Management of Intracranial PressureThomas J. Wolfe, MD, and Michel T. Torbey, MD, MPH

Corresponding authorThomas J. Wolfe, MDDepartment of Neurology, Medical College of Wisconsin and Froedtert Hospital, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA.E-mail: wolfe_thomas@hotmail.com

Current Neurology and Neuroscience Reports 2009, 9:477–485Current Medicine Group LLC ISSN 1528-4042Copyright © 2009 by Current Medicine Group LLC

Although intracranial hypertension may arise from diverse pathology, several basic principles remain paramount to understanding its dynamics; however, the management of elevated intracranial pressure (ICP) may be very complex. Initial management of common ICP exacerbants is important, such as addressing venous out! ow obstruction with upright midline head positioning and treating agitation and pain with sedation and analgesia. Surgical decom-pression of mass effect may rapidly improve ICP elevation, but the impact on outcome is unclear. Considerable effort has been put forth to understand the roles of multimodal intensive care monitoring, osmolar therapy, cerebral metabolic suppression, and temperature augmentation in the advanced manage-ment of elevated ICP. Establishing a protocol-driven approach to the management of ICP enables the rapid bedside assessment of multiple physiologic variables to implement appropriate treatments, which limit the risk of developing secondary brain injury.

IntroductionNumerous neurologic and nonneurologic diseases may contribute to the formation of intracranial hypertension. Through advances in emergency response systems and neuroimaging, the rapid identi" cation of these patients has become easier, allowing for earlier initiation of treat-ment. Recent technical innovations in neuromonitoring and the establishment of specialized neurointensive care units may allow for improvements in morbidity and mor-tality rates attributable to elevated intracranial pressure (ICP). We present a review of ICP physiology and data to support the evidence-based management of these patients. In addition, we present a possible treatment algorithm for refractory intracranial hypertension, incorporating the application of multimodal monitoring in the neurointen-sive care unit.

ICP DynamicsThe cranial vault of a normal adult is a noncompliant structure containing an average volume of approximately 1500 mL, comprising 88% brain matter, 7.5% blood, and 4.5% cerebrospinal ! uid (CSF) [1]. The Monroe-Kellie hypothesis contends that to maintain a constant ICP, any increase in the volume of an intracranial element must be met with an equal compensatory decrease in the volume of another component, or pressure will increase. Because of the skull’s noncompliance, uncompensated changes in the volume of any given component may have an impact on ICP, with a potential exponential increase in ICP.

Normal ICP is not constant throughout life; healthy adults and older children have a normal ICP of 10 to 15 mm Hg, whereas the ICP of young children and infants is more than half this value [2,3]. There is level II evidence to support treatment initiation if ICP levels remain per-sistently above 20 mm Hg [4]. For the purposes of this review and the proposed treatment algorithm (Fig. 1), sustained ICP elevation greater than 20 mm Hg without stimulation ful" lls the criteria for intervention.

Cerebral blood ! ow and perfusion pressure The brain receives 15% to 20% of total cardiac output, which at rest is approximately 800 mL/min, and absorbs 25% of all oxygen consumed by the body [5]. Systemic mean arterial perfusion pressure (MAP) is the most important factor in maintaining cerebral perfusion. Cere-bral perfusion pressure (CPP), the pressure at which the brain is perfused, is determined by taking the difference between MAP and ICP (CPP = MAP – ICP), where MAP = (1/3 systolic blood pressure [BP]) + (2/3 diastolic BP). Normally, cerebral blood ! ow (CBF) is estimated to be 50 mL/100 g per minute. When CBF falls below 12 mL/100 g per minute, irreversible ischemic injury occurs [5].

Maintaining a constant CBF depends on autoregula-tion, a complex system of arterial and venous modulation. Autoregulation has three main levels of control: myogenic, metabolic, and neurogenic [5,6]. Pressure autoregulation refers to the cerebrovascular system’s ability to maintain normal levels of CBF with CPP between 50 and 150 mm Hg, mediated mainly by the variable vascular resistance of arteriolar myogenic responses. The metabolic regulation of arteriolar vascular resistance is variably affected by CO2, O2, pH/lactate formation, adenosine, and nitric oxide. Neu-rogenic regulation refers to sympathetic tone on the cerebral arteries leading to mild tonic vasoconstriction, allowing for higher limits on the autoregulation curve; in contrast, the

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parasympathetic nervous system plays little role in cerebral autoregulation [5]. Measuring the limits of cerebral vascular autoregulation is possible using transcranial Doppler tech-nology by comparing beat-to-beat spontaneous variability in systemic BP with CBF velocities [6].

If CPP levels fall below the lower limit of autoregu-lation, CBF will fall and contribute to oligemia. If CPP exceeds the upper limit of autoregulation, an excess of CBF would occur beyond the metabolic necessity of the brain. This is an uncoupled increase in CBF, or luxury perfusion. Recent animal data suggest that the lower limit of cerebral autoregulation rises as ICP increases, which might mandate a progressively higher CPP goal to main-tain constant CBF [7].

Causes of elevated ICPAcute identi" cation and treatment of the primary cause of elevated ICP are necessary to reduce the risk of developing further secondary injury, and other, secondary causes of

ICP elevation also must be addressed [8]. Common causes of ICP elevation are outlined in Table 1.

Patterns of ICP elevation The natural history of intracranial hypertension depends on the underlying pathogenesis. In traumatic brain injury with a mass lesion, elevations in ICP may present acutely, prompting urgent surgical intervention. In a prospective evaluation of the time course of intracranial hypertension following traumatic brain injury (TBI), half the patients had their highest ICP within 3 days of the injury, whereas 25% had the highest mean ICP after 5 days [9]. The patients who experienced the later peak in ICP tended to have a poorer clinical grade and were more refractory to treatment. O’Phelan et al. [10] also described a signi" -cant number of patients who experienced late peak rises in ICP, and identi" ed four patterns of ICP elevation fol-lowing severe TBI: increases beginning within 72 hours (early); increases beginning after 72 hours (late); early

Figure 1. Medical College of Wisconsin algorithm for the management of increased intracranial pressure (ICP). Multimodal monitoring and second-tier therapies can be introduced for refractory elevations in ICP. CPP—cerebral perfusion pressure; EAC—external auditory canal; Hct—hematocrit; MAP—mean arterial pressure; PtO2—parenchymal oxygen partial pressure; SjO2—jugular bulb venous oxygen saturation.

Management of Intracranial Pressure I Wolfe and Torbey I 479

increases with resolution, followed by a second rise after 72 hours (bimodal); and continuously increased ICP. Disease processes that develop delayed edema formation (eg, ischemic stroke, hematomas) may require extended monitoring periods, with cranial imaging to guide the dis-continuation of monitoring. Prolonged ventriculostomy use or permanent CSF shunt placement may be required for hydrocephalus following subarachnoid hemorrhage or mass effect onto the normal CSF-draining pathway.

ICP Monitoring Indications for ICP monitoring Headache, nausea and vomiting, somnolence, and pupillary dilatation are signs of elevated ICP. Although papilledema is a speci" c indicator of intracranial hyper-tension, it may be present only in a minority of patients [8]. Imaging guidance (midline shift, effaced basal cis-terns) also may assist in the identi" cation of patients with a suspected increase in ICP, but signi" cant ICP elevations may occur without these " ndings.

The Brain Trauma Foundation has formulated guide-lines for the use of ICP monitors, helping standardize the approach to their placement [11]. Level II evidence exists to support monitoring in all salvageable patients with a severe TBI (Glasgow Coma Scale score of 3–8 after resus-citation) and an abnormal CT scan. An abnormal CT scan of the head is de" ned as one that reveals hematomas, contusions, swelling, herniation, or compressed basal cis-terns. Level III evidence supports monitoring in patients with severe TBI who have a normal CT scan, if two or more of the following features are noted at admission: age over 40 years, unilateral or bilateral motor posturing, or systolic BP less than 90 mm Hg. Some variability exists in patient selection for the placement of an ICP monitor because of the lack of prospective randomized trials sup-

porting their role. Sha" et al. [12•] reported a retrospective analysis of the National Trauma Data Bank suggesting a 45% reduction in survival when ICP monitoring was performed according to guidelines similar to those stated previously; only 43% of patients meeting guideline criteria underwent ICP monitoring. The signi" cance of this " nd-ing is unclear and may represent morbidity related to the treatment prompted by monitoring, or may suggest that the patient’s severity of injury was overestimated at the time of monitor placement.

Guidelines for the use of ICP monitoring for pathology other than trauma are less clearly established. However, adopting inclusion criteria similar to those used for TBI may help guide appropriate application in patients with nontraumatic intracranial hypertension. Clinical deterio-ration and imaging consistent with mass effect may serve as important selection criteria.

ICP monitors and waveforms Various intracranial monitoring devices exist, with the ventricular drain being the gold standard [8]. Ventricular catheters can be zeroed repetitively, whereas parenchy-mal or subarachnoid bolt strain monitors are subject to delayed drift and cannot be re-zeroed after placement. Ventricular catheters also offer a therapeutic function, allowing CSF volume reduction.

Normal ICP waveforms are similar to the arterial waveform, with a " rst peak correlating with systole, a second peak correlating with aortic valve closure, and a third peak correlating with antegrade arterial ! ow during diastole; with reduced brain compliance, the second peak may be higher than the " rst. Self-perpetuating ICP eleva-tions (plateau waves) may occur when reductions in CBF lead to vasodilation and subsequent increases in ICP that in turn impair CBF, ultimately leading to further vasodi-lation and increases in ICP.

Table 1. Causes of elevated intracranial pressure

Primary intracranial pathology Primary extracranial pathology

Traumatic injury (contusion, diffuse axonal injury) Hypoxia

Intracranial hemorrhages (epidural, subdural, subarachnoid, parenchymal, tumoral)

Hypercarbia

Hyperpyrexia

Ischemic infarction with cytotoxic edema Hypertension

Neoplasm and associated vasogenic edema Hyponatremia

Hydrocephalus Jugular venous obstruction

Infection (meningitis, encephalitis, abscess, neurocysticercosis, malaria)

Agitation and valsalva

Convulsive seizure or depolarizing paralytic

Status epilepticus Mechanical ventilation (when peak end expiratory pressure > baseline intracranial pressure)Postoperative: hemorrhage, retraction, edema,

or cerebrospinal fl uid obstruction Hepatic failure

High-altitude cerebral edema

Toxins and medications (lead, tetracycline, doxycycline, rofecoxib, retinoic acid)

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Initial Clinical Management of ICPThe initial management of patients suspected of having elevated ICP should include resuscitation to ensure airway protection, normal oxygenation monitored with pulse oximetry and arterial blood gases (O2 saturation > 90% or Pa#2 > 60 mm Hg), and systolic BP greater than 90 mm Hg. Insurance of euvolemia and strict monitoring of in/out balance with a Foley catheter are necessary. Head of bed should be maintained at 30°, and the patient’s head should remain in midline positioning, without jugular compression, to promote venous return. For patients with loss of consciousness and cranial imaging abnormalities, prophylactic antiepileptic medication should be consid-ered to limit the possibility of seizure-related ischemia and hypertension. Sedation should be initiated (allowing for clinical assessments) and paralysis considered; the use of non-depolarizing paralytics is preferred to avoid ICP elevations associated with muscular contraction. Hyper-ventilation should be used only acutely to achieve P$#2 of approximately 33 mm Hg; prolonged hyperventila-tion should be avoided because of the sustained changes in autoregulation that may occur, and extensive acute reduction in P$#2 may cause vasoconstriction, contribut-ing to cerebral ischemia. The initial CPP goal should be maintained at greater than 60 mm Hg; values less than 60 mm Hg may be associated with worsened mortality [13], although CPP greater than 70 mm Hg has not been shown to improve outcome [14].

Surgical InterventionSurgical decompression of an intracranial space-occupy-ing lesion remains an acute intervention that can have an immediate impact on ICP elevations that are refractory to medical therapies, often with a durable effect. Decom-pressive craniectomy has been evaluated as the primary surgical intervention for hemorrhagic contusion following TBI, illustrating safety and ef" cacy, with reductions in both mortality and the need for additional surgery [15]. Although patients undergoing craniectomy had somewhat improved outcomes compared with those undergoing craniotomy with focal lesion evacuation, there was no difference in hospital or rehabilitation length of stay. A 40% rate of improved outcome in patients undergoing craniectomy for severe TBI has been seen, with older age as a potential exclusionary criterion [16]. The impact of decompressive craniectomy on cerebral oxygenation, vascular reactivity, and neurochemistry following severe TBI was assessed, suggesting that in patients who had good functional outcomes, these physiologic parameters normalized [17]. These " ndings may offer insight into factors that can help aid in prognostication. The HAM-LET (Hemicraniectomy After Middle Cerebral Artery Infarction With Life-Threatening Edema) trial speci" cally enrolled patients with middle cerebral artery infarction and life-threatening mass effect from edema prospectively at multiple centers [18]. This trial in 64 patients found an

absolute risk reduction in mortality of 38%. In addition, poor outcomes may be reduced if the procedure is per-formed within 48 hours of stroke onset, a bene" t that may not persist if delayed up to 96 hours; this bene" t on func-tional outcome has not been validated. The RESCUEicp (Randomised Evaluation of Surgery With Craniectomy for Uncontrollable Elevation of Intra-Cranial Pressure) trial is an international multicenter prospective randomized trial that will assess the ef" cacy of craniectomy in the manage-ment of ICP elevation attributable to many different causes [19••]. As of April 2009, one third of an anticipated 600 patients were enrolled. Once completed, this study should help de" ne the role of craniectomy in ICP management. Although surgery may have an acute impact on ICP, its use in the management of ICP should be considered on an individual basis, as the effect on meaningful outcome has not been fully proven for all patients.

Second-Tier Medical Management of ICPWhen ICP elevations remain refractory to initial medical therapy and the patient does not meet surgical criteria, or if the pressure remains elevated following surgery, more intensive measures must be implemented. No large prospectively validated randomized trials have been per-formed to evaluate the use of multimodal monitoring on outcome, or the relative ef" cacy of one intervention over the others. Despite this limitation, the application of these interventions and newer technology allow for improving goal-directed care. Forming an evidence-based treatment algorithm enables the rapid interpretation of multiple physiologic parameters. Figure 1 is an example of the pro-tocol employed at our institution. Some potential adverse effects encountered during ICP management are outlined in Table 2.

Multimodal monitoringMultimodal neuromonitoring may allow insight into the deranged cerebral metabolic balance that occurs follow-ing a brain injury or stroke. Although the measurement of ICP and evaluation of CPP remain the foundation of current intracranial hypertension management, the adjunctive use of more complex monitoring methodology may help limit secondary injury.

CBF is closely linked to the metabolism of oxygen, and the arteriovenous difference in oxygen content (AVTO2) can be measured to evaluate the adequacy of cerebral perfusion. The monitoring of a jugular bulb venous oximetry (SjO2) can be achieved with bedside catheter placement and provides a continuous estimate of cerebral venous oxygen saturation; suggested normal values for SjO2 range from 50% to 65% [20]. In Figure 1, strict SjO2 targets are set higher to reduce the chances of hypoxemia. If frequent or sustained hyperventilation is utilized, SjO2 monitoring may help prevent vasocon-striction-related ischemia. Similarly, when cerebral perfusion is inadequate or below the lower threshold for

Management of Intracranial Pressure I Wolfe and Torbey I 481

autoregulation, low levels of SjO2 and high AVTO2 might represent excessive O2 extraction. With pressure-passive

elevations of ICP, when the upper limit of autoregulation is exceeded or autoregulation is lost, high values of SjO2

Table 2. Some potential adverse effects associated with intracranial pressure treatments

Treatment Adverse effects

Seizure prophylaxis Encephalopathy

Sedation

Neuromuscular blockade/chemical paralysis Loss of clinical examination

Myopathy

Prolonged paralysis

Raised intracranial pressure (with muscular contraction from depolarizing blockers)

Hyperventilation Vasoconstriction-related ischemia

Chronic changes in autoregulation

Intracranial pressure monitoring Intracranial hemorrhage (epidural, subdural, parenchymal, ventricular)

Infection

Pain at insertion site

Mannitol/osmotic diuretics Congestive heart failure

Volume depletion

Pulmonary and peripheral edema

Electrolyte abnormalities (pseudo-hyponatremia)

Osmotic nephropathy (especially when volume depleted)

Hypertonic saline Congestive heart failure

Hypotension (during bolus)

Pulmonary and peripheral edema

Hyperchloremic metabolic acidosis

Osmotic myelinolysis

Rebound edema on discontinuation

Pharmacologic metabolic suppression

Barbiturates Sedation/loss of clinical examination

Respiratory depression and hypercarbia

Hypotension and cardiac suppression

Infection

Propofol Similar to barbiturates

Propofol infusion syndrome

Acute refractory bradycardia leading to asystole, with one or more of the following:

Metabolic acidosis

Rhabdomyolysis

Hyperlipidemia (triglycerides)

Enlarged or fatty liver

Therapeutic hypothermia Electrolyte abnormalities (hypokalemia, hypocalcemia)

Cardiac suppression, both atrial and ventricular arrhythmias (including asymptomatic electrocardiographic changes)

Infection due to immune suppression

Reduced creatinine clearance (during the active phase of hypothermia)

Pancreatitis

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and low AVTO2 may be seen because of an uncoupled increase in luxury perfusion.

The exact signi" cance of parenchymal oxygen tension (PbO2) is unclear, but its application in ICP management is important. It has been seen that SjO2 of approximately 50% correlates with PbO2 of approximately 8.5 mm Hg (range, 3–12 mm Hg); PbO2 is possibly a more durable method for longer monitoring [21]. In a small cohort of TBI patients, it was determined that measurements of PbO2 more accurately represented CBF and the cerebral AVTO2 than direct measurement of total cerebral oxygen delivery or oxygen metabolism [22]. If this relationship is validated, these " ndings may preempt the need for SjO2 or AVTO2 monitoring while PbO2 is being assessed, espe-cially in patients with cervical spine injury or cerebral venous occlusion. In a larger prospective trial implement-ing treatment thresholds of PbO2 greater than 20 mm Hg and ICP greater than 20 mm Hg, reduced mortality rates were seen using an ICP/PbO2-directed protocol [23]. Improved 6-month outcomes over standard ICP/CPP therapy also were seen. The assessment of autoregulation also may be possible through oxygen pressure reactiv-ity assessment, which correlates with cerebrovascular pressure reactivity [24]. These detailed evaluations may be appropriate mostly for patients with refractory ICP despite escalating therapies and require additional data processing hardware.

Electrophysiologic monitoring in the neurointensive care unit is common. Recently, the concept of detecting neurologic deterioration using electroencephalography and somatosensory evoked potentials was de" ned [25]. Of the patients in this study who had elevations in ICP, 68% had worsening of evoked responses either before or during the worsened ICP. Interpretation of these bedside data could allow earlier thresholds for initiat-ing an additional level of therapy. Intraparenchymal electrographic recording has been introduced as an addition to the multimetric bolt monitors. This technol-ogy may allow for detection of seizure activity surface electroencephalography cannot discern because of the underlying brain injury.

Cerebral microdialysis is another method that is being re" ned for the evaluation of metabolism and biochemistry. Microdialysis catheters are placed within the parenchyma, and with the use of variably sized semipermeable mem-branes, molecules are collected and evaluated. Markers of glucose metabolism (lactate, pyruvate), excitotoxicity (glutamate), and membrane breakdown (glycerol) are most commonly evaluated using microdialysis [26•]. Although monitoring of microdiasylate glucose and lactate concen-trations might help with tailoring glycemic control, the exact role of this evaluation in the routine management of ICP is not clear at this time.

Osmolar therapy The blood–brain barrier (BBB) is relatively impermeable to most low molecular weight solutes present in blood (pre-

dominantly sodium and chloride), as well as to the plasma proteins. The permeability of an osmotic agent across a semipermeable membrane such as the BBB is quanti" ed by a re! ection coef" cient, where values approaching 0 represent high permeability and those approaching 1 have low permeability [27]. Therefore, an increase in plasma osmolality always leads to decreases in brain parenchymal ! uid volume. The most frequently used osmoles today are mannitol and sodium (re! ection coef" cient ~ 0.9 and 1, respectively). Other osmolar solutes, such as glycerol, sor-bitol, and urea, have lower re! ection coef" cients and may lead to increases in parenchymal total ! uid volume after diffusing into the brain and exerting osmotic pressure. Analysis of perfusion imaging may allow insight into the integrity of the BBB following brain injury [28], possibly offering a marker for limitations on osmolar therapy use.

Additional effects may be imparted by mannitol and hypertonic saline. Mannitol has been found to upregu-late subsets of cerebral aquaporin receptors, which may facilitate the redistribution of water between normal and abnormal regions of the brain [29]. Hypertonic saline may also contribute to increases in CBF [30].

The rate of administration of an osmolar load may affect the ef" cacy of lowering ICP. Sustained administra-tion and lower weight-based dosing of mannitol have been shown to have a less pronounced and less enduring impact on elevated ICP [31•]. Bolus dosing may create a higher osmolar gradient across the BBB, ultimately inducing a larger decrease in parenchymal ! uid. When the ef" cacy of mannitol was compared with that of hypertonic saline, there was a signi" cant decrease in ICP from hypertonic saline compared with mannitol, along with signi" cant increases in MAP and CPP; improvements in cerebral oxy-genation also have been seen with hypertonic saline [32]. This difference may be explained by the diuretic effect of mannitol, causing reductions in intravascular volume. Following initial dosing of mannitol during resuscitation, the adjunctive use of hypertonic saline should be consid-ered for persistent ICP elevations.

In refractory cases, mannitol and hypertonic sodium may be alternated or given simultaneously. Monitoring the serum osmolar gap is helpful for monitoring the extent of mannitol administration and estimating serum concentra-tion. After initiating osmolar therapy with mannitol, the measured serum osmolality goal traditionally has been 320 mOsm/L. However, with the use of hypertonic sodium solutions for elevated ICP occurring more commonly, stan-dardized osmolality goals may become obsolete. A more rational approach may be the osmolar gap calculation—gap = measured – calculated osmolality; calculated osmolality = (2Na) + (glucose/18) + (blood urea nitrogen/2.8)—to estimate serum levels and guide the administration of mannitol [33]. Gap values less than 10 would suggest it is safe for administration of additional mannitol, with an increased risk of adverse effects if gap persists at greater than 20. If hyperchloremic metabolic acidosis develops with hypertonic saline administration, hypertonic sodium

Management of Intracranial Pressure I Wolfe and Torbey I 483

bicarbonate solutions may serve as an effective alternative [34]; partial or complete substitution of chloride for acetate (bicarbonate equivalent) is another alternative.

Metabolic suppression Metabolic suppression may be used to treat elevations in ICP, assuming tissue viability and coupling of blood ! ow to the metabolic demand of the brain. By inducing a reduced meta-bolic requirement, the amount of blood ! ow required by the brain also is reduced. Additional excitotoxic processes also may be attenuated. Here, more emphasis has been placed on therapeutic hypothermia, which is an emerging therapy compared with pharmacologic suppression.

Pharmacologic suppressionBarbiturate therapy to induce electroencephalographic burst suppression has been a mainstay of pharmacologic metabolic suppression for elevated ICP, although it is not indicated for prophylactic administration [35]. Signi" -cant morbidity may be associated with this therapy and should be reserved for cases of ICP refractory to standard " rst-line medical care, and hemodynamic stability is mandatory before and after induction. Traditionally, an electroencephalogram has been used to monitor neural activity, although this may be assessed using bispectral index monitoring to allow for easier evaluation [36], especially in non–neurointensive care units. Barbiturate coma may lower ICP and improve cerebral oxygenation [37]. This improvement in cerebral oxygenation has been partly validated in additional reports, although in areas of impaired cerebral physiology, worsening oxygenation may be seen [38]. The worsening may re! ect dif" culties maintaining adequate CPP in regions of the brain with impaired autoregulation.

Propofol, along with other sedative/hypnotics, has been used to induce sedation and coma in place of bar-biturates, demonstrating safety and ef" cacy [35,39]. In addition to neural suppression caused by activation of the -aminobutyric acid A receptor and inhibition of the N-methyl-%-aspartate receptor, propofol may have a direct neuroprotective effect [40]. The bene" cial effects of propofol may be countered by cardiovascular suppression affecting CPP, leading to reduced cerebral ! ow in areas with impaired autoregulation.

Therapeutic hypothermia and temperature augmentationFever is common following brain injury, and avoidance of hyperthermia may be an important part of the man-agement of brain injury from any cause [41•,42,43]. Intracranial temperature has been shown to be higher than core body temperature [42], representing an impor-tant treatment consideration because of the relationship between elevations in ICP and intracranial temperature. Fever reduction in acute brain injury also may signi" cantly reduce systemic metabolic demand, although this may depend on control of shivering [43]. The adverse effects of temperature elevations above 37°C may be mediated by

multiple pathogenic mechanisms, including excitotoxic-ity, free radical generation, in! ammation, apoptosis, and genetic differences in response to injury [44].

The application of mild therapeutic hypothermia, main-taining core body temperature near 33°C, is a novel strategy used to provide neuroprotection following brain injury in many clinical scenarios presenting with coma [41•]. Several modalities are available for the induction of hypothermia: external cooling devices, intravenous cold saline infusion, and intravascular cooling catheters. Each of these methods is associated with individual risks and bene" ts.

There may be a treatment window for hypothermia induction to impart measurable clinical bene" t, with a possible lack of bene" t seen in instances of delayed appli-cation for TBI [45]. The rate of rewarming is another important aspect in treatment ef" cacy, with elevations beyond normothermia potentially imparting deleterious effects because of impaired cerebrovascular regulation [41•,46•,47].

Although initial reports supported the role of hypo-thermia induced within 6 hours of TBI, subsequent studies failed to show a bene" t on neurologic recovery [48]. Patients with ICP elevations refractory to standard osmolar therapy may bene" t from hypothermia, but any bene" t over medication-induced metabolic suppression is unclear [49]. It is possible that if a patient fails to improve with phar-macologic metabolic suppression, there may not be any further improvement following induction of hypothermia, although it may act synergistically when a response is seen. If hypothermia is applied in the setting of refractory eleva-tions in ICP, further reduction in temperature beyond 32°C has not been shown to impart further ef" cacy, and more complications may be encountered [50]. However, if recur-rent elevations in ICP are encountered during rewarming, slowing the rate of rewarming or extending the duration of hypothermia may be necessary. This may pose a problem with regard to accurately assessing neurologic prognosis in a timely manner, because sedatives and paralytics often are required during hypothermia.

ConclusionsRecent advances in technology have allowed signi" cant improvement in the management of intracranial hyper-tension. Using bedside physiologic data, including ICP transduction and waveform analysis and monitoring of SjO2, PbO2, and cerebral temperature, optimization of cere-bral perfusion and oxygenation and prevention of additional secondary injury may be possible. Establishing protocols to aid in the management of intracranial hypertension may improve the quality of care through standardization of treatment, based on real-time physiologic analysis.

AcknowledgmentDr. Wolfe is the 2009–2010 Daniel M. Soref Clinical Neurosciences fellow.

484 I Critical Care

DisclosureNo potential con! icts of interest relevant to this article were reported.

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