deaths-related to opioid toxicity: themes from a narrative ... · 1. toxicity from opioids may...
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Deaths-Related to Opioid Toxicity: Themes from a
Narrative Review
Parvaz Madadi, PhD
January 28th, 2014
Ontario Harm Reduction Distribution Program
Centre for Disease Control and Prevention, 2011
In 2008, there were ~ 14, 800 prescription opioid deaths in the United States.
Dhalla et al., CMAJ, 2009
Ontario data 1991 - 2004: Opioid analgesics and related mortality
Prescription practices & opioid-related deaths
Long-acting oxycodone introduction
Regions with high incidence of opioid-related deaths per capita have high opioid prescription utilization
Deaths appear to be concentrated amongst patients treated by physicians who prescribed opioids more frequently
High prescribed doses significantly associated with an increase risk of mortality
Dhalla et al. CMAJ, 2009
Gomes et al. Healthc Q, 2011
Dhalla et al. Can Fam Phys, 2011
Gomes et al. Arch Intern Med, 2011
Need for more individualized evidence and insight into why and how opioid-related deaths occur…
To identify patterns and characteristics amongst opioid-users whose cause of death was related to opioid toxicity in Ontario
Years: 2006 to 2008
Study Design: Retrospective, descriptive, population study in Ontarians
Objective:
Method Ontario: ~ 13 million individuals; diverse municipalities and regions Ontario Coroners Act: all sudden and unexpected deaths, and/or deaths thought to be from any cause other than disease must be reported to the Coroner’s Office from anywhere in the province of Ontario.
Death investigations involve classification of the cause of death as well as the manner of death
Coroner/medical, toxicology, pathology, police investigations reviewed
Opioid deaths isolated and studied
All drug related deaths in Ontario reviewed
Non-medical route of drug administration:
Coroner, police, autopsy Death scene investigations, puncture sites, patch debris
Indicators of diversion: Analysis of prescription
records, bottles, interviews (family , friends, healthcare
providers)
Method
More about the process…
Boxes of files, each file representing a
person who was no longer living…
Recurring themes, stories, and life trajectories….
SIX SELECTED THEMES FOR TODAY
Deaths which involve opioids tend to be
accidents
A range of potent opioids are involved in opioid-related deaths
Opioid misuse and diversion account for 30% of opioid-related
death
Opioid switching and dose adjustments are temporally associated
with opioid deaths
Substance abuse features are associated
with opioid-related accidental deaths
Opioid-related deaths are associated with
release from jail
Theme One: Deaths which involve opioids tend to be accidents
PLOS One, 2013
Demographic Characteristics Opioid-related deaths (n=1359)
Non-opioid drug-related deaths (n=971) p-value
Gender (male) 867 (64%) 572 (59%) 0.03
Age (yr); Median (IQR) Range
44 (25-51) [16-89]
46 (37-54) [14-94] <0.001
Coroner Death Classification
Accident 924 (68%) 437 (46%) <0.001
Undetermined 221 (16%) 163 (17%) 0.73
Suicide 214 (16%) 371 (38%) <0.001
Results
Mr. H was in his sixties, with a history of non-insulin dependent diabetes, sleep apnea, depression, cancer and migraines. He also suffered from chronic back pain and used regular doses of potent narcotic analgesics. He had been golfing over the few days prior to his death and had been using fentanyl patches as well as other narcotics to manage his pain. He was noted to be somewhat drowsy over the last few days. He was breathing forcefully during the night, which was not terribly unusual as he had sleep apnea. He was found unresponsive in the early morning. The cause of death was attributed to mixed drug intoxication involving fentanyl, morphine, oxycodone.
Theme One: Deaths which involve opioids tend to be accidents
Take Home Lessons
1. Toxicity from opioids may occur over a number of days
• Not entirely clear that a naloxone intervention was
needed
2. Underlying respiratory issues (sleep apnea, COPD,
smoking, bronchitis, flu) may predispose users to opioid-toxicity
• Mechanism of fatality is respiratory depression
Theme Two: A range of potent opioids are involved in opioid-related deaths
Distribution of opioids amongst single-opioid related deaths (n=1040) PLOS One, 2013
PLOS One, 2013
Of single opioid related deaths n = 1040
Manner of death per opioid type
Theme Three: Opioid misuse and diversion account for ~ 30% of opioid-related death
PLOS One, 2013
Indicators of diversion and misuse
Distribution of opioids amongst deaths related to “inappropriate route” of opioid administration (n=263)
Oxycodone34%
Morphine27%
Methadone
14%
Fentanyl9%
Hydromorphone8%
Codeine6%
Others2%
Unpublished
Using a deceased family member’s medication A woman was grieving the loss of her sister who had passed away recently from cancer. She did not show up to her sister’s funeral. The family found the woman motionless on her bed, with
dried vomitus on the pillow and sheets. The woman had her deceased sister’s
hydromorphone pills in her room which had been prescribed for cancer.
Healthcare professional diversion An Ontario nurse came home from work, went
into the bathroom, and did not emerge for half an hour. Her husband went into the bathroom, found his wife unconscious, and called the
ambulance. The ambulance crew observed an empty IV bag, tubing, and a butterfly IV in the
bathroom. The IV bag had a label indicating that it contained fentanyl .
Using friend’s medication A man was visiting his friend who had methadone
in his possession. The man was not feeling well and drank his friend’s methadone, ate some soup and had ointment rubbed on his back. The friend
went to work in the morning and left the man sleeping. On returning home from work the
friend found the man still in the same position in the bed lying on this left side. Post-mortem exam
confirmed acute methadone intoxication.
Using friend’s medication A woman was discovered unresponsive in the
basement of a friend’s house. She was pronounced dead at the scene. The day before she had been
complaining of abdominal pain. She used someone else’s hydromorphone to try to deal with the pain. An autopsy did not reveal an anatomical cause for the death but did show evidence of gastritis and possible pancreatitis. Toxicology revealed a high
dose of hydromorphone.
Case Narratives of Opioid Misuse and Diversion
Theme Four: Opioid switching and dose adjustments are temporally associated with opioid deaths
Ms. P was a 43 year old female who was recovering from crack cocaine and prescription medication abuse. In addition, she suffered from smoker’s bronchitis. She was receiving benzodiazepines, oxycodone and had started on the methadone program two weeks before her death. Her dose had just been increased to 40 mg from 25 mg prior to death. One day before her death she complained of feeling woozy. The cause of death was attributed to combined CNS effects of the drugs (mixed drug intoxication).
Theme Four: Opioid switching
Opioid Switching Prior to Death: 3.6% of cohort
1. Methadone --- n = 15
2. Oxycodone ---- n = 10
3. Fentanyl -------- n = 10
4. Hydromorphone n = 4
5. Morphine --------- n = 3
Take Home Lessons 1. Switching to a more potent opioid, adding an opioid
to someone taking methadone, or adjusting a methadone dosage, are practices that can be potentially lethal if not done with great caution.
2. The mix of ‘downers’ (benzodiazpeines + opioids + alcohol) is often associated with multidrug intoxications
3. Patients and healthcare providers should recognize what the early signs of opioid overdose may be (woozy, drowsy, tired)
Theme Five: Substance abuse features are associated with opioid-related accidental deaths
PLOS One, 2013
Substance abuse-related Features
Accidents (n=921)
Suicides (n=215) OR 95% CI P-value
History of alcohol abuse 221 (24%) 25 (12%) 2.3 [1.5-3.6] 0.0001
Cirrhosis 70 (8%) 5 (2%) 0.003
History of illicit drug abuse 486 (53%) 17 (8.1%) 8.3 [5.2-12.8] <0.0001
Cocaine/metabolite detected 308 (34%) 22 (11%) 4.32 [2.7-6.9] <0.0001
Depression 167 (18%) 112 (54%) 5.2 [3.8-7.1] <0.0001
Hepatitis 123 (13%) 3 (1%) <0.0001
Theme Six: Opioid-related deaths are temporally associated with release from jail
PLOS One, 2013
4% of deaths temporally related to incarceration (n=46)
Take Home Lessons 1. A high rate of acute drug-related mortality amongst
prison populations in the immediate post-release period has been described in other settings
2. Decreased tolerance during incarceration - upon release may utilize previous doses
3. Coordinated effort between prison and public health systems are needed to provide education to inmates on these issues.
Summary
• Deaths which have resulted from the use, abuse, and misuse of opioids have touched every community in Ontario. – Opioid-related deaths span across age, geographical,
and demographic specifications.
• This data assists in quantifying the contribution of opioid abuse and illicit opioid diversion to mortality • 1 in 5 opioid deaths: injection, inhalation, or chewing • Diversion: at least 7.4% of deaths
Summary
• Support targeted prevention, harm reduction, and educational strategies based on sub-populations of users • Both accidental and intentional opioid-related deaths
• Engagement of diverse stakeholders
• Assist in identifying and providing resources for vulnerable individuals
• Examples within Ontario data set: Prior to release from
incarceration, mental health support
Collaborators
• Dr. Gideon Koren (Clinical Pharmacology and Toxicology at SickKids)
• Dr. Bert Lauwers (formerly from the Office of the Chief Coroner of Ontairo)
• Ms. Doris Hildebrandt (Office of the Chief Coroner of Ontario)
• Funding Support: Postdoctoral Fellowship from the Canadian Institutes for Health Research
Death Classifications
• Accidental: due to an occurrence, incident, or event that happens without foresight or expectation
• Suicide: an intentional act of omission or commission in a person knowing the probable consequence of what he/she is about to do
• Undetermined: (a) there is no evidence for any specific classification; (b) there is equal evidence, or a significant contest, among two or more classifications, or (c) a death is a suicide that does not meet a high degree of probability.