Review and critique of the 2017 Draft Recommendations for use of Opioids inChronic Non-Cancer Pain8/12/2017
It is well established chronic pain is a major health care problem that is largely ignored in the
health care field and by those making health care policy decisions. People with pain can attest to this as they continue to be stigmatized, marginalized and often simply ignored. These draft guidelines re-enforce these ideas and raise another barrier to the treatment and management of pain. These guidelines, which is appears were influenced by the extremely flawed and biased guidelines by the CDC in the United States, written by a small group of anti-opiate crusaders with strong ties to a large drug rehab chain seem to reflect more attention to people with addictions and not people with pain. We would note that publishing the draft recommendations without the guideline’s main text and the supporting evidence provides limited information for anyone to sufficiently evaluate them. We strongly suggest, before moving forward with them, that you publish a draft of the complete guidelines and then opening it up for comments from readers so they may adequately comprehend the guidelines’ content and adequately provide comments. We would also strongly suggest that if your wish to receive comments leave it at that and don’t ask people to answer your preconceived survey. In addition, it would be helpful to have access to the panel members’ backgrounds and ALL their affiliations. How many of the voting panel were medical doctors with front line pain experience? Our initial research concerning the panel members indicates most have little or no experience on the front lines of pain medicine, but are inextricably intertwined, which leaves the impression that perhaps balance may have been difficult to achieve. We do believe increasing awareness of the opioid overdose risk is appropriate, but claiming certain unsubstantiated risks outweigh the benefits of using opioids to treat pain lacks scientific foundation. According to a recent study by Dasgupta et al., of 2,181,372 patients prescribed opioids, 478 deaths were reported (0.022% per year). In addition the CDC Guidelines, which this Canadian(?) effort appears to be based on, are in direct conflict with the National Institutes of Health Guidelines published in 2014. They were based on an extensive literature review by an unbiased expert panel which concluded: “What was particularly striking to the panel was a realization that there is insufficient evidence for every clinical decision that a provider needs to make regarding the use of opioids for chronic pain, leaving the provider to rely on his or her own clinical experience.” It was also observed the target should be, what the patient and their healthcare provider have decided between themselves as a reasonable goal to accomplish. We concur. It is also baffling why we would create guidelines to affect a profession which has little education about chronic pain, and little experience or understanding about the treatment and management of pain. Educate them first and then develop guidelines they will actually understand. We are not opposed to guidelines when they are relevant and appropriate, but feel these are premature and don’t reflect the realities of pain medicine. This is obvious when one looks at the official Guideline Panel. As pointed out, based on initial research, almost all have no real experience on the front lines of pain medicine and the close relationships between the majority of the panel, gives the impression of a biased outcome. It is sheer folly to think this process will do anything to solve the present ILLICIT substance misuse problem, which it appears is another false underlying reason for this project. It will simply create another tragic situation for many people with pain. Pain patients feel strongly the authors and policy makers behind these guidelines have missed another golden opportunity to create real change in this area of medicine. They would have impacted pain medicine for more positively if they had used their resources to develop forward thinking educational programs and incorporate them into the curricula in our teaching hospitals. This would have a far greater impact on addressing the chronic pain pandemic and the problem with addictions. By putting forth guidelines like this, at this time, to influence (or control) a profession that has little education and understanding about chronic pain is myopic and similar to the last attempt at guidelines will simply encourage more physicians to dump pain patients they now have. Or is that the real goal? As we have stated it is difficult to sufficiently evaluate the guidelines without the supporting evidence behind them and the background of the official panel members. However we will make the following observations: 1. We take issue with some of the language that has been used. In Recommendation #1 and #2, in the Rationale it sites….”very frequent dependence and frequent addiction” and …”dependence and addiction”. Physiological dependence may be an expected outcome of long term opioid use…but this is not addiction. You appear to refer to this throughout the document along with addiction (more as the addiction aspect as opposed to the physiological aspect of opioid use. This is quite misleading and should be removed. There is a distinction that physical dependence is not the same as addiction. You also make the insinuation, throughout the document, that addiction is almost guaranteed with opioid use. This again is incorrect and should be deleted. 2. In reference to Recommendations #6 and #7 it is recognized there are various limitations to assigning a morphine equivalent daily dose (MEED) cut-off that could adversely affect patient care and create barriers and other challenges in clinical practice. First, there is no universally accepted opioid conversion method and heterogeneity in calculating morphine equivalence among clinicians. Shaw et al evaluated 8 online opioid dose conversion calculators and identified a percent variation of -55% to +242%. Rennick et al, surveyed 319 healthcare professionals (MD/DO, PharmD/RPh, NP) on calculating MEDD for several opioids and found wide variability. The study authors asked participants to calculate MEDD for hydrocodone 80mg, fentanyl 75mg/hour (1800mcg/day), methadone 40 mg, oxycodone 120 mg, and hydromorphone 48 mg. The calculated MEDD for fentanyl, hydrocodone, hydromorphone, methadone, and oxycodone were: 176 (±117) mg, 88 (±42) mg, 192 (±55) mg, 193 (±201) mg, and 173 (±39) mg respectively. In the cases of fentanyl and methadone, the SD in just one direction was greater than your proposed cut-off of 90mg MEDD. All other cases approached or exceeded 90mg MEDD when considering the entire SD range from positive to negative. Assigning a standard MEDD cut-off in absence of a standardized approach to calculate morphine equivalence is not feasible to implement uniformly in clinical practice and will pose challenges to clinicians. It should also be noted that 25 mcg of fentanyl exceeds the 90mg cut-off as well. 3. Recommendation #7 has been labeled as a “strong recommendation”. However, the rationale section discusses findings from an observational study that is deemed “moderate quality evidence”. A strong recommendation requires high quality supporting evidence opposed to moderate quality evidence from an observational study. After reviewing the implications associated with strong recommendations on different stakeholders (as per your charts on Implications), it appears that strong recommendations will be disseminated and adopted throughout healthcare. Therefore, we believe there should be strong supporting evidence based on high quality studies before they are applied “to all or almost all patients” or “adopted as policy in most situation.” To label the recommendation as “strong recommendation” based on moderate quality evidence from observational studies is unscientific, unprofessional, unethical, and quite frankly should be inconceivable to any legitimate scientific panel. In the absence of strong evidence, we believe this recommendation should be deleted or at best totally reconsidered and reviewed by a different panel. 4. The 50mg and 90mg dose recommendations are arbitrary numbers with no evidence supporting them. These again have been plucked from the flawed CDC Guidelines which has a number of contradicting statements within them on the presented evidence and the recommendation strength of its recommendations. For instance, according to the National Guideline Clearinghouse, “Level A rating requires at least two consistent Class 1 studies. However, all 12 of the CDC recommendations provided are based on case studies (level 3 evidence) or expert opinion (level 4 evidence) yet all were assigned a Grade A recommendation. For instance, according to the guidelines providers should implement additional precautions when increasing dosage to ≥50 morphine equivalents (MME/day, and should generally avoid increasing dosage to ≥90 MME/day (recommendation category A, evidence type: 3)”. This recommendation was based on ONE randomized un-blinded study of only 135 patients (94% male; 74% had musculoskeletal pain) who has received 40 MME/day compared to 52 MME/day, yet this recommendation was then generalized to “chronic non cancer pain” and the recommendation “to avoid increasing dosage to ≥90 MME/day” was NOT EVEN EVALUATED by the referenced study. This makes it even more astonishing you would use the CDC Guidelines as the template for these Canadian(?) guidelines. 5. In regard to the last sentence in the rationale for recommendations #6 and #7, “These serious outcomes are very rare in those prescribed less than 50mg MEDD, but increase in those prescribed dose of 50 to 90, and though rare, are very concerning in those prescribed doses over 90”. The guidelines should fairly and accurately define the aforementioned frequencies “rare vs. very rare” and define “serious outcomes”. As mentioned in the large cohort study by Dasgupta et al, out of 2,181,372 patients prescribed opioids, 478 overdose deaths were reported (0.022% per year) Dasgupta et al concluded a dose-dependent opioid overdose risk but did not show evidence of a distinct threshold. Furthermore, rates of overdose deaths were 10-fold higher among patients co- prescribed benzodiazepines and opioids than opioids alone. Zedler et al developed a validated risk assessment tool using a multivariate linear regression model for overdose or serious opioid-induced respiratory depression. The risk assessment tool was first validated in a cohort of U.S. veterans and subsequently validated in the general population. Zedler’s validated risk assessment tool identified variables associated with increased risk for opioid-induced respiratory depression including various medical and psychiatric co-morbidities and presence of concomitant.. Why were these types of tools not spoken of in the draft guidelines? Relying solely on the morphine equivalent dose when developing the guidelines indicates a disturbing bias against the use of opioids perpetuated by the anti-opiate drug rehab group involved in the CDC Guidelines which has led to the present “Pied Piper” movement across Canada and the premature acceptance of their myopic views. It will be confusing to some readers and contradicts with part of the rationale for recommendation #7 that reads “Some patients may gain important benefit over 90mg morphine equivalents, but not on lower doses.” We recommend distinguishing “persistent problematic pain” from “problematic side effects”. There are various reasons a patient may have persistent pain on a 90mg morphine dose that should be considered when making a clinical decision such as pharmacogenetics variability affecting drug metabolism, weight, drug interactions, tolerance, and variable pain pathology. For example, oxycodone is metabolized through CYP3A4 to inactive metabolite noroxycodone and through CYP2D6 and CYP3A4 enzyme expression can yield different serum concentrations and exposure between patients taking the same dose. Additionally, there are more than 100 polymorphisms in the mu-opioid peptide receptor gene (OPMR1) that can increase or decrease analgesic effect from opioids. Therefore, having a MEDD cut-off to taper opioids may be oversimplified, especially when considering variable half-livrs (consider methadone) and partial agonists/antagonists (consider buprenorphine) and opioids mixed with mixed activity (consider tapentadol). None of these three should ever be given a “hard stop” morphine equivalent. With this we must reiterate the National Institute of Health committee conclusion: “What was particularly striking to the panel was the realization that there is insufficient evidence for every clinical decision that a provider needs to make regarding the use of opioids for chronic pain, leaving the provider to rely on his or her clinical experience.” The target should be what the patient and their healthcare provider have decided between themselves as a reasonable goal to accomplish. Again, we could not concur more. We recommend these guidelines be scrapped totally and strong efforts be incorporated to move toward this goal. Or scrap these guidelines and have them rewritten by real doctors involved in pain medicine and patients. Leave the “Pied Piper” out of it. References: 1. Rennick A, Atkinson TJ, Cimino NM, Strassels SA, McPherson ML. Fudin J. Variability in opioid equivalence calculations. Pain Med. 2015 Sep 9; Epub. 2. Shaw K, Fudin J. Evaluation and comparison of online equianalgesic opioid dose conversion calculators. Pract Pain Manag. 2013;13:61-66 3. Dowell D. Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain – United States, 2016 MMWR Recomm Rep 2016;65(No. RR-1):1- 49. Barry D. Ulmer Executive Director The Chronic Pain Association of Canada 11247 11 Avenue NW Edmonton, Alberta T6J 6S3 (780) 482-6727 Comments are closed.
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