Hypothermia for Ischemic Stroke

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Early clinical data have shown promise for induced hypothermia for the treatment of acute ischemic stroke. Hypothermia acts by decreasing the cerebral metabolic rate, stabilizing cell membranes, preserving the integrity of the BBB, reducing the release of destructive enzymes, reducing the inflammatory response, and decreasing the release of excitotoxic neurotransmitters, such as glutamate and dopamine. Early treatment with hypothermia may reduce total infarct volume, and may prevent the development of cerebral edema. However, its use is associated with several potential adverse side effects, including an increased risk of infection, coagulopathy, hypokalemia, hyperglycemia, and cardiovascular suppression. Furthermore, when hypothermia is discontinued, a rebound elevation of ICP has also been noted, which may be fatal. The timing, degree, and duration of hypothermia in ischemic stroke have not been fully worked out, nor has the safest rate of re-warming.

Numerous small studies have been conducted for hypothermia in ischemic stroke, but most of these were feasibility phase II studies, and often did not include control patients.71 Schwab et al.72 found hypothermia to be useful and feasible in 25 patients with severe MCA strokes, cooling them to 33°C for 48-72 hours, with a significant reduction in ICP. However, this study poignantly demonstrated the problems with re-warming, as fatal herniation occurred in a significant proportion of patients as they returned to normothermia. Pneumonia also occurred in 40% of patients, perhaps higher than would be expected from the natural history of large MCA stroke patients. Controlled rewarming was then evaluated, and appeared to be more effective in controlling the ICP in a more graduated and safe fashion.73

The COOL AID study36 randomized 40 patients within 12 hours of ischemic stroke, 18 to hypothermia with a target temperature of 33°C for 24 hours, and 22 to standard medical management. The two groups had similar clinical outcomes, as well as similar lesion growth as measured on magnetic resonance imaging (MRI). They concluded that induced hypothermia for ischemic stroke appears safe, but could make no conclusions regarding efficacy. The Nordic Cooling Stroke Study (NOCSS), currently in progress, is a multicenter, multinational trial planning to enroll 1000 patients at 25 centers. Patients with ischemic stroke within 6 hours will be eligible, but they must have moderate-to-severe hemispheric strokes. Patients will be randomized to standard medical management or induced hypothermia to 35°C with surface cooling methods, using meperidine to control shivering. Table 8.4 provides a review of the randomized studies of hypothermia in stroke patients.

Multiple methods of inducing hypothermia are currently available. Traditional methods, such as the use of ice packs, cooling blankets, or mattresses that deliver cold air, are often ineffective and difficult to control. Overshooting of the target temperature is not uncommon with these techniques, and with lower temperatures comes a higher rate of complications, including dangerous cardiac dysrhythmias. More advanced methods include the use of intravenous cooling catheters,74 external cooling vests,75 and selective head cooling via a helmet device76 or local brain cooling used in conjunction with surgical management.77 The advantage of these techniques is that they are more effective at bringing the patient to the target temperature and do not have significant overshoot. However, they are more expensive, and the intravenous catheters pose the additional risk of infection and DVT.

Shivering is common with the induction of hypothermia, and may inhibit the ability to get the patient to the target temperature. Multiple agents have been evaluated in the prevention of shivering. Tylenol is only modestly effective, and is complicated by significant hypotension.78 Other agents that may be effective include buspirone, meperidine, and dexmedetomidine, the last two of which may be highly effective when used in combination.79 These agents have mild sedating effects and may affect the neurological exam in stroke patients.

Author

Publication

Design

Number of Patients

Clinical Question

Outcome

Els et al.

Georgia et al.

Georgiadis et al.

Schwab et al.

Cerebrovasc Diseases 2006; 21 (1-2): 79-85

Stroke 2004; 63:312-317

Stroke 2002;

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