Evaluation and management of elevated intracranial pressure in adults

INTRODUCTION — Elevated intracranial pressure (ICP) is a potentially devastating complication of neurologic injury. Elevated ICP may complicate trauma, central nervous system (CNS) tumors, hydrocephalus, hepatic encephalopathy, and impaired CNS venous outflow (table 1) [1]. Successful management of patients with elevated ICP requires prompt recognition, the judicious use of invasive monitoring, and therapy directed at both reducing ICP and reversing its underlying cause [2,3].

The evaluation and management of adult patients with elevated ICP will be reviewed here. Elevated ICP in children and specific causes and complications of elevated ICP (eg, ischemic stroke, intracerebral hemorrhage, traumatic brain injury) are discussed separately. (See "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis" and "Management of acute moderate and severe traumatic brain injury", section on 'Intracranial pressure management' and "Initial assessment and management of acute stroke" and "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis", section on 'Early complications' and "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis", section on 'Intracranial pressure management'.)

PHYSIOLOGY — ICP is normally ≤15 mmHg in adults, and pathologic intracranial hypertension is present at pressures ≥20 mmHg. ICP is normally lower in children than adults, and may be subatmospheric in newborns [4]. Homeostatic mechanisms stabilize ICP, with occasional transient elevations associated with physiologic events, including sneezing, coughing, or Valsalva maneuvers.

Intracranial components — In adults, the intracranial compartment is protected by the skull, a rigid structure with a fixed internal volume of 1400 to 1700 mL. Under physiologic conditions, the intracranial contents include (by volume) [5]:

●Brain parenchyma – 80 percent

●Cerebrospinal fluid (CSF) – 10 percent

●Blood – 10 percent

ICP is a function of the volume and compliance of each component of the intracranial compartment, an interrelationship known as the Monro-Kellie doctrine [6,7]. Because the overall volume of the cranial vault cannot change, an increase in the volume of one component (eg, hydrocephalus) or the presence of mass lesions (eg, tumor, hematoma, or abscess) necessitate the displacement of other structures, an increase in ICP, or both.

The volume of brain parenchyma is relatively constant in adults, although it can be altered by mass lesions or in the setting of cerebral edema (figure 1). The volumes of CSF and blood in the intracranial space vary to a greater degree. Abnormal increases in the volume of any component may lead to elevations in ICP.

CSF is produced by the choroid plexus and elsewhere in the central nervous system (CNS) at a rate of approximately 20 mL/hour (500 mL/day) [8]. CSF is normally resorbed via the arachnoid granulations into the venous system. Problems with CSF regulation generally result from impaired outflow caused by ventricular obstruction or venous congestion; the latter can occur in patients with sagittal (or other) venous sinus thrombosis. Much less frequently, CSF production can become pathologically increased; this may be seen in the setting of choroid plexus papilloma. (See "Cerebrospinal fluid: Physiology, composition, and findings in disease states".)

Cerebral blood flow (CBF) determines the volume of blood in the intracranial space. CBF increases with hypercapnia and hypoxia. Other determinants of CBF are discussed below. Autoregulation of CBF may be impaired in the setting of neurologic injury, and may result in rapid and severe brain swelling, especially in children [9-11].

In summary, the major causes of increased ICP include:

●Intracranial mass lesions (eg, tumor, hematoma)

●Cerebral edema (such as in acute hypoxic-ischemic encephalopathy, large cerebral infarction, severe traumatic brain injury)

●Increased CSF production (eg, choroid plexus papilloma)

●Decreased CSF absorption (eg, arachnoid granulation adhesions after bacterial meningitis)

●Obstructive hydrocephalus

●Obstruction of venous outflow (eg, venous sinus thrombosis, jugular vein compression, neck surgery)

●Idiopathic intracranial hypertension (pseudotumor cerebri)

Intracranial compliance — The interrelationship between changes in the volume of intracranial contents and changes in ICP defines the compliance characteristics of the intracranial compartment. Intracranial compliance can be modeled mathematically (as in other physiologic and mechanical systems) as the change in volume over the change in pressure (dV/dP).

The compliance relationship is nonlinear, and compliance decreases as the combined volume of the intracranial contents increases. Initially, compensatory mechanisms allow volume to increase with minimal elevation in ICP. These mechanisms include:

●Displacement of CSF into the thecal sac

●Decrease in the volume of the cerebral venous blood via venoconstriction and extracranial drainage

However, when these compensatory mechanisms have been exhausted, significant increases in pressure develop with small increases in volume, leading to abnormally elevated ICP (figure 2).

Thus, the magnitude of the change in volume of an individual structure determines its effect on ICP. In addition, the rate of change in the volume of the intracranial contents influences ICP. Changes that occur slowly produce less of an effect than those that are rapid. This can be recognized clinically in some patients who present with large meningiomas and minimally elevated or normal ICP. Conversely, other patients may experience symptomatic elevations in ICP from small hematomas that develop acutely.

Cerebral blood flow — Following a significant increase in ICP, brain injury can result from brainstem compression and/or a reduction in CBF. CBF is a function of the pressure drop across the cerebral circulation divided by the cerebrovascular resistance, as predicted by Ohm's law [12]:

where CAP is carotid arterial pressure, JVP is jugular venous pressure, and CVR is cerebrovascular resistance.

Cerebral perfusion pressure (CPP) is a clinical surrogate for the adequacy of cerebral perfusion. CPP is defined as mean arterial pressure (MAP) minus ICP.

Autoregulation — CBF is normally maintained at a relatively constant level by cerebrovascular autoregulation of CVR over a wide range of CPP (50 to 140 mmHg) (figure 3) [13,14]. However, autoregulation of CVR can become dysfunctional in certain pathologic states, most notably stroke or trauma. In this setting, the brain becomes exquisitely sensitive to even minor changes in CPP [15-17].

Another important consideration is that the set-point of autoregulation is also changed in patients with chronic hypertension. With mild to moderate elevations in blood pressure (BP), the initial response is arterial and arteriolar vasoconstriction. This autoregulatory process both maintains tissue perfusion at a relatively constant level and prevents the increase in pressure from being transmitted to the smaller, more distal vessels [15]. As a result, acute reductions in BP, even if the final value remains within the normal range, can produce ischemic symptoms in patients with chronic hypertension (figure 3) [15].

Cerebral perfusion pressure — Conditions associated with elevated ICP, including mass lesions and hydrocephalus, can be associated with a reduction in CPP. This can result in devastating focal or global ischemia. On the other hand, excessive elevation of CPP can lead to hypertensive encephalopathy and cerebral edema due to the eventual breakdown of autoregulation, particularly if the CPP is >120 mmHg [15,18,19]. A higher level of CPP is tolerated in patients with chronic hypertension because the autoregulatory curve has shifted to the right (figure 3) [15,19]. (See "Moderate to severe hypertensive retinopathy and hypertensive encephalopathy in adults", section on 'Mechanisms of vascular injury'.)

Ultimately, global or local reductions in CBF are responsible for the clinical manifestations of elevated ICP. These manifestations can be further divided into generalized responses to elevated ICP and herniation syndromes.

CLINICAL MANIFESTATIONS — Global symptoms of elevated ICP include headache, which is probably mediated via the pain fibers of cranial nerve (CN) V in the dura and blood vessels, depressed global consciousness due to either the local effect of mass lesions or pressure on the midbrain reticular formation, and vomiting.

Signs include CN VI palsies, papilledema secondary to impaired axonal transport and congestion (picture 1), and a triad of bradycardia, respiratory depression, and hypertension (Cushing triad, sometimes called Cushing reflex or Cushing response) [5]. While the mechanism of Cushing triad remains controversial, many believe that it relates to brainstem compression. The presence of this response is an ominous finding that requires urgent intervention.

Focal symptoms of elevated ICP may be caused by local effects in patients with mass lesions or by herniation syndromes. Herniation results when pressure gradients develop between two regions of the cranial vault. The most common anatomic locations affected by herniation syndromes include subfalcine, central transtentorial, uncal transtentorial, upward cerebellar, cerebellar tonsillar/foramen magnum, and transcalvarial (figure 4) [5,20]. (See "Stupor and coma in adults", section on 'Neurologic examination' and "Stupor and coma in adults", section on 'Coma syndromes'.)

One notable false localizing syndrome seen following neurologic injury, referred to as Kernohan's notch phenomenon, consists of the combination of contralateral pupillary dilatation and ipsilateral weakness and is caused by compression of the tectum of the midbrain [21,22]. Because the diagnostic accuracy of signs and symptoms is limited, the findings described above may be inconstant or unreliable in any given case. Use of radiologic studies may support the diagnosis; however, the most reliable method of diagnosing elevated ICP is to measure it directly.

ICP MONITORING — Empiric therapy for presumed elevated ICP is unsatisfactory because cerebral perfusion pressure (CPP) cannot be monitored reliably without measurement of ICP. Furthermore, most therapies directed at lowering ICP are effective for limited and variable periods of time. In addition, these treatments may have serious side effects. Therefore, while initial steps to control ICP may, by necessity, be performed without the benefit of ICP monitoring, an important early goal in management of the patient with presumed elevated ICP is placement of an ICP monitoring device.

The purpose of monitoring ICP is to improve the clinician's ability to maintain adequate CPP and oxygenation. The only way to reliably determine CPP (defined as the difference between mean arterial pressure [MAP] and ICP) is to continuously monitor both ICP and blood pressure (BP). In general, these patients are managed in intensive care units (ICUs) with an ICP monitor and arterial line. The combination of ICP monitoring and concomitant management of CPP may improve patient outcomes, particularly in patients with closed head trauma [23-26]. A randomized controlled trial (BEST TRIP) conducted in low-resource countries compared management of traumatic brain injury guided by continuous ICP monitoring versus management guided by serial clinical and radiologic examinations and did not find differences in functional outcomes between the two strategies [27]; however, various limitations of this trial make its results less generalizable to specialized trauma centers in high-resource environments. The specific therapeutic targets for CPP in patients with traumatic brain injury are discussed separately. (See "Management of acute moderate and severe traumatic brain injury", section on 'Hemodynamic management'.)

Indications — The diagnosis of elevated ICP generally is based on clinical findings and corroborated by imaging studies and the patient's medical history. Closed head injury is one of the most frequent and best-studied indications for ICP monitoring. Much of the current practice of ICP monitoring has been derived from clinical experience with closed head trauma patients [28]. Indications for ICP monitoring in patients with traumatic brain injury are discussed in detail separately. (See "Management of acute moderate and severe traumatic brain injury", section on 'Intracranial pressure management'.)

Since ICP monitoring is associated with a small risk of serious complications, including central nervous system (CNS) infection and intracranial hemorrhage, it is reasonable to try to limit its use to patients most at risk of elevated ICP [29]. In general, invasive monitoring of ICP is indicated in patients who are [30]:

●Suspected to be at risk for elevated ICP

●Comatose (Glasgow Coma Scale [GCS] <8) (table 2)

●Diagnosed with a process that merits aggressive medical care

Although computed tomography (CT) scans may suggest elevated ICP based on the presence of mass lesions, midline shift, or effacement of the basilar cisterns (image 1), patients without these findings on initial CT may have elevated ICP.

Several studies have shown that up to one-third of patients with initially normal scans developed CT scan abnormalities within the first few days after closed head injury [31,32]. Together, these findings demonstrate that ICP can be elevated even in the setting of a normal initial CT, demonstrating the importance of invasive monitoring in high-risk patients and the role of follow-up imaging in patients who develop clinical evidence of increased ICP during hospitalization. Conversely, patients with unilateral hemispheric mass lesions may cause major compression and tissue shift before produce global ICP elevation [33,34].

Types of monitors — There are four main anatomic sites used in the clinical measurement of ICP: intraventricular, intraparenchymal, subarachnoid, and epidural (figure 5) [35]. Noninvasive and metabolic monitoring of ICP has also been studied, but the clinical value of these methods is unclear at present. Each technique requires a unique monitoring system and has associated advantages and disadvantages.

Intraventricular — Intraventricular monitors are considered the "gold standard" of ICP monitoring catheters. They are surgically placed into the ventricular system and affixed to a drainage bag and pressure transducer with a three-way stopcock. Intraventricular monitoring has the advantage of accuracy, simplicity of measurement, and the unique characteristic of allowing for treatment of some causes of elevated ICP via drainage of cerebrospinal fluid (CSF).

The primary disadvantage is infection, which may occur in up to 20 percent of patients. This risk increases the longer a device is in place [36,37]. Prophylactic antibiotic use is warranted [38]. Prophylactic catheter changes and administration of antimicrobials for the duration of ventricular catheter use do not appear to reduce the risk of infection [37]. (See "Infections of cerebrospinal fluid shunts".)

A further disadvantage of intraventricular systems includes a small (approximately 2 percent) risk of hemorrhage during placement; this risk is greater in coagulopathic patients. In addition, it may be technically difficult to place an intraventricular drain into a small ventricle, particularly in the setting of trauma and cerebral edema complicated by ventricular compression [39].

Intraparenchymal — Intraparenchymal devices consist of a thin cable with an electronic or fiberoptic transducer at the tip. The most widely used device is the fiberoptic Camino system. These monitors can be inserted directly into the brain parenchyma via a small hole drilled in the skull. Advantages include ease of placement and a lower risk of infection and hemorrhage (<1 percent) than with intraventricular devices [40-42].

Disadvantages include the inability to drain CSF for diagnostic or therapeutic purposes and the potential to lose accuracy (or "drift") over several days, since the transducer cannot be recalibrated following initial placement [35]. In addition, there is a greater risk of mechanical failure due to the complex design of these monitors. The reliability of intraparenchymal devices has been debated. One group found only a small (1 mmHg) drift in a group of 163 patients [43]; however, a second report found that readings varied by >3 mmHg in more than half of the 50 patients studied [44].

Subarachnoid — Subarachnoid bolts are fluid-coupled systems within a hollow screw that can be placed through the skull adjacent to the dura. The dura is then punctured, which allows the CSF to communicate with the fluid column and transducer. The most commonly used subarachnoid monitor is the Richmond (or Becker) bolt; other types include the Philly bolt, the Leeds screw, and the Landy screw. These devices have low risk of infection and hemorrhage, but often clog with debris and are unreliable; therefore, they are rarely used. Additionally, they are believed to be less accurate than ventricular ICP devices [35].

Epidural — Epidural monitors contain optical transducers that rest against the dura after passing through the skull. They often are inaccurate, as the dura damps the pressure transmitted to the epidural space, and thus are of limited clinical utility [35,45]. They are used in the management of coagulopathic patients with hepatic encephalopathy complicated by cerebral edema. In this setting, use of these catheters is associated with a significantly lower risk of intracerebral hemorrhage (4 versus 20 and 22 percent for intraparenchymal and intraventricular devices, respectively) and fatal hemorrhage (1 versus 5 and 4 percent, respectively) [46]. (See "Acute liver failure in adults: Management and prognosis".)

Waveform analysis — ICP is not a static value; it exhibits cyclic variation based on the superimposed effects of cardiac contraction, respiration, and intracranial compliance. Under normal physiologic conditions, the amplitude of the waveform is often small, with B waves related to respiration and smaller C waves (or Traube-Hering-Mayer waves) related to the cardiac cycle [12].

Pathological A waves (also called plateau waves) are abrupt, marked elevations in ICP of 50 to 100 mmHg, which usually last for minutes to hours (waveform 1). The presence of A waves signifies a loss of intracranial compliance and heralds imminent decompensation of autoregulatory mechanisms [12,47,48]. Thus, the presence of A waves should suggest the need for urgent intervention to help control ICP.

Noninvasive systems — A number of devices designed to record ICP noninvasively have been studied, but most have not demonstrated reproducible clinical success or have not been studied in large clinical trials. We do not use these in clinical practice.

●Transcranial Doppler (TCD) measures the velocity of blood flow in the proximal cerebral circulation. TCD can be used to estimate ICP based on characteristic changes in waveforms that occur in response to increased resistance to cerebral blood flow (CBF) [49,50]. Generally, TCD is a poor predictor of ICP, although in trauma patients TCD findings may correlate with outcome at six months [51-54].

●Tissue resonance analysis (TRA), an ultrasound-based method, has shown some promise. In one trial 40 patients underwent both invasive and TRA ICP monitoring, with good correlation between concomitant invasive and TRA measurements [55].

●Ocular sonography can provide a noninvasive measure of optic nerve sheath diameter, which has been found to correlate with ICP. A number of studies have found that diameters of 5 to 6 mm have the ability to discriminate between normal and elevated ICP in patients with intracranial hemorrhage and traumatic brain injury [56-62].

●Intraocular pressure can be assessed noninvasively using an ultrasonic handheld optic tonometer. While some evidence suggests that intraocular pressure correlates with ICP in the absence of oculofacial trauma or glaucoma [63], most other studies' findings disagree [64-66].

●Tympanic membrane displacement (measured using an impedance audiometer) has been compared to direct monitoring, based on the hypothesis that increased ICP will transmit a pressure wave to the tympanic membrane via the perilymph [67,68].

Advanced neuromonitoring — In order to supplement ICP monitoring, several technologies have been developed for the treatment of severe traumatic brain injury. These techniques allow for the measurement of cerebral physiologic and metabolic parameters related to oxygen delivery, CBF, and metabolism with the goal of improving the detection and management of secondary brain injury. These are discussed separately. (See "Management of acute moderate and severe traumatic brain injury", section on 'Advanced neuromonitoring'.)

GENERAL MANAGEMENT — The best therapy for elevated intracranial pressure (ICP) is resolution of the proximate cause of elevated ICP. Examples include evacuation of a blood clot, resection of a tumor, cerebrospinal fluid (CSF) diversion in the setting of hydrocephalus, or treatment of an underlying metabolic disorder.

Regardless of the cause, elevated ICP is a medical emergency, and treatment should be undertaken as expeditiously as possible. In addition to definitive therapy, there are maneuvers that can be employed to reduce ICP acutely. Some of these techniques are generally applicable to all patients with suspected elevated ICP; others (particularly glucocorticoids) are reserved for specific causes of elevated ICP.

Resuscitation — The urgent assessment and support of oxygenation, blood pressure (BP), and end-organ perfusion are particularly important in trauma, but applicable to all patients [69-71]. If elevated ICP is suspected, care should be taken to minimize further elevations in ICP during intubation through careful positioning, appropriate choice of paralytic agents (if required), and adequate sedation. Pretreatment with lidocaine has been suggested as a useful intervention to decrease the rise in ICP associated with intubation; however, good clinical evidence supporting this approach is limited [72]. (See "Overview of inpatient management of the adult trauma patient" and "Advanced cardiac life support (ACLS) in adults" and "Adult basic life support (BLS) for health care providers".)

Large shifts in BP should be minimized, with particular care taken to avoid hypotension. Although it might seem that lower BP would result in lower ICP, this is not the case. Hypotension, especially in conjunction with hypoxemia, can induce reactive vasodilation and elevations in ICP. As noted above, pressors have been shown to be safe for use in most patients with intracranial hypertension, and may be required to maintain cerebral perfusion pressure (CPP) >60 mmHg [23]. (See "Use of vasopressors and inotropes".)

Urgent situations — Life-saving measures may need to be instituted prior to a more detailed workup (eg, imaging or ICP monitoring) in a patient who presents acutely with history or examination findings suggestive of elevated ICP. Many of these situations will rely upon clinical judgment, but the following combination of findings suggests the need for urgent intervention [73,74]:

●A history that suggests elevated ICP (eg, head trauma, sudden severe headache typical of subarachnoid hemorrhage)

●An examination that suggests elevated ICP (unilateral or bilaterally fixed and dilated pupil[s], decorticate or decerebrate posturing, bradycardia, hypertension and/or respiratory depression)

●A Glasgow Coma Scale (GCS) ≤8

●Potentially confounding and reversible causes of depressed mental status, such as hypotension (systolic BP [SBP] <60 mmHg in adults), hypoxemia (PaO₂ <60 mmHg), hypothermia (<36ºC), or obvious intoxication, are absent

In such patients, osmotic diuretics may be used urgently. (See 'Mannitol' below.)

In addition, standard resuscitation techniques should be instituted as soon as possible:

●Head elevation

●Hyperventilation to a PCO₂ of 26 to 30 mmHg

●Intravenous mannitol (1 to 1.5 g/kg)

Concomitant with these measures should be aggressive evaluation of the underlying diagnosis, including neuroimaging, detailed neurologic examination, and history gathering. Hyperventilation may be contraindicated in the setting of traumatic brain injury and acute stroke, and is discussed separately (see 'Hyperventilation' below). If appropriate, ventriculostomy is a rapid means of simultaneously diagnosing and treating elevated ICP.

Monitoring and the decision to treat — If a diagnosis of elevated ICP is suspected and an immediately treatable proximate cause is not present, then ICP monitoring should be instituted. The use of ICP monitoring is associated with decreased mortality in patients with traumatic brain injury [24]. (See "Management of acute moderate and severe traumatic brain injury", section on 'Intracranial pressure management'.)

The type of monitoring device employed should be based on an assessment of the advantages and disadvantages discussed previously (figure 5). (See 'ICP monitoring' above.)

The goal of ICP monitoring and treatment should be to keep ICP <20 mmHg [75]. Interventions should be utilized only when ICP is elevated above 20 mmHg for >5 to 10 minutes. As discussed above, brief physiologic elevations in ICP may occur in the setting of coughing, movement, suctioning, or ventilator asynchrony.

Fluid management — In general, patients with elevated ICP do not need to be severely fluid restricted [76]. Patients should be kept euvolemic and normo- to hyperosmolar. This can be achieved by avoiding all free water (including D5W, 0.45 percent [half normal] saline, and enteral free water) and employing only isotonic fluids (such as 0.9 percent [normal] saline). Serum osmolality should be kept >280 mOsm/L, and often is kept in the 295 to 305 mOsm/L range. Hyponatremia is common in the setting of elevated ICP, particularly in conjunction with subarachnoid hemorrhage. (See "Causes of hypotonic hyponatremia in adults" and "Treatment of hyponatremia: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) and reset osmostat", section on 'Subarachnoid hemorrhage'.)

Similarly, the value of colloid compared with crystalloid fluid resuscitation in patients with elevated ICP has been studied, but findings have been inconclusive with respect to the superior approach [77]. A subgroup analysis in one large study, however, suggested that in patients with traumatic brain injury, fluid resuscitation with albumin was associated with a higher mortality as compared with normal saline [78]. (See "Management of acute moderate and severe traumatic brain injury".)

Hypertonic saline in bolus doses may acutely lower ICP, but further investigations are required to define a role, if any, for this approach in the management of elevated ICP. (See 'Hypertonic saline bolus' below.)

Sedation — Keeping patients appropriately sedated can decrease ICP by reducing metabolic demand, ventilator asynchrony, venous congestion, and the sympathetic responses of hypertension and tachycardia [79]. Establishing a secure airway and close attention to BP allow the clinician to identify and treat apnea and hypotension quickly.

Propofol has been utilized to good effect in this setting, as it is easily titrated and has a short half-life, thus permitting frequent neurologic reassessment. (See "Sedative-analgesia in ventilated adults: Management strategies, agent selection, monitoring, and withdrawal".)

Blood pressure control — In general, BP should be sufficient to maintain CPP >60 mmHg. As discussed above, pressors can be used safely without further increasing ICP. This is particularly relevant in the setting of sedation, when iatrogenic hypotension can occur. Hypertension should generally only be treated when CPP >120 mmHg and ICP >20 mmHg.

Caution should be taken to avoid CPP <50 mmHg or, as noted above, normalization of BP in patients with chronic hypertension in whom the autoregulatory curve has shifted to the right (see 'Autoregulation' above). General issues regarding BP management following stroke are presented elsewhere. (See "Antihypertensive therapy for secondary stroke prevention".)

Position — Patients with elevated ICP should be positioned to maximize venous outflow from the head. Important maneuvers include reducing excessive flexion or rotation of the neck, avoiding restrictive neck taping, and minimizing stimuli that could induce Valsalva responses, such as endotracheal suctioning.

Patients with elevated ICP have historically been positioned with the head elevated above the heart (usually 30 degrees) to increase venous outflow. It should be noted that head elevation may lower CPP [23,80]; however, given the proven efficacy of head elevation in lowering ICP, most experts recommend raising the patient's head as long as the CPP remains at an appropriate level [81].

Fever — Elevated metabolic demand in the brain results in increased cerebral blood flow (CBF) and can elevate ICP by increasing the volume of blood in the cranial vault. Conversely, decreasing metabolic demand can lower ICP by reducing blood flow.

Fever increases brain metabolism and has been demonstrated to increase brain injury in animal models [82]. Therefore, aggressive treatment of fever, including acetaminophen and mechanical cooling, is recommended in patients with increased ICP. Intracranial hypertension is a recognized indication for neuromuscular paralysis in selected patients [83]. (See "Neuromuscular blocking agents in critically ill patients: Use, agent selection, administration, and adverse effects".)

Antiseizure therapy — Seizures can both complicate and contribute to elevated ICP [84,85]. Anticonvulsant therapy should be instituted if seizures are suspected; prophylactic treatment may be warranted in some cases. There are no clear guidelines for the latter, but examples include high-risk mass lesions, such as those within supratentorial cortical locations, or lesions adjacent to the cortex, such as subdural hematomas or subarachnoid hemorrhage.

SPECIFIC THERAPIES — As mentioned previously, the best treatment of elevated ICP is to address its underlying cause. If this is not possible, a series of steps should be instituted to reduce ICP in an attempt to improve outcome. In all cases, the clinician should bear in mind the themes of resuscitation, reduction of intracranial volume, and frequent reevaluation discussed above.

Osmotic therapy and diuresis — With growing familiarity of use, hypertonic saline has increasingly been employed as a first-line agent, supplanting mannitol at numerous institutions.

Hypertonic saline bolus — Hypertonic saline in bolus doses can acutely lower ICP; however, the effect of this early intervention on long-term clinical outcomes remains unclear [86-94]. The volume and tonicity of saline (7.2 to 23.4 percent) used in these reports have varied widely. As an example, one controlled trial randomly assigned 226 patients with traumatic brain injury to prehospital resuscitation with 250 mL hypertonic saline (7.5 percent) or the same volume of Ringer's lactate [86]. Survival until hospital discharge, six-month survival, and neurologic function six months after injury were similar in both groups. In a retrospective review of patients treated at a single study, the safety and efficacy of 14.6 and 23.4 percent saline boluses appeared to be similar [95].

Mannitol and hypertonic saline have been compared in at least eight randomized trials of patients with elevated ICP from a variety of causes (traumatic brain injury, stroke, tumors) [93,96-99]. Meta-analyses of these trials have found that hypertonic saline appears to have greater efficacy in managing elevated ICP, but clinical outcomes have not been systematically examined [100,101]. Further clinical trials are required to clarify the appropriate role of hypertonic saline infusion versus mannitol in the management of elevated ICP [102,103].

The role of hypertonic saline in the management of elevated ICP in traumatic brain injury is discussed separately. (See "Management of acute moderate and severe traumatic brain injury", section on 'Osmotic therapy'.)

Mannitol — Osmotic diuretics reduce brain volume by drawing free water out of the tissue and into the circulation, where it is excreted by the kidneys, thus dehydrating brain parenchyma [104-107]. The most commonly used agent is mannitol. It is prepared as a 20 percent solution, and given as a bolus of 1 g/kg. Repeat dosing can be given at 0.25 to 0.5 g/kg as needed, generally every six to eight hours. Use of any osmotic agent should be carefully evaluated in patients with renal insufficiency.

The effects are usually present within minutes, peak at approximately one hour, and last 4 to 24 hours [30,108]. Some have reported a "rebound" increase in ICP; this probably occurs when mannitol, after repeated use, enters the brain though a damaged blood-brain barrier and reverses the osmotic gradient [109,110]. Useful parameters to monitor in the setting of mannitol therapy include serum sodium, serum osmolality, and renal function.

Concerning findings associated with the use of mannitol include serum sodium >150 mEq, serum osmolality >320 mOsm, or evidence of evolving acute tubular necrosis (ATN). In addition, mannitol can lower systemic blood pressure (BP), necessitating careful use if associated with a fall in cerebral perfusion pressure (CPP). Patients with known renal disease may be poor candidates for osmotic diuresis. (See "Complications of mannitol therapy".)

Other agents — Furosemide, 0.5 to 1.0 mg/kg intravenously, may be given with mannitol to potentiate its effect. However, this effect can also exacerbate dehydration and hypokalemia [111-113].

Glycerol and urea were used historically to control ICP via osmoregulation; however, use of these agents has decreased because equilibration between brain and plasma levels occurs more quickly than with mannitol. Furthermore, glycerol has been shown to have a significant rebound effect and to be less effective in ICP control [114,115].

Glucocorticoids — Glucocorticoids were associated with a worse outcome in a large randomized clinical trial of their use in moderate to severe head injury [116,117]. They should not be used in this setting. (See "Management of acute moderate and severe traumatic brain injury".)

In addition, glucocorticoids are not considered to be useful in the management of cerebral infarction or intracranial hemorrhage. (See "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis".)

By contrast, glucocorticoids may have a role in the setting of intracranial hypertension caused by brain tumors and central nervous system (CNS) infections. (See "Management of vasogenic edema in patients with primary and metastatic brain tumors" and "Treatment and prognosis of bacterial brain abscess".)

Hyperventilation — Use of mechanical ventilation to lower PaCO₂ to 26 to 30 mmHg has been shown to rapidly reduce ICP through vasoconstriction and a decrease in the volume of intracranial blood; a 1 mmHg change in PaCO₂ is associated with a 3 percent change in cerebral blood flow (CBF) [118]. Hyperventilation also results in respiratory alkalosis, which may buffer post-injury acidosis [118]. The effect of hyperventilation on ICP is short-lived (1 to 24 hours) [119-121]. Following therapeutic hyperventilation, the patient's respiratory rate should be tapered back to normal over several hours to avoid a rebound effect [122].

Therapeutic hyperventilation should be considered as an urgent intervention when elevated ICP complicates cerebral edema, intracranial hemorrhage, and tumor. Hyperventilation should not be used on a chronic basis, regardless of the cause of increased ICP.

Hyperventilation should be minimized in patients with traumatic brain injury or acute stroke. In these settings, vasoconstriction may cause a critical decrease in local cerebral perfusion and worsen neurologic injury, particularly in the first 24 to 48 hours [28,119,121,123-126]. Thus, the need for hyperventilation should be carefully considered, and prophylactic hyperventilation in the absence of elevated ICP should be avoided. (See "Management of acute moderate and severe traumatic brain injury", section on 'Ventilation'.)

Barbiturates — The use of barbiturates is predicated on their ability to reduce brain metabolism and CBF, thus lowering ICP and exerting a neuroprotective effect [127-130]. Pentobarbital is generally used, with a loading dose of 5 to 20 mg/kg as a bolus, followed by 1 to 4 mg/kg per hour [131,132]. Treatment should be assessed based on ICP, CPP, and the presence of unacceptable side effects. Continuous electroencephalography (EEG) monitoring is generally used; EEG burst suppression is an indication of maximal dosing.

The therapeutic value of this maneuver is somewhat unclear. In a randomized trial of 73 patients with elevations in ICP refractory to standard therapy, patients treated with pentobarbital were 50 percent more likely to have their ICP controlled. However, there was no difference in clinical outcomes between groups [133]. In general, the use of barbiturates is a "last-ditch" effort, as several studies show that their ability to lower ICP does not appear to affect outcomes [118,134].

Barbiturate therapy can be complicated by hypotension, possibly requiring vasopressor support. The use of barbiturates is also associated with a loss of the neurologic examination, requiring accurate ICP, hemodynamic, and often EEG monitoring to guide therapy. In this setting, thiopental has been reported to produce hypokalemia with induction and rebound hyperkalemia on drug cessation [135].

Therapeutic hypothermia — First reported as a treatment for brain injury in the 1950s, induced or therapeutic hypothermia has remained a controversial issue in the debate concerning the management of elevated ICP [118,136,137]. It is not currently recommended as a standard treatment for increased ICP in any clinical setting.

Hypothermia decreases cerebral metabolism and may reduce CBF and ICP. Initial studies of hypothermia were limited by systemic side effects, including cardiac arrhythmias and severe coagulopathy. However, later work suggested that hypothermia can lower ICP and may improve patient outcomes [138]. Hypothermia also appeared to be effective in lowering ICP after other therapies have failed [139,140].

Hypothermia can be achieved using whole-body cooling, including lavage and cooling blankets, to a goal core temperature of 32 to 34ºC. The best method of cooling (local versus systemic), the optimal target core temperature, and the appropriate duration of treatment are not known [141]. It appears that rewarming should be accomplished over a period of less than 24 hours [142].

The value of therapeutic hypothermia has been best assessed in patients after traumatic brain injury, but its role has not been well established in that setting. (See "Management of acute moderate and severe traumatic brain injury", section on 'Hypothermia' and "Elevated intracranial pressure (ICP) in children: Management", section on 'Temperature control'.)

Given the uncertainties surrounding the appropriate use of therapeutic hypothermia in patients with elevated ICP, this treatment should be limited to clinical trials, or to patients with intracranial hypertension refractory to other therapies.

Removal of CSF — When hydrocephalus is identified, a ventriculostomy should be inserted (figure 6). Rapid aspiration of cerebrospinal fluid (CSF) should be avoided because it may lead to obstruction of the catheter opening by brain tissue. Also, in patients with aneurysmal subarachnoid hemorrhage, abrupt lowering of the pressure differential across the aneurysm dome can precipitate recurrent hemorrhage.

CSF should be removed at a rate of approximately 1 to 2 mL/minute, for two to three minutes at a time, with intervals of two to three minutes in between until a satisfactory ICP has been achieved (ICP <20 mmHg) or until CSF is no longer easily obtained. Slow removal can also be accomplished by passive gravitational drainage through the ventriculostomy. A lumbar drain is generally contraindicated in the setting of high ICP due to the risk of transtentorial herniation.

Decompressive craniectomy — Decompressive craniectomy removes the rigid confines of the bony skull, increasing the potential volume of the intracranial contents and circumventing the Monroe-Kellie doctrine. There is a growing body of literature supporting the efficacy of decompressive craniectomy in certain clinical situations [143-152]. Importantly, it has been demonstrated that in patients with elevated ICP, craniectomy alone lowered ICP 15 percent, but opening the dura in addition to the bony skull resulted in an average decrease in ICP of 70 percent [153]. Decompressive craniectomy also appears to improve brain tissue oxygenation [154].

Observational data suggest that rapid and sustained control of ICP, including the use of decompressive craniectomy, improves outcomes in trauma, stroke, and subarachnoid hemorrhage in carefully selected cases [155-162]. The indications for decompressive craniectomy in these settings are discussed separately (see "Malignant cerebral hemispheric infarction with swelling and risk of herniation" and "Management of acute moderate and severe traumatic brain injury", section on 'Decompressive craniectomy'). Obvious mass lesions associated with an elevated ICP should be removed, if possible.

Potential complications of surgery include herniation through the skull defect, spinal fluid leak, wound infection, and epidural and subdural hematoma [163].

Paradoxical transtentorial herniation is an uncommon but potentially lethal complication in patients with hemicraniectomy and a large skull defect who subsequently undergo lumbar puncture (LP) or CSF drainage [164,165]. This results from the combined effects of atmospheric pressure with the negative pressure of the LP or ventriculostomy. It has also been described as a delayed complication three to five months after decompressive craniectomy for cerebral infarction in the absence of LP or ventriculostomy [166]. Marked decompression of the skin and dura over the skull defect accompanies and may precede neurologic signs of herniation. Standard treatments to lower ICP can hasten herniation. Instead, the patient should be placed supine or in the Trendelenburg position, CSF drains should be clamped, crystalloid fluid should be administered intravenously, and an epidural blood patch placed for patients with dural leak.

SUMMARY — The best therapy for intracranial hypertension is resolution of the proximate cause of elevated ICP. Regardless of the cause, treatment should be undertaken as expeditiously as possible, and should be based on the principles of resuscitation, reduction of the volume of the intracranial contents, and reassessment. Interventions should be based on careful assessment of the individual clinical scenario rather than on strict protocols. Specific recommendations regarding the assessment and treatment of elevated intracranial pressure (ICP) in individual disease settings, including trauma, cerebrovascular disease, and other conditions, are discussed separately. As examples:

●(See "Management of acute moderate and severe traumatic brain injury", section on 'Intracranial pressure management'.)

●(See "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis", section on 'Intracranial pressure management'.)

●(See "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis".)

●(See "Intracranial epidural hematoma in adults", section on 'Intracranial pressure'.)

●(See "Subdural hematoma in adults: Management and prognosis", section on 'Patients on antiplatelets'.)

●(See "Malignant cerebral hemispheric infarction with swelling and risk of herniation".)

●(See "Cerebral venous thrombosis: Treatment and prognosis", section on 'Elevated intracranial pressure and herniation'.)

●(See "Management of vasogenic edema in patients with primary and metastatic brain tumors".)

●(See "Neurologic complications of bacterial meningitis in adults", section on 'Increased intracranial pressure'.)

●(See "Clinical management and monitoring during antifungal therapy for cryptococcal meningoencephalitis in persons with HIV", section on 'Monitoring of intracranial pressure'.)

●(See "Acute liver failure in adults: Management and prognosis", section on 'Cerebral edema'.)