileptic therapy since tumors in this region are not associated with seizure formation. A postoperative MRI with and without contrast is typically done within 72 hours of the surgery to limit the artifact from normal postoperative changes. This study will provide a radiographic determination of the extent of resection, and it will also provide a clear image of the fourth ventricle and its patency. As mentioned earlier, an MRI of the total spine with and without contrast to look for spinal cord hemangioblastomas can also be performed in the postoperative period and can conveniently be scheduled to coincide with the routine postoperative MRI of the brain.

Pituitary apoplexy refers to a condition in which either hemorrhage or infarction of a pituitary tumor leads to the following clinical symptoms: abrupt-onset headache, visual changes (diplopia, loss of visual acuity, restriction of visual fields), nausea, vomiting, vertigo, and/or a decreased level of arousal.¹³ The type of lesion most commonly associated with this condition is a pituitary adenoma, which makes up approximately 10% of all intracranial tumors. According to various studies, pituitary apoplexy arises in about 2% to 7% of all pituitary adenomas.¹⁴ In fact, although adenomas make up only 10% of intracranial neoplasms, they give rise to 25% of tumor-associated hemorrhages.¹³ An essential element of the definition of pituitary apoplexy is acuity: patients seek urgent medical attention for the abrupt onset of the symptoms described above. Importantly, these symptoms are due to an acutely enlarging mass in the sellar, parasellar, and/or suprasellar compartments.¹⁵ The tumor expands because of edema from infarction or from the mass effect from hemorrhage into the tumor. Although it is an uncommon condition, prompt diagnosis of pituitary apoplexy is critical given the possibility that initial visual changes may progress to permanent visual deficits if not addressed by early surgery. In this case, the symptoms and neurologic findings were concerning enough to warrant urgent noncontrast head CT in the ED, which in turn located the pituitary mass. Oftentimes, the clinical picture of pituitary apoplexy mimics that of a ruptured intracranial aneurysm (as they both share headache and oculomotor palsies in their respective presentations), and so a head CT is a logical and important step in the evaluation of this symptomatology. Once the pituitary mass is identified on CT with associated hemorrhage, this activates a cascade of further steps as detailed below.

One of the initial concerns when a patient is diagnosed with pituitary apoplexy is the possibility of an adrenal crisis; the majority of these patients present with panhypopituitarism.¹⁵ Therefore, the recommendation is to immediately administer 100 mg of IV hydrocortisone, followed by 100 mg IV hydrocortisone every 6 to 8 hours leading up to surgery.^13,16 As part of the endocrinologic workup, the patient should have blood sent for levels of all the relevant hormones (prolactin, growth hormone [GH], insulinlike growth factor 1 [IGF1], thyroid-stimulating hormone [TSH], adrenocorticotropic hormone [ACTH], luteinizing hormone [LH], follicle-stimulating hormone [FSH], free thyroxine [T₄], free triiodothyronine [T₃], and serum cortisol). Patients may also present with electrolyte disturbances such as hyponatremia (likely due to cortisol deficiency), so electrolytes must be monitored and managed accordingly by the NICU team. ICU management must also pay close attention to ophthalmologic, endocrine, and neurologic function while the patient awaits surgical intervention.

Beyond medical treatment and evaluation, the CT scan must be assessed for evidence of hydrocephalus. Some patients (not the one included here) present with a decreased level of consciousness and have evidence of hydrocephalus and/or ventricular hemorrhage. These patients must be considered for urgent EVD placement prior to or at the time of surgery.

In addition to the medical and procedural interventions described above, it is recommended that an MRI with and without contrast, including a dedicated pituitary protocol, be obtained prior to operative intervention. CT scan will detect hemorrhage and/or infarct anywhere from 20% to 30% of the time, while MRI will identify these features in pituitary tumors in more than 90% of cases (Figure 8-11).¹³ Prior studies have established that contrasted MRI reveals evidence of hemorrhage, mainly as high- signal intensity on T1-weighted images; low- and high-signal intensity on T2-weighted images suggestive of old and recent hemorrhages; and various patterns of peripheral and heterogeneous tumoral enhancement on T1 sequences with gadolinium (with the nonenhanced areas suggestive of infarcted or necrotic tissue).¹⁷ A recent study demonstrates that the additional MRI sequences, DWI and apparent diffusion coefficient (ADC) can help to identify areas of tumor infarction.¹⁸ Moreover, and more importantly for the operating neurosurgeon, this study will provide significantly greater anatomic detail and, therefore, aid in surgical planning. It is possible that the lesion will require a craniotomy either in addition to or instead of the customary transsphenoidal approach, depending on location and extension of the hemorrhage among other factors.¹³

Based on the severity and acuity of this patient's symptoms, urgent surgical decompression of the hemorrhagic pituitary mass is indicated. In any patient who presents with worsening visual acuity, expanding visual field deficits, declining level of arousal, or deteriorating oculomotor function, surgery is the recommended intervention.^13,19,20 Conservative management runs the risk of allowing the symptoms to worsen and perhaps become permanent since the processes of edema and ongoing bleeding may be at work. The decision to proceed with surgery, therefore, is based on the patient's symptoms once radiographic evidence of pituitary apoplexy has been established.

In the majority of cases, the transsphenoidal approach is adequate for tumor removal. As mentioned above, extension of hemorrhage to a hemisphere or a poorly aerated sphenoid sinus might prompt a craniotomy.¹³ The transsphenoidal approach will permit decompression of the optic chiasm and the surrounding neural elements including the cranial nerves passing within the cavernous sinus. Recovery of oculomotor function occurs more often and more completely than improvement in visual fields and visual acuity, although expeditious removal has a very high success rate of restoring all of these functions.¹⁹ Tumor removal may also help reestablish normal endocrine function by decompressing the functional pituitary gland.^13,14

The timing of expeditious surgery varies according to different reports. Studies show that improvement in neurologic and endocrine function is achieved if surgery is performed anywhere from 48 hours to 1 week after symptom onset.^13-15,19 There are even studies that show significant improvement in oculomotor function and mild, but quantifiable, improvement in visual acuity and visual fields after 2 to 3 weeks and in one case up to 2 months.²¹

The patient should be monitored for diabetes insipidus (DI), which occurs in a small percentage of patients (2% to 3%) with pituitary apoplexy who undergo urgent surgery.¹³ Sodium levels should be checked every 6 hours, while urine output should be monitored on an every-2-hour basis with accompanying specific gravities measured by urinalysis or urine dipstick. In general, if the urine output exceeds 250 mL per hour for two consecutive hours and is accompanied by a specific gravity of less than 1.005, the patient should be administered DDAVP (1-deamino-8-d-arginine vasopressin) by either intranasal dosing (10 μg), subcutaneous dosing (typically one-tenth the intranasal dose), or oral dosing (from 0.1 to 0.2 mg three times a day). An endocrinologist should be involved in the long-term management of this patient's hormonal issues, and it is reasonable to have such a specialist involved in the immediate postoperative management of this patient.

If the patient had hydrocephalus requiring EVD placement, this EVD should be rapidly weaned postoperatively based on the patient's neurologic status and the ICP readings. Progressive elevation of the drain by 5 to 10 cm H₂O per day from a likely initial level of 10 cm H₂O above the external auditory meatus (EAM) is a reasonable strategy given that surgical removal of the mass will allow for improved CSF outflow. If the hydrocephalus is secondary to ventricular hemorrhage, the patient may not tolerate a rapid wean, and so the goals must be titrated to the patient's symptoms (headache, level of arousal), ICP values, and interval CT scans to evaluate ventricular size. If the patient continues to fail attempts at raising and/or clamping the EVD, then placement of a ventriculoperitoneal shunt (VPS), although rare in cases of pituitary apoplexy, is likely.¹⁵

Outside of persistent hydrocephalus requiring EVD, even patients in active DI are typically stable enough to be managed on the floor. The goal is to transfer the apoplectic patient out of the NICU on the first postoperative day.

Due to the patient's distant history of lung cancer and the sudden-onset presentation of his symptoms, the guiding thought in the management of this case is that these hemorrhagic lesions represent brain metastases of his lung cancer. In addition to lung cancer (bronchogenic carcinoma), other primary cancers commonly associated with a hemorrhagic presentation include melanoma, renal cell and thyroid carcinoma, and choriocarcinoma.²² Lung cancer, as the most common hemorrhagic metastasis to the brain and among the most likely to present with multiple lesions, fits in with this patient's history and presentation. It is, therefore, important to immediately implement the medical therapies associated with treating metastatic lesions: corticosteroids (typically Decadron) and anticonvulsants. A 10-mg bolus of IV Decadron, followed by maintenance dosing of around the same dose two to four times per day (typically dosed anywhere from 2 mg every 6 hours to 10 mg every 6 hours depending on the severity of the edema), is a well-accepted dosing range as noted in prior cases.²³ In this patient, the combination of vasogenic edema surrounding the left frontal lesion and its associated mass effect makes corticosteroid administration an important initial step.

In terms of anticonvulsants, the recommendations are less clear. In patients who present with a seizure (unlike the patient described here), administration of anticonvulsants is advised. For patients who first present with cerebral metastases in the absence of a clear seizure, prophylactic administration of anticonvulsants is actually not recommended. These medications have failed to demonstrate efficacy in preventing first seizures; they are often subtherapeutic when their plasma levels are measured; and the side-effect profile appears to be more profound in patients with brain tumors as opposed to those patients in the general population. This latter issue is in part due to the fact that many anticonvulsants, including the commonly utilized Dilantin, stimulate the cytochrome P450 system, which increases metabolism of corticosteroids and certain chemotherapeutic agents.²⁴ However, in the case of patients with multiple metastases and/or hemorrhagic metastases (both of which apply to our patient here), the efficacy of prophylactic anticonvulsants is less clear as these situations have not been systematically studied. Certainly, these patients are at higher risk for developing seizures and as such would seem to benefit from prophylactic administration of these medications.⁵ In the end, it is left up to clinician preference, and in the case here, IV Dilantin was bolused (20 mg/kg) and then maintained at 100 mg IV every 8 hours. IV Keppra is also an option at a bolus dose of 1 g followed by 500 mg to 1 g every 12 hours as a maintenance regimen.

While these medications are administered, the patient should also undergo routine laboratory tests, including a complete blood count and coagulation profile. The patient should be evaluated for thrombocytopenia and elevated coagulation parameters given the presence of intracerebral hemorrhage. If either of these laboratory values prove abnormal, it is likely that they are contributing to the current condition and as such should be treated (thrombocytopenia through platelet administration, elevated International Ratio [INR] with fresh-frozen plasma [FFP] administration and possibly vitamin K for longer-term correction).

The question of blood pressure control should also be raised. In this case, the neurointensivist is functioning under the principle that this patient has multiple hemorrhagic metastases that have bled. In other situations, a patient may have multiple intracranial hemorrhages (ICHs) from cerebral amyloid angiopathy (CAA) or from hypertension, among the more likely etiologies. In these alternative cases, blood pressure control is necessary. In our patient, and in all patients with hemorrhagic cerebral metastases, there is no standard recommendation for blood pressure control. A guideline that may be applied here is to keep the systolic blood pressure (SBP) less than 140 mm Hg, which is the guideline typically used for postoperative patients and in patients with a presumed hypertensive ICH.

After the patient is transferred from the admitting facility to the tertiary-level NICU, it is recommended to repeat a noncontrast head CT to determine whether there is more midline shift or hemorrhage in the newly diagnosed metastatic lesions. In this case, the repeat head CT was read as unchanged compared to the prior CT obtained 6 hours earlier. Once the patient is considered stable for a longer imaging study, it is recommended to obtain an MRI with and without contrast with an MRA of the head and neck. The MRA will help to evaluate for a vascular malformation, such as an arteriovenous malformation (AVM), but is of less utility than the standard MRI with and without contrast, which can identify AVMs, cavernous malformations, and dural AV fistulas independent of an MRA sequence. In this case, an MRI with or without contrast may reveal an enhancing nodule adjacent to hemorrhage suggestive of an underlying neoplastic lesion. On gradient-echo sequencing, the MRI may also show heterogeneous signal changes within the lesion suggestive of hemorrhages of multiple ages; T2-weighted sequences may show a surrounding hypointense hemosiderin ring with increased peripheral signal suggestive of edema. Although MRI is quite often limited by the hemorrhage in identifying an underlying neoplastic growth, these findings point to metastasis as a likely diagnosis. Moreover, mass effect and edema out of proportion to what one would expect from an acute hematoma is a fundamental indicator of an underlying neoplastic process.²⁵ It is important to note any evidence of dural enhancement, which may represent meningeal seeding and carries a worse prognosis. This finding could impact the surgical management of the patient, perhaps leading to more palliative measures.

In this case, the patient underwent MRI, revealing vague ring enhancement of both left frontal lesions with central necrosis and hemorrhage; right thalamic lesion with hemorrhage and minimal ring enhancement; and a newly identified right occipital lesion with a heterogeneous enhancement pattern that was not seen on CT (Figure 8-13). The enhancement pattern of these three lesions is very suggestive of a metastatic process.

Additionally, the patient should undergo a CT with and without contrast of the chest, abdomen, and pelvis as part of a metastatic workup. Although the patient here has a remote history of lung cancer, it is important to establish whether there is diffuse multiorgan involvement of these metastases. Such a finding may factor into the overall prognosis for the patient and, therefore, may impact the decision among the neurosurgeon, neurointensivist, oncologist, and the patient's family regarding aggressive surgical intervention.

In this situation where a patient has presented with multiple hemorrhagic metastases, the idea is to treat the lesion(s) that is causing the neurologic symptoms. The patient's clinical presentation, including dysarthria and disorientation, indicates that the twin left frontal lesions are to blame. The radiographic characteristics of these lesions are suggestive as well: the size (the anterior lesion is approximately 5 × 4 cm, the mid-frontal lesion is 4 × 3 cm), location (likely involving Broca's area through edematous extension and focal compression), and mass effect all point to the left frontal complex as the appropriate target for surgical intervention. Accordingly, the patient underwent a large left frontal craniotomy to allow for resection of both hemorrhagic left frontal lesions, and the surgery proceeded without incident. Subsequently, and typically beginning 1 to 2 weeks postoperatively, the patient underwent a chemotherapeutic regimen with whole-brain radiation (WBRT) under the care of a neurooncologist.

As mentioned above, postoperative systolic blood pressure control is of paramount concern in this patient given the existence of acute hemorrhage in his nonsurgically treated lesions. Also, the extent of the craniotomy and the size of the resected lesions increase the risk of postoperative hemorrhage. Therefore, strict SBP control between 90 and 140 mm Hg, coupled with a low threshold for urgent noncontrast head CT in the event of a neurologic change, are the necessary guidelines. Antiepileptic medications should be continued for at least a week, and probably maintained for a month if the patient remains seizure-free, although the recommendations remain vague. Decadron should be progressively tapered from a 10-mg oral dose every 6 hours for the first 24 hours down to 2 mg orally every 6 hours for the duration of WBRT (the duration of the taper typically extends well beyond the patient's stay in the ICU). The patient should remain in the NICU for at least 24 hours following surgery and then be discharged to the floor if no untoward events arise.

There are two important time points here: (1) within a reasonable postoperative window, the patient was noted to return to her neurologic baseline and (2) a few hours beyond this initial time point, the patient was noted to have deteriorated to a neurologic state worse than her preoperative condition. This is suggestive of an active process, which could include the interval development of a hematoma, stroke or a new-onset seizure. The first step in evaluating a neurologic change in a postoperative tumor patient is to obtain an urgent noncontrast head CT. In this case, the CT revealed a sizable hemorrhage in the resection cavity with intraventricular extension (Figure 8-15). The presence of this hematoma and the patient's clinical decline warrants urgent surgical intervention for evacuation of the clot. Thus, the patient was taken back to the operating room for a reoperation and the hematoma was evacuated. A second postoperative CT revealed complete removal of the hematoma and interval resolution of the intraventricular hemorrhage (IVH) (see Figure 8-15). Following this second operation, the patient gradually returned to her preoperative neurologic baseline over the span of 2 to 4 hours.

It is important for neurointensivists to be cognizant of postoperative tumor patients who are at a higher risk for bleeding complications. This patient underwent a subtotal resection given the size and contralateral extent of the tumor. With residual tumor, there is great difficulty in achieving tumor bed hemostasis even when intraoperative coagulation strategies are rigorously employed, as was done in this case. It therefore behooves the neurointensivist to query the operating neurosurgeon regarding the extent of resection, the intraoperative blood loss, the friability of the tumor tissue, and the possible sacrifice of any important arteries or veins (distal middle cerebral artery [MCA] branch, superior sagittal sinus). All of these intraoperative issues can result in postoperative hemorrhage, as in the case presented here, or in postoperative stroke. Awareness of these issues will allow the neurointensivist to act swiftly and decisively in such cases.

The patient's clinical symptoms are suggestive of hydrocephalus and the CT scan confirms this diagnosis. Retraction injury of the cerebellum during surgery can cause delayed swelling, which is very similar to the process of an ischemic stroke. The swelling may take a few days before it causes significant compression of the fourth ventricle, thereby causing an obstructive hydrocephalus. Posterior fossa surgery very often involves cerebellar retraction and, in certain approaches, involves sacrifice of some cerebellar veins.²⁶ The resulting edema can be significant enough to cause obstruction at the level of the fourth ventricle, leading to hydrocephalus as was seen in this case. Untreated hydrocephalus will progress to herniation and death, and so identification of this situation constitutes a clinical emergency.

This patient should be immediately transferred to the NICU for placement of an EVD. Beyond the lifesaving intervention of the EVD, it is also recommended to increase the patient's Decadron dosage to help combat postoperative edema; hypertonic saline is also an additional option (as is mannitol), with a goal sodium level greater than 140 (or serum osmolality greater than 320 in the case of mannitol). In this case, the patient's Decadron was increased from 6 mg orally every 6 hours to 10 mg orally every 6 hours, and 2% hypertonic saline was begun at an infusion of 75 mL per hour. Following EVD placement, the patient's level of arousal improved significantly. The EVD was maintained at 20 cm H₂O above the EAM for 2 to 3 days while the patient was weaned back to a Decadron dose of 6 mg every 6 hours and transitioned from 2% hypertonic saline to normal saline. The specific weaning parameters were the same as those utilized in an earlier case presented above. When a follow-up noncontrast head CT demonstrated adequate resolution of the cerebellar swelling and a patent fourth ventricle (Figure 8-17), the EVD was removed and the patient was considered ready for transfer to the floor. Since the EVD was kept at a high level above the EAM, weaning was not considered necessary in this case.

It is critical that the neurointensivist maintain awareness of postoperative tumor patients who have undergone approaches to the posterior fossa and the possibility of retraction injury giving rise to obstructive hydrocephalus. Although this complication may take days to unfold, more severe types of this injury and instances where a major stroke is induced may lead to earlier onset of hydrocephalus and its associated symptoms. Again, the threshold for a noncontrast head CT should be low, and the use of corticosteroids and hypertonic agents represent the key elements in the neurointensivist's armamentarium.