One quantum of solace for all?

The opioid crisis in the United States has resulted in a veritable avalanche of data and studies that reflect the situation as it has evolved there. Although there are similarities with the situation in Australia and New Zealand, the medical and illicit drug environment here have features that differ significantly from that in the US. Randomised controlled trials on the perioperative efficacy, adverse effects and outcomes with opioids are likely to be applicable in Australia and New Zealand but audit data on prescribing patterns, community use and harms need to be collected locally. Responses need to be designed for our local context in order to maximise the wise use of opioids.

Reports that provide comparisons of opioid use and harms in countries with similar health systems to ours can demonstrate remarkable disparities. The Australian Institute of Health and Welfare 2018 report into opioid harm in Australia and Canada, ¹ for example, showed that heroin accounts for 95% of all controlled substance opioid seizures in Australia, while in Canada, illicit fentanyl is the most common opioid seized. In Australia, fentanyl does not even rank as a separate category for drug seizures, while in British Columbia three of five overdose deaths are due to drugs containing fentanyl. This difference has profound implications for the injecting population. Fentanyl is more likely to be lethal than heroin, so fewer users survive to receive acute care or progress to opioid agonist treatment. This difference has ramifications for the care of injecting users in Australia.

In the same way, local data, in the form of the New Zealand and Australian Atlases of Healthcare Variation series, have provided an important geographic analysis of community prescription opioid use to inform locally appropriate research and care of prescribed opioids. The Australian Atlas found that, between 2013–14 and 2016–17, the rate of opioid medicines dispensing per head of population increased by 5% nationally, whereas in New Zealand rates of use of opioids plateaued in the five years to 2017. The Penington Institute Annual Overdose Report has provided vital demographic and geographic data on total and unintentional prescription and illicit opioid overdose deaths.

The New Zealand Atlas was one of the first local sources to point to public hospital attendance or admission as the ‘trigger event’ for dispensing a strong opioid in almost half of opioid prescriptions. General practitioners may indeed write the lion’s share of opioid prescriptions, but the NZ Atlas identified hospitals as a frequent site of opioid initiation.

To assess whether surgery was a trigger event for longer term use locally, Stark et al. published in this journal the result of a prospective audit of 970 opioid-naïve surgical patients in an Australian private metropolitan hospital. An alarming 10.5% of all surgical patients were still using opioids after 90 days postoperatively, the majority of these after orthopaedic (13.7%) and spinal (23.6%) surgery. ² Another larger audit of Australian veterans also showed high rates after musculoskeletal surgery but had a broader range of procedures, with an overall rate of use after 90 days of 3.9%. ³ These pointed to surgery as a potential ‘gateway’ to unintentional long-term use. It is alarming that the rates of conversion to long-term use were the equal of rates reported from the US.

Provision of a supply of opioids in excess of need or ‘just in case’ after surgery has in the past been viewed as a kind act with little downside. There is now ample evidence that the magnitude of the opioid supplied has a greater influence on consumption than does the severity of postoperative pain, and that a larger supply can predispose to inadvertent long-term use. ⁴ With higher consumption postoperatively also comes a dose-dependent increase in side-effects.

There are now Australasian data to show that excess opioid supply at post-surgical discharge is widespread. In a previous Australian retrospective audit, 27.7% of patients given opioids for discharge after surgery in a 2013 period had no indication for that prescription. ⁵ These were patients who had used no or minimal opioid in the 48 hours prior to discharge and therefore were unlikely to require opioids post-discharge.

Six years on we now have a local multicentre prospective cohort study in this issue of the journal from Allen et al., showing that opioids are still being prescribed in excess postoperatively. ⁶ In their study a majority (70%) of the 581 patients who completed follow-up had leftover opioids, with only a small proportion (5%) disposing of the surplus. This provides a source of opioids for diversion, or more commonly, for future inappropriate use for pain such as headache or acute back pain where simple analgesics should be utilised.

There have been concerns raised about the increased need for GP refill prescriptions if patients are discharged with fewer opioids, but this has not been shown to be the case in a number of studies, with patient pain scores and satisfaction with analgesia unchanged and no increase in the requirement for refill prescriptions.^7,8 This reinforces the view that we have been providing opioid prescriptions when only simple analgesics are indicated and also prescribing a much larger number of tablets than the patient requires. This was evident in an Australian emergency department prospective ‘before and after’ study where the quantity of opioid for dispensing on the electronic medical record system was altered to show a smaller default number first. The percentage of prescriptions for oxycodone with a quantity of five tablets increased from 3% pre‐intervention to 32% post‐intervention, while the number of prescriptions for quantity of 20 tablets fell from 40% pre‐intervention to 24% post‐intervention (P < 0.01). Despite this reduction in supply, 58% of patients in both pre‐ and post‐intervention groups used half or less of the medication prescribed, ⁹ reinforcing the idea that consumption varies more with supply than with other factors like pain severity.

So, what actions should be taken, and have any been tested in a local context, and which changes fall within the purview of the anaesthetist?

In another recent study, Allen et al. received survey responses from anaesthetists at 45 hospitals in Australia and New Zealand describing opioid stewardship measures currently in place at their institution. ¹⁰ The survey asked about compliance with nine components of opioid stewardship including use of simple analgesics, education of junior doctors, communication with GPs, limitations on prescribing amounts, and opioid disposal information for patients. Presence of the different components varied widely, with use of simple analgesics and junior doctor education occurring in 89% and 78% of institutions, respectively, while adequate communication with GPs occurred in only 18%–22% of hospitals.

Academic detailing combined with individualised audit feedback of junior doctors has had sustainable success in an Australian teaching hospital in reducing inappropriate immediate-release opioid prescription at the time of discharge by 60% (P = 0.002) and in reducing numbers of tablets prescribed at discharge by approximately 50% (P = 0.001). ⁵ This is an inexpensive intervention that involves short education sessions about analgesic prescribing for their specialty with surgical team junior doctors by anaesthesia or pain specialists. It incorporates pharmacy discharge data to give the doctor information about their performance compared with historical and contemporaneous peers, and has been replicated with similar success (unpublished audit data).

Information provided to patients at the time of discharge about opioid disposal is a fairly rare example of substantial behaviour change with a pamphlet or other written information, and can easily be reinforced verbally by the anaesthetist, acute pain service or pharmacist. This is again a simple and inexpensive intervention that can significantly reduce the supply of redundant opioids in our nations’ medicine cabinets.

Electronic ‘nudges’ in prescription software that suggest a smaller number of discharge opioid tablets or make it easier to prescribe amounts less than a packet of 20 have proven local success predominantly in emergency departments, but overseas studies suggest postoperative prescribing may also be altered by similar methods. Pharmacies are increasingly familiar with dividing packs, and smaller pack sizes are appearing on the market locally.

In March 2018 the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine released the position statement on the use of slow-release opioid preparations in the treatment of acute pain. ¹¹ The statement was in response to significant adverse events, particularly an increase in respiratory depression with use of slow-release opioids in opioid-naïve patients. An increased risk of long-term opioid use when initiating slow-release opioids for new acute pain was also cited as a concern.

The statement may also prove to have utility beyond reduction in respiratory depression and unintended long-term opioid use. Tan et al. (in press), in a retrospective Australian audit six months prior to and post release of the statement, showed a reduction in prescription of slow-release opioids to opioid-naïve surgical patients from 40% to 11% (P = 0.001). There was also a reduction in slow-release prescription at the time of discharge from 26% to 9% (P = 0.02). This change was associated with a reduction in total daily opioid dose while in hospital. Despite this reduction in dose, median pain scores were higher for those given slow-release plus immediate-release opioids compared with immediate-release alone. Even after adjusting for adjuvant use and surgical specialty, the pain scores during movement were significantly higher when slow-release opioids were used (P = 0.004).

This local research gives us more confidence that following the recommendations of the statement on slow-release opioids can occur without an increase in postoperative pain. If daily opioid doses are reduced with use of immediate-release only without an increase in pain, then discharge prescribing can be modified to reflect this without impacting patients adversely.

The use of slow-release oral preparations alongside immediate-release for postoperative pain removes a degree of patient control. It presumes that we can predict opioid requirements. Use of background infusions with patient-controlled analgesia and the use of slow-release oral formulations with immediate-release as-required oral formulations consistently do one thing in studies: both increase the daily dose of opioid administered to postoperative patients. This is our unstated aim when we use these techniques. We aim to prevent any gaps in opioid exposure by increasing total daily dose. In order for this to be an effective technique in reducing postoperative pain there should be a dose–response curve that is basically linear; increasing dose providing consistent incremental increases in analgesia. There is plenty of evidence that this is not the case for opioids. In an excellent example, investigators examined individual patient alfentanil dose–response curves for the relief of spontaneous postoperative pain after elective abdominal surgery. ¹² They found that individual dose–response curves were primarily quantal: small decreases in pain intensity with initial doses and then a rapid substantial decrease in pain at rest with a further incremental dose (two-thirds of total effect). The extent of variability between patients, however, meant that graphs of the collective response concealed the wide interindividual variability and appeared to show a graded continuous response where none existed for the majority of patients. No statistically significant relationship was noted between pre-drug pain intensity and the cumulative dose of alfentanil necessary to produce pain relief. The authors concluded that in a population of patients with postoperative pain, the intensity of spontaneous pain cannot be the primary factor determining the dose of alfentanil necessary for its relief. The quantum of opioid required to provide substantial analgesia for any individual is difficult to predict.

Use of multimodal analgesia including immediate-release opioids for acute pain recognises that there is for most patients a dose at which a large and satisfactory increment in analgesia occurs. Increasing opioid doses beyond that, or attempting to predict for an individual patient what that dose will be by using slow-release opioids, may increase side-effects without substantial changes in analgesia. These side-effects extend beyond the respiratory depression, nausea and itch that have been traditional measures. Retrospective outcome data from more than one million joint arthroplasties and 200,000 spinal surgeries in the US showed that even after adjusting for preoperative chronic pain and substance use the highest quartile opioid dose compared with the lowest quartile in the first 48 hours postoperatively was associated with a 50% increase in deep vein thrombosis and infective complications, with significant increases in urinary, gastrointestinal complications as well as length of stay. ¹³

As a significant driver of increased postoperative opioid use without measurable benefit, measures of use of slow-release opioids in acute pain should be included as a measure for local opioid stewardship programs in future.

Wise use of opioids to maximise benefits and minimise harms for our patients in Australia and New Zealand requires research that measures our local environment and practices. Opioid stewardship programs, while informed by international research, should be tailored to reflect programs that work in a local context.