Opioid Safety is Job One

Considering the grim statistics regarding the rising number of accidental deaths and injuries associated with the medical and non-medical use of prescription pain medications, it should be clear by now that physicians and patients need to learn more about safe and responsible pain care. Samantha Libby-Cap, Director of the American Pain Foundation’s (AFP) Pain Safety & Access For Everyone (PainSAFE) educational initiative (http://hcp.lv/n7JcYv) agrees, saying that “both patients and physicians are responsible parties in treating pain. This responsibility applies to all types of pain treatment, not just medications. A patient receiving implantable pain therapy is responsible for understanding it and knowing the safety issues associated with it. Safety is not just the medical professional’s responsibility, but the person with the pain, the caregiver, and the pharmacist.”

PainSAFE is designed to increase awareness of safety issues associated with prescription pain medications and improve access to quality pain care. The program “is about educating people with chronic pain and the professionals who use pain management therapies,” says Libby-Cap, who also notes that communication between patients and health care professionals is an essential element of safe and effective pain management. PainSAFE also focuses on improving communication between patients and physicians, offering a variety of resources on the website. “We saw a gap in the messaging between information sources for patients versus health care professionals. In addition to educating clinicians, we want to be a resource they can recommend to their patients,” says Libby-Cap.

Launched in September 2010 by the American Pain Foundation, PainSAFE offers a variety of high-quality patient education tools, such as “Chronic Opioid Therapy: Preparing for Your Appointments,” (http:// hcp.lv/ny1Ka3) which helps patients prepare to talk about their current pain levels and functional abilities, any side effects, and other medications they’re taking. “Chronic Opioid Therapy: Do’s and Don’ts to Help Avoid Problems” (http://hcp.lv/nARYtD) helps set appropriate expectations around opioid therapy. Libby-Cap says these resources were created because the APF found that “many pain patients did not know what to expect at their visits. Being unprepared, they didn’t get all their questions answered, resulting in additional visits. A prepared patient can communicate better, strengthening the partnership with health care providers.”

PainSAFE also includes additional initiatives that extend the focus beyond chronic opioid therapy to cover topics in implantable pain treatments and acetaminophen safety. More recent efforts have included public safety announcements about acetaminophen doses and publicizing a “National Prescription Drug Take-Back” event in April. A “Family” section on the “Safety Tools & Resources” page (http://hcp.lv/pV7scH) includes educational information about teen prescription drug abuse.

Precursor to PainSAFE: Zero Unintentional Deaths

The Centers for Disease Control in 2009 reported that opioid-related poisoning deaths tripled between 1999 and 2006 in the United States, increasing from 4,000 to 13,800 annually. Opioid analgesics were implicated in 40% of all poisoning deaths in 2006. (http://hcp.lv/r5hVLF). Unintentional deaths from opioids vary widely among states, with 16 states above the national rate of 4.6 deaths per 100,000 people. Among these outlier states is Utah, home to national pain expert, Lynn Webster, MD, FACPM, FASAM, who became aware of this problem several years ago when he read a newspaper article in which the Utah state medical examiner stated there was an epidemic in prescription overdose deaths.

Webster, who was president of the Utah Academy of Pain Medicine (http://hcp.lv/oOUub2) and ran the largest pain practice in the state at the time, says that “I knew I couldn’t rely on someone else to address this issue,” so he started looking into the causes of unintentional prescription drug deaths. Webster found that at least 30% to 50% of deaths occurred because of preventable errors by patients or physicians. In response, in 2006 he helped launch “Zero Unintentional Deaths” (http://hcp.lv/onlWcr), a state-wide physician and patient educational project in Utah with the goal of reducing the number of opioid-related unintentional deaths in the state by 15% in two years. In part due to the efforts of this project, Utah’s medicationrelated death rate dropped 14% from 2007 to 2008. The June 2011 issue of Pain Medicine includes a free supplement that explores the issues around unintentional deaths related to opioids and solutions with lessons from Zero Unintentional Deaths in Utah and Project Lazarus in Wilkes County, North Carolina (http://hcp.lv/jsRT0q).

Lessons learned from the Zero Unintentional Deaths initiative have been expanded to the national level through the PainSAFE initiative, which publishes opioid prescribing guidelines for clinicians, “Six Opioids Safety (SOS) steps for patients,” and other resources that outline the path to making pain management safer (http://hcp. lv/lMBGlp).

Opioid safety goes beyond misuse and abuse

Reducing unintentional deaths from prescription pain medications requires clinicians to do more than assess patients for abuse risk and monitor them for ongoing mental health issues. Physicians interested in responsible pain management must also consider other factors such as the dangers of sleep apnea and other respiratory impairments associated with opioid treatment.

“In a perfect world, every chronic pain patient would get a sleep study,” says Bruce Nicholson, MD, director of Pain Specialists of the Greater Lehigh Valley and medical reviewer for PainSAFE. Webster once sent 400 patients consecutively for sleep studies to confirm whether a local sleep medicine pulmonologist colleague who claimed that patients on opioids had irregular abnormalitites in the sleep lab was correct. It turns out that sleep disordered breathing dominated for patients who were on longterm opioid therapy, with 75% having abnormal apnea-hypoxia index scores (http:// hcp.lv/qBhZ0L). Research has shown a dosedependent relationship between chronic use and the development of sleep apnea (http:// hcp.lv/q7W9sq). Obstructive sleep apnea was present in 39% of the patients tested by Webster. Central sleep apnea, a rare condition associated with neurologic disorders like stroke or congestive heart failure, occurred in 24% of the chronic pain patients on opioid therapy. “The results were astounding: 20% to 30% of patients had life-threatening levels of apnea,” says Webster. “Some of these patients may have gone home, developed a respiratory infection that diminished their reserves even more, so that they might not have awoken the next morning. And maybe we would have thought it due to heart attack or some natural cause.”

In Nicholson’s practice, any patient who is overweight or obese gets a sleep study. Also, “any patient on 150 morphine equivalents daily or 50 mg methadone needs a sleep study,” says Nicholson. Clinicians evaluating patients for sleep studies can also use the Epworth Sleepiness Scale (http://hcp.lv/pghwju), a quick, eight-question measure that evaluates excessive daytime sleepiness symptoms. However, Webster says that a major lesson learned from the “Zero Unintentional Deaths” project was that Medicaid often will not cover a sleep study. “When I encounter this scenario, I either don’t put the patient on opioids higher than 150 mg morphine equivalents or use supplemental oxygen during sleep if a higher dose is needed,” says Webster.

A positive sleep study creates a new clinical conundrum. “It’s a Catch-22: not adequately treating a patient’s pain is unacceptable but using opioids in patients with sleep disorders increases the risk. No clinical guidelines exist to advise us on how to manage these patients,” admits Nicholson. Webster is more optimistic, given that more information exists now than five years ago when he ran his study. “Although we don’t know exactly how to treat the problems of sleep apnea relative to or due to opioids, there are options available—they just have to be individualized like most things in medicine.”

The first option is try a lower opioid dose through opioid rotation. “With opioid rotation, we often see that a patient gets adequate analgesia at a lower dose,” notes Webster. Another treatment option is supplemental oxygen, since apneas are an oxygen-saturation respiratory issue. “I’ve found with simple sleep apnea, 50% of patients will normalize with supplemental oxygen during sleep. An inexpensive option, though a hassle, but the opioid dose can be maintained,” says Webster. Continuous positive airway pressure (CPAP) controlling the patient’s ventilation produces mixed results, sometimes making the problem worse. Webster advises clinicians to engage their sleep medicine-pulmonology colleagues when working with patients on opioids with sleep apneas. Through experience, Webster has also found that the timing of breakthrough pain medication often affects the outcomes of sleep studies. “It is a challenge, but we can’t ignore the problem. I believe some unintentional overdose deaths have occurred because of the association between opioids and sleep apnea,” he says.

A second respiratory-related prescribing guideline is to reduce opioid doses when patients have upper respiratory infections or asthma attacks. Extrapolating from the sleep apnea findings in chronic opioid therapy patients, Webster says that “patients who are already at a borderline level cannot tolerate any further decrease in sleep oxygenation or they won’t wake up.” Increased impairments in apnea-hypoxia indexes are documented with seasonal allergies and upper respiratory tract infections. When a patient starts opioid therapy in Webster’s practice, he advises them to decrease their afternoon and bedtime doses by 25% when upper respiratory tract infections, asthma flares, or severe seasonal allergies are present.

Other safety concerns

Whether it’s the “Kentucky cocktail” of Oxycontin, Klonapin, and Soma, or elderly females and their “nerve pills,” improving pain management safety involves tackling some tough regional prescribing issues.

Benzodiazepine-opioid polypharmacy

In his Pennsylvania pain practice, Nicholson says that “Every older lady who comes to me on opioids is also on a benzodiazepine, despite the fact that we have no clinical evidence that supports the practice. In fact, data suggest that combining benzodiazepines with opioids contributes to treatment refractoriness for chronic pain.” To address the issue, Nicholson counsels patients that this medication combination is not in their best interest and titrates patients off the benzodiazepines. Webster also recommends a sleep study for any patient who remains on opioids and benzodiazepines to maximize safety.

Limiting concurrent benzodiazepine use, especially during sleeping hours, is another prescribing measure that can improve respiratory safety. Research indicates that combination treatment with benzodiazepines increases the rates of apneic events in chronic opioid therapy patients. (http://hcp.lv/q7W9sq). Benzodiazepines were involved in 17% of the opioid-related unintentional deaths from the CDC study (http://hcp.lv/r5hVLF).

Opioid conversion tables

Prescribers should use caution with conversion tables for switching opioids. “Conversion tables are developed based on studies in opioid-naïve patients and can be highly misleading for clinicians”, says Nicholson. Webster also feels strongly about this and cautions that “opioid conversion tables are potentially lethal.” He says that “it’s impossible to come anywhere close to knowing where the safe level is for a different opioid, especially at high doses, because of the pharmacogenetic and pain-related individual patient differences.”

Conversion to methadone disproportionately causes prescription-drug deaths relative to other opioids. Although it is used in only 5% of pain patients nationwide, methadone is involved in one-third of opioidrelated deaths. In Utah, 70% of deaths with methadone occurred within the first seven days of treatment, indicating conversion and dose titration errors. One source of these errors can be found in the discrepancy between methadone’s elimination halflife (8 to 59 hours) relative to its duration of analgesia (4 to 8 hours) (http://hcp.lv/ qwE0fa). Webster says he is against the use of a conversion table when rotating patients to methadone from another opioid. The PainSAFE guidelines for methadone recommend for clinicians to assume the patient is opioid-naïve and start at the lowest dose (however, given that methadone is cheap and effective, some payers require it as firstline treatment). Webster recommends courses on safe methadone prescribing such as those offered during the American Academy of Pain Management annual meeting.

Given their views that the conversion tables in product package inserts are flawed, Webster and Nicholson suggest modified approaches for safely rotating opioids in patients. Nicholson recommends that clinicians should “automatically drop the dose of the new opioid by 25% to 50% in morphine equivalents,” a conversion approach advocated in Fine and Portnoy’s textbook on opioid analgesia (http://hcp.lv/oNuab0). “This guide nicely covers the variances in mu receptor occupancy among drugs and individual patient metabolism,” he says. Webster uses a slow titration-switching approach for opioid rotation and recommends that clinicians “drop the current opioid dose by 25% and start the new opioid at 25% equivalents. Drop the current opioid and increase the new opioid by 25% each week.”

EIGHT Prescribing Guidelines

Following these will help minimize harm when prescribing opioids and other psychotherapeutics

1. Assess your patients for risk of abuse before opioid therapy and manage accordingly.

2. Watch for and treat comorbid mental health disorders when they occur.

3. Use conventional conversion tables cautiously when rotating (switching) from one opioid to another.

4. Avoid combining benzodiazepines with opioids, especially during sleep hours.

5. Start methadone at a very low dose and titrate slowly regardless of whether your patient is opiod tolerant or not.

6. Assess for sleep apnea in your patients on high daily doses of methadone or other opioids and in those with a predisposition.

7. Tell your patients on long-term opioid therapy to reduce opioid dose during upper respiratory infections or asthmatic episodes.

8. Avoid using long-acting opioid formulations for acute postoperative or trauma-related pain.

Source: PainSAFE “Six Opioid Safety Steps”

Mental health issues

In addition to individual variation in metabolism, another individual factor affecting opioid safety is the risk for abuse and comorbid mental health problems. Webster says that “previous treatment and/or admission for substance abuse were found in half of the cases of unintentional opioid deaths. Comorbid mental health disorder is a key element that leads to self-medication and over-mediating. We need to identify anyone who has a history of substance abuse.” Webster recommends tools like the Opioid Risk Tool or the SOAPP tool.

However, the presence of a comorbid mental illness doesn’t preclude adequate pain management. “These patients with mental health issues or substance abuse history do also have a severe pain problem. But we must recognize they cannot self-manage their medications and plan accordingly,” says Webster. Options include giving higher risk patients three 10-day prescriptions instead of one 30-day opioid prescription. The June 2011 Pain Medicine supplement mentioned above explores the comorbid mental health issue in depth.

PainSAFE patient responsibilities

Patients have just as many responsibilities as their physicians when it comes to medication safety and pain management. The officeready “Six Opioid Safety (SOS) Steps” handout prepared by PainSAFE (http://hcp.lv/qgCAI3) outlines several steps patients must take to ensure safe pain management, including: never taking an opioid medication that is not prescribed or taking more than the prescribed amount; avoiding mixing opioids with alcohol, sedatives, or benzodiazepines; and locking up pain medications. If Webster gets pushback from patients on locking up medication, he leverages the current stigmas as persuasion for patients and tells them “If you need this medication and it’s stolen, there is a chance you will never get this medicine again. Doctors are going to assume that you’re either selling it or overusing it and have a substance abuse problem. So if you need the medicine, you have a responsibility to yourself, your clinic and provider, and also the larger society to lock up your medicine.”

The six opioid safety steps are based on the findings from studies of the causes of unintentional deaths. Webster says that “A combination of one or more opioid safety factors led to most of the unintentional deaths from opioids.” According to Nicholson, “the patient is the common denominator; the SOS just capture what all opioid patients do.”

Although it’s implied in the six steps that patients should not share their medications with friends and family, this message must constantly be reinforced by prescribers. Nicholson says that “Not a day goes by that I couldn’t ask one of my patients whether they have ever given their pain medicine to their spouse, etc. Almost every one of them would say ‘Yes, I have.’”

Opinions vary widely among experts about how to implement the SOS in practice. PainSAFE has pamphlets that can be ordered with the SOS and prescribing guidelines. Webster, who would like to see the SOS for patients posted in the office and handed out by physicians and pharmacists when patients are given a prescription, says “Patients need to understand these basic principles when they are prescribed these medications.” Nicholson, who takes a more cautious view, disagrees and is against general postings in the office. “I don’t think it’s good for patients to interpret the opioid safety steps on their own. Physicians should be conducting the six opioid safety step conversation with their patients,” he says.

Next steps in the fight for safer pain management

Projects in the PainSAFE pipeline include a guide for pain patients who travel internationally, efforts to build alliances to deliver consistent messages about opioid therapy safety, and guidelines that address complementary and alternative pain therapies. Scheduled for publication later this year, the comprehensive education section on complementary and alternative medicine for pain management was developed in conjunction with the National Center for Complementary and Alternative Medicine (http://hcp.lv/nXaN1R).

Physicians who are interested in spreading the message about safe and responsible pain management practices can access presentations to use for grand rounds and other speaking engagements (http://hcp.lv/pDv250). A trainthe- trainer program is also in the works. Contact PainSAFE directly at painsafe@ painfoundation.org for slides and other resources. Webster is excited by the PainSAFE initiatives because they are a continuation of the successful efforts implemented in Utah. He says that “We can all make a difference and prevent unintentional deaths from opioids while maintaining access to pain treatment.”

Heather Haley enjoys writing chronic pain CME in the hopes of making the world a better place and eliminating the Kentucky Cocktail, which is becoming an epidemic in her home state of Ohio.