Anesthesia for neurosurgery

Divya Chander, M.D.

Adrian W. Gelb, MB,ChB, DA, FRCPC
Department of Anesthesia and Perioperative Care
University of California, San Francisco, USA
The practice of neuroanesthesia is unique in that the target organ of both the surgeon and
the anesthetist is one and the same. Thus, the surgical goals have a profound impact on
the constraints that the anesthesiologist must work within. In order to appropriately
anesthetize the patient for neurosurgery, an understanding of the interrelationships of
neurophysiology, pathophysiology and pharmacology is important. This chapter will
review: 1) basic neurophysiological principles, 2) specific approaches to the management
of intracranial pressure (ICP) as they relate to clinical neuroanesthesia, and 3)
intraoperative management of the patient with a supratentorial mass lesion.

I. Basic principles of neurophysiology

There are six interrelated components that are important to the practice of
neuroanesthesia. They are maintenance of cerebral perfusion pressure (CPP), cerebral
blood flow (CBF), cerebral blood volume (CBV), intracranial pressure (ICP), CO2
responsiveness (CO2R) and cerebral oxygen metabolism (CMRO2).
1. Cerebral Perfusion Pressure. CPP is the difference between mean arterial pressure
(MAP) and intracranial pressure (ICP) [CPP = MAP ICP], although in the occasional
patient where central venous pressure is higher than ICP, CPP = MAP - CVP. Both
intracranial pathology and drugs may compromise CPP through effects on MAP and/or

ICP. CPP is usually >70 mmHg. An optimal CPP has not been defined but in the context
of head trauma, a CPP < 60 is associated with a poorer outcome; a benefit of higher CPP
has not been shown [1].

2. Cerebral Blood Flow. The average CBF is ~40-50ml/100gm/min with gray matter
having a higher flow than white matter (60 ml/100gm/min and 20 ml/100gm/min
respectively). CBF is autoregulated that is, blood flow is maintained over a wide range
(~50 150 mmHg) of perfusion pressures in order to avoid ischemia when blood
pressure is reduced and edema or hemorrhage at higher blood pressures. Static
autoregulation refers to changes in flow that occur slowly (minutes) in response to
changes in blood pressure and dynamic autoregulation is used to describe changes that
occur within seconds. The autoregulatory range and the relationship between CBF and
perfusion pressure can change rapidly as one would want from a homeostatic response.
When sympathetic tone is reduced the entire response can shift to lower pressures and
when tone is increased such as during stress it moves to a higher pressure range. With
hyperventilation the response shifts to lower CBF and covers a wider perfusion pressure
range while an increased CO2 results in a narrower range at a higher CBF.
Volatile anesthetics affect CBF both indirectly and directly. When cerebral metabolism
(CMRO2) is decreased, vasoconstriction occurs to appropriately reduce CBF. However,
direct vasodilation also occurs in a dose-dependent fashion [2]; [3]; [4]; [5] but may not
manifest as increased CBF except at higher concentrations. Evidence from both animal
and humans suggest that the increase in CBF is more pronounced with desflurane and
least with sevoflurane [6]; [7]; [8]; [2]].

Both static and dynamic autoregulation remain essentially intact with both sevoflurane
and isoflurane up to 1 MAC [[9]; [10] but preservation is better and persists to a higher
concentration with sevoflurane [11]. Desflurane >1 MAC abolishes autoregulation [10].
Static autoregulation also appears to be intact in children undergoing non-neurosurgical
procedures with doses of sevoflurane up to 1.5 MAC [12]. The effect of volatile
anesthetics on cerebral hemodynamics including CBF and autoregulation has been well
reviewed[6, 8].
Propofol, barbiturates and etomidate are potent cerebral vasoconstrictors reducing CBF
secondary to decreasing CMRO2 [13-15]. The effect on CBF is greater with propofol and
thiopental than etomidate. Propofol and thiopental do not alter autoregulation[10].
Opioids have minimal effect on CBF [16].
3. Cerebral Blood Volume. Approximately 15% of CBV is in the arterial tree and ~15%
in the major venous sinuses. The remainder is in the capillary and venous systems. CBF
is often incorrectly used as a surrogate for blood volume, probably because it has been
easier to measure. Changes in CBF and CBV are generally proportional to one another
but, for instance, changes in head position from standing to supine to head down can
increase CBV without changing CBF.
Propofol decreases CBV in humans and sevoflurane increases it but less than isoflurane
[17, 18].

4. Intracranial Pressure. Maintenance or reduction of ICP (normal value ~10 mm Hg)

of ICP is one of the important aims of neuroanesthesia. ICP is a critical determinant of
CPP and by extension CBF and brain function. As ICP increases above ~20 mmHg, focal
reductions in CBF occur and further increases eventually result in global cerebral
ischemia. The three major components of the intracranial cavity are brain (~80%),
cerebrospinal fluid (CSF) (~10%) and CBV (~10%). If one component increases its
volume, it must be compensated for by a decrease in another to prevent ICP from
increasing.
5. CO2 responsiveness. CO2R of the cerebral arterial tree is important in that
hypercarbia results in vasodilation and increased CBV. Conversely, hyperventilation
causes cerebral arterial vasoconstriction, decreased CBF & CBV and a decreased ICP.
While the reduction in ICP is beneficial, the reduced CBF can result in ischemia so that
caution must be exercised with the extent and duration of hyperventilation (see below).
CO2 reactivity is maintained with both sevoflurane and isoflurane up to 1.5 MAC in
adults [3, 19, 20] and with sevoflurane, isoflurane and halothane up to 1.0 MAC in
children[21, 22]. Intravenous anesthetics do not influence CO2 R significantly.
6. Cerebral oxygen metabolism. CMRO2 is a key determinant of the risk of ischemic
insult. If metabolic rate is high, then a reduced CBF is more likely to disrupt neuronal
function and integrity. This is the rationale behind decreasing CMRO2 in order to prevent
ischemia. While this notion is appealing in its simplicity, there are no clinical trials in
neuroanesthesia to support such a practice and animal studies indicate that any benefit
from anesthetics probably reflects both intra- and extra-cellular effects[23].

Intravenous anesthetics potently reduce CMRO2. As CBF is closely coupled to CMRO2,

CBF is reduced in parallel with an associated reduction in CBV and ICP which makes
them very useful agents in patients with intracranial hypertension. Volatile anesthetics in
contrast reduce CMRO2 but increase CBF through direct effects on the vasculature.
Although often referred to as uncoupled, experimental studies in rats suggest that flow
and metabolism continue to track in the same direction but with CBF at a higher set
point[24].

II. Clinical neuroanesthesia

The common types of neurosurgery can be divided into excision of intracranial mass
lesions, especially supratentorial tumors, decompressive procedures in major head trauma
and aneurysm clipping. This review will focus on managing elevated ICP as this is a
problem common to all types of intracranial surgery and then specifically the
management of supratentorial masses.
1. Management of Intracranial Pressure
ICP may be affected by four major variables in the operating room - hyperventilation,
anesthetic drugs, diuretics such as mannitol, and head position.
A. Hyperventilation constricts the cerebral arterioles with concomitant decreases in CBF
and CBV. The effect takes place rapidly and may be especially useful for decreasing ICP
in situations in which ICP is critically elevated or the surgeon is having difficulty with
brain bulk. However, cerebral vasoconstriction may lead to critical hypoperfusion and

brain ischemia with no improvement or worsened outcomes especially with prolonged

use [25-28].
Therefore, current recommendations are that hyperventilation: 1. should not be used
prophylactically in the traumatically brain injured patient and should only be used for
brief periods to manage significant increases in ICP not responsive to alternate
treatments[25, 26]. 2. Similar concerns prevail in the operating room although no trials
have addressed outcomes in this context. In either case, unless neurosurgical conditions
demand it, ventilation to moderate levels of hypocapnia (PaCO2 32-35 mmHg) rather
than severe (PaCO2 < 32 mmHg) should be used.
B. Anesthetic drugs
Volatile anesthetics produce direct vasodilatation and thus have the potential to increase
ICP. However the effect on ICP, in both pediatric and adult patients with spaceoccupying lesions is clinically insignificant when anesthetic concentrations are
maintained below 1.2 MAC and if the ICP is not critically elevated [4, 29-32].
Propofol, barbiturates (thiopental) and etomidate have minimal effect or decrease ICP
[32]. Few randomized controlled trials have compared intravenous and inhalation agents
and their effect on ICP. In a trial of 117 patients with supratentorial tumors undergoing
elective resection, subjects received propofol or isoflurane or sevoflurane as well as a
fentanyl infusion (2-3 g/kg/hr). ICP was lower, brain swelling less, and CPP better
preserved in the propofol group[33]. An earlier trial on 121 patients undergoing elective
removal of supratentorial tumors found no difference in mean ICP amongst
propofol/fentanyl, fentanyl/nitrous oxide, or isoflurane/nitrous oxide[34]. However, there

were significantly more patients in the isoflurane/nitrous oxide group that had an
intraoperative ICP > 24 mm Hg.
The benefits of high dose barbiturate coma in the management of elevated ICP have not
been demonstrated while deleterious outcomes including increased mortality have been
shown [35].

Opioids do not increase or decrease ICP[36]. However, when blood pressure decreases,
the cerebral vasculature dilates to maintain CBF; this dilation may increase ICP if it is
critically increased [16].
C. Mannitol has become the mainstay of ICP management protocols. An osmotic
diuretic, mannitol draws water from the brain and other tissues into the intravascular
compartment. Mannitol may also lower ICP by decreasing blood viscosity and
expanding plasma volume which increase CBF. When autoregulation is intact this
prompts vasoconstriction to restore CBF towards normal [37].
A small, randomized trial concluded that there may be a mortality benefit to using
mannitol instead of barbiturate infusion in cases of elevated ICP [35]. Other prospective,
randomized studies evaluated long-term outcomes in TBI patients. In each study, one
group received early, pre-operative treatment of high-dose mannitol whereas the other
group did not. The early, high-dose mannitol groups had clinical reversal of impending
signs of brain death, better postoperative control of ICP, and better cerebral perfusion
[38-41]. Thus current guidelines advocate use of high-dose mannitol boluses for elevated
ICP as long as hypovolemia and excessive serum osmolalities (>320 mOsm) are avoided.

The use of mannitol to reduce brain bulk in the OR has not been as well investigated;
current practice guidelines are drawn from the head trauma literature.

Hypertonic saline is being investigated as an alternative to mannitol [42]. It has been

suggested that by using a hypertonic saline solution, a similar ICP lowering effect to
mannitol may be achieved with better outcomes, better preservation of MAP and a
potentially longer duration of effect [42, 43].
D. Head-up position is an effective intervention to reduce ICP although there is concern
that MAP and consequently CPP would drop. There have been two cohort craniotomy
trials examining 10 degree head up position. One involved 40 patients, the other 15.
Head-up position of 10 degrees significantly decreased ICP and MAP but left CPP
unaffected [44]. Similar results have been found in head trauma patients subjected to 30
degree head up [45].

2. Anesthesia for a patient with a supratentorial mass

The most common mass is a supratentorial tumor. Resection of the tumor requires
maintenance of adequate cerebral perfusion to prevent ischemia while ensuring that ICP
is not dangerously elevated. Timely wake-up is desirable in order to facilitate
neurological evaluation soon after surgery.
Pre-operative evaluation. Besides the routine assessments the patient should be assessed
for signs of elevated ICP (nausea/vomiting, papilledema, headache, visual changes,
altered mental status, altered breathing patterns, hypertension, bradycardia) and the

neurological deficits documented. It is better if the anesthesiologist does his/her own

examination but the neurologist or neurosurgeons examination may be more complete.
The diagnostic imaging should be seen so as to identify the type of tumor, its location,
vascularity, evidence of midline shift and presence of hydrocephalus. Often, patients are
taking steroids and anti-epileptic medications which can have an impact on glucose
homeostasis and pharmacodynamics of neuromuscular blockers respectively. Premedication for anxiolysis may be offset by sedation that may hamper neurological
assessment and hypercarbia which may increase ICP. In most patients, a carefully
titrated dose of intravenous benzodiazepine can safely be given if needed.
Monitors consist of standard monitors. Continuous blood pressure measurement,
preferably via peripheral artery catheter is useful in detecting and treating abrupt
hemodynamic changes that might compromise CPP or ICP. Core temperature should be
monitored and kept in the normal range. A Foley catheter is important if diuretics are to
be used or the surgery will be long.
Induction of anesthesia is a critical time because of the highly stimulating effects of direct
laryngoscopy and intubation which is followed a short time later with pinning the head
for optimal positioning which is painful. Excessive increases in blood pressure and
coughing should be avoided. The most common induction agents are propofol or
thiopental with etomidate or ketamine occasionally used in the hemodynamically
unstable patient. These are supplemented with an opioid such as fentanyl 2-3 ug/kg or a
remifentanil infusion [46]. In addition 1-1.5 mg/kg lidocaine IV or esmolol 5-10 mg IV
may help blunt the hemodynamic effect on ICP but the effect may be incomplete [47].

Either succinylcholine or a nondepolarizing muscle relaxant may be used. There has been
controversy about succinylcholine in patients with elevated ICP but the effects are
usually of short duration and can be buffered by some additional propofol. The efficacy
of lidocaine has not been demonstrated [48]. Level 2 evidence exists to support use of a
defasciculating dose of a nondepolarizing relaxant to blunt the increase in ICP with
succinylcholine [49]. Expeditious intubation followed by oxygenation and
hyperventilation is much preferred to the avoidance of succinylcholine but with a delayed
and problematic intubation. Neuromuscular blockade may not be needed during the
procedure but should be used during positioning and head pinning.
Maintenance of anesthesia. There needs to be constant attention to the balance between
ICP and CPP together with adequacy of anesthetic depth. Attention to ICP is especially
important before the dura is opened; once the dura is open, ICP is effectively zero.
Another important consideration is the need for neuromonitoring, e.g. somatosensory or
motor evoked potentials which are used with increasing frequency during neurosurgical
procedures. Good communication between anesthesiologist, neurosurgeon and
monitoring technician is essential as local preferences tend to dictate drug choices. This is
especially true for direct stimulation of the motor cortex as there is a paucity of clinical
studies to support the use of one drug over another. SSEPs are only minimally influenced
by total intravenous anesthesia (TIVA) and are suppressed by inhalational agents in a
dose dependent manner although good signals can be obtained with <0.75MAC vapor.

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A typical maintenance anesthetic might consist of a vapor anesthetic at <1 MAC and an
opioid (fentanyl, sufentanil or remifentanil) infusion or alternatively a TIVA. The latter is
especially appropriate where ICP is markedly elevated or there is acute decompensation.
Recovery. If the patient is to be extubated at the end of surgery, the anesthetic drugs
should be appropriately tapered as the scalp is sutured. If fentanyl or sufentanil have been
used by infusion, these are usually terminated at dural closure. Remifentanil should be
continued till scalp closure and transitional analgesia such as fentanyl 50 -100 g
given[46]. The goal is a comfortable patient in whom a neurological examination can be
conducted early after the surgery.

III. Summary & recommendations

Management of the patient for neurosurgery requires a good understanding of the
interrelationships of neurophysiology, pathophysiology and pharmacology. Good data
(mostly level 1) exist to describe the effects of volatile and intravenous anesthetics on
cerebral hemodynamics (CBF, autoregulation, CBV, CO2 reactivity). Based on this data,
one would recommend using < 1 MAC sevoflurane or isoflurane over desflurane in
adults with elevated ICP with a slight preference for sevoflurane. In children, a similar
recommendation can be made. For patients with critically elevated ICP, a TIVA
anesthetic may be preferred. Most studies, however, have used physiological
measurements such as CBF or ICP intraoperatively. No level 1 study exists which
measured clinical outcomes.

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Induction of anesthesia may be achieved with IV agents normally used (e.g. propofol,
thiopental or etomidate). There is level 2 data to support pre-treatment with lidocaine to
minimize elevation in ICP (Grade B recommendation). There is also level 2 data to
support the use of a defasciculating dose of non-depolarizing muscle relaxant if
succinylcholine is to be used.
The clinical data for management of ICP come mostly from studies of patients with head
trauma. Level 2 Data (Grade B recommendation) support the use of the head-up position
for significantly reducing ICP without compromising CPP. With respect to
hyperventilation and mannitol, this data has been subjected to formal Cochrane reviews
and review by the Brain Trauma Foundation. There are Grade A recommendations for the
use of: 1) brief, moderate hyperventilation (PaCO2 32-35 mm Hg) in cases of acutely
elevated ICP, and 2) high-dose mannitol (1.2-1.4 g/kg) in place of conventional dose
mannitol (< 1 g/kg) for the treatment of acutely elevated ICP (in comatose patients).
These guidelines can be applied to the OR for non head trauma patients. More
randomized control trials that explore these interventions for elevated ICP specifically in
this setting are needed.

REFERENCES:
1.

Juul, N., et al., Intracranial hypertension and cerebral perfusion pressure:

influence on neurological deterioration and outcome in severe head injury. The
Executive Committee of the International Selfotel Trial. J Neurosurg, 2000.
92(1): p. 1-6.

12

2.

Matta, B.F., et al., Direct cerebral vasodilatory effects of sevoflurane and

isoflurane. Anesthesiology, 1999. 91(3): p. 677-80.

3.

Bundgaard, H., et al., Effects of sevoflurane on intracranial pressure, cerebral blood

flow and cerebral metabolism. A dose-response study in patients subjected to
craniotomy for cerebral tumours. Acta Anaesthesiol Scand, 1998. 42(6): p. 621-7.

4.

Cold, G.E., et al., ICP during anaesthesia with sevoflurane: a dose-response study.
Effect of hypocapnia. Acta Neurochir Suppl, 1998. 71: p. 279-81.

5.

Matta, B.F., T.S. Mayberg, and A.M. Lam, Direct cerebrovasodilatory effects of
halothane, isoflurane, and desflurane during propofol-induced isoelectric
electroencephalogram in humans. Anesthesiology, 1995. 83(5): p. 980-5;
discussion 27A.

6.

De Deyne, C., L.M. Joly, and P. Ravussin, [Newer inhalation anaesthetics and
neuro-anaesthesia: what is the place for sevoflurane or desflurane?]. Ann Fr
Anesth Reanim, 2004. 23(4): p. 367-74.

7.

Monkhoff, M., et al., The effects of sevoflurane and halothane anesthesia on

cerebral blood flow velocity in children. Anesth Analg, 2001. 92(4): p. 891-6.

8.

Duffy, C.M. and B.F. Matta, Sevoflurane and anesthesia for neurosurgery: a
review. J Neurosurg Anesthesiol, 2000. 12(2): p. 128-40.

9.

Gupta, S., K. Heath, and B.F. Matta, Effect of incremental doses of sevoflurane on
cerebral pressure autoregulation in humans. Br J Anaesth, 1997. 79(4): p. 469-72.

10.

Strebel, S., et al., Dynamic and static cerebral autoregulation during isoflurane,
desflurane, and propofol anesthesia. Anesthesiology, 1995. 83(1): p. 66-76.

13

11.

Summors, A.C., A.K. Gupta, and B.F. Matta, Dynamic cerebral autoregulation
during sevoflurane anesthesia: a comparison with isoflurane. Anesth Analg, 1999.
88(2): p. 341-5.

12.

Fairgrieve, R., et al., The effect of sevoflurane on cerebral blood flow velocity in
children. Acta Anaesthesiol Scand, 2003. 47(10): p. 1226-30.

13.

Petersen, K.D., et al., ICP is lower during propofol anaesthesia compared to

isoflurane and sevoflurane. Acta Neurochir Suppl, 2002. 81: p. 89-91.

14.

Roberts, I., Barbiturates for acute traumatic brain injury. Cochrane Database Syst
Rev, 2000(2): p. CD000033.

15.

Bazin, J.E., [Effects of anesthetic agents on intracranial pressure]. Ann Fr Anesth

Reanim, 1997. 16(4): p. 445-52.

16.

Werner, C., et al., Effects of sufentanil on cerebral hemodynamics and intracranial

pressure in patients with brain injury. Anesthesiology, 1995. 83(4): p. 721-6.

17.

Kaisti, K.K., et al., Effects of sevoflurane, propofol, and adjunct nitrous oxide on
regional cerebral blood flow, oxygen consumption, and blood volume in humans.
Anesthesiology, 2003. 99(3): p. 603-13.

18.

Lorenz, I.H., et al., Subanesthetic concentration of sevoflurane increases regional

cerebral blood flow more, but regional cerebral blood volume less, than
subanesthetic concentration of isoflurane in human volunteers. J Neurosurg
Anesthesiol, 2001. 13(4): p. 288-95.

19.

Nishiyama, T., et al., Cerebrovascular carbon dioxide reactivity during general

anesthesia: a comparison between sevoflurane and isoflurane. Anesth Analg,
1999. 89(6): p. 1437-41.

14

20.

Mielck, F., et al., Effects of one minimum alveolar anesthetic concentration

sevoflurane on cerebral metabolism, blood flow, and CO2 reactivity in cardiac
patients. Anesth Analg, 1999. 89(2): p. 364-9.

21.

Leon, J.E. and B. Bissonnette, Cerebrovascular responses to carbon dioxide in

children anaesthetized with halothane and isoflurane. Can J Anaesth, 1991. 38(7):
p. 817-25.

22.

Rowney, D.A., R. Fairgrieve, and B. Bissonnette, Cerebrovascular carbon dioxide

reactivity in children anaesthetized with sevoflurane. Br J Anaesth, 2002. 88(3):
p. 357-61.

23.

Gelb, A.W., J.X. Wilson, and D.F. Cechetto, Anesthetics and cerebral ischemia-should we continue to dream the impossible dream? Can J Anaesth, 2001. 48(8):
p. 727-31.

24.

Hansen, T.D., et al., The role of cerebral metabolism in determining the local
cerebral blood flow effects of volatile anesthetics: evidence for persistent flowmetabolism coupling. J Cereb Blood Flow Metab, 1989. 9(3): p. 323-8.

25.

The Brain Trauma Foundation. The American Association of Neurological

Surgeons. The Joint Section on Neurotrauma and Critical Care. Hyperventilation.
J Neurotrauma, 2000. 17(6-7): p. 513-20.

26.

The Brain Trauma Foundation. The American Association of Neurological

Surgeons. The Joint Section on Neurotrauma and Critical Care. Initial
management. J Neurotrauma, 2000. 17(6-7): p. 463-9.

15

27.

Muizelaar, J.P., et al., Adverse effects of prolonged hyperventilation in patients

with severe head injury: a randomized clinical trial. J Neurosurg, 1991. 75(5): p.
731-9.

28.

Roberts, I. and G. Schierhout, Hyperventilation therapy for acute traumatic brain

injury. Cochrane Database Syst Rev, 2005(4): p. CD000566.

29.

Sponheim, S., et al., Effects of 0.5 and 1.0 MAC isoflurane, sevoflurane and
desflurane on intracranial and cerebral perfusion pressures in children. Acta
Anaesthesiol Scand, 2003. 47(8): p. 932-8.

30.

Kaye, A., et al., The comparative effects of desflurane and isoflurane on lumbar
cerebrospinal fluid pressure in patients undergoing craniotomy for supratentorial
tumors. Anesth Analg, 2004. 98(4): p. 1127-32, table of contents.

31.

Fraga, M., et al., The effects of isoflurane and desflurane on intracranial pressure,
cerebral perfusion pressure, and cerebral arteriovenous oxygen content difference
in normocapnic patients with supratentorial brain tumors. Anesthesiology, 2003.
98(5): p. 1085-90.

32.

Ravussin, P., et al., Effect of propofol on cerebrospinal fluid pressure and cerebral
perfusion pressure in patients undergoing craniotomy. Anaesthesia, 1988. 43
Suppl: p. 37-41.

33.

Petersen, K.D., et al., Intracranial pressure and cerebral hemodynamic in patients

with cerebral tumors: a randomized prospective study of patients subjected to
craniotomy in propofol-fentanyl, isoflurane-fentanyl, or sevoflurane-fentanyl
anesthesia. Anesthesiology, 2003. 98(2): p. 329-36.

16

34.

Todd, M.M., et al., A prospective, comparative trial of three anesthetics for

elective supratentorial craniotomy. Propofol/fentanyl, isoflurane/nitrous oxide,
and fentanyl/nitrous oxide. Anesthesiology, 1993. 78(6): p. 1005-20.

35.

Schwartz, M.L., et al., The University of Toronto head injury treatment study: a
prospective, randomized comparison of pentobarbital and mannitol. Can J Neurol
Sci, 1984. 11(4): p. 434-40.

36.

Guy, J., et al., Comparison of remifentanil and fentanyl in patients undergoing

craniotomy for supratentorial space-occupying lesions. Anesthesiology, 1997.
86(3): p. 514-24.

37.

Bouma, G.J. and J.P. Muizelaar, Cerebral blood flow in severe clinical head
injury. New Horiz, 1995. 3(3): p. 384-94.

38.

Cruz, J., G. Minoja, and K. Okuchi, Improving clinical outcomes from acute
subdural hematomas with the emergency preoperative administration of high
doses of mannitol: a randomized trial. Neurosurgery, 2001. 49(4): p. 864-71.

39.

Cruz, J., G. Minoja, and K. Okuchi, Major clinical and physiological benefits of
early high doses of mannitol for intraparenchymal temporal lobe hemorrhages
with abnormal pupillary widening: a randomized trial. Neurosurgery, 2002. 51(3):
p. 628-37; discussion 637-8.

40.

Cruz, J., et al., Successful use of the new high-dose mannitol treatment in patients
with Glasgow Coma Scale scores of 3 and bilateral abnormal pupillary widening:
a randomized trial. J Neurosurg, 2004. 100(3): p. 376-83.

41.

Wakai, A., I. Roberts, and G. Schierhout, Mannitol for acute traumatic brain
injury. Cochrane Database Syst Rev, 2005(4): p. CD001049.

17

42.

Vialet, R., et al., Isovolume hypertonic solutes (sodium chloride or mannitol) in

the treatment of refractory posttraumatic intracranial hypertension: 2 mL/kg 7.5%
saline is more effective than 2 mL/kg 20% mannitol. Crit Care Med, 2003. 31(6):
p. 1683-7.

43.

Mirski, A.M., et al., Comparison between hypertonic saline and mannitol in the
reduction of elevated intracranial pressure in a rodent model of acute cerebral
injury. J Neurosurg Anesthesiol, 2000. 12(4): p. 334-44.

44.

Haure, P., et al., The ICP-lowering effect of 10 degrees reverse Trendelenburg

position during craniotomy is stable during a 10-minute period. J Neurosurg
Anesthesiol, 2003. 15(4): p. 297-301.

45.

Ng, I., J. Lim, and H.B. Wong, Effects of head posture on cerebral
hemodynamics: its influences on intracranial pressure, cerebral perfusion
pressure, and cerebral oxygenation. Neurosurgery, 2004. 54(3): p. 593-7;
discussion 598.

46.

Gelb, A.W., et al., Remifentanil with morphine transitional analgesia shortens

neurological recovery compared to fentanyl for supratentorial craniotomy. Can J
Anaesth, 2003. 50(9): p. 946-52.

47.

Samaha, T., et al., [Prevention of increase of blood pressure and intracranial

pressure during endotracheal intubation in neurosurgery: esmolol versus
lidocaine]. Ann Fr Anesth Reanim, 1996. 15(1): p. 36-40.

48.

Robinson, N. and M. Clancy, In patients with head injury undergoing rapid

sequence intubation, does pretreatment with intravenous lignocaine/lidocaine lead

18

to an improved neurological outcome? A review of the literature. Emerg Med J,

2001. 18(6): p. 453-7.
49.

Clancy, M., et al., In patients with head injuries who undergo rapid sequence
intubation using succinylcholine, does pretreatment with a competitive
neuromuscular blocking agent improve outcome? A literature review. Emerg Med
J, 2001. 18(5): p. 373-5.

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