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Denver—Chronic noncancer pain patients may find relief from an unlikely source, according to a team of Canadian researchers. Their retrospective study found that IV infusion of lidocaine plus ketamine significantly reduced the intensity of chronic pain, with few side effects.

“In 2013, we started offering these treatments for patients with neuropathic pain in our clinic,” said Shadi Babazadeh, MD, a clinical research associate with Allevio Pain Management in Toronto. “These patients were not responding to different pain medications, so Ramin Safakish, MD, the senior anesthesiologist at the clinic, decided to give the combination of lidocaine and ketamine to address their pain.

“Many clinicians use lidocaine and ketamine separately, but not as a combination,” Dr. Babazadeh added. “This combination seems to be unique.”

To help assess the safety and efficacy of the treatment, the investigators studied the electronic health records of 670 consecutive patients (mean age, 53.2 years; 508 women) who received the infusion at the clinic between March 2013 and May 2017. The most common diagnoses included fibromyalgia, diabetic neuropathy, postherpetic neuralgia and complex regional pain syndrome.

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Patients underwent a median of three infusions each (interquartile range [IQR], 1-8); 38% of patients received more than five infusions. A total of 3,741 infusions were reviewed.

“Some of these patients have been coming to the clinic every two months for five years,” Dr. Babazadeh explained. “Their quality of life has really improved. They can manage their pain and are almost able to lead a pain-free life.

“That said, demonstrating the change in long-term pain management for these patients was not the goal of this study,” she added.

The primary outcome of the analysis was the proportion of patients achieving reductions in pain scores of at least 30%.

As reported at the 2019 annual meeting of the American Academy of Pain Medicine (abstract 211), the median pain score immediately before the infusion was 8 (IQR, 6-9). After the infusion, it dropped to a mean of 2 (IQR, 0-4). Half of the patients experienced an improvement in their baseline pain score of at least 75% after the infusion.

Of note, patients reported clinically meaningful reductions in pain regardless of age, sex and diagnosis. The overwhelming majority of patients (88%; 3,271/3,741) experienced pain score reductions of at least 30%.

“We believe every infusion should begin with 4.5 mg/kg of lidocaine and 10 mg of ketamine, and then titrated according to the patient’s response,” Dr. Safakish said. “In our clinic, we have a limit of 600 mg lidocaine and 40 mg ketamine over 45 minutes.

“This is the dose where you don’t see side effects in the majority of people,” Dr. Safakish continued. “We’ve had practitioners who increased the ketamine dose to 60 to 70 mg over 45 minutes, and at these doses, people started reporting significantly more side effects.” Nausea and vomiting are the most common adverse events, he added.

The investigators also performed univariable and multivariable analyses regarding the odds of experiencing reductions in pain scores of at least 30%. The univariable analysis revealed that only the combination of lidocaine and ketamine had a statistically significant effect on pain improvement.

Specifically, for each 1-mg increase in lidocaine, the odds of achieving the 30% pain relief benchmark increased by 0.2%. As such, a 100-mg increase in lidocaine dose would result in an 18% increase in the chance of achieving a 30% reduction in pain (odds ratio [OR], 1.18; 95% CI, 1.02-1.37).

Similarly, every 10-mg increase in the ketamine dose was associated with a 21% increase in the odds of achieving a 30% reduction in pain scores (OR, 1.2; 95% CI, 1.09-1.36).

Despite these findings, the researchers acknowledged the potential shortcomings of the retrospective cohort study. Of note, the study did not track patients’ pain levels after discharge from the facility. They also did not have a standard measurement of patients’ quality of life.

To help address these shortcomings, the investigators are performing a prospective observational study. “In that prospective study, we are using a standard questionnaire that will allow us to track how long the pain relief lasts,” Dr. Babazadeh said.

Anecdotally, Dr. Safakish is convinced the combination offers long-term pain relief, the product of his many years of experience treating the same individuals. “The patients who come back, they are all patients for life,” he said in an interview with Pain Medicine News. “I’ve been seeing some of them every two months for the last 12 years.”

Enas Kandil, MD, an assistant professor of anesthesiology and pain management at the University of Texas Southwestern Medical Center, in Dallas, also has witnessed the efficacy of lidocaine and ketamine in various pain conditions, although she noted that the agents are not typically used together. “I’m in favor of both ketamine and lidocaine infusions,” Dr. Kandil said. “I think they’re great adjuvant medications for patients who have failed opioid interventions.

“We use them quite a bit here for our patients who have neuropathic and cancer pain when we’re trying to limit opioid use or we’ve reached our limit with our other adjuvant medications,” she added.

As Dr. Kandil related, she has only once administered the agents concomitantly, in a patient with intractable pain due to hemophilia. “And the only way we were able to control it was by adding ketamine and lidocaine infusions.”

Nevertheless, she did not see any specific contraindications to using the agents together, unless one or both agents was specifically contraindicated by the case in question.

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