Background and Purpose-Hypothermia reduces neuronal damage in animal stroke models. Whether hypothermia is neuroprotective in patients with acute stroke remains to be clarified. In this case-control study, we evaluated the feasibility and safety of inducing modest hypothermia by a surface cooling method in awake patients with acute stroke. Methods-We prospectively included 17 patients (cases) with stroke admitted within 12 hours from stoke onset (mean 3.25 hours). They were given hypothermic treatment for 6 hours by the "forced air" method, a surface cooling method that uses a cooling blanket with a flow of cool air (10°C). Pethidine was given to treat compensatory shivering. Cases were compared with 56 patients (controls) from the Copenhagen Stroke Study matched for age, gender, initial stroke severity, body temperature on admission, and time from stroke onset to admission. Blood cytology, biochemistry, ECGs, and body temperature were monitored during hypothermic treatment. Multiple regression analyses on outcome were performed to examine the safety of hypothermic therapy. Results-Body temperature decreased from t 0 ϭ36.8°C to t 6 ϭ35.5°C (PϽ0.001), and hypothermia was present until 4 hours after therapy (t 0 ϭ36.8°C versus t 10 ϭ36.5°C; Pϭ0.01). Mortality at 6 months after stroke was 12% in cases versus 23% in controls (Pϭ0.50). Final neurological impairment (Scandinavian Stroke Scale score at 6 months) was mean 42.4 points in cases versus 47.9 in controls (Pϭ0.21). Hypothermic therapy was not a predictor of poor outcome in the multivariate analyses. Conclusions-Modest hypothermia can be achieved in awake patients with acute stroke by surface cooling with the "forced air" method, in combination with pethidine to treat shivering. It was not associated with a poor outcome. We suggest a large, randomized clinical trial to test the possible beneficial effect of induced modest hypothermia in unselected patients with stroke. (Stroke. 2000;31:2251-2256.)

Background and Purpose-Body temperature is considered crucial in the management of acute stroke patients. Recently hypothermia applied as a therapy for stroke has been demonstrated to be feasible and safe in acute stroke patients. In the present study, we investigated the predictive role of admission body temperature to the long-term mortality in stroke patients. Methods-We studied 390 patients with acute stroke admitted within 6 hours from stroke onset. Admission clinical characteristics (age, sex, admission stroke severity, admission blood glucose, cardiovascular risk factor profile, and stroke subtype) were recorded for patients with hypothermia (body temperature Յ37°C) versus patients with hyperthermia (body temperature Ͼ37°C). Univariately the mortality rates for all patients were studied by Kaplan-Meier statistics. To find independent predictors of long-term mortality for all patients, Cox proportional-hazards models were built. We included all clinical characteristics and body temperature as a continuous variable. Results-Patients with hyperthermia had more severe strokes and more frequently diabetes, whereas no difference was found for the other clinical characteristics. For all patients mortality rate at 60 months after stroke was higher for patients with hyperthermia (73 per 100 cases versus 59 per 10 cases, Pϭ0.001). When body temperature was studied in a multivariate Cox proportional-hazards model, a 1°C increase of admission body temperature independently predicted a 30% relative increase (95% CI, 4% to 57%) in long-term mortality risk. For 3-month survivors we found no association between body temperature and long-term survival when studied in a multivariate Cox proportional hazard model (hazards ratio, 1.11 per 1°C; 95% CI, 0.82 to 1.52). Conclusion-Low body temperature on admission is considered to be an independent predictor of good short-term outcome. The present study suggests that admission body temperature seems to be a major determinant even for long-term mortality after stroke. Hypothermic therapy in the early stage in which body temperature is kept low for a longer period after ictus could be a long-lasting neuroprotective measure.

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BackgroundThe use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia.MethodsFirst, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies. Finally we tested the hypothermic properties in a large animal. The screening was in conscious rats, the dose-response experiments in conscious rats and in cynomologus monkeys, and the finally we tested the hypothermic properties in conscious young cattle (calves with a body weight as an adult human). The investigated TRPV1 agonists were administered by continuous intravenous infusion.ResultsScreening: Dihydrocapsaicin (DHC), a component of chili pepper, displayed a desirable hypothermic profile with regards to the duration, depth and control in conscious rats. Dose-response experiments: In both rats and cynomologus monkeys DHC caused a dose-dependent and immediate decrease in body temperature. Thus in rats, infusion of DHC at doses of 0.125, 0.25, 0.50, and 0.75 mg/kg/h caused a maximal ΔT (°C) as compared to vehicle control of -0.9, -1.5, -2.0, and -4.2 within approximately 1 hour until the 6 hour infusion was stopped. Finally, in calves the intravenous infusion of DHC was able to maintain mild hypothermia with ΔT > -3°C for more than 12 hours.ConclusionsOur data support the hypothesis that infusion of dihydrocapsaicin is a candidate for testing as a primary or adjunct method of inducing and maintaining therapeutic hypothermia.