New Non-Opioid Analgesic Gets Priority Review from FDA

By Pat Anson

The Food and Drug Administration could approve an experimental non-opioid analgesic early next year, potentially making it the first new medication for acute pain in over two decades.

Vertex Pharmaceuticals says the FDA has accepted its New Drug Application for suzetrigine, giving the drug a priority review with a target action date of January 30, 2025. Suzetrigine has previously been granted FDA Fast Track and Breakthrough Therapy designations for the treatment of moderate-to-severe acute pain.

“Today’s FDA filing acceptance for suzetrigine marks a critical milestone toward bringing this new, transformative non-opioid analgesic to the millions of patients,” Nia Tatsis, PhD, an Executive Vice President and Chief Regulatory and Quality Officer for Vertex, said in a statement.

“The FDA’s granting of a priority review further reinforces the high unmet need in treating acute pain, and the filing brings us one step closer to our objective of filling the gap between medicines with good tolerability but limited efficacy and opioid medicines with therapeutic efficacy but known risks, including addictive potential.”

Suzetrigine is designed to block pain in the peripheral nervous system, rather than the brain. That means it won’t have the “liking” effects of opioids or be as addictive.  

In Phase 3 clinical studies, suzetrigine was more effective in reducing post-operative pain than a placebo after minimally invasive surgeries.  Over 80% of patients rated suzetrigine as good or excellent in treating acute pain, but it was not more effective than a combination of the opioid hydrocodone and acetaminophen, more commonly known as Vicodin.

Vertex hopes suzetrigine will eventually be approved for a variety of pain conditions, not just post-operative pain.  The company has been studying the drug as a treatment for pain caused by diabetic peripheral neuropathy.

“In my 24 years practicing medicine, I have seen firsthand the desperate need for new non-opioid therapies for treating pain. Too many people today are either undertreated, dealing with negative side effects of currently available therapies or foregoing pain medications altogether for fear of becoming dependent on opioids,” said Scott Weiner, MD, a Vertex consultant and Associate Professor of Emergency Medicine at Harvard Medical School.

The Biden Administration has been under pressure from lobbyists, politicians and anti-opioid activists to have the FDA approve more non-opioid medications like suzetrigine. The new analgesics are expected to be far more expensive than opioids and other older pain relievers.

If the FDA approves suzetrigine in January, it will coincide with implementation of the NOPAIN Act, which will expand access to non-opioid analgesics in outpatient surgical settings by making them eligible for higher Medicare reimbursement rates.

Experimental Non-Opioid Drug Effective in Treating Acute Pain

By Pat Anson, PNN Editor

An experimental non-opioid analgesic was effective in treating post-operative pain in two Phase 3 clinical trials, setting the stage for a New Drug Application to the FDA by Vertex Pharmaceuticals later this year.

The drug – called VX-548 – was given orally to patients with moderate-to-severe pain in the first 48 hours after an abdominoplasty or bunionectomy, two minimally invasive surgeries. VX-548 was more effective in reducing pain than the placebo, but it was not more effective than a combination of the opioid hydrocodone and acetaminophen, more commonly known as Vicodin.

In a third Phase 3 study, VX-548 was effective for up to 14 days across a broad range of surgical and non-surgical acute pain conditions. Over 80% of patients in that study rated VX-548 as good, very good, or excellent in treating pain.

“We are very pleased with the results from the VX-548 pivotal program, which demonstrate a compelling and consistent combination of efficacy and safety across multiple acute pain conditions and settings. The VX-548 benefit-risk profile ideally positions it to potentially fill the gap between medicines with good tolerability but limited efficacy and opioid medicines with therapeutic efficacy but known risks, including addictive potential,” Reshma Kewalramani, MD, CEO and President of Vertex, said in a press release.

“With FDA Breakthrough and Fast Track Designations in hand, we are working with urgency to file the New Drug Application for VX-548 and bring this non-opioid medicine to the millions of patients who suffer from acute pain each year in the U.S.”

VX-548 was generally safe and well tolerated in all three Phase 3 studies. Most of the adverse events reported by patients were mild to moderate, such as nausea and constipation.

Unlike opioids, VX-548 blocks pain in the peripheral nervous system, rather than the brain. That means it won’t have euphoric effects or be addictive. If approved for use by the FDA, experts say it would give patients and providers a much-needed alternative to opioids.

“As a physician treating patients suffering from pain for many years, I know firsthand the critical need for new, efficacious and safe treatment options,” said Jessica Oswald, MD, a Vertex consultant and Associate Physician in Emergency Medicine and Pain Medicine at University of California San Diego.

“The Phase 3 safety and efficacy across the three studies are impressive and demonstrate VX-548’s potential to change the paradigm of pain management. I look forward to the potential of having a new class of acute pain medicine — the first in more than two decades — to use as an alternative to opioids to help the millions of people impacted by acute pain.”

The risk of a surgery patient misusing opioids or becoming addicted is actually quite low – less than one percent. One recent study even found that restricting the use of opioids during surgery leads to more post-operative pain.

Vertex hopes to have VX-548 approved for a wide variety of pain conditions, not just post-operative pain.  Last month, the company released positive results for the drug in reducing pain from diabetic peripheral neuropathy.

Vertex also recently won approval from the FDA for its CRISPR gene cell therapy for sickle cell disease, which potentially offers a cure for the painful blood disorder.

New CBD Drug Developed for Postoperative Pain

By Pat Anson, PNN Editor

An investigational drug containing a fast-acting formula of cannabidiol (CBD) reduced postoperative pain in patients after shoulder surgery, according to small new study.

Patients who took ORAVEXX tablets after minimally invasive rotator cuff surgery had an average of 23 percent less pain after the first day of surgery than those taking a placebo, according to researchers at NYU Langone Health. The tablets are designed to quickly dissolve in the mouth and the CBD absorbed into the bloodstream in less than 3 seconds.

“There is an urgent need for viable alternatives for pain management, and our study presents this form of CBD as a promising tool after arthroscopic rotator cuff repair,” says lead investigator Michael Alaia, MD, associate professor in the Department of Orthopedic Surgery at NYU Langone Health.

“It could be a new, inexpensive approach for delivering pain relief, and without the side effects of anti-inflammatory drugs like NSAIDs and addiction risks linked to opiates. Additionally, CBD has the benefit of pain relief without the psychotropic effects associated with THC or marijuana.”

There are a few caveats about the study. First, only 99 patients were enrolled in this early-stage Phase 1/2 trial. They were divided into two groups: one group took 50 mg of CBD in ORAVEXX tablets three times a day for 14 days, while the other group received a placebo or 25 mg of CBD during the study period.

Importantly, patients in both groups were also prescribed opioids, a low dose of Percocet, and told to wean themselves off the medication as soon as possible.

There were no major side effects reported by either group, but the group receiving 50 mg of CBD reported less pain and greater satisfaction in their pain control.

ORAVEXX is manufactured by Orcosa, which has developed a proprietary drug delivery system called the RITe Platform. The company says it buccal tablets dissolve so quickly in the mouth that fewer active ingredients are needed for a medication to work.

In addition to postoperative pain, the company is also planning studies to evaluate ORAVEXX as a treatment for acute and chronic pain, osteoarthritis pain and inflammation. While the initial results are promising, researchers say it could be years before ORAVEXX is available.

“Our study is examining a well-designed, carefully scrutinized product under an investigational new drug application sanctioned by the FDA. This is currently still experimental medicine and is not yet available for prescription,” said Alaia, who presented the initial findings this week at the annual meeting of the American Academy of Orthopaedic Surgeons.

Medical Societies Have New Advice for Treating Surgery Pain in Patients Taking Opioids

By Pat Anson, PNN Editor

The American Medical Association and 14 other medical societies have released new advice for physicians managing surgical pain in “complex patients” who have chronic pain, substance use disorders, or those taking opioid medication prior to surgery.

The seven guiding principles emphasize the coordination of pain care with other providers, and that patients taking opioids be allowed to stay on them before, during and after surgery.  

“Every surgical patient deserves adequate pain relief that aims to prevent opioid reliance, chronic pain and other negative outcomes, but it may be more challenging to achieve this in certain patient populations,” Randall Clark, MD, President of the American Society of Anesthesiologists (ASA), said in a statement.

“The new principles were created to build upon an original set established last year during our first pain summit, but specifically address patients undergoing surgery with chronic pain, those taking opioids preoperatively, and those with substance use disorders.  The new principles give the perioperative care team more guidance to care for these particularly complex patients.”

The new principles come at a time when many U.S. hospitals are reducing the use of opioids for surgical pain. As result, some people in pain have postponed or cancelled surgeries because they fear their postoperative pain would be poorly treated or their current opioid therapy would be disrupted.

For patients on long-term opioid therapy, the principles urge physicians to “continue the baseline opioid dose” and to provide “supplemental analgesia” for postoperative pain. The additional pain treatment should be the coordinated with the patient’s opioid-prescribing clinician, with the goal of returning to “the preoperative dose or lower as soon as possible.”

“This really is meant to be a patient-centered document that says we should invest in making sure these patients have a good experience,” said David Dickerson, MD, chair of the ASA’s Committee on Pain Medicine. “A lot of people don’t even get their baseline meds continued during their surgery. They don’t even get their home meds. And so this now creates a principle that says you need to have a really good reason why you’re going to withhold those meds.

“In our health system, if someone has pre-op opioid use, we know that they’re going to need more opioids in the wake of their surgery or they’re going to need more anesthetic even while they’re on the table having their care,” said Dickerson, an anesthesiologist who is section chief for pain medicine at the NorthShore University HealthSystem in Chicago.

In addition to the ASA and AMA, these medical organizations have adopted the new guiding principles:

• American Academy of Orthopaedic Surgeons

• American Academy of Otolaryngology-Head and Neck Surgery

• American Association of Neurological Surgeons

• American Association of Oral and Maxillofacial Surgeons

• American College of Obstetricians and Gynecologists

• American College of Surgeons

• American Hospital Association

• American Society of Addiction Medicine

• American Society of Breast Surgeons

• American Society of Plastic Surgeons

• American Society of Regional Anesthesia and Pain Medicine

• American Urological Association

• Society of Thoracic Surgeons

‘CDC Guideline Falls Flat’

Dickerson emphasized the new guiding principles are only meant as a resource for physicians managing surgical pain and are not intended to be a guideline or standard of care. He also expressed concern about some of the proposed changes to the CDC’s opioid prescribing guideline, which now includes recommendations for treating postoperative pain.

“I think that the CDC guidelines, as they are proposed in their draft format right now, is not an incredibly functional document. It doesn’t really shape what great pain care looks like. All it talks about really is mitigating the effects of opioid injury. It offers up ideas, but I don’t think it’s a comprehensive summary of what we do for patients,” Dickerson told PNN.

The CDC’s draft revision is actually quite similar to the medical societies’ new principles for treating surgery pain. It allows for patients on long-term opioid therapy to get additional opioids “for the duration” of their postoperative pain, with a return to their baseline doses as soon as possible.  

But Dickerson says there are many different types of surgery that require different forms of pain control, and some complicated patients may need more pain relief and different therapies than others. He thinks medical societies should set their own guidelines for their own specialties, and not rely on the generic advice of the CDC.

“I think that societies when they come together to do things like this are really best-tasked as experts to do this. To expect primary care physicians to write a guideline about how to manage surgical populations is limited from the start,” he said. “I think the CDC guideline falls flat.”

Are NSAIDs Really Better Than Opioids for Post-Operative Pain?

By Pat Anson, PNN Editor

There have been a rash of recent studies promoting the use acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) over opioids for post-operative pain.

One such study at a Houston hospital led surgeons to conclude that patients were better off with Tylenol. "This study provides us with a strategy to successfully manage pain after surgery using over-the-counter pain medication,” said Min Kim, MD, head of thoracic surgery at Houston Methodist Hospital.  

But critics point out that most of the studies never examine how patients feel about the effectiveness of their pain treatment — focusing instead on the number of opioid pills and smaller opioid doses being prescribed. Pain relief was a secondary consideration, if it was considered at all.

A rare exception to that is a study recently published in the Canadian Medical Association Journal (CMAJ), which found that ibuprofen and other NSAIDs gave better post-operative pain relief than the opioid codeine. In a systematic review of 40 clinical trials involving over 5,000 patients who had outpatient procedures, researchers said patients who took NSAIDs had lower pain scores 6 and 12 hours after surgery than patients taking low doses of codeine.

"In all surgery types, subgroups and outcome time points, NSAIDs were equal or superior to codeine for postoperative pain," wrote lead author Matthew Choi, MD, Associate Professor of Surgery at McMaster University in Ontario. "We found that patients randomized to NSAIDs following outpatient surgical procedures reported better pain scores, better global assessment scores, fewer adverse effects and no difference in bleeding events, compared with those receiving codeine.

“These findings are of general importance to any clinician performing painful medical procedures. The various trials in our meta-analysis evaluated a range of procedures, different NSAID types and various degrees of acetaminophen coadministration.”

But critics say the McMaster study also has flaws. The claim that “all surgery types” and “a range of procedures” were included in the analysis is misleading at best. Most of the studies — 28 of the 40 that were analyzed — involved dental surgery, a fact that is not sufficiently disclosed. The rest of the outpatient procedures were for plastic surgery and orthopedic corrections – which can hardly be compared to more serious surgeries that require more pain relief and days or weeks of recovery, not just 6 to 12 hours.      

Another issue is the use of codeine as a research subject. Stefan Franzen, PhD, a chemistry professor at North Carolina State who has an extensive background in biomedical research, questions whether low doses of codeine should even be compared to NSAIDs.

“I question the premise that codeine is the drug that is or should be used by dentists,” said Franzen, author of “Patient Z,” a book the examines the criminalization of pain care. “I read a few papers not cited by this report and they too do not find a great efficacy for codeine. Part of this may be dose. Most commonly they are using 30-60 mg of codeine, which is 5-10 mg of morphine. Not very much if you have severe pain.

“Codeine may be a poor choice, but it may also be a straw man. Why not use tramadol, for example?”

‘Manipulated Data’

Patient advocate Bill Murphy also has doubts about the selection criteria used in studies touting the benefits of non-opioid pain relievers. He believes some researchers cherry-pick evidence to support a conclusion they’ve already reached.

“Opioid sparing post-op surgery programs are nothing more than an attempt to solve a non-problem and in doing so, patients suffer needlessly. The data produced from such programs are very often manipulated by those who designed the program in an obvious attempt to skew the results in favor of a program they endorsed,” said Murphy, who helped get legislation passed in New Hampshire to ensure that pain patients have access to opioid medication.

Murphy has advocated on behalf of patients at Portsmouth Regional Hospital, which has an “Enhanced Surgical Recovery” program that significantly reduced the use of opioids. Instead of Vicodin, patients get Neurontin or nerve blocks for pain relief.

“I was personally called in to advocate on behalf of several patients who were left to suffer in pain following surgery only to have staff assure them their pain was being well managed,” Murphy explained in an email. “Surgeons and nurses reported they were doing very well with Portsmouth Regional’s new protocol for managing post-op pain when in fact, they were not doing ‘very well’ at all.

“These patients were in horrible pain. Of the three I spoke with, none were ever provided any relief. I was with one patient as she was discharged. She was in tears and moved at a glacial pace due to pain as her son and I helped her into his vehicle outside. It was heartbreaking to watch. Her adult son was furious. I stayed in touch with each patient for several weeks afterwards. Each suffered greatly, one was not making any gains in physical therapy due to her lasting pain.”

In 2019, only 11% of patients were prescribed an opioid while at the Portsmouth hospital, and less than 6% were discharged with an opioid prescription. Murphy says the hospital’s policy inevitably leads to some patients with poorly treated pain.  

“What Portsmouth Regional Hospital’s ‘Enhanced Surgical Recovery’ program was doing is akin to making patients bite down on a piece of wood, grind it out, and then convince them the whole experience was for their own good,” says Murphy.    

Pilot Study Shows Neuromodulation Effective for Postoperative Pain

By Pat Anson, PNN Editor

In recent years, many U.S. hospitals have adopted policies that reduce or eliminate the use of opioids after surgery. For some, that means giving their patients Tylenol or Lyrica for postoperative pain. For others, it means trying neuromodulation — a non-pharmacological therapy that new research shows may have some potential.

In a placebo-controlled pilot study led by researchers at University of California San Diego, patients who received percutaneous peripheral nerve stimulation (PNS) had significant reductions in their pain levels after outpatient joint surgery.

Percutaneous PNS is a form of neuromodulation that involves the placement of a tiny wire or “lead” alongside a peripheral nerve. The implanted lead is then connected to a small external pulse generator that sends a mild electric current to the nerve, interrupting pain signals. PNS has been used for years to treat chronic pain, but this was the first clinical trial to assess its use for postoperative acute pain.    

In the pilot study, 65 adult patients scheduled for operations on their shoulders, knees or ankles had leads placed before surgery in the affected joint. After surgery, half of the patients were given neuromodulation, while the other half received a "sham" treatment with a pulse generator that appeared active but did not deliver any electric current.

Patients in both groups received opioids as needed for their postoperative pain, and after one week their pain scores and opioid use were compared.

Researchers reported in the journal Anesthesiology that the results were “much greater than we had anticipated.” Pain scores were over 50 percent lower in patients who received neuromodulation. The mean pain score (on a zero to ten scale) was 1.1 in patients receiving PNS treatment, compared to 3.1 in the sham group.

Nerve stimulation was also associated with an 80 percent reduction in opioid consumption. The median opioid dose (oral morphine equivalent) in the first week after surgery was 5 milligrams in the active treatment group, compared to 48 milligrams in the sham group.

“This multicenter, randomized, double-masked, sham- controlled pilot study provides evidence that ultra-sound-guided percutaneous peripheral nerve stimulation concurrently improves analgesia and decreases opioid requirements to a statistically significant and clinically meaningful degree for at least a week after moderately to severely painful ambulatory orthopedic surgery,” wrote lead author Brian Ilfeld, MD, a professor of anesthesiology at UC San Diego.

Ilfeld and his colleagues say the pain-relieving benefits of neuromodulation continued after the leads were removed 14 days after surgery, but they appeared to wear off after one month. They plan on conducting a larger clinical trial with 250 surgery patients and to follow them for a year to see if there are any long-term benefits from neuromodulation.

Contrary to popular belief, opioid addiction is rare after surgery. A large 2016 study found only 0.4% of older adults were still taking opioids a year after major elective surgery. Another large study in 2018 found only 0.2% of patients who took opioids for post-surgical pain were later diagnosed with opioid dependence, abuse or had a non-fatal overdose.

Nevertheless, the now defunct American Pain Society (APS) released guidelines in 2016 that encourage physicians to use non-opioid medication such as acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), gabapentin (Neurotin) and pregabalin (Lyrica) for post-operative pain. The APS also recommended non-pharmacological therapies such as cognitive behavioral therapy and transcutaneous elective nerve stimulation (TENS) as adjunct treatments.

The lead author of the APS guideline was Roger Chou, MD, who also co-authored the 2016 CDC opioid guideline.

Gabapentinoids Riskier for Surgery Patients

By Pat Anson, PNN Editor

Another study is casting doubt on the use of gabapentinoids such as Lyrica (pregabalin) and Neurontin (gabapentin) for pain relief during and after surgery.

Gabapentioids are a class of nerve medication originally developed to treat convulsions, but the drugs are increasingly being used as a trendy alternative to opioids for acute and chronic pain. Some U.S. hospitals are even using gabapentinoids for surgical pain and have phased out or reduced the use of opioids.

In an analysis of over 5 million adults admitted for major surgery in the U.S. from 2007 to 2017, researchers at Harvard Medical School found that using gabapentinoids with opioids increases the risk of overdose, respiratory depression and other adverse events. Researchers say the additional risk was “extremely low” and would result in one additional overdose for every 16,000 patients.

“Our findings add to the growing evidence that gabapentinoids can potentiate the respiratory depressant effects of opioids,” researchers reported in JAMA Network Open. “The events were rare… (but) patients receiving multimodal pain management therapy that includes gabapentinoids should be closely monitored for possible respiratory depression.”

The study did not examine whether gabapentiniods were effective in treating surgical pain or if they improved the analgesic effect of opioids.

In an editorial also published in JAMA Network Open, a pain management expert said more studies were needed to see if gabapentiniods were worth the additional risk.

“The evidence in support of the analgesic benefit of gabapentinoids combined with opioids for postoperative analgesia is equivocal; there is no real support that adding gabapentinoids to opioid pain relievers offers additive, much less synergistic, enhancements to pain control,” wrote Joseph Pergolizzi, Jr, MD, Chief Operating Officer of NEMA Research.  

“Considering that combination analgesic regimens generally reduce overall opioid consumption, this study is important because it shows that this may not necessarily translate to reducing opioid-associated adverse events. As combination analgesia gains traction for in-hospital acute painful conditions, such as postsurgical pain, it is important to be guided by evidence rather than intuition.”

No Significant Analgesic Effect

A recent study by Canadian researchers also found little evidence to support the use of gabapentinoids for surgical pain.

“No clinically significant analgesic effect for the perioperative use of gabapentinoids was observed. There was also no effect on the prevention of postoperative chronic pain and a greater risk of adverse events,” wrote lead author Michael Verret, MD, a resident at Laval University in Quebec City.  

These and other findings contradict guidelines published by the American Pain Society in 2016, which advocate “around the clock” use of gabapentin, pregabalin and other non-opioid drugs both before and after surgery.

The risk of becoming addicted or dependent on opioids after surgery is actually quite low. A 2016 study found that only 0.4% of elderly patients who were prescribed opioids for post-operative pain were still using them a year after their surgeries. Another study by Harvard researchers found that only 0.2% of surgery patients prescribed opioids were later diagnosed with opioid dependence, abuse or a non-fatal overdose.

Music and ‘Positive Suggestions’ Reduce Need for Opioids in Surgery Patients

By Pat Anson, PNN Editor

Studies have shown that long term opioid use and addiction are rare in patients given opioids for pain control during and after surgery.  Nevertheless, many hospitals are adopting policies that reduce or eliminate the use of opioids for postoperative pain; opting instead for non-opioid pain relievers such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs).

A new placebo-controlled study suggests that relaxing music and comforting words played during surgery might also be a substitute for opioids in some patients.  

Researchers at five German hospitals recruited 400 patients scheduled for elective surgery lasting 1 to 3 hours. While under general anesthesia and unconscious, half the patients listened through earphones to a tape that played soothing background music and “positive suggestions” for 20 minutes. The tape played repeatedly until surgery ended. The other patients were assigned to a blank tape and served as a control group.     

Researchers found that patients in the music group had lower pain scores and required lower opioid doses – about 2.8 MME less per patient -- in the first 24 hours after surgery. Over a third (37%) did not need opioids at all, compared to 26% in the control group.

“This study found a statistically significant reduction in use of postoperative opioids in patients who received therapeutic suggestions by audiotape during surgery, which comprised background music and mindful text. Furthermore, the number of patients who requested and received opioids was significantly lower after the intervention,” researchers reported in the British Medical Journal.

“A mean saving of 2.8 MME for each patient might seem unimportant; however, in most pain studies the focus is generally on relative saving and not the absolute dose, and an opioid dose reduction of 30%, as reported here, is considered relevant.”

In addition to less pain and need for analgesics, patients in the music group also had less nausea and recovered faster from surgery.

Connected Consciousness

The study findings also suggest that – even under general anesthesia – patients can still hear and process words subconsciously. This “connected consciousness” runs against long-held beliefs that patients under anesthesia don’t have thoughts and feelings. In an editorial, one researcher called this finding “astonishing.”

“Usually there is no reaction to auditory or other stimuli, including surgery, expected or observed in patients under general anaesthesia,” wrote corresponding author Ernil Hansen, MD, a professor of Anesthesiology at the University Hospital of Regensburg, Germany.

“This knowledge and appreciation of intraoperative perception should lead us to more thoughtful behaviour in the operating theatre, for example, what noise levels or potentially unnecessary conversations are we exposing patients to, and to consider a wide use of therapeutic communication as a feasible, non-drug support of medical interventions and an integral part of therapy and care.”

This isn’t the first study to find that music can be a useful tool to reduce pain and anxiety.

Mozart’s “Sonata for Two Pianos” has been found to be helpful in treating patients with epilepsy. And a 2006 study found that listening to music for an hour each day helped reduce pain, depression and disability in patients with chronic non-cancer pain.

Caution Recommended on Cannabis Use Before Surgery

By Roger Chriss, PNN Columnist

The U.S. House of Representatives voted last week for the first time to legalize marijuana at the federal level. While passage by the Senate appears unlikely, the historic House vote on the MORE Act shows how much public attitudes about marijuana have changed.

A recent Gallup poll found that 68 percent of the country now favors having legal access to marijuana. Last month voters in four states approved recreational cannabis measures, raising to 15 the number of states where cannabis is completely legal. Thirty-six states have approved it for medical use.

As cannabis use becomes more accepted and widespread, healthcare providers need to take cannabis into consideration when treating patients, especially those undergoing surgery.

The Perioperative Pain and Addiction Interdisciplinary Network (PAIN) recently convened a panel of 17 experts to develop new guidelines on the care of cannabis-consuming surgery patients. The result is a set of recommendations that include cannabis weaning before surgery and close monitoring during surgery, particularly for heavy cannabis users.

Because of the potential for cannabis to interfere with anesthesia, the guidelines recommend that patients who use a cannabis product more than 2 or 3 times per day should be considered for tapering or cessation several days before surgery. That includes patients who use more than 1.5 grams per day of smoked cannabis, more than 300 mg per day of CBD oil, or more than 20 mg per day of THC oil. Cannabis users may also need additional medication for postoperative nausea and vomiting.

There is only limited research on how cannabis interacts with analgesics and other medications. But the few studies that have been done suggest caution is warranted.

A 2006 study done in Germany looked at patients after surgery. None of the patients was able to achieve sufficient pain relief at any dose of Cannador, a cannabis plant extract. Several experienced significant side effects, including sedation and nausea. And the study had to be halted because of a severe adverse event in one patient.

A recent study at the University of Michigan looked at cannabis use and surgical outcomes in 1,335 adults undergoing elective surgery. About half reported using cannabis medically, recreationally or both. The results are concerning.

"On the day of surgery, cannabis users reported worse pain, more centralized pain symptoms, greater functional impairment, higher fatigue, greater sleep disturbances and more symptoms of anxiety and depression versus non-cannabis users,” the researchers said.

Medication use, including opioids and benzodiazepines, was also higher in the cannabis group. The study authors concluded that "cannabis users have higher clinical pain, poorer scores on quality of life indicators, and higher opioid use before and after surgery."

Another recent study at the University of Colorado Hospital was smaller and more specific, looking at 118 patients who had surgery for a broken leg. About one-fourth of the patients reported prior cannabis use. Although cannabis use was not associated with a higher dose of the anesthetic propofol during surgery, it was associated with more post-operative pain. Cannabis users also required significantly more pain medication than the control group.

Lead study author Ian Holmen, MD, told Practical Pain Management that it was important for clinicians to ask patients about their cannabis use before any surgical procedures.

“A provider just needs to know if the patient uses cannabis or not. It doesn’t matter if it’s a daily situation, just so [providers] are aware that the post-operative and possibly interoperative period are going to appear different in a patient who’s using cannabis than one who is not,” Holmen said.

Further study is needed to better understand how cannabis use affects surgical outcomes and how the effects may change at various doses of cannabis products. But the concerns of the Perioperative Pain and Addiction Interdisciplinary Network appear well-founded. Guidelines for the perioperative management of cannabis use are a necessary and useful step forward as cannabis use becomes more common.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research. 

Gabapentinoids Ineffective for Pain Relief After Surgery

By Pat Anson, PNN Editor

Would you want to take Lyrica (pregabalin) or Neurontin (gabapentin) for pain relief after a major surgery? Both drugs belong to a class of nerve medication called gabapentinoids that are increasingly being prescribed to patients perioperatively (after surgery) as an alternative to opioid medication.

But gabapentinoids also have risks and there is little evidence to support their use for postoperative pain relief, according to a large new study by a team of Canadian researchers.  

“No clinically significant analgesic effect for the perioperative use of gabapentinoids was observed. There was also no effect on the prevention of postoperative chronic pain and a greater risk of adverse events. These results do not support the routine use of pregabalin or gabapentin for the management of postoperative pain in adult patients,” wrote lead author Michael Verret, MD, a resident at Laval University in Quebec City.  

Verret and his colleagues conducted a meta-analysis of 281 clinical trials involving nearly 25,000 patients undergoing a wide range of surgeries, including orthopedic, spinal and abdominal operations.

Their findings, recently published in the journal Anesthesiology, indicate that the analgesic benefits of pregabalin and gabapentin after surgery are negligible, regardless of the dose or type of operation. Gabapentinoids were also ineffective in preventing chronic pain from developing after surgery, one of the primary justifications for using the drugs postoperatively.

“Gabapentinoids were also associated with a greater incidence of adverse events, namely dizziness and visual disturbance, while other major adverse events such as respiratory depression and addiction are not reported or are underreported,” said Verret.

The findings contradict guidelines published by the American Pain Society (APS) in 2016,  which advocate “around the clock” use of gabapentin, pregabalin and other nonopioid drugs both before and after surgery.

“The panel recommends use of gabapentin or pregabalin as part of a multimodal regimen in patients who undergo surgery. Both medications are associated with reduced opioid requirements after major or minor surgical procedures, and some studies reported lower postoperative pain scores,” the APS guideline states.

“The panel suggests that clinicians consider a preoperative dose of gabapentin or pregabalin, particularly in patients who undergo major surgery or other surgeries associated with substantial pain, or as part of multimodal therapy for highly opioid-tolerant patients.”

‘Evidence of Harm’

Although opioid addiction is relatively rare after surgery, dozens of U.S. hospitals followed the lead of the APS and other medical guidelines by stopping the use of opioids for certain surgeries.

Cleveland Clinic Akron General Hospital, for example, adopted a policy of only using gabapentin and other non-opioid analgesics for colorectal operations.

“It is now clear that over the past two decades, evidence of benefit from routine perioperative administration of gabapentinoids has diminished, while evidence of harm has increased.”

— Dr. Evan Kharasch

Critics say gabapentinoids have become a trendy alternative for post-surgical pain relief, even though evidence supporting their use is minimal.

“It is now clear that over the past two decades, evidence of benefit from routine perioperative administration of gabapentinoids has diminished, while evidence of harm has increased. If any potential benefits exist in ‘special populations,’ published reports have yet to identify the benefits or the populations,” lead author Evan Kharasch, MD, Editor-in-Chief of Anesthesiology, wrote in an editorial.

“The good intentions that led to routine gabapentinoid use should be redirected to lead the way out. The French Society of Anesthesia and Intensive Care Medicine now states that gabapentinoids should not be used systematically or in outpatient surgery. Other societies should follow. As the weight of evidence has shifted and the risk–benefit balance tilted away from benefit, evidence-based practice impels revising if not eliminating the routine use of perioperative gabapentinoids in adults.”

It's too late for the APS to change its guideline. The organization filed for bankruptcy in 2019, ironically because of the high cost of legal fees in defending itself against opioid litigation.

While the CDC’s controversial opioid guideline does not advocate using gabapentinoids for post-surgical pain, it does recommend their use in treating chronic pain -- with little to no mention of their side effects.

One of the co-authors of the CDC guideline, Dr. Roger Chou, also played a significant role in drafting the APS guideline. Chou is currently heading much of the research being conducted by the CDC as it prepares to update and possibly expand its 2016 guideline.

Treating Chronic Pain With Lasers

By Madora Pennington, PNN Columnist

Months after surgery for my badly broken foot, the last scab finally fell off, revealing to my horror that the surgical incision had not closed. I have Ehlers-Danlos Syndrome (EDS), a genetic condition that prevents my body from building proper collagen. Poor wound healing is a common complication for people like me. 

A search for a treatment that would help led me to Dr. Harold Kraft, a Southern California anesthesiologist who has built an entire practice around using high-powered lasers. Kraft’s main focus is pain --- from sciatica and back pain to neuropathy, neuralgia and myalgia, as well as post-surgical pain and soft tissue injuries. 

Another thing lasers do is facilitate wound healing. After a few appointments, my wound closed but appeared fragile and Frankenstein-looking. With more treatments, it rapidly filled in, coming to look smooth, strong and, surprisingly, pretty.

I was eager to try laser for my Ehlers-Danlos aches as well. My strange body seems to sustain soft-tissue injuries from the ordinary tasks of life, draining my energy and taxing my nervous system. From the laser treatments, I experienced relief I had never before felt.

Kraft has learned a lot from administering over 20,000 treatments on patients. He noticed Ehlers-Danlos patients got exceptional pain relief from the laser treatments, and came to find that nearly all are super-responders.

“About 90% of EDS patients respond to laser treatment, and get faster and more profound pain relief than typical patients,” Kraft notes.

Light Amplification

The word “laser" is an acronym for Light Amplification by the Stimulated Emission of Radiation. No longer limited to science fiction movies, lasers are now a part of everyday life. You’ve probably seen lasers used as pointers during presentations, as bar code scanners, and in DVD players. In medicine, lasers can be used for precision cutting, such as in LASIK vision surgery or for excising a tumor. For cosmetic purposes, a laser can improve skin imperfections or whiten teeth.

Light particles, or photons, from the laser pass through the skin and stimulate the cells’ mitochondria to release anti-inflammatory modulators, nerve and vascular growth factor. This causes healing and repair.

Kraft came to having a pain practice late in life. He had retired from a long career of performing anesthesia during surgery and left medicine entirely for the business world, developing software for data aggregation. All that changed when his wife took their long-suffering pug for a new treatment.

Harley, a most beloved dog, had trouble walking. He had not benefited from joint supporting supplements like glucosamine and chondroitin, nor acupuncture and doggie physical therapy. But after four treatments of high dose laser from a veterinarian, Harley could walk again. The Kraft’s were elated and also intrigued.

Kraft convinced a family friend who had back pain to see that same veterinarian for lasering, even though she is a human. Like Harley, she found pain relief.

Seeing the promise of what this could offer, Kraft began training in laser techniques and got laser machines of his own. He went back to practicing medicine, treating pain exclusively with lasers. Kraft uses Class IV lasers, which are the most powerful available. He employs them at high doses, in order to do the most good for patients. Great care must be taken in this endeavor.

“The more power you use, the more care you need to operate and the more likely that misapplication can cause harm,” Kraft says. “There is no discomfort during treatment, although the patient may feel the heat from the laser. It is powerful, non-invasive, and the results can be permanent or long-lasting.”

Kraft says about 7 out of 10 patients get significant improvement, including chronic pain sufferers who failed at other treatments. Genetics seem to play a factor in how well a patient responds. Some are just faster than others. A small percentage respond immediately. Most experience benefit between 4 and 10 treatments, and only about 30% do not respond after 14 or so treatments.

What does the science say about laser therapy? While there isn’t an abundance of research on the healing power of Class IV laser, some exist and are worth noting:

• A small study in the Journal of Athletic Training concluded that Class IV laser therapy is “an effective treatment modality to increase blood flow in the soft tissues” to promote healing.

• A pilot study assessed Class IV laser therapy for postoperative pain in 100 patients who had coronary bypass surgery, and found it to be effective.

• A double-blind study of tendonitis caused by repetitive-motion found Class IV laser treatments gave long-term relief with no adverse effects.

• Another double-blind study on 38 women with fibromyalgia showed that Class IV laser therapy improves pain, upper body range of motion, and quality of life. 

Chronic and acute pain are notoriously difficult to treat, especially in an era when fewer doctors are willing to treat pain or prescribe opioid medication. Pain patients have fewer options.

Dr. Kraft imagines a world where patients will have easy access to laser therapy at their primary care doctor or physical therapist. In addition to running his busy practice, Dr. Kraft has invented an improved laser, one that would optimize treatment regimen. He hopes to have it to market in two years.

Madora Pennington writes about Ehlers-Danlos and life after disability at LessFlexible.com. Her work has also been featured in the Los Angeles Times.

Surgeons Reduce Rx Opioids Without Increasing Pain

By Pat Anson, PNN Editor

Surgeons in Michigan have reduced the amount of opioid medication prescribed to patients recovering from common operations by nearly a third -- without causing patients to feel more postoperative pain.

In a new research letter published in the New England Journal of Medicine, a team from the Michigan Opioid Prescribing Engagement Network (OPEN) reported on the results of a statewide effort to get surgical teams to follow prescribing guidelines for postoperative pain.

In just one year, surgeons at 43 Michigan hospitals reduced the number of opioid pills prescribed to patients after nine common operations, from an average of 26 pills per patient to an average of 18.

The surgeries included minor hernia repair, appendix and gallbladder removal, and hysterectomies. Most were minimally invasive laparoscopic surgeries.

The ratings patients gave for their post-surgical pain and satisfaction didn't change from the ratings given by patients treated in the six months before opioids were reduced.

Researchers say patients only took about half the opioids prescribed to them, even as the prescription sizes shrank. They attribute this to improved counseling about pain expectations and non-opioid pain control options.

"The success of the statewide effort suggests an opportunity for other states to build on Michigan's experience, and room for even further reductions in prescription size," said Michael Englesbe, MD, a University of Michigan surgery professor. "At the same time, we need to make sure that patients also know how to safely dispose of any leftover opioids they don't take."

The study involved over 11,700 patients who had operations at hospitals participating in the Michigan Surgical Quality Collaborative. About half of the patients also filled out surveys sent to their homes after their operations, asking about their pain, satisfaction and opioid use after surgery.

The Michigan-OPEN team has been working since 2016 to reduce opioid prescribing and quantify the appropriate number of pills patients should take. Their research led to the the development of new guidelines that were first tested on gallbladder surgery patients before being expanded to other types of surgery.

Some hospitals have stopped giving opioids to surgical patients. Patients at Cleveland Clinic Akron General Hospital get acetaminophen, gabapentin and nonsteroidal anti-inflammatory drugs (NSAIDs) to manage their pain before and after colorectal operations – and their surgeons say the treatment results in better patient outcomes

It’s a common misconception that many patients become addicted to opioids after surgery. A 2016 Canadian study, for example, found that long term opioid use after surgery is rare, with less than one percent of older adults still taking opioid pain medication a year after major elective surgery.

Another large study in the British Medical Journal found similar results. Only 0.2% of patients who were prescribed opioids for post-surgical pain were later diagnosed with opioid dependence, abuse or a non-fatal overdose.

Another fallacy is that leftover pain medication is often stolen, sold or given away. The DEA says less than one percent of legally prescribed opioids are diverted.

Tylenol for Postoperative Pain?

By Margaret Aranda, MD, Columnist

I saw them do it to our veterans. Now they were going to do it to me.

I heard the veterans scream decades ago, when I was president of a pre-med club at a VA hospital in Los Angeles. There was a little local anesthetic, no oxygen, no vital signs and no anesthesiologist. The hematologist-oncologist did the bone marrow extraction herself.

Now I was about to have the same procedure myself, to get an early diagnosis of mastocytosis, an orphan disease.  No one was going to tell me that I won’t hurt. The veterans fought in a war, yet they screamed.

After taking my vital signs, the intake nurse interrogated me, eyes peering over her bifocals.

“When was the last time you took OxyContin?” she asked.

(My thoughts: We never asked such a scrutinizing question. They could draw an opioid blood level, to “check” and see if I was telling the truth. Sure, my blood levels would be low, because it’s been a week. I’m not a drug addict. Big breath. Don’t let your thoughts get negative. Just get through this day.)

Postoperative pain was a big concern for me.

“What will I get for post-op pain?” I asked the anesthesiologist.

(My thoughts: I don't want to cry. I don't want to hurt. I've had a lifetime of pain, and I live with it daily. Sores pervade me. They are all over my head, itchy ones that feel like cold sores mixed with chicken pox. If I scratch one, they all itch, including the sores on my arms and back. How much worse is my life about to get?)

"Tylenol. No post-op opioids for pain," was his reply.

You bet my world crashed.

"I can't do Tylenol. I need to save my liver. Everyone knows the smallest dose of Tylenol can hurt the liver. Besides, I don’t want to lose my empathy. Studies show acetaminophen causes a lack of empathy,” I said.

“Ibuprofen,” was his answer.

(My thoughts: How much lower can my world crash? What the heck? Do you really know I’m a doctor, too? Do you know how many patients I’ve personally intubated through a GI bleed so they could breathe?)

“I can’t do ibuprofen,” I told him. “I can’t have a GI bleed. Or a heart attack. Or a stroke.”

“Oh, okay! Morphine and fentanyl, a mixture. Morphine lasts longer," the anesthesiologist said.

(My thoughts: I can breathe again. Now I have to be the perfect patient.)

The pathologist was cheery, polite and smiled a lot. We went over the pathology of mastocytosis, WHO classifications, the systemic vs. cutaneous forms, early diagnosis, and the bone marrow procedure I was about to have. He asked if I had enough opioids for post-op pain. I did. I concluded that he does not write his own pain prescriptions.

Once on the operating table, the surgeon caressed my head, patting it before I fell asleep. I inwardly smiled as I laid straight on my right side. Cold prep solution dripped down my lower back as I sunk into sleep.

The surgeon bore into the ileum, then sucked out the bone marrow with a syringe.

When I woke up, my butt was numb and I did not need any more pain medication. But I was not given a prescription for postoperative pain for when I went home. I was told to use my existing opioid prescription for pain, which is reasonable, as long as my doctor doesn't "count" them against me.

(My thoughts: How do patients defend themselves to get opioids for during and after surgery? I mean, I’m a doctor and I had to stick up for myself. What if the patient does not even know to ask about postoperative pain at all? They must wake up screaming, an insult to any anesthesiologist. What has happened to patient care?

They profession of anesthesiology has changed.

Dr. Margaret Aranda is a Stanford and Keck USC alumni in anesthesiology and critical care. She has dysautonomia and postural orthostatic tachycardia syndrome (POTS) after a car accident left her with traumatic brain injuries that changed her path in life to patient advocacy.

Margaret is a board member of the Invisible Disabilities Association. She has authored six books, the most recent is The Rebel Patient: Fight for Your Diagnosis. You can follow Margaret’s expert social media advice on Twitter, Google +, Blogspot, Wordpress. and LinkedIn.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Study Advocates Guidelines for Postoperative Pain

By Pat Anson, Editor

Patients recovering from gallbladder surgery need only about a third of the opioid painkillers that are prescribed to them, according to a small new study that could lay the groundwork for new national guidelines on treating postoperative pain.

Researchers at the University of Michigan looked at prescribing data on 170 people who had their gallbladders surgically removed in a laparoscopic cholecystectomy and found that the average patient received an opioid prescription for 250mg morphine equivalent units. That's about 50 pills.

But when the researchers interviewed 100 of those patients, the amount of opioid medication they actually took after their surgeries averaged only 30mg, or about 6 pills. The remaining pills were often left sitting in their medicine cabinets for years.

"For a long time, there has been no rhyme or reason to surgical opioid prescribing, compared with all the other efforts that have been made to improve surgical care," says lead author Ryan Howard, MD, a resident in the U-M Department of Surgery who began the study while attending the medical school.

"We've been overprescribing because no one had ever really asked what's the right amount. We knew we could do better."

When U-M surgical leaders heard about the findings, they gave Howard and his colleagues permission to develop a new prescribing guideline that recommended just 15 opioid pills for gallbladder patients.

Five months later, the average prescription for the first 200 patients treated under the guideline dropped by 66 percent -- to 75mg morphine equivalent units. Requests for opioid refills didn't increase, as some had feared, but the percentage of patients getting a prescription for “safer” non-opioid painkillers such as acetaminophen or ibuprofen more than doubled.

Interviews with 86 of the patients who received the smaller prescriptions showed they had the same level of pain control as those treated before -- even though they took fewer opioid painkillers. A new education guide for patients counseled them to take pain medication only as long as they have pain, and to reserve the opioid pills for pain that's not controlled by ibuprofen or acetaminophen.

"Even though the guidelines were a radical departure from their current practice, attending surgeons and residents really embraced them," said U-M researcher Jay Lee, MD. "It was very rewarding to see how effective these guidelines were in reducing excess opioid prescribing."

Researchers estimate that implementing the new guideline has kept more than 13,000 excess opioid pills out of circulation in the year since the rollout began. Their findings were published in JAMA Surgery.

U-M researchers have expanded on their efforts by developing prescribing guidelines for 11 other common surgeries, including hysterectomies and hernia repair. They believe the guidelines could serve “as a template for statewide practice transformation” and could be adopted nationally as well.   

It’s a common misconception that many patients become addicted to opioid medication after surgery. According to a recent national survey, one in ten patients believe they became addicted or dependent on opioids after they started taking them for post-operative pain. But a recent study in Canada found that long term opioid use after surgery is rare, with less than one percent of older adults still taking opioid pain medication a year after major elective surgery.

Another fallacy is that leftover pain medication is often stolen, sold or given away. The DEA says less than one percent of legally prescribed opioids are diverted.

Many patients are dissatisfied with the quality of pain care in hospitals. In a survey of over 1,200 patients by Pain News Network and the International Pain Foundation, 60 percent said their pain was not adequately controlled in a hospital after a surgery or treatment. And over half rated the quality of their hospital pain care as either poor or very poor.