Title:Anesthetic Neuroprotection: Antecedents and An Appraisal of Preclinical and Clinical Data Quality
Volume: 20
Issue: 36
Author(s): Kazuyoshi Ishida, Miles Berger, Jacob Nadler and David S. Warner
Affiliation:
Keywords:
Anesthetic, intravenous, volatile, brain, ischemia.
Abstract: Anesthetics have been studied for nearly fifty years as potential neuroprotective compounds in both perioperative and resuscitation
medicine. Although anesthetics present pharmacologic properties consistent with preservation of brain viability in the context of an
ischemic insult, no anesthetic has been proven efficacious for neuroprotection in humans. After such effort, it could be concluded that anesthetics
are simply not neuroprotective in humans. Moreover, pharmacologic neuroprotection with non-anesthetic drugs has also repeatedly
failed to be demonstrated in human acute brain injury. Recent focus has been on rectification of promising preclinical neuroprotection
data and subsequent failed clinical trials. This has led to consensus guidelines for the process of transferring purported therapeutics
from bench to bedside. In this review we first examined the history of anesthetic neuroprotection research. Then, a systematic review was
performed to identify major clinical trials of anesthetic neuroprotection. Both the preclinical neuroprotection portfolio cited to justify a
clinical trial and the design and conduct of that clinical trial were evaluated using modern standards that include the Stroke Therapy Academic
Industry Roundtable (STAIR) and Consolidated Standards of Reporting Trials (CONSORT) guidelines. In publications intended to
define anesthetic neuroprotection, we found overall poor quality of both preclinical efficacy analysis portfolios and clinical trial designs
and conduct. Hence, using current translational research standards, it was not possible to conclude from existing data whether anesthetics
ameliorate perioperative ischemic brain injury. Incorporation of advances in translational neuroprotection research conduct may provide a
basis for more definitive and potentially successful clinical trials of anesthetics as neuroprotectants.
