Anesthesia and Neurotoxicity Study Design, Execution, and Reporting in the Non-Human Primate: A Deep Dive

Feng Gao, MD, Investigator, Baylor College of Medicine

What is the quality of nonhuman primate (NHP) studies used to support the concern for anesthesia-related neurodevelopmental delay in children? This poster session at the IARS 2021 Annual Meeting described a systematic review of 18 manuscripts from studies in NHPs at postnatal ages 0 to 40 days with early anesthesia exposure.

Findings show deficits and inconsistencies in study design, execution, and reporting. Problems in study design include a lack of blinding during data acquisition and analysis with supra therapeutic anesthetic maintenance dosing in 28% of studies and a lack of sample size justification in 89% of studies. Critical inconsistencies also appear in or are due to 1) documentation of anesthesia provider, 2) electrocardiogram monitoring, 3) continuous arterial blood pressure monitoring, 4) use of spontaneous ventilation, 5) failed intubations with co-mingling of data analysis on ventilated and unventilated animals, 6) few studies reporting on survival, and 7) where anesthetics induce brain cell death. Additionally, a majority of behavioral outcomes studied were not significantly different from control groups.

Dr. Gao discussed the implications of his study.

How does your research advance the field of pediatric anesthesiology?

“Our study demonstrated that drawing concrete conclusions about anesthesia safety in neonates from neonatal nonhuman primates is challenging due to the complexity and expense of conducting research with these scarce animals.”

What is most significant about your research and/or the most significant result?

“We found that the design, conduct, and analysis of the primate studies used to support the concern for anesthesia-related neurodevelopmental delay were flawed in many of the same ways that compromised the rodent studies.”

What is the overall significance of your research?

“We hope our work will push for stronger rigor, design, reporting, and critical review of animal studies on neonatal animal models in pediatric anesthesia safety research.”

What may/will be different as a result of your research?

“We urge the scientific journals and the FDA to apply more stringent criteria to the evaluation of studies such as these, bringing in unbiased reviewers and statisticians from outside the field of anesthesiology to the process.”