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778 PART 6: Neurologic Disorders

function. For augmentation of cardiac output dobutamine titrated to showed that tirilazad was associated with better outcomes compared
a goal cardiac index (CI) can augment cerebral perfusion and reverse to control patients, but this was not confirmed in a subsequent North
neurological deficits. 99 American study. 103,104 In a multicenter, randomized, double-blind,
When therapy is initiated, the MAP should be raised to 15% to 20% placebo-controlled trial, nicaraven, a hydroxyl radical scavenger, sig-
above baseline rather than to an arbitrary value. If after 1 to 2 hours nificantly reduced the incidence of severe vasospasm and poor outcome
the delayed ischemic deficit has not resolved, the MAP should be at 1 month but not at 3 months. Ebselen, another lipid peroxidation
105
raised further. The MAP is increased progressively until the neuro- inhibitor, did not lower the incidence of symptomatic vasospasm in a
logic deficit is completely resolved or the risk of systemic toxicity controlled study. Clazosentan, an endothelin receptor antagonist, is
106
becomes unacceptable. Some patients may require a MAP of 150 to one of the more promising medical treatment options currently in phase
160 mm Hg to completely reverse the neurologic symptoms. For car- 3 clinical trials. A phase 2 study demonstrated a reduction in moderate
diac output augmentation, dobutamine should be titrated to a goal CI to severe vasospasm and clazosentan appeared safe. Other potential
107
of at least 3.5 L/min/m and titrated further as needed to reverse the therapies being studied include statins, magnesium infusions, nitric
2
neurological deficits. The neurologic status should be reevaluated oxide donors, and albumin infusions. 108
100
several times a day to determine MAP or CI goals. Both approaches
are reported to produce neurologic improvement. It has not yet been
determined whether the optimal therapy is to enhance cardiac output,
MAP, or both. KEY REFERENCES
Once instituted, the therapy is generally continued for 3 to 4 days • Anderson CS, Huang Y, Arima H, et al. Effects of early intensive
before attempts are made to wean the patient from it. Weaning should blood pressure-lowering treatment on the growth of hema-
be done gradually, with very close monitoring of neurologic status. If toma and perihematomal edema in acute intracerebral hemor-
the initial attempt at weaning is unsuccessful, a second attempt should rhage: the Intensive Blood Pressure Reduction in Acute Cerebral
be made after 1 to 2 days. The patient usually is weaned from vasoactive Haemorrhage Trial (INTERACT). Stroke. 2010;41:307-312.
drugs first, aggressive hydration being continued for several more days. • Dorhout Mees SM, Rinkel GJE, Feigin VL, et al. Calcium antag-
Hemodynamic augmentation is not without complications. Early
reports indicated high rates of fluid overload, heart failure, and myo- onists for aneurysmal subarachnoid haemorrhage. Cochrane
Database Syst Rev. 2007:CD000277.
cardial ischemia; however, when administered in a closely monitored
setting, even in patients with preexisting cardiac disease it can be done • Fisher CM, Kistler JP, Davis JM. Relation of cerebral vasospasm
safely. Cardiovascular monitoring should include continuous display to subarachnoid hemorrhage visualized by computerized tomo-
101
of the electrocardiogram, peripheral oxygen saturation, MAP, and graphic scanning. Neurosurgery. 1980;6:1-9.
frequent measurements of cardiac filling pressures and cardiac output. • Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase
In patients with a history of ischemic heart disease, daily electrocar- 3 to 4.5 hours after acute ischemic stroke. N Engl J Med.
diograms and cardiac enzyme measurements may be helpful. Close 2008;359:1317-1329.
monitoring of potassium, magnesium, and phosphate levels is important • Jüttler E, Unterberg A, Woitzik J, et al. Hemicraniectomy in older
because of large losses in the urine. patients with extensive middle-cerebral-artery stroke. N Engl J
Endovascular Therapies: Percutaneous Transluminal Angioplasty and Direct Intra-Arterial Med. 2014;370:1091-1100.
Vasodilators Balloon angioplasty can be used to dilate proximal segments • Molyneux A, Kerr R, Stratton I, et al. International Subarachnoid
of intracranial vessels, but it is not well suited for use in the distal vascula- Aneurysm Trial (ISAT) of neurosurgical clipping versus endovas-
ture. The dilation achieved appears to be long-lasting. Complications that cular coiling in 2143 patients with ruptured intracranial aneu-
have been reported include artery rupture and displacement of aneurysm rysms: a randomised trial. Lancet. 2002;360:1267-1274.
clips. In most cases there is clear-cut angiographic improvement, but the
clinical efficacy of angioplasty has not been clearly established. • Potter JF, Robinson TG, Ford GA, et al. Controlling hyperten-
Direct intra-arterial injection of vasodilators into the vessel affected sion and hypotension immediately post-stroke (CHHIPS): a
by vasospasm has become routine in many centers. The most commonly randomised, placebo-controlled, double-blind pilot trial. Lancet
used agents currently used include verapamil and nicardipine. While Neurol. 2009;8:48-56.
the radiographic improvement is usually evident, the clinical effect has • Robinson TG, Potter JF, Ford GA, et al. Effects of antihypertensive
been less clear. There have not been any randomized controlled trials treatment after acute stroke in the Continue or Stop Post-Stroke
demonstrating a benefit on patient outcome. These therapies are usually Antihypertensives Collaborative Study (COSSACS): a prospec-
reserved for patients who do not tolerate or do not respond to hemody- tive, randomised, open, blinded-endpoint trial. Lancet Neurol.
namic augmentation. 2010;9:767-775.
Other Potential Therapies Prevention rather than treatment of the conse- • Sandercock PAG, Counsell C, Tseng M-C. Low-molecular-weight
quences of vasospasm would significantly reduce the morbidity, mortal- heparins or heparinoids versus standard unfractionated hepa-
ity, and cost of SAH. Intracisternal instillation of thrombolytic agents rin for acute ischaemic stroke. Cochrane Database Syst Rev.
has been employed in an attempt to dissolve clots around the circle of 2008:CD000119.
Willis and thereby decrease vasospasm. A multicenter, randomized, • The National Institute of Neurological Disorders and Stroke rt-PA
blinded, placebo-controlled study found trends toward reduction of Stroke Study Group: tissue plasminogen activator for acute isch-
angiographic vasospasm, reduced delayed neurologic worsening, lower emic stroke. N Engl J Med. 1995;333:1581-1587.
14-day mortality, and improved 3-month outcome that did not achieve • Vahedi K, Hofmeijer J, Juettler E, et al. Early decompressive
statistical significance in patients treated with intracisternal t-PA. surgery in malignant infarction of the middle cerebral artery:
Patients with thick subarachnoid clots had a significant reduction in the a pooled analysis of three randomised controlled trials. Lancet
incidence of severe vasospasm with intracisternal t-PA. 102 Neurol. 2007;6:215-222.
The degradation of blood deposited during an SAH involves the
conversion of oxyhemoglobin to methemoglobin, which releases an acti-
vated form of oxygen that catalyzes free radical reactions, including lipid
peroxide formation. The 21-aminosteroid, tirilazad mesylate, a potent REFERENCES
scavenger of oxygen free radicals, inhibits lipid peroxidation and reduces
vasospasm in animal models. A European-Australian multicenter study Complete references available online at www.mhprofessional.com/hall

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