Chapter 4. Resuscitation of blood pressure and oxygenation andprehospital brain-specific therapies for the severe pediatrictraumatic brain injury patient

I. RECOMMENDATIONS

A. Standards. There are insufficientdata to support a treatment standard forthis topic.

B. Guidelines. Hypotension should beidentified and corrected as rapidly as pos-sible with fluid resuscitation. In children,hypotension is defined as systolic bloodpressure below the fifth percentile for ageor by clinical signs of shock. Tables de-picting normal values for pediatric bloodpressure by age are available (1). Thelower limit of systolic blood pressure (5thpercentile) for age may be estimated bythe formula: 70 mm Hg � (2 � age inyears) (2). Evaluation for associated ex-tracranial injuries is indicated in the set-ting of hypotension.

C. Options. Airway control should beobtained in children with a GlasgowComa Score �8 to avoid hypoxemia, hy-percarbia, and aspiration. Initial therapywith 100% oxygen is appropriate in theresuscitation phase of care. Oxygenationand ventilation should be assessed con-tinuously by pulse oximetry and end-tidalCO2 monitoring, respectively, or by serialblood gas measurements.

Hypoxia (defined as apnea, cyanosis,PaO2 �60–65 mm Hg, or oxygen satura-tion �90%) should be identified and cor-rected rapidly. Hypoventilation (definedas ineffective respiratory rate for age,shallow or irregular respirations, fre-quent periods of apnea, or measured hy-percarbia) is also an indication for airwaycontrol and assisted ventilation with100% oxygen in the resuscitation phaseof care.

Blood pressure should be monitoredfrequently and accurately. Timely fluidadministration should be provided tomaintain systolic blood pressure in thenormal range. Charts with normal valuesbased on age are available (1). Median(50th percentile) systolic blood pressure

for children older than 1 yr may be esti-mated by the formula: 90 � (2 � age inyears) (2).

Sedation, analgesia, and neuromuscu-lar blockade can be useful to optimizetransport of the patient with traumaticbrain injury (TBI). The choice of agentsand timing of administration are best leftto local Emergency Medical Services pro-tocols.

The prophylactic administration ofmannitol is not recommended. Mannitolmay be considered for use in euvolemicpatients who show signs of cerebral her-niation or acute neurologic deterioration.

Mild prophylactic hyperventilation isnot recommended. Hyperventilation maybe considered in patients who show signsof cerebral herniation or acute neuro-logic deterioration, after correcting hypo-tension or hypoxemia.

D. Indications from the Adult Guide-lines. In the adult guidelines for the pre-hospital management of severe TBI (3, 4),specific age-dependent ventilatory rateswere provided as shown in Table 1.

II. OVERVIEW

In TBI literature on both children andadults, there is a growing understandingof the extreme sensitivity of the injuredbrain to secondary insults, both systemicand intracranial (3, 5–15). Secondary sys-temic insults are common in pediatricsevere TBI. The systemic secondary in-sults that appear to have the most impacton outcome are hypoxia and hypotension.

The adult neurosurgical literature hastraditionally defined hypotension as sys-tolic blood pressure �90 mm Hg. In chil-dren, hypotension can be defined as lessthan the 5th percentile of normal systolicblood pressure for age. However, itshould be emphasized that hypotension isa late sign of shock in children. Pediatricpatients may maintain their blood pres-

sure despite significant hypovolemia andclinical signs of shock. Signs of decreasedperfusion include tachycardia, loss ofcentral pulses, decreased urine outputbelow 1 mL·kg�1·hr�1, or increased cap-illary filling time of �2 secs.

In children, fluid resuscitation is indi-cated for clinical signs of decreased per-fusion even when an adequate blood pres-sure reading is obtained. Shock is almostnever due to head injury alone; evalua-tion for internal or spinal cord injury isindicated (16). Fluid restriction to avoidexacerbating cerebral edema is contrain-dicated in the management of the head-injured child in shock (17). If peripheralvascular access is difficult in children,intraosseous infusion of fluids and medi-cations is indicated (18).

Apnea and hypoventilation are com-mon in pediatric severe TBI. As in adults,hypoxia may be defined by PaO2 �60–65torr or oxygen saturation �90%. How-ever, hypoxia develops more rapidly inthe child than in the adult during apneaor hypoventilation (19). Central cyanosisis neither an early nor a reliable indicatorof hypoxemia in children. Also, adequateoxygenation does not necessarily reflectadequate ventilation. Respiratory rateand effort should be monitored and cor-rected to age-appropriate parameters.

III. PROCESS

We searched Medline and Healthstarfrom 1966 to 2001 by using the searchstrategy for this question (see AppendixA) and supplemented the results with lit-erature recommended by peers or identi-fied from reference lists. Of 133 poten-tially relevant studies, eight were used asevidence for this question (Table 2).

IV. SCIENTIFIC FOUNDATION

The negative impact of hypoxia andhypotension on the outcome of severe

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TBI has been demonstrated repeatedly instudies of mixed adult and pediatric pop-ulations (3, 6, 7, 12–14). In these studies,hypoxia, hypercarbia, and hypotensionwere common and correlated with in-creased morbidity and mortality rates.

Hypoxia

Pigula et al. (10) analyzed the influ-ence of hypoxia and hypotension on mor-tality from severe TBI (Glasgow ComaScale �8) in two prospectively collectedpediatric (age �16 yrs) databases. Hyp-oxia was defined as an emergency depart-ment admission PaO2 �60 mm Hg. Forboth the single-center database (n � 58)and the multiple-center database (n �509, including the 58 from the singlecenter), the presence of hypoxia alone didnot significantly alter mortality rate. Thecombination of hypotension and hypoxiaonly slightly (and not significantly) in-creased the mortality rate over hypoten-sion alone. It was concluded that hypo-tension is the most influential secondaryinsult determining short-term mortalityrate. Hypotension with or without hy-poxia was associated with mortality ratesapproaching those found in adults. Nei-ther the degree nor the duration of hyp-oxia was quantified. The participatingcenters were well-developed pediatrictrauma centers. As such, the apparentdiminution in the effect of hypoxia onoutcome might partially reflect the in-creased availability of effective airwaymanagement protocols for the prehospi-tal situation.

Michaud et al. (20) found that level ofoxygenation was associated with bothmortality rate and the severity of disabil-ity of survivors. Concurrent chest inju-ries were strongly associated with in-creased mortality and morbidity rates.Children with PaO2 levels between 105and 350 mm Hg had significantly worseoutcomes than those with PaO2 �350mm Hg.

In a prospective study of 200 children,Mayer and Walker (21) found that mor-

tality rate was 55% in the presence ofhypoxia, hypercarbia, or hypotension andonly 7.7% without any of these factorspresent (p � .01). In a prospective cohortstudy by Ong et al. (22) in Kuala Lumpur,the presence of hypoxia increased theprobability of a poor outcome by two- tofour-fold. In the setting of abusive headtrauma, Johnson et al. (23) found thatapnea was present in the majority of pa-tients and 50% were also hypotensive. Itwas concluded that cerebral hypoxiaand/or ischemia was more strongly asso-ciated with poor outcome than mecha-nism of injury.

Resuscitation of Blood Pressure

Five studies directly addressed the in-fluence of early hypotension on outcomefrom TBI. The impact of hypertension onsurvival was also addressed in two stud-ies.

In the aforementioned study by Pigulaet al. (10), they reported an 18% inci-dence of hypotension (defined as either asystolic blood pressure �90 mm Hg or asystolic blood pressure �5th percentilefor age) on arrival to the emergency de-partment. A mortality rate of 61% wasassociated with hypotension on admis-sion vs. 22% among patients without hy-potension. When hypotension was com-bined with hypoxia, the mortality ratewas 85%. Hypotension was a statisticallysignificant predictor of outcome with apositive predictive value of 61%. Earlyhypotension negated the improvement insurvival from severe TBI that is generallyafforded by youth.

Kokoska et al. (24) performed a retro-spective chart review of all pediatric pa-tients admitted to a single level 1 traumacenter over a 5-yr period. They limitedtheir patient populations to children withnonpenetrating TBI with postresuscita-tion age-adjusted Glasgow Coma Scalescores between 6 and 8 (n � 72). Theyindexed secondary insults occurring dur-ing transport to the emergency depart-ment up through the first 24 hrs in theintensive care unit. Hypotension was de-fined as �5 min at or below the 5thpercentile for age according to the TaskForce on Blood Pressure Control in Chil-dren (1). The majority of hypotensive ep-isodes occurred during resuscitation inthe emergency department (39%) and thepediatric intensive care unit (37%). Pa-tients left with moderate and severe dis-ability had significantly more hypotensiveepisodes than those with good outcomes.

Michaud et al. (20) found that hypo-tension in the field and emergency de-partment was significantly related tomortality rate in children. In a data bankstudy from four centers, Levin et al. (25)found that outcome was poorest in pa-tients 0–4 yrs old, which was the groupthat demonstrated high rates of hypoten-sion (32%).

In a prospective series of 6,908 adultsand 1,906 children �15 yrs of age at 41centers, Luerssen et al. (26) found thathypotension was significantly associatedwith higher mortality rates in children.They reported a greater deleterious effectof hypotension in children than adults.Notably, children with severe hyperten-sion had the lowest mortality rate.

In a recent retrospective study, Whiteet al. (27) found that odds of survival insevere pediatric TBI increased 19-foldwith maximum systolic blood pressure�135 mm Hg, also suggesting that su-pranormal blood pressures are associatedwith improved outcome. In contrast, pre-vious retrospective studies (28, 29) corre-lated early arterial hypertension with aworse neurologic outcome.

Brain Injury Specific Treatmentsin Prehospital Management

There is no evidence specifically deal-ing with the efficacy of any of the keybrain-directed prehospital therapies, in-cluding sedation and neuromuscularblockade, mannitol, hypertonic saline, orhyperventilation on the outcome from se-vere pediatric TBI. The scientific founda-tion for the in-hospital use of theseagents is discussed in separate sections ofthis document. Extrapolation of their useto the prehospital setting may be appro-priate and is provided by consensus at thelevel of options in the recommendationssection.

Key Elements From the AdultGuidelines Relevant to PediatricTBI

The evidence-based review of the lit-erature on prehospital airway, breathing,and ventilation management in the adultTBI population published as the Guide-lines for Pre-Hospital Management ofTraumatic Brain Injury (4) produced twoclass II studies (6, 7) demonstrating thatprehospital hypoxia has a statistically sig-nificant negative impact on outcome.These studies led to the following recom-mendation, “Hypoxemia (apnea, cyanosis,

Table 1. Age-dependent ventilatory rates(breaths/min) for eucapnea and hyperventilation

AgeRate for

EucapneaRate for

Hyperventilation

Adults 10 20Children 20 30Infants 25 35

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Table 2. Evidence table

Reference Description of StudyDataClass Conclusion

Johnson et al. (23),1995

Retrospective medical record and imaging review of 28children with confirmed child abuse with significant headinjury (75% male, 50% age �3 mos, stratified GCS). Thosewith GCS 3–8 included five shaken, seven impact injuries.

Presence of fracture, GCS, SAH, SDH, contusion, DBS, IVH,apnea, intubation, early seizure, retinal hemorrhage, andoutcome were noted.

Analysis: Two-way tables with Fisher’s exact test forcategorical and Cochran-Mantel-Haenszel test for ordinal.Significance at p �.05.

III No patient with clinical evidence of cerebral hypoxiaand/or ischemia had a good outcome.

Trauma-induced apnea causes cerebral hypoxia,which is more fundamental to outcome thanmechanism of injury.

Kokoska et al. (24),1998

Retrospective chart review, 1990–95 level I, single center, 72children (3 mos–14 yrs 6 mos) GCS 6–8.

Measures: age, gender, mechanism, injury type, durationventilation and length of stay. Presence of hypoxia,hypotension, or hypercarbia during transport, ED, OR, andfirst 24 hrs in PICU.

Analysis: ANOVA on continuous data. �2 or Fisher’s exact testfor nominal data. p �.05 was significant.

Ages: 0–4 yrs, 5–9 yrs, and �10 yrsTransport time in 15-min intervals.

III 97% survival.Early hypotension linked to prolonged length of stay

and worse 3-month GOS.

Levin et al. (25),1992

Prospective databank cohort study of 103 children (�16 yrs)with severe TBI (GCS �9) at four centers. Patients receivedCT scan and ICP monitoring “treatment protocol.”

Hypotension was defined as below the age-dependent lowerlimit of normal systolic blood pressure.

Measures: age, race, gender, mechanism, time to center, worstGCS, median ICP, pupillary reactivity, hypoxia, shock, masslesion, skull fracture, GOS at 6 mos (86%) and 1 yr (73%).

Analysis: mean/SD, box plots, logistic and linear regression.

III Outcome was poorest in 0–4 yrs age group, whichhad an increased incidence of evacuated subduralhematomas (20%) and hypotension (32%).

14–21% in all age ranges were hypoxic.

Luerssen et al.(26), 1988

Prospective series of 8,814 adult and pediatric TBI patientsadmitted to 41 metropolitan hospitals in NY, TX, and CA in1980–81. 21.6% pediatric TBI patients (1,906 �15 yrs)compared with adult TBI patients (6,908 �15 yrs).

Measures: age, gender, admission vital signs, injurymechanism, GCS post resuscitation, pupillary response,associated injury/AIS, “major symptoms,” brain injury byimaging or at surgery, and mortality rate before hospitaldischarge. Hypoxia not studied.

Profound hypotension: systolic BP 30 mm Hg below medianfor age.

Analysis: Two-by-two tables by Pearson’s �2 test with Yatescorrection. Ordered contingency tables by Mantel-Haentzel.Logistic regression for age vs. survival.

II Only hypotension was associated with highermortality rate in children. Children with severehypertension had the lowest mortality rate.

Both hypotension and hypertension were associatedwith higher adult mortality rate.

Pediatric mortality rate was significantly lower thanadult mortality rate, with notable exceptions ofchildren with profound hypotension (33.3% �15yrs vs. 11.8% �15 yrs) or subdural hematoma(40.5% �15 yrs vs. 43.9% �15 yrs).

Age, even within the pediatric age group, is a majorindependent factor affecting TBI mortality.

Mayer and Walker(21), 1985

Prospective study (1978–1981) of 200 consecutive children (3wks–16 yrs, mean 5.6 yrs) with severe TBI (GCS �8).

124 male76 female43% IHI57% HI/MtMeasures: age, GCS, mass lesions, oculovestibular reflexes,

pupils, ICP, apnea, hypotension, hypoxia (PO2 �60),hypercarbic (�35 torr), multiple trauma, MISS score.

Interventions: ICP monitor for GCS �6, GCS 6, 7, andabnormal CT. ICP �20 (79%) received hyperventilation(PCO2 25–28 torr), diuretic, and barbiturate protocol.

Analysis: �2.

III Mortality rate 21.5%IHI 10.5%HI�MT 30%33% fixed dilated pupils29% hypotension, hypercarbia, or hypoxia28% altered OVR26% mass lesionsMortality rate 55% with any hypotension,

hypercarbia, or hypoxia vs. 7.7% without. 88% ofHI�MT group had hypotension, hypercarbia, orhypoxia.

GCS �4, increased ICP, MISS �25, hypotension,hypoxia, hypercarbia significant (p �.01) for pooroutcome.

Michaud et al. (20),1992

Retrospective study of prospectively collected Trauma Registrydata in 75 children presenting to Harborview Medical Centerwith severe TBI (GCS �8) between January 1, 1985, andDecember 31, 1986.

Mean 8.2 yrs; 67% male; 16% �2 yrs; 65% 3–14 yrs; 19%�14 yrs.

Assessed fatality rate in system with advanced EMS andregional trauma center (83% received EMS field care).

Identified factors predictive of survival and/or disability. GOSat discharge from acute care hospital measured.

EMS, ED, hospital, autopsy records analyzed.Analysis: SPSS; logistic regression with EGRET; �2 or Fisher’s

exact test statistical significance; p � .05.

II 33% fatality rate60% associated injuries86% intentional injuries fatalMortality rate increased if hypotension or abnormal

pupils noted in the field.ISS and pupillary reactivity predicted survival; 72-hr

motor GCS and ED PO2 predicted disability.ED PO2 � 350 better outcome; PO2 105–350 same

outcome as hypoxic group.

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or arterial hemoglobin oxygen saturation[SaO2] �90 mm Hg) must be avoided, ifpossible, or corrected immediately. Whenavailable, oxygen saturation should bemonitored on all patients with severe TBIas frequently as possible or continuously.Hypoxemia should be corrected by ad-ministering supplemental oxygen.” Is-sues specifically pertaining to the man-agement of airway are addressed inChapter 3.

The “Guidelines for the Managementof [Adult] Severe Traumatic Brain Injury”(3) and the Guidelines for Pre-HospitalManagement of Traumatic Brain Injury(4) produced class II (6, 7, 27, 30, 31) andclass III (32–37) evidence from the adultliterature that early hypotension is a sta-tistically significant and independent fac-tor associated with worsening outcomefrom TBI. From the evidence report onprediction of outcome from TBI (38), hy-potension was one of the five factorsfound to have a �70% positive predictivevalue for mortality. Despite the solid ev-idence of the negative influence of earlyhypotension on outcome from TBI, thereis much less evidence that reducing or

preventing such secondary insults im-proves outcome.

Regarding the use of brain-specifictherapies in the prehospital setting, the“Guidelines for the Management of[Adult] Severe Traumatic Brain Injury”(3) and the Guidelines for Pre-HospitalManagement of Traumatic Brain Injury(4) collectively addressed the use of seda-tion, neuromuscular blockade, mannitol,and hyperventilation in managing severeTBI during the prehospital period. Withrespect to sedation and neuromuscularblockade, they found no studies dealingdirectly with the effects of prehospital useof these agents on outcome from severeTBI. It was recommended at the optionlevel that “sedation, analgesia, and neu-romuscular blockade can be useful to op-timize transport of the head-injured pa-tient. Because no outcome studiesprovide guidance on the use of these ad-juncts, the timing and choice of agentsare best left to local Emergency MedicalServices (EMS) protocols.” (4)

The adult guidelines suggested nosupport for the prehospital use of man-nitol. However, in two studies deleteri-

ous effects were not reported. Anequally acceptable alternative positionwould be that mannitol is an effectivebut potentially hazardous method oflowering intracranial pressure and thatits use during the prehospital periodshould be specifically limited to the eu-volemic patient with evidence of cere-bral herniation (a definite decrease inthe level of consciousness, motor pos-turing or flaccidity, or pupillarychanges such as anisocoria or bilateralpupillary dilation). Prophylactic usecannot be supported.

The Guidelines for Pre-Hospital Man-agement of Traumatic Brain Injury (4)found no studies of the effect on outcomeof the use of hyperventilation during theprehospital period. Recommendations,based on adult studies of the influence ofhyperventilation used during the in-hospital period on physiologic indexes andoutcome, stated; “hyperventilation (20 bpmin an adult, 25 bpm in a child, and 30 bpmin an infant) is the first line of interventionin the patient with suspected cerebral her-niation.” (4) Prophylactic hyperventilationwas not supported.

Table 2. (Continued)

Reference Description of StudyDataClass Conclusion

Ong et al. (22),1996

Prospective cohort study of 151 consecutive children (�15 yrs)admitted within 24 hrs of head injury (GCS �15) from 1993to 1994 in Kuala Lumpur.

Age groups: 0–4 yrs (n � 51); 5–9 yrs (n � 55); 10–14 yrs (n� 45).

Stratified GCS 3–5; 6–8Measured; age, gender, GCS admit and 24-hr, pupils, motor

response, deficits, major extracranial injury, mass lesion,skull fracture, hypotension, and hypoxia.

Follow-up GOS at discharge and 6 mos.Analysis: �2 for categorical variables. Student’s t-test for

continuous variables, association clinical/radiological factors,and outcome. Logistic regression for combination of factorsto predict poor outcome.

II Poor outcome related to GCS �8, abnormal pupils,motor deficits, hypoxia, hypotension, and extracranialinjury.

Hypoxia increases poor outcome by two- to four-fold insevere TBI.

Five independent factors predict poor outcome:GCS at 24 hrs hypoxia on admissionSAHDAIbrain swelling on CT

Pigula et al. (10),1993

Five-yr prospective cohort study of 58 children (�17 yrs) and amatched set of 112 adults with severe TBI (GCS �8).

Group I—normal BP and PaO2.Group II—hypotension or hypoxia or both. Adults compared to

this subgroup.ABG, BP, GCS, ISS, PaO2, age on admission, and survival were

measured.Analysis: Outcome by two-tailed �2, Fisher’s exact test, and

ANOVA with Bonferroni’s adjusted t-test.Statistical significance p �.05.

II Hypotension with or without hypoxia causes significantmortality rate in children compared with levels foundin adults (p � .9). Adequate resuscitation probablythe single most critical factor for optimal survival.

Survival increased four-fold with neither hypoxia norhypotension compared with either hypoxia orhypotension (p �.001).

When added cohort to NPTR/509 children: Hypotensionincreased mortality rate even without hypoxia (p�.00001). If both hypoxia and hypotension present,only slightly increased mortality rate than withhypotension alone (p � .056).

GCS, Glasgow Coma Scale; SAH, subarachnoid hemorrhage; SDH, subdural hemorrhage; DBS, diffuse brain swelling; IVH, intraventricular hemorrhage;ED, emergency department; OR, operating room; PICU, pediatric intensive care unit; ANOVA, analysis of variance; GOS, Glasgow Outcome Scale; TBI,traumatic brain injury; CT, computed tomography; ICP, intracranial pressure; AIS, Abbreviated Injury Severity; BP, blood pressure; IHI, isolated headinjury; HI, head injury; MT, multiple trauma; MISS, Modified Injury Severity Scale; OVR, oculovestibular reflexes; ISS, Injury Severity Score; EMS,emergency medical service; DAI, difuse axonal injury; ABG, arterial blood gas; NPTR, National Pediatric Trauma Registry.

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V. SUMMARY

The literature on the influence of hyp-oxia and hypotension on outcome fromsevere TBI in adults is fairly clear. Hypo-tension and hypoxia are serious, and po-tentially preventable, secondary insultsthat significantly increase the morbidityand mortality rates of TBI.

Unfortunately, there is minimal spe-cific evidence to indicate that prehospitalprotocols effective in preventing or min-imizing hypoxic and hypotensive insultsimprove outcome. Therefore, despite theuse of multivariate statistics to attempt tocontrol for such confounding, the possi-bility remains that some, most, or allsecondary insults occurring during theprehospital period that are associatedwith poor recovery are simply manifesta-tions of the severity of injury and are nottreatable entities.

A similar argument may be made forthe pediatric literature on hypotension.Decreases in systolic blood pressure be-low some threshold (vide supra) appearto be quantitatively associated with wors-ening of recovery. As such, despite theabsence of treatment efficacy data, maxi-mizing efforts directed at rapid and com-plete volume resuscitation, coupled withprotocols to minimize volume loss, aremost consistent with the present body ofliterature and should be strongly empha-sized components of prehospital care.

The situation with respect to prehos-pital hypoxia in pediatrics is less clear. Incontrast to the adult literature, the onlystudy that looked at prehospital hypoxiain any detail found that the presence ofhypoxia alone did not significantly altermortality rate. Such a finding, if not sim-ply an artifact, could reflect either anincreased resistance of the pediatric pop-ulation to hypoxic insults in the face ofsevere TBI or, alternatively, unquantifiedefficiency of the prehospital care provid-ers in preventing or minimizing hypoxicinsults in the setting of these studies. Ingeneral, it is believed that the pediatricbrain recovers better than an adult brainfrom a given traumatic insult. Pigula etal. (10), however, stated that they be-lieved the occurrence of a hypotensiveepisode eliminated the improvement insurvival from severe TBI that is generallyafforded by youth. If an improved resis-tance to hypoxia is responsible for thelack of a demonstrated adverse influenceon outcome, it is unlikely that such re-sistance is absolute. Therefore, althoughit is not proper to suggest altering treat-

ment in the absence of specific data, it iscertainly reasonable to recommend thatthe hypoxia avoidance/airway protectionprotocols afforded the patients studied byPigula et al. (10) be set as a favorableexample. Although these protocols werenot specified, they did use a populationfrom a pediatric trauma registry as alarge part of their study cohort. Sincesuch patients were treated by pediatrictrauma centers, this population samplecannot be assumed to represent routinepediatric prehospital trauma care. Assuch, the article by Pigula et al. (10)would seem strong, albeit indirect, sup-port for basic life support/advancedtrauma life support and pediatric ad-vanced life support protocols to be uni-versally applied as a minimum.

There is no contributing scientific lit-erature on the role of the prehospitaladministration of brain-specific therapiesin improving outcome from pediatricTBI. For the same period in adults, thereis no literature on neuromuscular block-ade or hyperventilation, one study on asingle sedative agent with very limitedapplicability to TBI, and two studies thatindirectly address the prehospital admin-istration of mannitol. As such, the Guide-lines for Pre-Hospital Management ofTraumatic Brain Injury base their rec-ommendations on data from the in-hospital period and consensus opinion. Inthe absence of evidence that their recom-mendations should be specifically alteredfor the pediatric population, we have sug-gested that the adult guidelines be con-sidered as the first line of approach. Theone area where we differ in our approachis that of mannitol; the adult guidelinesdispute its use, whereas we conclude thatthe absence of evidence for or against thisagent is more consistent with the stancethat mannitol is an effective but poten-tially hazardous method of lowering in-tracranial pressure and that its use dur-ing the prehospital period should bespecifically limited to the euvolemic pa-tient with evidence of cerebral hernia-tion. Prophylactic use cannot be sup-ported.

The presence of hypoxia or hypoten-sion after severe TBI in children increasesmorbidity and mortality rates. Specificthreshold values for ideal levels of oxy-genation and blood pressure support inthe pediatric age group have not beenclearly defined. Guidelines are warrantedto support avoidance or rapid correctionof systolic blood pressure less than thesecond standard deviation of normal for

age or of clinical signs of shock, apnea orhypoventilation, cyanosis, oxygen satura-tion �90%, or PaO2 �60 mm Hg in chil-dren with severe head injury.

Early control of the airway and recog-nition and treatment of associated ex-tracranial injuries are indicated. Despiteendotracheal intubation, head-injuredchildren remain at high risk for hypox-emia, hypercarbia, and major airwaycomplications (39). The frequency ofcomplications in airway procedures sup-ports the use of protocols including med-ications for cerebral protection, anesthe-sia, pain control, and paralysis (40).

The “golden hour” clearly begins atthe time of trauma. Although it is recog-nized that the field care of any traumapatient is encumbered both by the natureof the injury as well as by the often un-favorable and sometimes hostile environ-ment in which it is encountered, it isapparent that whatever function is com-promised by secondary insults duringthat period is generally not amenable tofull recovery. It is therefore critical tooptimize the prehospital care of the TBIpatient. Ideally, this would be realized bybringing hospital-type care to the acci-dent scene. Given the enormous variabil-ity of the early posttrauma period and thegenerally challenging environment inwhich care must be delivered, such a con-cept is not realistic. Indeed, the very con-cept itself continues to be the topic ofraging debate (the “scoop and run” versus“stay and play” controversy). As such, it isexpedient to simply select what seem tobe the most salient points of prehospitalTBI management and address them in anevidence-based fashion.

The goal of initial resuscitation inboth adults and children is to prevent

R esuscitation and

stabilization of

the cardiovascu-

lar and respiratory systems

in the field, during transfer,

and in the hospital need to

be emphasized in an effort to

optimize outcome from se-

vere pediatric brain injury.

S16 Pediatr Crit Care Med 2003 Vol. 4, No. 3 (Suppl.)

secondary brain injury by restoring oxygen-ation, ventilation, and perfusion. Resuscita-tion and stabilization of the cardiovascularand respiratory systems in the field, duringtransfer, and in the hospital need to beemphasized in an effort to optimize out-come from severe pediatric brain injury.

VI. KEY ISSUES FOR FUTURERESEARCH

Unfortunately, there is a lack of pediat-ric studies on the ability of protocols di-rected at minimizing or preventing hypo-tensive episodes to improve outcome fromTBI. Therefore, the link between the pre-dictive value of hypotension in predictingoutcome and the treatment value of pre-venting hypotension in improving out-come, albeit logical, remains conjectural.

Hypotension

The determination of treatmentthresholds for hypotension is not amena-ble to randomized controlled trials forethical reasons. As such, it is necessary toaddress this issue by using large, prospec-tively collected observational databasesthat allow analysis of this variable whilecontrolling statistically for confoundingvariables. It has also been suggested thatsupranormal blood pressures may be ac-ceptable or even associated with im-proved outcome in children with severetraumatic brain injury. Further investi-gation in this area is also warranted.

Given the critical need to minimize oreliminate prehospital hypotensive epi-sodes, randomized controlled trials ad-dressing management protocols are nec-essary. Study of the timing, amount, andcomposition of resuscitation fluids to beused is warranted. Given the evidence onthe efficacy of in-hospital administrationof hypertonic saline plus the adult datasupporting its use in the prehospital careof the adult TBI patient, a formal study ofhypertonic prehospital resuscitation inpediatric TBI should be considered.

Hypoxia

Given the unclear nature of the pedi-atric literature on prehospital hypoxia,the first order of research should be tofurther define the nature of its occur-rence and influence on outcome. Studiesare needed with sufficient patient popu-lations that have the statistical power tomake definitive statements. The level ofoxygenation during this period needs to

be accurately and repeatedly measured(such as by serial monitoring of periph-eral oxygen saturation in the field) toaddress the influence of thresholds ofmagnitude and duration of hypoxia. Thiswould allow us to assess the role of pre-hospital hypoxia on outcome as well as toaccurately compare the efficacy of variousmanagement methods. Finally, since mor-bidity rate is generally believed to be morerelevant to measuring outcome from hy-poxic insults than mortality rate, we needto use functional recovery measures as ourdependent variables in such investigations.

The effect of hypercarbia, with orwithout hypoxemia, on outcome is alsonot clearly defined and deserves investi-gation. Potential use of more aggressiveoxygenation variables in the resuscitationperiod deserves further investigation.

Brain-Specific Treatments in thePrehospital Setting

The absence of pediatric literature inthis area is striking. Clearly, we need toaccomplish quantitative evaluation of vari-ous methods of managing the pediatric pa-tient with suspected TBI. Comparativestudies of different approaches to patientsedation are fundamental to every aspect ofmanaging such patients. Similar studies re-garding the use of hyperventilation andmannitol are also required. Althoughagent-specific, controlled studies would beoptimal, a large, multiple-center prospec-tive observational study might be a reason-able first-order approach.

REFERENCES

1. Horan MJ: Task Force on Blood PressureControl in Children, report of the SecondTask Force on Blood Pressure in Children.Pediatrics 1987; 79:1

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APPENDIX: LITERATURE SEARCH STRATEGIES

SEARCHED MEDLINE AND HEALTHSTAR FROM 1966 TO 2001

Chapter 4. Resuscitation and Prehospital Brain-Specific Therapies: Strategy A—Resuscitation ofBlood Pressure and Oxygenation

1. exp craniocerebral trauma/2. head injur$.tw.3. brain injur$.tw.4. 1 or 2 or 35. exp anoxia/ or “hypoxia”.mp.6. exp hypotension/ or “hypotension”.mp.7. 5 or 68. 4 and 79. limit 8 to (newborn infant �birth to 1 month� or infant �1 to 23 months� or preschool child �2 to 5 years� or

child �6 to 12 years� or adolescence �13 to 18 years�)

Strategy B—Integration of Brain-Specific Treatments Into the Initial Resuscitation of the Severe HeadInjury Patient

1. exp craniocerebral trauma/2. head injur$.tw.3. brain injur$.tw.4. 1 or 2 or 35. exp analgesia/ or exp analgesics, opioid/ or exp “hypnotics and sedatives”/ or Midazolam/ or Propofol/ or “sedation”.mp.6. neuromuscular blockade/ or “neuromuscular blockade”.mp.7. exp resuscitation/ or “resuscitation”.mp.8. “ACUTE CARE”.mp.9. exp emergency medical services/ or “prehospital”.mp.

10. exp Ambulances/11. exp intensive care units/12. intensive care/ or “intensive care”.mp.13. 5 or 6 or 7 or 8 or 9 or 10 or 11 or 1214. 4 and 1315. limit 14 to (newborn infant �birth to 1 month� or infant �1 to 23 months� or preschool child �2 to 5 years� or

child �6 to 12 years� or adolescence �13 to 18 years�)16. limit 15 to english language

S18 Pediatr Crit Care Med 2003 Vol. 4, No. 3 (Suppl.)