2014 opioids eastern or ems conferencePresentation Transcript
Opioids: Old Friends
EASTERN OREGON EMS CONFERENCE
"Among the remedies which it has pleased
Almighty God to give to man to relieve his
sufferings, none is so universal and so efficacious
-THOMAS SYDENHAM (1624 -1689)
Discuss the basic pharmacology of opioids
Discuss the epidemiology of illicit opioid use
Describe common treatment modalities
Describe treatment variations for uncommon presentations
Describe common pitfalls in the emergency care of opioid overdoses
Who am I?
Ada County Paramedics for 15
EMS for 23 (and counting) years
I have no financial conflicts of interest
This presentation is not a substitute for basic clinical
Follow your protocols!
Before we get Yourself….
Doing your own research…
Knowing where to look
Staying up to date
EMS Textbooks SUCK!
Hundreds of Metropolitan/Suburban Hospitals and Coroners/ME offices across
A DAWN case is any ED visit or death related to recent drug use. The criteria for
inclusion in DAWN are intentionally broad and simple, with few exceptions
Thousands of drugs of all types are included in DAWN. These include:
Illegal drugs of abuse;
Prescription and over-the-counter medications;
Alcohol in combination with other drugs (adults and children)
Alcohol alone (age < 21).
Opioids of all types are a significant cause of ED visit (approximately 35%)
Heroin accounts for approximately 9% of opioid related visits
Heroin has resulted in a 67% increase of ED related visits from 2004 though 2011
Illicit use of pharmaceutical opioids accounts for about 26%
Oxycodone containing products had a 158% increase from 2004 through 2011
Source: 2011 DAWN statistics
What is Diversion?
Diversion is the use of prescribed substances (Opioids are just one drug class that is often
diverted) for illicit or recreational use.
How are Drugs Diverted?
Hospice/Home Health Care
Health Care providers
Public Safety Workers
Opioids: What are we talking about?
Illicit vs. Legal?
Synthetic vs. naturally occurring opioids?
Clinical vs Recreational use?
The Opium Poppy
Use/Abuse goes back At least to 4000 BC
The poppy contains numerous opioid alkaloids
The most common Opioid Alkaloids are:
Opioid Receptors (Continued)
μ (MU) receptors:
◦ Located in the CNS (Brain/Spinal Cord) AND the
◦ CNS depression
◦ ↓ GI Motility (Constipation)
◦ ↑ Euphoria
◦ Located in CNS
◦ Analgesia, Dissascoiation
What is a Toxidrome?
1. a group of symptoms that consistently occur
together or a condition characterized by a set
of associated symptoms.
1. a group of signs and symptoms constituting
the basis for a diagnosis of poisoning.
In other words: A toxidrome is a “syndrome” that specifically relates to a specific toxin
Be cautious, many syndromes/toxidromes are subtle and overlap their symptoms. Thorough assessment is
The Opiate Toxidrome consists of:
Altered mental status
Slow respiratory rate
Decreased bowel sounds
* these symptoms are very subjective, and may not be present in
Miosis and Hypotension are not definitive for ruling in or ruling out a opioid
Methods of use:
Chasing the dragon
◦ With Grapefruit Juice
◦ Laudanum and Perigoric
So why do people overdose?
IV opioid use
Returning to opioid use from abstinence
The Weekend Warrior
Using opioids alone
New supply of Drug
Types of Opioids
The raw Latex (sap) of the poppy plant
Naturally occurring in raw opium
◦ First isolated in 1804
◦ First IV opioid in 1857
The gold standard by which other opioids are
Potent Respiratory / CNS depressant
“Equipotent” euphoria to Heroin, though
Intermediate Duration (3-6 hours)
Many “ER” (extended release) formulations
Codeine naturally occurs in the
Hydrocodone is a semi-synthetic
derivative of codeine. Often
taken as a oral tablet or an elixir
◦ Often co-ingested with an
NSAID (such as APAP, Motrin or
◦ Norco, Vicodin
Homicide, Buick, super Buick, twilight sleep
Old verses New
Oxycodone is Another semi-synthetic
Derived from Thebaine
Roughly twice as potent as Morphine
Also More potent than Hydrocodone
Most often available in Tablet form
◦ Like Hydrocodone, Often co-ingested with an NSAID (such as APAP, Morin or ASA)
Extended release versions known as Oxycodone
Time released capsules, some may have more than 100 mg
Often crushed and snorted, eliminating the “time release”
May be crushed, diluted, and injected like traditional heroin
Becoming much more common
Comparable with Oxycontin and Dilaudid.
Longer acting than most other Analgesic
◦ Typically 4-8 hours
Like other prescription opiates, WIDELY
One study showed of 18 methadone related
◦ Less than ½ were prescribed methadone
◦ Only three were prescribed methadone through a
methadone tx program
◦ Technically found in small quantities in the poppy
◦ Synthesized in 1924 directly from Morphine
Very potent analgesic
Very potent CNS/ Respiratory Depressant
Faster acting than Morphine (similar to Heroin for
rate of onset)
◦ 10 times more potent than Morphine
◦ 5 times more potent than Heroin
Very common medically, Increasingly common recreational
◦ Difficult to detect on standard drug assays
◦ Purely Synthetic
◦ 80-100 times potency of Morphine
Low Euphoric properties
Moderate respiratory/CNS depressant
Both pharmaceutical and illicitly prepared
Rapid Onset, short Duration
Comes in multiple formulations
◦ Typically IV/IM
◦ Oral (lollypops)
◦ Transdermal (Duragesic)
Used in chronic pain patients
100 times the potency of morphine
Commonly Used for chronic pain
Duragesic- methods of abuse
Almost 70 fold increase in use from 1995-2002 (DAWN)
Rate of use is increasing.
Street price between $10-100/PATCH
Methods of abuse
◦ Injected – increased Mortality (Woodall et al, 2007)
Up to 50% may be lost in conversion, so it is often frozen first.
Preservatives may cause liver problems
25 ug/hr = 2.5 mg avail
50 ug/hr = 5 mg avail
75 ug/hr = 7.5 mg avail
100 ug/hr = 10 mg avail
Synthetic Opioid , first described in 1932
Clandestinely produced and derived from Codeine in a method similar to Methamphetamine production
(Relatively) new trend in Eastern Europe/Western Asia Since early 2000’s
Incidence is more directly related to Heroin use than Prescription opioid use
Important note: Huge difference in pharmaceutical Desomophine and illicit “Krocodil”
◦ Actual Krocodil is only 5-20% opioid
Fast Acting (similar to Heroin)
Strong analgesic, Strong Euphoric
◦ 8-10 times analgesia of Morphine, no data on other properties
Potent sedative but Low respiratory depressant
Krocodil in the US?
Much hype, few questions
Production and availability directly tied to availability of pre-cursers (Codiene)
◦ Typically $30-50 of product will render about $500 of end product (European/Western Asia Reports)
Predictions (also known as educated guesses):
Much hype, most likely will fizzle out
Predominantly an IV drug market
Will be misbranded as heroin and mixed with heroin
Will be most common in the users of Black Tar and Low end heroin out of Mexico
We will not see the extensive morbidity and mortality patterns seen in the former USSR due to the
differences in health care and social safety nets as well as differences in Opioid use/abuse demographics
◦ Will still see some (rare) dramatic cases in the homeless/forgotten populations
Much Hype, Little actual Bite to this
Increasingly common practice of mixing one type of opioid (typically Heroin)
with another , more potent opioid.
◦ This increases the “potency” (increasing profit) without increasing the
“purity” (i.e. the cost)
◦ Retains the eurphoric effects of some opioids while getting the heavier nod of
REMEMBER: Opioid overdoses are
AMS calls first, opioid overdoses last
• A - alcohol, alcohol withdrawal, and anoxia
• E . epilepsy and other neurological disorders
• I - insulin (Hyper or Hypo-glycemia)
• O- overdose (Poly-pharmacy?)
• U - uremia, underdose of current medications.
• T- trauma
• I - infection
• P - psychiatric
• S . stroke, shock states
According to DAWN Data:
◦ About 18% of opioid related cases will also have alcohol.
◦ This is about 137% more common now than 10 years ago.
◦ About 10% of opioid related cases will also involve another pharmaceutical
or illicit substance
◦ This is about 84% more common today than 10 years ago
In order to treat an opioid patient we need to understand HOW opioids kill…
Primary Causes of Mortality:
◦ Respiratory failure
◦ Airway Failure
Secondary Causes of Mortality
(Rarely) hypothermia and hypotension
MIS-TREATMENT by providers
Potential Respiratory Effect of Certain Opioids (i.e.
Potential Respiratory Effect of Other Opioids
(i.e. Morphine, Methadone)
Threshold of Respiratory
NOTE: Sufficient quantities of ANY opioid may
induce respiratory compromise!
THIS IS YOUR FIRST LINE
TREATMENT AT ALL LEVELS
Narcan is a Competitive Opioid Antagonist
◦ Synthetic, derived from Thebain since the 1960’s
◦ Competitive means it will KICK OFF Opioids from receptors
Predominantly works on μ (MU) receptors
◦ Minimal effects on other opioid receptors
It will NOT work on other CNS depressants (with few exceptions)
Clinical effects last 20-45 minutes depending on circumstances
◦ Most opioids last longer (exception IV fentanyl)
Some studies on use in Septic Shock and other situations
Slow admin of Narcan, just enough to make them breath
◦ ABSOLUTELY NO PUNATIVE ADMINISTRATION!!!
◦ IV, SL: 0.1-2 mg PRN to a max of 10 mg.*
◦ IN/IM/ETT, IV in cardiac arrest: 2 mg.
◦ 0.01-0.05 mg/kg IV, IO, IM, SubQ, ET. Repeat PRN.
◦ MAX 2 mg/dose
High doses may be needed if drug is synthetic
Watch for re-sedation due to Narcan’s short duration (about 20-30 minutes)
It should be noted that a response to (or failure to
respond) naloxone is not considered a reliable diagnostic
tool in determining if a patient has consumed opoiods.
Failure to respond to a total dose of 10 mg of naloxone
◦ That poisoning is not due to opioids (or opioids alone);
◦Or that hypoxic brain damage has occurred.
◦Or that the AMS is not opioid related at all
Narcan in Cardiac Arrest
Poorly studied but very reasonable
In one AHA study:
Small study , 36 patients
Asytole and PEA were predominant rhythm. Down times varied but were typically extended.
42% of cardiac arrest patients with a suspected opioid etiology showed improvement in EKG rhythm s/p Narcan administration
27% had ROSC by arrival at ER
1% had survival to discharge.
“…Although we cannot support the routine use of naloxone during cardiac arrest, we recommend its administration with any
suspicion of opioid use. Due to low rates of return of spontaneous circulation and survival during cardiac arrest, any potential
intervention leading to rhythm improvement is a reasonable treatment modality.”
◦ Inhibits the adverse effects of the opioids in cardiac arrest, specifically hypotension
◦ Narcan may cause a endogenous sympathetic response (i.e. release of endogenous epinephrine) in the opioid addicted patient
◦ May have indirect, poorly understood antiarrhythmic effects
Source : Resuscitation. 2010 Jan;81(1):42-6. doi: 10.1016/j.resuscitation.2009.09.016. Epub 2009 Nov 13. Naloxone in
cardiac arrest with suspected opioid overdoses. Saybolt MD1, Alter SM, Dos Santos F, Calello DP, Rynn KO, Nelson
DA, Merlin MA.
Narcan, OPIOID Withdrawal, and
OPIOID WITHDRAWAL IS RARELY FATAL.
◦ WHY DO WE HAVE FATAL EVENTS WITH NARCAN INDUCES WITHDRAWAL?
Have you ever heard Narcan causing :
◦ Cardiac Arrest (VT)
MOST (not all ) WITHDRAWAL SYNDROMES ARE RELATED DIRECTLY TO THE EFFECTS OF THE
◦ Then WHY do these S/S occur?
Avoiding BAD OUTCOMES
◦ EPINEPHERINE RELEASE!
RESPIRATORY DEPRESSION CAUSES:
We Treat Sympathetic response by SLOWING DOWN NARCAN
ADMIN with SMALLER DOSES
We treat the RESPIRATORY CAUSES WITH CORRECTIVE BVM
Smaller doses of Narcan?
“The short time between naloxone administration and the occurrence of complications, as well as the type
of complications, are strong evidence of a causal link. In 1000 clinically diagnosed intoxications with heroin
or heroin mixtures, from 4 to 30 serious complications can be expected. “
“…Development of ventricular tachycardia or fibrillation; atrial fibrillation; asystole; pulmonary edema;
convulsions; vomiting; and violent behavior within ten minutes after parenteral administration of
“Such a high incidence of complications is unacceptable and could theoretically be reduced by artificial
respiration with a bag valve device (hyperventilation) as well as by administering naloxone in minimal
divided doses, injected slowly.”
◦ Osterwalder JJ. “Naloxonefor intoxications with intravenous heroin and heroin mixtures: harmless or hazardous? A
prospective clinical study.” J Toxicol Clin Toxicol 34 (1996): 409-416
◦ Cuss FM, Colaço CB, & Baron JH Cardiac arrest after reversal of effects of opiates with naloxone. Br Med J, 288(1984):
Narcan infusions are a MAINTANANCE therapy, ideal for LONG transports (20-30 minutes or greater)
Many different methods/compositions/protocols
Administer NARCAN as normal to achieve respiratory and airway stability
Mix the TOTAL effective dose in 100 cc (or 250 cc) NS
Set rate to infuse over 1 hour
◦ 100 cc Bag: 90 gtts a minute ( 1.5 gtt/sec)
◦ 250 cc Bag: 250 gtts a minute (4 gtts / sec)
If re-sedation occurs:
◦ Evaluate for other causes
◦ Titrate upward for effect
◦ Rebolus IV Narcan
LAYPERSON/ BLS Narcan?
IM clinically safer than IN
◦ Both should be an option
NARCAN Treat & Release Criteria
◦ The patient can mobilize as usual;
◦ The patient has an oxygen saturation on room air of >92%; 3) have a respiratory rate >10 breaths/min and <20
◦ The patient has a temperature of >35.0°C and <37.5°C;
◦ The patient has a heart rate >50 beats/min and <100 beats/min; and
◦ The patient has a Glasgow Coma Scale score of 15.
◦ Follow up with IM (or SQ) Narcan
◦ Christenson J, Etherington J, Grafstein E, et al. Early discharge of patients with presumed opioid overdose:
development of a clinical prediction rule. Acad Emerg Med 2000;7(10);1110-18.
◦ Wanger K, Brough L, MacMillan I, et al. Intravenous vs subcutaneous naloxone for out-of-hospital management of
presumed opioid overdose. Acad Emerg Med 1998;5(4);293-9.
When to avoid Narcan all together
Semi- Awake patients
POLY PHARM OD’s
It is generally unwise to treat these patients with an opioid antagonist unless life threatening
respiratory depression is a reasonable concern..
"Inappropriate use of naloxone in cancer patients with pain.."
J Pain Symptom Manage. 11(2)(1996): 131-134.
In the End
Stay up to date
Don’t believe the Hype
Overdose patients are AMS patients first, opioid overdoses last
CORRECT HYPOXIA, ACIDOSIS , HYPERCARBIA BEFORE NARCAN
When giving Narcan: SLOW and LOW (Slow Push and Low Doses repeated)
◦ Goal is airway and respiratory correction, not to wake them up