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Persistent postoperative opioid use

The scale of the problem of persistent postoperative opioid use
Hand reaching for a box of pills that has toppled over, spilling pills across the table

In Week 1, Dr Jane Quinlan introduced the concept of PPOU and looked at the case of a patient who found it difficult to stop taking opioids after an elective operation.

This is thought to be one of the main negative outcomes from the use of opioids perioperatively, and a major contributor to the increased use of opioids in the community in the United States. In this step Dr Jamie Smart, Consultant in Anaesthesia and Pain Medicine at University College London Hospitals, discusses the scale of the problem.

If we were to consider completing this course as a therapeutic intervention in itself, then the primary outcome we would be looking for would be a reduction in persistent postoperative opioid use (PPOU) in your patients.

PPOU doubles the risk of developing opioid use disorder (OUD), doubles the risk of opioid-related overdose and dramatically increases the incidence of opioid-related adverse drug events (ORADEs).

When comparing rates of PPOU in different studies and countries it is important to bear in mind that the definition used to interpret the data hugely alters the results given. A 2020 literature review identified 39 different definitions for PPOU. The authors applied these 39 definitions to the same cohort of over 100,000 opioid-naïve patients to see how they would affect the calculated incidence of PPOU—the resulting range was 0.01% to 15%.

A 2019 consensus statement from the American Society of Enhanced Recovery and Perioperative Quality has suggested that for research purposes PPOU should be defined as “filling prescriptions totalling over 60 days’ supply of opioid between days 90 and 365 post-surgery”. They also noted the wide variance in incidence of PPOU of 0.6%-26% in the studies they reviewed caused by the lack of consistent definition. Hopefully increasing numbers of studies in the future will adopt this definition of PPOU and we will develop some truly comparable data to work with.

A review of the data currently available indicates that the most significant influence healthcare professionals can exert on PPOU is by refining prescribing practices. This involves prudent opioid selection, optimising postoperative pain management, and enhancing post-discharge prescribing.

Research comparing the PPOU in cohorts receiving different opioids suggest that patients prescribed oxycodone face up to an 80% higher risk of PPOU compared to those given morphine. Furthermore, the risk of PPOU could be up to three times higher for patients prescribed modified release opioids compared to immediate release medication. It is also likely that the duration and dosage of initial postoperative opioid prescriptions are linked to the development of PPOU, the most important of these appears to be the duration of the prescription. Therefore, rational post-discharge prescribing may also mitigate these risks.

It may be tempting to try to eliminate opioids from our postoperative prescribing altogether, however it is very likely that this would be counterproductive. Poor analgesia in the immediate postoperative period is also predictive of increased risk of PPOU and persistent postoperative pain. Rather than eliminating opioids, good opioid stewardship and judicious use of immediate-release opioids as part of a multimodal analgesic regime may be more effective in reducing the risk of PPOU than an opioid-free postoperative period with higher pain scores.

Other PPOU risk factors may be more difficult or impossible to modify. It can still be helpful to identify these factors as they can function as risk markers, prompting closer monitoring for potential escalation in opioid use.

A history of substance abuse, notably opioids and cocaine, may raise the risk of PPOU by up to 300-500%, while alcohol and tobacco use disorders increase this risk by 50%. Mechanisms responsible for this link may include increasing opioid tolerance and the development of opioid-induced hyperalgesia, along with the presence of concomitant psychological disorders.

Anxiety, depression and post-traumatic stress disorder (PTSD) may increase the risk of PPOU by up to 80%, and patients with 2 or more pre-existing co-morbidities (especially diabetes, respiratory and cardiac co-morbidities) have a similarly increased risk. Back pain is associated with a 200% increase in risk and fibromyalgia and migraine around 50%. Those taking antineuropathic agents are also at increased risk.

We can aspire to a future of safer more effective postoperative pain management where PPOU is minimised by promoting opioid stewardship and improving preoperative patient education and pre-habilitation. We will explore in greater depth what specific interventions and changes in practice can help us to achieve these goals in Week 3. Comparable and consistent measuring of the factors contributing to PPOU is essential in improving perioperative patient care, and mitigating these risk factors through monitoring and early intervention is crucial. Also, addressing the broader influences that encourage PPOU will lead to a further reduction in the overuse of opioids in the postoperative period.


1. Kent ML, Hurley RW, Oderda GM, Gordon D, Sun E, Mythen M et al. American Society for Enhanced Recovery and Perioperative Quality Initiative-4 Joint Consensus Statement on Persistent Postoperative Opioid Use: Definition, Incidence, Risk Factors, and Health Care System Initiatives. Anes Analg 2019;129(2):543-552.

2. Sitter T, Forget P. Persistent postoperative opioid use in Europe: a systematic review. Eur J Anaesthesiol 2021;38(5):505-511.

3. Lawal OD, Gold J, Murthy A, 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.

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Opioids and Surgery

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