Elevated intracranial pressure (ICP) in children: Management

INTRODUCTION — The management of elevated ICP in children will be reviewed here.

The clinical manifestations and diagnosis of elevated ICP in children and the initial approach to severe traumatic brain injury in children are discussed separately. (See "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis" and "Severe traumatic brain injury (TBI) in children: Initial evaluation and management".)

RECOGNITION — The assessment and management of elevated ICP are performed jointly in practice. Acutely elevated ICP should be suspected in children with any one of the following findings (see "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis", section on 'Acutely elevated ICP'):

●Severe headache with vomiting

●Coma

●Hypertension with bradycardia or tachycardia

●Papilledema

●Signs of transtentorial herniation (figure 1 and table 1)

●Abrupt onset of weakness or hemiplegia

These findings are especially associated with intracranial hypertension in patients with head injury, known intracranial lesions (eg, brain tumor, cerebral abscess, or intracranial hemorrhage), shunted hydrocephalus, or findings of child abuse (table 2).

After stabilization, the diagnosis of elevated ICP is usually established by neuroimaging (typically noncontrast computed tomography [CT] of the head). CT is also necessary to identify underlying causes for intracranial hypertension (table 3). (See "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis", section on 'Computed tomography'.)

Direct measurement of increased ICP ≥20 mmHg (27 cmH₂O) using an external ventricular drain or intraparenchymal ICP monitor is the definitive way to confirm the presence of intracranial hypertension. However, invasive measurement of ICP is reserved for the most severely affected children in whom the benefits of direct measurement outweigh the risks of bleeding and infection (eg, Glasgow coma score ≤8 (table 4) following head trauma or a child diagnosed with a condition that warrants aggressive treatment to manage ICP). (See "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis", section on 'Invasive measurement of ICP'.)

The clinical manifestations and diagnosis of intracranial hypertension in children are discussed in greater detail separately. (See "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis".)

THRESHOLD FOR TREATMENT — Measured ICP ≥20 mmHg (27 cmH₂O) is considered elevated [1]. When the invasively measured ICP is ≥20 mmHg for longer than five minutes in symptomatic patients, then emergency treatment is indicated [2]. (See "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis", section on 'Intracranial pressure'.)

In patients in whom ICP is not known, signs of herniation (figure 1 and table 1) also warrant emergency treatment pending noncontrast CT of the head and placement of an intracranial monitor. (See 'Emergency treatment of brain herniation' below.)

INITIAL STABILIZATION — The treatment of intracranial hypertension (ICP ≥20 mmHg [27 cmH₂O]) depends upon the condition of the child and the etiology of ICP elevation. The approach that follows is consistent with Neurocritical Care Society principles of resuscitation and initial management of acute elevations of ICP contained in their educational materials on Emergency Neurologic Life Support [3], and the 2019 Brain Trauma Foundation guidelines for the management of pediatric severe traumatic brain injury (TBI) [1,4,5].

Stabilization of airway, breathing, and circulation according to the principles of Pediatric Advanced Life Support and, for injured children, Advanced Trauma Life Support is essential to the successful treatment of elevated ICP. (See "Pediatric advanced life support (PALS)" and "Trauma management: Approach to the unstable child", section on 'Initial approach'.):

●Ensuring normal oxygenation and ventilation prevents vasodilation caused by hypoxemia and hypercapnia which, in turn, can increase ICP. (See "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis", section on 'Physiology'.)

●Maintenance of blood pressure is necessary to prevent cerebral ischemia by promoting adequate cerebral perfusion pressure (CPP) which is calculated as the difference between mean arterial pressure (MAP) and ICP.

During stabilization, elevation of the head from 15 to 30 degrees while maintaining a midline position, avoidance of fever, and providing adequate pain control are supplementary measures to treat elevated ICP. (See 'General measures for all patients' below.)

Whenever possible, consultation with a neurosurgeon with pediatric expertise should occur before administration of hyperosmolar therapy or therapeutic hyperventilation.

Once the child is stable, rapid neuroimaging, typically CT of the head without contrast, should be performed. (See "Pediatric advanced life support (PALS)" and "Trauma management: Approach to the unstable child" and "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis", section on 'Noninvasive detection of elevated ICP'.)

Airway — A secure airway must be established in all patients with altered mental status to prevent hypoxia, hypercarbia, and pulmonary aspiration. The steps for emergency intubation in children are discussed in detail separately. (See "Technique of emergency endotracheal intubation in children", section on 'Procedure'.)

Indications for endotracheal intubation in children with elevated ICP include any one of the following:

●Refractory hypoxia

●Hypoventilation

●Glasgow coma score (GCS) of ≤8 (table 4) or GCS <12 and rapidly declining

●Loss of airway protective reflexes

●Acute herniation requiring controlled hyperventilation

Intubation, if necessary, should be undertaken by someone who has experience performing this procedure in children with intracranial hypertension. Adequate oxygenation should be maintained before and during the procedure. Cervical spine stabilization must be maintained in patients with potential cervical spine injury.

Rapid sequence intubation — Precautions must be taken during endotracheal intubation to minimize elevations in ICP that are associated with this procedure. Rapid sequence intubation (RSI) should be performed (table 5). Awake intubation is contraindicated. (See "Rapid sequence intubation (RSI) in children for emergency medicine: Approach".)

Our approach to medications for RSI in children with concern for intracranial hypertension is as follows:

●Hemodynamically unstable patients – For hemodynamically unstable patients we use etomidate and rocuronium (initial dose 1.2 mg/kg to facilitate rapid onset of paralysis). (See "Rapid sequence intubation (RSI) in children for emergency medicine: Medications for sedation and paralysis", section on 'Rocuronium' and "Rapid sequence intubation (RSI) in children for emergency medicine: Medications for sedation and paralysis", section on 'Etomidate'.)

Ketamine instead of etomidate is proposed by some experts as an option for hypotensive patients. Evidence suggesting that ketamine elevates ICP and is therefore harmful for patients with head injury is now considered weak. However, it is not our practice to use ketamine for these patients. Furthermore, ketamine should be avoided in hypertensive patients with elevated ICP. (See "Induction agents for rapid sequence intubation in adults for emergency medicine and critical care", section on 'Elevated intracranial pressure'.)

Some experts also administer lidocaine (1 to 2 mg/kg, maximum dose 200 mg, given three to five minutes before laryngoscopy) although evidence supporting its ability to blunt further increases of ICP during laryngoscopy is inconsistent. We do not routinely use lidocaine for RSI in patients with elevated ICP because our experience suggests that etomidate is adequate, and RSI without lidocaine is simpler to perform. (See "Pretreatment medications for rapid sequence intubation in adults for emergency medicine and critical care", section on 'Lidocaine'.)

●Hemodynamically stable or hypertensive patients – Propofol (1 to 3 mg/kg/dose intravenously [IV]), fentanyl (1 mcg/kg/dose IV), and rocuronium (initial dose 1.2 mg/kg to facilitate rapid onset of paralysis); etomidate may be used instead of propofol. If propofol is used, the physician should monitor the blood pressure carefully and take measures to avoid hypotension because the neuroprotective effect of propofol can be offset by a decrease in CPP as a result of decreased arterial pressure. (See "Rapid sequence intubation (RSI) in children for emergency medicine: Medications for sedation and paralysis", section on 'Propofol'.)

After intubation, we maintain hemodynamically stable patients with a combination of the following medications:

●Analgesia – Fentanyl or morphine infusion, morphine is associated with a greater hypotensive effect

●Sedation – Midazolam infusion

●Paralysis – Vecuronium infusion

Breathing — Hyperventilation (PaCO₂ <35 mmHg) decreases cerebral blood flow and may cause cerebral ischemia. Consequently, PaCO₂ should be maintained between 35 and 40 mmHg unless there are signs of acute or impending herniation that require emergency measures prior to a more definitive intervention. (See 'Therapeutic hyperventilation' below.)

It is essential that oxygenation and ventilation be closely monitored after intubation using a combination of arterial blood gas measurements, continuous pulse oximetry, and quantitative end-tidal capnography. (See "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis", section on 'Cerebral blood flow'.)

Temporary therapeutic hyperventilation (PaCO₂ 30 to 35 mmHg for up to two hours) may be initiated under direction by a neurosurgeon in patients with signs of impending herniation (figure 1 and table 1) in whom surgical intervention is planned.

Aggressive hyperventilation with PaCO₂ below 30 is indicated only if there are clinical signs of acute herniation. Aggressive hyperventilation may prevent herniation by relieving the pressure differential in the intracranial compartments. However, the associated risk of cerebral ischemia with excessive lowering of cerebral blood flow (CBF) can be justified only in patients who have signs of ongoing herniation [6,7].

Circulation — Cerebral perfusion must be maintained to prevent secondary ischemic injuries. Patients with elevated ICP should have adequate venous access (eg, two large-bore peripheral IV catheters) in place so that shock can be rapidly treated. Ancillary studies should be obtained to help identify specific etiologies of increased ICP, comorbid conditions in trauma patients, and to differentiate elevated ICP from other causes of coma. Suggested studies are provided separately. (See "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis", section on 'Ancillary studies'.)

Hypovolemia should be avoided because it decreases cerebral perfusion. When present, hypovolemia should be treated with isotonic fluids (eg, normal saline) with a goal of attaining a state of normal, rather than excess, volume. Excess intravascular volume may exacerbate the development of cerebral edema. The administration of hypotonic fluids, such as D5W, should be avoided because they deliver too much free water, which may exacerbate cerebral edema and cellular destruction. (See "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis", section on 'Cerebral edema'.)

In patients with distributive shock caused by central nervous system or spinal cord injury, appropriate mean arterial pressure for age should be maintained using IV fluids and pharmacologic vasopressors with alpha adrenergic effects (eg, norepinephrine or phenylephrine) as needed. Bradycardia caused by cervical spinal cord or high thoracic spinal cord disruption may require external pacing or administration of atropine. (See "Acute traumatic spinal cord injury", section on 'Cardiovascular complications'.)

Blood pressure monitoring using an arterial catheter should also be initiated as soon as possible but should not delay aggressive treatment of intracranial hypertension. The performance of arterial catheter placement in children is discussed separately. (See "Arterial puncture and cannulation in children", section on 'Arterial cannulation'.)

Temperature control — Children with increased ICP should be prevented from becoming febrile through the use of antipyretics, and if necessary, cooling blankets. Most centers do not use hypothermia early in treatment. However, some centers still reserve the use of hypothermia therapy for control of refractory intracranial hypertension.

Although small trials indicate futility for hypothermia and a potential for increased mortality, evidence is insufficient to determine the role of hypothermia for the treatment of increased ICP in children and further study is needed. In a meta-analysis of eight trials (492 children), controlled hypothermia was associated with increased mortality [8]. However, two trials included in this meta-analysis contained subsets of cases reported from another included trial [9]. A separate meta-analysis that accounted for this duplication (seven trials, 472 children) suggested a concerning trend to more death among children who received hypothermia (risk ratio 1.4, 95% CI 0.8 to 2.6) that was not impacted by duration of hypothermia (24, 48, and 72 hours) but could not reject a potential benefit [9]. If hypothermia is used, it should be part of a carefully controlled protocol and, preferably, part of a large multicenter trial.

Neurosurgical consultation — Early neurosurgical consultation should be obtained in any child with intracranial hypertension to direct management decisions regarding ICP monitoring, medical management (eg, osmolar therapy or hyperventilation), ventricular cerebrospinal fluid drainage, or surgical interventions (eg, evacuation of an epidural hematoma, excision of a mass lesion or decompressive craniectomy) [6,7].

EMERGENCY TREATMENT OF BRAIN HERNIATION — In the period before imaging has been acquired, and before invasive ICP measurements and possible emergency surgery can be accomplished, medical management of brain herniation includes [1]:

●Administration of hyperosmolar therapy – For patients with brain herniation, initial hyperosmolar therapy consists of:

•Intravenous (IV) mannitol (0.5 to 1 g/kg infused over 10 minutes) (see 'Mannitol' below)

Mannitol causes a brisk diuresis. For this reason, when possible, all patients receiving mannitol should have a Foley catheter placed to prevent bladder overdistension and to monitor urine output. Isotonic fluids (eg, normal saline) should be available and given, as needed, to prevent hypotension and dehydration.

OR

•IV hypertonic saline (eg, 3 percent; 1 to 3 mL/kg up to a maximum dose of 250 mL, or, if a central line has been placed, 23.4 percent; 0.5mL/kg up to a maximum dose of 30 mL over 10 minutes) (see 'Hypertonic saline' below)

●Manual hyperventilation – While hyperosmolar therapy is given, ventilation should be titrated to a PaCO₂ of 30 to 35 mmHg. If hyperosmolar therapy is not rapidly effective, the clinician should titrate manual hyperventilation with fraction of inspired oxygen (FiO₂) of 1.0, to reversal of pupillary dilation. Aggressive hyperventilation with PaCO₂ below 30 mmHg may be necessary to achieve this endpoint.

Hyperventilation cannot be accomplished by bag-mask ventilation. Thus, all spontaneously breathing patients with signs of brain herniation require rapid sequence intubation. (See 'Airway' above.)

●Maintenance of hemodynamic stability – Hypovolemic patients should receive isotonic fluids to restore circulating volume. Hypotension should be avoided. (See 'Circulation' above.)

Hypertension reflects the body's compensatory mechanism to maintain cerebral perfusion pressure (CPP; the difference between mean arterial pressure [MAP] and ICP); thus, antihypertensive treatment is contraindicated.

TREATMENT OF ELEVATED ICP — Therapy of elevated ICP follows a stepwise progression of interventions that have an increasing risk of adverse effects.

General measures for all patients — Some general measures for treating elevated ICP have a low risk of adverse effects and can be used in all patients in whom increased ICP is suspected. The vital signs, including temperature, of all patients should be continuously monitored.

Initial measures include [1,2,7]:

●Rapid treatment of hypoxia, hypercarbia, and hypotension – Even brief derangements in these parameters can adversely affect outcome. Isotonic fluids (eg, 0.9 percent [normal] saline) should be administered to patients to maintain adequate mean arterial pressure (MAP); if this fails because of distributive shock caused by central nervous system or spinal cord injury, infusions of vasopressors can be initiated. (See 'Circulation' above.)

●Elevation of the head from 15 to 30 degrees – Mild head elevation can lower ICP without adversely affecting MAP or cerebral perfusion pressure (CPP) [10-12]. For most patients, elevation greater than 40 degrees may decrease CPP and should be avoided.

For patients who exhibit poor ICP control, there may be value in identifying optimal head-of-bed (HOB) position that produces the lowest ICP and maximizes CPP. However, such maneuvers require consultation with a neurosurgeon and close attention to the correct calibration position of the arterial line and the ICP monitors (intraparenchymal monitors have a fixed position). As an example, in a series of 18 patients with severe traumatic brain injury (TBI) who had HOB position varied between 0 and 50 degrees during the acute postinjury phase, an optimal position was found in 13 patients; this position varied over time and was outside of the commonly recommended height of 15 to 30 degrees in some patients [13].

●Head position – The head should be maintained in the midline position to avoid obstruction of venous return from the head to the thorax.

●Hypoglycemia – Obtain a rapid blood glucose and treat hypoglycemia (glucose <60 mg/dL [3.3 mmol/L]).

●Maintain normal body temperature – Aggressively treating fever with antipyretics and cooling blankets is important because hyperpyrexia increases cerebral metabolism and increases cerebral blood flow (CBF), further elevating ICP.

●Anemia – Maintain hemoglobin >7 g/dL (4.34 mmol/L) (optimization to higher levels may be indicated based upon brain tissue oxygen monitoring, if available).

●Administer prophylactic anticonvulsants – Anticonvulsants (eg, levetiracetam, fosphenytoin, or phenobarbital, depending on availability and feasibility of administration) should be given to patients who are at high risk of developing seizures (eg, those who have parenchymal abnormalities, depressed skull fractures, or severe TBIs). Seizures are associated with increases in ICP [14]. Breakthrough seizures are best treated with benzodiazepines (eg, midazolam or lorazepam). (See "Management of convulsive status epilepticus in children".)

●Pain control – Maintaining adequate analgesia to blunt the response to noxious stimuli also prevents spiking of ICP.

Measures in intubated patients — Additional measures can be taken in patients who require endotracheal intubation. These include [15]:

●Head position and securing of the endotracheal tube – Maintain the head in a midline position and taping the endotracheal tube to the face, rather than tying it around the neck, to prevent obstruction of venous outflow.

●Ventilator settings – Avoid high positive pressures (PIP) and high positive end expiratory pressures (PEEP) as long as oxygenation remains adequate; otherwise high PIP and PEEP may increase intrathoracic pressure and impede venous drainage.

●Sedation and muscle relaxation – Maintain adequate sedation to permit controlled ventilation; neuromuscular blockade may be required if ICP remains elevated despite adequate sedation. Muscle relaxation can also prevent shivering, fighting against the ventilator, and permit hyperventilation if it is required. Intermittent dosing of short-acting agents (eg, vecuronium or rocuronium) are preferred and can be withheld periodically to permit neurologic evaluation.

●Prophylactic lidocaine prior to endotracheal tube suctioning – Administer lidocaine (1 mg/kg intravenously [IV] or 2 mg/kg endotracheally [ETT]) before endotracheal tube suctioning to blunt the gag and cough responses; careful attention must be paid to the cumulative dose to avoid lidocaine toxicity, particularly in young children. Either route of administration is effective.

Medical treatment of sustained intracranial hypertension or impending herniation — We suggest an approach to patients with sustained (>5 minutes) and symptomatic intracranial hypertension (ICP >20 mmHg [27 cmH₂]) or impending herniation that is based upon the principles of Emergency Neurologic Life Support (algorithm 1) [2]. Whenever possible, a neurosurgeon with pediatric expertise should be involved with the decision to administer osmolar therapy with hypertonic saline or mannitol or the initiation of hyperventilation and to determine the need for surgical intervention.

The goals of therapy are to minimize ICP elevation and maintain adequate CPP. Limited observational evidence suggests that target CPP in children should be age-specific as follows [2,16]:

●0 to 5 years of age – 40 to 50 mmHg

●6 to 17 years of age – 50 to 60 mmHg

Of note, extreme elevations in CPP (eg, 60 to 70 mmHg) may exceed the capabilities of cerebral blood flow autoregulation and further increase ICP [2].

Hyperosmolar therapy

Choice of agent — Evidence is limited regarding the best single drug regimen for osmolar therapy in children with increased ICP and significant practice variation exists [2,17]. For most patients, osmolar therapy with either mannitol or hypertonic saline has a similar effect on reducing ICP and increasing CPP [2,17]. For the acute treatment of brain herniation, some experts prefer mannitol [6]. For children with severe TBI (Glasgow coma score [GCS] ≤8), guidelines suggest hypertonic saline as the first-line agent, although some experts prefer mannitol [6,17]. Proponents of hypertonic saline for children with severe TBI note that unlike mannitol, hypertonic saline does not cause osmotic diuresis, may reduce elevated ICP to a greater degree, and can be administered as a continuous infusion. In a multicenter, observational study of over 500 children with severe TBI who received 3 percent hypertonic saline or mannitol (nearly 2500 total bolus doses), both therapies were associated with similar changes in ICP and CPP. However, hypertonic saline was associated with a greater reduction in ICP than mannitol in patients with ICP >25 mmHg (adjusted difference -2.94 mmHg, 95% CI -5.13 to -0.75) [17]. Study limitations include lack of long-term clinical outcomes and institutional variation in drug dosing and administration. These findings suggest that hypertonic saline may be more effective in reducing ICP in selected children with severe TBI than mannitol, but this difference may not be clinically meaningful.

When combined treatment is given with both agents, hypertonic saline administration helps to offset the hyponatremia and hypovolemia that frequently follow the rapid diuresis associated with mannitol treatment. On the other hand, mannitol helps to offset potential worsening of vasogenic cerebral edema that may occur with prolonged use of hypertonic saline as described below. However, evidence is lacking regarding improved outcomes for combination hyperosmolar therapy versus single drug therapy for increased ICP in children.

The hyperosmolar strategy for treating cerebral edema relies on the principle of "osmotic reflection coefficient" and the Starling equilibrium across a capillary membrane [18]. A membrane that is impermeable to ions and molecules, such as the intact blood-brain barrier, has a reflection coefficient of 1, whereas a freely permeable membrane has a coefficient of 0. Administration of hypertonic saline or mannitol creates an osmotic gradient that causes free water to come out of the extracellular space and pass into the circulation. This effect leads to shrinkage of brain volume and a reduction in ICP. (See "Pathophysiology and etiology of edema in adults", section on 'Capillary hemodynamics'.)

However, the reflection coefficient is not constant with some pathologic processes. For example, in patients with vasogenic cerebral edema caused by tumors, intracranial hematomas, infarcts, cerebral abscesses, or other central nervous system infections (eg, meningitis or encephalitis), there is an expected fall in the reflection coefficient for sodium (decrease from 1 to 0). In such patients, prolonged and repeated IV dosing of 3 percent hypertonic saline is not without risk: It will eventually have limited effect and may even worsen the edema as the blood brain barrier fails [18]. Thus, for patients with vasogenic cerebral edema, it is appropriate to start with 3 percent hypertonic saline to gain acute control, but mannitol should also be introduced because it typically maintains a higher reflection coefficient due to its higher molecular weight relative to sodium and can reestablish the osmotic gradient.

Mannitol — There is limited evidence to compare mannitol with hypertonic saline for intracranial hypertension. (See 'Choice of agent' above.)

The recommended initial dose for mannitol is 0.5 to 1 g/kg (2.5 to 5 mL/kg of the 20 percent solution which contains 200 mg/mL mannitol concentration) given as an IV infusion through an in-line filter over 20 to 30 minutes [19]. Mannitol should never be run as a continuous infusion.

The higher dose is preferred in patients with acute herniation or severe head trauma. Although there is no maximum dose for mannitol, the 20 percent solution is typically supplied in a volume of 500 mL or 250 mL. We typically do not exceed one full 500 mL bag which is equivalent to a 1 g/kg dose for a 100 kg patient.

In other patients, starting with the lower dose is recommended, because there is no proven benefit to the higher dose [2,7].

With monitoring of measured serum osmolality prior to each mannitol dose, it can be administered as often as every four hours. The osmolar gap (measured serum osmolality – calculated serum osmolality (calculator 1 and calculator 2)) is a way to measure clearance of mannitol and should remain <20 mOsm/kg. A gap that exceeds this threshold indicates that uncleared mannitol remains in the circulation and increases the risk of nephrotoxicity and reverse osmotic shift (ie, movement of mannitol through the damaged blood brain barrier with a worsening of cerebral edema). As with any osmotic agent, the use of mannitol should be carefully evaluated in patients who have renal insufficiency. Mannitol use is contraindicated in patients with active intracranial bleeding, except while the patient is undergoing craniotomy.

Mannitol causes a brisk diuresis. For this reason, all patients receiving mannitol should have a Foley catheter placed to prevent bladder overdistension and to monitor urine output [2]. Isotonic fluids (eg, normal saline) should be available and given, as needed, to prevent hypotension and dehydration.

Mannitol administration also has the potential side effects of hyperosmolarity, hypovolemia, electrolyte imbalance, and acute renal failure [20]. These adverse effects are more common with chronic or high-dose administration, and patients who receive mannitol in this manner should be monitored carefully Serum osmolarity, serum electrolytes, and renal function should be measured at least every six to eight hours, preferably before administration of the next dose. In addition, when administered chronically and in high doses, mannitol may cross the injured blood-brain barrier at the site of the cerebral lesion and cause an exacerbation of cerebral edema referred to as rebound ICP elevation [19,20].

Mannitol acts by establishing an osmotic gradient between plasma and parenchymal tissue, resulting in a net reduction in brain water content [21-24]. Mannitol has a rapid onset of action and maintains its effect for a period of 1.5 to 6 hours. Settings in which mannitol can be used to decrease ICP and improve CPP include acute herniation, acute elevation of ICP, and ICP elevation that does not respond to other therapies.

Mannitol has the potential to fail in treating cerebral edema. An IV bolus dose is distributed throughout the extracellular fluid within three minutes, except in areas protected by the intact blood-brain barrier (BBB). There is an acute rise in extracellular osmolality in body tissues because mannitol (molecular weight 182, reflection coefficient of 0.9 at the BBB) causes an influx of water from the intracellular compartment; this restores osmotic equilibrium between the intracellular and extracellular compartments at a higher volume than before the drug was given [19]. This water shift dilutes and lowers serum sodium concentration. Subsequent renal clearance of mannitol from the circulation produces an osmotic diuresis and elimination of free water, further raising total body osmolality and serum sodium concentration. The net effect of the initial single dose of mannitol is no change or small net rise in total body osmolality. However, repeated dosing of mannitol over 48 hours, with coadministration of isotonic saline, will lead to a consistent rise in serum osmolality and serum sodium concentration. Serum osmolality should be kept between 300 to 320 mOsm/kg.

Hypertonic saline — There is limited evidence to compare hypertonic saline with mannitol for the treatment of intracranial hypertension. Hypertonic saline is preferred by many experts for the treatment of severe TBIs. Hypertonic saline does not cause osmotic diuresis, may reduce elevated ICP to a greater degree, and can be administered as a continuous infusion. (See 'Choice of agent' above.)

We use the following dosing regimen for hypertonic saline [2]:

●Initial IV bolus of 5 mL/kg of 3 percent saline which corresponds to an expected rise in serum sodium of 5 mEq/L; this dose may be repeated, hourly, as needed until the serum sodium reaches 160 mEq/L. Hypertonic saline typically fails to further reduce ICP when the serum sodium exceeds 160 mEq/L. Although differing concentrations of hypertonic saline ranging from 3 to 29 percent have been used in adults and children [25,26], we favor 3 percent saline because initial dosing can be given through a peripheral vein, is widely available, and familiar to most physicians.

●Continuous infusion of 3 percent saline at rates of 0.5 to 1.5 mL/kg per hour adjusted to maintain ICP <20 mmHg may also be used after the ICP is controlled by hypertonic saline boluses.

IV hypertonic saline, alone or in combination with dextran or hydroxyethyl starch, has been shown to decrease ICP and increase CPP in adult and pediatric patients with elevated ICP [27,28]. It is thought to act by establishing an osmotic gradient that reduces brain water content and appears to maintain efficacy with repeat dosing even in patients who have stopped responding to mannitol [26]. In addition, based upon observational data, hypertonic saline appears to be superior to pentobarbital and fentanyl for treatment of acute elevations of ICP. As an example, in a prospective observational study that evaluated cerebral hemodynamic effects of hypertonic saline, pentobarbital, and fentanyl, administration of hypertonic saline was associated with the fastest decreased in ICP with an increase in CPP [28].

Unlike mannitol, 3 percent hypertonic saline does not cause profound osmotic diuresis, and the risk of hypovolemia as a complication is decreased. Additional proposed benefits include:

●Restoration of normal cellular resting membrane potential and cell volume,

●Stimulation of atrial natriuretic peptide release,

●Inhibition of inflammation, and

●Enhancement of cardiac output.

The half-life for equilibration of sodium across the intact blood brain barrier is about one hour, but less if the barrier is disrupted. This means that change in serum sodium concentration as a strategy for treating cerebral edema will, theoretically, become less effective the longer one adopts this strategy, unless, of course, one is prepared to continue to escalate serum level to very high values. Given that the choroid plexus behaves more like the peripheral circulation (ie, the reflection coefficient to sodium of zero), changing serum sodium concentration will have no effect on limiting water flow across the endothelium within the choroid plexus, but mannitol would have such an effect.

Rebound increased ICP has occurred after 3 percent hypertonic saline administration [29,30]. Other potential complications associated with hypertonic saline administration include hypernatremia and hyperosmolality with acute kidney injury, fluid overload with pulmonary edema and/or heart failure, metabolic acidosis, and osmotic demyelination syndrome (formerly called central pontine myelinolysis) [19].

Therapeutic hyperventilation — Because of the risk of cerebral ischemia, therapeutic hyperventilation is reserved for episodes of acute brain herniation or ICP elevation that fail to respond to general measures and hyperosmolar therapy and when some other intervention such as emergency surgery or decompressive craniectomy is planned as follows:

●Temporary therapeutic hyperventilation (PaCO₂ 30 to 35 mmHg) may be initiated under direction by a neurosurgeon for patients with signs of impending herniation (figure 1 and table 1) in whom surgical intervention is planned.

●Aggressive hyperventilation (PaCO₂ <30 mm Hg) is indicated only if there are clinical signs of acute herniation. (See 'Emergency treatment of brain herniation' above.)

Aggressive hyperventilation may decrease CBF enough to cause cerebral ischemia and actually increase the extent of brain injury. In one study of 23 pediatric patients with severe TBI, a range in PaCO₂ (>35, 25 to 35, and <25 mmHg) induced by hyperventilation showed a clear dose-response relationship between the frequency of cerebral ischemia and hypocarbia [31]

Refractory intracranial hypertension — Decisions regarding the next steps in patients whose intracranial hypertension cannot be controlled by medical management and who do not have a specific surgical treatment for the underlying cause should be guided by a neurosurgeon with pediatric expertise.

Options include:

●CSF drainage – In cases of uncontrolled intracranial hypertension, an intracranial or lumbar drain may be placed by the neurosurgeon to remove cerebrospinal fluid (CSF) and monitor ICP. The choice to do either is based on feasibility of placement and, in the case of lumbar drain, brain imaging showing communication for CSF circulation. In cases that have ventricular fluid drainage via the lateral ventricle small volumes of fluid (ie, as little as 1 mL CSF) can be removed and lead to significant reductions in ICP (figure 2). (See "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis", section on 'Intracranial pressure'.)

CSF diversion is often the first treatment chosen for children with refractory intracranial hypertension confirmed by an intraparenchymal monitoring device. However, if a CSF drainage system cannot be placed due to technical (eg, shift of normal ventricular anatomy due to a mass lesion) or medical reasons (eg, coagulopathy), or if CSF diversion has been decided against, then barbiturate coma with or without surgical decompression (as determined by the neurosurgeon) is recommended.

Although CSF diversion usually decreases ICP, long-term clinical benefit is uncertain. For example, in a comparative effectiveness study of 1000 children with severe TBI, 314 pediatric patients underwent CSF diversion and 686 did not during acute care [32,33]. In 98 propensity-matched pairs, the authors found no difference in outcomes six months after the acute management, which was the primary outcome. However, regarding the secondary outcome (ie, mean ICP over seven days, or until the monitor was removed), there was a significant decrease in overall mean ICP in the CSF diversion group compared with the non-CSF diversion group (3.97 ± 0.12 mmHg). Based upon these findings, further evidence is needed to determine if CSF diversion improves patient-important outcomes.

●Barbiturate coma – Barbiturates are used to treat intracranial hypertension that is refractory to other modalities. Pentobarbital is the barbiturate that is best studied and most commonly used. It decreases the cerebral metabolic rate, which causes a reduction in cerebral blood flow and, thus, in ICP [34]. It may also provide some protective effect for the brain tissue during periods of hypoxia or hypoperfusion [35].

Barbiturates produce cardiac suppression, which often results in hypotension. This should be anticipated and treated promptly with fluids and, if necessary, inotropic support [25]. Invasive cardiopulmonary monitoring may be needed. These patients should also undergo continuous electroencephalographic (EEG) monitoring with the goal of achieving a burst suppression pattern, with a suppression interval of 5 to 15 seconds [2]. The physician should administer the minimum dose of barbiturate necessary to induce this burst suppression pattern. In this way, it is hoped that secondary cardiac depressant effects can be limited.

There is no evidence to support the prophylactic use of barbiturates in patients with elevated ICP, and their use in this manner may result in adverse side effects [36]. In one study, 53 severely head-injured patients (>12 years of age) were randomly assigned to receive pentobarbital (regardless of the ICP) or the control group. All patients received aggressive resuscitation, prompt diagnosis and treatment of mass lesions, and intensive care. The outcome was similar in both groups with respect to incidence of elevated ICP, duration of ICP elevation, and response of ICP elevation to treatment. However, arterial hypotension was more common in the treatment group (54 versus 7 percent).

●Surgical decompression – In a decompressive craniectomy (DC), a substantial portion of the skull is removed in order to reduce increased ICP. This can be done in combination with an evacuation procedure of a mass lesion, such as a subdural hematoma, or as a primary treatment for increased ICP. DC may be helpful for patients with rapid deterioration from a focal space-occupying brain lesion (eg, brain tumor, cerebral abscess, and lobar parenchymal hemorrhages) and is performed at the neurosurgeon's discretion.

For severe TBI, the use of this technique is controversial, and its efficacy is uncertain. In adults, DC is associated with lower mortality but an increased numbers of survivors in a vegetative or chronic dependency state compared with medical management [37,38]. Although some older children and adolescents were included in these studies, they were the minority of patients. Thus, the efficacy is uncertain for children with severe TBI. (See "Management of acute moderate and severe traumatic brain injury", section on 'Decompressive craniectomy'.)

Patients with vasogenic edema — In addition to the measures described above, it is recommended that patients with vasogenic edema caused by mass lesions (eg, tumors or abscesses) receive dexamethasone (0.25 to 0.5 mg/kg) administered every six hours, with a maximum dose of 16 mg per day.

Possible side effects of this regimen include sodium and water retention and gastric or peptic ulcer. An H2-blocker (eg, famotidine) should be prescribed concomitantly. Careful monitoring of the patient's glucose, electrolytes, blood pressure, hemoglobin, and stool for occult blood is necessary for patients receiving systemic corticoid therapy. (See "Major adverse effects of systemic glucocorticoids".)

The evidence base supporting the use of corticosteroids for vasogenic edema is strongest for patients with brain tumors as discussed separately. (See "Management of vasogenic edema in patients with primary and metastatic brain tumors", section on 'Symptomatic treatment'.)

Corticosteroids are not useful in the management of elevated ICP caused by infarction, hemorrhage, or head trauma [6].

Contraindicated therapies — Certain therapies should be avoided in children who have severe head injuries and/or elevated intracranial hypertension. These include:

●Vasodilators (eg, nitroglycerin and nitroprusside)

●Ketamine in patients with obstructive hydrocephalus (see "Pediatric procedural sedation: Pharmacologic agents", section on 'Ketamine')

●Hypotonic solutions (eg, D5W) that deliver too much free water and can exacerbate cerebral edema

●Prolonged (>12 hours) propofol infusion that can result in metabolic acidosis (propofol infusion syndrome) and death (see "Pediatric procedural sedation: Pharmacologic agents", section on 'Propofol')

ONGOING MANAGEMENT — The goal of ongoing management of children with intracranial hypertension is to maintain cerebral perfusion pressure (CPP) and alleviate ICP elevation through treatment of the underlying condition, or if specific treatment is not available, medical management to reduce the degree of intracranial hypertension.

The best therapy for elevated ICP is resolution of the underlying cause (table 3). Management of traumatic brain injury (TBI), hydrocephalus, brain tumors, and meningitis in children are discussed in detail separately:

●(See "Severe traumatic brain injury (TBI) in children: Initial evaluation and management" and "Intracranial epidural hematoma in children" and "Intracranial subdural hematoma in children: Clinical features, evaluation, and management".)

●(See "Hydrocephalus in children: Clinical features and diagnosis".)

●(See "Overview of the management of central nervous system tumors in children".)

●(See "Bacterial meningitis in children older than one month: Treatment and prognosis".)

Once ICP becomes controlled, there are multiple approaches that can be taken for de-escalation, and evidence is limited to support a preferred approach. Our approach consists of first removing the last supportive treatment used to control ICP ("last on; first off"). If tolerated, we usually wait 24 hours before the next treatment is withdrawn. These steps are repeated until removal of ICP management has been accomplished.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Increased intracranial pressure and moderate-to-severe traumatic brain injury".)

SUMMARY AND RECOMMENDATIONS

●Recognition – Acutely elevated ICP should be suspected in children with any one of the following findings:

•Severe headache with vomiting

•Coma

•Hypertension with bradycardia or tachycardia

•Papilledema

•Signs of transtentorial herniation (figure 1 and table 1)

•Abrupt onset of weakness or hemiplegia

After stabilization, these findings warrant emergency neuroimaging with a non-contrast CT of the head and, for injured children with a Glasgow coma score (GCS) ≤8 (table 4) or diagnosed with a condition that warrants aggressive management of ICP, placement of an intracranial monitor by a neurosurgeon. (See 'Recognition' above.)

●Neurosurgical consultation – Early neurosurgical consultation should be obtained in any child with acute intracranial hypertension to direct care and to determine the need for surgical interventions (eg, placement of an ICP monitor or external ventricular device, evacuation of an epidural hematoma, or excision of a mass lesion). (See 'Neurosurgical consultation' above.)

●Initial stabilization – Stabilization of airway, breathing, and circulation according to the principles of Pediatric Advanced Life Support and, for injured children, Advanced Trauma Life Support are essential to the successful treatment of elevated ICP. (See 'Initial stabilization' above.)

•Airway – Indications for rapid sequence endotracheal intubation (RSI) in children with elevated ICP include any one of the following (see 'Airway' above):

-Refractory hypoxia

-Hypoventilation

-GCS of ≤8 (table 4) or GCS <12 and rapidly declining

-Loss of airway protective reflexes

-Acute herniation requiring controlled hyperventilation

Maintain cervical spine motion restriction during RSI in patients with potential cervical spine injury. Our approach to RSI in children with elevated ICP is provided. (See 'Rapid sequence intubation' above.)

•Breathing – After intubation, maintain PaCO₂ between 35 and 40 mmHg with monitoring of blood gases and quantitative end-tidal capnography. (See 'Breathing' above.)

•Circulation – Treat hypovolemia with isotonic fluids (eg, normal saline) to achieve normal, rather than excess, volume status. Avoid administration of hypotonic fluids (eg, D5W). (See 'Circulation' above.)

In patients with spinal shock, maintain an appropriate mean arterial pressure for age with intravenous (IV) isotonic fluids and norepinephrine or phenylephrine, as needed.

Bradycardia caused by cervical spinal cord or high thoracic spinal cord disruption may require administration of atropine or external pacing.

•Temperature control – Treat fever with antipyretics, and if necessary, cooling blankets. However, avoid hypothermia. (See 'Temperature control' above.)

●Treatment of elevated ICP – General measures to be used in all children with increased ICP are listed in the table (table 6). (See 'General measures for all patients' above and 'Initial stabilization' above.)

●Approach – Our approach to children with sustained (>5 minutes) intracranial hypertension (ICP ≥20 mmHg [27 cmH₂)]) or impending herniation (figure 1 and table 1) is based upon the principles of Emergency Neurologic Life Support (algorithm 1) with therapeutic goals to minimize ICP elevation and to maintain adequate cerebral perfusion pressure (CPP). Our target CPP in children is (see 'Medical treatment of sustained intracranial hypertension or impending herniation' above):

•0 to 5 years of age – 40 to 50 mmHg

•6 to 17 years of age – 50 to 60 mmHg

●Hyperosmolar therapy – For patients with sustained intracranial hypertension persisting despite general measures including adequate sedation, we suggest hyperosmolar therapy rather than other interventions (Grade 2C). Either mannitol or hypertonic saline are effective. In our practice, we use, mannitol, hypertonic saline, or both. (See 'Choice of agent' above.)

●Hyperventilation – Therapeutic hyperventilation (PaCO₂ 30 to 35 mmHg) under the direction of a neurosurgeon is reserved for episodes of acute brain herniation or ICP elevation that fail to respond to general measures and hyperosmolar therapy and when another intervention (eg, emergency surgery or decompressive craniectomy) is planned. Aggressive hyperventilation (PaCO₂ <30 mmHg) is indicated only if there are clinical signs of acute herniation. (See 'Emergency treatment of brain herniation' above.)

●Dexamethasone – In addition to the measures described above, for patients with vasogenic edema caused by mass lesions (eg, brain tumors or abscesses), we recommend dexamethasone (Grade 1C). (See 'Patients with vasogenic edema' above.)

●Refractory intracranial hypertension – For patients with refractory intracranial hypertension and without a specific surgical treatment for the underlying cause, treatment options, as determined by a neurosurgeon with pediatric expertise, include cerebrospinal fluid drainage, barbiturate coma, and/or surgical decompression. (See 'Refractory intracranial hypertension' above.)