Whenever a sustained ICP elevation of 20 mm Hg or more occurs, the clinician should consider (or reconsider) surgical decompression. A CT scan should be considered, and if increased mass effect or CSF volume is detected, surgical intervention such as CSF drainage, mass evacuation, or hemicraniectomy may be performed.
By opening the cranial vault, hemicraniectomy can reverse brain tissue displacement and herniation, and effectively improve and usually normalize ICP. Hemicraniectomy is increasingly being used as a final salvage therapy for patients with malignant middle cerebral artery area infarction and other space-occupying mass lesions. It is considered as a definitive therapeutic option as an alternative to instituting barbiturate therapy or mild-to-moderate hypothermia. Several studies have found that hemicraniectomy definitely improves survival after malignant middle cerebral artery (MCA) infarction.14 A meta-analysis of hemicraniectomy for MCA infarction found that survival with a good functional outcome is most likely among younger patients.15
Agitation must be avoided because it can aggravate ICP elevation through straining (increasing thoracic, jugular venous, and systemic blood pressure) and increased CMRo2. During an ICP spike, sedation must be maximized and may be all that is necessary to control the ICP. For this reason, adequate sedation must be the first pharmacologic intervention in managing ICP crisis. The preferred regimen is the combination of a short-acting opioid such as fentanyl (1 to 3 μg/kg per hour) or remifentanil (0.03 to 0.25 μg/kg per minute) to provide analgesia and propofol (0.3 to 3 mg/kg per hour) because of its extremely short half-life (despite its well-known side effect of systemic hypotension), which makes it ideal for periodic interruption for neurologic assessments. Bolus injections of opioids, however, should be used with caution in patients with elevated ICP because they can transiently lower MAP and increase ICP due to autoregulatory vasodilation of cerebral vessels.16 Compared to an opioid-based sedation regimen, in one trial propofol was associated with lower ICP and fewer ICP interventions in patients with severe TBI.17
After adequate sedation, if ICP remains elevated, attention should be directed to optimizing CPP. CPP low enough to induce ischemia can trigger reflex vasodilation and aggravate ICP elevation. Conversely, a high CPP (greater than 110 mm Hg) can sometimes cause breakthrough cerebral edema and also potentially elevate ICP. For these reasons, in general, CPP should be maintained between 60 and 110 mm Hg. Appropriate vasopressors to raise blood pressure and CPP include phenylephrine (2 to 10 μg/kg per minute), dopamine (5 to 30 μg/kg per minute), or norepinephrine (0.01 to 0.6 μg/kg per minute). Useful agents to lower blood pressure and CPP include labetalol (5 to 150 mg per hour) and nicardipine (5 to 15 mg per hour); nitroprusside should be avoided because of its dilating effects on all cerebral vasculature, which may exacerbate the ICP. Sodium nitroprusside is also difficult to titrate compared to other agents.
Numerous studies have attempted to define optimal CPP management in acute TBI, with various conclusions. In recent years, two distinct approaches have developed with differing views on whether CPP should be maintained at a higher or lower level. The high-CPP approach, popularized by Rosner et al, focuses on pharmacologic means to elevate MAP and CPP in order to maintain adequate CBF.18,19 Support for this method comes from case series demonstrating good clinical outcomes and higher brain tissue oxygen levels with this management approach, and clinical examples demonstrating that induced hypertension can lead to the termination of plateau waves, presumably by causing reflex vasoconstriction.20 The main argument against the high-CPP approach comes from a randomized trial by Robertson et al that found no clinical benefit with CPP-targeted therapy (CPP greater than 70 mm Hg) compared with traditional ICP-targeted therapy (CPP greater than 50 mm Hg). In this study, the high-CPP approach led to fewer jugular venous desaturations, but a fivefold increase in the risk of acute respiratory distress syndrome (ARDS).21
The low-CPP approach, popularized in Lund, Sweden, concentrates on ICP reduction by minimizing CPP and reducing CBV and intravascular hydrostatic pressure.22 The fundamental principles of the Lund approach include the maintenance of normal colloidal pressure to prevent extravascular fluid shifts, reduction of intracapillary hydrostatic pressure through systemic blood pressure reduction, and minimization of CBV by suppressing CMRo2 with thiopental and promoting precapillary vasoconstriction with dihydroergotamine. Evidence in support of the Lund approach includes case series managed according to this protocol with good outcomes,22 and cerebral microdialysis studies demonstrating that significant oxidative stress in the form of increased lactate/pyruvate ratios does not consistently occur until CPP falls below 50 mm Hg.23
It seems most likely that both the high- and low-CPP strategies described above are valid depending on the individual circumstances of the patient. In this view, no single approach should be generalized to all patients; instead, CPP should be optimized based on individualized physiologic monitoring. Advanced multimodality monitoring techniques such as brain tissue oxygen monitoring, jugular bulb oximetry, signal-processed electroencephalography (EEG), and micro-dialysis may eventually allow clinicians to fine tune CPP and MAP goals based on the specific physiologic circumstances in a particular patient at any given point in time during acute injury. This approach makes better physiologic sense and may eventually be the ultimate goal in the future.
Hyperventilation has long played a role in ICP therapy. A decrease in Pco2 causes vasoconstriction, which lowers CBV and thus ICP. The effect is almost immediate, but often transient, with a steady loss of effect occurring within the first hour. In conditions characterized by excessive vasodilation and cerebral hyperemia, the effect of hyperventilation may be sustained for days. Intracranial pressure is directly related to CBV. Hyperventilation works by directly reducing CBF through vasoconstriction. A reduction of CBF could potentially limit blood flow to ischemic areas of the brain, with only a modest reduction in ICP through its indirect effects on CBV.
Studies have demonstrated a risk of exacerbation of cerebral ischemia with ongoing hyperventilation. As such, the use of hyperventilation should occur in the setting of ICP crisis and emergency as a transient method before other therapies are available. The routine application of extreme hyperventilation (less than 30 mm Hg) within the first few hours of TBI is generally considered harmful because of the risk of exacerbation of ischemia.24 If necessary, jugular venous oxygen saturation or brain tissue oxygen monitoring can be used as a guide during hyperventilation to ensure adequate brain oxygen delivery.25,26
If CPP is optimized, the patient is sedated, and ICP remains elevated, osmotherapy should be initiated. Mannitol, given in a 20% solution at a dose of 0.25 to 1.5 g/kg, mediates an ICP-lowering effect through two mechanisms. First, it is an osmotic diuretic that creates a concentration gradient across the blood-brain barrier and extracts free water from the brain. This decreases brain volume and lowers ICP.20 Also, mannitol increases CPP through plasma expansion, and promotes vasoconstriction and CBV reduction by decreasing blood viscosity and improving CBF.27 Mannitol can lower ICP within minutes. It should be given in a single rapid bolus (0.25 to 1.5 g/kg), and may be repeated as frequently as once an hour when ICP is elevated. Complications of mannitol therapy include dehydration and renal failure. Hypertonic saline (2 to 5 mL/kg of 7.5% saline or 0.5 to 2.0 mL/kg of 23.4% saline over 30 minutes) is an alternative to mannitol for treating acutely elevated ICP. It has been shown to be at least as effective28,29 for acutely lowering ICP, and has the advantage of boosting MAP, CPP, and intravascular volume when patients are dehydrated. The main complication specific to hypertonic saline therapy is congestive heart failure due to fluid overload. For this reason, the use of a continuous IV infusion of 3% hypertonic saline (at a certain rate: typically starting at 50 mL per hour, titrating up to the serum sodium target of about 150 mEq/L) may not be the best method if volume overload is a concern. In such a case, a bolus dosing may be preferred. Once patients are on a steady dose of continuous IV 3% saline with a serum sodium level approximately 150 mEq/L, it is advised that the hypertonic saline should be weaned very slowly (over several days), if deemed appropriate, as it is not uncommon to observe rebound intracranial hypertension upon abrupt cessation of the infusion (patients with space-occupying lesions may even herniate).
Currently, there are insufficient data to suggest one concentration or method (continuous or bolus) over another. Hypertonic saline bolus therapy does appear to be as effective as mannitol in reducing refractory elevated ICP and improving CPP transiently. However, many issues remain to be clarified, including the exact mechanism of action of hypertonic saline, the best mode of administration and concentration, and its risks and complications.
Failure of hyperventilation and osmotherapy to control ICP should prompt consideration of the initiation of pentobarbital infusion.30 Consideration of pentobarbital in this setting should also trigger reconsideration of performing hemicraniectomy or the application of hypothermia. The mechanism of action of pentobarbital is a profound reduction of the cerebral metabolic rate. Pentobarbital can be given in repeated 5-mg/kg boluses every 15 to 30 minutes until the ICP is controlled (usually 10 to 20 mg/kg is required), and then continuously infused at 1 to 4 mg/kg per hour. An EEG should be continuously recorded, and the pentobarbital titrated to produce a burst-suppression pattern, with approximately 6- to 8-second interbursts, to avoid overmedication (although the goal is ICP control, not burst suppression on EEG, per se). The most common complication of pentobarbital therapy is hypotension owing to its cardiac suppression, and vasopressors and inotropes are often needed for hemodynamic support. Ileus may occur as well, and feeding may have to be given parenterally during treatment. Delayed, inadequate hemodynamic support may lead to acute kidney failure (and hence multiorgan failure) and severe acid-base imbalance, leading to a much more difficult situation.
If all of the above therapies fail to control ICP, induced hypothermia to 32°C to 34°C can effectively lower otherwise refractory ICP. Hypothermia reduces ICP by lowering CMRo2 requirements and thus CBV. The recommended temperature goal is 32°C to 34°C, which is considered mild-to-moderate hypothermia because there are fewer complications than at lower temperatures. Hypothermia can be achieved using various surface and endovascular cooling methods coupled to a rectal, esophageal, pulmonary artery, or bladder thermometer. Rapid infusion of large-volume cold fluids (30 mL/kg of 0.9% saline cooled to 4°C to 5°C) may be suitable for core cooling, especially as an effective, cost-effective method of administering a hypothermia-induction agent. Cold saline infusion should be used from the beginning while trying to set up a more controllable temperature-modulatory device. Therapeutic hypothermia has been clinically demonstrated to control ICP in a small series of patients refractory to pentobarbital,31 but large controlled studies are lacking in this regard. Common potential complications of hypothermia include nosocomial infection, hypotension, cardiac arrhythmias, coagulopathy, shivering, hypokalemia, hyperglycemia, and ileus. Particular caution should be exercised when rewarming patients because rebound ICP readily occurs. Rewarming must be done slowly (0.10°C to 0.33°C per hour) and in a controlled fashion.
! Critical Considerations
The Monro-Kellie hypothesis states that the brain is encased in a confined space, and any space-occupying lesion or increased volume of intracranial constituents may lead to elevated ICP.
ICP values should be considered along with CPP (therefore MAP), as it is important to understand that the ICP value alone as an absolute value may not carry any clinical significance. Evidence supports that an extremely low CPP (less than 50 mm Hg), especially in the setting of systemic hypotension, may lead to worse outcomes.
The injured brain may not have adequate compliance, and therefore has a low threshold for a rapidly rising ICP. Any clinician dealing with an ICP crisis should be aware of pathologic waves and poorly compliant ICP waveforms.
It is important to understand that a normal ICP value with poor compliance seen on the waveform may suggest that any minor change in patient's condition such as head position and pain/sedation status may trigger an ICP crisis.
Understanding the compliance helps neurointensivists and surgeons make decision about the duration and magnitude of CSF diversion and ventricular drain management.
Currently, optimizing CPP at this time is being done in an arbitrary fashion, but with continued data from multimodality monitoring, it may be possible to tailor individualized, goal-directed therapy for brain resuscitation in the future. It is important to remember that a higher CPP does not necessarily mean better perfusion.
ICP management should be done in an organized, stepwise approach. Traditionally accepted medical therapy for ICP includes sedation, osmotherapy, and pentobarbital. There are multiple small series in the literature reporting hypothermia (target core body temperature of 32°C to 34°C) as an effective method of reducing an otherwise refractory ICP. While this needs to be studied with large prospective trials before recommending it as a routine therapy, it is not unreasonable to consider this therapy as one of the last resorts.