Normal intracranial pressure (ICP) is between 5 and 15 mmHg in supine subjects. Intracranial hypertension (ICP >20 mmHg) is common in many central nervous system diseases and in fatal cases is often the immediate cause of death.
Aetiology and pathogenesis—increases in intracranial volume and hence—given the rigid skull—ICP may be the consequence of (1) brain oedema, (2) increased cerebral blood volume, (3) hydrocephalus, and (4) space-occupying lesions. Brain perfusion depends on the difference between mean arterial pressure and ICP, termed cerebral perfusion pressure (CPP). The normal brain autoregulates cerebral blood flow down to a lower limit of CPP of about 50 mmHg in healthy subjects, and perhaps 60 to 70 mmHg in disease. CPP reduction to below these values results in cerebral ischaemia.
Clinical features—the cardinal symptom of intracranial hypertension is headache, which may be accompanied by vomiting, visual disturbance, and alterations in mental function or conscious state. Papilloedema is the classical sign, but may be absent. Severe elevation of ICP can result in bradycardia and hypertension (Cushing’s response), abnormalities of breathing (Cheyne–Stokes respiration, central neurogenic hyperventilation, ‘ataxia of breathing’), and various forms of cerebral herniation.
Investigation—if clinical features suggest intracranial hypertension, a lumbar puncture must be preceded by CT imaging, and avoided if the basal cisterns are effaced by cerebral oedema.
Management—this involves (1) ensuring normoxia and normocapnia (PaO2 >11 kPa, PaCO2 4.5–5 kPa), with tracheal intubation and ventilatory support where required; (2) treating precipitating factors such as fits, pyrexia, and electrolyte abnormalities; (3) treating raised ICP with mannitol, dexamethasone (for tumours), hyperventilation (if pupillary dilatation/clinical picture merits); and (4) monitoring ICP if appropriate (e.g. trauma).
The normal intracranial pressure (ICP), measured at the level of Monro’s foramen, is between 5 and 15 mmHg in supine subjects. Intracranial hypertension (ICP >20 mmHg) is a common accompaniment of many central nervous system (CNS) diseases. In many of these situations intracranial hypertension is the most important cause of symptoms and modulator of outcome, and in fatal cases is often the immediate cause of death.
The cranial cavity contains brain (80%), blood (10%), and cerebrospinal fluid (CSF; 10%). These incompressible contents are bounded by a rigid skull with a fixed capacity. Consequently, an increase in volume of any of these contents, or the presence of any space-occupying pathology, results in an increase in ICP unless one of the other constituents can be displaced or its volume decreased (Fig. 17.6.1). This principle is referred to as the Monro–Kellie doctrine. Increases in intracranial volume may be the consequence of:
◆ Brain oedema, which may have different pathogenic mechanisms:
• Cytotoxic oedema occurs as a result of cell swelling, most commonly due to ischaemic energy depletion and rises in intracellular Na+ and water.
• Vasogenic oedema results from an increased permeability of the blood–brain barrier with an expansion of the extracellular fluid compartment.
• Interstitial oedema occurs in the context of hydrocephalus, where increased intraventricular CSF pressures result in permeation of CSF into adjacent brain, typically in the frontal periventricular regions.
◆ Vascular engorgement that results from increased cerebral blood volume. This may be due to the vasodilatation that accompanies normal or abnormal (e.g. epileptiform) neuronal activity. In other situations vasodilatation may be due to loss of vasoregulation, either due to disease (vasoparalysis), or due the effect of potent physiological (carbon dioxide) or pharmacological (nitrates and other nitric oxide donors) cerebral vasodilators.
◆ Hydrocephalus, which may be noncommunicating (where an obstruction prevents the ventricular system communicating with the subarachnoid space), or communicating (where there is a defect in CSF reabsorption).
◆ Space-occupying lesions (SOL), which may be either chronic (e.g. intracranial tumours) or acute (e.g. intracranial haematomas associated with trauma).
Temporal patterns of ICP change
Initial increases in intracranial volume are buffered by displacement or reduction in volume of other contents. Thus, cerebral oedema may result in compression of the ventricles, with translocation of CSF to the spinal subarachnoid space, and compression of cerebral vasculature. Over longer time periods, normal brain may be compressed and CSF production diminished. The relationship between intracranial volume (ICV) and ICP is commonly depicted as a hyperbolic curve, with an initial flat part during which compensatory mechanisms are effective, a knee which represents their progressive exhaustion, and a steep phase when even small increases in intracranial volume produce large increases in ICP. However, the extent and efficiency with which these mechanisms buffer increases in volume depend on the speed of progression of disease. Given these considerations, it is more appropriate to depict the evolution of pathophysiology as a family of curves, with variable rates of progression (Fig. 17.6.2). It is important to make three further points in this context:
◆ First, a precipitating factor may suddenly increase the speed of progression of a relatively slow pathophysiological process, and be the proximate cause of symptomatic decompensation.
◆ Secondly, acute changes in cerebrovascular physiology are an important cause of such deterioration. Both hypoxia and hypercarbia can cause cerebral vasodilatation and elevate ICP. While severe hypertension may result in cerebral oedema, it is far more common to find that relatively minor reductions in mean arterial pressure compromise cerebral perfusion and trigger reflex vasodilatation and secondary increases in ICP. Such haemodynamic instability may be the underlying cause of phasic increases in ICP (Fig. 17.6.3).
◆ Finally, since patients with significant intracranial hypertension operate on the steep part of the ICV/ICP curve, even small decreases in intracranial volume (e.g. a 5 ml decrease in cerebral blood volume produced by mild hyperventilation) can have gratifyingly large effects on ICP.
Why treat intracranial hypertension?
Brain perfusion depends on the difference between mean arterial pressure (MAP) and ICP, termed cerebral perfusion pressure (CPP). While the normal brain autoregulates cerebral blood flow across a large range of CPP values, the lower limit of such autoregulation is about 50 mmHg in healthy subjects, and may be significantly higher (60–70 mmHg) in disease. CPP reduction below the lower limit of autoregulation results in cerebral ischaemia, and even minor reductions in CPP may trigger reflex vasodilatation and increase ICP in a noncompliant intracranial cavity. Such cerebral ischaemia is important in its own right. Therefore, for instance, intracranial hypertension may be the direct cause of neurocognitive deficits in survivors of head injury.
An expanding focal mass can generate pressure gradients within the intracranial cavity, and the resulting displacement of brain against rigid structures, and protrusion (herniation) of brain through narrow openings between intracranial compartments can press on vital structures and result in death (Fig. 17.6.4).
Prolonged intracranial hypertension may result in permanent damage to critical structures. Thus, benign intracranial hypertension rarely results in herniation syndromes, but if left untreated, frequently results in optic atrophy.
The symptoms that accompany ICP elevation can be nonspecific and insensitive. The cardinal feature of intracranial hypertension is headache, which may be described as severe (‘worst ever’) and explosive in onset in the setting of intracranial haemorrhage. The headache of intracranial tumour is often progressive, worst on awakening (possibly due to ICP elevations associated with the supine position and PaCO2 elevation in sleep), and is exacerbated by coughing and straining. However, it may be indistinguishable from common tension headache, and dangerous intracranial hypertension may occur without headache.
The headache is often accompanied by vomiting, which is classically described as projectile and not preceded by nausea. Visual disturbances are often reported, which may be attributable to optic or oculomotor nerve compression (with accompanying visual failure or diplopia, respectively). Alterations in mental function or conscious state may be observed, ranging from impaired concentration, through increased irritability, impaired cognition and memory, and altered personality, to increased somnolence and deep coma.
While papilloedema is the classical sign associated with ICP elevation, it is not seen with acute intracranial hypertension, and may be absent even with large intracranial masses. Pressure on cranial nerves may result in weakness of ocular movement. The abducens nerve is often involved in such a process due its long intracranial course, and the resultant diplopia provides the classical example of a false localizing sign. Lesions that irritate the posterior fossa dura can produce neck stiffness.
Progressive rises in ICP result in bradycardia and hypertension, which constitute the Cushing’s response and signify stimulation of brainstem autonomic nuclei. Worsening brain stem compression and/or ischaemia result progressively in Cheyne–Stokes respiration, central neurogenic hyperventilation, and irregular respiratory patterns (‘ataxia of breathing’). Both neurogenic pulmonary oedema and the adult respiratory distress syndrome have been associated with intracranial hypertension.
Severe elevation of ICP may result in herniation of the temporal lobe through the tentorial notch (Fig. 17.6.4). This produces clinical features due to pressure on the ipsilateral oculomotor nerve (ipsilateral pupillary dilatation), pyramidal tract (contralateral weakness), and brainstem (Cushing’s response and abnormal respiratory patterns followed by circulatory collapse and respiratory arrest). The posterior cerebral artery is frequently compressed by the herniating temporal lobe, and successful resuscitation from threatened or early transtentorial herniation may leave a patient with an ipsilateral occipital infarction.
The most informative standard imaging in patients with intracranial hypertension is computed tomography (CT), which may reveal subarachnoid or intracerebral blood, contusions, or a tumour. In addition, cerebral oedema may be manifest by loss of sulci, compression of the third and lateral ventricles, and effacement of the perimesencephalic and suprasellar cisterns. Unilateral lesions may result in midline shift (which can occur without pupillary asymmetry), compression of the ipsilateral lateral ventricle, and in some cases dilatation of the contralateral ventricle due to obstruction of Monro’s foramen. It is important to recognize that overt ventricular dilatation may be absent when hydrocephalus coexists with cerebral oedema. Indeed, the presence of normal sized ventricles in the context of intracranial hypertension (demonstrated by ICP monitoring) should suggest the possibility of coexisting hydrocephalus and trigger the consideration of CSF drainage as a means of therapy.
MRI may provide better definition of underlying pathology, particularly in the posterior fossa, and its multiplanar capability may provide a better appreciation of the extent of space-occupying lesions. Modern imaging methods can also detect patients who may have relatively normal ICP, but are at high risk of severe intracranial hypertension. For example, patients with a middle cerebral artery (MCA) territory infarction are at high risk of severe brain swelling if more than 50% of the MCA territory is hypodense.
A lumbar puncture offers the opportunity to directly measure CSF pressure, and can be the defining investigation in meningitis, subarachnoid haemorrhage, or benign intracranial hypertension. However, in the context of clinical features that suggest intracranial hypertension, a lumbar puncture must be preceded by CT, and avoided if the basal cisterns are effaced by cerebral oedema. Removal of CSF from the lumbar subarachnoid space under these circumstances can markedly increase the pressure differential between the infratentorial and supratentorial compartments, or the intracranial and spinal compartments, and precipitate transtentorial or cerebellar herniation, respectively.
Monitoring intracranial pressure
The clinical evaluation of intracranial hypertension is difficult due to its nonspecific clinical picture and phasic variations. Management may therefore be greatly facilitated by direct monitoring of ICP using intraparenchymal or ventricular monitoring devices. Such monitoring is mandatory in severe intracranial hypertension and in sedated or deeply unconscious patients, in whom changes in clinical signs do not provide an alternative means of assessing progress and response to therapy. Although Class I evidence to support its use is lacking, ICP monitoring remains part of authoritative guidelines for traumatic brain injury.
Strategies for therapy
Monitoring progression of disease and response to therapy
Monitoring will depend on the clinical context. Repeated clinical examination with regular charting of the Glasgow Coma Scale may suffice in many cases. Patients with benign intracranial hypertension may require regular visual field assessment, while those with head injury, intracranial haemorrhage, or severe cerebral oedema may benefit from direct ICP monitoring. The value of ICP monitoring may be substantially enhanced by the use of other monitoring modalities such as jugular bulb oximetry.
Hyponatraemia and low plasma osmolality will tend to worsen cerebral oedema by favouring water entry into the brain, and should be vigorously corrected. Maintenance of cerebral perfusion pressure with fluid resuscitation and vasoactive agents will prevent cerebral ischaemia. Comatose patients should have arterial blood gas levels measured, and intubation and ventilatory support provided if airway protection is required or gas exchange is impaired (see Chapter 17.5). While hyperventilation has been widely used to control ICP in the past, there is increasing concern regarding the induction of critical cerebral ischaemia by hypocapnic vasoconstriction. Current recommendations suggest that near normal PaCO2 levels (4.5–5 kPa) should be maintained, with moderate hyperventilation (PaCO2 4.0–4.5 kPa) guided by jugular bulb oximetry and reserved for control of acute episodes of severe intracranial hypertension. Attention should also be paid to treating epilepsy and significant pyrexia, both of which can precipitate rises in ICP, and to discontinuing or reversing the action of drugs such as opioids, which may be responsible for physiological derangements that precipitate ICP elevation.
Treatment of the underlying condition
Early neurosurgical evaluation and operative therapy may be life-saving if a patient has an acute intracranial haematoma, a large tumour, or established hydrocephalus. Specific antimicrobial therapy may be required for meningitis, encephalitis, or brain abscess. Systemic hypertension commonly accompanies intracranial hypertension, and should generally not be treated because it may be needed to preserve cerebral perfusion. If therapy is needed for extreme hypertension or for hypertensive encephalopathy, then it is best to avoid nitric oxide donors such as nitrates, which can cause cerebral vasodilatation and further increase ICP.
Specific treatment of intracranial hypertension
Several therapies can be used to reduce intracranial pressure, and their application will depend on the cause and severity of ICP elevation. Commonly used interventions and their indications are outlined in Table17.6.1, but it must be pointed out that few of these have been assessed by good quality outcome studies. Treatment pathways for the emergency management of an unconscious patient with suspected intracranial hypertension are outlined in Fig. 17.6.5.
Table 17.6.1 Treatment of intracranial hypertension
CPP augmentation by increasing MAP
Maintenance of CPP >60–70 mmHg prevents ischaemia, and further increases (90–100 mmHg) may reduce ICP by autoregulatory cerebral vasoconstriction. Efficacy demonstrated in head injury
Reduce vasogenic oedema by restoring BBB integrity. Particularly effective in peritumoural oedema and benign intracranial hypertension. No outcome benefit in trauma. Prophylactic use may reduce incidence of hydrocephalus and other sequelae in tuberculous and acute bacterial meningitis
Furosemide used to potentiate mannitol. Acetazolamide and thiazide diuretics used in benign intracranial hypertension
Mannitol is effective in emergencies and can be used repeatedly if effective and plasma osmolality ≤325 mOsm/litre. Hypertonic NaCl (3–30%) may reduce ICP when mannitol is ineffective and tends to cause less problems with major fluid shifts. Hyperosmotic agents may be less effective when there is widespread disruption of the blood–brain barrier
Reduction of cerebral blood volume
Mild to moderate hypothermia (33–36 °C) may be directly neuroprotective, but this benefit remains unproven except following cardiac arrest. It is clearly effective at controlling refractory intracranial hypertension by multiple mechanisms, including metabolic suppression and anti-inflammatory effects, but clear outcome benefits have not been demonstrated
When used in the absence of severe intracranial hypertension, decompressive craniectomy worsens outcome in traumatic brain injury. A trial of decompressive craniectomy for refractory intracranial hypertension in head injury is currently underway. Decompressive craniectomy improves survival, and probably functional outcome, in ‘malignant’ MCA stroke with severe cerebral oedema. Optic nerve decompression may prevent visual deterioration in benign intracranial hypertension
BBB, blood–brain barrier; CBF, cerebral blood flow; CBV, cerebral blood volume; CPP, cerebral perfusion pressure; CSF, cerebrospinal fluid; ICP, intracranial pressure; MAP, mean arterial pressure; MCA, middle cerebral artery.
Brain Trauma Foundation. Guidelines for the treatment of severe head injury. http://www.braintrauma.org/site/PageServer?pagename=Guidelines.
Chesnut RM, et al. (2012). A trial of intracranial-pressure monitoring in traumatic brain injury. N Engl J Med, 367, 2471–81.Find this resource:
Cooper DJ, et al. (2011). Decompressive craniectomy in diffuse traumatic brain injury. N Engl J Med, 364, 1493–502.Find this resource:
Hofmeijer J, et al. (2009). Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial. Lancet Neurol, 8, 326–333.Find this resource:
Plum F, Posner JB (eds) (1992). Diagnosis of stupor and coma, 3rd edition. F.A. Davis Company, Philadelphia.Find this resource:
Reilly PL (2005). Management of intracranial pressure and cerebral perfusion pressure. In: Reilly PL, Bullock R (eds) Head injury, pp. 331–355. Hodder Arnold, London.Find this resource:
Roberts I, Schierhout G, Alderson P (1998). Absence of evidence for the effectiveness of five interventions routinely used in the intensive care management of severe head injury: a systematic review. J Neurol Neurosurg Psychiatr, 65, 729–33.Find this resource:
Sahuquillo J, Arikan F (2006). Decompressive craniectomy for the treatment of refractory high intracranial pressure in traumatic brain injury. Cochrane Database Syst Rev, 1, CD003983.Find this resource:
Skau M, et al. (2006). What is new about idiopathic intracranial hypertension? An updated review of mechanism and treatment. Cephalalgia, 26, 384–99.Find this resource:
van de Beek D, et al. (2006). Community-acquired bacterial meningitis in adults. N Engl J Med, 354, 44–53.Find this resource: