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Cerebral Pathophysiology and Critical Care Neurology:Basic Hemodynamic Principles, Cerebral Perfusion,

and Intracranial Pressure

Edward R. Smith and Joseph R. Madsen

ediatric neurologic intensive care differs from standard pediatric intensive care in two important respects. First,he diagnosis, monitoring, and management of problems related to disorders of cerebral perfusion and intracranialressure (ICP) are central to nearly all of pediatric neurologic and neurosurgical intensive care. Second, variouslinical problems normally encountered in the intensive care unit (ICU) have additional implications whenssociated with neurologic disease. Regardless of the cause, treatment should be undertaken as expeditiously asossible and should be based on the principles of resuscitation, reducing the volume of the intracranial contents,nd reassessment. This chapter aims to outline some basic principles underlying the diagnosis and managementf elevated ICP in children.
2004 Elsevier Inc. All rights reserved.
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EDIATRIC NEUROLOGIC intensive care difers from standard pediatric intensive care in

mportant respects. First, the diagnosis, monitond management of problems related to disordeerebral perfusion and intracranial pressure (ICPentral to nearly all of pediatric neurologic and nosurgical intensive care. Second, various clinroblems normally encountered in the intensivenit (ICU) have additional implications when assoted with neurologic disease. These consideratioombination with the rapid advances in pediaritical care, merit discussion, with a focus on clincenarios commonly encountered in the pediCU setting. The relationship between the basic piples of neuroresuscitation—airway, breathing,irculation (the ABCs)—and the pathophysiologyerebral perfusion and ICP is emphasized, alongreatment.

ELEVATED INTRACRANIAL PRESSURE

The diagnosis, monitoring, and managemenisorders of ICP are often crucial to the treatmf neurologic disease. Elevated ICP is a potentevastating complication of neurologic injury.vated ICP may complicate trauma, centralous system (CNS) tumors, hydrocephalus, Cnfections, metabolic encephalopathy, andaired CNS venous outflow.1 Successful manag-ent of patients with elevated ICP requires pro

ecognition, judicious use of invasive monitorinnd therapy directed at both reducing ICPeversing its underlying cause. The evaluationanagement of patients with elevated ICP is

iewed here. Specific causes and complication
levated ICP are discussed elsewhere in this issue.
eminars in Pediatric Neurology, Vol 11, No 2 (June), 2004: pp 89-104

Pathophysiology of Elevated ICP

ICP is normally�20 mmHg in adults; increaseCP is considered pathological if sustained at pures�20 mmHg. ICP is normally lower in chiren, with older children having an ICP of about

o 15 mmHg, infants with�5 to 10 mmHg, anewborns with reportedly subatmospheric pures.2 Intrinsic regulatory mechanisms maintCP in a homeostatic range, with occasional tient elevations associated with physiologvents, including sneezing, coughing, and Valsaneuvers.The brain and its contents are surrounded by

kull, a bony structure with a fixed volumedults. This volume, about 1400 to 1700 mL indult, is filled with essentially three componeistributed in the following manner:3

Brain parenchyma, 80%Cerebrospinal fluid, 10%Blood, 10%Pathological processes, including mass lesi

bscesses, and hematomas, also may be pithin the intracranial compartment. Becauseverall volume of the cranial vault is fixed, ireases in the volume of one component ordditional presence of pathological componeecessitate the displacement of other structure

From the Department of Neurosurgery, Children’s Hospital,oston, MA.Address reprint requests to Edward R. Smith, MD, Depart-

ent of Neurosurgery, Children’s Hospital 300 Longwoodve., Boston, MA 02115.© 2004 Elsevier Inc. All rights reserved.1071-9091/04/1102-0000$30.00/0
doi:10.1016/j.spen.2004.04.001
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ncrease in ICP, or both. Thus ICP is a function ofoth the volume and compliance of each compo-ent of the intracranial compartment, an interrela-ionship known as the Monro-Kellie doctrine.4,5

The volume of brain parenchyma is relativelyonstant, although it can be altered by mass lesionsr in the setting of cerebral edema. The volumes oferebrospinal fluid (CSF) and blood in the intra-ranial space vary to a greater degree, and abnor-al increases in the volume of either componentay lead to elevations in ICP.CSF is produced by the choroid plexus and

lsewhere in the CNS at a rate of approximately 20L/hour, for a total of about 500 mL/day.6 CSF is

ormally resorbed via the arachnoid granulationsnto the venous system. Problems with CSF regu-ation generally result from impairment of normalechanisms of CSF removal from the CNS. Most

ommonly, these problems with CSF removal areecondary to either ventricular obstruction or ve-ous congestion; the latter can occur in patientsith sagittal (or other) venous sinus thrombosis.uch less frequently, CSF production can become

athologically increased; this may be seen in theetting of choroid plexus papilloma (Fig 1).

Cerebral blood flow (CBF) determines the volumef blood in the intracranial space. CBF increases withypercapnia and hypoxia. Other determinants of CBFre discussed later. Autoregulation of CBF may bempaired in the setting of neurologic injury and mayesult in rapid and severe brain swelling, especially inhildren.7-9

ntracranial Compliance

The interrelationship between changes in the

Fig 1. Sagittal magnetic resonance imaging scan of a pa-ient with a brain tumor in the posterior fossa. The lesion islocking outflow of CSF from the fourth ventricle, causingbstructive hydrocephalus and elevated ICP.

olume of intracranial contents and changes in ICP I

efine the compliance characteristics of the intra-ranial compartment. Intracranial compliance cane modeled mathematically (as in other physio-ogic and mechanical systems) as the change inolume over the change in pressure (dV/dP).The compliance relationship is nonlinear, and

ompliance decreases as the combined volume ofhe intracranial contents increases. Initially, com-ensatory mechanisms allow volume to increaseith minimal elevation in ICP. These mechanisms

nclude displacement of CSF into the thecal sacnd decreases in the volume of the cerebral venouslood via venoconstriction and extracranial drain-ge. However, when these compensatory mecha-isms have been exhausted, significant increases inressure develop with small increases in volume,eading to abnormally elevated ICP (Fig 2).

Thus the magnitude of the change in volume ofn individual structure determines its effect onCP. In addition, the rate of change in the volumef the intracranial contents also influences ICP.hanges that occur slowly produce less of an effect

han those that occur rapidly, because the brain hasore time to accommodate to the lesion. This can

e recognized clinically in some patients whoresent with large meningiomas and minimallylevated or normal ICP. Conversely, other patientsay experience symptomatic elevations in ICP

rom small hematomas that develop acutely. How-ver, even with slowly developing lesions, com-ensatory mechanisms are often exhausted, andltimately elevated ICP ensues.

Fig 2. Graphic representation of changes in ICP withhanges in intracranial volume. The elevation of ICP withncreased intracranial volume is modest until compensatory

echanisms are exhausted, after which marked elevations in
CP occur with only small changes in volume.

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91CEREBRAL PATHOPHYSIOLOGY AND CRITICAL CARE NEUROLOGY

erebral Blood Flow

Following sustained elevations in ICP, neuro-ogic injury can occur as a result of brainstemompression and/or a reduction in CBF. CBF is aunction of the relationship between a pressureifferential across the cerebral circulation and ce-ebrovascular resistance. This relationship can bexpressed mathematically by a variation of Ohm’saw:10

CBF � (CAP � JVP) � CVR,

here CAP is carotid artery pressure, JVP is jug-lar venous pressure, and CVR is cerebrovascularesistance.

Cerebral perfusion pressure (CPP) is often useds a measure of the adequacy of blood supply tohe brain (ie, cerebral perfusion). CPP is defined as

ean arterial pressure (MAP) minus ICP:

CPP � MAP � ICP.

utoregulation

CBF is normally maintained at a relatively con-tant level by cerebrovascular autoregulation ofVR over a wide range of CPP (50 to 100mHg).11 However, autoregulation of CVR can

ecome dysfunctional in certain pathologicaltates, most notably stroke or trauma. In this set-ing, the brain becomes exquisitely sensitive toven minor changes in CPP.12,13

Although rare in the pediatric population, pa-ients with chronic hypertension will have alteredetpoints of CPP autoregulation. With mild tooderate elevations in blood pressure, the initial

esponse is arterial and arteriolar vasoconstriction.his autoregulatory process maintains tissue per-

usion at a relatively constant level and also pre-ents the increase in pressure from being transmit-ed to the smaller, more distal vessels.11 As aesult, rapid reductions in blood pressure, even ifhe corrected blood pressure is considered normo-ensive for the patient’s age group, can produceschemic symptoms in patients with chronic hyper-ension.12

erebral Perfusion Pressure

Conditions associated with elevated ICP, includ-ng mass lesions and hydrocephalus, can be asso-iated with reduced CPP. This can result in devas-ating focal or global ischemia. In contrast,
xcessive elevation of CPP can lead to hyperten- n
ive encephalopathy and cerebral edema due to theventual breakdown of autoregulation, particularlyf the CPP is �120 mmHg.11,12,14,15

Clinical Manifestations of Elevated ICP

Ultimately, global or local reductions in CBF areesponsible for the clinical manifestations of ele-ated ICP. These manifestations can be furtherivided into generalized responses to elevated ICPnd herniation syndromes.

Generalized symptoms of elevated ICP includeeadache, which is probably mediated via the painbers of the trigeminal nerve (cranial nerve [CN]) in the dura and blood vessels, depressed global

onsciousness due to either the local effect of massesions or pressure on the midbrain reticular for-ation, and vomiting. Signs include CN VI pal-

ies, papilledema (secondary to impaired axonalransport and congestion, a process that developsubacutely and as such is not usually seen until theatient has had elevated ICP for at least severalays), and a triad of bradycardia, respiratory de-ression, and hypertension (Cushing’s triad).3 Al-hough the mechanism of Cushing’s triad remainsontroversial, it is generally considered to be in-icative of brainstem compression. This responses an ominous finding that requires urgent interven-ion.

Focal symptoms of elevated ICP may be causedy local effects in patients with mass lesions or byerniation syndromes. Herniation results whenressure gradients develop between two regions ofhe cranial vault. The most common anatomicocations affected by herniation syndromes includeubfalcine, central transtentorial, uncal transtento-ial, upward cerebellar, cerebellar tonsillar/fora-en magnum, and transcalvarial.3,16

One notable false localizing syndrome seen aftereurologic injury, known as Kernohan’s notchhenomenon, involves a combination of contralat-ral pupillary dilation and ipsilateral weakness.17

ecause the diagnostic accuracy of signs andymptoms is limited, the aforementioned findingsay be inconsistent or unreliable in any given

ase. Nonetheless, their presence, although notlways localizing, is an important herald of severencreased ICP and necessitates rapid treatment. Inearly all cases, the most reliable method of diag-
osing elevated ICP is to measure it directly.

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MONITORING ICP AND DIAGNOSINGELEVATED ICP

Empiric therapy for presumed elevated ICP isnsatisfactory, because CPP cannot be monitoredeliably without accurate ICP measurement. Fur-hermore, most therapies directed at lowering ICPor are effective for only limited and variableeriods. In addition, these treatments may haveerious side effects. Therefore, although initialteps to control ICP may, out of necessity, beerformed without the benefit of ICP monitoring,n important early goal in managing a patient withresumed elevated ICP is to place an ICP moni-oring device.

The purpose of monitoring ICP is to improve thelinician’s ability to maintain adequate CPP andxygenation. The only way to reliably determinePP is to continuously monitor both ICP and bloodressure. In general, the patient is managed in anCU with an ICP monitor and arterial line. Theombination of ICP monitoring and concomitantanagement of CPP may improve outcome, par-

icularly in patients with closed head trauma.18-20

CPP should be kept above 50 mmHg, ideallybove 70 mmHg, in patients with elevated ICP inn attempt to avoid hypoperfusion and ischemicnjury.18,21-23 One study of 158 patients with headrauma and a Glasgow Coma Scale (GCS) score

7 found that ICP monitoring and maintenance ofPP �70 mmHg resulted in improved outcomeshen compared with historical controls. This study

lso demonstrated that ICP generally did not in-rease with elevations in CPP until a critical level,110 mmHg, was reached.18 These data support

he somewhat counterintuitive concept that pressorgents can be used safely in patients with elevatedCP as long as CPP is not elevated.

However, a common problem arising in the caref pediatric patients is the scenario in which ICP ist a physiological level (�15 to 20 mmHg), bloodressure is within normal physiological parametersor the patient’s age, but CPP is �50 mmHg. Theuestion that arises relates to the need to artificiallylevate blood pressure pharmacologically to meetPP parameters. In our institution, if the ICP andAP are physiologic, we have generally not arti-

cially elevated the blood pressure to maintainPP �50.

Indications

The diagnosis of elevated ICP generally is based
n clinical findings and corroborated by imaging a
tudies and the patient’s medical history. Closedead injury is one of the most frequent and best-tudied indications for ICP monitoring. Much ofhe current practice of ICP monitoring has beenerived from clinical experience with closed headrauma patients.24 Other potential indications forCP monitoring include stroke, intracerebral hem-rrhage, hydrocephalus, subarachnoid hemor-hage, Reye’s syndrome, hepatic encephalopathy,nd sagittal sinus thrombosis.

The Guidelines for the Management of Severeead Injury suggest that ICP monitoring is indi-

ated in comatose head-injured patients with GCScores between 3 and 8 and abnormal cranialndings on computed tomography (CT) scan.25-27

As noted earlier, invasive monitoring is usuallyot indicated in patients who are awake and able toollow commands. An exception to this rule occurshen an awake patient is at risk for elevated ICP

nd needs to undergo general anesthesia for sur-ery, rendering clinical evaluation impossible dur-ng anesthesia. Clinically, this may occur in pa-ients who have sustained trauma, have evidence of

small petechial hemorrhage on CT, and requireonneurologic surgery, such as treatment of ortho-edic injuries.

Role of Computed Tomography

Although CT scans may suggest elevated ICPased on the presence of mass lesions, midlinehift, or effacement of the basilar cisterns, patientsithout these findings on initial CT may still have

levated ICP. This was demonstrated in a prospec-ive study of 753 patients treated at four major U.S.ead injury research centers that found that pa-ients whose initial CT scan did not show a massesion, midline shift, or abnormal cisterns had a0% to 15% chance of developing elevated ICPuring hospitalization.28 Other studies have shownhat up to 33% of patients with initially normalcans developed CT scan abnormalities within therst few days after closed head injury.29,30 To-ether, these findings demonstrate that ICP can belevated even in the setting of a normal initial CTcan, demonstrating the importance of invasiveonitoring in high-risk patients and of follow-up

maging in patients who develop clinical evidencef increased ICP during hospitalization.25

Because ICP monitoring is associated with amall risk of serious complications, including CNSnfection and intracranial hemorrhage, it is reason-
ble to try to limit its use to those patients at

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reatest risk for elevated ICP. In general, invasiveonitoring of ICP is indicated in patients who

re:31

Suspected to be at risk for elevated ICPComatose (GCS score �8)Diagnosed with a process that merits aggressivemedical care.The various options for ICP monitors are dic-

ated by the underlying pathophysiologic processnd the protocols of the neurosurgical staff at theocal institution. Types of invasive ICP monitorsre discussed elsewhere in this issue.

Noninvasive and Metabolic Systems

A number of devices designed to noninvasivelyecord ICP have been studied, but none has dem-nstrated reproducible clinical success. However,issue resonance analysis (TRA), an ultrasound-ased method, has shown some promise. One trialf 40 patients who underwent both invasive andRA ICP monitoring demonstrated good correla-

ion between concomitant invasive and TRA mea-urements.32

Other proposed noninvasive methods of moni-oring ICP include transcranial Doppler (TCD),hich measures the velocity of blood flow in theroximal cerebral circulation. TCD can be used tostimate ICP based on characteristic changes inaveforms that occur in response to increased

esistance to CBF.33 Generally, TCD is poor pre-ictor of ICP, although in trauma patients TCDndings may correlate with outcome at 6onths.34-36

Tympanic membrane displacement is based onhe hypothesis that increased ICP will transmit aressure wave to perilymph, and, by extension, tohe tympanic membrane. These changes are theneasured using an impedance audiometer.37,38 To

ate, this technique has not been studied in largelinical trials.

Finally, the metabolic state of the brain can bessessed using jugular venous oxygen saturationonitoring. This method is a way of quantifying

egional oxygen consumption based on the Fickrinciple. Investigators have used catheters withxygen monitors in the jugular bulb, as well asxperimental sensors that use near-infrared spec-roscopy, to quantify the oxygen content in bloodraining from the CNS.39 Evidence of jugularenous oxygen desaturation suggests impaired ox-gen delivery and an ischemic state in the brain,

40-42
onsistent with elevated ICP. (
Waveform Analysis

ICP is not a static value; rather, it exhibits cyclicariation based on the superimposed effects ofardiac contraction, respiration, and intracranialompliance. Under normal physiological condi-ions, the amplitude of the waveform is oftenmall, with B waves related to respirations andmaller C waves (or Traube-Hering-Mayer waves)f the cardiac cycle.10

Pathological A waves (also called plateauaves) are abrupt, marked elevations in ICP of 50

o 100 mmHg usually lasting for minutes to hours.he presence of A waves signifies a loss of intra-ranial compliance and heralds imminent decom-ensation of autoregulatory mechanisms.10,43-45

hus A waves should suggest the need for urgentntervention to help control ICP.

MANAGEMENT OF ELEVATED ICP

The best therapy for intracranial hypertensionICH) is to resolve the proximate cause of elevatedCP. Examples include evacuation of a blood clot,esection of a tumor, CSF diversion in the settingf hydrocephalus, and treatment of an underlyingisorder, such as an infectious or metabolic disor-er.Regardless of its cause, ICH is a medical emer-

ency, and treatment should be undertaken as ex-editiously as possible. In addition to definitiveherapy, a series of maneuvers can be used tocutely reduce ICP. Some of these techniques areenerally applicable to all patients with suspectedCH, whereas others (particularly corticosteroiddministration) are reserved for specific causes ofCH. A set of clinical guidelines for managingevere brain injury has been developed at Chil-ren’s Hospital Boston (Fig 3 a-d). Although de-igned for trauma patients, these guidelines arelso a useful resource for many clinical scenariosn which elevated ICP is a problem.

General Management

esuscitation

The emergent assessment and support of oxy-enation, blood pressure, and end-organ perfusions particularly important in trauma, but is applica-le to all patients.46-48 When elevated ICP is sus-ected, care should be taken to minimize furtherlevations in ICP during intubation through carefulositioning, appropriate choice of paralytic agents
if required), and adequate sedation. Pretreatment

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94 SMITH AND MADSEN

Fig 3. Clinical guideline for managing patients with severe brain injury. (Reprinted with permission from Children’s Hospital
oston.)

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ith lidocaine has been suggested as a usefulntervention to decrease the rise in ICP associatedith intubation; however, good clinical evidence

upporting this approach is limited.49

Large shifts in blood pressure should be mini-ized, with particular care taken to avoid hypo-

ension. Although it might seem that lower bloodressure would result in lower ICP, in fact this isot the case. Hypotension, especially in conjunc-

Fig

ion with hypoxemia, can induce reactive vasodi- i

ation and elevations in ICP. As noted earlier,ressor agents have proven safe for use in mostatients with ICH and may be needed to maintainPP �70 mmHg.18

mergent Situations

Patients can present emergently with history orxamination findings suggestive of elevated ICP.n this setting, life-saving measures may need to be

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maging or ICP monitoring. In addition to standardesuscitation, the following measures should benstituted as soon as possible:

Head elevationHyperventilation to a PCO2 of 26 to 30 mmHgAdministration of intravenous mannitol (0.5 to1.5 g/kg)Concomitant with these measures should be an

ggressive evaluation of the underlying diagnosis,

Fig

ncluding neuroimaging, detailed neurologic exami- a

ation, and history-taking. Hyperventilation is oftenontraindicated in the setting of traumatic brain injurynd acute stroke, and is discussed separately (see theater section on hyperventilation). If appropriate, ven-riculostomy provides a rapid means of simulta-eously diagnosing and treating elevated ICP.

onitoring and the Decision to Treat

If a diagnosis of elevated ICP is suspected and

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resent, then ICP monitoring should be instituted.he use of ICP monitoring is associated withecreased mortality in patients with traumaticrain injury.19 The choice of monitoring devicehould be based on an assessment of advantagesnd disadvantages, as discussed previously.

The goal of ICP monitoring and treatmenthould be to maintain ICP �20 mmHg and CPP

25

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70 mmHg. Interventions should be undertaken r

nly when ICP is elevated above 20 mmHg forore than 5 to 10 minutes. As discussed earlier,

rief physiological elevations in ICP may occur inhe setting of coughing, movement, suctioning, orentilator asynchrony.

luid Management

In general, patients with elevated ICP do not50

nt’d)

equire severe fluid restriction. Patients should be

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98 SMITH AND MADSEN

ept euvolemic and normo-osmolar to hyperosmo-ar. This can be achieved by avoiding all free waterincluding dextrose 5% in water, 0.45% [half-ormal] saline, and enteral free water) and usingnly isotonic fluids (such as 0.9% [normal] saline).

comparison of colloid and crystalloid fluid re-uscitation in patients with elevated ICP has beentudied, but findings have been inconclusive withespect to the superior approach.51

Serum osmolality should be maintained above80 mOsm/L, and often is kept between 295 and05 mOsm/L. Hypertonic saline in bolus dosesay acutely lower ICP; however, clinical out-

omes after hypertonic saline therapy have beenixed.52,53 Hyponatremia is a common finding in

he setting of elevated ICP, particularly in conjunc-ion with subarachnoid hemorrhage.

edation

Keeping patients appropriately sedated can de-rease ICP by reducing metabolic demand, ventilatorsynchrony, venous congestion, and the sympatheticesponses of hypertension and tachycardia.54 Estab-ishing a secure airway and paying close attention tolood pressure allows the clinician to quickly identifynd treat apnea and hypotension. Propofol has beensed to good effect in this situation, because it isasily titrated and has a short half-life, thus permittingrequent neurologic reassessment. However, propofolhould be used with caution in the pediatric popula-ion due to the risk of metabolic derangement, par-icularly with prolonged use.

One common clinical scenario is the problem ofeaning children off of sedation in the setting ofotentially elevated ICP. A protocol for this haseen developed at Children’s Hospital Boston thatncludes an algorithm to aid in this process (Fig 4).

lood Pressure Control

In general, blood pressure should be sufficient toaintain CPP �70 mmHg. However, in children

here may not be a need to maintain CPP at thisevel. Some data suggest that there are worseutcomes in patients with CPP �40 mmHg, butot necessarily better outcomes with CPP �70 mmg.55,56 A comparison of management strategiesesigned to maintain ICP �20 mm Hg versushose to maintain CPP �70 mmHg in adults foundo significant difference in survival between thewo groups, but did find that the CPP managementroup had a five-fold increase in the incidence of

57
cute respiratory distress syndrome.
As discussed earlier, pressor agents can be usedafely without increasing ICP any further. This isarticularly relevant in the setting of sedation, inhich iatrogenic hypotension can occur. The deci-

ion of when to treat hypertension is a matter ofebate, but generally treatment should be consid-red when ICP is physiological and CPP is �40 to0 mmHg. Caution should be taken to avoid lettingPP drop to �40 to 50 mmHg or, as noted earlier,

o avoid normalization of blood pressure in pa-ients with chronic hypertension in whom the au-oregulatory curve has shifted to the right.

ositioning

Patients with elevated ICP should be positionedo maximize venous outflow from the head. Impor-ant maneuvers include reducing excessive flexionr rotation of the neck, avoiding restrictive neckaping, and minimizing stimuli that could inducealsalva responses, such as endotracheal suctioning.Patients with elevated ICP have historically

een positioned with the head elevated above theeart (usually 30 degrees) to increase venous out-ow. It should be noted that head elevation may

ower CPP;58 however, given the proven efficacyf head elevation in lowering ICP, most expertsecommend raising the patient’s head as long ashe CPP remains at an appropriate level.59

etabolic Demand Reduction

Increased metabolic demand in the brain resultsn increased CBF and can elevate ICP by increas-ng the volume of blood in the cranial vault. Con-ersely, decreased metabolic demand can lowerCP by reducing blood flow. Fever increases brainetabolism, and has been demonstrated to increase

rain injury in animal models.60 Therefore, aggres-ive treatment of fever, including acetaminophennd mechanical cooling, is recommended in pa-ients with increased ICP. ICH is a recognizedndication for neuromuscular paralysis in selectedatients.61

Seizures can both complicate and contribute tolevated ICP.62,63 Anticonvulsant therapy shoulde instituted if seizures are suspected; prophylacticreatment may be warranted in some cases. Finally,arbiturate sedation and hypothermia may reduceCP and should be considered in the patients withefractory ICH (see below).

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ummary of General Management Strategies

The basic principles of neuroresuscitation (theBCs) must be adhered to in all critical neurologic

ituations, because these have a direct relationshipo cerebral perfusion and ICP, through effects pri-

Fig 4. Clinical guideline for weaning patients with severe bospital Boston.)

arily on oxygen and carbon dioxide concentra- g

ions and mean arterial pressure. Cerebral autoreg-lation is also important. Autoregulation is theeans by which the autonomic nervous system

elivers a relatively constant CBF when the MAPs between 50 and 100 mmHg. With intact cerebralutoregulation, hypoxemia or hypercarbia will trig-

jury off sedation. (Reprinted with permission from Children’s
rain in
er a compensatory increase in CBF. This could

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esult in an increase in ICP, which could poten-ially cause herniation in the presence of an alreadylevated ICP.

Hypoxemia or hypercarbia occur when there isirway obstruction, hypoventilation, or apnea. Sys-emic hypotension could produce a decrease inBF; systemic hypertension, an increase in CBF.ith increased ICP, systemic hypotension results

n a further decrease in CBF, whereas systemicypertension results in an elevation in ICP due tohe increased CBF. If autoregulation is lost, thenBF becomes directly proportional to the MAP. It

s therefore important to maintain blood pressureithin the normal range (avoiding hypotension orypertension); prevent hypoxemia, hypercarbia,nd hypoglycemia; and treat hyperthermia in situ-tions with a potential for increased ICP.

Specific Therapies

As mentioned previously, the best approach toreatmenting elevated ICP is to address its under-ying cause. If this is not possible, then a series ofeasures should be instituted to reduce ICP in an

ttempt to improve outcome. In all cases, thelinician should bear in mind the these of resusci-ation, reduction of intracranial volume, and fre-uent reevaluation discussed earlier.

emoval of Mass Lesions or CSF

Obvious mass lesions associated with elevatedCP should be removed, if possible. Similarly,hen hydrocephalus is identified, a ventriculos-

omy or other CSF diversion technique should besed. CSF should be removed slowly; this is par-icularly important in patients with symptomaticydrocephalus due to aneurysmal subarachnoidemorrhage. In this setting, rapid removal of CSFan result in a marked pressure differential acrosshe clot in the dome of an aneurysm and lead toecurrent hemorrhage. Therefore, CSF should beemoved 3 to 5 mL at a time to gradually reduceCP and minimize the risk of rebleeding.

smotherapy

Osmotic diuretics reduce brain volume by draw-ng free water out of the tissue and into the circu-ation, where it is excreted by the kidneys, thusehydrating the brain parenchyma.61,64-66 Theost commonly used agent is mannitol. It is pre-

ared as a 20% solution and given as a bolus of 0.5o 1 g/kg. Repeat doses can be given at 0.25 to 0.5
/kg as needed, generally every 6 to 8 hours. The c
se of any osmotic agent should be carefully eval-ated in patients with renal insufficiency. In addi-ion, recent literature has supported the use ofyperosmolar saline (3%) as an osmotic agent, at aose of 0.25 to 1 mL/kg. Of note, it appears thathildren treated with hyperosmolar saline can tol-rate much higher serum osmolarity than can theame patient treated with mannitol (350 to 360Osm for 3% NaCl vs 320 mOsm for mannitol).The effects usually occur within minutes, peak

t about 1 hour, and last for 4 to 24 hours.31,67

ome have reported “ rebound” ICP; this proba-ly occurs when mannitol, after repeated use,nters the brain though a damaged blood-brainarrier and reverses the osmotic gradient.68 Use-ul parameters to monitor during mannitol ther-py include serum sodium level, serum osmola-ity, and renal function. Findings of concernssociated with mannitol therapy include serumodium �150 mEq, serum osmolality �320Osm, or evidence of evolving acute tubular

ecrosis (ATN). In addition, mannitol can lowerystemic blood pressure, necessitating carefulse if associated with a drop in CPP. Furosemideppears to be synergistic with mannitol; how-ver, this effect can also exacerbate dehydrationnd hypokalemia.69-71

Glycerol and urea were historically used to con-rol ICP via osmoregulation; however, the use ofhese agents has decreased in recent years, becausequilibration between brain and plasma levels oc-urs more quickly than with mannitol. Further-ore, glycerol has been shown to have a signifi-

ant rebound effect and to be less effective thanannitol in controlling ICP.72,73

orticosteroids

Corticosteroids are not useful in managing ele-ated ICP resulting from infarction, hemorrhage,r head trauma.74-80 They may have a role in theetting of ICH caused by brain tumors and someNS infections. In these patients, dexamethasone

usually a bolus of 10 mg intravenously (IV),ollowed by 4 to 10 mg IV every 6 hours) isssociated with a decrease in ICP.81-85

yperventilation

Using mechanical ventilation to lower PaCO2 to6 to 30 mmHg has been shown to rapidly reduceCP by producing vasoconstriction and decreasinghe volume of intracranial blood. A 1-mmHg
hange in PaCO2 is associated with a 3% change in

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BF.86 Hyperventilation also results in respiratorylkalosis, which may buffer postinjury acidosis.86

he effect of hyperventilation on ICP is short-lived1 to 24 hours), however.87-89 After therapeuticyperventilation, the patient’s respiratory ratehould be tapered back to normal over severalours to avoid a rebound effect.90

Therapeutic hyperventilation should be consid-red as an emergent intervention when elevatedCP complicates cerebral edema, intracranial hem-rrhage, or tumor. Hyperventilation should not besed on a chronic basis, regardless of the cause ofCH. Furthermore, hyperventilation is contraindi-ated in patients with traumatic brain injury orcute stroke. In these patients, vasoconstrictionay cause a critical decrease in local cerebral

erfusion and worsen neurologic injury.24,87,89

arbiturates

The use of barbiturates is predicated on theirbility to reduce brain metabolism and CBF, thusowering ICP and exerting a neuroprotective ef-ect.91-94 Generally pentobarbital is used, with aoading dose of 5 to 20 mg/kg as a bolus, followedy 1 to 4 mg/kg/hour.43,95 Therapy should bessessed based on ICP, CPP, and the presence ofnacceptable side effects. Continuous EEG moni-oring is generally used; EEG burst suppression isn indication of maximal dosing.

The therapeutic value of barbiturate therapy re-ains somewhat unclear. In a randomized trial of

3 patients with elevated ICP refractory to stan-ard therapy, patients treated with pentobarbitalere 50% more likely to achieve control of ICP;owever, there was no difference in clinical out-omes between groups.96 In general, barbiturateherapy represents a “ last-ditch” effort, becauseeveral studies show that their ability to lower ICPoes not appear to affect outcomes.86,97

Barbiturate therapy can be complicated by hy-otension, possibly requiring vasopressor support.he use of barbiturates is also associated with a

oss of the neurologic examination, requiring ac- r

REFERENC

4. Monro A: Observations in the Structure and Functions of

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urate ICP, hemodynamic, and often EEG moni-oring to guide therapy.

ypothermia

First reported as a treatment for brain injury inhe 1950s, hypothermia has remained a controver-ial strategy in the management of elevatedCP.10,86,98 Hypothermia decreases cerebral me-abolism and thus may reduce CBF and ICP. Initialtudies were limited by systemic side effects, in-luding cardiac arrhythmias and coagulopathies;owever, later work has demonstrated that hypo-hermia can lower ICP and improve patient out-ome for up to 6 months after injury.99 Hypothermialso may be effective in lowering ICP significantlyven after other therapies have failed.100,101

Hypothermia can be achieved using whole-bodyooling, including lavage and cooling blankets, togoal core temperature of 32 to 34°C. The bestethod of cooling (local vs systemic) and the

ptimal target core temperature are not known withertainty at present.102

ecompressive Craniectomy

Decompressive craniectomy removes the rigidonfines of the bony skull, increasing the potentialolume of the intracranial contents and circum-enting the Monro-Kellie doctrine. The indicationsor this procedure are increasing, and its use isiscussed in more detail elsewhere in this issue.

SUMMARY

The best therapy for elevated ICP is resolvinghe proximate cause of elevated ICP. Regardless ofhe cause, treatment should be undertaken as ex-editiously as possible and should be based on therinciples of resuscitation, reducing the volume ofhe intracranial contents, and reassessment. Theole of evidence-based guidelines in the clinicalanagement of elevated ICP is evolving.103 How-

ver, it is important to remember that individualatients respond differently to different therapies,nd thus interventions should be based on carefulssessment of the individual clinical scenario

104
ather than on strict protocols.
ES

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cerebral pathophysiology and critical care neurology: basic hemodynamic principles, cerebral...

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