This Invited Commentary accompanies the following article:
Stromer W, Michaeli K, Sandner-Kiesling A. Perioperative pain therapy in opioid abuse. An approach to pain management. Eur J Anaesthesiol 2013; 30:55–64.
Anaesthesiologists involved in Acute Postoperative Pain Services and working in Emergency Departments are currently under pressure to provide their patients with the most effective therapy. Despite our efforts, international audits have highlighted the fact that acute pain still remains a problem for a substantial number of patients. Apart from the humanitarian aspect, severe unrelieved acute pain can compromise recovery after a surgical procedure or trauma, and in some patients may lead to the development of persistent pain. In the present issue of the European Journal of Anaesthesiology, Stromer et al.1 discuss the perioperative pain management of patients with opioid abuse, which is often challenging. They provide us with an opportunity to question our practice, and specifically our responsibility, in the prescription of postoperative opioids.
To this day, opioids remain one of the mainstays of our therapeutic arsenal in the management of acute pain. When prescribing opioids, often as part of a multimodal therapeutic approach in patients with severe acute pain, we are more concerned about the immediate adverse effects of these drugs, such as nausea and vomiting, sedation, dizziness, constipation and urinary retention. After day surgery, we may also fear driving accidents. We usually consider that opioid addiction does not arise as a consequence of opioid treatment of pain because several experimental studies have shown that pain attenuates the euphoria and rewards induced by opioid intake.2
However, we should keep in mind that short-term opioid therapy can lead to longer-term use, at least in some patients. This important issue has recently been explored in two interesting reports assessing the longitudinal use of postoperative opioids after patient discharge. Alam et al.3 have conducted a retrospective cohort study evaluating the risk of long-term analgesic use after low-risk surgery in older adults who were previously opioid-naive. They found that 10% of those who were prescribed opioids within 7 days after a low-pain surgical procedure were still using them 1 year later. In other words, patients receiving an opioid prescription after surgery seem to be 44% more likely to become long-term opioid users [adjusted odds ratio, 1.44; 95% confidence interval (CI) 1.39 to 1.50] compared to patients who did not receive an opioid prescription. In a prospective longitudinal cohort study, Carroll et al.4 have not only examined the duration of opioid use after surgery but, more specifically, have tried to highlight the determinants of long-term opioid intake. The main finding of the study is that 6% of the patients continued their postoperative opioid prescription for more than 150 days after surgery. In this study, about a quarter of patients having undergone total hip or knee arthroplasty were still taking opioids at the end of the follow-up period, about 2 years later. Interestingly, postoperative pain duration and severity only seemed to account for 48% variance in the development of longer-term use, whereas preoperative factors such as legitimate prescribed opioid use, self-perceived risk of addiction and depressive symptoms were better predictors of prolonged use.4 Of the small amount of data currently available for Europe, recent work from Andersen et al.5 highlights that 56 and 22% of patients are still on opioids 30 days after total knee and total hip arthroplasty, respectively (Table 1). It is worth noting that among these patients with postsurgical pain, some decide to stop opioid intake, whereas others do not, a decision that seems to occur early (Table 1). In the systematic reviews on long-term opioid management for chronic non-cancer pain, patients usually discontinue oral opioid intake as a result of either adverse effects (mean, 23%; 95% CI 15 to 26%) or insufficient pain relief (mean, 10%; 95% CI 8 to 14%).6 The fact that opioids, particularly morphine, reduce the affective rather than the sensory dimension of pain7 might explain why postoperative analgesic consumption is inappropriate for evaluating analgesic efficacy.8 It also explains why some patients with higher levels of affective distress are more likely to continue to use prescribed postoperative opioids.4
Should we be worried that our patients remain on opioid therapy for a prolonged period of time? The answer is probably Yes. After all, the risks and benefits of long-term opioid use are still poorly understood, especially when chronic non-malignant pain is concerned. A large epidemiological study from Denmark reports that opioid usage is associated with poor pain relief, decreased quality of life and low functional capacity.9 Although a causative relationship cannot be ascertained from such a study, the authors concluded that opioid treatment of chronic non-cancer pain does not seem to fulfil its goals.9 Recently published studies also underline that long-term opioid use might be associated with poorer functional outcome, specifically after orthopaedic procedures such as anterior cervical arthrodesis and knee arthroplasty.10
Although some opioid-induced side-effects, such as nausea, vomiting, constipation, tolerance and addiction, are well known, that may not be the case for new complications such as hypogonadism, osteoporosis, immune suppression, cognitive impairment and hyperalgesia. All these could potentially cause an increase in morbidity of patients on long-term opioid therapy. Older patients may well be at particular risk for these various complications. Although opioid usage has increased tremendously in recent years, and the American Geriatric Society has recommended their use for elderly patients,11 there have been some alarming reports. In a propensity-matched cohort study by Solomon et al.12 comparing the safety of opioids and non-steroidal anti-inflammatory drugs in more than 12 000 elderly patients with arthritis, those on opioids had an increased relative risk for many safety events (fractures, cardiovascular events, hospitalisations) compared with non-steroidal anti-inflammatory drugs.
Despite these misgivings, opioids are sometimes inevitable and the question then becomes which one to choose and how to prescribe it. Although we do not have a definitive answer, the literature provides us with some clues. In a propensity-matched cohort analysis comparing the safety of different opioids in an elderly population with chronic non-malignant pain, Solomon et al.12 found that the rates of safety events varied significantly between the different agents. Tramadol (relative risk 0.21; 95% CI 0.16 to 0.28) and propoxyphene (0.54; 0.44 to 0.66) users were less likely than hydrocodone users to suffer a fracture, whereas oxycodone (2.43; 1.47 to 4.00) and codeine (2.05; 1.22 to 3.45) users had a higher risk of mortality from all causes. Codeine users also had a higher rate of cardiovascular events at 180 days (relative risk 1.62; 95% CI 1.27 to 2.06).12 Concerning endocrine side-effects, buprenorphine and tramadol are reported to have no impact on testosterone levels.13 Regarding falls and fractures, initiating treatment with slow-release preparations also seems to decrease the risk of fracture, at least during the first weeks of treatment.14
Finally, we should probably try to keep the opioid dose as low as possible. In a population-based nested case–control study of about 600 000 patients treated with opioids for chronic malignant pain, high daily doses (> 200 mg day−1) have been associated with an almost three-fold increase in opioid-related mortality compared with small daily doses (<20 mg day−1).15 In addition, opioid tolerance and hyperalgesia may develop rapidly, within 1 month of oral morphine treatment with doses ranging from 30 to 120 mg per day.16 Tolerance and hyperalgesia contribute to the loss of analgesic efficacy that might lead to an escalation in opioid dose. Alam et al.3 found that many patients initially prescribed weak opioids switched to strong opioids. The incidence of oxycodone prescription rose from 5% within the first 7 days postsurgery to 16% within 1 year of surgery.
So, what is the way forward? First, we should become better at identifying the patients who are at risk of needing prolonged postoperative opioids. The list includes those with preoperative opioid use, psychological fragility and those who might be particularly vulnerable to their side-effects, generally the elderly. Second, we should make every effort possible to adapt our perioperative treatments to reduce the need for opioids to a minimum, promoting preventive analgesia, multimodal analgesia with regional analgesia and anti-hyperalgesics, whenever possible. Finally, only a closer follow-up of our patients after their discharge, for example in a dedicated subacute pain unit, will enable us to better understand their outcomes and thus adapt our treatments accordingly.17 The importance of iatrogenic opioid exposure in the development of opioid misuse and addiction has been highlighted in various clinical studies; Carroll et al.4 tell us that among those prescribed opioids (legitimate use), one third also report taking illicit opioids. So when we have matched the best therapy to the individual need, we must be aware of what happens to our patients when they leave hospital because, in the end, we are responsible for the consequences of the opioids we prescribe.
Assistance with the commentary: none declared.
Financial support and sponsorship: none declared.
Conflicts of interest: none declared.
Comment from the Editor: this Invited Commentary was checked and accepted by the editors, but was not sent for external peer review. PL is an associate editor of the European Journal of Anaesthesiology.
1. Stromer W, Michaeli K, Sandner-Kiesling A. Perioperative pain therapy in opioid abuse: an approach to pain management. Eur J Anaesthesiol
2. Ballantyne JC, LaForge KS. Opioid dependence and addiction during opioid treatment of chronic pain. Pain
3. Alam A, Gomes T, Zheng H, et al. Long-term analgesic use after low-risk surgery: a retrospective cohort study. Arch Intern Med
4. Carroll I, Barelka P, Wang CK, et al
. A pilot cohort study of the determinants of longitudinal opioid use after surgery. Anesth Analg
5. Andersen LO, Gaarn-Larsen L, Kristensen BB, et al. Subacute pain and function after fast-track hip and knee arthroplasty. Anaesthesia
6. Noble M, Treadwell JR, Tregear SJ, et al
. Long-term opioid management for chronic noncancer pain. Cochrane Database Syst Rev
7. Kupers RC, Konings H, Adriaensen H, Gybels JM. Morphine differentially affects the sensory and affective pain ratings in neurogenic and idiopathic forms of pain. Pain
8. Moore RA, Mhuircheartaigh RJ, Derry S, McQuay HJ. Mean analgesic consumption is inappropriate for testing analgesic efficacy in postoperative pain: analysis and alternative suggestion. Eur J Anaesthesiol
9. Eriksen J, Sjogren P, Bruera E, et al. Critical issues on opioids in chronic noncancer pain: an epidemiological study. Pain
10. Zywiel MG, Stroh DA, Lee SY, et al. Chronic opioid use prior to total knee arthroplasty. J Bone Joint Surg Am
11. Kuehn BM. New pain guideline for older patients: avoid NSAIDs, consider opioids. JAMA
12. Solomon DH, Rassen JA, Glynn RJ, et al. The comparative safety of opioids for nonmalignant pain in older adults. Arch Intern Med
13. Seyfried O, Hester J. Opioids and endocrine dysfunction. Br J Pain
14. Miller M, Sturmer T, Azrael D, et al. Opioid analgesics and the risk of fractures in older adults with arthritis. J Am Geriatr Soc
15. Gomes T, Mamdani MM, Dhalla IA, et al. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med
16. Chu LF, Clark DJ, Angst MS. Opioid tolerance and hyperalgesia in chronic pain patients after one month of oral morphine therapy: a preliminary prospective study. J Pain
17. De Kock M. Expanding our horizons: transition of acute postoperative pain to persistent pain and establishment of chronic postsurgical pain services. Anesthesiology