Indian Journal of Neurotrauma (IJNT)

81
Review Article
2006, Vol. 3, No. 2, pp. 81-94

Intensive care management of the head injured patient

V. Bhadri Narayan, MD
Associate Professor
Department of Neuroanaesthesia, NIMHANS, Bangalore

Abstract : Traumatic brain injury is a significant cause of mortality and morbidity in patients below
the age of 40 years, and is a socio-economic burden on the society. Patients with severe head injury
require comprehensive care preoperatively, intraoperatively and postoperatively. The aim would be
to prevent secondary brain injury by maintaining cerebral perfusion pressure, intracranial pressure
and cerebral blood flow. Head injury is often associated with intracranial and extracranial
complications. Timely diagnosis and correction of these complications will improve outcome in these
patients.
Keywords: brain injury, cerebral perfusion pressure, cerebral blood flow, monitoring, intracranial
pressure

INTRODUCTION has been proposed in dealing with risk-taking behaviors

Traumatic brain injury is a major cause of death,
disability and is a serious socio-economic problem. The
mortality in patients with brain injury is unacceptably
high between 35-50 % and over the last few decades the
mortality has shown a decrease of about 10% per decade.
This has been possible because of improved
understanding of the pathophysiology, new modalities
of monitoring and therapeutic strategies. However,
despite enormous efforts and huge investments the search
for the magic bullet for cerebral protection is still elusive.
As we understand the complex pathophysiology following
head injury it is unlikely that such a magic bullet will
ever be found. The strategy that is most likely to help in
the management will be a pharmacologic cocktail aimed
at the multiple pathomechanisms.
The role of prevention
Emergency physicians can have an important role in the
prevention of TBI by promoting safety legislation,
designing prevention programs, and serving as educators
and teachers. One example of a prevention program,
called THINK FIRST, has been developed by
neurosurgical associations. This program teaches school-
age children behavioral and preventive measures to
reduce the risk of head injury and spinal cord injury1.
Early evaluations of this program suggest that it may be
effective in changing risk-taking behavior2. In terms of
emergency practice, the concept of a “teachable moment”
Corresponding author:
Dr Bhadri Narayan, MD
Department of Neuroanaesthesia
NIMHANS, Bangalore-560029
and substance abuse. The basic premise is that a patient
who has suffered an injury event may be more open to
counseling on safe behaviors, and more willing to change
behaviors, if approached in the emergency setting.
Further research is needed to assess what methods are
most effective at changing risky behaviors. Seatbelt use
in automobiles and helmet use by motorcyclists and
bicyclists have also been demonstrated to be effective
ways of reducing TBI but are not in universal practice,
and should be implemented to reduce the incidence of
head injuries3,4.
Physiological Alterations
The injured brain itself has systemic effects on physiology
and homeostasis that may result in secondary injury. A
posttraumatic sympathetically mediated catecholamine
release may result in a hyperdynamic cardiovascular
response that may lead to any of three clinical complexes:
severe neurogenic hypertension, cardiac dysrhythmias,
and myocardial ischemia.5. The hyperdynamic response
in the patient with severe TBI is typically characterized
by sustained, severe hypertension, with an associated
increase in cardiac index and heart rate and a normal to
decreased systemic vascular resistance. The patient may
be relatively hypervolemic, even with a normal
pulmonary capillary wedge pressure. There is typically
an associated increase in urine output. There may be an
increase in plasma epinephrine and norepinephrine levels.
Electrocardiographic findings may include a prolonged
QT interval (in 89% of patients), U waves, peaked T
waves, and premature atrial contractions. Subendocardial
hemorrhages have been documented in 50% of autopsied
patients.

Indian Journal of Neurotrauma (IJNT), Vol. 3, No. 2, 2006

82 V. Bhadri Narayan
Pulmonary effects appear in two varieties. The most
common effect, occurring in over 85% of severe TBI
patients, is that of neurogenic hypoxia. This is manifested
as an increase in the alveolar-arterial oxygen
concentration gradient without a radiographic
abnormality. It may last a few days in survivors but
persists in nonsurvivors. The cause of this ventilation-
perfusion mismatch is unknown but is presumed to be
related to hypothalamic dysfunction or microatelectasis.
A rarer but more obvious pulmonary effect of severe
brain injury, typically associated with the most severe
injuries, is neurogenic pulmonary edema. This classically
has an immediate onset and becomes clinically evident
as dyspnea, tachypnea, hypoxemia, and “fluffy” infiltrates
on chest x-ray from 2 to 12 hours after injury. It is
typically a transient, self-limited process lasting hours to
days. The etiology is relatively undefined, but may result
from increased pulmonary intravascular pressure caused
by a catecholamine-mediated decrease in pulmonary
vascular resistance in the setting of a hyperdynamic
increase in cardiac output, or from increased
permeability due to direct endothelial injury6. Pulmonary
vascular endothelial and parenchymal damage could
theoretically result from the cytokine release that follows
TBI7. Depletion of lung surfactant and pulmonary
microembolism may also play a role. Other pulmonary
complications of severe TBI include aspiration, infection,
and pulmonary embolus.
Electrolyte abnormalities can result from severe TBI.
Hyponatremia, either from the release of antidiuretic
hormone, the syndrome of inappropriate secretion of
antidiuretic hormone (SIADH), or, uncommonly,
cerebral salt wasting, is the most common electrolyte
abnormality following TBI. SIADH is associated with
hyponatremia, serum hypo-osmolarity, and urine
hyperosmolarity. Diabetes insipidus, which occurs in
less than 1% of TBI patients, may result in hypernatremia,
with an associated serum hyperosmolarity and urine
hypo-osmolarity.
Perhaps the most insidious abnormality after TBI is
coagulopathy. Parenchymal disruption of brain tissue is
known to activate the coagulation system, presumably
from activation of the extrinsic pathway by tissue
thromboplastin8. An abnormal level of fibrin degradation
products (FDP) has been found to be the most prevalent
abnormality, in one study occurring in all patients with
severe TBI.9,10. An elevation of the activated partial
thromboplastin time (APTT) can be found in over 25%
Indian Journal of Neurotrauma (IJNT), Vol. 3, No. 2, 2006
of head injured patients. Blunt brain injury activates the
coagulation process, and in two thirds of TBI patients
results in parameters suggestive of disseminated
intravascular coagulation (DIC) (i.e., elevated D-Dimer,
decreased fibrinogen, increased PT and PTT). Patients
tend to demonstrate a two-phase coagulopathy. In the
first 4 hours after injury, a state of relative
hypercoagulability mediated by plasmin and thrombin
develops; by 4 hours posttrauma, coagulation pathway
substrates are exhausted and a subsequent stage of
consumptive coagulopathy ensues. The degree of
posttraumatic perturbation in the prothrombin time (PT),
platelet count, thrombin clotting time (TCT), and
especially the APTT has a strong association with
mortality. Patients with coagulopathy are nine times more
likely to die, and commonly demonstrate an interval
progression of injury or development of new lesions on
repeated brain imaging11.
PATHOPHYSIOLOGY
Primary Brain Injury
The underlying pathophysiology of TBI can be divided
into primary and secondary events. Primary brain injury
results directly from the disruptive mechanical forces
imparted to the brain during the traumatic event.
Manifestations of such injury can be either focal or
diffuse. Focal injury includes cerebral contusions,
intracerebral hematomas, epidural hematomas, subdural
hematomas, or subarachnoid hemorrhage12. Diffuse
primary brain injury may result from the shear forces
generated by trauma and is manifested as diffuse axonal
injury (DAI)13. Axonal injury is common in TBI and
appears to account for much of its morbidity14.
Secondary Brain Injury
Neurochemical events: Secondary brain injury results
from physiological processes and neurochemical
cascades, either triggered by or associated with the
primary injury, that continue after the initial traumatic
event. Delayed axonal injury may occur 4 to 24 hours
after the initial injury and is thought to involve secondary
calcium-mediated proteolytic processes that compromise
the axonal cytoskeleton15. The accumulation of delayed
secondary axotomies appears to constitute a more
prominent injury process than that from primary
axotomies. Histological studies on experimentally injured
animals, corroborated by postmortem histological studies
on humans, reveal a process that starts with a focal
impairment of anterograde axonal transport followed by
 Intensive Care Management of the Head Injured Patient
axonal swelling and disconnection, and then formation
of axonal retraction balls16.
Somatic neuronal injury is mediated in part by the
release of excitatory amino acid neurotransmitters,
which leads to widespread neuronal depolarization,
followed by massive calcium ion influx through voltage-
sensitive channels such as the N-methyl-D-aspartate
(NMDA) receptor complex. Free-radical generation and
lipid peroxidation result in neuronal membrane
deterioration and subsequent cell lysis. Other injurious
biochemical cascades, involving agents such as nitric oxide
and cytokines, result in further and delayed damage, with
subsequent brain swelling and edema17,18,19.
The cranial vault is a fixed space containing three
compartments: brain tissue, cerebrospinal fluid (CSF),
and blood (intravascular volume). As posttraumatic brain
swelling ensues, the CSF and vascular compartments are
less and less able to compensate through the relative
extrusion of their respective components, and intracranial
pressure (ICP) begins to rise sharply20. This can lead to
regional ischemia and herniation. Increased ICP (over
20 mmHg) has significant adverse effects on outcome
and survival from severe TBI 21,22,23.
MANAGEMENT IN THE ICU
Nutrition: Nutritional assessment of the critically ill
patient is crucial as deterioration in nutritional status
can have a profound effect on the outcome. The route,
manner, adequacy of nutritional support affects the
degree of stress response, incidence of nosocomial
infections/ multiorgan failure, length of hospitalization,
morbidity and mortality. While short periods of starvation
over hours or a day or two may not be detrimental for
most patients, the difficulty of maintaining or increasing
lean body mass during critical illness is too great to delay
instituting artificial feeding long, even if the patient is
well nourished at the outset.
Although the brain does not participate in mechanical
work, osmotic work, or extensive biosynthesis, processes
which use quite large amounts of energy. Nutritional
management in some patients can be an essential factor
necessary for survival. After the initial neurologic insult
the incidence of death from extracranial causes such as
sepsis increases dramatically 23 . Bodily defense
mechanisms against such secondary insults as septicemia,
pneumonia, and meningitis rely heavily on adequate
nutritional support24. Assessment of nutritional needs in
the neuro-ICU patient is similar to methods employed
83
for other types of critically ill patients.
Nutritional Assessment
Body weight: Though seemingly straight-forward, body
weights in ICU are difficult to measure as they are often
distorted by changing fluid distribution. Consequently,
the patient’s current weight should be compared with
his/her usual or ideal body weight. A weight loss
exceeding 10% signifies that the patient is at high risk
of malnutrition. Devices are available which will measure
body weight daily in ICU.
Anthropometric measurements: Mid-arm circumference
and triceps skin fold thickness can be used but are not
reliable in the ICU as they can get obscured by severe
edema and nutritional deficiencies.
Laboratory tests: A number of biochemical investigations
can guide the state of preexisting nutrition in patients.
The levels of albumin, prealbumin and transferrin will
normally give a balanced view of patient status but are
less reliable in the ICU during periods of critical illness
resulting from aggressive fluid resuscitation. Prolonged
stays in the ICU also can change these values. The total
leukocyte count gives a reliable indicator of the
immunological status of the patient, which indirectly
reflects the nutritional status.
Body mass index: This is more optimal indicator of
nutrition. BMI is given by body weight in kilograms
divided by squares of the height in metres. BMI The
Harris-Benedict equation provides a satisfactory method
to develop an initial estimate of basal energy expenditure
(BEE) based on weight and gender. BMI values for women
are 1-22.4, 2-26.9, 3-31.4 and for men 1-22.7, 2-27.2,
2-31.8; 1 is normal and 2 and 3 are over weight.
Goals of nutritional support
The fundamental goal of nutritional support for the
critically ill head-injured patient is to provide protein
and calories in amounts sufficient to match the demands
of hypermetabolism and increased protein breakdown.
In addition, it is important to provide adequate
micronutrients in order to meet the increased demand
imposed by stress. Full nutritional support is generally
not initiated immediately after injury. Reasons for the
delay include the time required for accurate assessment,
the need for resuscitation and/or early trauma care, and
the potential complicating metabolic effects of aggressive
feeding during the early, unstable period. Virtually all
severely injured patients, therefore, experience a period
Indian Journal of Neurotrauma (IJNT), Vol. 3, No. 2, 2006
84 V. Bhadri Narayan
of temporary starvation. Nutritional support should,
however, be started as soon as possible after injury and
should be maintained as long as the patient does not eat
adequately25. Support can almost always be initiated
within 2 to 4 days after the injury. The current approach
to nutritional support of the critically ill head injured
patient is to provide a broad array of the macronutrients
and micronutrients that are necessary for health. If
catabolic illness alters the requirements for specific
nutrients, then the administration of required substrates
might facilitate a patient’s anabolic response to a life-
threatening illness26. Enteral nutrition is the preferred
route of nutrient administration in the critically ill head
injured patient. It maintains the integrity of gut mucosa
and has immunologic advantages over parenteral
nutrition. Because it is usually not possible to start enteral
nutrition immediately in the critically ill or injured
patient, parenteral nutrition is an important therapeutic
modality. Patients who cannot tolerate full enteral
nutrition may be managed with parenteral nutrition alone
or with combination feeding, a modality in which
parenteral nutrition is gradually tapered off as the enteral
formula’s use is advanced.
Hypermetabolism, an accelerated catabolic rate and
rampant nitrogen losses are consistent sequelae to major
trauma, particularly acute traumatic brain injury and
acute spinal cord injury (ASCI). A well-documented
hypermetabolic, catabolic injury cascade is initiated
immediately after central nervous system injury that
results in depletion of whole-body energy stores, loss of
lean muscle mass, reduced protein synthesis, and
ultimately, loss of gastrointestinal mucosal integrity and
compromise of immune competence. Severely brain-
injured and spinal cord injury (SCI) patients, therefore,
are at risk for prolonged nitrogen losses and advanced
malnutrition within 2 to 3 weeks after injury with
resultant increased susceptibility for infection, impaired
wound healing and difficulty in weaning from mechanical
ventilation.
The basic aim is to provide an optimal environment
for survival and repair of the damaged neuronal pool.
While short periods of starvation over hours or a day or
two may not be detrimental to most of the patients, the
difficulty of maintaining or increasing lean body mass
during critical illness is too great to delay instituting
artificial feeding long, even if the patient is well nourished
at the outset. The route should be enteral when possible.
Enteral feeds tend to be more complete than parenteral
Indian Journal of Neurotrauma (IJNT), Vol. 3, No. 2, 2006
feeds, are much less expensive and may minimise
intestinal mucosal atrophy, bacterial translocation and
endotoxinemia. Lack of bowel sounds alone is not a
reason to withhold enteral feeding and does not correlate
well with rates of gastric emptying.
Calories/Energy Needs
Overall caloric assessment in TBI patients is determined
by the Harris-Benedict equation, which provides a
satisfactory method to develop an initial estimate of basal
energy expenditure (BEE) based on weight and gender.
BEE(men)= 66.47 + 13.75W + 5.00H – 6.76A
BEE(women)= 655.10 + 9.56W + 1.85H – 4.68A
(W=weight in kg, H=height in cm, A=age in years)
Indirect calorimetry
Whenver possible, because indirect calorimetry
quantifies oxygen conumption and CO2 production as
determinants of energy use, which helps prevent under-
and over-feeding of patients. Short-term second hourly
indirect calorimetry reliably reflects 24-hour metabolic
utilization in clinically stable, sedated, ventilated patients.
Metabolic rate of patients with temperature fluctuations
may vary as much as 25% in the course of a day and
benefit from ongoing measurement. Calories can be
estimated at 35 to 40 kcal/kg/d to account for the large
increase in metabolic rate. Monitoring for hyperglycemia
is necessary to prevent adverse effects.
Protein needs in TBI patients
Protein requirement in TBI patients is estimated at 1.5
– 2.2 g/kg of body weight. Non-supplemented TBI
patients can lose up to 10% of lean body mass in a week,
up to 25% in two weeks and 30-40% in three weeks.
Negative nitrogen balance is determined by estimating
nitrogen losses, which can be as high as 30 g/day in
acute TBI patients. Negative nitrogen balance usually
persists for 2-3 weeks, regardless of the protein provided,
with a peak at about 10 days post-injury. The amount of
nitrogen loss correlates with serum levels of epinephrine,
norepinephrine, glucagons and hormones associated with
hypermetabolism. The hypermetabolic response and the
release of hormones correlated with the severity of injury.
Immobility may potentiate nitrogen losses, as does
steroid administration during the first six days post-injury.
Provisionof more protein than 1.5 to 2.2 mg/kg of body
weight results in heightened nitrogen excretion.
 Intensive Care Management of the Head Injured Patient
Amino acid patterns in TBI patients
There are large fluxes in alanine and glutamine, which
demonstrate skeletal muscle protein release lower levels
of leucine, isoleucine and valine and high levels of
phenylalanine.
Vitamins, mineral and fluid patterns in TBI
patients
There are decreased plasma levels of many B vitamins
and vitamin C, increased urinary zinc excretion/low
serum zinc levels and salt wasting in some patients.
Phosphorus, potassium and magnesium decreases in
some patients with the initiation of feeding.
Supplementation with vitamins and minerals is
recommended if the nutrition regimen falls below the
recommended dietary allowances (RDA).
Lipids
It is essential to provide a lipid source with 50-70%
medium chain triglycerides and an omega-3 ratio of
2:1 to 8:1 27. A minimum of 10% of the caloric
requirement must be in the form of lipids to prevent
essential fatty acid deficiency. Care should be taken to
ensure that excessive lipids are not administered, as it
can cause immunosuppression. If triglyceride levels
become more than 300 mg, then the lipids will have to
be reduced.
The initial caloric estimate is adjusted based on the
qualitative assessment of factors altering the need. Head
trauma patients have a 1.5 to two-fold increase in the
metabolic needs associated with a massive nitrogen loss.
There is debate about optimal inputs of nitrogen in the
context of the short- to medium-term artificial feeding
in trauma, sepsis and critical illness, and no outcome
trials allow resolution of the argument. Emphasis has
been traditionally placed on the maintenance of zero or
positive nitrogen balance and numerous studies examine
optimal inputs under various clinical conditions. Some
show improving balance with increasing input to levels
of 364 mg N/kg per day28 in depleted patients or 400 mg
N/kg per day in patients who were described as well
nourished or minimally undernourished27. Patients with
GCS of 4-5 have the highest energy expenditure. Patients
who are brain dead or who are receiving sedatives,
barbiturates or musculoskeletal blocking agents have an
average of 14% lower energy expenditure.
Feeding should be started as early as possible as non
85
feeding in head injured patient has been shown to
increase the mortality 30. Enteral feeding following
neurosurgical procedures was associated with accelerated
normalized nutritional status and improved substrate
tolerance31. Enteral nutrition is equivalent or superior
to parenteral nutrition in patients with head injuries.
Early enteral feeding has established benefits over feeding
later in course of hospitalization. Patients with TBI are
candidates for parenteral nutrition when they cannot
tolerate enteral nutrition because of ileus or a high risk
of aspiration. The recommendation at present is to
provide 30-35Kcal/kg: 60% of the caloric requirement
is with carbohydrates, 15-20% as proteins at 1.5 -2gms
of proteins /kg and the remainder as fats. The
complications of enteral therapy are overfeeding,
azotemia, fat overload syndrome, hypertriglyceridemia,
hepatic steatosis, hypercapnia, metabolic acidosis,
diarrhea, refeeding syndrome, central line
complications32.
Refeeding syndrome
Initiation of nutritional support to patients with severely
depleted nutrient stores is associated with clinically shifts
in phosphorus, magnesium and potassium from
extracellular to intracellular space 33 . Additionally,
starvation causes a catabolic release of intracellular
phosphate which is excreted in urine. The total body
stores of intracellular electrolytes are slowly depleted.
Refeeding and the early stages of over feeding are both
demanding on the cardiovascular system. Patients who
are chronically malnourished have depletion in cardiac
muscle, and are unable to meet circulatory demands
imposed by aggressive nutritional support. Approaches
to prevention of refeeding syndrome are to slowly
introduce nutritional support and at the same time allow
for the addition of vitamins, zinc and other minerals.
Refeeding syndrome carries considerable morbidity and
mortality34.
Guideline for Closed Head Injury patients :
Fever and sepsis increases calorie requirement by 7.2%
for every degree Fahrenheit above normal temperature.
Seizures and extensor posturing increases calorie
requierement by 20-30% to a maximum of 3500-4000
calories (total). Non-sedated coma increases BEE by
140%, while pentobarbital coma increases BEE by 100-
120%. Standard TBI range is 140-200% BEE. Calories
are therefore supplied at 40-70% above basal needs, with
30-40% as lipids to minimize hyperglycemia based in
Indian Journal of Neurotrauma (IJNT), Vol. 3, No. 2, 2006
86
part on the patient’s GCS and MREE (measured resting
energy expenditure).
Deep Vein Thrombosis Prophylaxis
Thromboembolic phenomena continue to be a significant
cause of morbidity and mortality in neurosurgical
patients. Deep vein thrombosis formation is encouraged
by a number of clinical situations. A number of
predisposing factors have been identified which can
promote deep vein thrombosis such as recent surgery,
malignancy, immobilization, trauma, acute stroke,
pregnancy, antithrombin , protein C and protein S
deficiency . Many of these factors coexist in
neurosurgical patients, which puts them in the high risk
category for the development of deep vein thrombosis35.
The primary concern is the potential for pulmonary
embolism.
Methods to prevent DVT include the use of
intermittent pneumatic compression, elastic compression
stockings, early ambulation, physical therapy and low
dose anticoagulation. These methods have been found
to effectively prevent DVT. In neurologic or
neurosurgical patients there is concern that
anticoagulation may predispose these patients to
intracranial hemorrhage though there is no evidence to
support this36. Recently perioperative minidose heparin
has been found to be safe in patients undergoing
craniotomy for supratentorial tumors37.
Gastric Ulcer Prophylaxis
Stress ulcers occur frequently in intensive care unit (ICU)
patients who have intracranial disease. After major
physiological stress such as brain injury, endoscopic
evidence of mucosal lesions can appear within 24 hours,
and 17% of these erosions can progress to clinically
significant bleeding38. Gastrointestinal (GI) hemorrhage
has been associated with mortality rates of up to 50%
39,40,41,42
. The pathogenesis of stress ulcers may not be
completely understood, but gastric acid and pepsin
appear to play significant roles.
Sedation and Analgesia
Sedation is a fundamental element in the intensive care
unit, but maybe problematic in the neuroICU as it could
make assessment difficult. The primary aim of the
neurointensive care is to maintain cerebral perfusion
pressure, reduce intracranial pressure and cerebral
metabolic requirement. There are different
pharmacologic agents available each with advantages and
Indian Journal of Neurotrauma (IJNT), Vol. 3, No. 2, 2006
V. Bhadri Narayan
disadvantages. The rationale for sedation are multifaceted
include analgesia, anxiety, agitation control, reduction
of the stress response and adaptation to ventilatory
support43.
Problems of under sedation are increased stress
symptoms such as hypermetabolism, sodium and water
retention, lipolysis, cardiovascular symptoms like
tachycardia, increased blood pressure, increased oxygen
consumption, altered respiratory rates and changes in
coagulation parameters. On the other hand over-sedation
also carries risks like increased venous thrombosis,
decreased blood pressure, increased stay in the ICU and
prolonged use may result in withdrawal symptoms44.
There are a number of agents available for use in
clinical practice .The most commonly used drugs are
morphine, pethidine, fentanyl, midazolam, propofol,
lorezapam and recently the µ2 agonist dexmedetomidine
has been found to be a very useful agent and may play a
major role in the management of patients in the future.
Intracranial Pressure and Cerebral perfusion
pressure
The intracranial pressure is elevated in 50-75 % of
patients with severe head injury who remain comatose
after resuscitation. ICP (Intracranial pressure) is more
than 20 mm Hg during the first 24 hours and generally
comes down within 48 hours. In the severely brain
injured patient, signs of increased ICP include a change
or asymmetry in pupillary reactivity to light or a new
eccentricity in one of the pupils. A dilated unreactive
pupil and Cushings triad of hypertension, bradycardia,
and irregular respirations are late signs45. This incidence
of elevated ICP approaches 60% if at least two of the
following risk factors are present: (1) age over 40 years;
(2) SBP less than or equal to 90 mmHg; and (3) unilateral
or bilateral motor posturing, either flexor or extensor46.
It is therefore recommended that ICP monitoring be
instituted for all severe TBI patients with abnormality
on head CT and for all severely brain injured patients
with a normal head CT but two or more of the risk
factors mentioned. Normal ICP in humans is between
0 and 10 mmHg. Eisenberg et al noted that patients
whose ICP could be controlled with pentobarbital had a
better outcome than those in whom ICP could not be
controlled; 92% of those who responded to ICP reduction
therapies survived, whereas 83% of those who did not
respond died47. A widely accepted treatment threshold
is an ICP above 20 mmHg sustained for over 10 minutes.
 Intensive Care Management of the Head Injured Patient 87

Studies have shown that as the ICP increases the mortality
also increases48.
The major cause of raised ICP, apart from hematomas
is brain swelling. The factors responsible for post-
traumatic brain swelling are not clear, however there is
convincing evidence for both cytotoxic and ischemic -
hypoxic influences. The goal will be to control ICP,
provide adequate cerebral perfusion pressure (CPP),
oxygenation and to prevent herniation. The CPP should
be maintained greater than 70mm Hg. Treatment should
be based on knowledge of regional cerebral blood flow
(rCBF) metabolism and function. ICP and CPP can be
measured easily and provide the best indirect
measurements of tissue perfusion. Advance monitoring
technology like Jugular venous oxygen saturation (SjVO2),
Brain tissue oxygen tension (PbtO 2), Transcranial
Doppler (TCD), Near Infrared Spectroscopy (NIRS),
evoked potentials and intracerebral microdialysis
provides the information on both regional and global
cerebral blood and metabolism and will probably guide
therapy of the head injured patient in the future. Table
1 shows cerebral and systemic characteristics of various
pharmacological agents used in head injury for cerebral
protection.
Cardiovascular Management
The major goals in the management of the patient with
head injuries is to prevent and treat hypotension,
hypertension, arrhythmias, acute myocardial infarction
and pulmonary edema. Hypotension is one of the most
important factors and is an independent predictor of
outcome. A single episode of hypotension increases
mortality two fold49,50. The maintenance of cerebral
perfusion pressure (CPP) is crucial in the prevention of
cerebral ischemia. There is a correlation between CPP
and outcome that is stronger than that of
ICP and outcome. A CPP of less than 60 mmHg for
over 33% of the time is strongly associated with death,
whereas a CPP of greater than 90 mmHg is associated
with a 75% incidence of good outcome51. Maintaining
a CPP of greater than 70 mmHg, even with induced
hypertension, is associated with significant
improvements in the morbidity, mortality, and outcome
of severe TBI patients when compared with management
using ICP control alone52.
Pressor therapy is begun with the presumption that
any deficits in intravascular volume have been adequately
corrected. Agents that have been used successfully
include norepinephrine (4 mg/250 mL 0.9% NaCl) to a
maximum dose of 0.4 micrograms/kg per minute and
phenylephrine (40 to 80 mg/250 mL 0.9% NaCl) to a
maximum dose of 4.0 µg/kg per minute. Dopamine (400
mg in 250 mL of 0.9% NaCl), at 1.5 to 3.0 µg/kg per
minute, should be added for renal protection. The
minimum vasopressor dose necessary to augment CPP
to an efficacious level should be used, keeping in mind

Table 1: Cerebral and systemic characteristics of pharmacological agents

Propofol Midazolam Lorazepam Fentanyl Remifentanil

Rapid onset +++ +++ + +++ +++

Fast recovery +++ ++ + ++ +++
Easily titrated +++ ++ + ++ +++
ICP reduction ↓↓ ↓ ↓ ↓/↔ ↓/↔
CBF reduction ↓↓ ↓↓ ↓ ↔ ↔
CMRO2 reduction ↓↓ ↓ ↓ ↓ ↓
MAP ↓↓ ↓ ↓ ↓ ↓

↔ no clear effect , ↓ modest decrease , ↓↓ pronounced decrease , +++ very favorable , ++ favorable +
not favorable , CBF –cerebral blood flow , CMRO2 cerebral metabolic rate of oxygen , ICP intracranial
pressure , MAP mean arterial pressure

Indian Journal of Neurotrauma (IJNT), Vol. 3, No. 2, 2006

88 V. Bhadri Narayan
that a supranormal CPP (e.g., 80 to 90 mmHg) may be
necessary. At the same time, a CPP greater than 113
mmHg may result in a reversal of therapeutic effect53,54.
Hypertension
Blood pressure management in a important issue in the
neurointensive care unit. Concern arises that systemic
hypertension may exacerbate cerebral edema, intracranial
hemorrhage and have deleterious cardiopulmonary
effects such as pulmonary edema and myocardial
ischemia. Conversely a decrease in blood pressure may
lead to insufficient perfusion and it has been well
documented that the drop in pressure may be a
forerunner for the genesis of plateau waves. Neurogenic
hypertension is common following head injury and
appears to be sympathetically mediated and is directly
proportional to the catecholamine release. Increased ICP,
brain stem compression and medullary ischemia may
be associated with severe hypertension 55. When or
whether to treat hypertension is controversial. An
elevated systemic arterial pressure may be an intrinsic
compensatory mechanism for impaired cerebrovascular
autoregulation and low perfusion pressure. Lowering
arterial pressure to normal levels may lead to ischemia,
cellular hypoxia and cerebral edema56.
Blood pressure should be treated when the pressure
exceeds 180/110 mm Hg or a mean greater than 150
mm Hg. The choice of antihypertensive agent is not
straightforward. Therapeutic urgency, brain protective
effect and the potential to increase ICP are all important
considerations in the choice of the drug. In the face of
an elevated ICP beta blockers are the preferred drugs57.
Arrhythmias
A wide range of cardiac arrhythmias may occur as a
result of centrally mediated sympathetic and vagal
discharge. Tachyarrhythmias are predominantly
supraventricular and include atrial fibrillation, flutter and
paroxysmal atrial tachycardia. Ventricular
tachyarrhythmias are uncommon. Nodal and sinus
bradycardia are associated with sustained intracranial
hypertension and rarely require treatment.
Myocardial Injury
Myocardial injury in the absence of coronary artery
disease is seen in upto 50% of head injured patients.
The changes observed are similar to those found after
myocardial infarction, subarachnoid haemorrhage and
prolonged catecholamine therapy. Inhibition of
Indian Journal of Neurotrauma (IJNT), Vol. 3, No. 2, 2006
catecholamine release with adequate sedation and beta
blockers maybe able to prevent or ameliorate myocardial
injury58. It has been suggested that electrocardiographic
changes seen following head injury may indicate a more
severe head injury and thus carry a higher mortality59.
Neurogenic Pulmonary Oedema
This is one of the most dramatic sympathetically
mediated processes. It follows a profound sympathetic
discharge which leads to a redistribution of blood from
the systemic to the pulmonary vasculature resulting in a
rapid rise in pulmonary pressures60. ther mechanisms
that may be involved are neurogenic depletion of
pulmonary surfactant61. Typically neurogenic pulmonary
oedema is self limiting. Treatment is primarily supportive
and is aimed at ensuring oxygenation with mechanical
ventilation and positive end expiratory pressure.
Respiratory Care
The goal of mechanical ventilation in patients with brain
injury is to optimize blood gas exchange and minimizing
the intrathoracic pressure. The goals to achieve are a:
PaO2 >90 mm Hg and PaCO2 between 35 and 45 mm
Hg. How these goals can be achieved is still matter of
controversy. The use of normal tidal volume (VT) and
low positive end expiratory pressure (PEEP) level is
suggested as the “gold standard” ventilatory strategy after
acute brain injury. This accomplishes cerebral
hemodynamic requirements: mild hyperventilation to
control intracranial pressure (ICP), minimizing
intrathoracic pressure to reduce interference with
cerebral venous drainage. On the other hand, there is
evidence that the use of high VT with low level of PEEP
can induce and exacerbate acute lung injury62.63. Therefore
the ventilatory management of patients with acute severe
brain injury remains a challenge for clinicians.
Airway Management
Patients with acute severe brain injury are unable to
protect their airways and should therefore be intubated.
The technique of intubating patients will depend on
cervical spine (C-spine) clearance. It is imperative that
C-spine injury is ruled out as early as possible. Those
involved in managing the airway of patients with
confirmed or potential C-spine injury must be aware of
the advantages and disadvantages of the possible
techniques so that the safest one is chosen for the patient.
Patients with injuries above the calvicles are at increased
risk, and this risk is increased 4-fold64, if there is clinically
 Intensive Care Management of the Head Injured Patient
significant head injury (GCS<9). Cervical spine injury
is often occult, and present in upto 20% of patients with
head injuries and hence secondary injury to the spinal
cord must be avoided. Patients with acute severe brain
injury are unable to protect their airways and should
therefore be intubated. The techniaue of intubating
patients will depend on C-spine clearance. It is prudent
to have C-spine clearance to prevent untoward incidents.
C-spine clearance in a conscious individual is dependable
based on clinical signs described. The five criteria are
no posterior cervical midline tenderness, alert patient,
no focal neurological deficits, no intoxication and no
painful distracting injuries 65. Criteria for C-spine
clearance are more controversial in the unconscious
patient. In the unconscious patient the recommendation
is to have three views of C-spine radiograph: anterior-
posterior, lateral and open mouth views to rule out C-
spine injury. If C-spine is not cleared, intubation is
attempted as if a C-spine injury is present. Direct
laryngoscopy has been shown to disturb the cervical spine
both in anesthetized volunteers and in cadavers66,67.
Manual axial in-line neck stabilization reduces this
movement by 60%. Atlantooccipital extension is
necessary to bring the vocal cords within line-of sight of
the mouth. Thus, patients with unstable C1 or C2 injuries
might be at more risk from this technique. The
commonest site of fractures is at C2, and dislocations
occur commonly at C5/C6 and C6/C7.
Patients requiring tracheal intubation should be
anesthetized unless they are very cooperative. In the
obtunded head-injured patient, anesthesia is vital to
prevent pressor responses to intubation which increases
intracranial pressure. The ideal intubation agent probably
does not exist, and is dependent on individual experience.
Thiopentone is very effective and is the standard for
rapid sequence induction. Propofol is not recommended
for trauma because of the potential for hypotension and
should be used with caution, though its ability to provide
total intravenous analgesia with good control over the
depth of anesthesia may be very valuable. Etomidate has
been reported to produce less cardiovascular depression
than other intravenous induction agents, but the potential
adrenal and immunological suppression caused by even
one bolus of etomidate puts a question mark on its use
in these patients. Ketamine is very under-used drug which
maintains cardiovascular stability better than any of the
other intravenous drugs. Its use is currently
contraindicated in patients at risk from raised intracranial
pressure as it is known to increase cerebral blood flow
89
and ICP in head-injured patients. Evidence is
accumulating that this may not be the case, especially in
hypotensive patients. Ketamine is a non-competetive
NMDA receptor antagonist and has been shown to have
neuroprotective effects.
Failed Intubation
Failed or difficult intubation is always a problem. It is
important to preoxygenate patients before attempted
intubation to avoid desaturation while making repeated
attempts at intubation. Alternative methods of securing
the airway should be instituted as soon as a problem is
recognized. The methods that are available to secure
the airway are the laryngeal mask airway (LMA),
combitube, cricothyrotomy and emergency
tracheostomy if trained hands are available.
Two aspects of airway management that are prominent
in the ICU are the decisions regarding oral versus nasal
intubation and timing of tracheostomy. Orotracheal
intubation is the fastest and surest method of intubating
the trachea. Oral intubation is preferred particularly if
basilar skull fractures are present. Nasotracheal
intubation is contraindicated in patients with potential
base of skull fractures or unstable mid-face injuries. In
addition, it may produce hemorrhage in the airway,
making other airway manipulations difficult or
impossible. Risk factors associated with radiologic
maxillary sinusitis and the incidence of infection among
patients who are critically ill and mechanically ventilated
have been determined 68. The four independent risk
factors identified were nasal placement of endotracheal
tube, nasal placement of the gastric tube, duration of
endotracheal tube, and duration of nasogastric tube
placement. The incidence of maxillary sinus
abnormalities is upto 75% in the critically ill patients
and oral intubation decreases this complication by 50%.
Acute severely brain injured patients require early
endotracheal intubation and may need prolonged
mechanical ventilation in the ICU. The timing of
tracheostomy is still controversial. Some studies suggest
that prolonged endotracheal intubation results in
increased glottic and subglottic stenosis, others suggest
that tracheostomy can wait upto five weeks. An ideal
approach would be to assess the patient at the end of
seven days and if the patient is likely to need mechanical
ventilation further, or have a poor GCS then it is advisable
to do a tracheostomy to optimize airway management
and to prevent post-extubation complications69.
Indian Journal of Neurotrauma (IJNT), Vol. 3, No. 2, 2006
90 V. Bhadri Narayan

Infection Control blood volume in SIADH and a decreased volume in

CSWS. The other difference is a high ADH level in
Fever is common following head injury and is
SIADH and a normal level in CSWS.
documented to worsen outcome70. In addition fever can
raise metabolic requirements, and being a potent Hypernatremia
vasodilator can increase intracranial pressure. Invasive
Diabetes insipidus (DI) is frequent occurrence in the
monitoring in patients with head injuries can predispose
ICU and results from decreased levels of ADH and an
these patients to infection, and should be investigated
inability to concentrate urine. The free water loss causes
with appropriate cultures and antibiotics. The common
hypovolemic hypernatremia. DI is managed by correcting
sources of infection will be from intravascular lines,
the free water deficit with non salt containing solutions
urinary catheters, chest, wound infection and meningitis.
and controlling urinary volume by the administration of
The efficacy of prophylactic antibiotics in patients with
pitressin (vasopressin) 5-10 units subcutaneously ,
traumatic cerebrospinal fistulas is controversial.
desmopressin acetate 2-4 µg intravenously or as a nasal
Antibiotics are recommended only when signs or
spray 2µg73.
symptoms of meningitis develop. Nosocomial infections
are common in neurological and neurosurgical patients Hyperglycemia
with pneumonia, catheter related infection and
meningitis contributing significantly to morbidity and Hyperglycemia has been associated with a poor
mortality. Prevention of infection plays an important role neurological outcome in patients with head injuries74,75.
in reduction of nosocomial infections. The approaches Neurologic damage can be exacerbated when associated
recommended are hand-washing, prevention of cross with secondary insults. TBI is associated with stress
contamination, sterilization and disinfection of medical response that includes hyperglycemia and has been shown
equipment and appropriate use of antibiotics to prevent to worsen neurological outcome during cerebral ischemia
emergence of resistant organisms71. and hypoxia. Patients with severe head injury have
significantly higher serum glucose levels than those with
Fluid and Electrolytes moderate injury, and those with significantly higher
glucose levels have an unfavorable outcome. Among the
Electrolyte abnormalities are common in patients with
patients with more severe head injury, a glucose level
head injuries and occur at least once during
greater than 200 mg/dl was associated with a worse
hospitalization72. The most common abnormalities seen
outcome. A significant relationship was found between
are hyponatremia, hypernatremia and hypokalemia.
postoperative glucose levels, pupillary reaction and
Hyperglycemia is also common and is frequently seen
maximum intracranial pressure during the first 24 hours,
and is part of the stress response to injury and should be
and postoperative glucose level was an independent
controlled with the use of insulin and should be kept
predictor of outcome76. Patients with a GCS of 8 or less
below 150mg/dl. Meticulous attention should be paid
had significantly higher serum glucose levels than patients
to fluid management and normal balance established.
with GCS of 12 to 15. Patients who subsequently
Hyponatremia syndromes remained in vegetative state or died had significantly
higher glucose levels both on admission and
The differential diagnosis of hyponatremia in head
postoperatively than patients who had good outcome or
injured patients consists of two entities – syndrome of
moderate disability. Severely head-injured patients
inappropriate antidiuretic hormone secretion (SIADH)
frequently develop hyperglycemia and the elevated serum
and cerebral salt wasting syndrome (CSWS). The
glucose levels above 200 mg/dl may aggravate ischemic
diagnosis of SIADH requires the following criteria:
insults and worsen neurological outcome in these patients.
serum sodium less than 135 mEq/L, serum osmolarity
Blood glucose is associated with brain tissue acidosis in
less than 289 mOsm/L, urine osmolarity greater than
severe TBI. Insulin therapy significantly reduced the
serum, specific gravity exceeding 1010 and an
blood glucose levels but the brain tissue pH did not change
inappropriately elevated urinary sodium. In CSWS,
much, though there was a suggestion of improvement if
serum sodium should be less than 135mEq/L, osmolarity
the change in blood glucose was large77.
less than 280 mOsm/L, urinary sodium more than 25
mEq, specific gravity exceeding 1010 .The volume status Intensive insulin therapy titrated to maintain blood
is the critical clinical distinction, there being an increased glucose level between 4.4 and 6.1 mmol/l during intensive

Indian Journal of Neurotrauma (IJNT), Vol. 3, No. 2, 2006

 Intensive Care Management of the Head Injured Patient
care unit stay has been shown to significantly decrease
mortality, septic morbidity, sepsis-related organ failure,
transfusion requirements and polyneuropathies.
Hyperglycemia on admission is related to susceptibility
to infections and worse outcomes following myocardial
and cerebral ischemic events. Additional beneficial effects
of insulin, unrelated to the control of glycemia, have
also been reported and need to elucidated further78.
Transient hyperglycemia affected cerebral energy
metabolism at blood glucose concentration above 15
mmol/l has been shown by a moderate increase in
interstitial lactate level. Moderate hyperglycemia did not
change intracerebral levels of lactate, pyruvate, glutamate,
glycerol, or lactate/pyruvate ratio. Pronounced cerebral
lactic acidosis and a moderate increase in interstitial
glycerol concentration indicating cell membrane
degradation was observed in long-lasting hyperglycemia79.
MONITORING
Neurological monitoring in the neurointensive care unit
is centred around two important secondary injury
processes, elevated intracranial pressure and cerebral
ischemia. The modalities that are available in a well
established neurocentre are monitoring cerebral
hemodynamics with Transcranial Doppler
Ultrasonography, Laser Doppler Flowmetry and Xenon
enhanced computed tomography80. Cerebral oxygenation
can be monitored by Jugular venous oxygen saturation,
Near Infrared Spectroscopy and brain tissue oxygen
monitoring and neuronal function can be monitored by
electroencephalography and evoked potentials 81-86.
Intracranial pressure is monitored with an
intraventricular catheter which will guide therapy.
Intracerebral microdialysis is a very useful monitor which
provides information on cerebral metabolism87.
CONCLUSION
Head injuries are a major cause of morbidity and
mortality especially in the young and is a serious
socioeconomic problem. The aim should be to optimize
the management early so as to enable a favourable
outcome. Intensive care treatment should be managed
by monitoring these patients to prevent secondary brain
damage. A well organized secondary brain damage
protocol should be established, with the help of the state
of the art monitoring of cerebral function, so that patients
have a favourable outcome. Dexanabinol, hypertonic
saline, decompressive craniectomy and hypothermia are
91
four therapies that target multiple mechanisms of cerebral
ischemia , neurotoxic cascades , inflammation and brain
swelling and will play a significant role in the future .
REFERENCES
1. Eyester E, Watts C. An update of the National Head and
Spinal Cord Injury Prevention Program of the American
Association of Neurological Surgeons and the Congress of
Neurological Surgeons.
Clin Neurosurg 1992; 38:252-60.
2. Avolio AEC, Ramsey FL, Neuwelt EA. Evaluation of a program
to prevent head and spinal cord injuries: a comparison between
middle and high schools.
Neurosurgery 1992:31:557-562.
3. Watson GS, Zador PL, Wilks A. The repeal of helmet use
laws and increased mortality in the United States 1975-1978.
Am J Public Health 1980; 70: 529-85.
4. Thompson RS, Rivara FP, Thompson DC. A case-control
study of the effectiveness of bicycle helmets.
N Engl J Med 1989; 320: 1361-7.
5. Kaufman HH, Timberlake G, Voelker J, Pait TG. Medical
complications of head injury.
Med Clin N Amer 1993; 77: 43-60.
6. Demling R, Riessen R. Pulmonary dysfunction after cerebral
injury.
Crit Care Med 1990; 18: 768-74.
7. Ott L, McClain CJ, Gillespie M, Young B. Cytokines and
metabolic dysfunction after severe head injury.
J Neurotrauma 1994; 11: 447-72.
8. Goodnight SH, Kenoyer G, Rapaport SI, Patch MJ, Lee JA,
Kurze T. Defibrination after brain tissue destruction.
N Engl J Med 1974; 290:1043-7.
9. Olson JD, Kaufman HH, Moake J et al. The incidence and
significance of hemostatic abnormalities in patients with head
injuries.
Neurosurgery 1989; 24:825-32.
10. Hulka F, Mullins RJ, Frank EH. Blunt brain injury activates
the coagulation process.
Arch Surg 1996; 131:923-8.
11. Stein SC, Young GS, Talucci RC, Greenbaum BH, Ross SE.
Delayed brain injury after head trauma: significance of
coagulopathy.
Neurosurgery 1992; 30:160-165.
12. Teasdale GM. Head Injury.
J Neurol Neurosurg Psychiat 1995; 58:526-39.
13. King BS, Gupta R, Narayan RK. The early assessment and
intensive care unit management of patients with severe
traumatic brain and spinal cord injuries.
Surg Clin N Amer 2000; 80:855-71.
Indian Journal of Neurotrauma (IJNT), Vol. 3, No. 2, 2006
92 V. Bhadri Narayan
14. Fitzpatrick MO, Maxwell WL, Graham DI. The role of the
axolemma in the initiation of traumatically induced axonal
injury.
J Neurol Neurosurg Psychiat 1998; 64:285-7.
15. Letarte PB. Neurotrauma care in the new millennium.
Surg Clin N Amer 1999; 79:1449-71.
16. Povlishock JT. Pathobiology of traumatically induced axonal
injury in animals and man.
Ann Emerg Med 1993; 22:980-7.
17. Hovda DA, Lee SM, Smith ML, et al. The neurochemical
and metabolic cascade following brain injury: moving from
animal models to man.
J Neurotrauma 1995; 12:903-6.
18. Gennarelli TA.The pathobiology of traumatic brain injury.
Neuroscientist 1997; 3:73-81.
19. Zink BJ. Traumatic brain injury outcome: concepts for
emergency care.
Ann Emerg Med 2001; 37:318-32.
20. Marik P, Chen K, Varon J, Fromm R, Sternbach GL.
Management of increased intracranial pressure: a review for
clinicians.
J Emerg Med 1999; 17:711-9.
21. Jaggi JL, Obrist WD, Gennarelli TA, Langfitt TW.Relationship
of early cerebral blood flow and metabolism to outcome in
acute head injury.
J Neurosurg 1990;7 2:176-82.
22. Marmarou A, Anderson RL, Ward JD, et al. Impact on ICP
instability and hypotension on outcome in patients with severe
head trauma.
J Neurosurg 1991; 75(suppl):S59-S66.
23. Pazzaglia P, Frank G, Frank F, Gaist G. Clinical course and
prognosis of acute post traumatic coma.
J Neurol Neurosurg Psychiat 1975; 38:149-54.
24. Gadisseux P, Ward JD : Nutritional support of head injured
patients . In Becker DP , Gudeman SK(eds) : Textbook of
Head Injury. Philadelphia , Saunders , 1989; 241-54.
25. Van Way CW III. Nutritional support in the injured patient.
Surg Clin N Amer 1991; 71:537-48.
26. Wilmore DW. Catabolic illness. Strategies for enhancing
recovery.
N Engl J Med 1991; 325:695-702.
27. Twayman D. Nutritonal management of the critically ill
neurologic patient.
Crit Care Clin 1997; 13:39-49.
28. Shaw SN, Elwyn DH, Askenazi J et al. Effects of increasing
nitrogen intake on nitrogen balance and energy expenditure
in nutritionally depleted adult patients receiving parenteral
nutrition.
Am J Clin Nutr 1983; 37: 930-40.
29. Cerra F, Hirsch J, Mullen K et al.The effect of stress level,
Indian Journal of Neurotrauma (IJNT), Vol. 3, No. 2, 2006
amino acid formula, and nitrogen dose on nitrogen retention
in traumatic and septic stress.
Ann Surg 1987; 205: 282-7.
30. Rapp RP, Young B et.al .The favourable effect of early
parenteral feeding on survival in head injured patients .
J Neurosurg 1983; 58: 906-12.
31. Suchner U, Senftleben U et.al Enteral versus parenteral
nutrition :Effects on gastrointestinal function and metabolism.
Nutrition 1996; 12: 13-22.
32. D S Slone. Nutritional support of the critically ill and injured
patient.
Crit Care Clin 2004; 20:135-57.
33. Brooks MJ, Melnik G. The refeeding syndrome: an approach
to understanding its complications and preventing its
occurrence.
Pharmacotherapy 1995; 15:713-26.
34. Weinster RL, Krumdieck CL. Death resulting from
overzealous total parenteral nutrition: The refeeding syndrome
revisited.
Am J Clin Nutr 1981; 34:393-9.
35. DeGeorgia MA et.al .Prophylaxis of deep vein thrombosis .In
Hacke W et.al (eds): Neurocritical Care.Berlin , Springer-
Verlag, 1994; 162-6.
36. Powers SK , Edwards MSB .Prophylaxis of thromboembolism
in the neurosurgical patient : A review.
Neurosurgery 1982; 10: 509.
37. Shlomi Constantini, Andy Kanner, Adi Freidmen, et al. Safety
of perioperative minidose heparin in patients undergoing brain
tumor surgery : a prospective randomized double blind study.
J Neurosurg 2001;94: 918-21.
38. Kamada T, Fusamoto H, Kawano S, Noguchi M, Hiramatsu
K, Masuzawa M, Abe H, Fujii C, Sugimoto T: Gastrointestinal
bleeding following head injury: A clinical study of 433 cases.
J Trauma 1977; 17: 44-7.
39. Peura DA, Johnson LF: Cimetidine for prevention and
treatment of gastroduodenal mucosal lesions in patients in an
intensive care unit.
Ann Intern Med 1985; 103:173-7.
40. Pinilla JC, Oleniuk FH, Reed D, Malik B, Laverty WH:
Does antacid prophylaxis prevent upper gastrointestinal
bleeding in critically ill patients?
Crit Care Med 1985; 13:646-50.
41. Schuster DP, Rowley H, Feinstein S, McGue MK, Zuckerman
GR: Prospective evaluation of the risk of upper gastrointestinal
bleeding after admission to a medical intensive care unit.
Am J Med 1984; 76:623-30.
42. Shuman RB, Schuster DP, Zuckerman GR: Prophylactic
therapy for stress ulcer bleeding: A reappraisal.
Ann Intern Med 1987; 106:562-7.
43. Giuseppe Citerio , Manuela Cormia . Sedation in
 Intensive Care Management of the Head Injured Patient
neurointensive care: advances in understanding and practice .
Curr Opin Crit Care 2003; 9: 120-6.
44. Peter H Tonner , Norbert Weiler , Andrea Paris et.al . Sedation
and analgesia in the ICU.
Curr Opin Anaesthesiol 2003; 16:113-21.
45. Marik P, Chen K, Varon J, Fromm R, Sternbach GL.
Management of increased intracranial pressure: a review for
clinicians.
J Emerg Med 1999;17:711-9.
46. Narayan RK, Kishore PRS, Becker DP, et al. Intracranial
pressure: to monitor or not to monitor?
J Neurosurg 1982;56:650-9.
47. Eisenberg HM, Frankowski RF, Constant RF et.al High dose
barbiturates control elevated intracranial pressure in severely
head injured patients.
J Neurosurg 1988;69; 15-23.
48. Miller JD. Head injury and brain ischaemia – Implications for
therapy.
Br J Anaesth 1985; 57;120-9.
49. Chestnut RM, Marshall LF, Klauber MR, et al. The role of
secondary brain injury in determining outcome from severe
head injury.
J Trauma 1993;34:216-22.
50. Fearnside M R, Cook RJ et.al. The Westmead Head Injury
outcome in severe head injury . A comparative analysis of pre-
hospital, clinical and CT variables.
Br J Neurosurg 1993; 7 : 267-79.
51. Changaris DG, McGraw CP, Richardson JD, Garretson HD,
Arpin EJ, Shields CB. Correlation of cerebral perfusion pressure
and Glasgow Coma Scale to outcome.
J Trauma 1987;27:1007-12.
52. Rosner MJ, Rosner SD, Johnson AH. Cerebral perfusion
pressure: management protocol and clinical results.
J Neurosurg 1995;83:949-62.
53. Rosner MJ, Coley I. Cerebral perfusion pressure: a
hemodynamic mechanism of mannitol and the postmannitol
hemogram.
Neurosurgery 1987;21:147-56.
54. Rosner MJ, Daughton S. Cerebral perfusion pressure
management in head injury.
J Trauma 1990;30:933-41.
55. Graf CJ, Rossi NP .Catecholamine response to intracranial
hypertension.
J Neurosurgery 1978; 49: 862-8.
56. Kong DL, Prough DS, Whitley DM et.al . Haemorrhage and
intracranial hypertension in combination increase cerebral
production of thromboxane A2.
Crit Care Med 1991; 19: 532-8.
57. Robertson CS , Clifton GL, Taylor AA, et al. Treatment of
hypertension associated with head injury.
93
J Neurosurg 1983; 59: 455 – 60.
58. Cruickshank JM, Degaute JP, Kuurne T, et al . Reduction of
stress/ catecholamine – induced cardiac necrosis by beta
blockade.
Lancet 1987; ii 585-9.
59. Kirland LL , Wilson GL. Extracranial effects of acute brain
injury.
Problems in Critical Care 1991;5: 292-306.
60. Demling R, Reissen R. Pulmonary dysfunction after cerebral
injury.
Crit Care Med 1990; 18: 768-74.
61. Beckman DL, Bean JW, Baslock DR . Neurogenic influence
on pulmonary compliance.
J Trauma 1974; 14:111-5.
62. Amato MB, Barbas CS, Medeiros DM, et al. Effect of
protective ventilation strategy on mortality in the acute
respiratory distress syndrome.
N Engl J Med 1998; 338:347–54.
63. Ranieri VM, Suter PM, Tortorella C, et al. Effect of mechanical
ventilation on inflammatory mediators in patients with acute
respiratory distress syndrome.
JAMA 1999, 282:54–61.
64. Ross SE, O’Malley KF, DeLong WG, Born CT, Schwab CW.
Clinical predictors of unstable cervical spine injury in multiply
injured patients.
Injury 1992; 23:317-9.
65. Peter Ford, Jerry Nolan.Cervical spine injury and airway
management.
Curr Opin Anaesthesiol 2002; 15:193-201.
66. Bivins HG, Ford S, Bezmalinovic Z, Price HM, Williams JL.
The effect of axial traction during orotracheal intubation of
the trauma victim with an unstable cervical spine.
Ann Emerg Med 1988; 17:25-9.
67. Majernick TG, Bieniek R, Houston JB, Hughes HG. Cervical
spine movement during orotracheal intubation.
Ann Emerg Med 1986; 15:417-20.
68. Rouby JJ, Laurent P, Gosnach M, et al. Risk factors and
clinical relevance of nosocomial maxillary sinusitis in the
critically ill.
Am J Resp Crit Care Med 1994; 150:776–83.
69. Koh WY, Lew TWK, Chin NM, Wong MFM. Tracheostomy
in neurointensive care setting: Indications and timing.
Anaesth Intens Care 1997; 25:365–8.
70. Jones PA, Andrew PJD, Midgley S, et al. Measuring the
burden of secondary insults in head injured patients during
intensive care.
J Neurosurg Anesthesiol 1994; 6: 4-14.
71. Philippe Eggimann, Didier Pittet. Infection control in the
ICU.
Chest 2001; 120:2059-93.
Indian Journal of Neurotrauma (IJNT), Vol. 3, No. 2, 2006
94 V. Bhadri Narayan

72. Piek J, Chestnut RM, Marshall LF, et al. Extra cranial 80. MTV Chan, JMK Lam. New monitors of neurological
complications of severe head injuries. functions. Part-1 and 2.
J Neurosurg 1992; 77: 901-7. Curr Anaes Crit Care 1999; 10: 87-97.
73. Satwant K Tiwana Samra. Neuroendocrinolgy. In Maurice S 81. Schell RM, Cole DJ. Cerebral monitoring: jugular venous
Albin (ed). Textbook of Neuroanaesthesia. McGraw-Hill, 165- oximetry.
70. Anesth Analg 2000; 90: 559-66.
74. Young B, Ott I, Dempsey R, et al. Relationship between 82. Vigué B, Ract C, Benayed M, et al. Early SjvO2 monitoring in
admission hyperglycemia and neurologic outcome of severely patients with brain trauma.
brain injured patients. Intens Care Med 1999; 25: 445-51.
Ann Surg 1989; 210: 466-72.
83. Howard L, Gopinath S, Uzura M, et al. Evaluation of a new
75. Lam AM, Wina HR, Cullen BF, et al. Hyperglycemia and fiberoptic catheter for monitoring of jugular venous oxygen
neurological outcome in patients with head injury. saturation.
J Neurosurg 1991; 75: 545-51. Neurosurgery 1999; 44: 1280-5.
76. Rovlias A, Kotsou S. The influence of hyperglycemia on 84. Owen-Reece H, Smith M, Elwell CE, Goldstone JC. Near
neurological outcome in patients with head injury. infrared spectroscopy.
N Neurosurg 1991; 75:545-51. Br J Anaesth 1999; 82: 418- 26.
77. Zygun David A, Steiner Luzius A, Johnston Andrew, et al. 85. Van Santbrink H, Maas AI, Avezaat CJ. Continuous
Hyperglycemia and brain-tissue pH after traumatic brain monitoring of partial pressure of brain tissue oxygen in patients
injury. with severe head injury.
Neurosurgery 2004; 55:877-84. Neurosurgery 1996; 38: 21-31.
78. Schurr Avital. Tight control of glycemia in critically ill patients. 86. Hoffman WE, Charbel FT, Edelman G. Brain tissue oxygen,
Curr Opinion inClin Nutr Met Care 2002; 5:533-7. carbon dioxide, and pH in neurosurgical patients at risk for
ischemia.
79. Pedro Diaz-Parejo, Nils Ståhl, Wangbin Xu, Peter Reinstrup,
Anesth Analg 1996; 82: 582-6.
Urban Ungerstedt, Carl-Hendrik Nordstrom. Cerebral energy
metabolism during transient hyperglycemia in patients with 87. Valadka A, Goodman JG, Gopinath S, et al. Comparison of
severe brain trauma. brain tissue oxygen tension to microdialysis-based measures
Intens Care Med 2003; 29:544-50. of cerebral ischemia in fatally head-injured patients.
J Neurotrauma 1998; 15: 509-19.

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