Opioids: Old Friends and NewEASTERN 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 as opium." -THOMAS SYDENHAM (1624-1689)

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

Who am I? Steve Cole croaker260@gmail.com Ada County Paramedics for 15 years

EMS for 23 (and counting) years

Disclaimer I have no financial conflicts of interest This presentation is not a substitute for basic clinical judgment. Follow your protocols!

Before we get started….. Doing your own research… Knowing where to look Staying up to date

Educating Yourself….

EMS Textbooks SUCK!

?

http://www.samhsa.gov/data/DAWN.aspx Hundreds of Metropolitan/Suburban Hospitals and Coroners/ME offices across the US.

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;◦ Dietary supplements;◦ Non-pharmaceutical inhalants;◦ Alcohol in combination with other drugs (adults and children)◦ Alcohol alone (age < 21).

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 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◦ 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

Opioid Receptors

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

Opioid Receptors (Continued) μ (MU) receptors:

◦ Located in the CNS (Brain/Spinal Cord) AND the digestive tract.

◦ CNS depression◦ Analgesia◦ ↓ GI Motility (Constipation)◦ ↑ Euphoria

ⱪ (Kappa) Receptors:◦ Located in CNS◦ Analgesia, Dissascoiation◦ DYSphoria,

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

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

Opium The raw Latex (sap) of the poppy plant

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

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

Heroin Black Tar

China White

Speed Ball

Homicide, Buick, super Buick, twilight sleep

Old verses New

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”

Oxycontin /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

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 Very common medically, Increasingly common recreational abuse

◦ Difficult to detect on standard drug assays◦ Purely Synthetic

Potent Analgesic◦ 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)

Duragesic Fentanyl Citrate

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- 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◦ Topical◦ Injected – increased Mortality (Woodall et al, 2007)◦ Chewed

Oral Conversion◦ 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

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

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 Krocodil

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.

Treatment

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

Important note: 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

Why?

Treatment 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

Effec

t

Time

Threshold of Respiratory Arrest/Failure

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!

THIS IS YOUR FIRST LINE TREATMENT AT ALL LEVELS

Narcan (Naloxone) 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 to a max of 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 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)

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 opoiods. 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)

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.”

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.

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

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!

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 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?

Thoughts IM clinically safer than IN

◦ Both should be an option

Protocols/Training should mandate BVM/Airway Management first

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.

When to avoid Narcan all together

Semi- Awake patients

Pregnancy

Aspiration

POLY PHARM OD’s

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

Questions?

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