Editorial - Journal of Clinical Respiratory Medicine (2018) Journal of Clinical Respiratory Medicine (Special Issue 1-2018)
Opioid induced respiration is a major problem.
Department of Anesthesia, Naples Anesthesia and Pain Associates, USA
- Corresponding Author:
- Joseph Pergolizzi, MD
Sr. Partner, Naples Anesthesia and Pain Associates
868 106th Avenue North, Naples, FL 34108, USA
E-mail: [email protected]
Accepted date: December 19, 2017
Citation: Pergolizzi J. Opioid induced respiration is a major problem. J Clin Respir Med. 2017;1(1):12-14.
Opioid use disorder has emerged as a major American public health crisis, and the majority of the half-million American drug overdose deaths from 2000 to 2015 were opioid related . Opioid overdose fatalities are typically caused by respiratory depression which occurs as a result of an opioid-induced decrease in respiratory drive combined with a decrease in the supraglottic airway tone [2,3]. The risk of potentially fatal respiratory depression may increase with certain comorbid conditions, such as obstructive sleep apnea or with high doses of opioids or certain drug combinations . Naloxone can reverse opioid toxicity by competing with the ingested opioid for mu-opioid-receptors; naloxone can effectively reverse respiratory depression in moments. Naloxone dosing is empirical and emergency responders increasingly find that multiple doses are necessary for street users [4,5]. This is due in part to the fact that the use of very potent illicit fentanyl is increasing among those who take street opioids . However, even in the home or hospital setting where opioids are taken appropriately under medical supervision, opioid-induced respiratory depression may still occur, particularly in deeply sedated patients .
A murine study of seven opioid agents found that no two had the same profile in terms of antinociception, rates of constipation or respiratory depression . Indeed, the “ceiling effect” of buprenorphine for respiratory depression is well described in the literature [9-11]. Buprenorphine does not exhibit a ceiling effect for analgesia [9,10,12].
The opioid crisis in America is complex and involves the overprescribing or mis-prescribing of prescription opioids (and the concomitant lack of physician education in terms of opioid prescribing), recreational use of opioids, lack of patient and consumer education about opioids, and a sudden abundance of cheap heroin and illicit fentanyl. The healthcare system can only control a few of these factors, namely physician/patient education and appropriate opioid prescribing. The “ideal opioid” analgesic product for prescribers would likely possess certain attributes. It would have to be a safe, effective pain reliever with a low potential for abuse. This describes buprenorphine with its ceiling effect for respiratory depression, its potency as an analgesic (it may be effective at low doses in treating pain) [13-15] and its abuse potential. In the United States, buprenorphine is categorized as a Schedule III controlled substance, unlike morphine and oxycodone and other opioids (Schedule II) . In studies of individuals with opioid use disorder, buprenorphine is less “likeable” than other opioids, such as oxycodone, where likeability is related to how often the drug is abused [17,18]. This is not to say that buprenorphine cannot be abused — that is not true — but it is among the least likely opioids to be taken inappropriately .
This stands in direct contrast to the better “liked” opioid of oxycodone, which is among the most frequently abused opioids in America . Efforts have been made in developing abusedeterrent formulations of oxycodone (and other opioids, such as morphine) in an effort to deter tampering with the tablets for use by alternate routes of administration, for example, by inhalation or injection .
Unfortunately, insurance companies in the U.S. as well as the Centers for Medicare and Medicaid Services (CMS) encourage the use of the least expensive opioid analgesics, which often means reimbursing for generic oral formulations of Schedule II opioids (such as morphine, oxycodone) rather than an effective Schedule III opioid such as buprenorphine or an abuse-deterrent oral opioid product. Reimbursement can often mandate that a patient get a riskier Schedule II opioid, even though products with lower abuse potential are readily available.
Transdermal and buccal buprenorphine is in many ways the closest thing to an “ideal opioid pain reliever” on the market. It is a Schedule III controlled substance, meaning it has a lower potential for abuse than most other opioids. It is a potent opioid — much more potent than morphine — meaning that in some cases pain control can be achieved with relatively low doses . It has been clinically evaluated and shown to be safe and effective in studies with patients suffering from chronic cancer and non-cancer pain [14,23-25]. Furthermore, the unique pharmacology of buprenorphine allows it to be used with dosing adjustments in geriatric patients and patients with renal dysfunction . The transdermal delivery system and the buccal formulation are convenient for patients and may enhance compliance because it does not increase the pill burden. They both allow for easy administration of the dose and may be particularly suitable for patients with dysphagia. The role of buprenorphine should be expanded in light of the opioid public health crisis and the need for safer but effective analgesics.
- CDC. Drug overdose deaths in the United States continue to increase in 2015. Understanding the epidemic 2016; https://www.cdc.gov/drugoverdose/epidemic/index.html. Accessed March 18, 2017.
- Macintyre PE, Loadsman JA, Scott DA. Opioids, ventilation and acute pain management. Anaesth Intensive Care. 2011;39(4):545-58.
- Cashman JN, Dolin SJ. Respiratory and haemodynamic effects of acute postoperative pain management: Evidence from published data. Br J Anaesth. 2004;93(2):212-23.
- FDA Advisory Committee on the most appropriate dose or doses of Naloxone to reverse the effects of life-threatening Opioid overdose in the community settings. Advisory Committee Brief Materials. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AnestheticAndAnalgesicDrugProductsAdvisoryCommittee/UCM522688.pdf. Accessed April 4, 2017.
- Faul M, Lurie P, Kinsman JM, et al. Multiple Naloxone administrations among emergency medical service providers is increasing. Prehosp Emerg Care. 2017;21(4):411-9.
- Drug Enforcement Administration DoJ. Control of immediate precursor used in the illicit manufacture of fentanyl as a schedule II controlled substance. Final rule. Fed Regist. 2010;75(124):37295-9.
- Gupta K, Prasad A, Nagappa M,et al. Risk factors for opioid-induced respiratory depression and failure to rescue: A review. Curr Opin in Anaesthesiol. 2017.
- Kuo A, Wyse BD, Meutermans W, et al. In vivo profiling of seven common opioids for antinociception, constipation and respiratory depression: No two opioids have the same profile. Br J Pharmacol. 2015;172(2):532-48.
- Khanna IK, Pillarisetti S. Buprenorphine - An attractive opioid with underutilized potential in treatment of chronic pain. J Pain Res. 2015;4(8):859-70.
- Pergolizzi J, Aloisi AM, Dahan A, et al. Current knowledge of buprenorphine and its unique pharmacological profile. Pain Pract. 2010;10(5):428-50.
- Sporer KA. Buprenorphine: a primer for emergency physicians. Ann Emerg Med. 2004;43(5):580-4.
- Dahan A, Yassen A, Romberg R, et al. Buprenorphine induces ceiling in respiratory depression but not in analgesia. Br J Anaesth. 2006;96(5):627-32.
- James IG, O'Brien CM, McDonald CJ. A randomized, double-blind, double-dummy comparison of the efficacy and tolerability of low-dose transdermal buprenorphine (BuTrans seven-day patches) with buprenorphine sublingual tablets (Temgesic) in patients with osteoarthritis pain. J Pain Symptom Manage. 2010;40(2):266-78.
- Yoon DH, Bin SI, Chan SK, et al. Effectiveness and tolerability of transdermal buprenorphine patches: A multicenter, prospective, open-label study in Asian patients with moderate to severe chronic musculoskeletal pain. BMC Musculoskelet Disord. 2017;18(1):337.
- Uberall MA, Muller-Schwefe GH. Low-dose 7-day transdermal buprenorphine in daily clinical practice - Perceptions of elderly patients with moderate non-malignant chronic pain. Curr Med Res Opin. 2012;28(10):1585-95.
- DEA. Buprenorphine. Drug & Chemical Evaluation Section. http://www.deadiversion.usdoj.gov/drug_chem_info/buprenorphine.pdf. Accessed 24 April, 2014.
- Pergolizzi JV Jr, Scholten W, Smith KJ, et al. The unique role of transdermal buprenorphine in the global chronic pain epidemic. Acta Anaesthesiol. 2015;53(2):71-6.
- Wightman R, Perrone J, Portelli I, et al. Likeability and abuse liability of commonly prescribed opioids. J Med Toxicol. 2012;8(4):335-40.
- Coplan PM, Sessler NE, Harikrishnan V, et al. Comparison of abuse, suspected suicidal intent, and fatalities related to the 7-day buprenorphine transdermal patch versus other opioid analgesics in the National Poison Data System. Postgrad Med. 2017;129(1):55-61.
- Setnik B, Roland CL, Pixton G, et al. Measurement of Drug Liking in Abuse Potential Studies: A Comparison of Unipolar and Bipolar Visual Analog Scales. J Clin Pharmacol. 2017;57(2):266-74.
- Setnik B, Bass A, Bramson C, et al. Abuse potential study of ALO-02 (Extended-release Oxycodone Surrounding Sequestered Naltrexone) compared with immediate-release oxycodone administered orally to nondependent recreational opioid users. Pain Med (Malden, Mass). 2017;18(6):1077-88.
- Pergolizzi J, Raffa R, Taylor R. Low-dose transdermal buprenorphine system: An update. Pain Europe. 2012;1:8-9.
- Apolone G, Corli O, Negri E, et al. Effects of transdermal buprenorphine on patients-reported outcomes in cancer patients: results from the Cancer Pain Outcome Research (CPOR) Study Group. Clin J Pain. 2009;25(8):671-82.
- Gatti A, Dauri M, Leonardis F, et al. Transdermal buprenorphine in non-oncological moderate-to-severe chronic pain. Clin Drug Investig. 2010;30:31-8.
- Karlsson M, Berggren AC. Efficacy and safety of low-dose transdermal buprenorphine patches (5, 10 and 20 µg/h) versus prolonged-release tramadol tablets (75, 100, 150 and 200 mg) in patients with chronic osteoarthritis pain: A 12 week, randomized, open-label, controlled, parallel-group non-inferiority study. Clin Ther. 2009;31(3):503-13.
- Pergolizzi JV, Raffa RB, Marcum Z, et al. Safety of buprenorphine transdermal system in the management of pain in older adults. Postgrad Med. 2017;129(1):92-101.