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CHAPTER 86: Intracranial Pressure: Monitoring and Management 809

barbiturates in TBI. However, it has important side effects including utilization of different hypertonic solutions and small sample sizes.
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hypovolemia, electrolyte disturbances, and acute renal failure. Mannitol A recent meta-analysis of mannitol-HTS comparative trials employ-
is typically used in a 20% solution. Its ICP-lowering effect is dose ing random-effects models evaluated a total of 184 ICP crises in
dependent, and it appears to be maximal with a 1 g/kg dose infused over 112 patients summarized from five published trials. Mannitol and
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30 minutes. 93,94 For continuous use, it is tapered to a maintenance dose HTS were effective in ICP control in 78% (CI 67%-86%) and 93% (CI
of 0.25 to 0.50 g/kg IV bolus every 4 to 6 hours. The duration of benefit 85%-97%) of ICP crises respectively, with a mean ICP reduction of
from an initial high-dose infusion regimen is limited to several hours; 2.0 mm Hg in favor of HTS. 119
after continuation over extended treatment periods, terminal dose ICP
elevations beyond the pretreatment values can occur. This is due to Hypertonic Sodium Lactate: Hypertonic sodium lactate (HSL) is primar-
the accumulation of mannitol within the brain, which is most marked ily utilized in post-cardiac arrest patients for fluid resuscitation. The
in patients with a disrupted blood-brain barrier and when mannitol is presence of lactate is not harmful and can act as a key intracellular
in circulation for long periods. 21,37,93,95-99 Mannitol may enter damaged metabolite in many organs as it involves the regulation of glycolysis
brain tissue and decrease the osmotic gradient, which may reverse the and oxidative phosphorylation, which are also essential pathways in the
prior osmotic effects of intravenous administration. Such “rebound” injured brain. 120,121 These solutions aim to combine a source of lactate
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edema can especially be seen when mannitol is abruptly discontinued with the advantages of a hypertonic solution in the treatment of brain
after prolonged use. Preferably, mannitol is administered as repeated injury and ICP elevation. Some laboratory evidence suggests that hyper-
boluses rather than a continuous infusion and over the shortest time tonic sodium lactate results in improved cognitive function post-TBI
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interval needed to stabilize ICP. 101-103 Unfortunately, clinical trials com- when compared to the use of hypertonic sodium chloride solution.
paring different doses and modes of administration of mannitol are Lactate solution may be administered peripherally and it is not associ-
lacking. Reduction in ICP after a mannitol bolus should be apparent ated with hyperchloremia.
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within 15 minutes, and failure of a response is ominous. If mannitol fails Loop Diuretics: Selected series show that loop diuretics such as furo-
to control ICP, one may opt to use a hypertonic solution. Combining semide, alone or in conjunction with osmotic agents, can reduce
mannitol and hypertonic saline has not been well studied but is prac- ICP. The use of furosemide as the sole treatment of cerebral edema,
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ticed in some centers. Alternatively, single doses of mannitol with large however, is controversial. Diuretics exert their ICP-lowering effects
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time interval repetitions are effective in reducing ICP and improving through a combination of an osmotic gradient created by intravas-
intracranial compliance; monitoring of plasma osmolality in this setting cular diuresis, reduction in CSF formation, and reduction in brain
is of little value. water. Similar to mannitol, loop diuretics can produce profound
Important complications of mannitol therapy include electrolyte volume and electrolyte loss, requiring close monitoring and appropri-
disturbance (hypernatremia, pseudohyponatremia, and hypokalemia), ate replacement. In patients who have severe congestive heart failure
prerenal azotemia and acute renal failure, and congestive heart failure. and intolerance to mannitol, furosemide can be administered as an
Rapid diuresis as a result of mannitol administration leads to intravascular alternative agent. Another strategy to rapidly raise serum sodium
volume depletion and vasoconstriction, which can decrease CBF and is to administer an intravenous bolus of furosemide (10-20 mg) to
place the patient at risk for ischemia. It is advisable to have appropriate enhance free water excretion, replacing the lost volume with a 250-mL
replacement fluids and vasoactive drugs readily available in any patient intravenous bolus of 2% or 3% hypertonic saline. Acetazolamide is a
with critically low CPP treated with osmotherapeutics. carbonic anhydrase inhibitor that acts as a weak diuretic also modu-
Hypertonic Saline: Hypertonic saline solutions (HTS) have been used lating CSF production. It has no role in ICP treatment in patients with
with renewed enthusiasm in patients with brain swelling and intra- acute brain injuries but it is employed in the treatment of pseudotu-
cranial hypertension. 105-108 The osmolality of variously employed HTS mor cerebrii. 125
is listed in Table 86-13. The principal effect on ICP is due to osmotic Metabolic Suppression: Suppressing the metabolic state of the brain may
mobilization of water across the blood-brain barrier that reduces cere- treat elevated ICP via decreasing the metabolic demand and maintaining
bral water content, similar to the mechanism of mannitol. Effects on the tissue viability by decreasing oxygen requirements.
microcirculation may also play an important role in decreasing ICP and
improving oxygen delivery and utilization, as HTS dehydrate swollen Therapeutic Hypothermia: Fever is common following brain injury, and
endothelial cells and circulating erythrocytes, expand plasma volume, avoidance of hyperthermia is an important part of the management of
and improve overall rheology in the distal cerebral circulation. brain injury from any cause. 126-128,160,161 The adverse effects of tempera-
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and achievement of higher CPP ture elevations above 37°C are mediated by multiple pathogenic mecha-
Significant improvements in brain P O 2
targets have been reported with hypertonic saline. 110 nisms, including excitotoxicity, free radical generation, inflammation,
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Variable formulations of hypertonic saline have been used (up to apoptosis, and genetic differences in response to injury. Intracranial
23.4%) with different bolus volumes (up to 75 mL). Some institutions temperature has been shown to be higher than core body temperature,
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use a single bolus of 30 mL of 23.4% saline or 250 mL bolus of 3% saline representing an important consideration because of the intimate rela-
to treat elevated ICP. 111,112 The dose and concentration of HTS depends tionship between elevations in ICP and intracranial temperature. There
on factors such as clinician preference, central versus peripheral venous has been renewed interest in moderate hypothermia (33°C-35°C) as an
access, urgency of ICP reduction, and baseline serum sodium level. adjunct therapy for patients with intracranial hypertension. It can lower
A maximum target serum osmolality of 360 mOsm/L can be targeted ICP and improve CPP in some patients, and it theoretically limits brain
in patients with refractory ICP elevations. HTS may lead to pulmo- injury secondary to hypoperfusion. Iced normal saline infusion studies
nary edema in patients with cardiac or lung injuries, fluid overload, demonstrated that the use of intravenous cold saline is a safe, easy, and
hyperchloremic acidosis, coagulopathy, and rebound intracranial hyper- effective method of inducing mild systemic temperature control. The
tension with too rapid serum sodium normalization. Hypernatremia use of 2 L of cold normal saline (4°C) over 20 to 30 minutes will tempo-
and hyperosmolarity, however, are usually well tolerated in brain injury rarily decrease the temperature by 1.4°C. Cooling blankets or cooled,
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patients in the absence of multisystem organ failure or sepsis. In contrast gel-containing surface pads can be placed around the patient, with the
to mannitol, hypertonic solutions do not cause hypovolemia and have latter being more effective. Endovascular cooling devices inserted into
a lower nephrotoxicity risk. 113 the subclavian or femoral vein are powerful but invasive tools with
Several randomized trials have been published on the merits of precise and fast temperature targeting. Figure 86-17 illustrates the dif-
sodium-based hypertonic solutions and their superiority to manni- ferent cooling methods. When hypothermia is applied, shivering can be
tol in reducing elevated ICP. 106,114-118 These studies are limited by the a complicating factor, especially when the body temperature is below

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