Monkey Business in the ORs: When Veterinary Anesthetics Collide with Human Medicine

Jordan Francke, MD, MPH

As substance use-related deaths in the United States continue to rise, anesthesiologists play a critical role in recognizing warning signs and intervening in patients who utilize dangerous recreational drugs, particularly ultrapotent analgesics such as carfentanil and xylazine. In a riveting session on Friday, May 17 at the 2024 Annual Meeting, presented by IARS and SOCCA, entitled “Tranq Dope and Elephant Tranquilizers – Veterinary Anesthetics in Human Medicine,” a multidisciplinary panel comprising anesthesiologists with subspecialty focuses of veterinary anesthesia, pain anesthesia, and addiction medicine exchanged expert opinions on this emerging threat. This engaging session was moderated by Kristopher Schroeder, MD, FASA, vice chair of faculty development and interim vice chair of education at University of Wisconsin.

Carrie Schroeder, DVM, DACVAA, faculty veterinary anesthesiologist at the University of Wisconsin-Madison within the Department of Surgical Sciences, opened the session by differentiating between three subfields of veterinary anesthesia: small animal anesthesia (e.g., dogs and cats), large animal anesthesia (e.g., horses and cattle), and zoo/wildlife anesthesia (e.g., bears and giraffes). Due to their distinct anatomies, aggression levels, and sheer masses, animals within each of these subgroups require individualized approaches. This includes pharmacologic agents with potencies and onset times that are uncharacteristic of drugs used in human patients. Dr. Schroeder illustrated this point comparing four different veterinary drugs commonly employed as alpha-2 agonists: xylazine (used for years by veterinarians, but becoming increasingly a drug of abuse in humans), detomidine, medetomidine, and dexmedetomidine (the only one routinely used clinically in human patients). While pediatric anesthesiologists may occasionally utilize an intramuscular ketamine injection (colloquially called a “ketamine dart”) to provide sedation to an agitated patient before intravenous access can be obtained, Dr. Schroeder and her team routinely use an actual dart gun containing drug-filled barbs to sedate large mammals safely. She illustrated the impressive power of these tranquilizers with an anesthetic record of a tiger whose anesthesia was induced with just a few milliliters of hyperconcentrated alpha-2 agonists, ketamine, and fentanyl derivatives. Unlike in humans, it is then customary with large mammals to reverse the sedation with drugs such as atipamezole and naltrexone, allowing an animal to go from intubated to ambulating within minutes.

Daniel Larach, MD, MSTR, assistant professor of Pain Medicine at Vanderbilt University Medical Center, subsequently explained the pharmacologic basis of why these drugs are so dangerous. Carfentanil, an extremely potent veterinary synthetic opioid, is becoming an increasingly common additive in recreational drugs of abuse. It has an exceptionally high affinity for the µ-opioid receptor (higher even than naloxone), coupled with an exceptionally low dissociation constant. It is 10,000 times more potent than morphine, such that even microscopic amounts that inadvertently enter the body through inhaling the drug or touching an injection site ungloved can lead to fatal outcomes. Dr. Larach refuted a common misconception surrounding carfentanil that it “cannot be reversed” by naloxone, but rather that unusually large amounts of naloxone (>10x the typical dose) are required to reverse the opioid (https://pubmed.ncbi.nlm.nih.gov/38445085/). He ended his portion of the panel with three salient takeaways: (1) in the setting of carfentanil overdose, a dose of at least 2 mg of naloxone should be employed initially, (2) give more if no clinical response is seen, and (3) have a low threshold for beginning an infusion or redosing naloxone.

Sudheer Potru, DO, FASA, FASAM, is a triple-boarded physician in anesthesiology, pain medicine, and addiction medicine and assistant professor at Emory University School of Medicine, where he serves veteran patients with substance-use disorders. Dr. Potru provided the audience evidence that drugs of abuse hijack a mammal’s intrinsic mesolimbic reward pathway that guides the dopamine-fueled enjoyment of routine behaviors such as eating, exercise, and sexual activity. Some drugs provide more dopamine release than all these behaviors combined. He reviewed the risk factors that tie many of his patients together: namely genetic predispositions, family dysfunction, race, and adverse childhood experiences.

Dr. Potru also reminded the audience that nearly all anesthetic subspecialties overlap with an aspect of addiction medicine: from trauma patients whose judgment was impaired by substances to an acutely intoxicated patient undergoing general anesthesia to neonate abstinence syndrome. It also is becoming increasingly common: in the year 2019, only a handful of states had reported a positive case of human xylazine intoxication (https://pubmed.ncbi.nlm.nih.gov/35770859/). By 2021, nearly all 50 states had. While this might sound discouraging, Dr. Potru equipped the audience with a few key steps to mitigate the problem: (1) avoid stigmatizing language when discussing substance use with patients, (2) treat patients as you would your loved ones, (3) call your state representatives in support of the Illicit Xylazine Act and (4) advocate for new research on drugs to reverse potent alpha-2 agonists that are becoming increasingly common drugs of abuse.