While we cannot provide an exhaustive delineation of management recommendations for all causes of intracranial hypertension, in this section we address some disease-specific recommendations for some of the causes most commonly encountered in a medical critical care setting, and not covered in other chapters of this textbook.
Hypertensive Encephalopathy and Eclampsia
Hypertensive encephalopathy occurs when the blood pressure is elevated beyond autoregulatory thresholds. This leads to an increase in extracellular water, predominantly by hydrostatic mechanisms. In addition, there can be variable degrees of parenchymal hemorrhage, most often localized in the end-arterial border zones along the frontal and posterior parietal convexities (see Fig. 65-9). This is an important reversible cause of brain swelling in which the extent of brain swelling does not necessarily correlate with neuronal injury. Blood pressure lowering is obviously the focus of treatment of the brain swelling with this disease. However, blood pressure lowering does not achieve immediate resolution of the cerebral edema. So, if the patient already has important intracranial hypertension and diminished intracranial compliance (an estimate guided by clinical and imaging parameters), ICP monitoring is necessary to guide the pace and degree of blood pressure lowering so as to not compromise cerebral perfusion. Any type of ICP monitor can be used, but most often global cerebral edema is associated with a loss of CSF spaces and compression of the ventricles. When that occurs, the ventricular catheters are more difficult to place, their readings are less consistently accurate, and they do not allow enough CSF removal to justify their higher risk. We find parenchymal monitors to be a more rational choice in these cases.
An unenhanced CT of the brain in a patient with the complications of hypertensive encephalopathy. The arrows are pointing to the end-arterial border zones with changes consistent with ischemic and hemorrhagic changes.
While the mechanism of brain swelling from eclampsia is similar but not exactly the same as hypertensive encephalopathy, the management of intracranial hypertension complicating eclampsia is generally the same. However, the management of eclampsia-associated intracranial hypertension has the added priority of urgent fetal delivery. The presence and suspected severity of intracranial hypertension should be considered when determining the method of delivery and anesthesia. Cesarean section is the preferred mode of delivery in almost all cases. Spinal anesthesia should be avoided due to the risk of precipitating central herniation with CSF drainage. General anesthesia should include close attention to the blood pressure to avoid degrees of lowering that could compromise cerebral perfusion. In general, successful management of intracranial hypertension is best guided with an ICP monitor, and easy and predominantly uncomplicated bedside placement of parenchymal monitors provides little justification for not using them.
Both hypertensive encephalopathy and eclampsia can be associated with ominous clinical presentations and imaging studies. Neither midposition unreactive pupils with extensor posturing nor CT changes suggestive of bilateral end-arterial border zone infarctions with hemorrhage should deter aggressive and optimistic management of such patients. In our experience, both scenarios can potentially lead to good outcomes when treated promptly and aggressively.
Fulminant Hepatic Failure
Cerebral edema complicates fulminant hepatic failure (FHF) in up to 50% of cases.58 Similarly to hypertensive encephalopathy and eclampsia, the brain swelling from FHF is global and usually symmetric (Fig. 65-10). Its etiology is thought to be predominantly glial swelling from intracellular glutamine accumulation, but a variety of other mechanisms have been shown to play a variable role in its development.59–62
Unenhanced CT of the brain of a patient with cerebral edema from fulminant hepatic failure. Note the attenuation of CFS spaces and the global nature of the swelling.
The development of brain swelling from FHF should be anticipated in all patients. Early detection of cerebral edema is imperative in order to pace its development and proactively manage its complications. However, bedside clinical evaluation does not allow its accurate detection due to the worsening hepatic encephalopathy concurrently developing in FHF patients. For example, stage IV encephalopathy patients frequently have diffuse hyperreflexia and increased motor tone with decerebrate posturing in the absence of any cerebral edema. It is not possible to differentiate uncomplicated hepatic encephalopathy from FHF-associated cerebral edema in patients with higher-stage encephalopathy. However, significant cerebral edema most often occurs in patients with higher-stage encephalopathy (III or IV). CT scans should be done in all patients with FHF, particularly those with stage III or IV encephalopathy, to rule out intracerebral hemorrhage and to estimate the presence and severity of cerebral edema. In our experience, patients in the early stages of cerebral edema have their CT scans misread as normal by inexperienced physicians. In addition, the presence of intracranial hypertension has been reported in FHF patients with normal CT scans.63,64
Once a patient drifts into the higher stages of encephalopathy with FHF, significant cerebral edema and cerebral hypoperfusion can be occurring and be undetectable in the absence of ICP monitoring. So an ICP monitor should be placed prior to stage IV encephalopathy in FHF patients. Often the frequent and severe coagulopathy observed in these patients justifiably demands thoughtful reflection on the risks and benefits of the intervention. However, in our experience, even with coagulopathy, bedside parenchymal monitors can be inserted without significant complications. We prefer to use a parenchymal monitor in the nondominant standard location. We insert it with the administration of 2 units of fresh frozen plasma (FFP) before, 1 unit of FFP during, and 2 units of FFP after the procedure. This should be carried out in collaboration with other caregivers, so invasive line insertions can be coordinated while the FFP infusions are being administered for ICP monitor insertion. Small pediatric patients require a different strategy to minimize bleeding during invasive procedures. While some neuroclinicians prefer to insert ventriculostomies in patients with potential intracranial hypertension (to allow CSF drainage as one therapeutic maneuver to treat plateaus in ICP), this modality carries a higher risk of hemorrhagic complications and the ventricles collapse (not allowing CSF drainage) in patients with consequential cerebral edema from FHF.
Once an ICP monitor is in place, management should focus on maintenance of adequate cerebral perfusion pressure. Given the likelihood of impaired autoregulation in FHF patients, extremes of blood pressure should be avoided. The patient's blood pressure should be maintained in the mid-normal range for the previously normotensive patient. In addition, normal intravascular volume should be maintained, and a state of readiness for acute response to any systemic hypotension is critical.
In patients with an elevation in ICP and poor intracranial compliance, ICP lowering may be necessary, particularly those with tenuous CPP (<60 mm Hg). Mannitol can be useful in some patients with FHF.65,66 It should mainly be considered in nonoliguric/anuric patients without significant hypernatremia. We generally use 0.25- to 0.5-g/kg aliquots of mannitol infused over a 20 to 30 minute period. The maintenance intravenous fluid should be isotonic with serum; normal saline is a good choice, with added 5% dextrose and/or potassium, depending on the specific clinical situation.
When using osmotic agents with FHF, the patient is already in quite a hyperosmolar state, so we do not titrate the mannitol to a specific serum osmolality. Rather, it is used intermittently to achieve the desired affect of improved intracranial compliance and ICP lowering. It may lose its effectiveness after several dosings, and so other therapeutic strategies should be considered concurrently. As is typical with the use of an osmotic diuretic, volume depletion can be an important complication with resultant hypotension. Maintaining euvolemia is ideal and requires thoughtful attention to fluid balance and intermittent replacement. Administration of hypotonic fluids such as 50% dextrose without electrolytes (commonly used in FHF in some settings) should be avoided.
Most patients with FHF will develop spontaneous hyperventilation, and this can be related to an increase in circulating free fatty acids and ammonia. While the institution of hyperventilation can be beneficial in lowering ICP acutely, it has no prolonged benefit in FHF as is true with most etiologies of cerebral edema and intracranial hypertension.67
Induced hypothermia can be a favorable strategy for both neuroprotection and deterring the development of cerebral edema, but further research is required to clarify its preventive role in this population. A recent study supported the promising role of moderate hypothermia for lowering ICP in patients with FHF.68 Seven consecutive FHF patients with intracranial hypertension refractory to osmotherapy and ultrafiltration were studied. Moderate hypothermia to 32° to 33°C was achieved with cooling blankets. The mean ICP before and after cooling was 45 mm Hg and 16 mm Hg, respectively. The mean CPP before and after cooling was 45 mm Hg and 70 mm Hg, respectively. The mean CBF before and after cooling was 103 mL/100 g per minute and 44 mL/100 g per minute, respectively.
We induce hypothermia in patients with refractory intracranial hypertension prior to significant cerebral hypoperfusion events. We strive for a body temperature of 32° to 34°C with the use of cooling blankets above and below the patient. Proactive strategies to allow early detection and treatment of fever should be an important part of the care plan for these patients, independent of whether hypothermia is used.
Like most other therapeutic strategies for ICP lowering in FHF, there have been few reliable clinical studies to guide the indications for and use of barbiturate therapy. It has been shown to have an impact on controlling ICP in Reye's syndrome.69 It probably would be best considered in patients with either refractory intracranial hypertension and/or those with oliguria or anuria. One study of 13 FHF patients with acute renal failure and refractory intracranial hypertension administered thiopental slowly to a maximum of 500 mg to achieve an ICP <20 mm Hg, CPP >50 mm Hg, or until hypotension developed.70 In each case, the ICP was reduced with the administration of anywhere between 185 and 500 mg (median = 250 mg) of thiopental over a 15-minute infusion period. In eight patients, a constant infusion was required (50 to 250 mg/h) to maintain adequate ICP and CPP. Given the small number of patients and unclearly defined end points, it is difficult to assess the true benefit of the ICP-lowering accomplishments of this strategy. However, unique to FHF, impaired barbiturate metabolism and clearance often precludes the need for a maintenance infusion after the desired effect is accomplished using a loading dose. See the section on treatment recommendations for the management of barbiturate coma elsewhere in this chapter.
Global Cerebral Hypoperfusion
The potential benefits of hypothermia on outcome in patients after cardiac arrest is beyond the scope of this chapter and is discussed in Chap. 16. However, when intracranial hypertension does occur as a result of global cerebral hypoperfusion it is a reflection of diffuse neuronal injury. As a result, when secondary intracranial hypertension occurs in this situation, it signals widespread injury and poor neurologic outcome. We strongly discourage aggressive management of this complication in these patients.
Large Supratentorial Hemispheric Infarctions
While large supratentorial cerebral hemispheric infarctions (LHI) are not common (accounting for less than 10% of all ischemic strokes), they are among the most disabling and deadly. As a result, physicians involved with the management of these patients must be equipped with a contemporary management strategy to minimize disability and mortality in patients in whom survival is desired as the appropriate medical care focus in keeping with the patient's life philosophy. LHI defines a group of patients with disabling strokes, variable degrees of collateral circulation, and brain swelling and life-threatening deterioration from brain herniations and intracranial hypertension.
In addition to the usual priorities of general systemic care (e.g., respiratory, cardiovascular, and nutritional), and general stroke care (e.g., blood sugar control, fever management, and deep vein thrombosis prophylaxis), patients who suffer a LHI should receive thoughtful application of medical treatments and monitoring for optimizing brain perfusion (or avoiding cerebral hypoperfusion), minimizing brain swelling, and limiting brain tissue shifts. There should be early discussion with the patient, family, and surrogate regarding the patient's life priorities as they may apply to practical life-and-death decision making and procedures in the context of the disabling stroke event; a strategic monitoring plan for early detection of deterioration and brain swelling; and engagement of other professionals necessary for the timely application of treatments necessary in the case of significant worsening (e.g., neurosurgeons).
There have been a variety of clinical predictors studied and identified to correlate with fatal outcome from LHI. Some of these factors include high National Institutes of Health Stroke Scale scores, early drowsiness, and early nausea and vomiting.71–75 The various identified prognostic factors are generally associated with larger infarctions, and not surprisingly, CT and magnetic resonance imaging (MRI) analyses have confirmed a correlation between infarction volume and outcome from supratentorial infarctions.76,77 While new evolving approaches to predicting brain swelling in patients with LHI are exciting, and our wisdom on their best application will evolve over time, at this point all acute patients with LHI should be considered at risk for severe, life-threatening deterioration. This is supported by the preliminary results of the recently completed HeADDFIRST study, a prospective randomized pilot clinical trial on LHI and surgical decompression. In that study, 65% of the registered patients with at least complete MCA territory infarction (based on acute clinical and CT imaging criteria) developed life-threatening brain swelling and tissue shifts (≥7 mm of anteroseptal shift or ≥4 mm of pineal shift from midline) within 96 hours of stroke onset.78
While patients with acute ischemic stroke are a heterogeneous group with variable baseline blood pressure and stroke mechanisms, those patients with LHI more likely have large-vessel narrowing or occlusion, autoregulatory dysfunction, and/or are vitally dependent on collateral circulation. At this point in our understanding, blood pressure lowering should only be done with great reluctance in patients with LHI, with clearly prioritized goals, thoughtful agent selection (to be discussed), and vigilant monitoring to avoid overtreatment. Depending on the extent of brain swelling and the degree of blood pressure lowering desired, it may be rational and appropriate to consider parenchymal ICP or CBF monitoring to avoid exacerbating regional cerebral hypoperfusion. In most cases, we recommend maintenance of the blood pressure at least in the high-normal range with LHI in order to maintain collateral perfusion, since cerebral edema progressively challenges this vital brain-preserving source of cerebral blood flow.
It has been shown that the majority of patients who deteriorate from LHI do not have important ICP elevations or cerebral hypoperfusion as an early contributing factor to their worsening.35 Their clinical deterioration is mainly due to BTD from evolving brain pressure differentials caused by regional cerebral edema (Fig. 65-11). Indiscriminant administration of mannitol or contralateral ventricular drain insertion and CSF drainage (the ipsilateral ventricle is usually collapsed) can lead to accentuation of the pressure differentials that drive BTD and augment the clinical worsening. However, early ICP elevation, when it does occur with LHI, stratifies the patient to higher risk of death from brain swelling, and younger patients are at higher risk for such early elevations.35,79 It has not been shown that ICP-focused management (whether or not under the guidance of ICP monitoring) improves the outcome in LHI patients, but it has not been well-studied with appropriate standardized medical treatment protocols. In fact, some of the more widely quoted studies on LHI with aggressive ICP lowering–focused treatment strategies report some of the most dismal outcomes for this disease.80,81
A schematic diagram demonstrating the concept of evolving pressure differentials with regional brain swelling from large supratentorial hemispheric infarction. Note that the clinical worsening in its early states correlates with brain tissue displacement.
We use ICP monitoring in young patients with LHI who already have shown evidence of significant regional brain swelling and compression of ipsilateral cerebrospinal fluid spaces. These patients have declining intracranial compliance and are at risk for ICP plateau waves. The presence of early ICP elevation in the young patient should put everyone on the alert for the escalating risk of death in that individual patient, and this can be factored into decisions regarding treatment escalation and the possible application and timing of surgical decompression. In addition, ICP monitoring in such patients may assist with strategies (positioning and medical) to improve intracranial compliance, and attempt to avoid catastrophic cerebral hypoperfusion during transport and various nursing maneuvers. When ICP monitoring is employed, we recommend using an ipsilateral (to the infarction) parenchymal monitor, since it will be the region of greatest ICP elevation. The ipsilateral placement is because the ICP will be maximal in the region of dominant brain swelling, and the ventricle ipsilateral to the infarction collapses as swelling progresses, with the various disadvantages mentioned earlier in this section.
When ICP is elevated, medical management alone carries a high mortality. However, with respect to ICP reduction, the application of conventional ICP-lowering strategies can be very helpful early in the course of management. These include: optimizing head and body positioning, avoidance of behaviors that elevate ICP in patients with poor cerebral compliance (fighting the ventilator, agitation, and seizures), tight fever control, hyperventilation, and the administration of mannitol. We rarely administer multidose regimens of mannitol in LHI patients, because its misapplication and overuse has hypothetical dangers in these patients. When ICP elevations are considered important to medically treat in patients with LHI, use of hypertonic saline can also be an effective strategy.
The theme of fluid management in patients with LHI should be avoidance of volume depletion. There is no role for dehydration as a management strategy to limit the development of brain edema. Isotonic fluids (0.9% saline) are generally recommended without clear scientific evidence for their unique advantage for patients with LHI. When patients have been exposed to hyperosomolar treatments, the use of only isotonic fluids is critical, as the hyperosmolar brain may be at risk for worsened cerebral edema when exposed to hypotonic fluids. There is some evidence of a possible benefit of albumin infusions in experimental animals with LHI from MCA occlusion, but this has not been widely applied in humans.82,83
The potential for surgical decompression as a method to limit infarct volume and mortality from brain swelling after stroke has been demonstrated in experimental animals and with more recently promising human work.78,81,84−86 Unfortunately, the selection of patients for this procedure and its best timing are still unclear; the decision making for this step requires a delicate balance between the patient's medical condition, the pace and anticipated severity of clinical progression, the prognosis, premorbid patient wishes, and various ethical and psychosocial issues.