Search

Ancrod has been used in Europe for over 15 years for peripheral vascular disease, deep vein thrombosis, and central retinal venous thrombosis, and in patients at risk for thromboembolism. In a double-blind, randomized, placebo-controlled study at University Hospitals in Cincinnati, 20 acute cerebral infarction patients received a series of IV infusions of ancrod (ten) or placebo (ten) for seven days. Early fibrinolysis with a small decrease in fibrinogen was observed, and d-dimers were elevated at four hours, indicating early clot lysis. At three months, patients with moderate to severe strokes (less than 40 on the Scandinavian Stroke Scale) in the ancrod group showed average improvement by a factor of 3 over the placebo group. No bleeding, abnormal laboratory results, or deaths occurred, but ancrod was discontinued in one patient who had seizures. As a result of this study, a double-blind multicenter international clinical trial to further assess the safety and effectiveness of ancrod is being planned.

The effects of high dose naloxone in humans have not been studied extensively. We treated 36 patients who had acute ischemic cerebral infarction with high doses of naloxone to evaluate potential efficacy and toxicity. All patients were treated with a 160-mg/m2 (4-mg/kg) loading dose followed by 80 mg/m2.h (2 mg/kg.h) x 24 h. There were no statistically significant changes in group mean arterial pressure, respiratory rate, or heart rate in response to the loading dose or infusion, although clinically significant changes did occur in four patients. Twenty-three patients had adverse reactions possibly related to naloxone, the most common of which were nausea (n = 20), bradycardia and/or hypotension (n = 3), myoclonus (n = 1), and hypertension (n = 1). Seven patients had naloxone discontinued for possible adverse reactions. All adverse reactions abated with discontinuation of naloxone and/or pharmacologic therapy when indicated. No deaths were attributable to naloxone treatment. High dose naloxone appears to be well tolerated in the majority of elderly patients with acute cerebral infarction.

As part of a prospective therapy study of 65 patients with acute, nonhemorrhagic, cerebral infarction, computed tomographic scans of the head were obtained at admission, 7-10 days, and 3 months. The scans were analyzed for the presence, site, size, and volume measurement of the infarction. At 7-10 days, the mean infarction volume as measured by computed tomography was 55 cm3 or about 4 x 4 x 3.5 cm (range = 0-507 cm3). At 3 months, the mean infarction volume decreased by 25% to 41 cm3. For the 26 scans showing infarction at the time of admission, the mean lesion volume was 33 cm3 at admission, 51 cm3 at 7-10 days, and 49 cm3 at 3 months. With lesion size at 7-10 days expressed as percentage of total brain volume, the mean infarction size was only 5%. Of the 49 patients with lesions revealed by computed tomography at 7-10 days, 20 had an infarction of 1% or less of total brain volume, while only six had an infarction of 20% or more of total brain volume. The lesion volumes as measured by the 7-10-day computed tomography correlated with the neurologic examination scores on admission (Spearman's rank-order correlation = 0.78) and with the scores at 1 week (Spearman's rank-order correlation = 0.79).

Although time has been recognized as a critical factor in the treatment of other arterial occlusive disorders, it has been an underemphasized variable in the treatment of acute stroke. Animal models of cerebral arterial occlusion have demonstrated that neurologic recovery is more likely the shorter the duration of occlusion. Complete recovery does not occur if the occlusion persists more than six hours. Prior trials have only rarely begun treatment within six hours of stroke onset. Over the past five years, we have participated in three stroke trials and have tried to identify factors that lead to delays in treatment. Factors that affect the time from stroke onset to arrival at the hospital include recognition of acute stroke by the patient, prehospital care personnel, and physicians. After arrival at the hospital, factors that can significantly delay treatment include the time to obtain computed tomography and the site of treatment (emergency department vs ICU). With proper attention, the time from patient arrival until treatment should be less than one hour. Future efforts should be directed toward reducing the time from stroke onset until arrival at the hospital. Education of the public, high-risk patients, prehospital care providers, and physicians may aid in these efforts.

We studied the ability of serum glucose concentration and neurologic deficits at admission in predicting the outcome of acute cerebral ischemia in 65 patients given naloxone. Among our patients, the volume of infarction on computed tomograms and outcome were strongly related to the severity of neurologic deficits found at admission. Neither a history of diabetes nor hyperglycemia when added to the results of the initial neurologic assessment improved prediction of outcome after acute cerebral infarction.

Editorial. Discusses the difficulty of early treatment for ischemic stroke. Reason for the impracticality of early treatment for ischemic stroke; Description of acute cerebral infarction; Variables limiting early stroke treatment in humans.