Stroke clinical hypothermia

De Georgia et al. Stroke 2004 63 312-317 Prospective, randomized cooling vs. standard therapy for feasibility and safety 18 of40tx with hypothermia Hypothermia to 33°C with endovascular catheter on safety in pts with anterior circulation stroke and NIHSS >8 Similar clinical outcomes and lesion growth as measured on DWI MRI. Nonsignificant reduction in DWI volume in patients who cooled well. 

Georgiadis et al. Stroke 2002 33(6) 1584-1588 Nonblinded prospective hemicraniectomy for nondominant and cooling for dominant hemisphere 19 of 36 tx with hypothermia Hypothermia to 33°C with cooling blankets or endovascular technique on clinical course in pts with >2/3 MCA infarct 12% vs. 47% mortality for surgery vs. hypothermia. Hypothermia with increased complications of hypotension and electrolyte abnormalities. Both tx with longer ICU course... 

The most extreme manifestation of untreated hypothyroidism is myxedema coma, which even if detected early and appropriately treated, carries a mortality rate of 30 to 60%. Myxedema coma is a misnomer. Most patients exhibit neither the myxedema nor coma. Patients with myxedema coma usually have longstanding hypothyroidism with the classic symptoms of hypothyroidism. Decompensation into myxedema coma may occur when the homeostatic mechanisms of the severely hypothyroid patient are subject to a stressful precipitating event (e.g., infection, trauma, some medications, stroke, surgery). The principal manifestation of myxedema coma is a deterioration of mental status (apathy, confusion, psychosis, but rarely coma). Other common clinical features include hypothermia, diastolic hypertension (early), hypotension (late), hypoventilation, hypoglycemia, and hyponatremia. If myxedema coma is suspected, the patient is usually admitted to an intensive care unit for pulmonary and cardiovascular support... 

The main role of mild hypothermia against stroke may, perhaps, be to extend the therapeutic window of other treatment modalities. On the other hand, hypothermia is by far the most potent neuroprotectant available against experimental cerebral ischemia, and new technological advances are now facilitating its implementation in the clinical setting. Understanding the mechanisms by which mild hypothermia exerts its neuroprotective effects will allow us to optimize its use as a therapeutic strategy. 

A large effort examining the potential efficacy of mild hypothermia to protect neurons from ischemic injury has shown promise in experimental stroke models and is now being translated into clinical trials. To develop the use of mild hypothermia as an efficacious and safe... 

In addition, any proposed treatment with other agent(s) in conjunction with hypothermia will require very careful scrutiny of efficacy in preclinical models because of the marked benefit of hypothermia alone reported in many experimental studies. The addition of the alternative agent(s) must result in a clear-cut additional benefit compared with hypothermia treatment alone. Moreover, as previously discussed, it would be helpful to prove in both clinical and preclinical studies that each agent individually has some degree of benefit, as neither hypothermia nor neuroprotective pharmaceuticals have yet been definitively proven to be beneficial in clinical studies of acute stroke treatment. 

No preclinical studies of neuroprotectives plus hypothermia in permanent occlusion stroke models without thrombolysis have been reported. This is of particular importance because these permanent ischemia models may better simulate the events that occur clinically in the vast majority of stroke patients who do not receive reperfusion therapy with a thrombolytic agent. Such studies will be necessary before proceeding with clinical trials in stroke patients. 

Nevertheless, the possibility of combining hypothermia with other types of neuroprotection or thrombolysis is intriguing, and certainly deserves future study. However, if this treatment is ever to impact clinical practice, it is essential that appropriate preclinical studies be conducted. In particular, the rigorous evaluation of these combinations in a variety of ischemic models that most closely simulate the pathophysiology of acute ischemic stroke, is needed. Only after such extensive testing should the possibility of combination therapy be subsequently evaluated in randomized clinical trials. 

Deliberate mild hypothermia has been shown to be an extremely effective means of neuroprotection during periods of ischemia in experimental models. Intraoperative mild hypothermia has become a standard of practice for many neurosurgeons performing complex intracranial procedures. Recent findings of neurologic benefit in prospective, randomized, controlled clinical studies of cardiac arrest patients are encouraging, but more research is required to confirm and extend these positive results to other patients with stroke and traumatic insults. Further investigation must be completed to establish the optimal time and duration when treatment should be instituted to offer the optimal protection for patients with acute ischemic and traumatic injuries. 

CLINICAL EXPERIENCE WITH HYPOTHERMIA FOLLOWING STROKE... 

In this chapter, we discuss the relationship between the body temperature and clinical outcome in acute stroke patients and describe our experience with the clinical application of mild hypothermia for the treatment of acute stroke. Finally, we comment on the future direction of hypothermic research and clinical practice. 

In the acute group, in which the hypothermia was initiated at KM-2 h after stroke, the clinical outcome varied depending on the time of hypothermia initiation. A patient who underwent the therapy beginning at 10 h after stroke became completely independent. Another patient who underwent the therapy at 24 h after stroke had a moderate right hemiparesis, but was able to walk with a cane. The remaining patient who underwent the therapy at 42 h after stroke became disabled and died in the chronic phase. Thus, it seems that the time for initiating hypothermia critically influences the clinical outcome. This supports the view that the hypothermia therapy may be best indicated for hyperacute stroke. 

Comprehensive and up-to-date, Hypothermia and Cerebral Ischemia Mechanisms and Clinical Applications summarizes for clinicians and basic scientists alike all that is known about the use of hypothermia as a neuroprotective strategy in the treatment of today s stroke and TBI patients. 

Resurgence of Hypothermia as a Treatment for Brain Injury. The Effects of Hypothermia and Hyperthermia in Global Cerebral Ischemia. Mild Hypothermia in Experimental Focal Cerebral Ischemia. Hypothermic Protection in Traumatic Brain Injury. Postischemic Hypothermia Provides Long-Term Neuroprotection in Rodents. Combination Therapy With Hypothermia and Pharmaceuticals for the T reatment of Acute Cerebral Ischemia. Intraoperative and Intensive Care Management of the Patient Undergoing Mild Hypothermia. Management of Traumatic Brain Injury With Moderate Hypothermia. Hypothermia Clinical Experience in Stroke Patients. Hypothermia Therapy Future Directions in Research and Clinical Practice. Index. 

Hypothermia and Cerebral Ischemia Mechanisms and Clinical Applications is intended to provide a comprehensive review of mild hypothermia s therapeutic potential, its limitations, and recent developments in both basic and clinical research. We hope that this volume serves to educate clinicians, other health professionals, and basic scientists, as well as promote interest in the study and implementation of mild hypothermia for the treatment of stroke and TBI. 

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