perioperative management of the pediatric patient with traumatic brain injury

REVIEW ARTICLE

Perioperative management of the pediatric patient withtraumatic brain injuryTarun Bhalla1, Elisabeth Dewhirst1, Amod Sawardekar1, Olamide Dairo1 & Joseph D. Tobias1,2

1 Departments of Anesthesiology, Nationwide Children’s Hospital and the Ohio State University, Columbus, OH, USA

2 Departments of Pediatrics, Nationwide Children’s Hospital and the Ohio State University, Columbus, OH, USA

Introduction

The National Center for Injury Prevention and Con-

trol estimates that over 510 000 traumatic brain inju-

ries (TBI) occur annually in children, 0–14 years of

age in the United States (1). Of these, there are 35 000

hospitalizations and 2000–3000 deaths. Men are 1.5

times more likely to sustain TBI than women (2).

Although falls are the leading cause of TBI when con-

sidering all children from 0 to 14 years of age, there

are etiological variations between age groups. Nonacci-

dental trauma (shaken baby syndrome or child abuse)

should always be in the differential diagnosis in infants

and young children (3). Motor vehicle accidents and

assault become more prevalent with increasing age.

Among motor vehicle-related injuries in this age

group, motor-pedestrian injuries are more common

than motor vehicle occupant injuries (4,5). School-aged

children exhibit a rise in bicycle-related injuries,

whereas adolescents experience a rise in motor vehicle

injuries, sports-related injuries, and assault (6). When

compared with data from the 1980s, although the mor-

tality of TBI has decreased, its total incidence has

more than tripled, possibly due to the increased popu-

lation, recognition of diagnosis, and presentation to

emergency departments (7).

With an improved understanding of the pathophysi-

ology of TBI, refinements of monitoring technology,

and ongoing research to determine optimal care, the

prognosis of TBI continues to improve. In 2003, the

Society of Critical Care Medicine published guidelines

for the acute management of severe TBI in infants,

children, and adolescents (8–10). To ensure their dis-

semination and visibility, the guidelines were published

simultaneously in three journals. As pediatric anesthe-

siologists are frequently involved in the perioperative

Keywords

neurosurgery; trauma; audit; general

anesthesia; traumatic brain injury;

adolescent; neuroanesthesia; child; age

Correspondence

Tarun Bhalla, Department of Anesthesiology

and Pain Medicine, Nationwide Children’s

Hospital, 700 Children’s Drive, Columbus,

OH 43205, USA

Email: [email protected]

Section Editor: Andrew Davidson

Accepted 3 March 2012

doi:10.1111/j.1460-9592.2012.03842.x

Summary

TBI and its sequelae remain a major healthcare issue throughout the world.

With an improved understanding of the pathophysiology of TBI, refine-

ments of monitoring technology, and ongoing research to determine opti-

mal care, the prognosis of TBI continues to improve. In 2003, the Society

of Critical Care Medicine published guidelines for the acute management

of severe TBI in infants, children, and adolescents. As pediatric anesthesiol-

ogists are frequently involved in the perioperative management of such

patients including their stabilization in the emergency department, familiar-

ity with these guidelines is necessary to limit preventable secondary damage

related to physiologic disturbances. This manuscript reviews the current

evidence-based medicine regarding the care of pediatric patients with TBI

as it relates to the perioperative care of such patients. The issues reviewed

include those related to initial stabilization, airway management, intra-

operative mechanical ventilation, hemodynamic support, administration of

blood and blood products, positioning, and choice of anesthetic technique.

The literature is reviewed regarding fluid management, glucose control,

hyperosmolar therapy, therapeutic hypothermia, and corticosteroids.

Whenever possible, management recommendations are provided.

Pediatric Anesthesia ISSN 1155-5645

ª 2012 Blackwell Publishing Ltd 1

management of such patients including their stabiliza-

tion in the emergency department, familiarity with

these guidelines is necessary to limit preventable sec-

ondary damage related to physiologic disturbances.

This manuscript aims to provide an up-to-date sum-

mary of recommendations for the management of

pediatric TBI as relevant to the field of anesthesia.

Pathophysiology of TBI

The pathophysiology and subsequent sequelae of TBI

involve both primary and secondary injuries to the

brain. Primary injury is caused by the initial trauma. It

involves the physical impact to the brain tissue from

acceleration to deceleration or rotational forces and

may result in skull fracture, brain contusion, intracra-

nial (intraparenchymal, epidural, and subdural) hema-

toma, or diffuse axonal injury (DAI) (11).

DAI refers to the widespread axonal damage caused

by the shearing forces that occur with rapid accelera-

tion and deceleration of the head. Motor vehicle acci-

dents are the most frequent cause; however, falls,

assault, and nonaccidental trauma are also implicated.

Occurring in approximately half of all patients with

TBI, it is a common injury with devastating effects.

Patients with DAI frequently do not regain conscious-

ness after their injury, leading to persistent vegetative

state. Patients who do recover have severe residual

impairment of cognitive function. Imaging may reveal

multiple white matter lesions, although as microscopic

injury may be more prevalent than macroscopic injury,

even MRI may miss DAI. Its presence can be inferred

when areas of punctate hemorrhage are visible in the

corpus callosum or the cerebral cortex. As well as the

primary injury, axonal damage in DAI may also result

from secondary biochemical cascades, leading to a

delayed onset or a clinical deterioration in a patient.

Recent attention has focused on the significance of

secondary injury and its effect on the eventual out-

come of patients with TBI. Inflammatory and excito-

toxic processes following injury result in further edema

formation, increases in intracranial pressure (ICP), and

reduced cerebral perfusion pressure (CPP) (12,13). Sec-

ondary injury may also result from physiologic

changes after the initial injury including hypoxemia

and hypotension. The adult literature have demon-

strated that the two major factors that result in sec-

ondary injury in patients with TBI are hypotension

defined as a systolic blood pressure £90 mmHg and

hypoxemia (PaO2 £ 60 mmHg) (13).

A challenge specific to the pediatric population is

the increased severity of cerebral edema as well as its

diffuse nature, when compared with adults (14). The

anatomic differences in the pediatric trauma patient

include an immature or unstable neck, a larger head-

to-torso ratio especially in infants, and a more compli-

ant skull. These characteristics may result in more pro-

found consequences from acceleration–deceleration

injuries. Additionally, as there is limited brain atrophy

in children in comparison with adults, there is little

room to compensate for edema in the rigid skull. The

immature brain also has a high water content and

lacks complete axonal myelination. Finally, inflamma-

tory mediators in the developing brain likely lead to

more significant edema when compared with adult

patients (15).

Initial stabilization and resuscitation

Given the potential for poor outcomes of TBI and the

significant impact of secondary insults, treatment strat-

egies are aimed not only at assessment and stabiliza-

tion, but also early therapeutic interventions to

decrease secondary injuries. Thus, the cornerstones of

modern TBI management are field resuscitation, expe-

ditious triage, emergent surgical evacuation of mass

lesions, control of ICP, support of CPP, multimodal

monitoring, and optimization of physiologic environ-

ment. The anesthesia provider is likely to be faced with

such patients either in the emergency department when

called upon for airway management or as these

patients are urgently transported to the operating

room for evacuation of space occupying lesions. As

secondary injury is preventable and treatable, the peri-

operative period remains a key time to initiate inter-

ventions that may improve the outcome of TBI.

Additionally, alterations in physiologic function

induced by anesthetic care or the surgical intervention

may result in secondary injury. The key components of

perioperative management include rapid evaluation,

ongoing resuscitation, early surgical intervention,

intensive monitoring, and anesthetic planning.

The initial assessment and stabilization of the

patient with TBI is usually achieved in the emergency

department. Following the initial assessment, resuscita-

tion, and stabilization, the patient is likely going to be

transported to the computed tomography (CT) scanner

and then to the operating room. As in many cases,

there are no family members available and the patient

is unable to provide any information, the anesthesia

provider will have limited historical data on which to

base their anesthetic care. Upon arrival, the anesthesia

team performs a rapid assessment of the patient. The

assessment should always begin with airway, breathing,

and circulation, followed by a rapid assessment of

neurologic status (GCS and papillary response) and

Perioperative management of the pediatric patient with neurotrauma T. Bhalla et al.

2 ª 2012 Blackwell Publishing Ltd

associated extracranial injuries. Information about the

time and mechanism of injury can be valuable. Associ-

ated injuries involving the thorax, abdomen, pelvis,

and long bones may be stable or evolve during the

perioperative period. Should intra-operative decompen-

sation occur, the potential impact of these associated

injuries must be considered when attempting to deter-

mine the etiology of new onset hemodynamic instabil-

ity, anemia, or ventilator difficulties.

Airway management

Patients with TBI requiring surgery will invariably

require endotracheal intubation. The decision to per-

form endotracheal intubation is not only determined

by the patient’s respiratory status or the need for an

operative procedure, but more importantly by their

Glasgow Coma Scale at the time of presentation. Cur-

rent trauma guidelines recommend immediate endotra-

cheal intubation for patients with a GCS <9 based on

the high probability that such an altered level of con-

sciousness is indicative of a brain injury of such sever-

ity that progressive cerebral edema is likely to occur

(16,17).

Airway management is complicated by a number of

factors including the urgency of situation with upper

airway obstruction or preexisting hypoxia, uncertainty

of cervical spine status, uncertainty regarding the air-

way because of the presence of blood, vomitus, debris

in the oral cavity or laryngo-pharyngeal injuries, a full

stomach, intracranial hypertension, and uncertain vol-

ume status. Although many of the tenets of airway

management are the same regardless of the clinical sce-

nario, all TBI patients should be considered to have a

full stomach and an underlying cervical spine injury

(CSI). Additionally, as patients may not be able to

effectively cooperative with a physical examination

that is key in ruling out a CSI by identifying neuro-

logic deficits or point tenderness in the neck, the air-

way is managed with the assumption that their may be

a CSI with a RSI and manual inline stabilization

(18,19). Such initiatives are imperative as the recent

data in the adult population suggest that an associated

CSI is not infrequent in patients with TBI. Although it

had been previously suggested that TBI patients had

an incidence of CSI similar to that of the general

trauma population, a higher incidence of CSI has been

noted in patients with TBI especially those with

increasing severity of injury as determined by low GCS

score and unconsciousness (20–22).

Of equal importance is the choice of agents used for

sedation/analgesia and neuoromuscular blockade dur-

ing RSI. Sodium thiopental, etomidate, and propofol

are commonly used in the operating room to induce

anesthesia before endotracheal intubation. All these

agents decrease the systemic hemodynamic response to

intubation, blunt increases in ICP, and decrease the

cerebral metabolic rate for oxygen (CMRO2). How-

ever, thiopental or propofol may not be appropriate

for critically ill patients given their vasodilatory and

negative inotropic effects that are exaggerated by co-

morbid conditions (23,24). In the trauma scenario,

alternative agents such as etomidate or ketamine are

frequently chosen (25). To date, the data regarding the

potential deleterious effects of etomidate on outcome

are limited to patients with presumed sepsis (26–28).

Outside of that scenario, there are no data to demon-

strate a deleterious effect on outcome despite the fact

that adrenal suppression does occur. Given that etomi-

date has a limited effect on MAP and effectively

decreases the CMRO2, thereby decreasing ICP, the net

effect is maintenance or an increase in CPP, thereby

making it a potentially valuable agent for patients with

TBI.

Ketamine’s popularity in the trauma setting relates

to its beneficial effects on cardiac and respiratory func-

tion. Ketamine generally increases heart rate and

blood pressure as well as provides bronchodilatation

because of the release of endogenous catecholamines

(29). In vitro and animal studies suggest ketamine has

direct negative inotropic properties (30,31), although

clinically the indirect sympathomimetic effects from

endogenous catecholamine release are generally over-

riding. The controversy with ketamine surrounds its

effects on ICP and whether it is contraindicated in

patients with TBI and altered intracranial compliance.

Although the literature from the 1970s and 1980s sug-

gested that ketamine increased ICP and was contrain-

dicated in patients with altered intracranial compliance

(32), more recent evidence has suggested no effect or

even that ketamine may decrease ICP when used to

prevent pain from invasive procedures (33–35).

Given the need to achieve rapid neuromuscular

blockade and optimal conditions for endotracheal intu-

bation, the choices for the neuromuscualar blocking

agent for RSI are succinylcholine and rocuronium

(36). Although succinylcholine may mildly increase

ICP (37–40), increases in ICP secondary to hypoxia

and hypercarbia are well documented and much more

likely to be clinically important. Therefore, rapid endo-

tracheal intubation and control of oxygenation and

ventilation are of paramount importance and far out-

weigh the risk of the mild increase in ICP from succi-

nylcholine. If sugammadex is locally available,

rocuronium may be a more feasible option. Although

frequently considered as an adjunct to endotracheal

T. Bhalla et al. Perioperative management of the pediatric patient with neurotrauma


intubation of patients with increase ICP, there is no

evidence-based medicine to show the efficacy of lido-

caine (41). In the pediatric population, the process of

endotracheal intubation with larygnoscopy in a patient

with increased ICP may result in bradycardia.

Although there are limited data to support its used,

pretreatment with atropine is generally suggested

(18,19). The incidence of bradycardia is further magni-

fied by associated hypoxemia, hypothermia, and the

administration of succinylcholine.

Intra-operative anesthetic care

The perioperative period may provide an opportunity

to either continue ongoing resuscitation or correct the

preexisting secondary insults that have not been ade-

quately addressed because of the urgency to get

patients to the operating room. Furthermore, surgery

and anesthesia may predispose the patient to the onset

of potentially new secondary injuries (such as intra-

operative hypotension because of surgical blood loss

or the effect of anesthetic agents, hyperglycemia

because of stress response), which may impact out-

come. The primary goals of anesthetic management

can be summarized as follows: (i) provide adequate

anesthesia and analgesia; (ii) optimize surgical condi-

tions; (iii) avoid secondary insults including hypoten-

sion, hypoxemia, hypocarbia, hypercarbia,

hypoglycemia, and hyperglycemia; (iv) maintain an

adequate CPP; and (v) avoid increases in ICP.

Respiratory support and mechanical ventilation

The basic tenets of ventilator support for the trauma

patient are the same as for all patients in the OR.

These include the provision of adequate oxygenation

and ventilation while limiting the potentially deleteri-

ous effects of mechanical ventilation on cardiovascular

function.

The goal of oxygenation is to maintain the PaO2 ‡60 mmHg (PaO2 ‡ 8 kPa) as CBF, CBV, and ICP

increases linearly with PaO2 values £ 60 mmHg

(PaO2 £ 8 kPa). Although PaO2 levels are routinely

‡60 mmHg (‡8 kPa) during anesthetic care, values

above this level have no impact on CBF, CBV, or

ICP. If adequate oxygenation cannot be maintained at

inspired oxygen concentrations (FiO2) of 0.5–0.6, the

usual practice is to increase positive end expiratory

pressure (PEEP). However, it must be remembered

that as PEEP increase, it may impact the overall CPP

because of its effects not only on cardiovascular func-

tion, but also its effects on ICP. Based on lung compli-

ance, PEEP is transmitted to the intracranial vault and

may impact ICP (42,43). Therefore, in patients with

TBI, it may be better to attempt to increase mean air-

way pressure and augment oxygenation by first

increasing the inspiratory time, FiO2, and peak inflat-

ing pressure rather than PEEP.

Although practiced routinely in the past for patients

with TBI, hyperventilation is generally avoided unless

there is a precipitous increase in ICP with impending

herniation (44,45). Prehospital ventilation has been

shown to have a significant impact on outcome with

increased in-hospital mortality in patients presenting

with either hypocarbia or hypercarbia (46). Others

have demonstrated a similar negative impact of in-hos-

pital hyperventilation on outcomes (47). Although

hyperventilation induces hypocapnia which causes

cerebral vasoconstriction and a reduction in CBF and

CBV and a corresponding decrease in ICP, there is a

disconnect between CBF and CMRO2 as hypocarbia

decreases CBF without effect CMRO2, thereby poten-

tially exposing the patient to ischemia especially during

the trauma period where there may be preexisting

alterations in CBF and autoregulation. Skippen et al.

(48) demonstrated a relationship between hypocarbia

and frequency of cerebral ischemia. Given this infor-

mation, hyperventilation should be used judiciously

intra-operatively for short-term control of ICP and to

facilitate surgical exposure during craniotomy. Prior to

dural closure, normocarbia should be restored to avoid

tension pneumocephalus. In situations where hyperven-

tilation is necessary, it may be beneficial to increase

the FiO2 as this may avoid the deleterious effects of

hypocarbia on CBF and cerebral tissue oxygenation

(49). Given the inaccuracy of ETCO2 monitoring and

the importance of PaCO2 control in these patients,

direct monitoring of arterial PaCO2 is recommended

(50,51).

Summary:

1. Maintain PaO2 ‡ 60 mmHg (PaO2 ‡ 8 kPa)

2. PEEP may increase ICP

3. Hyperventilation should only be used if impending

herniation

4. Avoid intra-operative hypoxemia

Hemodynamic support

As noted earlier, the role that hemodynamic support

may play in prevention of secondary injury cannot be

overemphasized. In both the adult and pediatric popu-

lation, data demonstrate that even a single periopera-

tive episode of hypotension can impact outcome

(52,53). A meta-analysis of 8721 patients (IMPACT

study) emphasizes the importance of secondary impact

and its effect on outcome (54). The study noted that



both hypotension and hypoxemia were significantly

associated with unfavorable 6-month outcome. Intra-

operative hypotension can be equally as devastating.

Pietropaoli et al. demonstrated that intra-operative

hypotension increased the incidence of mortality by a

factor of three (55). Additionally, the duration of

intra-operative hypotension was also inversely associ-

ated with functional outcome. Intra-operatively if

problems arise with the control of ICP, a slight eleva-

tion of the MAP may be effective in ameliorating such

issues. With intact autoregulation, as the MAP is

increased, there is a secondary cerebral vasoconstric-

tion to maintain CBF at baseline. The cerebral vaso-

constriction results in a decrease in CBV that may

decrease ICP in patients with altered intracranial com-

pliance. This relationship further demonstrates the

need to effectively control the intra-operative MAP.

Three small prospective, crossover trials have com-

pared norepinephrine with dopamine to treat hypoten-

sion and maintain MAP (56–58). There were no

differences in mean cerebral flow velocity, cerebral

oxygenation, or cerebral metabolism. However, the

authors reported that norepinephrine had a more pre-

dictable and consistent effect while dopamine resulted

in a higher ICP. A recent single-center retrospective

study of patients with severe TBI who received phenyl-

ephrine, norepinephrine, or dopamine reported that

phenylephrine resulted in the maximum increase in

MAP and CPP from baseline (59).

Summary:

1. Effective control of intra-operative MAP

2. A single intra-operative episode of hypotension can

effect outcome

3. Maintain optimal CPP

Anesthetic agents

There are significant differences when comparing the

effects of intravenous anesthetic agents and the volatile

agents in regard to their effects on CBF, CBV, and

CMRO2. However, to date, there are no evidence-

based data to demonstrate a significant difference in

outcome when comparing these two groups of agents.

The intravenous agents including thiopental, propofol,

and etomidate reduce CMRO2, which results in cere-

bral vasoconstriction and a decrease in CBF, CBV,

and ICP. However, agents such as thiopental and

propofol may result in significant hypotension and a

reduction in CPP. Additionally, with intact autoregula-

tion, the decrease in MAP is compensated for by cere-

bral vasodilatation to maintain CBF, which results in

an increase in CBV and may increase ICP. A similar

effect has been observed following the administration

of fentanyl and sufentanil although these agents have

no direct effect on the cerebral vasculature (60,61).

This effect can be treated by the administration of a

vasoactive agent such as phenylephrine to restore the

MAP back to baseline.

All of the volatile anesthetic agents (isoflurane, sevo-

flurane, and desflurane) decrease CMRO2 and may

cause cerebral vasodilatation, thereby increasing CBF,

CBV, and ICP. These effects are generally minimal at

exhaled concentrations of <1 minimum alveolar con-

centration. Therefore, they may be used in low concen-

trations in patients with TBI (62,63). However, nitrous

oxide should be avoided as it can increase CMRO2

causing cerebral vasodilatation and increased ICP (63).

As far as choice of neuromuscular blocking agent, the

issues related to succinylcholine and its potential

effects on ICP have been previously discussed. The

nondepolarizing agents have no direct effect on ICP

and can be used as needed to provide surgical relaxa-

tion and ensure immobility in critically ill patients.

Although neuromuscular blocking agents decrease oxy-

gen consumption and may transiently decrease ICP as

they eliminate thoracic skeletal tone and increase

venous drainage; postoperatively, their use is generally

not recommended (64). The adult literature clearly

demonstrates no outcome benefit and increased

adverse effects including infection and prolongation of

hospitalization (65).

Summary:

1. No significant difference in outcomes comparing

intravenous and inhalational anesthetic agents

2. Avoid nitrous oxide, increases CMRO2 and possible

increase in ICP

3. NMB are generally not recommended postopera-

tively, but are routinely used intra-operatively

ICP Monitoring

Preventing and treating intracranial hypertension that

would lead to deleterious secondary injury is vital to

the care of patients with TBI. While in common prac-

tice, monitoring of ICP for this purpose is presented as

an option rather than a guideline for children with

severe TBI (GCS < 8), because of insufficient evidence

in the pediatric population (8). Typically the choice of

monitor is between an intraparenchymal device and an

intraventricular device connected by catheter to an

external drain gauge. Correlation between the two has

been shown (66), and while the former may result in

less local tissue damage, the later allows CSF drainage

and is the suggested device in adult TBI guidelines

(67). An ICP greater or equal to 20 mmHg warrants

treatment in children. CPP should be maintained



above 40 mmHg; (68–70) however, there is no clear

age-related adjustment of this target value up to the

adult recommendation of 70 mmHg. Also in neonates

and infants, the minimum CPP is still unclear. Most

commonly, the device is placed at the end of surgery,

and thus, measured values are available for ICU care

and not intra-operatively, except in the case of a

patient returning to the OR. Complicating infection

from an ICP monitoring device is rare, and theoretical

complications of hemorrhage and seizure have not

been reported, indicating safety of ICP monitors (71).

Noninvasive transcranial doppler pulsatility index as

an indicator of ICP is controversial, however may be

useful on admission, having high sensitivity to predict

ICH and abnormal CPP (72). Another alternative to

direct ICP monitors is ocular ultrasound, which has

been suggested to detect ICH in adults.

Although not standard of care or in routine practice,

as the technology improves, perioperative cerebral

monitoring may become more commonplace (73–75).

Such technology may be particularly relevant in

patients receiving more aggressive systemic interven-

tions to manage refractory ICH, such as hyperventila-

tion. Jugular venous oxygen saturation (SjvO2),

measured by retrograde placement of a catheter from

the internal jugular into the jugular bulb (73), gives a

measure of cerebral oxygen delivery. In adults with

TBI, episodes of decreased SjvO2 have been associated

with poor neurologic outcome. Cerebral oximetry via

near infrared spectroscopy (NIRS) monitoring has

been shown to correlate with SjvO2, and in many cen-

ters, NIRS-based cerebral oximeters are used routinely

for children undergoing repair of congenital heart

defects. Other monitoring technologies to considered

in the perioperative period that may help in adjusting

therapies include transcranial Doppler ultrasonography

to evaluate middle cerebral blood flow and direct mea-

surement of brain tissue oxygenation using invasive

devices (73–75).

Summary:

1. ICP ‡ 20 mmHg warrants intervention

2. CPP should be maintained at >40 mmHg

3. Monitoring ICP helps to avoid further secondary

injury

Positioning

As the patient is moved and positioned on the operat-

ing room table, the head position is generally man-

dated by the surgical procedure to be performed.

However, several studies have demonstrated the poten-

tial impact of head positioning and head elevation on

ICP. Whenever feasible, the patient’s head should

remain in neutral and midline position to avoid jugular

venous obstruction. Flexion of the head, rotation of

the head to the right or the left, or lowering the

patient into the Trendelenburg position can signifi-

cantly increase ICP especially in patients with altered

intracranial compliance (76–78). A more controversial

issue that relates primarily to the ICU care of these

patients is whether head elevation should be routine.

While elevation of the head of the bed has been shown

to lower ICP by promoting venous drainage, some

studies have shown that a decrease in CPP may also

occur. Furthermore, rebound autoregulatory responses

to reduced CPP involve lowering of CBR to increase

CBV, which may actually predispose these patients to

episodes of intracranial hypertension and more prob-

lematic control of ICP (79). Overall, it has been sug-

gested that a moderate elevation of 15–30� is an

appropriate measure to lower ICP as long as adequate

CPP is vigilantly maintained and the degree of eleva-

tion titrated to the individual based on ICP and CPP

measurements (8). Head elevation has the added bene-

fit of minimizing ventilator-associated pneumonia.

Summary:

1. Head of bed should be maintained at 15–30�2. Reverse Trendelenburg may improve venous drain-

age, but may induce rebound increase in ICH

3. Patients head should remain neutral and midline

Fluid management including glucose control

Given the risks of hypovolemia and hypotension,

patients with TBI should receive initial volume resusci-

tation to achieve a normovolemic state. Although sig-

nificant fluid restriction was previously the acceptable

standard for patients with TBI, the current trend has

evolved to suggest that euvolemia is the optimal end-

point. In the consideration of fluid therapy, the issues

to be addressed include the type of fluid to be used

and the control of serum glucose. Issues related to

hyperosmolar therapy are discussed in the next section.

For the vast majority of patients, an isotonic fluid

should be chosen. Although lactated Ringers (LR) is

commonly used during the perioperative period, it

must be remembered that the sodium concentration of

130 mEqÆl)1 is less than that of the serum sodium con-

centration. When compared with the administration of

normal saline, patients receiving LR will have a

decrease in the serum sodium level and osmolarity

(80). Given this information, normal saline should be

used for the initial resuscitation and then the ongoing

provision of maintenance and replacement fluids for

the majority of patients with TBI. When comparing

the potential advantages and disadvantages of



crystalloid vs colloid, recent data from an adult trial

suggest that resuscitation with albumin containing flu-

ids may impact outcome (81). In the posthoc analysis

of a larger trial, the authors reported that the risk of

death was increased in patients who received albumin

compared with those who received normal saline.

Among patients with severe brain injury (GCS 3–8),

61 of 146 patients in the albumin group died (41.8%)

as compared with 32 of 144 in the saline group

(22.2%, relative risk of 1.88) (81).

Although hypertonic fluids have been shown to be

effective in the treatment of increased ICP (see below),

there are few data to demonstrate their superiority

over normal saline for the initial resuscitation of

patients with TBI. Prehospital hypertonic saline resus-

citation has been shown to be associated with a reduc-

tion in serum biomarker levels (S100B, neuron-specific

enolase and membrane basic protein) (82). However, a

prospective and randomized trial comparing prehospi-

tal resuscitation of TBI patients with hypotension

found no difference in neurologic outcome when com-

paring resuscitation with hypertonic saline or standard

fluid resuscitation protocols (83).

Another controversial issue regarding care of

patients with TBI is the association of hyperglycemia

with a poor outcome. As such, there remains some

divergence in the opinions regarding the need to

aggressively treat hyperglycemia in this population.

Causes of hyperglycemia after TBI include an increase

in gluconeogenesis and glycogenolysis from catechol-

amine response, cortisol release, and glucose intoler-

ance (84–86). Hyperglycemia is more prevalent after

severe TBI and in patients under 4 years old (84). Sec-

ondary brain injury from hyperglycemia can occur,

leading to an increase in glycolytic rates as shown by

increased lactate/pyruvate ratio, resulting in metabolic

acidosis within brain parenchyma, overproduction of

reactive oxygen species, and ultimately neuronal cell

death through alterations in immune, inflammatory,

and mitochondrial function (87). Several studies in

both children and adults support an association

between hyperglycemia and a poor neurologic outcome

following TBI; however, there are limited data to

prove whether treatment of the hyperglycemia will

improve outcome (88–90). In a retrospective review of

pediatric patients admitted to the regional trauma cen-

ter over a 1-year period, Cochrane et al. note that

patients who died had significantly higher admission

glucose values (mean of 267 vs 135 mgÆdl)1) and that

a serum glucose on admission of >300 mgÆdl)1

(16.7 mM) was uniformly fatal (88). Lam et al. (89)

noted that in severely injured patients with a GCS £8that a serum glucose ‡200 mgÆdl)1 (11.1 mM) was

associated with a worse outcome. Smith et al. (90)

reported that in children with severe traumatic brain

injury, hyperglycemia beyond the initial 48 h is associ-

ated with a greater likelihood of a poor neurologic

outcome.

Intensive insulin therapy for the control of hypergly-

cemia in critically ill adult patients has received a lot

of press in the literature following the report of Van

den Berghe et al. (91) which reported that intensive

insulin therapy (target blood glucose 80–110 mgÆdl)1)in critically ill patients was associated with lower mor-

tality. However, subsequent work has demonstrated

that this may not be that case and that there is an

increased risk of hypoglycemia (92,93). In a prospec-

tive trial, Billotta et al. (93) randomized 97 adults with

severe TBI to insulin therapy to maintain a blood glu-

cose at 80–120 mgÆdl)1 (4.4–6.7 mM) or conventional

insulin therapy to maintain a blood glucose concentra-

tion below 220 mgÆdl)1 (12.2 mM). They reported that

both the groups had similar mortality and neurologic

outcome at 6 months and a similar incidence of infec-

tious complications. Although the more strict control

of glucose resulted in a shorter duration of ICU stay,

there was a higher incidence of hypoglycemia. Given

the potential for an increased risk of hypoglycemia in

children and its potentially devastating neurologic con-

sequences if unrecognized and untreated, an aggressive

approach to the control of perioperative glucose can-

not universally be suggested in children with TBI.

Additionally, when reviewing the data, the studies

focus on ICU care and not the intraoperaive manage-

ment of such patients. Given these issues, it seems pru-

dent to suggest that glucose containing fluids not be

administered to the pediatric patient with TBI unless

the serum glucose is £70 mgÆdl)1. Given the potential

impact of both hyperglycemia and hypoglycemia, inter-

mittent monitoring of blood glucose concentrations

during intra-operative care is suggested. This can easily

be accomplished using bedside, point-of-care testing

devices. Moreover, the anesthesia provider may want

to take into account that there may be differential

effects of the individual anesthetic agents on blood

and brain glucose concentrations (94,95).

Summary:

1. Intra-operative euvolemia is optimal

2. Normal saline should be used as maintenance fluid

3. Glucose containing fluids should not be infused

unless the serum glucose is £70 mgÆdl)1 (3.9 mM)

Hyperosmolar therapy

Mannitol remains the standard agent used in hyper-

osmolar therapy. The principle of hyperosmolar



therapy is based on establishing an osmotic gradient

between the plasma and parenchymal brain tissue,

thereby reducing brain water content and thus ICP.

An intact blood–brain barrier is necessary for this

process. In addition to its osmotic effect, a rapid

decrease in ICP may be seen following its administra-

tion as mannitol improves blood rheology and

thereby results in an increase in cerebral vascular

resistance (cerebral vasoconstriction) with a decrease

in CBV and ICP. Available as a 20% solution (stan-

dard solution bag) or a 25% solution (bottle), dosing

regimens vary from 0.25 to 1 gmÆkg)1 and aim not to

exceed serum osmolarity of 320 mOsmÆl)1 (96,97).

The osmotic diuresis from mannitol can result in hyp-

ovolemia and hypotension, and concern has been

expressed regarding adverse effects following mannitol

administration if there is an intracranial collection of

blood (epidural or subdural hematoma). It is

postulated that a reduction in the brain volume may

result in relief of the tamponade that is preventing

ongoing bleeding. Therefore, it has been suggested

mannitol not be administered until the blood has

been evacuated.

More recently, there has been considerable interest

and work performed with the use of hypertonic saline

solutions. Generally, a 3% solution is used, although

concentrations up to 23.4% have been studied (98). A

serum sodium level of 145–160 mEqÆl)1 has been rec-

ommended, and while patients have tolerated a serum

osmolality up to 360 mOsmÆl)1, caution above

320 mOsmÆl)1 is recommended (99,100). In addition

to its effects on the brain, hypertonic saline has bene-

ficial hemodynamic effects including the restoration of

intravascular volume, increased inotropy, constriction

of capacitance vessels, and a decrease in resistance

vessels. These effects result in an increased MAP and

CPP in the majority of patients. Studies in both the

adult and pediatric population have demonstrated the

efficacy of these solutions in treating refractory

increases in ICP that have failed to respond to con-

ventional therapy including mannitol (99–102). Vats

et al. (103) retrospectively reviewed their experience

with hypertonic saline (5 mlÆkg)1 of a 3% solution) or

mannitol (0.5–1 gmÆkg)1) to treat increased ICP in a

cohort of pediatric patients ranging in age from

9 months to 16 years. Fifty-six doses of mannitol

were administered to 18 patients, while 82 doses of

hypertonic saline were administered to 25 patients.

Although both reduced ICP at 60 and 120 min, only

hypertonic saline reduced the ICP at 30 min and

increased the CPP at 60 and 120 min. Although the

majority of studies comparing these agents have been

performed in the ICU setting, the efficacy of hyper-

tonic saline has also been demonstrated intra-opera-

tively (104). In a prospective, blinded trial, adults

scheduled for elective resection of a supratentorial

brain tumor were randomized to receive 160 ml of

3% hypertonic saline or 150 ml of 20% mannitol.

The surgeon was asked to judge the brain relaxation

conditions as soft, adequate, or tight. Brain relaxation

was better in the patients who received hypertonic sal-

ine than in the mannitol group. Serum sodium was

higher in the hypertonic saline group, while urine out-

put was greater in patients receiving mannitol. No

difference was noted in fluid administered, length of

ICU stay, or length of hospital stay. Despite the data

suggesting improved efficacy with hypertonic saline,

there are no data to demonstrate an improvement in

outcome. As such, either agent should be considered

intra-operatively when the treatment of ICP is neces-

sary or to provide intra-operative brain relaxation.

However, hypertonic saline should be considered in

patients who fail to respond to conventional therapy

including mannitol.

Summary:

1. Mannitol remains the standard for hyperosmolar

therapy

2. Hypertonic saline, although efficacious, has not

demonstrated improved neurologic outcome

3. Hypertonic saline should be considered for patients

who may be refractory to mannitol therapy

Temperature control and therapeutic hypothermia

Moderate hypothermia decreases the cerebral meta-

bolic rate of oxygen consumption (CMRO2) resulting

in cerebral vasoconstriction, a decrease in CBF/CBV

and ICP. Additional potential benefits include an

attenuation of the alteration in the blood–brain barrier

related to TBI and a decrease in the release of excit-

atory neurotransmitters including lactate, which have

been implicated in secondary brain injury (105). A

recent meta-analysis in adults with TBI noted no sta-

tistically significant reduction in mortality although

there was an increase in the favorable neurologic out-

come in patients that received hypothermia, particu-

larly when cooling was maintained for more than 48 h

(106). However, the authors noted that the potential

benefits of hypothermia may be offset by a significant

increase in the risk of nosocomial infections including

pneumonia. By contrast, the National Acute Brain

Injury Study (NABIS: HII) failed to show benefit

when investigating 108 adults post-TBI randomized to

early induction of hypothermia (33�C within 4.4 h of

injury) or normothermia (107). Similarly, the pediatric

literature has shown no clear benefit from the use of



routine hypothermia following TBI (108). In fact, in

the prospective trial of 225 children, there was a rela-

tive risk of mortality of 1.4 in patients that received

hypothermia with a mortality rate of 21% in the hypo-

thermia group and 12% in the normothermia group

(108). There was an increased need for vasopressor use

and an increased incidence of hypotension in the hypo-

thermia group. Several adverse effects have been

reported with hypothermia including hypotension, bra-

dycardia, arrhythmias, sepsis, and coagulopathy

(109,110). It has been suggested that the latter may

negate any significant outcome impact noted by hypo-

thermia. Despite these issues, other investigators have

continued to demonstrate the safety of hypothermia

with the suggestion that additional trials are needed in

the pediatric population to determine whether there is

an outcome benefit (111). The overall consensus from

the most recent set of guidelines for the care of pediat-

ric patients with TBI suggests that there is currently

no published support for the use of therapeutic hypo-

thermia in pediatric patients with TBI (8–10).

Summary:

1. No class I evidence of improved outcomes for

induced hypothermia

2. There are potential adverse effects with induced

hypothermia, including hypotension, bradycardia,

arrhythmias, sepsis, and coagulopathy

Corticosteroids

Historically, corticosteroids were used as part of the

pharmacological management of patients with TBI,

based on literature reporting edema reduction and

improved outcome in patients with brain tumors.

However, trials that specifically evaluated the use of

corticosteroids in patients with TBI have failed to

show an improvement in outcome (112,113). More

recently, the large multicenter CRASH study found an

increased mortality or severe disability in adult

patients with TBI who received methylprednisolone

within 8 h of the event treated (114). Adverse effects

related to the administration of corticosteroids to criti-

cally ill patients include adrenal suppression, increased

risk of infection, and gastrointestinal bleeding.

Although there are no data specific to the pediatric

population, given the strength and size of the CRASH

trial, corticosteroids should not be administered to

pediatric patients with TBI.

Summary:

1. Steroids do not provide benefit in TBI patients

2. CRASH trial showed increased mortality in adults

receiving methylprednisolone suffering from TBI

Blood product administration and coagulation function

Given the multisystem involvement of patients with

TBI, anemia is a common component related to

extracranial injuries. In adults with TBI, anemia has

been shown to be associated with increased in-hospi-

tal mortality and poor outcome in TBI (115–117).

However, there are limited data to support guidelines

regarding the use of blood products in patients with

TBI. More recently, there has been significant atten-

tion in the literature regarding the potential deleteri-

ous effects of the use of blood products in critically

ill patients including an increased risk of nosocomial

infections, adult respiratory distress syndrome, and

longer hospital/ICU stays (118–120). Although not

specifically studied in the pediatric population with

TBI, data from other clinical scenarios involving crit-

ically ill infants and children have demonstrated no

benefit to a liberal transfusion practice (hemoglobin

10 gÆdl)1) vs a restrictive transfusion practice (hemo-

globin 7 gÆdl)1) (121,122).

In addition to the need for packed red blood cells,

transfusions of allogeneic blood products may be

required to treat coagulation disorders. Tissue factor,

which is released following brain injury, activates the

coagulation cascade resulting in thrombin formation

and depletion of coagulation factors. Coagulation

function may be further compromised by hypothermia,

acidosis, and hypocalcemia. Disturbances of coagula-

tion function are a frequent occurrence in patients with

TBI with a reported incidence of more than 30% in

adults with TBI (123). Risk factors for coagulation dis-

turbances associated with TBI include GCS £ 8, a

higher severity of illness score, and anatomic features

noted on CT imaging including cerebral edema, sub-

arachnoid hemorrhage, and a midline shift (124). As in

all critically ill pediatric patients, the use of blood

products to treat coagulation disturbances should be

based on laboratory parameters including the pro-

thrombin time (PT), partial thromboplastin time, and

platelet count. In addition to the use of blood prod-

ucts, both antifibrinolytic agents such as tranexamic

acid and pro-coagulant drugs such as recombinant fac-

tor VII (rFVIIa) have been used in trials and case ser-

ies in patients with TBI. Anecdotal evidence has

suggested the efficacy of rFVIIa even in pediatric

patients with TBI not only in the control of bleeding

that is unresponsive to conventional therapy, but also

as a means of allowing patients to be taken rapidly to

the operating room instead of waiting for the adminis-

tration of routine blood products to reverse the coagu-

lation disturbances (125,126). A review from the



Cochrane database reported that their analysis of two

randomized controlled revealed that the cohorts were

too small to draw a conclusion regarding the effective-

ness of rFVIIa for TBI patients (127). Although not

performed solely in patients with TBI, but rather adult

trauma patients in general; the CRASH-2 trial

reported decreased mortality in patients who received

tranexamic acid (128).

Summary:

1. There is no defined optimal transfusion endpoint

2. Treatment of clinical symptoms in conjunction with

coagulation laboratory results should drive therapy

Anticonvulsant prophylaxis

When compared with the adult population, infants and

small children are at an increased risk of posttraumatic

seizures (PTS) compared with adults, because of

increased excitability of the developing brain (129). The

incidence has been reported between 12% and 40% for

early PTS (within 7 days of injury) following moderate

to severe TBI with the incidence being higher based on

the severity of the injury and the age of the patient

(130,131). Children who are <2 years of age are 2.5

times more likely to suffer PTS. PTS has been identified

as a poor prognostic indicator of recovery in the pediat-

ric population with TBI. Seizure activity may lead to an

increase in CMRO2 and ICP, excessive neurotransmitter

release, and fluctuations in systemic blood pressure, fac-

tors that may contribute to secondary brain injury. The

administration of phenytoin reduces the incidence of

early PTS with no effect on late occurring PTS (7 days

postinjury) or overall outcome (132). It is therefore rec-

ommended that prophylactic anticonvulsant therapy be

considered only in the first week following severe TBI

in patients at high risk of seizure activity including

those with intraparenchymal blood.

Summary:

1. Children are at higher risk of suffering from post-

traumatic seizures

2. Seizure activity may worsen secondary brain injury

3. Prophylactic anticonvulsant therapy should be given

for the first 7 days posttrauma

Summary

TBI and its sequelae are a major healthcare issue

throughout the world. With an improved understand-

ing of the pathophysiology of TBI, refinements of

monitoring technology, and ongoing research to

determine optimal care, the prognosis of TBI contin-

ues to improve. Regardless of whether these children

are in the Pediatric ICU or the operating room,

knowledge of the guidelines from the Society of Crit-

ical Care Medicine regarding the acute management

of severe TBI in infants, children, and adolescents

may be useful in guiding therapeutic interventions.

Of particular note over the past decade has been the

increasing evidence of the importance of the preven-

tion of secondary injury and its role in a favorable

outcome. As such, meticulous attention to ventilatory

and hemodynamic management is vital for these

patients. Of prime importance during the periopera-

tive period is attention to the hemodynamic status as

even a single episode of hypotension has been shown

to worsen outcome. One area that merits further

investigation is the optimal CPP in the pediatric

population. Although there is general consensus in

the adult population that the CPP should be main-

tained at >70 mmHg, there are no specific data for

the various ranges along the pediatric population

(133). A lower limit of acceptability in the pediatric

population has been set at a CPP of 40 mmHg;

however, there are no age-specific guidelines (68).

Additionally, the intra-operative focus in the care of

these patients remains on correcting or preventing

physiologic disturbances that may result in secondary

injury to the brain including hypocarbia, hypercar-

bia, hypoxemia, hypoglycemia, and hyperglycemia.

Additional perioperative goals are outlined in

Table 1 Intra-operative goals in the goal of TBI

Respiratory support Maintain PaO2 ‡ 60 mmHg and PaCO2 at 35–40 mmHg. Hyperventilation with a PaCO2 £ 30 mmHg is not

recommended except for the treatment of impending herniation or to temporarily treat inadequate

surgical relaxation of the brain

Hemodynamic Avoid hypotension. Use vasoactive agents (phenylephrine) to treat hypotension. Invasive blood pressure

monitoring. Maintain cerebral perfusion pressure at 40–70 mmHg depending on patient’s age

Hyperosmolar therapy Mannitol (0.25–1 gÆkg)1) to treat elevated intracranial pressure (ICP). Consider hypertonic saline for

elevated ICP that is refractory to treatment

Fluid therapy Normal saline without glucose unless serum glucose £70 mgÆdl)1. Monitor serum glucose. Avoid albumin

Temperature Avoid hyperthermia. No role for routine therapeutic hypothermia

Corticosteroids No role in TBI

Blood products Maintain hemoglobin at 7–10 gÆdl)1. Follow and treat coagulation function with blood products



Table 1. As much of the clinical practice and care of

children with TBI continues to be extrapolated from

the adult literature, future studies focusing on the

care of children with TBI should be considered.

With appropriate attention to the current recommen-

dations perioperatively, the outcomes of TBI will

continue to improve.

Conflict of interest

No conflicts of interest declared.

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