Evidence for the Use of Isoflurane as a Replacement for Chloral Hydrate Anesthesia in Experimental Stroke: An Ethical Issue

Abstract

Since an ethical issue has been raised regarding the use of the well-known anesthetic agent chloral hydrate, owing to its mutagenic and carcinogenic effects in animals, attention of neuroscientists has turned to finding out an alternative agent able to meet not only potency, safety, and analgesic efficacy, but also reduced neuroprotective effect for stroke research. The aim of this study was to compare the potential of chloral hydrate and isoflurane for both modulating the action of the experimental neuroprotectant MK801 and exerting analgesia. After middle cerebral artery occlusion in rats, no difference was observed in 24 h survival rate, success of ischemia, or infarct volume reduction between both anesthetics. However, isoflurane exerted a more pronounced analgesic effect than chloral hydrate as evidenced by formalin test 3 hours after anesthesia onset, thus encouraging the use of isoflurane in experimental stroke models.

Ginsenoside-Rb1 for Ischemic Stroke: A Systematic Review and Meta-analysis of Preclinical Evidence and Possible Mechanisms

“…Although it has relatively few effects on cardiovascular function and no neuroprotection in stroke studies (Ozden and Isenmann, 2004), chloral hydrate has raised questioned regarding its prolonged recovery, mutagenic effects, and carcinogenic effects in animal use. Currently, isoflurane has been suggested as a replacement for chloral hydrate, because it is easy to administer and to titrate, has a rapid onset and recovery period, an adequate and reproducible anesthesia depth, minimal cardiac depression, and ethical considerations (Maud et al, 2014). Although previous studies demonstrated that anesthetics including ketamine, isofl urane, and halothane had potential neuroprotective effects (Kapinya et al, 2002;Xiong et al, 2003;Kitano et al, 2007b;Wang et al, 2008;Deng et al, 2014;Tang et al, 2015), isoflurane can be an appropriate anesthetic agent when establishing the MCAO model (Kitano et al, 2007a).…”

Kaixinsan, a Well-Known Chinese Herbal Prescription, for Alzheimer's Disease and Depression: A Preclinical Systematic Review

“…Although chloral hydrate has not been shown to induce neuroprotection in rats (Ozden and Isenmann, 2004), it has been shown to induce systemic toxicity in rodents (Huske et al, 2016). In addition, chloral hydrate may also be a carcinogen in rodents, which is an ethical issue (Maud et al, 2014). It is essential to select appropriate anesthetics in neurological studies.…”

Refinement of anesthetic choice in procedures preceding psychopharmacological studies

“…The subanesthetic concentrations used were 0.5 and 1.5%. Anesthesia was inducted with 4% of isoflurane (approximately 5 minutes for induction) and maintained with 2% (Maud et al 2014). Administration was performed in a room with temperature varying between 22 and 24 ºC.…”

“…In rodents, chloral hydrate seems to generate an effective and prolonged anesthesia (1 hour and 30 minutes approximately) (Field et al, 1993;Maud et al, 2014). Thus, the use of this anesthetic is advantageous for long-term procedures, because it may not be necessary to reapply the anesthetic during the procedure.…”

“…Isoflurane is a volatile anesthetic that allows an appropriate control of anesthesia depth as well as rapid recovery. This anesthetic displays relatively safety for use in in both short and long-term procedures (Janssen et al 2004;Cesarovic et al 2010;Maud et al 2014). Our study adds another advantage, which means, isoflurane appears to be an adequate anesthetic for use in surgeries preceding tests for antidepressant or anxiety-like effects.…”