A systematic review of methodology applied during preclinical anesthetic XXXX studies: important issues and lessons relevant to the design of future clinical research.

@entity1 @entity137 @entity149 @entity2359
Preclinical evidence suggests that anesthetic agents harm the developing brain thereby causing long-term @entity149 . It is not clear if these findings apply to @entity1 , and retrospective epidemiological studies thus far have failed to show definitive evidence that anesthetic agents are harmful to the developing @entity1 brain. AIM: The aim of this systematic review was to summarize the preclinical studies published over the past decade, with a focus on methodological issues, to facilitate the comparison between different preclinical studies and inform better design of future trials. METHOD: The literature search identified 941 articles related to the topic of @entity2359 . As the primary aim of this systematic review was to compare methodologies applied in animal studies to inform future trials, we excluded a priori all articles focused on putative mechanism of @entity2359 and the neuroprotective agents. Forty-seven preclinical studies were finally included in this review. RESULTS: Methods used in these studies were highly heterogeneous-animals were exposed to anesthetic agents at different developmental stages, in various doses and in various combinations with other drugs, and overall showed diverse @entity137 profiles. Physiological monitoring and maintenance of physiological homeostasis was variable and the use of cognitive tests was generally limited to assessment of specific brain areas, with restricted translational relevance to @entity1 . CONCLUSION: Comparison between studies is thus complicated by this heterogeneous methodology and the relevance of the combined body of literature to @entity1 remains uncertain. Future preclinical studies should use better standardized methodologies to facilitate transferability of findings from preclinical into clinical science.
