View Article PDF

Opioid analgesics such as morphine or oxycodone are commonly prescribed for the treatment of acute postoperative pain. There is concern that inappropriate opioid prescribing following discharge can lead to prolonged opioid use in the community. In 2018 the Australian and New Zealand College of Anaesthetists (ANZCA) released a position statement recommending that slow or sustained-release (SR) opioids should not be routinely prescribed to patients for the management of acute postoperative pain.[[1]] This statement highlights the risks associated with these drugs, and the difficulties of dose titration for acute pain management.

Orthopaedic surgery is associated with greater amounts of postoperative pain when compared with other surgical procedures.[[2]] As such, orthopaedic operations are known to generate more opioid prescriptions than other specialties.[[3,4]] Total knee arthroplasty (TKA) is a common procedure associated with significant amounts of postoperative pain that subsides rapidly during the recovery period.[[5–7]] Given our ageing population, the number of arthroplasty procedures performed in New Zealand is expected to increase over the coming decades.[[8]] New Zealand data suggest that at three months following hip or knee replacement, which is beyond the expected duration of recovery from surgery, more than 30% of patients continue taking at least mild-strength opioid medications, and up to 8% of patients may still be receiving opioid medications at one-year following surgery.[[9]] These patients would meet the diagnostic criteria for chronic post-surgical pain (CPSP), for which opioid analgesics are not recommended as a part of the primary treatment strategy.[[10,11]]

To manage postoperative pain immediately after TKA, some institutions and professional societies have recommended the use of protocols that include regular SR opioids.[[5,6]] The Procedure Specific Postoperative Pain Management (PROSPECT) recommendations include the use of strong opioids in combination with non-opioid analgesia following TKA, but the strength of the evidence supporting this recommendation is questionable, as it is based on two small studies that compared SR opioids to placebo.[[6]] Currently, the international consensus is that SR opioids are associated with significant harm in the immediate postoperative period and should be avoided.[[1,12–16]] Prolonged or excessive use of opioids can lead to serious adverse effects, including respiratory depression, overdose, addiction and death.[[15]] When SR preparations are used, these harms are compounded due to the drug’s prolonged duration of action.[[3]] This consensus has been reinforced by a case reported on recently by the Health and Disability Commissioner, where a patient died following an elective TKA after routine protocolised SR opioids were used without an appropriate risk assessment.[[17]]

There has been limited research into the efficacy and sequalae of SR opioid use following TKA, and there is a dearth of information surrounding their use when compared with immediate-release (IR) preparations in New Zealand. This study explores the effect of inpatient SR opioid use on acute, inpatient opioid consumption and the longer-term dispensing of opioid medications in patients following TKA at two South Auckland hospitals.

Methods

Study cohort

Prior to study conduct, Health and Disability Ethics Committee (HDEC 19/NTA/27) and Hospital Research Office (Number 893) approval was obtained.

Patients who underwent primary unilateral TKA at Counties Manukau Health between 1 January 2018 and 31 December 2018 were retrospectively identified. This period coincided with the release of the ANZCA position statement on the use of SR opioids in patients with acute pain in late March 2018. Surgery took place at either Middlemore Hospital, a busy acute and elective surgical site, or the Manukau Surgical Centre, where only elective surgery is completed. Patients who underwent isolated uni-compartmental arthroplasty, one-stage or staged revisional TKA, or bilateral simultaneous TKA were excluded, as were patients for whom adequate data were unavailable or surgery was outsourced to an ancillary healthcare facility. These exclusions were made to standardise the magnitude of the surgical procedure and the associated nociceptive stimulus.

Patients were stratified into two groups by their use or avoidance (ie, no use) of strong SR opioids, defined as either M-Eslon® (morphine sulphate modified release capsule) or OxyContin® (oxycodone hydrochloride controlled release tablets), while an inpatient following their primary surgical procedure. The term “sustained-release” encompasses all medications that may be referred to as slow-release, extended-release, modified-release or long-acting.

Data sources

Demographic, anaesthetic, surgical and pharmaceutical data were collated from departmental databases and the electronic data warehouse maintained by HealthAlliance. Demographic and co-morbidity data were obtained from the Concerto Clinical Information Portal and linked with intra-operative data from PCIMS (the Anaesthesia Intraoperative Clinical Record) and PiMS (the Patient Information Management System).

Additional information surrounding comorbidities and procedural complications was obtained from ICD-10 coding completed at the time of hospital discharge. Inpatient dispensing data were extracted from paper medication charts or an electronic prescription system that was introduced during our study period. Outpatient pharmacy data were recorded electronically by the dispensing pharmacy and stored in the TestSafe system. Approximately 98% percent of pharmacies within our catchment area were making use of this system during the time of our study. These sources of information were merged across databases using each patient’s National Health Index (NHI) number. Outpatient dispensing data were obtained for the 90 days before and 90 days after the date of each patient’s surgical procedure, giving a 180-day window into their perioperative drug use once combined with their inpatient dispensing data.

Outcome measures

The primary outcome of this study was the number of patients dispensed strong opioids, either immediate- or sustained-release preparations of morphine or oxycodone, from the hospital pharmacy at discharge or a community pharmacy. This outcome was assessed in 30-day intervals following surgery for three months.

Strong opioid medications were defined as preparations containing morphine, oxycodone, fentanyl, pethidine or methadone. Mild to moderate opioids included preparations containing codeine or dihydrocodeine, tramadol and dextromethorphan. Gabapentinoids are defined as medications that are antagonists at the α2δ sub-unit of voltage gated calcium channels. This class of medications includes gabapentin and pregabalin. Data were collected on total opioid consumption for the first three inpatient days (72 hours) following TKA and expressed in oral morphine equivalents (OMEs). This period was selected as it corresponds to the timing of the maximal nociceptive stimulus, and from previous data we know that after this period most patients are nearing discharge. Data were also collected to calculate the percentage of patients who required additional prescriptions for strong opioid medications within 30-day intervals for three months following surgery.

Comparisons were made between the two groups for perioperative factors that may be associated with differences in acute and ongoing opioid consumption following surgery. “Pre-operative opioid” use was defined as the dispensing of either morphine or oxycodone in the three months (90 days) prior to surgery. We also compared patients who underwent surgery within the first six months of our study to those of the second six months, to evaluate any changes in inpatient SR opioid prescribing patterns as a result of the ANZCA position statement released in March 2018.

Statistical analyses

Information was stored in a Microsoft Excel spreadsheet (Microsoft Corporation, WA, United States) and statistical analysis completed using the Statistical Package for the Social Sciences Version 25 (International Business Machines, NY, United States). Ancillary analyses were completed using NCSS 2021 (NCSS, Utah, United States). Post-hoc power analyses were completed once the sample size had been established. Using the observed incidence of opioid dispensing within one-month following surgery, this study has 83.4% power to detect a statistically significant (two-tailed α=0.05) difference between the two groups.[[18]]

Testing for the normal distribution was through the Shapiro-Wilk test with a two-tailed p-value of <0.05 being indicative of non-normally distributed data. The decision was made to use non-parametric procedures to report data and comparisons. Patient and procedural data were presented as either number (percentage) and median (interquartile range), as appropriate for categorical and continuous data respectively. The Fisher exact test or a Chi Square test with a Yates correction and the Mann-Whitney U test were used to test for differences between categorical and continuous parameters respectively. A two-tailed p-value of p<0.05 defined statistical significance. Using a superiority/non-inferiority threshold of 10mg OME, a post-hoc analysis comparing the median inpatient OMEs consumed was also completed.

Table 1: Baseline characteristics of the two groups stratified by inpatient sustained-release (SR) opioid use. View Table 1.

Table 2: Opioid consumption in the perioperative and postoperative periods. View Table 2.

Results

Between the 1 January and 31 December 2018, 364 patients underwent primary, unilateral TKA at our institution. Complete prescribing information was available for 232 patients (64.1%), which constitutes the study population. While in hospital, 157 patients (67.7%) received at least one dose of SR opioid, and 75 (32.3%) did not receive any SR opioid. In those who received SR opioid, 45 (28.6%) received a morphine-based preparation and 124 (79.0%) received oxycodone. These values sum to more than 100.0% due to the 12 patients (7.6%) who received both morphine and oxycodone SR preparations. The baseline demographics of both groups were similar, with no differences found with regards to age, sex, body mass index, operation duration or hospital length of stay (Table 1). Following surgery, those who received SR opioids were less likely to receive an intravenous patient-controlled analgesia (PCA) device when compared to those who did not, but this difference did not reach statistical significance (9.6% versus 16.0%, p=0.19).

Strong opioid use as an outpatient prior to TKA was greater in the SR opioid use group (8.3% versus 2.7%, p=0.15), although this difference was not statistically significant. This was predominantly oxycodone (13 of 15 patients, or 86.7%). Those in the SR opioid avoidance group were more likely to have been dispensed tramadol or codeine pre-operatively (24.8 versus 41.3%, p=0.01), largely due to a difference in codeine dispensing between the two groups (16.6 versus 30.7%, p=0.02). There were no other differences in the use of pre-operative analgesic medications between the study groups (Table 1).

Inpatient opioid use between postoperative days zero and three (POD0–POD3) was lower in the SR opioid avoidance group, although this was not statistically significant (157.5 [IQR 110.0–220.0] versus 167.5mg OME [110.0–290.0], p=0.14) (Table 2). Following surgery, opioid use was consistently lower at all time intervals in SR opioid avoidance group, excepting POD1. These differences reached statistical significance for POD0 (p=0.003). Using an equivalence margin of 10mg (OME), non-inferiority and superiority analyses demonstrated that avoidance of SR opioid use was both non-inferior (p=0.01) and non-superior (p=0.21) when compared to SR opioid use for inpatient opioid consumption.

SR opioid use was associated with a greater number of patients being dispensed opioids during the first three months following hospital discharge. In the first month after discharge, 105 patients (67.3%) who received inpatient SR opioids continued to be dispensed strong opioids (either morphine or oxycodone) in the community, compared with 34 (47.2%) of the SR opioid avoidance group (p=0.01) (Table 2). During the second month following discharge, there remained a statistically significant difference for those dispensed oxycodone (p=0.03), but not for those dispensed morphine (Figure 1).

Between the first and second six-month periods of our study, the inpatient use of strong SR opioids reduced (84.0% versus 55.3%, p<0.001). This was associated with a non-significant reduction in POD0–POD3 opioid consumption (175.0 [113.75-297.50] versus 152.5mg OME [105.0-242.5], p=0.07).

Figure 1: Outpatient postoperative strong opioid (IR or SR) use.

Discussion

This study aimed to investigate the impact of inpatient SR opioid use on inpatient opioid consumption and persistent opioid dispensing after discharge in patients who undergo TKA. During their inpatient stay, patients who received SR opioids received a greater amount of opioid medication overall, but this difference did not reach statistical significance. The proportion of patients dispensed strong opioid medications within the first 30 days following surgery was significantly greater in the group who received SR opioids as inpatients. There remained a statistically significant difference in oxycodone dispensing for the first two months after surgery, with greater numbers of patients receiving either morphine or oxycodone in the SR opioid use group across all three months. There were no differences between the two groups in the conduct of surgery or anaesthesia or the use of ancillary postoperative analgesic modalities such as PCA devices, peripheral nerve catheters or intrathecal morphine.

Oxycodone was the predominant opioid prescribed by both hospital doctors and general practitioners. There are concerns regarding the use of oxycodone in the community due to its high risk of misuse and drug diversion. Compared to morphine, oxycodone has a greater addictive potential due to its pharmacokinetic profile, including its higher oral bioavailability and the biphasic absorption mechanism of its SR preparations.[[19]] It is well known that OxyContin has contributed to the global opioid epidemic, with communities in North America being especially afflicted.[[19,20]] In New Zealand, there is regional variability in the use of oxycodone, with the number of prescriptions having decreased by 27% since 2011.[[21]] Despite this, our results demonstrate that oxycodone is still prescribed more frequently in those who undergo TKA at our institution, and this disparity continues once patients are discharged from hospital. This preference for prescribing oxycodone is a practice that is not backed up by strong evidence of patient benefit.[[22]]

TKA is generally performed in patients who have failed more conservative management of their knee pathology.[[23]] Arthritis of the knee can cause considerable functional impairment and necessitate the use of strong opioids prior to surgery. We identified differences in pre-operative analgesic dispensing between our study groups, with greater numbers of patients in the SR opioid avoidance group having been dispensed codeine. We might speculate on reasons for these differences, including differences in genetics, patient co-morbidities, psychosocial stressors and pain coping strategies between the two groups, or the effects of sustained opioid use in the lead up to surgery on perioperative pain management. It is well established that persistent or severe pre-operative pain is a risk factor for sub-optimal perioperative pain management and persisting postoperative pain.[[24,25]] Further studies are needed to better understand these mechanisms and evaluate mitigating strategies.

This study highlights the challenges of postoperative pain management after arthroplasty and reinforces the need to moderate the use of SR opioids.[[5,6]] Despite the move away from using SR opioids in patients with acute pain, there is minimal contemporaneous literature reviewing the implications of their use in this setting. Previous studies have described numerous “benefits” of SR drugs including a longer duration of action and improvements in recovery metrics.[[26]] These studies are now outdated, and many display conflicts of interest with drug manufacturers.[[26,27]] The current evidence base suggests that SR opioids have the potential to cause considerable long-term harm, precipitate postoperative complications and place an increased financial burden on the healthcare system.[[19,28,29]] The prescription of SR opioids during the early postoperative period is a major modifiable risk factor for subsequent dependence and persistent opioid use following surgery.[[12]]

ANZCA recommends that SR opioids are used for acute postoperative pain in limited circumstances, including prolonged severe pain or where opioid tolerance has developed.[[1]] This describes only a minority of patients undergoing TKA. The use of SR preparations can make titration and weaning more difficult and problematic. If SR opioids are prescribed beyond discharge, adverse effects such as sedation, opioid-induced ventilatory impairment and delirium are more likely to occur and persist for longer than adverse effects caused by IR preparations.[[30,31]] In our study cohort, patients who were not exposed to SR agents appeared to reduce their use of strong opioid medications more rapidly and consequently reduce the potential for harms associated with opioid use. Tan et al have investigated the impact of the ANZCA position statement on practice at an Australian hospital.[[3]] They noted a decrease in SR opioid prescribing after the release of the statement. Their findings also demonstrated that SR opioid use led to greater overall consumption of opioids while in hospital.[[3]] In this study, we demonstrated a reduction in inpatient use of SR opioids following TKA between the first and second six months of 2018, which corresponds with the release of the ANZCA position statement.

Organisations such as the Health Quality and Safety Commission, the Best Practice Advocacy Centre and district health boards have created national collaboratives or published guidelines to address safe prescribing of opioid medications.[[32,33]] Despite demonstrating a reduction in postoperative SR opioid use over the course of 2018, our results suggest that further education and awareness is required regarding the importance of appropriate opioid prescribing after discharge. This needs to target the multitude of prescribers within and outside the hospital system, including anaesthetists, orthopaedic surgeons, primary care physicians, nurse practitioners and pharmacists. In the hierarchy of a public hospital, discharge prescribing often falls to junior doctors, and so it is vital that initiatives to improve opioid prescribing and awareness include this frequently changing group.

As a retrospective cohort study, this analysis has several limitations. We were unable to assess the severity of pain, other objective measures of recovery from surgery, or patient-reported outcome measures. For approximately 36% of the patients who underwent TKA during our study period, we were unable to extract either the inpatient or outpatient prescribing data. This may be due to their surgery being outsourced to other facilities or that they opted out of linking their NHI number to regionally available electronic dispensing data. The indication for a strong opioid drug prescription was unable to be assessed—a patient may have had other conditions for which they were taking opioid medications. However, it is highly likely that in the first month(s) following TKA a patient’s analgesic dispensing is related to post-surgical pain. Although we were able to determine whether a prescription was dispensed from a pharmacy, we were unable to confirm whether or how those medications were consumed by that patient.

This study was carried out over the calendar year that coincided with the release of the ANZCA position statement on use of SR opioids for acute pain, and our sample size was only moderate. These results may not be suitable for extrapolation to other institutions or for patients undergoing a more diverse range of surgical procedures. As such, additional larger studies are required to confirm our findings. We were only able to extract opioid dispensing data for the three months following surgery. A longer period would be required to identify the relationship between immediate postoperative SR opioid use and prolonged opioid use. One of the strengths of this study was the similarity of the two groups at baseline. Further correction for anaesthetic, surgical or patient factors by propensity score matching could yield additional information on factors influencing opioid prescribing patterns at the time of surgery. We were also able to make comparisons to current national and speciality society guidelines to ensure the relevance of our prescribing patterns and support their recommendations.[[1,14–16]] Although a considerable number of patients continued to receive SR opioids in the second six-month period of 2018, there was a marked reduction seen from January to June of that year. Ongoing SR opioid prescribing may be indicative of prescribers’ resistance to change from their “standard” practice. Further audit of SR opioid use would be useful to determine whether this trend has been sustained.

Conclusion

Inpatient SR opioid use is associated with increased overall inpatient opioid use and persistent outpatient opioid dispensing (particularly of oxycodone) following TKA. Further studies are needed to better determine the current patterns and implications of perioperative SR opioid use, including quality of recovery scores and adequacy of pain control, with a view to improving perioperative pain management and reducing the potential for harm due to unnecessary or prolonged opioid use. This is particularly important where opioid use persists beyond three months after surgery, as best practice recommendations for chronic post-surgical pain management focus on the avoidance of opioid medications and emphasise the importance of physical and psychological therapies.[[11,34]]

Summary

Abstract

Aim

To determine the impact of perioperative sustained-release (SR) opioid use on total inpatient opioid consumption and longer-term outpatient dispensing for three months following elective total knee arthroplasty (TKA).

Method

Patients who underwent primary unilateral TKA between 1 January and 31 December 2018 at Counties Manukau Health were retrospectively identified. Participants were stratified into two groups by inpatient use or avoidance of strong SR opioids (OxyContin or M-Eslon). The primary outcome was the percentage of patients receiving prescriptions for opioid medications at thirty-day intervals for three months after discharge.

Results

Two hundred and thirty-two patients were eligible for inclusion. The baseline demographics of both groups were similar. In the SR opioid use group, the majority (79%) received OxyContin. Overall, inpatient opioid use between postoperative days (POD) zero and three was lower in the SR opioid avoidance group, although this was not statistically significant (157.5 [IQR 110.0–220.0] vs 167.5mg OME [110.0–290.0], p=0.14). Outpatient postoperative opioid dispensing between 0–30 days was significantly greater in patients who received inpatient SR opioids (p=0.01). Dispensing of oxycodone was significantly higher in the SR opioid use group at one- and two- months (p=0.01 and 0.03 respectively).

Conclusion

The postoperative use of SR opioids is not routinely recommended following TKA. Their use is associated with greater overall inpatient opioid use, sustained opioid dispensing during and after the expected recovery period, and the potential for significant harm.

Author Information

Taehoon Kim: Bachelor of Medical Science (Honours) Student, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. Chen (Eileen) Zhou: MBChB Registrar, Department of Emergency Medicine, Waitematā District Health Board, Auckland, New Zealand. Rachel A Sara: MBChB, FANZCA, FFPMANZCA, Consultant Anaesthetist and Pain Medicine Specialist, Department of Anaesthesia and Pain Medicine, Counties Manukau Health, Middlemore, New Zealand. Nicholas J Lightfoot: MBChB, FANZCA, Consultant Anaesthetist, Department of Anaesthesia and Pain Medicine, Counties Manukau Health, Middlemore, New Zealand.

Acknowledgements

I would like to thank my co-supervisors Dr Nicholas Lightfoot and Dr Rachel Sara, as well as the rest of the research team at Counties Manukau Health for their support and the culmination of work that has led to this publication.

Correspondence

Taehoon Kim, Faculty of Medical and Health Sciences, University of Auckland, Auckland, NZ, 85 Park Road, Grafton, Auckland 1023. Private Bag 92019

Correspondence Email

tkim270@aucklanduni.ac.nz

Competing Interests

Dr Lightfoot reports other from Merck Sharp and Dohme, personal fees from Merck Sharp and Dohme and other from Vifor Pharma outside the submitted work.

1) ANZCA [Internet]. Position statement on the use of slow-release opioid preparations in the treatment of acute pain. 2018 [cited 2021 Mar 14]. Available from: https://www.anzca.edu.au/getattachment/d9e2a7c5-0f17-42d3-bda7-c6dae7e55ced/Position-statement-on-the-use-of-slow-release-opioid-preparations-in-the-treatment-of-acute-pain

2) Saini S, McDonald EL, Shakked R, Nicholson K, Rogero R, Chapter M, et al. Prospective Evaluation of Utilization Patterns and Prescribing Guidelines of Opioid Consumption Following Orthopedic Foot and Ankle Surgery. Foot & Ankle International. 2018;39(11):1257-65.

3) Tan AC, Bugeja BA, Begley DA, Stevens JA, Khor K-E, Penm J. Postoperative use of slow-release opioids: The impact of the Australian and New Zealand College of Anaesthetists/Faculty of Pain Medicine position statement on clinical practice. Anaesthesia and Intensive Care. 2020;48(6):444-53.

4) Volkow ND. Characteristics of Opioid Prescriptions in 2009. JAMA. 2011;305(13):1299.

5) Byrne K, Clark J. Total knee arthroplasty – The optimal analgesic regime. Trends in Anaesthesia and Critical Care. 2015;5(4):104-10.

6) Fischer HBJ, Simanski CJP, Sharp C, Bonnet F, Camu F, Neugebauer EAM, et al. A procedure-specific systematic review and consensus recommendations for postoperative analgesia following total knee arthroplasty. Anaesthesia. 2008;63(10):1105-23.

7) Trasolini NA, McKnight BM, Dorr LD. The Opioid Crisis and the Orthopedic Surgeon. Journal of Arthroplasty. 2018;33(11):3379-82.e1.

8) The New Zealand Joint Registry N [Internet]. Twenty-One Year report January 1999 to December 2019. 2020 [cited 2021 Feb 16]. Available from: http://www.nzoa.org.nz/nzoa-joint-registry

9) Wilson R, Pryymachenko Y, Audas R, Abbott JH. Long-term opioid medication use before and after joint replacement surgery in New Zealand. N Z Med J. 2019;132(1507):33-47.

10) World Health Organization W [Internet]. International classification of diseases for mortality and morbidity statistics (11th Revision): WHO; 2018 [cited 2021 June 18]. Available from: https://icd.who.int/browse11/l-m/en

11) National Institute for Health and Care Excellence NICE [Internet]. Chronic pain (primary and secondary) in over 16s: assessment of all chronic pain and management of chronic primary pain UK: NICE; 2021 [cited 2021 June 19]. Available from: https://www.nice.org.uk/guidance/ng193

12) Shah A, Hayes CJ, Martin BC. Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use - United States, 2006-2015. MMWR Morb Mortal Wkly Rep. 2017;66(10):265-9.

13) Zin CS, Nazar NI, Rahman NSA, Ahmad WR, Rani NS, Ng KS. Patterns of initial opioid prescription and its association with short-term and long-term use among opioid-naïve patients in Malaysia: a retrospective cohort study. BMJ Open. 2019;9(7):e027203.

14) Chou R, Gordon DB, de Leon-Casasola OA, Rosenberg JM, Bickler S, Brennan T, et al. Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016;17(2):131-57.

15) US Food Drug Administration F. FDA’s opioid analgesic REMS education blueprint for health care providers involved in the treatment and monitoring of patients with pain. Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2018.

16) Schug S, Palmer G, Scott D, Halliwell R, Trinca J. Working Group of the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine (2015), Acute Pain Management: Scientific Evidence. 4th ed. ANZCA., FPM., editors. Melbourne2015.

17) Health & Disability Commisioner HDC [Internet]. Management of patient before and after surgery (Case 15HDC00850) NZ2018 [cited 2021 June 18]. Available from: https://www.hdc.org.nz/decisions/search-decisions/2018/15hdc00850/

18) Kane SP. Post-hoc Power Calculator: ClinCalc; 2018 [cited 2021 Apr 20]. Available from: https://clincalc.com/stats/Power.aspx.

19) Levy N, Mills P. Controlled-release opioids cause harm and should be avoided in management of postoperative pain in opioid naive patients. Br J Anaesth. 2019;122(6):e86-e90.

20) deShazo RD, Johnson M, Eriator I, Rodenmeyer K. Backstories on the US Opioid Epidemic. Good Intentions Gone Bad, an Industry Gone Rogue, and Watch Dogs Gone to Sleep. Am J Med. 2018;131(6):595-601.

21) Health Quality & Safety Commission New Zealand H [Internet]. Opioids 2019 [cited 2021 April 3]. Available from: https://www.hqsc.govt.nz/our-programmes/health-quality-evaluation/projects/atlas-of-healthcare-variation/opioids/

22) Best Practice Advocacy Centre B [Internet]. Oxycodone: how did we get here and how do we fix it? NZ: BPAC; 2014 [cited 2021 Apr 15]. Available from: https://bpac.org.nz/bpj/2014/july/oxycodone.aspx.

23) National Clinical Guideline Centre N. Osteoarthritis: Care and management in adults. National Institute for Health and Care Excellence; 2014 Feb. Contract No.: CG177.

24) Lawal OD, Gold J, Murthy A, Ruchi R, Bavry E, Hume AL, et al. Rate and Risk Factors Associated With Prolonged Opioid Use After Surgery: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020;3(6):e207367.

25) Huang A, Azam A, Segal S, Pivovarov K, Katznelson G, Ladak SS, et al. Chronic postsurgical pain and persistent opioid use following surgery: the need for a transitional pain service. Pain Management. 2016;6(5):435-43.

26) Illgen RL, Pellino TA, Gordon DB, Butts S, Heiner JP. Prospective Analysis of a Novel Long-acting Oral Opioid Analgesic Regimen for Pain Control After Total Hip and Knee Arthroplasty. The Journal of Arthroplasty. 2006;21(6):814-20.

27) Sunshine A, Olson NZ, Colon A, Rivera J, Kaiko RF, Fitzmartin RD, et al. Analgesic efficacy of controlled-release oxycodone in postoperative pain. J Clin Pharmacol. 1996;36(7):595-603.

28) Gold LS, Strassels SA, Hansen RN. Health Care Costs and Utilization in Patients Receiving Prescriptions for Long-acting Opioids for Acute Postsurgical Pain. Clin J Pain. 2016;32(9):747-54.

29) Sing DC, Barry JJ, Cheah JW, Vail TP, Hansen EN. Long-Acting Opioid Use Independently Predicts Perioperative Complication in Total Joint Arthroplasty. Journal of Arthroplasty. 2016;31(9 Suppl):170-4.e1.

30) Hah JM, Bateman BT, Ratliff J, Curtin C, Sun E. Chronic Opioid Use After Surgery: Implications for Perioperative Management in the Face of the Opioid Epidemic. Anesth Analg. 2017;125(5):1733-40.

31) Miller M, Barber CW, Leatherman S, Fonda J, Hermos JA, Cho K, et al. Prescription Opioid Duration of Action and the Risk of Unintentional Overdose Among Patients Receiving Opioid Therapy. JAMA Internal Medicine. 2015;175(4):608.

32) Best Practice Advocacy Centre B [Internet]. Oxycodone prescribing: New Zealand solutions to a global problem NZ: BPAC; 2016 [cited 2021 Apr 3]. Available from: https://bpac.org.nz/2016/oxycodone-prescribing.aspx.

33) Health Quality & Safety Commission New Zealand H [Internet]. Safe use of opioids national collaborative NZ: HQSC; 2018 [cited 2021 Apr 3]. Available from: https://www.hqsc.govt.nz/our-programmes/medication-safety/projects/safe-use-of-opioids/collaborative/.

34) Faculty of Pain Medicine of the Royal College of Anaesthetists FPM [Internet]. Surgery and Opioids: Best Practice Guidelines 2021 UK: FPM; 2021 [cited 2021 June 19]. Available from: https://fpm.ac.uk/sites/fpm/files/documents/2021-03/surgery-and-opioids-2021_4.pdf.

For the PDF of this article,
contact nzmj@nzma.org.nz

View Article PDF

Opioid analgesics such as morphine or oxycodone are commonly prescribed for the treatment of acute postoperative pain. There is concern that inappropriate opioid prescribing following discharge can lead to prolonged opioid use in the community. In 2018 the Australian and New Zealand College of Anaesthetists (ANZCA) released a position statement recommending that slow or sustained-release (SR) opioids should not be routinely prescribed to patients for the management of acute postoperative pain.[[1]] This statement highlights the risks associated with these drugs, and the difficulties of dose titration for acute pain management.

Orthopaedic surgery is associated with greater amounts of postoperative pain when compared with other surgical procedures.[[2]] As such, orthopaedic operations are known to generate more opioid prescriptions than other specialties.[[3,4]] Total knee arthroplasty (TKA) is a common procedure associated with significant amounts of postoperative pain that subsides rapidly during the recovery period.[[5–7]] Given our ageing population, the number of arthroplasty procedures performed in New Zealand is expected to increase over the coming decades.[[8]] New Zealand data suggest that at three months following hip or knee replacement, which is beyond the expected duration of recovery from surgery, more than 30% of patients continue taking at least mild-strength opioid medications, and up to 8% of patients may still be receiving opioid medications at one-year following surgery.[[9]] These patients would meet the diagnostic criteria for chronic post-surgical pain (CPSP), for which opioid analgesics are not recommended as a part of the primary treatment strategy.[[10,11]]

To manage postoperative pain immediately after TKA, some institutions and professional societies have recommended the use of protocols that include regular SR opioids.[[5,6]] The Procedure Specific Postoperative Pain Management (PROSPECT) recommendations include the use of strong opioids in combination with non-opioid analgesia following TKA, but the strength of the evidence supporting this recommendation is questionable, as it is based on two small studies that compared SR opioids to placebo.[[6]] Currently, the international consensus is that SR opioids are associated with significant harm in the immediate postoperative period and should be avoided.[[1,12–16]] Prolonged or excessive use of opioids can lead to serious adverse effects, including respiratory depression, overdose, addiction and death.[[15]] When SR preparations are used, these harms are compounded due to the drug’s prolonged duration of action.[[3]] This consensus has been reinforced by a case reported on recently by the Health and Disability Commissioner, where a patient died following an elective TKA after routine protocolised SR opioids were used without an appropriate risk assessment.[[17]]

There has been limited research into the efficacy and sequalae of SR opioid use following TKA, and there is a dearth of information surrounding their use when compared with immediate-release (IR) preparations in New Zealand. This study explores the effect of inpatient SR opioid use on acute, inpatient opioid consumption and the longer-term dispensing of opioid medications in patients following TKA at two South Auckland hospitals.

Methods

Study cohort

Prior to study conduct, Health and Disability Ethics Committee (HDEC 19/NTA/27) and Hospital Research Office (Number 893) approval was obtained.

Patients who underwent primary unilateral TKA at Counties Manukau Health between 1 January 2018 and 31 December 2018 were retrospectively identified. This period coincided with the release of the ANZCA position statement on the use of SR opioids in patients with acute pain in late March 2018. Surgery took place at either Middlemore Hospital, a busy acute and elective surgical site, or the Manukau Surgical Centre, where only elective surgery is completed. Patients who underwent isolated uni-compartmental arthroplasty, one-stage or staged revisional TKA, or bilateral simultaneous TKA were excluded, as were patients for whom adequate data were unavailable or surgery was outsourced to an ancillary healthcare facility. These exclusions were made to standardise the magnitude of the surgical procedure and the associated nociceptive stimulus.

Patients were stratified into two groups by their use or avoidance (ie, no use) of strong SR opioids, defined as either M-Eslon® (morphine sulphate modified release capsule) or OxyContin® (oxycodone hydrochloride controlled release tablets), while an inpatient following their primary surgical procedure. The term “sustained-release” encompasses all medications that may be referred to as slow-release, extended-release, modified-release or long-acting.

Data sources

Demographic, anaesthetic, surgical and pharmaceutical data were collated from departmental databases and the electronic data warehouse maintained by HealthAlliance. Demographic and co-morbidity data were obtained from the Concerto Clinical Information Portal and linked with intra-operative data from PCIMS (the Anaesthesia Intraoperative Clinical Record) and PiMS (the Patient Information Management System).

Additional information surrounding comorbidities and procedural complications was obtained from ICD-10 coding completed at the time of hospital discharge. Inpatient dispensing data were extracted from paper medication charts or an electronic prescription system that was introduced during our study period. Outpatient pharmacy data were recorded electronically by the dispensing pharmacy and stored in the TestSafe system. Approximately 98% percent of pharmacies within our catchment area were making use of this system during the time of our study. These sources of information were merged across databases using each patient’s National Health Index (NHI) number. Outpatient dispensing data were obtained for the 90 days before and 90 days after the date of each patient’s surgical procedure, giving a 180-day window into their perioperative drug use once combined with their inpatient dispensing data.

Outcome measures

The primary outcome of this study was the number of patients dispensed strong opioids, either immediate- or sustained-release preparations of morphine or oxycodone, from the hospital pharmacy at discharge or a community pharmacy. This outcome was assessed in 30-day intervals following surgery for three months.

Strong opioid medications were defined as preparations containing morphine, oxycodone, fentanyl, pethidine or methadone. Mild to moderate opioids included preparations containing codeine or dihydrocodeine, tramadol and dextromethorphan. Gabapentinoids are defined as medications that are antagonists at the α2δ sub-unit of voltage gated calcium channels. This class of medications includes gabapentin and pregabalin. Data were collected on total opioid consumption for the first three inpatient days (72 hours) following TKA and expressed in oral morphine equivalents (OMEs). This period was selected as it corresponds to the timing of the maximal nociceptive stimulus, and from previous data we know that after this period most patients are nearing discharge. Data were also collected to calculate the percentage of patients who required additional prescriptions for strong opioid medications within 30-day intervals for three months following surgery.

Comparisons were made between the two groups for perioperative factors that may be associated with differences in acute and ongoing opioid consumption following surgery. “Pre-operative opioid” use was defined as the dispensing of either morphine or oxycodone in the three months (90 days) prior to surgery. We also compared patients who underwent surgery within the first six months of our study to those of the second six months, to evaluate any changes in inpatient SR opioid prescribing patterns as a result of the ANZCA position statement released in March 2018.

Statistical analyses

Information was stored in a Microsoft Excel spreadsheet (Microsoft Corporation, WA, United States) and statistical analysis completed using the Statistical Package for the Social Sciences Version 25 (International Business Machines, NY, United States). Ancillary analyses were completed using NCSS 2021 (NCSS, Utah, United States). Post-hoc power analyses were completed once the sample size had been established. Using the observed incidence of opioid dispensing within one-month following surgery, this study has 83.4% power to detect a statistically significant (two-tailed α=0.05) difference between the two groups.[[18]]

Testing for the normal distribution was through the Shapiro-Wilk test with a two-tailed p-value of <0.05 being indicative of non-normally distributed data. The decision was made to use non-parametric procedures to report data and comparisons. Patient and procedural data were presented as either number (percentage) and median (interquartile range), as appropriate for categorical and continuous data respectively. The Fisher exact test or a Chi Square test with a Yates correction and the Mann-Whitney U test were used to test for differences between categorical and continuous parameters respectively. A two-tailed p-value of p<0.05 defined statistical significance. Using a superiority/non-inferiority threshold of 10mg OME, a post-hoc analysis comparing the median inpatient OMEs consumed was also completed.

Table 1: Baseline characteristics of the two groups stratified by inpatient sustained-release (SR) opioid use. View Table 1.

Table 2: Opioid consumption in the perioperative and postoperative periods. View Table 2.

Results

Between the 1 January and 31 December 2018, 364 patients underwent primary, unilateral TKA at our institution. Complete prescribing information was available for 232 patients (64.1%), which constitutes the study population. While in hospital, 157 patients (67.7%) received at least one dose of SR opioid, and 75 (32.3%) did not receive any SR opioid. In those who received SR opioid, 45 (28.6%) received a morphine-based preparation and 124 (79.0%) received oxycodone. These values sum to more than 100.0% due to the 12 patients (7.6%) who received both morphine and oxycodone SR preparations. The baseline demographics of both groups were similar, with no differences found with regards to age, sex, body mass index, operation duration or hospital length of stay (Table 1). Following surgery, those who received SR opioids were less likely to receive an intravenous patient-controlled analgesia (PCA) device when compared to those who did not, but this difference did not reach statistical significance (9.6% versus 16.0%, p=0.19).

Strong opioid use as an outpatient prior to TKA was greater in the SR opioid use group (8.3% versus 2.7%, p=0.15), although this difference was not statistically significant. This was predominantly oxycodone (13 of 15 patients, or 86.7%). Those in the SR opioid avoidance group were more likely to have been dispensed tramadol or codeine pre-operatively (24.8 versus 41.3%, p=0.01), largely due to a difference in codeine dispensing between the two groups (16.6 versus 30.7%, p=0.02). There were no other differences in the use of pre-operative analgesic medications between the study groups (Table 1).

Inpatient opioid use between postoperative days zero and three (POD0–POD3) was lower in the SR opioid avoidance group, although this was not statistically significant (157.5 [IQR 110.0–220.0] versus 167.5mg OME [110.0–290.0], p=0.14) (Table 2). Following surgery, opioid use was consistently lower at all time intervals in SR opioid avoidance group, excepting POD1. These differences reached statistical significance for POD0 (p=0.003). Using an equivalence margin of 10mg (OME), non-inferiority and superiority analyses demonstrated that avoidance of SR opioid use was both non-inferior (p=0.01) and non-superior (p=0.21) when compared to SR opioid use for inpatient opioid consumption.

SR opioid use was associated with a greater number of patients being dispensed opioids during the first three months following hospital discharge. In the first month after discharge, 105 patients (67.3%) who received inpatient SR opioids continued to be dispensed strong opioids (either morphine or oxycodone) in the community, compared with 34 (47.2%) of the SR opioid avoidance group (p=0.01) (Table 2). During the second month following discharge, there remained a statistically significant difference for those dispensed oxycodone (p=0.03), but not for those dispensed morphine (Figure 1).

Between the first and second six-month periods of our study, the inpatient use of strong SR opioids reduced (84.0% versus 55.3%, p<0.001). This was associated with a non-significant reduction in POD0–POD3 opioid consumption (175.0 [113.75-297.50] versus 152.5mg OME [105.0-242.5], p=0.07).

Figure 1: Outpatient postoperative strong opioid (IR or SR) use.

Discussion

This study aimed to investigate the impact of inpatient SR opioid use on inpatient opioid consumption and persistent opioid dispensing after discharge in patients who undergo TKA. During their inpatient stay, patients who received SR opioids received a greater amount of opioid medication overall, but this difference did not reach statistical significance. The proportion of patients dispensed strong opioid medications within the first 30 days following surgery was significantly greater in the group who received SR opioids as inpatients. There remained a statistically significant difference in oxycodone dispensing for the first two months after surgery, with greater numbers of patients receiving either morphine or oxycodone in the SR opioid use group across all three months. There were no differences between the two groups in the conduct of surgery or anaesthesia or the use of ancillary postoperative analgesic modalities such as PCA devices, peripheral nerve catheters or intrathecal morphine.

Oxycodone was the predominant opioid prescribed by both hospital doctors and general practitioners. There are concerns regarding the use of oxycodone in the community due to its high risk of misuse and drug diversion. Compared to morphine, oxycodone has a greater addictive potential due to its pharmacokinetic profile, including its higher oral bioavailability and the biphasic absorption mechanism of its SR preparations.[[19]] It is well known that OxyContin has contributed to the global opioid epidemic, with communities in North America being especially afflicted.[[19,20]] In New Zealand, there is regional variability in the use of oxycodone, with the number of prescriptions having decreased by 27% since 2011.[[21]] Despite this, our results demonstrate that oxycodone is still prescribed more frequently in those who undergo TKA at our institution, and this disparity continues once patients are discharged from hospital. This preference for prescribing oxycodone is a practice that is not backed up by strong evidence of patient benefit.[[22]]

TKA is generally performed in patients who have failed more conservative management of their knee pathology.[[23]] Arthritis of the knee can cause considerable functional impairment and necessitate the use of strong opioids prior to surgery. We identified differences in pre-operative analgesic dispensing between our study groups, with greater numbers of patients in the SR opioid avoidance group having been dispensed codeine. We might speculate on reasons for these differences, including differences in genetics, patient co-morbidities, psychosocial stressors and pain coping strategies between the two groups, or the effects of sustained opioid use in the lead up to surgery on perioperative pain management. It is well established that persistent or severe pre-operative pain is a risk factor for sub-optimal perioperative pain management and persisting postoperative pain.[[24,25]] Further studies are needed to better understand these mechanisms and evaluate mitigating strategies.

This study highlights the challenges of postoperative pain management after arthroplasty and reinforces the need to moderate the use of SR opioids.[[5,6]] Despite the move away from using SR opioids in patients with acute pain, there is minimal contemporaneous literature reviewing the implications of their use in this setting. Previous studies have described numerous “benefits” of SR drugs including a longer duration of action and improvements in recovery metrics.[[26]] These studies are now outdated, and many display conflicts of interest with drug manufacturers.[[26,27]] The current evidence base suggests that SR opioids have the potential to cause considerable long-term harm, precipitate postoperative complications and place an increased financial burden on the healthcare system.[[19,28,29]] The prescription of SR opioids during the early postoperative period is a major modifiable risk factor for subsequent dependence and persistent opioid use following surgery.[[12]]

ANZCA recommends that SR opioids are used for acute postoperative pain in limited circumstances, including prolonged severe pain or where opioid tolerance has developed.[[1]] This describes only a minority of patients undergoing TKA. The use of SR preparations can make titration and weaning more difficult and problematic. If SR opioids are prescribed beyond discharge, adverse effects such as sedation, opioid-induced ventilatory impairment and delirium are more likely to occur and persist for longer than adverse effects caused by IR preparations.[[30,31]] In our study cohort, patients who were not exposed to SR agents appeared to reduce their use of strong opioid medications more rapidly and consequently reduce the potential for harms associated with opioid use. Tan et al have investigated the impact of the ANZCA position statement on practice at an Australian hospital.[[3]] They noted a decrease in SR opioid prescribing after the release of the statement. Their findings also demonstrated that SR opioid use led to greater overall consumption of opioids while in hospital.[[3]] In this study, we demonstrated a reduction in inpatient use of SR opioids following TKA between the first and second six months of 2018, which corresponds with the release of the ANZCA position statement.

Organisations such as the Health Quality and Safety Commission, the Best Practice Advocacy Centre and district health boards have created national collaboratives or published guidelines to address safe prescribing of opioid medications.[[32,33]] Despite demonstrating a reduction in postoperative SR opioid use over the course of 2018, our results suggest that further education and awareness is required regarding the importance of appropriate opioid prescribing after discharge. This needs to target the multitude of prescribers within and outside the hospital system, including anaesthetists, orthopaedic surgeons, primary care physicians, nurse practitioners and pharmacists. In the hierarchy of a public hospital, discharge prescribing often falls to junior doctors, and so it is vital that initiatives to improve opioid prescribing and awareness include this frequently changing group.

As a retrospective cohort study, this analysis has several limitations. We were unable to assess the severity of pain, other objective measures of recovery from surgery, or patient-reported outcome measures. For approximately 36% of the patients who underwent TKA during our study period, we were unable to extract either the inpatient or outpatient prescribing data. This may be due to their surgery being outsourced to other facilities or that they opted out of linking their NHI number to regionally available electronic dispensing data. The indication for a strong opioid drug prescription was unable to be assessed—a patient may have had other conditions for which they were taking opioid medications. However, it is highly likely that in the first month(s) following TKA a patient’s analgesic dispensing is related to post-surgical pain. Although we were able to determine whether a prescription was dispensed from a pharmacy, we were unable to confirm whether or how those medications were consumed by that patient.

This study was carried out over the calendar year that coincided with the release of the ANZCA position statement on use of SR opioids for acute pain, and our sample size was only moderate. These results may not be suitable for extrapolation to other institutions or for patients undergoing a more diverse range of surgical procedures. As such, additional larger studies are required to confirm our findings. We were only able to extract opioid dispensing data for the three months following surgery. A longer period would be required to identify the relationship between immediate postoperative SR opioid use and prolonged opioid use. One of the strengths of this study was the similarity of the two groups at baseline. Further correction for anaesthetic, surgical or patient factors by propensity score matching could yield additional information on factors influencing opioid prescribing patterns at the time of surgery. We were also able to make comparisons to current national and speciality society guidelines to ensure the relevance of our prescribing patterns and support their recommendations.[[1,14–16]] Although a considerable number of patients continued to receive SR opioids in the second six-month period of 2018, there was a marked reduction seen from January to June of that year. Ongoing SR opioid prescribing may be indicative of prescribers’ resistance to change from their “standard” practice. Further audit of SR opioid use would be useful to determine whether this trend has been sustained.

Conclusion

Inpatient SR opioid use is associated with increased overall inpatient opioid use and persistent outpatient opioid dispensing (particularly of oxycodone) following TKA. Further studies are needed to better determine the current patterns and implications of perioperative SR opioid use, including quality of recovery scores and adequacy of pain control, with a view to improving perioperative pain management and reducing the potential for harm due to unnecessary or prolonged opioid use. This is particularly important where opioid use persists beyond three months after surgery, as best practice recommendations for chronic post-surgical pain management focus on the avoidance of opioid medications and emphasise the importance of physical and psychological therapies.[[11,34]]

Summary

Abstract

Aim

To determine the impact of perioperative sustained-release (SR) opioid use on total inpatient opioid consumption and longer-term outpatient dispensing for three months following elective total knee arthroplasty (TKA).

Method

Patients who underwent primary unilateral TKA between 1 January and 31 December 2018 at Counties Manukau Health were retrospectively identified. Participants were stratified into two groups by inpatient use or avoidance of strong SR opioids (OxyContin or M-Eslon). The primary outcome was the percentage of patients receiving prescriptions for opioid medications at thirty-day intervals for three months after discharge.

Results

Two hundred and thirty-two patients were eligible for inclusion. The baseline demographics of both groups were similar. In the SR opioid use group, the majority (79%) received OxyContin. Overall, inpatient opioid use between postoperative days (POD) zero and three was lower in the SR opioid avoidance group, although this was not statistically significant (157.5 [IQR 110.0–220.0] vs 167.5mg OME [110.0–290.0], p=0.14). Outpatient postoperative opioid dispensing between 0–30 days was significantly greater in patients who received inpatient SR opioids (p=0.01). Dispensing of oxycodone was significantly higher in the SR opioid use group at one- and two- months (p=0.01 and 0.03 respectively).

Conclusion

The postoperative use of SR opioids is not routinely recommended following TKA. Their use is associated with greater overall inpatient opioid use, sustained opioid dispensing during and after the expected recovery period, and the potential for significant harm.

Author Information

Taehoon Kim: Bachelor of Medical Science (Honours) Student, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. Chen (Eileen) Zhou: MBChB Registrar, Department of Emergency Medicine, Waitematā District Health Board, Auckland, New Zealand. Rachel A Sara: MBChB, FANZCA, FFPMANZCA, Consultant Anaesthetist and Pain Medicine Specialist, Department of Anaesthesia and Pain Medicine, Counties Manukau Health, Middlemore, New Zealand. Nicholas J Lightfoot: MBChB, FANZCA, Consultant Anaesthetist, Department of Anaesthesia and Pain Medicine, Counties Manukau Health, Middlemore, New Zealand.

Acknowledgements

I would like to thank my co-supervisors Dr Nicholas Lightfoot and Dr Rachel Sara, as well as the rest of the research team at Counties Manukau Health for their support and the culmination of work that has led to this publication.

Correspondence

Taehoon Kim, Faculty of Medical and Health Sciences, University of Auckland, Auckland, NZ, 85 Park Road, Grafton, Auckland 1023. Private Bag 92019

Correspondence Email

tkim270@aucklanduni.ac.nz

Competing Interests

Dr Lightfoot reports other from Merck Sharp and Dohme, personal fees from Merck Sharp and Dohme and other from Vifor Pharma outside the submitted work.

1) ANZCA [Internet]. Position statement on the use of slow-release opioid preparations in the treatment of acute pain. 2018 [cited 2021 Mar 14]. Available from: https://www.anzca.edu.au/getattachment/d9e2a7c5-0f17-42d3-bda7-c6dae7e55ced/Position-statement-on-the-use-of-slow-release-opioid-preparations-in-the-treatment-of-acute-pain

2) Saini S, McDonald EL, Shakked R, Nicholson K, Rogero R, Chapter M, et al. Prospective Evaluation of Utilization Patterns and Prescribing Guidelines of Opioid Consumption Following Orthopedic Foot and Ankle Surgery. Foot & Ankle International. 2018;39(11):1257-65.

3) Tan AC, Bugeja BA, Begley DA, Stevens JA, Khor K-E, Penm J. Postoperative use of slow-release opioids: The impact of the Australian and New Zealand College of Anaesthetists/Faculty of Pain Medicine position statement on clinical practice. Anaesthesia and Intensive Care. 2020;48(6):444-53.

4) Volkow ND. Characteristics of Opioid Prescriptions in 2009. JAMA. 2011;305(13):1299.

5) Byrne K, Clark J. Total knee arthroplasty – The optimal analgesic regime. Trends in Anaesthesia and Critical Care. 2015;5(4):104-10.

6) Fischer HBJ, Simanski CJP, Sharp C, Bonnet F, Camu F, Neugebauer EAM, et al. A procedure-specific systematic review and consensus recommendations for postoperative analgesia following total knee arthroplasty. Anaesthesia. 2008;63(10):1105-23.

7) Trasolini NA, McKnight BM, Dorr LD. The Opioid Crisis and the Orthopedic Surgeon. Journal of Arthroplasty. 2018;33(11):3379-82.e1.

8) The New Zealand Joint Registry N [Internet]. Twenty-One Year report January 1999 to December 2019. 2020 [cited 2021 Feb 16]. Available from: http://www.nzoa.org.nz/nzoa-joint-registry

9) Wilson R, Pryymachenko Y, Audas R, Abbott JH. Long-term opioid medication use before and after joint replacement surgery in New Zealand. N Z Med J. 2019;132(1507):33-47.

10) World Health Organization W [Internet]. International classification of diseases for mortality and morbidity statistics (11th Revision): WHO; 2018 [cited 2021 June 18]. Available from: https://icd.who.int/browse11/l-m/en

11) National Institute for Health and Care Excellence NICE [Internet]. Chronic pain (primary and secondary) in over 16s: assessment of all chronic pain and management of chronic primary pain UK: NICE; 2021 [cited 2021 June 19]. Available from: https://www.nice.org.uk/guidance/ng193

12) Shah A, Hayes CJ, Martin BC. Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use - United States, 2006-2015. MMWR Morb Mortal Wkly Rep. 2017;66(10):265-9.

13) Zin CS, Nazar NI, Rahman NSA, Ahmad WR, Rani NS, Ng KS. Patterns of initial opioid prescription and its association with short-term and long-term use among opioid-naïve patients in Malaysia: a retrospective cohort study. BMJ Open. 2019;9(7):e027203.

14) Chou R, Gordon DB, de Leon-Casasola OA, Rosenberg JM, Bickler S, Brennan T, et al. Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016;17(2):131-57.

15) US Food Drug Administration F. FDA’s opioid analgesic REMS education blueprint for health care providers involved in the treatment and monitoring of patients with pain. Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2018.

16) Schug S, Palmer G, Scott D, Halliwell R, Trinca J. Working Group of the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine (2015), Acute Pain Management: Scientific Evidence. 4th ed. ANZCA., FPM., editors. Melbourne2015.

17) Health & Disability Commisioner HDC [Internet]. Management of patient before and after surgery (Case 15HDC00850) NZ2018 [cited 2021 June 18]. Available from: https://www.hdc.org.nz/decisions/search-decisions/2018/15hdc00850/

18) Kane SP. Post-hoc Power Calculator: ClinCalc; 2018 [cited 2021 Apr 20]. Available from: https://clincalc.com/stats/Power.aspx.

19) Levy N, Mills P. Controlled-release opioids cause harm and should be avoided in management of postoperative pain in opioid naive patients. Br J Anaesth. 2019;122(6):e86-e90.

20) deShazo RD, Johnson M, Eriator I, Rodenmeyer K. Backstories on the US Opioid Epidemic. Good Intentions Gone Bad, an Industry Gone Rogue, and Watch Dogs Gone to Sleep. Am J Med. 2018;131(6):595-601.

21) Health Quality & Safety Commission New Zealand H [Internet]. Opioids 2019 [cited 2021 April 3]. Available from: https://www.hqsc.govt.nz/our-programmes/health-quality-evaluation/projects/atlas-of-healthcare-variation/opioids/

22) Best Practice Advocacy Centre B [Internet]. Oxycodone: how did we get here and how do we fix it? NZ: BPAC; 2014 [cited 2021 Apr 15]. Available from: https://bpac.org.nz/bpj/2014/july/oxycodone.aspx.

23) National Clinical Guideline Centre N. Osteoarthritis: Care and management in adults. National Institute for Health and Care Excellence; 2014 Feb. Contract No.: CG177.

24) Lawal OD, Gold J, Murthy A, Ruchi R, Bavry E, Hume AL, et al. Rate and Risk Factors Associated With Prolonged Opioid Use After Surgery: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020;3(6):e207367.

25) Huang A, Azam A, Segal S, Pivovarov K, Katznelson G, Ladak SS, et al. Chronic postsurgical pain and persistent opioid use following surgery: the need for a transitional pain service. Pain Management. 2016;6(5):435-43.

26) Illgen RL, Pellino TA, Gordon DB, Butts S, Heiner JP. Prospective Analysis of a Novel Long-acting Oral Opioid Analgesic Regimen for Pain Control After Total Hip and Knee Arthroplasty. The Journal of Arthroplasty. 2006;21(6):814-20.

27) Sunshine A, Olson NZ, Colon A, Rivera J, Kaiko RF, Fitzmartin RD, et al. Analgesic efficacy of controlled-release oxycodone in postoperative pain. J Clin Pharmacol. 1996;36(7):595-603.

28) Gold LS, Strassels SA, Hansen RN. Health Care Costs and Utilization in Patients Receiving Prescriptions for Long-acting Opioids for Acute Postsurgical Pain. Clin J Pain. 2016;32(9):747-54.

29) Sing DC, Barry JJ, Cheah JW, Vail TP, Hansen EN. Long-Acting Opioid Use Independently Predicts Perioperative Complication in Total Joint Arthroplasty. Journal of Arthroplasty. 2016;31(9 Suppl):170-4.e1.

30) Hah JM, Bateman BT, Ratliff J, Curtin C, Sun E. Chronic Opioid Use After Surgery: Implications for Perioperative Management in the Face of the Opioid Epidemic. Anesth Analg. 2017;125(5):1733-40.

31) Miller M, Barber CW, Leatherman S, Fonda J, Hermos JA, Cho K, et al. Prescription Opioid Duration of Action and the Risk of Unintentional Overdose Among Patients Receiving Opioid Therapy. JAMA Internal Medicine. 2015;175(4):608.

32) Best Practice Advocacy Centre B [Internet]. Oxycodone prescribing: New Zealand solutions to a global problem NZ: BPAC; 2016 [cited 2021 Apr 3]. Available from: https://bpac.org.nz/2016/oxycodone-prescribing.aspx.

33) Health Quality & Safety Commission New Zealand H [Internet]. Safe use of opioids national collaborative NZ: HQSC; 2018 [cited 2021 Apr 3]. Available from: https://www.hqsc.govt.nz/our-programmes/medication-safety/projects/safe-use-of-opioids/collaborative/.

34) Faculty of Pain Medicine of the Royal College of Anaesthetists FPM [Internet]. Surgery and Opioids: Best Practice Guidelines 2021 UK: FPM; 2021 [cited 2021 June 19]. Available from: https://fpm.ac.uk/sites/fpm/files/documents/2021-03/surgery-and-opioids-2021_4.pdf.

For the PDF of this article,
contact nzmj@nzma.org.nz

View Article PDF

Opioid analgesics such as morphine or oxycodone are commonly prescribed for the treatment of acute postoperative pain. There is concern that inappropriate opioid prescribing following discharge can lead to prolonged opioid use in the community. In 2018 the Australian and New Zealand College of Anaesthetists (ANZCA) released a position statement recommending that slow or sustained-release (SR) opioids should not be routinely prescribed to patients for the management of acute postoperative pain.[[1]] This statement highlights the risks associated with these drugs, and the difficulties of dose titration for acute pain management.

Orthopaedic surgery is associated with greater amounts of postoperative pain when compared with other surgical procedures.[[2]] As such, orthopaedic operations are known to generate more opioid prescriptions than other specialties.[[3,4]] Total knee arthroplasty (TKA) is a common procedure associated with significant amounts of postoperative pain that subsides rapidly during the recovery period.[[5–7]] Given our ageing population, the number of arthroplasty procedures performed in New Zealand is expected to increase over the coming decades.[[8]] New Zealand data suggest that at three months following hip or knee replacement, which is beyond the expected duration of recovery from surgery, more than 30% of patients continue taking at least mild-strength opioid medications, and up to 8% of patients may still be receiving opioid medications at one-year following surgery.[[9]] These patients would meet the diagnostic criteria for chronic post-surgical pain (CPSP), for which opioid analgesics are not recommended as a part of the primary treatment strategy.[[10,11]]

To manage postoperative pain immediately after TKA, some institutions and professional societies have recommended the use of protocols that include regular SR opioids.[[5,6]] The Procedure Specific Postoperative Pain Management (PROSPECT) recommendations include the use of strong opioids in combination with non-opioid analgesia following TKA, but the strength of the evidence supporting this recommendation is questionable, as it is based on two small studies that compared SR opioids to placebo.[[6]] Currently, the international consensus is that SR opioids are associated with significant harm in the immediate postoperative period and should be avoided.[[1,12–16]] Prolonged or excessive use of opioids can lead to serious adverse effects, including respiratory depression, overdose, addiction and death.[[15]] When SR preparations are used, these harms are compounded due to the drug’s prolonged duration of action.[[3]] This consensus has been reinforced by a case reported on recently by the Health and Disability Commissioner, where a patient died following an elective TKA after routine protocolised SR opioids were used without an appropriate risk assessment.[[17]]

There has been limited research into the efficacy and sequalae of SR opioid use following TKA, and there is a dearth of information surrounding their use when compared with immediate-release (IR) preparations in New Zealand. This study explores the effect of inpatient SR opioid use on acute, inpatient opioid consumption and the longer-term dispensing of opioid medications in patients following TKA at two South Auckland hospitals.

Methods

Study cohort

Prior to study conduct, Health and Disability Ethics Committee (HDEC 19/NTA/27) and Hospital Research Office (Number 893) approval was obtained.

Patients who underwent primary unilateral TKA at Counties Manukau Health between 1 January 2018 and 31 December 2018 were retrospectively identified. This period coincided with the release of the ANZCA position statement on the use of SR opioids in patients with acute pain in late March 2018. Surgery took place at either Middlemore Hospital, a busy acute and elective surgical site, or the Manukau Surgical Centre, where only elective surgery is completed. Patients who underwent isolated uni-compartmental arthroplasty, one-stage or staged revisional TKA, or bilateral simultaneous TKA were excluded, as were patients for whom adequate data were unavailable or surgery was outsourced to an ancillary healthcare facility. These exclusions were made to standardise the magnitude of the surgical procedure and the associated nociceptive stimulus.

Patients were stratified into two groups by their use or avoidance (ie, no use) of strong SR opioids, defined as either M-Eslon® (morphine sulphate modified release capsule) or OxyContin® (oxycodone hydrochloride controlled release tablets), while an inpatient following their primary surgical procedure. The term “sustained-release” encompasses all medications that may be referred to as slow-release, extended-release, modified-release or long-acting.

Data sources

Demographic, anaesthetic, surgical and pharmaceutical data were collated from departmental databases and the electronic data warehouse maintained by HealthAlliance. Demographic and co-morbidity data were obtained from the Concerto Clinical Information Portal and linked with intra-operative data from PCIMS (the Anaesthesia Intraoperative Clinical Record) and PiMS (the Patient Information Management System).

Additional information surrounding comorbidities and procedural complications was obtained from ICD-10 coding completed at the time of hospital discharge. Inpatient dispensing data were extracted from paper medication charts or an electronic prescription system that was introduced during our study period. Outpatient pharmacy data were recorded electronically by the dispensing pharmacy and stored in the TestSafe system. Approximately 98% percent of pharmacies within our catchment area were making use of this system during the time of our study. These sources of information were merged across databases using each patient’s National Health Index (NHI) number. Outpatient dispensing data were obtained for the 90 days before and 90 days after the date of each patient’s surgical procedure, giving a 180-day window into their perioperative drug use once combined with their inpatient dispensing data.

Outcome measures

The primary outcome of this study was the number of patients dispensed strong opioids, either immediate- or sustained-release preparations of morphine or oxycodone, from the hospital pharmacy at discharge or a community pharmacy. This outcome was assessed in 30-day intervals following surgery for three months.

Strong opioid medications were defined as preparations containing morphine, oxycodone, fentanyl, pethidine or methadone. Mild to moderate opioids included preparations containing codeine or dihydrocodeine, tramadol and dextromethorphan. Gabapentinoids are defined as medications that are antagonists at the α2δ sub-unit of voltage gated calcium channels. This class of medications includes gabapentin and pregabalin. Data were collected on total opioid consumption for the first three inpatient days (72 hours) following TKA and expressed in oral morphine equivalents (OMEs). This period was selected as it corresponds to the timing of the maximal nociceptive stimulus, and from previous data we know that after this period most patients are nearing discharge. Data were also collected to calculate the percentage of patients who required additional prescriptions for strong opioid medications within 30-day intervals for three months following surgery.

Comparisons were made between the two groups for perioperative factors that may be associated with differences in acute and ongoing opioid consumption following surgery. “Pre-operative opioid” use was defined as the dispensing of either morphine or oxycodone in the three months (90 days) prior to surgery. We also compared patients who underwent surgery within the first six months of our study to those of the second six months, to evaluate any changes in inpatient SR opioid prescribing patterns as a result of the ANZCA position statement released in March 2018.

Statistical analyses

Information was stored in a Microsoft Excel spreadsheet (Microsoft Corporation, WA, United States) and statistical analysis completed using the Statistical Package for the Social Sciences Version 25 (International Business Machines, NY, United States). Ancillary analyses were completed using NCSS 2021 (NCSS, Utah, United States). Post-hoc power analyses were completed once the sample size had been established. Using the observed incidence of opioid dispensing within one-month following surgery, this study has 83.4% power to detect a statistically significant (two-tailed α=0.05) difference between the two groups.[[18]]

Testing for the normal distribution was through the Shapiro-Wilk test with a two-tailed p-value of <0.05 being indicative of non-normally distributed data. The decision was made to use non-parametric procedures to report data and comparisons. Patient and procedural data were presented as either number (percentage) and median (interquartile range), as appropriate for categorical and continuous data respectively. The Fisher exact test or a Chi Square test with a Yates correction and the Mann-Whitney U test were used to test for differences between categorical and continuous parameters respectively. A two-tailed p-value of p<0.05 defined statistical significance. Using a superiority/non-inferiority threshold of 10mg OME, a post-hoc analysis comparing the median inpatient OMEs consumed was also completed.

Table 1: Baseline characteristics of the two groups stratified by inpatient sustained-release (SR) opioid use. View Table 1.

Table 2: Opioid consumption in the perioperative and postoperative periods. View Table 2.

Results

Between the 1 January and 31 December 2018, 364 patients underwent primary, unilateral TKA at our institution. Complete prescribing information was available for 232 patients (64.1%), which constitutes the study population. While in hospital, 157 patients (67.7%) received at least one dose of SR opioid, and 75 (32.3%) did not receive any SR opioid. In those who received SR opioid, 45 (28.6%) received a morphine-based preparation and 124 (79.0%) received oxycodone. These values sum to more than 100.0% due to the 12 patients (7.6%) who received both morphine and oxycodone SR preparations. The baseline demographics of both groups were similar, with no differences found with regards to age, sex, body mass index, operation duration or hospital length of stay (Table 1). Following surgery, those who received SR opioids were less likely to receive an intravenous patient-controlled analgesia (PCA) device when compared to those who did not, but this difference did not reach statistical significance (9.6% versus 16.0%, p=0.19).

Strong opioid use as an outpatient prior to TKA was greater in the SR opioid use group (8.3% versus 2.7%, p=0.15), although this difference was not statistically significant. This was predominantly oxycodone (13 of 15 patients, or 86.7%). Those in the SR opioid avoidance group were more likely to have been dispensed tramadol or codeine pre-operatively (24.8 versus 41.3%, p=0.01), largely due to a difference in codeine dispensing between the two groups (16.6 versus 30.7%, p=0.02). There were no other differences in the use of pre-operative analgesic medications between the study groups (Table 1).

Inpatient opioid use between postoperative days zero and three (POD0–POD3) was lower in the SR opioid avoidance group, although this was not statistically significant (157.5 [IQR 110.0–220.0] versus 167.5mg OME [110.0–290.0], p=0.14) (Table 2). Following surgery, opioid use was consistently lower at all time intervals in SR opioid avoidance group, excepting POD1. These differences reached statistical significance for POD0 (p=0.003). Using an equivalence margin of 10mg (OME), non-inferiority and superiority analyses demonstrated that avoidance of SR opioid use was both non-inferior (p=0.01) and non-superior (p=0.21) when compared to SR opioid use for inpatient opioid consumption.

SR opioid use was associated with a greater number of patients being dispensed opioids during the first three months following hospital discharge. In the first month after discharge, 105 patients (67.3%) who received inpatient SR opioids continued to be dispensed strong opioids (either morphine or oxycodone) in the community, compared with 34 (47.2%) of the SR opioid avoidance group (p=0.01) (Table 2). During the second month following discharge, there remained a statistically significant difference for those dispensed oxycodone (p=0.03), but not for those dispensed morphine (Figure 1).

Between the first and second six-month periods of our study, the inpatient use of strong SR opioids reduced (84.0% versus 55.3%, p<0.001). This was associated with a non-significant reduction in POD0–POD3 opioid consumption (175.0 [113.75-297.50] versus 152.5mg OME [105.0-242.5], p=0.07).

Figure 1: Outpatient postoperative strong opioid (IR or SR) use.

Discussion

This study aimed to investigate the impact of inpatient SR opioid use on inpatient opioid consumption and persistent opioid dispensing after discharge in patients who undergo TKA. During their inpatient stay, patients who received SR opioids received a greater amount of opioid medication overall, but this difference did not reach statistical significance. The proportion of patients dispensed strong opioid medications within the first 30 days following surgery was significantly greater in the group who received SR opioids as inpatients. There remained a statistically significant difference in oxycodone dispensing for the first two months after surgery, with greater numbers of patients receiving either morphine or oxycodone in the SR opioid use group across all three months. There were no differences between the two groups in the conduct of surgery or anaesthesia or the use of ancillary postoperative analgesic modalities such as PCA devices, peripheral nerve catheters or intrathecal morphine.

Oxycodone was the predominant opioid prescribed by both hospital doctors and general practitioners. There are concerns regarding the use of oxycodone in the community due to its high risk of misuse and drug diversion. Compared to morphine, oxycodone has a greater addictive potential due to its pharmacokinetic profile, including its higher oral bioavailability and the biphasic absorption mechanism of its SR preparations.[[19]] It is well known that OxyContin has contributed to the global opioid epidemic, with communities in North America being especially afflicted.[[19,20]] In New Zealand, there is regional variability in the use of oxycodone, with the number of prescriptions having decreased by 27% since 2011.[[21]] Despite this, our results demonstrate that oxycodone is still prescribed more frequently in those who undergo TKA at our institution, and this disparity continues once patients are discharged from hospital. This preference for prescribing oxycodone is a practice that is not backed up by strong evidence of patient benefit.[[22]]

TKA is generally performed in patients who have failed more conservative management of their knee pathology.[[23]] Arthritis of the knee can cause considerable functional impairment and necessitate the use of strong opioids prior to surgery. We identified differences in pre-operative analgesic dispensing between our study groups, with greater numbers of patients in the SR opioid avoidance group having been dispensed codeine. We might speculate on reasons for these differences, including differences in genetics, patient co-morbidities, psychosocial stressors and pain coping strategies between the two groups, or the effects of sustained opioid use in the lead up to surgery on perioperative pain management. It is well established that persistent or severe pre-operative pain is a risk factor for sub-optimal perioperative pain management and persisting postoperative pain.[[24,25]] Further studies are needed to better understand these mechanisms and evaluate mitigating strategies.

This study highlights the challenges of postoperative pain management after arthroplasty and reinforces the need to moderate the use of SR opioids.[[5,6]] Despite the move away from using SR opioids in patients with acute pain, there is minimal contemporaneous literature reviewing the implications of their use in this setting. Previous studies have described numerous “benefits” of SR drugs including a longer duration of action and improvements in recovery metrics.[[26]] These studies are now outdated, and many display conflicts of interest with drug manufacturers.[[26,27]] The current evidence base suggests that SR opioids have the potential to cause considerable long-term harm, precipitate postoperative complications and place an increased financial burden on the healthcare system.[[19,28,29]] The prescription of SR opioids during the early postoperative period is a major modifiable risk factor for subsequent dependence and persistent opioid use following surgery.[[12]]

ANZCA recommends that SR opioids are used for acute postoperative pain in limited circumstances, including prolonged severe pain or where opioid tolerance has developed.[[1]] This describes only a minority of patients undergoing TKA. The use of SR preparations can make titration and weaning more difficult and problematic. If SR opioids are prescribed beyond discharge, adverse effects such as sedation, opioid-induced ventilatory impairment and delirium are more likely to occur and persist for longer than adverse effects caused by IR preparations.[[30,31]] In our study cohort, patients who were not exposed to SR agents appeared to reduce their use of strong opioid medications more rapidly and consequently reduce the potential for harms associated with opioid use. Tan et al have investigated the impact of the ANZCA position statement on practice at an Australian hospital.[[3]] They noted a decrease in SR opioid prescribing after the release of the statement. Their findings also demonstrated that SR opioid use led to greater overall consumption of opioids while in hospital.[[3]] In this study, we demonstrated a reduction in inpatient use of SR opioids following TKA between the first and second six months of 2018, which corresponds with the release of the ANZCA position statement.

Organisations such as the Health Quality and Safety Commission, the Best Practice Advocacy Centre and district health boards have created national collaboratives or published guidelines to address safe prescribing of opioid medications.[[32,33]] Despite demonstrating a reduction in postoperative SR opioid use over the course of 2018, our results suggest that further education and awareness is required regarding the importance of appropriate opioid prescribing after discharge. This needs to target the multitude of prescribers within and outside the hospital system, including anaesthetists, orthopaedic surgeons, primary care physicians, nurse practitioners and pharmacists. In the hierarchy of a public hospital, discharge prescribing often falls to junior doctors, and so it is vital that initiatives to improve opioid prescribing and awareness include this frequently changing group.

As a retrospective cohort study, this analysis has several limitations. We were unable to assess the severity of pain, other objective measures of recovery from surgery, or patient-reported outcome measures. For approximately 36% of the patients who underwent TKA during our study period, we were unable to extract either the inpatient or outpatient prescribing data. This may be due to their surgery being outsourced to other facilities or that they opted out of linking their NHI number to regionally available electronic dispensing data. The indication for a strong opioid drug prescription was unable to be assessed—a patient may have had other conditions for which they were taking opioid medications. However, it is highly likely that in the first month(s) following TKA a patient’s analgesic dispensing is related to post-surgical pain. Although we were able to determine whether a prescription was dispensed from a pharmacy, we were unable to confirm whether or how those medications were consumed by that patient.

This study was carried out over the calendar year that coincided with the release of the ANZCA position statement on use of SR opioids for acute pain, and our sample size was only moderate. These results may not be suitable for extrapolation to other institutions or for patients undergoing a more diverse range of surgical procedures. As such, additional larger studies are required to confirm our findings. We were only able to extract opioid dispensing data for the three months following surgery. A longer period would be required to identify the relationship between immediate postoperative SR opioid use and prolonged opioid use. One of the strengths of this study was the similarity of the two groups at baseline. Further correction for anaesthetic, surgical or patient factors by propensity score matching could yield additional information on factors influencing opioid prescribing patterns at the time of surgery. We were also able to make comparisons to current national and speciality society guidelines to ensure the relevance of our prescribing patterns and support their recommendations.[[1,14–16]] Although a considerable number of patients continued to receive SR opioids in the second six-month period of 2018, there was a marked reduction seen from January to June of that year. Ongoing SR opioid prescribing may be indicative of prescribers’ resistance to change from their “standard” practice. Further audit of SR opioid use would be useful to determine whether this trend has been sustained.

Conclusion

Inpatient SR opioid use is associated with increased overall inpatient opioid use and persistent outpatient opioid dispensing (particularly of oxycodone) following TKA. Further studies are needed to better determine the current patterns and implications of perioperative SR opioid use, including quality of recovery scores and adequacy of pain control, with a view to improving perioperative pain management and reducing the potential for harm due to unnecessary or prolonged opioid use. This is particularly important where opioid use persists beyond three months after surgery, as best practice recommendations for chronic post-surgical pain management focus on the avoidance of opioid medications and emphasise the importance of physical and psychological therapies.[[11,34]]

Summary

Abstract

Aim

To determine the impact of perioperative sustained-release (SR) opioid use on total inpatient opioid consumption and longer-term outpatient dispensing for three months following elective total knee arthroplasty (TKA).

Method

Patients who underwent primary unilateral TKA between 1 January and 31 December 2018 at Counties Manukau Health were retrospectively identified. Participants were stratified into two groups by inpatient use or avoidance of strong SR opioids (OxyContin or M-Eslon). The primary outcome was the percentage of patients receiving prescriptions for opioid medications at thirty-day intervals for three months after discharge.

Results

Two hundred and thirty-two patients were eligible for inclusion. The baseline demographics of both groups were similar. In the SR opioid use group, the majority (79%) received OxyContin. Overall, inpatient opioid use between postoperative days (POD) zero and three was lower in the SR opioid avoidance group, although this was not statistically significant (157.5 [IQR 110.0–220.0] vs 167.5mg OME [110.0–290.0], p=0.14). Outpatient postoperative opioid dispensing between 0–30 days was significantly greater in patients who received inpatient SR opioids (p=0.01). Dispensing of oxycodone was significantly higher in the SR opioid use group at one- and two- months (p=0.01 and 0.03 respectively).

Conclusion

The postoperative use of SR opioids is not routinely recommended following TKA. Their use is associated with greater overall inpatient opioid use, sustained opioid dispensing during and after the expected recovery period, and the potential for significant harm.

Author Information

Taehoon Kim: Bachelor of Medical Science (Honours) Student, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. Chen (Eileen) Zhou: MBChB Registrar, Department of Emergency Medicine, Waitematā District Health Board, Auckland, New Zealand. Rachel A Sara: MBChB, FANZCA, FFPMANZCA, Consultant Anaesthetist and Pain Medicine Specialist, Department of Anaesthesia and Pain Medicine, Counties Manukau Health, Middlemore, New Zealand. Nicholas J Lightfoot: MBChB, FANZCA, Consultant Anaesthetist, Department of Anaesthesia and Pain Medicine, Counties Manukau Health, Middlemore, New Zealand.

Acknowledgements

I would like to thank my co-supervisors Dr Nicholas Lightfoot and Dr Rachel Sara, as well as the rest of the research team at Counties Manukau Health for their support and the culmination of work that has led to this publication.

Correspondence

Taehoon Kim, Faculty of Medical and Health Sciences, University of Auckland, Auckland, NZ, 85 Park Road, Grafton, Auckland 1023. Private Bag 92019

Correspondence Email

tkim270@aucklanduni.ac.nz

Competing Interests

Dr Lightfoot reports other from Merck Sharp and Dohme, personal fees from Merck Sharp and Dohme and other from Vifor Pharma outside the submitted work.

1) ANZCA [Internet]. Position statement on the use of slow-release opioid preparations in the treatment of acute pain. 2018 [cited 2021 Mar 14]. Available from: https://www.anzca.edu.au/getattachment/d9e2a7c5-0f17-42d3-bda7-c6dae7e55ced/Position-statement-on-the-use-of-slow-release-opioid-preparations-in-the-treatment-of-acute-pain

2) Saini S, McDonald EL, Shakked R, Nicholson K, Rogero R, Chapter M, et al. Prospective Evaluation of Utilization Patterns and Prescribing Guidelines of Opioid Consumption Following Orthopedic Foot and Ankle Surgery. Foot & Ankle International. 2018;39(11):1257-65.

3) Tan AC, Bugeja BA, Begley DA, Stevens JA, Khor K-E, Penm J. Postoperative use of slow-release opioids: The impact of the Australian and New Zealand College of Anaesthetists/Faculty of Pain Medicine position statement on clinical practice. Anaesthesia and Intensive Care. 2020;48(6):444-53.

4) Volkow ND. Characteristics of Opioid Prescriptions in 2009. JAMA. 2011;305(13):1299.

5) Byrne K, Clark J. Total knee arthroplasty – The optimal analgesic regime. Trends in Anaesthesia and Critical Care. 2015;5(4):104-10.

6) Fischer HBJ, Simanski CJP, Sharp C, Bonnet F, Camu F, Neugebauer EAM, et al. A procedure-specific systematic review and consensus recommendations for postoperative analgesia following total knee arthroplasty. Anaesthesia. 2008;63(10):1105-23.

7) Trasolini NA, McKnight BM, Dorr LD. The Opioid Crisis and the Orthopedic Surgeon. Journal of Arthroplasty. 2018;33(11):3379-82.e1.

8) The New Zealand Joint Registry N [Internet]. Twenty-One Year report January 1999 to December 2019. 2020 [cited 2021 Feb 16]. Available from: http://www.nzoa.org.nz/nzoa-joint-registry

9) Wilson R, Pryymachenko Y, Audas R, Abbott JH. Long-term opioid medication use before and after joint replacement surgery in New Zealand. N Z Med J. 2019;132(1507):33-47.

10) World Health Organization W [Internet]. International classification of diseases for mortality and morbidity statistics (11th Revision): WHO; 2018 [cited 2021 June 18]. Available from: https://icd.who.int/browse11/l-m/en

11) National Institute for Health and Care Excellence NICE [Internet]. Chronic pain (primary and secondary) in over 16s: assessment of all chronic pain and management of chronic primary pain UK: NICE; 2021 [cited 2021 June 19]. Available from: https://www.nice.org.uk/guidance/ng193

12) Shah A, Hayes CJ, Martin BC. Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use - United States, 2006-2015. MMWR Morb Mortal Wkly Rep. 2017;66(10):265-9.

13) Zin CS, Nazar NI, Rahman NSA, Ahmad WR, Rani NS, Ng KS. Patterns of initial opioid prescription and its association with short-term and long-term use among opioid-naïve patients in Malaysia: a retrospective cohort study. BMJ Open. 2019;9(7):e027203.

14) Chou R, Gordon DB, de Leon-Casasola OA, Rosenberg JM, Bickler S, Brennan T, et al. Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016;17(2):131-57.

15) US Food Drug Administration F. FDA’s opioid analgesic REMS education blueprint for health care providers involved in the treatment and monitoring of patients with pain. Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2018.

16) Schug S, Palmer G, Scott D, Halliwell R, Trinca J. Working Group of the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine (2015), Acute Pain Management: Scientific Evidence. 4th ed. ANZCA., FPM., editors. Melbourne2015.

17) Health & Disability Commisioner HDC [Internet]. Management of patient before and after surgery (Case 15HDC00850) NZ2018 [cited 2021 June 18]. Available from: https://www.hdc.org.nz/decisions/search-decisions/2018/15hdc00850/

18) Kane SP. Post-hoc Power Calculator: ClinCalc; 2018 [cited 2021 Apr 20]. Available from: https://clincalc.com/stats/Power.aspx.

19) Levy N, Mills P. Controlled-release opioids cause harm and should be avoided in management of postoperative pain in opioid naive patients. Br J Anaesth. 2019;122(6):e86-e90.

20) deShazo RD, Johnson M, Eriator I, Rodenmeyer K. Backstories on the US Opioid Epidemic. Good Intentions Gone Bad, an Industry Gone Rogue, and Watch Dogs Gone to Sleep. Am J Med. 2018;131(6):595-601.

21) Health Quality & Safety Commission New Zealand H [Internet]. Opioids 2019 [cited 2021 April 3]. Available from: https://www.hqsc.govt.nz/our-programmes/health-quality-evaluation/projects/atlas-of-healthcare-variation/opioids/

22) Best Practice Advocacy Centre B [Internet]. Oxycodone: how did we get here and how do we fix it? NZ: BPAC; 2014 [cited 2021 Apr 15]. Available from: https://bpac.org.nz/bpj/2014/july/oxycodone.aspx.

23) National Clinical Guideline Centre N. Osteoarthritis: Care and management in adults. National Institute for Health and Care Excellence; 2014 Feb. Contract No.: CG177.

24) Lawal OD, Gold J, Murthy A, Ruchi R, Bavry E, Hume AL, et al. Rate and Risk Factors Associated With Prolonged Opioid Use After Surgery: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020;3(6):e207367.

25) Huang A, Azam A, Segal S, Pivovarov K, Katznelson G, Ladak SS, et al. Chronic postsurgical pain and persistent opioid use following surgery: the need for a transitional pain service. Pain Management. 2016;6(5):435-43.

26) Illgen RL, Pellino TA, Gordon DB, Butts S, Heiner JP. Prospective Analysis of a Novel Long-acting Oral Opioid Analgesic Regimen for Pain Control After Total Hip and Knee Arthroplasty. The Journal of Arthroplasty. 2006;21(6):814-20.

27) Sunshine A, Olson NZ, Colon A, Rivera J, Kaiko RF, Fitzmartin RD, et al. Analgesic efficacy of controlled-release oxycodone in postoperative pain. J Clin Pharmacol. 1996;36(7):595-603.

28) Gold LS, Strassels SA, Hansen RN. Health Care Costs and Utilization in Patients Receiving Prescriptions for Long-acting Opioids for Acute Postsurgical Pain. Clin J Pain. 2016;32(9):747-54.

29) Sing DC, Barry JJ, Cheah JW, Vail TP, Hansen EN. Long-Acting Opioid Use Independently Predicts Perioperative Complication in Total Joint Arthroplasty. Journal of Arthroplasty. 2016;31(9 Suppl):170-4.e1.

30) Hah JM, Bateman BT, Ratliff J, Curtin C, Sun E. Chronic Opioid Use After Surgery: Implications for Perioperative Management in the Face of the Opioid Epidemic. Anesth Analg. 2017;125(5):1733-40.

31) Miller M, Barber CW, Leatherman S, Fonda J, Hermos JA, Cho K, et al. Prescription Opioid Duration of Action and the Risk of Unintentional Overdose Among Patients Receiving Opioid Therapy. JAMA Internal Medicine. 2015;175(4):608.

32) Best Practice Advocacy Centre B [Internet]. Oxycodone prescribing: New Zealand solutions to a global problem NZ: BPAC; 2016 [cited 2021 Apr 3]. Available from: https://bpac.org.nz/2016/oxycodone-prescribing.aspx.

33) Health Quality & Safety Commission New Zealand H [Internet]. Safe use of opioids national collaborative NZ: HQSC; 2018 [cited 2021 Apr 3]. Available from: https://www.hqsc.govt.nz/our-programmes/medication-safety/projects/safe-use-of-opioids/collaborative/.

34) Faculty of Pain Medicine of the Royal College of Anaesthetists FPM [Internet]. Surgery and Opioids: Best Practice Guidelines 2021 UK: FPM; 2021 [cited 2021 June 19]. Available from: https://fpm.ac.uk/sites/fpm/files/documents/2021-03/surgery-and-opioids-2021_4.pdf.

Contact diana@nzma.org.nz
for the PDF of this article

Subscriber Content

The full contents of this pages only available to subscribers.
Login, subscribe or email nzmj@nzma.org.nz to purchase this article.

LOGINSUBSCRIBE