Combined Neuroprotective Modalities Coupled with Thrombolysis in Acute Ischemic Stroke

A Pilot Study of Caffeinol and Mild Hypothermia

Sheryl Martin-Schild, Hen Hallevi, Hashem Shaltoni, Andrew D. Barreto, Nicole R. Gonzales, Jarek Aronowski, Sean I. Savitz, James C. Grotta

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Background: Both caffeinol and hypothermia are neuroprotective in preclinical models of transient middle cerebral artery occlusion. We tested whether combining caffeinol and hypothermia with tissue plasminogen activator (t-PA) in patients with acute stroke is safe and feasible. Methods: Twenty patients with acute ischemic stroke were treated with caffeinol (caffeine 8-9 mg/kg + ethanol 0.4 g/kg intravenously [IV] × 2 hours, started by 4 hours after symptom onset) and hypothermia (started by 5 hours and continued for 24 hours [target temperature 33-35°C] followed by 12 hours of rewarming). IV t-PA was given to eligible patients. Meperidine and buspirone were used to suppress shivering. Results: All patients received caffeinol, and most reached target blood levels. Cooling was attempted in 18 patients via endovascular (n = 8) or surface (n = 10) approaches. Two patients were not cooled due to catheter or machine failure. Thirteen patients reached target temperature; average time from symptom onset was 9 hours and 43 minutes. The last 5 hypothermia patients received surface cooling with iced saline induction and larger doses of meperidine; all patients reached target temperature, on average within 2 hours and 30 minutes from induction and 6 hours and 21 minutes from symptom onset. Three patients died: one from symptomatic hemorrhage, one from malignant cerebral edema, and one from unrelated medical complications. No adverse events were attributed to caffeinol. One patient had reduced respiratory drive due to meperidine, requiring BiPAP. Discussion: Combining caffeinol with hypothermia in patients with acute stroke given IV t-PA is feasible. A prospective placebo-controlled randomized study is needed to further assess safety and to test the efficacy of caffeinol, hypothermia, or both.

Original languageEnglish (US)
Pages (from-to)86-96
Number of pages11
JournalJournal of Stroke and Cerebrovascular Diseases
Volume18
Issue number2
DOIs
StatePublished - Mar 1 2009
Externally publishedYes

Fingerprint

Hypothermia
Stroke
Meperidine
Tissue Plasminogen Activator
Temperature
caffeinol
Buspirone
Shivering
Rewarming
Middle Cerebral Artery Infarction
Brain Edema
Caffeine
Ethanol
Catheters
Placebos
Hemorrhage
Safety

Keywords

  • Acute ischemic stroke
  • feasibility
  • hypothermia
  • neuroprotection
  • safety

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery
  • Rehabilitation
  • Cardiology and Cardiovascular Medicine

Cite this

Combined Neuroprotective Modalities Coupled with Thrombolysis in Acute Ischemic Stroke : A Pilot Study of Caffeinol and Mild Hypothermia. / Martin-Schild, Sheryl; Hallevi, Hen; Shaltoni, Hashem; Barreto, Andrew D.; Gonzales, Nicole R.; Aronowski, Jarek; Savitz, Sean I.; Grotta, James C.

In: Journal of Stroke and Cerebrovascular Diseases, Vol. 18, No. 2, 01.03.2009, p. 86-96.

Research output: Contribution to journalArticle

Martin-Schild, Sheryl ; Hallevi, Hen ; Shaltoni, Hashem ; Barreto, Andrew D. ; Gonzales, Nicole R. ; Aronowski, Jarek ; Savitz, Sean I. ; Grotta, James C. / Combined Neuroprotective Modalities Coupled with Thrombolysis in Acute Ischemic Stroke : A Pilot Study of Caffeinol and Mild Hypothermia. In: Journal of Stroke and Cerebrovascular Diseases. 2009 ; Vol. 18, No. 2. pp. 86-96.
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