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Quality & safety in the literature: January 2019
  1. Ashwin Gupta1,2,
  2. Nathan Houchens1,2,
  3. Jennifer Meddings1,2,3
  1. 1 Medicine Service, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan, USA
  2. 2 Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
  3. 3 Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Michigan, USA
  1. Correspondence to Dr Ashwin Gupta, Medicine Service, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI 48105, USA; ashwing{at}

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Healthcare quality and safety span multiple topics across the spectrum of academic and clinical disciplines. Keeping abreast of the rapidly growing body of work can be challenging. In this series, we provide succinct summaries of selected relevant studies published in the last 6 months. Some articles will focus on a particular theme, while others will highlight unique publications from high - impact medical journals.

Key points

  • Opioid-related deaths disproportionately affect males, those in lower socioeconomic classes and those with concurrent addiction or mental health disorders. Fentanyl and synthetic opioids have emerged as the new leading drugs implicated in opioid abuse and overdose in North America. BMJ. 29 Aug 2018.

  • Opioid-related adverse drug events in patients undergoing hospital-based procedures occur more often in older, sicker patients and those who receive higher cumulative doses and longer duration of opioids. These events are associated with deleterious quality outcomes for hospitals such as higher odds of inpatient mortality, 30-day readmission, longer length of stay and higher cost of hospitalisation. JAMA Surgery. 1 Aug 2018.

  • Following opioid overdose, pharmacological treatment with methadone maintenance therapy or buprenorphine results in decreased all-cause and opioid-related mortality. Annals of Internal Medicine. 7 Aug 2018.

Opioids now constitute a leading cause of premature death in much of the world.1 The opioid crisis has hit hardest in North America, with an exponential growth in mortality from unintentional drug overdose in the USA in the past three decades.1 2 Over 42 000 deaths in the USA annually are now attributable to opioids.3 In 2016, the opioid-related death rate per 100 000 people was 13.1 in the USA3 and 8.3 in Canada,4 with rates varying greatly by region of country. That year, North American healthcare leaders issued a call to action to address the opioid epidemic.5 6 In 2017, the US Department of Health and Human Services declared the opioid epidemic a public health emergency.

Outside of North America, similar problems are evident. In Australia, deaths from opioids nearly doubled in the past decade, with the majority related to prescription opioids.7 In England and Wales, after several years of consistent increases, drug-related deaths plateaued in 2017, but deaths attributed to fentanyl continued to rise.8 Ten countries in Europe now have take-home naloxone programmes, indicating increased attention and resources towards opioid-related deaths.9

In this inaugural instalment of Quality & Safety in the Literature, we highlight three recent articles from the rapidly growing scholarship on the opioid epidemic. These publications examine the magnitude and breadth of opioid-related deaths and adverse events, as well as medications to prevent them.

Contributions of prescribed and non-prescribed opioids to opioid related deaths: population based cohort study in Ontario, Canada

BMJ 29 Aug 2018

In this study, Gomes and colleagues10 sought to understand the role prescription and non-prescription opioids played in opioid-related deaths in Ontario, Canada’s most populous province. The authors accomplished this goal by linking routine databases (eg, the registry of every person ever issued a health card in Ontario) and specialised databases (eg, the Ontario Narcotics Monitoring System and a database of coroner investigations of all deaths that are sudden or unexpected). The analysis included over 2800 deaths in which an opioid contributed, either alone or in combination with another drug or alcohol, occurring between 1 January 2013 and 31 December 2016.

The average age of the deceased was 43 years. A majority (68%) were male, and over half lived in neighbourhoods in the bottom two-fifths of income. Concurrent mental health disorders or addictions were common, with a quarter carrying a diagnosis of alcohol abuse disorder and 4 in 10 experiencing an emergency visit for a mental health disorder in the prior 3 years. Over the study period, the proportion of deaths involving fentanyl more than doubled (20% in 2013 to 47.5% in 2016, p<0.001). Although the proportion of opioid-related deaths that occurred in those with active opioid prescriptions decreased (38.2% in 2013 to 32.5% in 2016, p=0.03), this hopeful improvement disappeared when deaths related to fentanyl were excluded 36.8% to 39.8%, p=0.18). Finally, toxicology studies suggested that over a third of people with active opioid prescriptions were concurrently found to have a non-prescribed opioid in their bloodstream at the time of death.

Association of opioid-related adverse drug events with clinical and cost outcomes among surgical patients in a large integrated health care delivery system

JAMA Surgery 1 Aug 2018

Shafi and colleagues11 retrospectively explored factors and outcomes associated with opioid-related adverse drug events (ORADEs) in over 135 000 patients admitted between 1 January 2013 and 30 September 2015 after undergoing a qualifying surgical or endoscopic procedure in 21 acute care hospitals in a large, integrated US healthcare delivery system (the largest not-for-profit healthcare system in Texas). Overall, greater than 10% of patients experienced at least one ORADE. Those who experienced an ORADE were more likely to be older, male, and Medicare beneficiaries, and demonstrated a higher number and severity of baseline comorbidities. Those who developed ORADEs received more days of treatment with opioids and higher morphine equivalent doses during their hospitalisation. Most patients experienced only one ORADE, most commonly respiratory complications, including the need for mechanical ventilation. After adjustment for age, race/ethnicity, sex, payer type, Charlson Comorbidity Index and any history of alcohol or drug abuse, patients with ORADEs experienced remarkably higher odds of inpatient mortality and significantly higher odds of discharge to a care facility, 30-day readmission, prolonged length of stay and higher cost of hospitalisation.

Medication for opioid use disorder after nonfatal opioid overdose and association with mortality: a cohort study

Annals of Internal Medicine 7 Aug 2018

This retrospective cohort study included nearly 18 000 Massachusetts adults without cancer who survived an opioid overdose between January 2012 and December 2014.12 Larochelle and colleagues identified opioid overdose patients by International Classification of Disease, Ninth Edition (ICD-9) codes for opioid poisoning and from ambulance records. In the 12 months following an index overdose, 30% of participants received one or more medications for opioid use disorder. Those receiving these therapies after overdose were generally younger than 45 years of age, more likely to have concurrent depression or anxiety, and more likely to have taken part in recent detoxification treatment. In total, 8% of participants received methadone maintenance therapy, 13% received buprenorphine, 4% received naltrexone and 5% received more than one medication for opioid use disorder. Reductions in both all-cause mortality and opioid-related mortality were noted with methadone maintenance therapy and with buprenorphine. The wide CIs for naltrexone limited the ability to reach conclusions.

Summary and conclusions

How can these studies help inform our next steps to address pervasive opioid overuse? They tell us a lot about the characteristics of persons likely to be affected. Opioid-related deaths disproportionately affect younger individuals, those of lower socioeconomic status, and those with mental health and other substance use disorders. Illicit use of opioids—including the particularly lethal fentanyl—is increasing. One useful outcome of these studies is to guide hospitals and health systems to dedicate additional resources to avoiding or reducing prescription of opioids in usual medical care, and to stimulate them to enhance access to treatment for opioid dependence for individuals who need it most.

The studies further show that among those undergoing invasive procedures, patients who are older, sicker or receive more days and higher doses of opioids more often experience opioid-related adverse events. These adverse events, in turn, lead to longer hospitalisations with higher inpatient mortality and readmissions. There is an opportunity here to be judicious with opioid use in these groups while still relieving patient suffering.

Finally, in those who suffer non-fatal opioid overdose, less than a third of patients are given medication to assist in the treatment of opioid use disorder, yet these therapies work. Those who receive methadone maintenance therapy and/or buprenorphine die less frequently from opioids and any cause. Expansion of these medication programmes may save lives.

There is no single panacea to the opioid crisis; rather, multiple changes are required, and they can work. Readers of BMJ Quality & Safety may recall reading a study by Vermaire et al, whose efforts led to decreased rates of opioid-related oversedation events in postoperative paediatric patients through multipronged and multidisciplinary quality improvement interventions.13 The US Veterans Health Administration provides another illustrative example. The 2013 VA Opioid Safety Initiative put forth a series of interventions focused on education, pain management, risk mitigation and addiction treatment. Through these efforts, opioid prescriptions were reduced by 25% between 2012 and 2016, and the rate of opioid overdose among Veterans who were dispensed a prescription opioid was cut in half.14

For prescribers, the lessons are clear. Just as patients are asked to dedicate themselves to behaviour change (eg, weight loss, exercise, smoking cessation), prescribers too must change behaviours, including those that have contributed to the widespread overuse of opioids. Preventing opioid addiction whenever possible is a priority, and implementing effective harm-reduction strategies for those already struggling with opioid dependence is an obligation.


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  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

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