Emergency Neurological Life Support: Intracranial Hypertension and Herniation

Abstract

Sustained intracranial hypertension and acute brain herniation are “brain codes,” signifying catastrophic neurological events that require immediate recognition and treatment to prevent irreversible injury and death. As in cardiac arrest, a brain code mandates the organized implementation of a stepwise management algorithm. The goal of this emergency neurological life support protocol is to implement an evidence-based, standardized approach to the evaluation and management of patients with intracranial hypertension and/or herniation.

Introduction

The ENLS-suggested algorithm for the initial management of intracranial hypertension or herniation is shown in Fig. 1.

Fig. 1.

ENLS intracranial hypertension or herniation protocol

The sum of intracranial contents—brain, blood, and cerebrospinal fluid (CSF)—represents a fixed volume determined by the invariant constraints of the cranial vault [1, 2]. Relative volumes of these contents will change to accommodate an acutely developing, space-occupying mass; however, this compensation is lost once a critical volume change has occurred, as demonstrated by the inflection point of the pressure–volume relationship (Fig. 2). Intracranial hypertension and cerebral herniation are “brain codes”—life-threatening neurological emergencies indicating that intracranial compliance adaptive mechanisms have been overwhelmed.

Fig. 2.

Intracranial compliance is biphasic

Although frequently linked, elevations of intracranial pressure (ICP) and brain herniation can occur independently. Intracranial hypertension is defined as a sustained (>5 min) elevation of ICP above 20 mmHg [3]. Detection requires invasive monitoring, but certain clinical and physiological signs may suggest elevated ICP prior to instrumentation. Herniation syndromes result from intracranial compartmental pressure gradients leading to parenchymal tissue shifts that compress or displace the brainstem, cranial nerves, or cerebral vasculature. Ischemia or infarction from vascular compression may cause edema and further deterioration in compliance.

The etiologies of brain codes are classified anatomically as extra-axial, focal, or diffuse intraparenchymal processes (Table 1). In the emergent setting of a brain code, resuscitative measures are pursued even if the etiological mechanism has not been fully characterized.

Table 1.

Etiologies of brain code

Extra-axial processes

Epidural hemorrhage

Subdural hemorrhage

Subdural empyema

Extra-axial brain tumor

Pneumocephalus

Focal brain processes

Brain tumor (primary, metastatic)

Ischemic stroke

Primary intracerebral hemorrhage

Brain abscess

Traumatic brain injury

Hydrocephalus

Diffuse brain processes

Traumatic brain injury

Aneurysmal subarachnoid hemorrhage

Infectious meningitides and encephalitides

Non-infectious neuroinflammatory disorders

Hepatic encephalopathy

Toxic-metabolic encephalopathies

Presentation

Clinically, symptoms of increased ICP include headache, nausea, and vomiting, or altered mental status with physical signs of hypertension, bradycardia, and irregular respirations or apnea (Cushing’s triad), although the concurrence of these three signs is less frequent [4]. Common sites for herniation are the cingulum (subfalcine herniation), medial temporal lobe (uncal herniation), and inferior cerebellum (tonsillar herniation).

The cardinal signs of transtentorial (uncal) herniation are an acute loss of consciousness associated with ipsilateral pupillary dilation and contralateral hemiparesis, resulting, respectively, from compression or displacement of ascending arousal pathways, oculomotor nerve (III), and corticospinal tract [5, 6]. In a subset of patients, herniation-associated shift of the midbrain compresses the contralateral anterior cerebral peduncle (crus cerebri) against the tentorium, resulting in hemiparesis that is ipsilateral to the lesion (Kernohan’s false localizing sign) [7]. Transtentorial herniation may cause ipsilateral cerebral infarction due to occlusion of the posterior cerebral artery.

Neuroimaging

In the emergent setting of a brain code, a cranial computed tomography (CT) scan should be obtained to identify a process that may require surgical intervention. Initial resuscitative measures and stabilization, including airway interventions, circulatory and ventilatory support, and initial hyperosmolar therapy, must be initiated prior to transport to the radiology suite. Cranial CT is preferred over magnetic resonance imaging (MRI) due to availability and speed of imaging. In the majority of cases, CT will identify the underlying process (see Table 1), although MRI may subsequently be needed for characterization. MRI should only be sought if the imminent risk of an additional brain code has been addressed by medical and/or surgical intervention.

ICP Monitoring

ICP monitors are invasive and are of several different types, including intraventricular catheters as well as intraparenchymal, subdural, and epidural devices. The decision to proceed with ICP monitoring is determined by the underlying process and the likelihood of its progression. In traumatic brain injury (TBI), neurosurgical guidelines recommended placement of an ICP monitor in patients with severe TBI who are comatose after resuscitation [Glasgow Coma Scale (GCS) of 3–8] and have either (1) abnormalities on cranial CT scan or (2) meet at least two of the following three criteria: age >40 years; systolic blood pressure <90 mmHg; or abnormal posturing [8]. Indications for ICP monitoring are less well established in nontraumatic coma. However, a recent international multidisciplinary consensus conference recommended that ICP and CPP should be monitored in patients at risk for ICP elevation based on clinical and/or imaging features to guide medical and surgical interventions [9].

Cerebral perfusion pressure (CPP), used as a surrogate for global cerebral blood flow (CBF), is approximated by the equation:

• CPP = Mean arterial pressure (MAP) – ICP.

In patients with TBI, available data support maintaining CPP >50–60 mmHg in adults to prevent cerebral ischemia [3]. Efforts to augment CPP greater than 60 mmHg may elevate the risk of systemic complications, including acute respiratory distress syndrome [10]. CPP targets for patients with non-traumatic intracranial hypertension have not been adequately studied.

Tier Zero

Brain code resuscitation begins with an assessment of circulation, airway patency, and ventilation. The head of the bed should be elevated to >30° and the head kept midline to facilitate cerebral venous drainage [11, 12]. Stimuli such as tracheal suctioning, that may elevate ICP, should be minimized. If hyperthermia is present, measures should be taken to normalize body and brain temperature. Only iso- or hyperosmotic fluids should be used as intravenous solutions. If hyponatremia is present, steps should be initiated for correction. High-dose corticosteroid therapy is initiated for vasogenic edema resulting from brain tumors, abscesses, or non-infectious neuroinflammatory conditions [13, 14]. If the brain has not yet been imaged, a non-contrast head CT scan should be performed when the patient can be transported safely.

Tier One

For acute elevations in ICP, hyperosmolar therapy with either mannitol or hypertonic saline (HTS) has shown equivalent efficacy in lowering of ICP [15–18]. Mannitol is administered as 0.5–1 g/kg intravenous (IV) bolus through a peripheral intravenous line and may be repeated every 4–6 h if serum osmolality is monitored [19]; no therapeutic benefit is appreciable with osmolality >320 mOsm/kg. HTS is available in concentrations from 2 to 23.4 % and can be administered as a bolus alone or in addition to mannitol. HTS concentrations boluses C7.5 % should be given via a central venous catheter; when using concentrations lower than this, peripheral lines may be used, but the infusion should be in a large vessel, and the IV site should be carefully monitored for infiltration. Since two pre-hospital trials using 7.5 and 3 % NaCl solutions via peripheral catheters had no negative effects, in the brain code setting these treatments should not be withheld simply because central access is yet be available [20, 21]. Bolus 23.4 % NaCl has been associated with ICP reduction and reversal of transtentorial herniation [22]. When infusing HTS, target serum sodium concentration should be determined and serum sodium level checked every 4–6 h. When acute obstructive hydrocephalus is present as determined by neuroimaging, an external ventricular drainage (EVD) system should be placed emergently. If an EVD system is already in place, drain 5–10 mL of CSF [23] for acute rises in ICP. As a temporizing measure, a brief course (<2 h) of hyperventilation to a PaCO2 of 30–35 mmHg may be considered, while definitive treatment is provided [24, 25]. If ICP is not controlled, and/or clinical signs of herniation do not resolve with Tier One interventions, review decompressive surgical options [26, 27]. If surgery is not appropriate or not undertaken, move to Tier Two. If ICP is controlled with Tier One interventions, consider repeating the head CT scan to rule out new processes.

Head CT

After Tier One or Tier Two (below), if brain imaging has not yet been performed, a head CT scan should be performed to determine the cause of herniation or intracranial hypertension, for the reasons explained in the neuroimaging section above.

Tier Two

If Tier One interventions have failed to control ICP, Tier Two should be engaged. If hyperosmolar therapy with HTS has been administered, serum sodium goals should be increased, although sodium levels >160 mmol/L are unlikely to provide additional benefit. The target for serum sodium is controversial and it depends on pathophysiological state. If the patient is continuing to have increased ICP (and needs to advance to Tier Two), one needs to maintain a gradient between brain and serum in order to promote the egress of water from the brain. Once the ICP has stabilized, one needs to maintain sodium at the current high level until the brain edema process is waning. Sedation should be increased to aid in ICP management. Propofol has been shown to reduce CMRO₂ and CBF volume and, consequently, ICP [28]. It is administered as a bolus of 1–3 mg/kg and may be continued as an infusion (titrate to maximum 200 µg/kg/min) in ventilated patients. Propofol, especially when given as a bolus dose, is associated with circulatory depression, which should be corrected with IV fluids and/or vasopressors to maintain CPP goals. A small subset of patients receiving propofol may develop a propofol infusion syndrome characterized by metabolic acidosis, cardiac dysfunction, rhabdomyolysis, and hypertriglyceridemia, often with a fatal outcome [29, 30]. Propofol infusion syndrome is more likely to develop at doses >100 mcg/kg/min administered for >48 h; so if propofol is increased to these extreme ranges (200 µg/kg/min), it should only be done temporarily, while other measures are put in place.

If ICP is not responsive to Tier Two interventions, rescue decompressive surgery should be considered. If the patient is ineligible for surgery, Tier Three (below) should be engaged.

Decompression

Surgery is considered for brain code patients who have failed medical management. Decompressive surgical interventions for the management of brain code include (a) placement of a ventricular drain, (b) evacuation of extra-axial lesion (e.g., epidural hematoma), (c) resection of intracerebral lesion (e.g., lobar hemorrhage), (d) removal brain parenchyma (e.g., cerebellar mass), and (d) uni- or bilateral craniectomies.

Selected patients with rapid neurological deterioration from focal space-occupying lesions may benefit from surgical decompression. This includes patients with brain tumors, brain abscesses, and parenchymal hemorrhages, particularly when the hemorrhages are lobar [31] or cerebellar [32, 33] in location. Decompressive craniectomy may also be considered in patients with diffuse brain swelling associated with TBI [34–37]; stroke with brain edema, the process in which hemicraniectomy has been most extensively studied [38, 39]; meningoencephalitis; or non-infectious neuroinflammatory conditions (e.g. acute demyelinating encephalomyelitis).

Tier Three

Tier Three measures represent the most aggressive level of management and carry the highest risk of adverse effects. Rigorous randomized prospective studies are lacking, and recommendations are driven by consensus. This tier includes administration of pentobarbital (bolus 10 mg/kg over 30 min–2 h, then 5 mg/kg/h × 3 h; maintenance infusion of 1–4 mg/kg/h) titrated to ICP goal. Some patients may not tolerate pentobarbital at these doses because of hypotension and arterial vasopressors may be necessary. The electroencephalogram (EEG) should be continuously monitored and pentobarbital titrated either to ICP or to EEG burst suppression of 5–20 s. The pentobarbital infusion is continued for 24–96 h, while the underlying processes driving ICP are treated [40–42]. Pentobarbital is associated with respiratory depression, cardiovascular instability, immune suppression, and paralytic ileus; neurological examination is limited to an assessment of pupillary reactivity. Pentobarbital plasma clearance may take days after discontinuation of infusion; however, it redistributes out of the CNS more rapidly.

Moderate hypothermia (target core temperature 32–34 °C) is associated with a predictable reduction in ICP. It may be induced with external cooling devices or with IV infusion of cooled fluids [43–48]. Hypothermia may be associated with shivering, cardiac arrhythmias, sepsis, and electrolyte disturbances and protocols for induction, maintenance, and rewarming should be used to optimally manage these complications.

Hyperventilation to achieve mild to moderate hypocapnia (PaCO₂ 25–35 mmHg) and cerebrovascular constriction may be considered in selected patients who have failed other interventions in the acute period. Prolonging hyperventilation for more than 6 h is unlikely to be beneficial and may cause or exacerbate ischemic injury [25]. Hence, hyperventilation should ideally be accomplished in conjunction with a cerebral oxygenation monitor (e.g. jugular venous oximetry and brain tissue oxygen probe), in order to detect cerebral ischemia.

Consider Additional Monitoring

Patients who have had or are at risk for a brain code may benefit from additional neuromonitoring, including jugular venous oximetry, brain tissue oxygenation, and cerebral microdialysis. Treatment based on ICP and CPP overlooks significant information on the physiologic and metabolic state of the injured brain. Moreover, assumptions regarding CPP may not hold if CBF autoregulation is impaired. Complementary neuromonitoring techniques should be considered to optimize medical management in selected patients with severe brain injury.

Studies using brain tissue oxygen sensors indicate that significant parenchymal hypoxia may occur even when ICP and CPP are normal [49, 50]. Cerebral microdialysis measures brain interstitial lactate, pyruvate, glucose, and glutamate, indicators of cerebral metabolic activity whose levels may be altered independently of ICP and CPP [51]. Dynamic indices of cerebral autoregulation express the correlation between a systemic hemodynamic parameter (arterial blood pressure or CPP) and an intracranial physiological parameter such as ICP (PRx), transcranial Doppler-derived CBF velocity (Mx), or brain tissue PO₂ (Orx). High degrees of correlation suggest a failure of autoregulation and an increased risk of injury due to hypo or hyperperfusion [52, 53].

Revise ICP/MAP Goals

Depending on the specific circumstances and the invasive or noninvasive monitoring that are available, the standard goals of MAP and ICP should be re-considered and customized to the patient. For example, a patient who is awake, without symptoms, and in whom ICP is in excess of 20 mmHg, or a CPP below 50 mmHg, may not require any intervention.

Pre-hospital

Recognition of a brain code in the pre-hospital setting is important because life-saving therapies can be initiated prior to arrival in the Emergency Department. Clinical signs of herniation may be apparent and include unilateral dilated pupil, loss of consciousness, posturing, as well as hypertension and bradycardia. Resuscitation begins with the management of circulation, airway patency, and ventilation. If capnography is available after intubation, a goal of end-tidal CO₂ of 30–35 mmHg should be targeted. The head of the bed should be elevated to facilitate cerebral venous drainage; although these patients are typically backboarded, it may be possible to place a rolled blanket or towel beneath the board during transport to elevate the head. Hyperventilation can be initiated using BVM ventilation. Pre-hospital notification is also important so that resources are available upon arrival.

Pediatric Considerations

Management for intracranial hypertension in the pediatric population should follow analogous tiers of treatment and indications for monitoring as in adults. Importantly, the presence of an open fontanel in infants does not preclude the development of intracranial hypertension and cerebral herniation [54]. In children with TBI <5 years old, CPP should be maintained >40 mmHg, whereas in children 6–17 years of age a target of >50 mmHg is appropriate [55, 56]. Establishment of optimal CPP may require advanced neuromonitoring (i.e., brain tissue oxygen tension) due to the lack of well-defined age-dependent CPP thresholds and the risk of abnormal cerebrovascular autoregulation [57].

Hyperosmolar therapy with either mannitol or 3 % HTS may be administered for ICP elevations >20 mmHg or for suspected herniation. Mannitol bolus dose is 0.5–1 g/kg. Mannitol can be administered every 4 h as needed for ICP >20 mmHg as long as the osmolar gap is less than 20 mOsm. A Foley catheter should be placed in children receiving mannitol to prevent bladder overdistention due to mannitol-induced diuresis. Such diuresis should be anticipated and additional boluses of normal saline provided to prevent hypotension.

Hypertonic 3 % saline may be given as a bolus dose of 5–10 mL/kg for acute elevations in ICP or signs of brain herniation. HTS may then be administered as a continuous infusion at 0.5–1.5 mL/kg/h [55]. The expected serum sodium rise is 1 mEq/L for every 1 mL/kg bolus dose given and 1 mEq/L/h for every 1 mL/kg/h continuous infusion. Levels of serum sodium >160–165 mEq/L are unlikely to provide additional benefit in reducing intracranial hypertension. Compared to mannitol, HTS has the added benefit of improved hemodynamic stability, an important consideration given the deleterious effect of hypotension in patients with acute brain injury.

Brain herniation is potentially reversible with appropriate and timely therapy. Reversal of transtentorial herniation has been observed in 50–75 % of adult patients with either TBI [58] or with supratentorial mass lesions [59]. Long-term outcomes after successful treatment for herniation may be more favorable in children than in adults [58].

A special category of children at risk for increased ICP and brain herniation are children with diabetic ketoacidosis (DKA). Approximately 0.5–1 % of children with DKA will have severe cerebral edema, which carries a mortality rate of 20–25 % [60, 61]. Factors thought to be associated with increased risk of neurologic complications in pediatric DKA are young age, duration and severity of symptoms, low pCO₂, overly aggressive fluid resuscitation, administration of hypotonic fluids, administration of sodium bicarbonate, and decreases in serum glucose >100 mg/dL/h [61, 62]. Hence, initial resuscitation should be administered with caution. Boluses of sodium bicarbonate must be avoided. Mental status should be checked at least hourly. Children with DKA will often become somnolent with initiation of treatment, possibly due to subtler cerebral edema, but they should remain arousable with stimulation. Children who are unarousable, those with papilledema and those with warning signs of cerebral herniation (Cushing’s triad) should receive hyperosmolar therapy and be hyperventilated to prevent further deterioration. HTS may be preferred to mannitol, since in DKA osmolality is already high due to elevated glucose concentrations and mannitol-induced diuresis may aggravate dehydration.