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"Awash in opioids!"

June 24th, 2016

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Evan Kharasch, MD, PhD

"Prescription opioids have become a gateway to heroin," Evan Kharasch, MD, PhD, told the audience at Grand Rounds on June 22. While it's well appreciated that deaths from opioid overdose are increasing at an alarming rate, he said, this isn't all due to prescription opioids. Deaths from heroin use are up 26 percent, and deaths from synthetic opioids, especially fentanyl, are up 80 percent.

Dr. Kharasch, the Director of the Division of Clinical and Translational Research in Anesthesiology at Washington University School of Medicine in St. Louis, visited UCLA as a guest professor of the Department of Anesthesiology & Perioperative Medicine. He chose as his Grand Rounds topic, "Perioperative Opioids, Public Health, and Anesthesiology," pointing out that one American dies every 18 minutes from narcotic overdose.

Of the people who use heroin today, Dr. Kharasch said, 79 percent started down the road of narcotic abuse because they were taking legitimately prescribed opioids for pain—after dental procedures, surgery, or back injuries. Current data suggest that people who become dependent on prescription opioids are 19 times more likely to try heroin than the average person.

"Today, it's not uncommon for heroin to be cut with fentanyl," Dr. Kharasch said, because fentanyl is cheap. "Street chemists are really good chemists," he explained. "It's easy to make gram and kilogram quantities of fentanyl." But mixing with fentanyl makes heroin far more potent, and increases the risk of death by overdose.

America uses 80 percent of the world's opioids, Dr. Kharasch explained. "But it's probably not because we have 80 percent of the world's pain!"

Dr. Kharasch believes that anesthesiologists face three clinical dilemmas regarding perioperative opioids and public health:

  • As many as 80 percent of patients report inadequate postoperative pain relief, and acute postoperative pain is the major risk factor for chronic pain
  • Postoperative respiratory depression is a persistent risk with opioids
  • Take-home opioids are overprescribed, leading to diversion, abuse, addiction, and overdose.

While we hear a great deal about the problem of patients who "prescription shop", seeking drugs from different physicians and emergency rooms, this is not the primary source of illicit opioids, Dr. Kharasch said. The problem often starts with friends and family members, who may have access to unused or leftover opioids that they find in a medicine cabinet.

"Diversion is rampant," Dr. Kharasch said, advising the audience members to go home and check their own medicine cabinets. "The system is awash in opioids!"

Reservoirs of unused drugs

The issue is not the legitimate use of opioids to treat postoperative pain, he said. The issue is that patients may stop taking opioids sooner than anticipated, or they may have leftover opioids once their pain has resolved. This results in reservoirs of unused drugs that are easy to access in private homes—for example, at a realtor's open house, during a social gathering, or when outside workers are on site. When postoperative opioids are overprescribed, they add to the reservoir that may be stolen, shared, or sold.

Dr. Kharasch made two recommendations:

  • Enable more "just-in-time" availability of prescription pain medications, so that physicians aren't tempted to write for a large supply in order to avoid middle-of-the-night phone calls;
  • Work with patients to adjust their expectations about postoperative pain.

There are large cultural differences between Europe and America about patient expectations of postoperative pain, Dr. Kharasch explained. In the US, pain is considered unacceptable, and the thinking is that nobody should have pain. In Europe, on the other hand, some postoperative pain is expected and not considered a treatment failure.

For anesthesiologists, the clinical dilemma is how to provide effective analgesia while minimizing side effects. The vast majority—88 percent—of cases of severe respiratory depression occur within 24 hours of surgery, Dr. Kharasch said. Patient-controlled analgesia (PCA) is not the answer, as half of these adverse events occur with the use of PCA.

Short-acting narcotics make problem worse

Recently, the trend has been to try to avoid adverse effects by using shorter-acting analgesics like fentanyl and remifentanil. But these may lead paradoxically to hyperalgesia, Dr. Kharasch noted, increasing the patient's pain medication requirements in the postoperative period.

"Are shorter-acting opioids optimal?" he asked the audience. Probably not, he said, because opioid analgesic effects ideally should match the duration of pain.

For Dr. Kharasch, the "sweet spot" for painful procedures such as spine surgery may be found with the use of methadone, a narcotic that may be given IV and has a duration of action of 24 to 36 hours. He described it as a "very utilitarian drug", that is conceptually safer because many patients require no subsequent doses after surgery, and incur less risk of respiratory depression. In his department in St. Louis, he said, the use of methadone has substantially reduced costly postoperative PCA use with just one IV dose given before the induction of anesthesia.

Does methadone alone have the potential to address all the challenges physicians face with regard to opioid abuse?

"Predictions are very difficult, especially about the future," Dr. Kharasch said, quoting Yogi Berra. Scientists may discover new drugs to treat pain, looking at genetic differences between populations and how these affect responses. He mentioned "biased signaling" as a new avenue for drug development, studying how different molecules that bind to opioid receptors have different effects on analgesia and respiratory depression.

Dr. Kharasch was appointed last fall as the new editor-in-chief of Anesthesiology, the official medical journal of the American Society of Anesthesiologists. He chairs the ASA Committee on Research, serves on the Executive Committee of the Foundation for Anesthesia Education and Research (FAER), and is an elected member of the National Academy of Medicine.



Karen Sibert, MD

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