2016 Eastern Oregon EMS ConferenceOpioids: Do’s and Don'ts

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"Among the remedies which it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium." -Thomas Sydenham (1624-1689)

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Objectives• 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

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• Steve Cole• croaker260@gmail.com

• Ada County Paramedics for 17 years

• EMS for 25 (and counting)

years

Disclaimer• I have no financial conflicts of interest

• This presentation is not a substitute for basic clinical judgment.

• Follow your protocols!

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Before we get started…..

• Doing your own research…• Knowing where to look• Staying up to date

Educating Yourself….

EMS Textbooks SUCK!

?

WWW.EROWID.ORG

Epidemiology

• 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 2011Source: 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– Visitors– Family– Health Care providers– Public Safety Workers– Professional Patients.

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:• Morphine (1-10%)• Codeine• Thebaine• Oripavine

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Opioid Receptors

Source: http://www.iuphar-db.org/DATABASE/FamilyIntroductionForward?familyId=50

What is a Toxidrome?

What is a Toxidrome? syn·drome (ˈsinˌdrōm/) noun

1. a group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms.

tox·i·drome (ˈtäksiˌdrōm/)

noun

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 toxinBe cautious, many syndromes/toxidromes are subtle and overlap their symptoms. Thorough assessment is essential

Opioid Toxidrome

• The Opiate Toxidrome consists of:– Altered mental status – Miosis*– Unresponsiveness – Shallow respirations – Slow respiratory rate – Decreased bowel sounds – Hypothermia– Hypotension*

• * these symptoms are very subjective, and may not be present in polypharmacy overdoses.

KEY POINT: Miosis and Hypotension are not definitive for ruling in or ruling out a opioid overdose.

Methods of use:

• Shooting• Skin Popping• Muscle Popping• Chasing the dragon• Freebasing• Plugging and Shelving• Dirty Hit• Tea

– With Grapefruit Juice• Tincture

– Laudanum and Perigoric

So why do people overdose?

• IV opioid use• Poly-pharmacy Overdose• Returning to opioid use from abstinence – Jail?– Detox?

• The Weekend Warrior• Using opioids alone • New supply of Drug

Types of Opioids

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Opium

• The raw Latex (sap) of the poppy plant

• The latex has:– Morphine– Thebaine– Codeine, – Oripavine

Source: http://www.aaronhuey.com/#/editorial-archive/afghanistan-drug-war/Opium_032

Morphine •Naturally occurring in raw opium• First isolated in 1804• First IV opioid in 1857

•The gold standard by which other opioids are judged

•Potent Respiratory / CNS depressant

•“Equipotent” euphoria to Heroin, though slower onset.

•Intermediate Duration (3-6 hours)

•Many “ER” (extended release) formulations

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Codeine, Hydrocodone•Codeine naturally occurs in the poppy plant•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 ASA)•Norco, Vicodin

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Sizzurp (Codeine, ETOH, and Phenergan mixes

Heroin• Black Tar• China White• Speed Ball• Homicide, Buick,

super Buick, twilight sleep

Old verses New

By Todd Huffman from Phoenix, AZ - Needle Exchange, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=5170947

Oxycontin/Oxycodone•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)• Percocet

•Extended release versions known as Oxycodone • “Oxy”

•May be crushed, diluted, and injected like traditional heroin

Methadone•Synthetic opioid•Comparable with Oxycontin and Dilaudid. •Longer acting than most other Analgesic• Typically 4-8 hours

•Like other prescription opiates, WIDELY Available•One study showed of 18 methadone related deaths:• Less than ½ were prescribed methadone• Only three were prescribed methadone

through a methadone tx program

Dilaudid•Hydromorphone

•Semi-Synthetic Opioid• Technically found in small

quantities in the poppy plant• Synthesized in 1924 directly from

Morphine

•Very potent analgesic

•Very Euphoric

•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

Fentanyl Citrate

Fentanyl• Synthetic opioid• Transdermal Absorption• Used in chronic pain patients• 100 times the potency of morphine• Commonly Used for chronic pain• Easily Acquired• Easily abused

Duragesic: Another form of Fentanyl

Poly-Opioid Mixes• 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 others.

Photo credit: NPR.orgTamika Moore/AL.com/Landov

Krocodil

Krocodil•Desomorphine• 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)•Short Duration•Strong analgesic, Strong Euphoric• 8-10 times analgesia of Morphine, no data on other properties

•Potent sedative but Low respiratory depressant

Much Hype, Little actual Bite to this Krocodil

Krocodil in the prisons?

Suboxone

• Buprenorphine- Partial Agonist• Naloxone – Antagonist • Ceiling effect• Precipitated withdrawal if injected

TREATMENT

REMEMBER: Opioid overdoses are AMS calls first, opioid overdoses last

A - alcohol, alcohol withdrawal, and anoxiaE -epilepsy and other neurological disordersI - insulin (Hyper or Hypo-glycemia)O - overdose (Poly-pharmacy?)U - uremia, underdose of current medications.T - traumaI - infectionP - psychiatricS - stroke, shock states

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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• Aspiration • (Rarely) hypothermia and hypotension • Situational Factors• MIS-TREATMENT by providers

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Effec

t

Time

Potential Respiratory Effect of Certain Opioids (i.e. Heroin, Dilaudid)

Potential Respiratory Effect of Other Opioids (i.e. Morphine, Methadone)

NOTE: Sufficient quantities of ANY opioid may induce respiratory compromise!

Threshold of Respiratory Arrest/Failure

THIS IS YOUR FIRST LINE TREATMENT AT ALL LEVELS

Don’t Forget this

Or this…

Narcan (Naloxone)

• “Precipitated Withdrawal”

• 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

Narcan (Naloxone)•Ventilation/stimulation first•Slow admin of Narcan, just enough to make them breath• ABSOLUTELY NO PUNATIVE ADMINISTRATION!!!

•Adult:• IV, SL: 0.1-2 mg PRN MAX Single dose of 0.4-0.5 mg. • Max total dose 10 mg.*• IN/IM/ETT, IV in cardiac arrest: 2 mg.

•Pediatrics:• 0.01-0.05 mg/kg IV, IO, IM, SubQ, ET. Repeat PRN.• MAX 0.4-0.5 mg/dose

•High (total) doses may be needed if drug is synthetic•Watch for re-sedation due to Narcan’s short duration (about 20-30 minutes)

KEY POINT:

•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 opioids.

•Failure to respond to a total dose of 10 mg of naloxone usually indicates:• 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

• (A-E-I-O-U-T-I-P-S)

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AHA statement

• Naloxone is a potent antagonist of the binding of opioid medications to their receptors in the brain and spinal cord. Administration of naloxone can reverse central nervous system and respiratory depression caused by opioid overdose. Naloxone has no role in the management of cardiac arrest.

Narcan doesn’t help in Cardiac Arrest, Or does it?•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.”

•Why?• 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.

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Narcan, OPIOID Withdrawal, and adverse events?•OPIOID WITHDRAWAL IS RARELY FATAL.• WHY DO WE HAVE FATAL EVENTS WITH NARCAN INDUCES WITHDRAWAL?

•Have you ever heard Narcan causing :• Seizures• Cardiac Arrest (VT)• Stroke?

•MOST (not all ) WITHDRAWAL SYNDROMES ARE RELATED DIRECTLY TO THE EFFECTS OF THE DRUG/SUBSTANCES INVOLVED.• Then WHY do these S/S occur?

•FOUR REASONS:• SYNPATHETIC RESPONSE• HYPOXIA• HYPERCARBIA• ACIDOSIS

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Avoiding BAD OUTCOMES•SYNPATHETIC RESPONSE• EPINEPHERINE RELEASE!

•RESPIRATORY DEPRESSION CAUSES:• HYPOXIA• HYPERCARBIA• ACIDOSIS

•We Treat Sympathetic response by SLOWING DOWN NARCAN ADMIN with SMALLER DOSES•We treat the RESPIRATORY CAUSES WITH CORRECTIVE BVM THERAPY!

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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 naloxone.”•“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.”• •Source: • 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): 363-364

Narcan Infusions?•Narcan infusions are a MAINTANANCE therapy, ideal for LONG transports (20-30 minutes or greater)

•Many different methods/compositions/protocols

•Administer BOLUS NARCAN as normal to achieve respiratory and airway stability. THEN give infusion

•Add 2mg of naloxone to 500ml of normal Saline or Dextrose 5% •(this gives a final concentration of 4 micrograms/ml). •Usual starting infusion rate is 25- 100ml/hr (100- 400micrograms/hr). •Rate of infusion should be adjusted according to the response.

NARCAN Treat & Release Criteria• 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 breaths/min; • 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

•References:• 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.

LAYPERSON/ BLS Narcan?

Thoughts

•IM clinically safer than IN• Both should be an option

•Protocols/Training should mandate BVM/Airway Management first

When to avoid Narcan all together

• Semi- Awake patients• Pregnancy• Aspiration• POLY PHARM OD’s

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If the patient is “awake” Narcan is not needed

Or you may get this…

NARCAN BAD…

MAY CAUSE ABRUPTED PLACENTA/ PRE-TERM LABOR/FETAL DISTRESS

NARCAN BAD…AIRWAY MANAGEMENT GOOD

ETT Better!

Other causes more likely, Use very small doses of Narcan as a last resort

Source: http://www.elephantjournal.com/2013/10/love-it-all-a-husbands-farewell-to-his-dying-wife-photos/

It is generally unwise to treat these patients with an opioid antagonist unless life threateningrespiratory 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

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Questions?

Source: http://paindr.com/wp-content/uploads/2013/04/Poppy-smiley-157x195.jpg

Links• https://www.youtube.com/watch?v=1yPrGNr4TQY • https://www.youtube.com/watch?v=sMuvTlU_mJg • https://www.youtube.com/watch?v=Mo6cfAnP7sc • https://www.youtube.com/watch?v=EFZzX9J_wXg • https://www.youtube.com/watch?v=WaAnGXRvv80 • https://www.youtube.com/watch?v=veomoaFzroc • https://www.youtube.com/watch?v=8a18abrzpEY