Management of Raised Intracranial Pressure SYMPOSIUM ON PICU PROTOCOLS OF AIIMS

Indian J Pediatr (2010) 77:1409–1416
DOI 10.1007/s12098-010-0190-2
Management of Raised Intracranial Pressure
Naveen Sankhyan & K. N. Vykunta Raju &
Suvasini Sharma & Sheffali Gulati
Received: 3 August 2010 / Accepted: 18 August 2010 / Published online: 7 September 2010
# Dr. K C Chaudhuri Foundation 2010
Abstract Appropriate management of raised intracranial
pressure begins with stabilization of the patient and
simultaneous assessment of the level of sensorium and the
cause of raised intracranial pressure. Stabilization is
initiated with securing the airway, ventilation and circulatory function. The identification of surgically remediable
conditions is a priority. Emergent use of external ventricular
drain or ventriculo-peritoneal shunt may be lifesaving in
selected patients. In children with severe coma, signs of
herniation or acutely elevated intracranial pressure, treatment should be started prior to imaging or invasive
monitoring. Emergent use of hyperventilation and mannitol
are life saving in such situations. Medical management
involves careful use of head elevation, osmotic agents, and
avoiding hypotonic fluids. Appropriate care also includes
avoidance of aggravating factors. For refractory intracranial
hypertension, barbiturate coma, hypothermia, or decompressive craniectomy should be considered.
either an increase in brain volume, cerebral blood flow, or
cerebrospinal fluid (CSF) volume. Despite its high incidence, there are few systematically evaluated treatments of
intracranial hypertension. Most management recommendations are based on clinical experience and research done in
patients with traumatic brain injury.
Intracranial Pressure: Normal Values
Intracranial pressure is the total pressure exerted by the
brain, blood and CSF in the intracranial vault. The MonroeKellie hypothesis states the sum of the intracranial volumes
of brain (≈80%), blood(≈10%), and CSF(≈10%) is constant,
and that an increase in any one of these must be offset by
an equal decrease in another, or else pressure increases. The
ICP varies with age and normative values for children are
not well established. Normal values are less than 10 to
15 mm Hg for adults and older children, 3 to 7 mm Hg for
young children, and 1.5 to 6 mm Hg for term infants [1].
ICP values greater than 20 to 25 mm Hg require treatment
in most circumstances. Sustained ICP values of greater than
40 mm Hg indicate severe, life-threatening intracranial
hypertension [2].
Raised intracranial pressure (ICP) is a common neurological complication in critically ill children. The cause may be
Cerebral Pressure Dynamics
N. Sankhyan : K. N. Vykunta Raju : S. Sharma : S. Gulati (*)
Child Neurology Division, Department of Pediatrics, All India
Institute of Medical Sciences,
New Delhi 110029, India
e-mail: [email protected]
Cerebral perfusion pressure (CPP) is a major factor that
affects cerebral blood flow to the brain. CPP measurement
is expressed in millimeters of mercury and is determined by
measuring the difference between the mean arterial pressure
(MAP) and ICP (CPP = MAP – ICP). It is apparent from
the formula that, CPP can reduce as a result of reduced
MAP or raised ICP, or a combination of these two. CPP
Keywords Coma . Critically ill child . Intracranial
hypertension . Traumatic brain injury
measurements aid in determining the amount of blood
volume present in the intracranial space. It is used as an
important clinical indicator of cerebral blood flow and
hence adequate oxygenation. Normal CPP values for
children are not clearly established, but the following
values are generally accepted as the minimal pressure
necessary to prevent ischemia: adults CPP>70 mm Hg;
children CPP>50–60 mm Hg; infants/toddlers CPP>40–
50 mm Hg [3].
Indian J Pediatr (2010) 77:1409–1416
Assessment and Monitoring
Identify children at risk for raised ICP (Table 1). Those at
greater risk are children with head trauma, suspected
neuroinfections, or suspected intracranial mass lesions.
Raised pressure usually manifests as headache, vomiting,
irritability, squint, tonic posturing or worsening sensorium.
However the symptoms depend on the age, cause, and
evolution of the raised ICP.
Initial Assessment
Causes of Raised ICP
The various causes of raised ICP (Table 1) can occur
individually or in various combinations. Based on the
Monroe-Kellie hypothesis, raised ICP can result from
increase in volume of brain, blood, or CSF. Frequently it is
a combination of these factors that result in raised ICP. The
causes of raised ICP can also be divided into primary or
secondary depending on the primary pathology. In primary
causes of increased ICP, normalization of ICP depends on
rapidly addressing the underlying brain disorder. In secondary causes of raised ICP the underlying systemic or
extracranial cause has to be managed.
Table 1 Causes of raised intracranial pressure
Increased brain volume
Intracranial space occupying lesions
Brain tumors
Brain abscess
Intracranial hematoma
Intracranial vascular malformation
Cerebral edema
Encephalitis (viral, inflammatory)
Hypoxic ischemic encephalopathy
Traumatic brain injury
Hepatic encephalopathy
Reye’s syndrome
Reye’s syndrome
Increase in CSF volume
Choroids plexus palpilloma
Increased blood volume
Vascular malformations
Cerebral venous thrombosis
Meningitis, encephalitis
As with any sick child, one begins with assessment and
maintenance of the airway, breathing and circulatory function.
An immediate priority is to look for potentially life threatening
signs of herniation (Table 2). If these signs are present then
measures to decrease intracranial pressure should be rapidly
instituted. Cushing’s triad (bradycardia, hypertension and
irregular breathing) is a late sign of herniation.
Neurological Assessment
After the initial stabilization, a thorough history and clinical
examination is performed to determine the possible etiology
and further course of management. Pupillary abnormalities and
abnormalities in ocular movements as determined by spontaneous, dolls eye or cold caloric testing are important clues to the
localization of brainstem dysfunction. The examination of
fundus is focused on detection of papilledema, keeping in mind
that its absence does not rule out raised ICP. The motor system
examination focuses on identifying posturing or flaccidity due
to raised ICP or focal deficits. Findings on the general physical
and systemic examination may provide clues to the underlying
cause for raised ICP (e.g. jaundice/hepatomegaly in hepatic
encephalopathy, rash in viral encephalitis etc.).
The imaging study of choice for the patient with raised
intracranial pressure presenting to the emergency room is a
computed tomography (CT) scan. A contrast study is
helpful to identify features of infection (meningeal enhancement, brain abscess etc.) and tumors. If CT scan is
normal, and the patient has clinical features of raised ICP,
then an MRI with MR venogram must be obtained once the
patient is stabilized. MRI can pick up early stroke, venous
thromboses, posterior fossa tumors and demyelinating
lesions which might be missed on CT.
Invasive ICP Monitoring
ICP monitoring is used mainly to guide therapy, such as
in determining when to drain CSF or administer
Indian J Pediatr (2010) 77:1409–1416
Table 2 Clinical recognition of herniation syndromes
Type of herniation
Clinical manifestations
Subfalcine herniation (medially, of the cingulate gyrus)
Central transtentorial
Impaired consciousness, monoparesis of the contralateral lower extremitya
Impaired consciousness, abnormal respirations, symmetrical small reactivea or
midposition fixed reactive pupils, decorticatea evolving to decerebrate posturing
Impaired consciousness, abnormal respirations, third nerve palsya (unilateral dilated
pupil, ptosis), hemiparesisa
Prominent brainstem signs, downward gaze deviation, upgaze palsy, decerebrate
Impaired consciousness, neck rigidity, opisthotonus, decerebrate rigidity, vomiting,
irregular respirations, apnea, bradycardia
Lateral transtentorial (downward and medially of uncus
and parahippocampal gyrus)
Upward Transtentorial (upward of the cerebellar
vermis and midbrain)
Transforaminal (downward of cerebellar tonsils and
Clinical signs of potentially reversible brain herniation
mannitol or sedation. In addition, invasive monitoring
allows for observation of the shape, height, and trends
of individual and consecutive ICP waveforms that may
reflect intracranial compliance, cerebrovascular status
and cerebral perfusion. Guidelines for ICP monitoring
are available for traumatic brain injury [4]. ICP
monitoring is indicated for a patient with Glasgow Coma
Scale (GCS) score of 3–8 (after resuscitation) with either
an abnormal admission head CT or motor posturing and
hypotension [4]. The role and benefit of ICP monitoring
in other conditions such as subarachnoid hemorrhage,
hydrocephalus, intracranial infections, and Reyes syndrome remains unclear. Also, the availability of this
modality is limited. In other brain injuries, such as
hypoxic and ischemic injuries, monitoring ICP has not
been shown to improve outcome [5].
Management of Intracranial Hypertension
The goal for patients presenting with raised ICP is to identify
and address the underlying cause along with measures to
reduce ICP (Fig. 1, Table 3). It is important not to delay
treatment, in situations where identifying the underlying cause
will take time. When elevated ICP is clinically evident, the
situation is urgent and requires immediate reduction in ICP.
Avoidance of factors aggravating or precipitating raised ICP is
an important goal for all children with intracranial hypertension. The availability of ICP monitors is not universal and
should not come in the way of emergent therapy.
The assessment and management of the airway, breathing
and circulation (ABCs) is the beginning point of management. Early endotracheal intubation should be considered
for those children with GCS <8, evidence of herniation,
apnea or have inability to maintain airway. Intubation
should proceed with administration of medications to blunt
the ICP during the procedure. Suggested medications are
lidocaine, thiopental and a short-acting non depolarizing
neuromuscular blockade agent (e.g.vecuronium, atracurium) [6]. Appropriate oxygenation should be ensured. If
there is evidence of circulatory failure, fluid bolus should
be given. Samples should be drawn for investigations as
suggested by history.
Mild head elevation of 15–30° has been shown to reduce
ICP with no significant detrimental effects on CPP or
CBF [7]. The child’s head is positioned midline with the
head end of the bed elevated to 15–30° to encourage
jugular venous drainage [7]. Sharp head angulations and
tight neck garments or taping should be avoided [8]. One
has to ensure that the child is euvolemic and not in shock
prior to placing in this position [6].
Decreasing the PaCO2 to the range of 30–35 mm of Hg, is
an effective and rapid means to reduce ICP [6, 9].
Hyperventilation acts by constriction of cerebral blood
vessels and lowering of CBF. This vasoconstrictive effect
on cerebral arterioles lasts only 11 to 20 h because the pH
of the CSF rapidly equilibrates to the new PaCO2 level.
Moreover, aggressive hyperventilation can dramatically
decreases the CBF, causing or aggravating cerebral ischemia [10, 11]. Hence, the most effective use of hyperventilation is for acute, sharp increases in ICP or signs of
impending herniation [12].
Indian J Pediatr (2010) 77:1409–1416
Fig. 1 Algorithmic approach to
a child with raised ICP
Child with signs/symptoms of raised ICP
Immediate Measures*
Maintain airway and adequate
ventilation and circulation
Head end elevation-15-
Ongoing care
Sedation and analgesia
Avoid noxious stimuli
Control fever
Prevention and treatment of
Hyperventilation: (target PCO2 : 30-35mm Hg ) To be
used in emergent situations like herniation to bridge more
definitive therapy. Not to be used for more than a few
Surgical intervention
Evacuation of hematoma
Maintain euglycemia
Neuroimaging : Suggestive of
surgically remediable cause;
hydrocephalous, large hematoma, etc
No hyotonic fluid infusions
Maintain Hb above 10gm%
CSF diversion
Decompressive craniectomy
“No” or delay
BP Normal: Mannitol
Hypotension, Hypovolemia Serum osmolality >320
mOsm/kg, Renal failure: Hypertonic Saline
Other options;***
Heavy sedation and paralysis
Barbiturate coma
Special situations
Steroids: Intracranial tumors with perilesional edema, neurocysticercosis with high lesion load,
ADEM, pyomeningitis,TBM, Abscess
Acetazolamide: Hydrocephalus, Benign intracranial, high altitude illness
(*- May be initiated immediately after brief evaluation if situation is urgent. Measures also used in children awaiting surgical/radiologial
procedures, ** -Preferable to monitor ICP, ***- undertake only with ICP monitoring)
Mannitol has been the cornerstone of osmotherapy in raised
ICP. However, the optimal dosing of mannitol is not
known. A reasonable approach is to use an initial bolus of
0.25–1 g/kg (the higher dose for more urgent reduction of
ICP) followed by 0.25–0.5 g/kg boluses repeated every 2–
6 h as per requirement. Attention has to be paid to the fluid
balance so as to avoid hypovolemia and shock. There is
also a concern of possible leakage of mannitol into the
damaged brain tissue potentially leading to “rebound” rises
in ICP [13]. For this reason, when it is time to stop
mannitol, it should be tapered and its use should be limited
to 48 to 72 h. Apart from hypotension, rebound rise in ICP,
mannitol can also lead to hypokalemia, hemolysis and renal
Hypertonic Saline
Hypertonic saline has a clear advantage over mannitol in
children who are hypovolemic or hypotensive. Other
situations where it may be preferred are renal failure or
serum osmolality >320 mosmol/Kg. It has been found
effective in patients with serum osmolality of up to
Indian J Pediatr (2010) 77:1409–1416
Table 3 Summary of measures to reduce intracranial pressure
Assessment and management of ABC’s (airway, breathing,
Early intubation if; GCS <8, Evidence of herniation, Apnea,
Inability to maintain airway
Mild head elevation of 15–30° (Ensure that the child is
Hyperventilation: Target PaCO2: 30–35 mm Hg (suited for acute,
sharp increases in ICP or signs of impending herniation)
Mannitol: Initial bolus: 0.25–1 g/kg, then 0.25–0.5 g/kg, q 2–6 h as
per requirement, up to 48 h
Hypertonic Saline: Preferable in presence of Hypotension,
Hypovolemia, Serum osmolality >320 mOsm/kg, Renal failure,
Dose: 0.1–1 ml/kg/hr infusion, Target Na+−145–155 meq/L.
Steroids: Intracranial tumors with perilesional edema,
neurocysticerocosis with high lesion load, ADEM,
pyomeningitis, TBM, Abscess
Acetazolamide: Hydrocephalous, benign intracranial, high altitude
Adequate sedation and analgesia
Prevention and treatment of seizures: use Lorazepam or
midazolam followed by phenytoin as initial choice.
Avoid noxious stimuli: use lignocaine prior to ET suctioning
[nebulized (4% lidocaine mixed in 0.9% saline) or intravenous
(1–2 mg/kg as 1% solution) given 90 sec prior to suctioning]
Control fever: antipyretics, cooling measures
Maintenance IV Fluids: Only isotonic or hypertonic fluids (Ringer
lactate, 0.9% Saline, 5% D in 0.9% NS), No Hypotonic fluids
Maintain blood sugar: 80–120 mg/dL
Refractory raised ICP:
• Heavy sedation and paralysis
• Barbiturate coma
• Hypothermia
• Decompressive craniectomy
360 mosmol/Kg [14]. Concerns with its use are bleeding,
rebound rise in ICP, hypokalemia, and hyperchloremic
acidosis, central pontine myelinolysis, acute volume overload, renal failure, cardiac failure or pulmonary edema [15–
17]. Despite these concerns, current evidence suggests that
hypertonic saline as currently used is safe and does not
result in major adverse effects [18]. In different studies the
concentration of hypertonic saline used has varied from
1.7% to 30% [18]. The method of administration has also
varied and hence, evidence based recommendations are
difficult. It would be reasonable to administer hypertonic
saline as a continuous infusion at 0.1 to 1.0 mL/kg/hr, to
target a serum sodium level of 145–155 meq/L [19, 20].
Serum sodium and neurological status needs to be closely
monitored during therapy. When the hypertonic saline
therapy is no longer required, serum sodium should be
slowly corrected to normal values (hourly decline in serum
sodium of not more than 0.5 meq/L) to avoid complications
associated with fluid shifts [6]. Monitoring of serum
sodium and serum osmolality should be done every 2–4 h
till target level is reached and then followed up with 12
hourly estimations. Under careful monitoring, hypertonic
saline has been used for up to 7 days [21].
Other Agents
Acetazolamide (20–100 mg/kg/day, in 3 divided doses, max
2 g/day) is a carbonic anhydrase inhibitor that reduces the
production of CSF. It is particularly useful in patients with
hydrocephalous, high altitude illness and benign intracranial
hypertension. Furosemide (1 mg/kg/day, q8hrly), a loop
diuretic has sometimes been administered either alone or in
combination with mannitol, with variable success [22, 23].
Glycerol is another alternative osmotic agent for treatment of
raised ICP. It is used in the oral (1.5 g/kg/day, q4–6hrly) or
intravenous forms. Given intravenously, it reduces ICP with
effect lasting for about 70 min without any prolonged effect
on serum osmolality [24]. Glycerol readily moves across the
blood brain barrier into the brain. Though not proven, there
is concern of rebound rise in ICP with its use.
Glucocorticoids are very effective in ameliorating the
vasogenic edema that accompanies tumors, inflammatory
conditions, infections and other disorders associated with
increased permeability of blood brain barrier, including
surgical manipulation [25]. Dexamethasone is the preferred
agent due to its very low mineralocorticoid activity (Dose:
0.4–1.5 mg/kg/day, q 6 hrly) [26]. Steroids are not routinely
indicated in individuals with traumatic brain injury [27].
Steroids have not been found to be useful and may be
detrimental in ischemic lesions, cerebral malaria and
intracranial hemorrhage [26, 28, 29].
Sedation and Analgesia
Raised ICP is worsened due to agitation, pain, and patientventilator asynchrony [8]. Adequate analgesia, sedation and
occasionally neuromuscular blockade are useful adjuvant in
the management of raised ICP. Appropriate Analgesia and
sedation is usually preferred over neuromuscular blockade,
as it is quickly reversible and allows for neurological
monitoring. For sedation it is preferable to use agents with
minimal effect on blood pressure. Short acting benzodiazepines (e.g. midazolam) are useful for sedation in children. If
the sedatives are not completely effective, then a neuromuscular blocking agent (e.g. Pancuronium, atracurium,
vecuronium) may be required.
Indian J Pediatr (2010) 77:1409–1416
Minimization of Stimulation
Prevention and Treatment of Seizures
Attempt must be made to reduce the number of elective
interventions that are likely to be painful or excessively
stimulating. Lidocaine instilled endotracheally has been
shown to prevent the endotracheal suctioning-induced
ICP increase and CPP reduction in adults with severe
traumatic brain injury [30]. It is recommended to instil
lidocaine at body temperature, slowly, and through a fine
tube advanced into the endotracheal tube within its length
(avoid direct contact with the mucosa) [30]. Lidocaine can
be given in nebulized (usually 4% lidocaine mixed in
0.9% saline) or intravenous forms (1–2 mg/kg as 1%
solution given 90 sec prior to suctioning) for the same
purpose [9].
Children with significant head injury and neuroinfections are at
risk for seizures. Seizures can increase CBF and cerebral blood
volume leading to increased ICP. They can also increase the
metabolic needs of the brain and predispose to ischemia [6].
Seizures, if clinically evident, must be treated. Given the lack
of studies in children and in patients with non traumatic raised
ICP, evidence based recommendation regarding prophylactic
anti-epileptic therapy are not possible. But it is reasonable,
and a common practice is to use prophylactic anticonvulsants
for short term in children with raised ICP, unless indicated
otherwise [6, 26]. If available, it is prudent to use continuous
electroencephalography (EEG) to identify subclinical seizure
activity in children with increased risk for seizures.
The main goal of fluid therapy is to maintain euvolemia,
normoglycemia and prevent hyponatremia. Children with
raised ICP should receive fluids at a daily maintenance
rate, as well as fluid boluses as indicated for hypovolemia, hypotension, or decreased urine output. Maintenance fluids usually consist of normal saline with daily
requirements of potassium chloride based on body
weight. All fluids administered must be isotonic or
hypertonic (e.g. Ringer lactate, normal saline) and
hypotonic fluids must be avoided (e.g. 0.18% saline in
5% dextrose, Isolyte P) [7]. Hyponatremia is to be
avoided and if it occurs, must be corrected slowly.
Theoretically, anemia would increase CBF and secondarily
raise ICP. There have been case reports of patients with severe
anemia presenting with symptoms of raised ICP and
papilledema [32]. Though not rigorously studied, it is
common practice to maintain hemoglobin above 10 g/dL
in patients with traumatic brain injury and raised ICP.
Blood Glucose
Blood glucose must be maintained between 80–120 mg/dL in
a child with raised ICP [7]. Studies in children with traumatic
brain injury have shown that hyperglycemia is associated
with poor neurological outcome and increased mortality [31].
On the other hand, hypoglycemia is known to induce a
systemic stress response and cause disturbances in CBF,
increasing the regional CBF by as much as 300% in severe
hypoglycaemia. Hypoglycemia can also lead to neuronal
injury and therefore, should be managed aggressively.
Temperature Regulation
Maintaining normothermia is important to prevent complications of temperature fluctuations. This is achieved by
frequent measurements of body temperature and correcting
any fluctuations using antipyretics, and assisted cooling or
heating per needed.
Surgical Therapy
Cerebrospinal Fluid Drainage CSF drainage using a
external ventricular drainage (EVD) or ventriculoperitoneal
shunt provides for an immediately effective means to lower
ICP. In addition EVD provides a method for continuously
monitoring ICP. CSF drainage is particularly useful in the
presence of hydrocephalus. But it may be considered even
in children without hydrocephalus. Its effectiveness in
lowering ICP has been shown to be comparable to
intravenous mannitol or hyperventilation [33]. However, it
is of limited utility in diffuse brain edema with collapsed
Resection of Mass Lesions Surgery should be undertaken
when a lesion amenable to surgical intervention is identified
as the primary cause of raised ICP. Common situations
where this neurosurgical intervention is preferentially
employed are acute epidural or subdural hematomas, brain
abscess, or brain tumors.
Target of Therapy
When facilities for ICP monitoring are available, the
management is tailored to maintaining an adequate CPP
Indian J Pediatr (2010) 77:1409–1416
(i.e. Children >50–60, infants/toddlers >40–50 mm Hg)
and lower ICP to acceptable levels (i.e. <20 mm Hg for
children older than 8 yrs, <18 for 1–8 yrs, and <15 mm
for infants).
Other Therapies for Refractory Raised ICP
Use of barbiturates is generally reserved for cases with
refractory raised ICP. Thiopentone can be used for this
purpose and the dosing of the drug is adjusted to a target
ICP as monitored on an ICP monitor. The drug is titrated to
a 90% burst suppression (2–6 bursts per minute) using an
EEG monitor. Monitoring a child in barbiturate coma
should include EEG, ICP monitoring, invasive hemodynamic monitoring (arterial blood pressure, central venous
pressure, SjvO2) and frequent assessment of oxygenation
status. The complication rate of barbiturate therapy is high
and includes hypotension, hypokalemia, respiratory complications, infections, hepatic dysfunction and renal dysfunction [34].
Evidence from carefully conducted studies in adults and
children does not show any improvement in the neurologic
outcome in head injured patients with the use of therapeutic
hypothermia [35, 36]. However, studies do suggest a
lowered ICP during the hypothermia therapy in children
[35, 37]. So, in children with refractory raised ICP,
controlled hypothermia may be considered.
Decompressive Craniectomy On rare occasions when all
other measures fail, decompressive craniectomy with
duraplasty may be valuable procedure. Reports of its use
in children with traumatic brain injury have shown benefit
[38, 39]. It may offer an alternative treatment option in
uncontrolled ICP refractory to other measures.
1. Welch K. The intracranial pressure in infants. J Neurosurg.
2. Castillo LR, Gopinath S, Robertson CS. Management of intracranial hypertension. Neurol Clin. 2008;26:521–41.
3. Mazzola CA, Adelson PD. Critical care management of head
trauma in children. Crit Care Med. 2002;30:S393–401.
4. Adelson PD, Bratton SL, Carney NA, et al. Guidelines for the
acute medical management of severe traumatic brain injury in
infants, children, and adolescents: chapter 5. Indications for
intracranial pressure monitoring in pediatric patients with
severe traumatic brain injury. Pediatr Crit Care Med. 2003;4:
Goldstein B, Aboy M, Graham A. Neurologic monitoring. In:
Nichols DG, editor. Rogers textbook of Pediatric intensive care,
4th Ed. Philadelphia: Lippincott Williams & Wilkins; 2008.
Marcoux KK. Management of increased intracranial pressure in
critically ill child with acute neurological injury. AACN Clin
Issues. 2005;16:212–31.
Feldman Z, Kanter MJ, Robertson CS, et al. Effect of head
elevation on intracranial pressure, cerebral perfusion pressure, and
cerebral blood flow in head-injured patients. J Neurosurg.
Layon JA, Gabrielli A. Elevated intracranial pressure. In: Layon
JA, Gabrielli A, Friedman WA, editors. Textbook of neurointensive care. 1st ed. Pennsylvania: Saunders; 2004. p. 709–32.
Marsh ML, Marshall LF, Shapiro HM. Neurological intensive
care. Anesthesiology. 1977;47:149–63.
Skippen P, Seear M, Poskitt K, Kestle J, et al. Effect of
hyperventilation on regional cerebral blood flow in head-injured
children. Crit Care Med. 1997;25:1275–8.
Robertson CS, Valadka AB, Hannay HJ, Contant CF, et al.
Prevention of secondary ischemia insult after severe head injury.
Crit Care Med. 1999;27:2086–95.
Miller JD, Dearden NM, Piper IR, et al. Control of intracranial pressure
in patients with severe head injury. J Neurotrauma. 1992;9:S317.
Kaufmann AM, Cardoso ER. Aggravation of vasogenic edema by
multiple –dose mannitol. J Neurosurg. 1992;77:584–9.
Ziai WC, Toung TJ, Bhardwaj A. Hypertonic saline: first-line
therapy for cerebral edema? J Neurol Sci. 2007;261:157–66.
Doyle JA, Davis DP, Hoyt DB. The use of hypertonic saline in the
treatment of traumatic brain injury. J Trauma. 2001;50:367–83.
Himmelseher S. Hypertonic saline solutions for treatment of
intracranial hypertension. Curr Opin Anaesthesiol. 2007;20:414–
Suarez JI. Hypertonic saline for cerebral edema and elevated
intracranial pressure. Cleve Clin J Med. 2004;71:S9–13.
Strandvik GF. Hypertonic saline in critical care: a review of the
literature and guidelines for use in hypotensive states and raised
intracranial pressure. Anaesthesia. 2009;64:990–1003.
Larive LL, Rhoney DH, Parker D, Coplin WM, Carhuapoma JR.
Introducing hypertonic saline for cerebral edema. Neurocrit Care.
Qureshi A, Suarez J, Bhardwaj A, et al. Use of hypertonic saline/
acetate infusion in the treatment of cerebral edema: effect on
intracranial pressure and lateral displacement of the brain. Crit
Care Med. 1998;26:440–6.
Peterson B, Khanna S, Fischer B, Marshall L. Prolonged hypernatremia controls elevated intracranial pressure in head injured
pediatric patients. Crit Care Med. 2000;28:1136–43.
Thenuwara K, Todd MM, Brian JE, et al. Effect of mannitol and
furosemide on plasma osmolality and brain water. Anesthesiology.
Tornheim PA, McLaurin RL, Sawaya R. Effect of furosemide on
experimental traumatic cerebral edema. Neurosurgery. 1979;4:48–
Berger C, Sakowitz OW, Kiening KL, Schwab S. Neurochemical
monitoring of glycerol therapy in patients with ischemic brain
edema. Stroke. 2005;36:e4–6.
French LA, Galicich JH. The use of steroids for control of cerebral
edema. Clin Neurosurg. 1964;10:212–23.
Rabinstein AA. Treatment of cerebral edema. Neurologist.
Edwards P, Arango M, Balica L, et al. Final results of
MRCCRASH, a randomised placebo-controlled trial of intrave-
nous corticosteroid in adults with head injury outcomes at 6
months. Lancet. 2005;365:1957–9.
Feigin VL, Anderson N, Rinkel GJ, Algra A, van Gijn J,
Bennett DA. Corticosteroids for aneurysmal subarachnoid
haemorrhage and primary intracerebral haemorrhage. Cochrane
Database Syst Rev 2005; CD004583.
Hoffman SL, Rustama D, Punjabi NH, et al. High-dose dexamethasone in quinine-treated patients with cerebral malaria: a doubleblind, placebo-controlled trial. J Infect Dis. 1988; 158:325–31.
Bilitta F, Branca G, Lam A, Cuzzone V, Doronzio A, Rosa G.
Endotraceal lidocaine in preventing endotracheal suctioning
induced changes in cerebral hemodynamics in patients with
severe head trauma. Neurocrit Care. 2008;8:241–6.
Cochran A, Scaife ER, Hansen KW, Downey EC. Hyperglycemia
and outcomes from pediatric traumatic brain injury. J Trauma.
Biousse V, Rucker JC, Vignal C, et al. Anemia and papilledema.
Am J Ophthalmol. 2003;135:437–46.
Fortune JB, Feustal PJ, Graca L, et al. Effect of hyperventilation,
mannitol, and ventriculostomy drainage on cerebral blood flow
after head injury. J Trauma. 1995;39:1091–9.
Indian J Pediatr (2010) 77:1409–1416
34. Schalen W, Sonesson B, Messeter K, et al. Clinical outcome
and cognitive impairment in patients with severe head injuries
treated with barbiturate coma. Acta Neurochir (Wien).
35. Hutchison JS, Ward RE, Lacroix J, et al. Hypothermia therapy
after traumatic brain injury in children. N Engl J Med.
36. Clifton GL, Miller ER, Choi SC, Levin HS, et al. Lack of effect of
induction of hypothermia after acute brain injury. N Engl J Med.
37. Adelson PD, Ragheb J, Kanev P, et al. Phase II clinical trial of
moderate hypothermia after severe traumatic brain injury in
children. Neurosurgery. 2005;56:740–54.
38. Berger S, Schwarz M, Huth R. Hypertonic saline solution and
decompressive craniectomy for treatment of intracranial hypertension in pediatric severe traumatic brain injury. J Trauma.
39. Taylor A, Butt W, Rosenfeld J, et al. A randomized trial of very
early decompressive craniectomy in children with traumatic brain
injury and sustained intracranial hypertension. Child’s Nerv Syst.