Table 14-1 lists different classifications of medical conditions that are associated with high intracranial pressure (ICP). In a neurologic intensive care unit (NeuroICU) setting, common conditions that are frequently associated with elevated ICP include acute aneurysmal high-grade SAH, severe traumatic brain injury (TBI), large intraparenchymal hemorrhage either spontaneous (such as hypertensive bleed) or in the setting of underlying coagulopathy (atrial fibrillation on warfarin therapy or coronary artery disease with cardiac stents on dual-antiplatelet therapy), malignant middle cerebral artery infarction with herniation, and severe meningitis and/or encephalitis. Although medical centers around the country have different patient populations, a great majority of all NeuroICU patients with high ICP would fall into one of these conditions, with severe TBI being the most common etiology for intracranial hypertension¹ at an annual incidence estimated to be 200 cases per 100 000 people.²

Monro-Kellie Hypothesis

The Monro-Kellie hypothesis is a widely accepted concept for explaining the elevation of ICP. In 1783, Alexander Monro first articulated this in his Observations on the Structure and Function of the Nervous System and later was supported by Kellie in 1824 by his observation in two humans: “Appearances observed in the dissection of two individuals; death from cold and congestion of the brain.” The hypothesis explains that the human cranium has a fixed amount of space with three main components: cerebrospinal fluid (CSF), brain parenchyma, and blood. If any space-occupying lesion or any of these constituents’ volumes are increased beyond the compliance, an elevation of ICP is inevitable.³

Intracranial Compliance

Intracranial compliance is defined as the change in volume over the change in pressure (DV/DP). The relationship between pressure and volume in the brain is linear in the beginning but may become (not always) exponential in the later phase. As volume increases, the ICP rises slowly, CSF is displaced into the spinal thecal sac, and blood is decompressed from the distensible cerebral veins. Once these compensatory and compliant redistribution mechanisms no longer continue, ICP can increase much more rapidly with just small increments of additional volume. As the compliance becomes poor, the ICP waveform may change. The amplitude of the ICP pulse wave may provide a clue that compliance is reduced; as compliance falls, the ICP pulse amplitude increases. During the high ICP crisis, ICP waveforms may show that the second peak (P2) may rise as high as (increased amplitude compared with normal waveforms) the first peak or even higher (Figure 14-1).

Cerebral Perfusion Pressure

The main negative consequence of elevated ICP is reduced cerebral blood flow (CBF) and secondary hypoxic-ischemic injury due to inadequate perfusion. Cerebral perfusion pressure (CPP) is calculated as mean arterial pressure (MAP) – ICP. CPP along with cerebral blood volume determines CBF; normally, autoregulation of the cerebral vasculature maintains CBF at a constant level between a CPP of approximately 50 and 100 mm Hg. Brain injury leading to impaired cerebral autoregulation may cause CBF to approximate a more straight-line relationship with CPP.⁴ Although the optimal CPP for a given patient may vary, in general, CPP optimization should be greater than 60 mm Hg (to avert ischemia) and below 110 mm Hg (to avoid breakthrough hyperperfusion and cerebral edema).^5,6 This concept of optimizing CPP is an important one at the bedside. With an adequate CPP, one may have more time to think about the next therapeutic strategies even if ICP is high (eg, MAP, 90 mm Hg; ICP, 30 mm Hg; and CPP, 60 mm Hg; ICP is abnormally elevated but CPP is adequate). One the other hand, for the same ICP, one may have unacceptably low CPP (eg, MAP, 60 mm Hg, ICP, 30 mm Hg, and CPP, 30 mm Hg; this may be considered unacceptable, and permanent neuronal damage may be inevitable especially if such condition continues). Therefore, ICP as an absolute and only value does not provide a full picture of the situation (and the seriousness of the injury).

Pathologic Pressure Waves

In patients with increased ICP, pathologic ICP waveforms may occur (Figure 14-2). Lundberg A waves (or plateau waves) represent prolonged periods of profoundly high ICP.⁷ These waves do not refer to the individual ICP waveform described in Figure 12-1, but rather a graphic representation of ICP values plotted over time. A plateau wave is considered a high risk for further (or ongoing) brain injury, with critically reduced perfusion as a result of a prolonged period of high ICP crisis, which often occurs abruptly when either CPP or intracranial compliance is low. The duration of either may vary from minutes to hours, and pressures as high as 50 to 100 mm Hg may be seen and considered ominous in the setting of acute brain injury. Lundberg B waves are of shorter duration, lower amplitude elevations in ICP that indicate that intracranial compliance reserves are simply compromised. The important thing is not to memorize which is Lundberg A or B per se, but to understand the trend of the ICP elevations and figure out the overall picture as to why there is intracranial hypertension and how brain compliance is coping with the injury. Accurate assessment of the underlying etiology will help guide the clinicians to choose the right method of treatment.

Clinical signs of intracranial hypertension may vary and depend on the underlying etiology. In general, the clinical manifestations are suggestive of global, or bilateral, hemispheric cerebral dysfunction rather than a focal finding such as arm weakness. Depressed level of consciousness, blurred vision, confusion, disorientation, nausea, vomiting, diplopia, and sixth cranial nerve palsy (false localizing sign) may be seen, especially if the increase in ICP is acute rather than chronic. It is important to once again emphasize that ICP as an absolute value by itself may not have much clinical significance; more important is the CPP and brain compliance. The Cushing triad, a well-known phenomenon of hypertension and bradycardia in the setting of critically elevated ICP, is more commonly seen with the late phase of intracranial hypertension, such as near brain dead/herniation syndrome rather than in the beginning of an acute injury. ICP elevation may become a local phenomenon and compartmentalized as a result of the rigid boundaries formed by the falx and tentorium cerebelli. Compartmentalized mass effect and pressure differentials, in turn, can lead to herniation of brain tissue from the area of higher to lower pressure. Different herniation syndromes are each marked by characteristic signs (Table 14-2).

Currently, the best level of evidence is the “level 2” recommendation of the Brain Trauma Foundation (2007 guidelines; http://tbiguidelines.org), which states that “treatment should be initiated with ICP > 20 mm Hg.” This is heavily driven by the large amount of observation data that showed poor outcome in TBI subjects with hypotension and ICP > 20 mm Hg. Systemic hypotension and high ICP leading to poor outcome further supports the theory that failure to optimize CPP is associated with an increased risk of poor flow and perfusion and, therefore, further injury.