Animal studies shouldn't alter anesthesiology practice in newborns

Jun 26 2007

Recent studies showing that commonly used anesthetic agents can cause brain damage in animals don't prove that similar harmful effects occur in human newborns - and shouldn't affect current approaches to anesthesia in preterm and ill infants, according to a leading expert on pain management in newborns.

The July issue of the journal Anesthesiology features an editorial by Dr. Kanwaljeet J.S. Anand, Professor of Pediatrics, Anesthesiology, Pharmacology, Neurobiology & Developmental Sciences in the College of Medicine, University of Arkansas for Medical Sciences and Director of the Pain Neurobiology Lab at Arkansas Children's Hospital Research Institute. "The weaknesses of these animal studies, coupled with substantial evidence from clinical studies that demonstrate the detrimental effects of unrelieved pain or stress during surgery, justify the continued clinical use of ketamine and other anesthetic agents for neonates and infants," said Dr. Anand.

The new editorial responds to recent studies suggesting that anesthetic agents have "neurotoxic" effects in the brains of newborn animals. Exposure to anesthetics has been linked to increases in apoptosis (programmed cell death) in the brains of newborn rats, mice and other animals. The reports have sparked controversy in the pages of Anesthesiology and elsewhere, with some commentators suggesting that newborns should not be exposed to anesthetics.

However, Dr. Anand points out some key weaknesses of the experimental models and proposes that findings are not relevant to clinical practice. "These experiments used very large doses of ketamine, which are not used clinically," said Dr. Anand. "The animals were also exposed to prolonged anesthesia without being subjected to ongoing surgery or other painful stimuli, which are the clinical indications for the use of anesthesia."

Dr. Anand also questions the use of simplistic rules of thumb equating the development of rodent and human brains during gestation, and suggests that more sophisticated comparisons are needed. "According to a novel method for extrapolating developmental time across ten different mammalian species, these effects occurred at a developmental maturity of the brain that corresponds to developmental stages occurring before viability of the human fetus," said Dr Anand. "Thus, the experimental findings are not applicable to the care of preterm newborn infants."

At an open public meeting, the voting members of an Advisory Committee of the Food & Drug Administration (FDA) unanimously reached the same conclusion. "Critical examination of these animal studies dispels concerns that practicing anesthesiologists and parents may have regarding the appropriate clinical use of anesthetic agents in newborns and small infants," Dr. Anand concluded.

For additional information on this study, go to: http://www.anesthesiology.org

Founded in 1905, the American Society of Anesthesiologists is an educational, research and scientific association with 41,000 members organized to raise and maintain the standards of the medical practice of anesthesiology and improve the care of the patient.

http://www.asahq.org