Guidelines for Use of IV Ketamine Infusions for Acute Pain Management Released

Steven P. Cohen, MD

The American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists have released consensus guidelines on the use of intravenous (IV) ketamine for the management of acute pain.

“The use of ketamine for chronic pain has skyrocketed, and because it is an off-label use of a generic drug, there has not been FDA oversight. This has led to a wide range of indications, and lack of standardization regarding indications, contraindications and dosing,” Steven P. Cohen, MD, a professor of anesthesiology and critical care medicine at the Johns Hopkins University School of Medicine, and a leading author of the new guidelines, told MD Magazine. "These guidelines have tried to provide a framework for major issues for which there is no consensus."

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The guidelines were developed to cover the following areas, all of which the group of authors was able to reach consensus on:

• Indications and contraindications for acute pain and whether they differ from those for chronic pain.
• Evidence for the use of ketamine as an adjunct to opioid-based therapy.
• Evidence supporting patient-controlled ketamine analgesia.
• Use of nonparenteral forms of ketamine.
• Subanesthetic dosage range and whether the evidence supports those dosages for acute pain.

The guidelines note that there is a variety of supporting evidence for the use of ketamine as a stand-alone option, adjunct to opioids, and—to a smaller degree—as a formulation for intranasal use. The contraindications agreed upon for acute are similar to those for chronic pain, in part, according to Cohen and colleagues, due to dosing range similarities.

“Larger studies evaluating different acute pain conditions are needed to enhance patient selection, determine the effectiveness of nonparenteral ketamine alternatives, define optimal treatment parameters, and develop protocols optimizing safety and access to care,” they wrote.

Ultimately, the guidelines sought to clear up the confusion about the therapy, some of which is a result of different regulations at the state level. Maryland, for example, considers ketamine an anesthetic, so nurses cannot push for its use, thus the guidelines try to define what is an anesthetic or subanesthetic dosage, Cohen said.

"There is confusion among healthcare providers, patients, regulators, institutions and payers about who might benefit from infusions, and how can they safely and effectively be implemented," he explained. "Considerations include how much medication should be given, and over what time period, how should patients be monitored, whether there is any benefit from non-parenteral forms of ketamine, and how to constitute a response."

As far as acute pain is concerned, it appears clear that ketamine is available to play a role. Cohen, as the Director of Pain Research at the Walter Reed National Military Medical Center and a retired army colonel, agrees that there is definitely a place for ketamine in its management, including military implications. "Ketamine can be used as a stand-alone drug, or in conjunction with opioids, in people who are opioid-tolerant," he said. "Because the total dosage is likely to be less than that administered for chronic pain—which may require multiple infusions—there may also be less of certain side effects."

With questions abound regarding the best pain management strategies, ketamine infusions, while a treatment option for decades, have recently gained momentum due in part to the ongoing national opioid crisis. That widespread use is what prompted the need for further guidance.

“As everybody knows, at this point, we have an opiate crisis in this country,” Steven P. Levine, MD, the founder and CEO of Actify Neurotherapies, told MD Magazine. “Opiates themselves are not very effective for treating chronic pain, and then we have the problems of addiction and abuse and the difficulties people have with getting off of these medicines once they start them, and then leading to illicit drug use.”

Levine's Actify Neurotherapies works closely with patients that have experiences with long-term opioid use, and for him, ketamine, in addition to its role in treating things like depression and post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD), has proven to be a very effective pain medication.

“Prescriptions [for opiates] are going down, but the conditions that require pain treatments haven't gone anywhere,” Levine said. “People still continue to struggle with chronic pain, chronic migraine, fibromyalgia—the same conditions that people were prescribed opiates for, we now need another solution. We wind up seeing many patients who either are currently on opiates or have a chronic pain condition that might otherwise have been treated with opiates, and they're looking for an alternative. And so, for many of these folks, ketamine can provide that alternative.”

Currently, the US Food and Drug Administration (FDA) classifies IV ketamine as an anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation. Recently, the FDA has focused much of its efforts to mitigate the use of opioids on increasing the ease of approval for abuse-deterrent generic opioids. The agency produced guidelines on opioid generics in November 2017.

“Our goal is to decrease the rate of new addiction, and thus any unnecessary legitimate and especially illicit use of opioids,” FDA Commissioner Scott Gottlieb, MD, said at the time. “Rather, this is an effort designed to encourage the shift—only when opioids are clinically appropriate—from existing, easily abused products to those that are harder to manipulate.

The full guidelines, “Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists,” were published in Regional Anesthesia and Pain Medicine.