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Opiate Overdose & Intranasal Naloxone Protocol
Amy Gutman MD ~ EMS Medical [email protected] / www.TEAEMS.com
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OBJECTIVES
• Review opiate pharmacology
• Review Naloxone / Narcan pharmacology
• Review needlestick injuries
• Review intranasal route advantages & pathophysiology
Fail!
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OPIOIDS / OPIATES
• Among oldest known drugs (i.e. poppy flowers)
• Analgesic effects of medications that stimulate brains’ “mu-opiod receptors” decreasing pain perception & increasing pain tolerance
• Therapeutic usage of opiods are for pain & cough suppression
• Side effects are potentially lethal, including sedation, hypotension, histamine reaction, respiratory depression, & euphoria (usually assoc with poor judgment)
• Dependence develops with ongoing administration, leading to a withdrawal syndrome with abrupt discontinuation (“Dope Sick”)– N/V, tremor, seizure, tachycardia, HTN, diaphoresis, agitation, anxiety– Opioid-induced hyperalgesia syndrome is paradoxically worsening pain as a result of
rapidly escalating dosage (often due to dependence)
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0
200
400
600
800
1000
1200
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
Dea
ths p
er y
ear
All Poisoning Deaths Motor Vehicle-Related Injury Deaths
*Registry of Vital Records and Statistics, MA DPH
Poisoning Deaths vs. Motor Vehicle-Related Injury Deaths, MA Residents (1997-2008)
MORE OPIOID OD DEATHS THAN MVC DEATHS IN MA*
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NEEDLESTICK INJURIES• CDC estimates >600,000 annual injuries involving contaminated sharps– High risk patients & high risk environments– AMS / combative– Scene control issues– Moving ambulance
• OSHA’s Needlestick Safety and Prevention Act (2001) & Occupational Exposure & Bloodborne Pathogens Standard (1991)
– “to reduce or eliminate hazards of occupational exposure, an employer must implement an exposure control plan…The plan must describe how an employer will use a combination of engineering & work practice controls. Engineering controls are the primary means & include use of safer medical devices”
– “Employees responsible for direct patient care must have input into employer decisions about WHICH engineering controls to adopt”
• Intranasal systems meet OSHA recommendations to improve occupational exposures by reducing Level III bloodborne exposures (HIV, hepatitis) by decreasing needlestick injuries
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IN DELIVERY ADVANTAGES
• Simple, rapid, convenient
• Nose is easy access point
• Minimal training required
• Painless
• Eliminates needlestick risk
• Compared to oral medications: – Faster bloodstream delivery– Higher blood levels– No destruction by stomach acid &
intestinal enzymes– No destruction by hepatic 1ST pass
metabolism
• Compared to IV medications:– Comparable blood levels – Higher brain levels if well absorbed
across nasal mucosa
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Naloxone should be made more widely available to trained laypersons in an effort to reduce deaths due to opioid overdose
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IN EFFECTIVENESS
• Olfactory mucosa in direct contact with brain
• This area termed “Nose-Brain-Pathway”, providing a rapid, direct route for CNS drug delivery
• Nasal mucosa has a large surface area, leading to high bioavailability
• Drugs absorbed via the nasal mucosa absorbed via rich nasal vascular plexus entering directly into brain circulation & CSF giving almost immediate high drug levels
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IN PHARMACOKINETICS
• Bioavailability– How much of the administered medication actually ends up in the blood stream– Oral meds 5%-25% bioavailable due to destruction in GI tract / liver– Intravenous / intraosseous meds usually 100% bioavailable– Intranasal meds 55% -100% bioavailable
• Not all drugs can be delivered via the nasal mucosa– Particle size– Volume – Concentration– Lipophilicity– pH (acidity)– Properties of the solution drug is solubilized within – Nasal mucosal characteristics
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IN MEDICATION CHARACTERISTICS
• 1st Pass Metabolism:– Molecules absorbed through GI tract into
liver “portal circulation” – Liver enzymes break down drug so little
“active med” enters bloodstream – IN meds avoid GI tract & 1st pass
metabolism
• Lipohilicity / “Lipid Loving”– Cell membranes composed of lipid layers– Lipophilic meds easily & rapidly absorbed
across mucous membranes
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IN MED CHARACTERISTICS
• Low volume, high concentration– Too large a volume or too weak a
concentration leads to failure as drug cannot be absorbed in high enough quantity to be effective
– Volumes >1ml per nostril too dilute & result in “runoff”
• If abnormal nasal mucosa drugs not absorbed effectively– Vasoconstriction from cocaine– Bloody nose, nasal congestion, mucous
discharge prevent drug mucosal contact – Destruction of mucosa from surgery or
injury prevent drug mucosal contact
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IN ABSORBTION
• IN naloxone absorption almost as fast as IV in animal & human models
• Hussain et al, Int J Pharm, 1984• Loimer et al, Int J Addict, 1994• Loimer et al, J Psychiatr Res, 1992
• “Atomization” of medications with better absorption via IN route
• Thorsson et al, Br J Clin Pharmacol, 1999
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IN DELIVERY SYSTEM CHARACTERISTICS
• Particle size– 10-50 microns best adheres to nasal mucosa– Smaller particles pass on to the lungs– larger particles form droplets & form run-off
• Atomization has higher bioavailability than either spray or drops
• The Mucosal Atomization Device (MAD) is the most common commercially available atomization device on the market– 30-60 micron spray ensure excellent mucosal coverage, stay in airstream & not “drift”
down to lungs– Single-use & disposable – Fits on standard syringe
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What Meds Can Be Used IN?• FDA has approved many medications
for IN use– Steroids, antibiotics, anesthetics,
antihistamines
• Non-FDA approved: – Many meds effective but
pharmaceutical companies have not pursued FDA IN clearance
• Drugs of interest to EMS systems:– Naloxone (Narcan)– Midazolam (Versed)– Glucagon
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Naloxone / Narcan• Opioid antagonist used to counteract life-
threatening CNS & respiratory depression
• Extremely high affinity for CNS μ-opioid receptors as a competitive antagonist producing rapid opiate withdrawal
• Most commonly injected IV for fastest action (within 1 min); SQ and IM slower & less predictable effects
• Use as an IN spray is “off-label”, but with significant evidence of effectiveness
• Effects last 20-45 mins; often requires re-dosing
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NALOXONE SIDE EFFECTS
• Puking, puking, puking
• 2-3% develop acute pulmonary edema & respiratory arrest
• Acute withdrawal may cause your unconscious patient to become violent, combative…& may require sedation (or police, or restraints….)
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Barton et al. “Intranasal Administration of Naloxone by Paramedics” PEC, 2002
• “The Denver Experience” of 600-800 IV doses of naloxone annually
• Sheathed needles not used or disposed of properly
• Study purpose was to test efficacy of prehospital IN naloxone– Number of IN responders? – Time to patient response?– How many required repeat doses?– Determine % IV placements that could
potentially be avoided
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STUDY METHODS
• Clinical indicators for naloxone: “Found down” (FD), “Suspected overdose” (OD), “Altered mental status” (AMS)
• Patients given 2mg IN naloxone at 1st contact– 1mg via MAD into each nostril (2mg of
2mg/2ml solution)– Same dose as IV protocol– Standard protocols followed including airway
management, establish IV, IV meds (naloxone, D50) if needed
– Medics could discontinue protocols if patient responded
– Times of initial pt contact, IN naloxone, IV placement, IV naloxone & pt response were recorded to nearest minute
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STUDY RESULTS & CONCLUSIONS
• 43/52 (83%) = “IN Naloxone Responders.”– Mean time to effect = 4 mins (range 1-11 mins)– Mean time from 1st contact = 10 mins– 12/43 (29%) no IV naloxone required– 7/43 (16%) required additional dose of IV naloxone due to recurring somnolence, slow
response, leakage of medication
• 9/52 (17%) = “IN Non-responders.”– 4 pts with “epistaxis,” “trauma,” or “septal abnormality”
• Conclusions– IN naloxone effective route with 83% prehospital response– Inexpensive device, easy to use– Decreased prehospital blood exposures
• 29% no IV required in a high risk population
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UTILIZING IN MAD NALOXONE
• Draw up solution / prefilled synringes of 2 mg/2 ml)
• Expel air from syringe
• Attach MAD device via luer lock
• Briskly compress the syringe plunger for controlled atomization• 1 ml up each nostril in rapid succession
– May require a 2nd dose (Medical Control)
– Do not forget all standard AMS protocol steps, including glucose measurement, stroke scale, trauma & medical emergency evaluation
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References
• Walley A. MD, MSc Assistant Professor of Medicine, Boston University School of Medicine
• Weber JM. Can nebulized naloxone be used safely and effectively by emergency medical services for suspected opioid overdose? PEC. 2012. Apr-Jun;16(2):289-92
• www.drugs.com• www.wikipedia.com• Barton ED, et al. Efficacy of intranasal naloxone as a needleless
alternative for treatment of opioid overdose in the prehospital setting. J Emerg Med. 2005 Oct;29(3):265-71.
• www.intranasal.net• www.lmana.com
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[email protected] / www.TEAEMS.com
• Immediately on decision to treat inject naloxone into nose with MAD, then begin standard AMS care
• Successful awakening eliminates the need for any IV
• Awakening gradual or abrupt, but adequate respiratory efforts occur rapidly
• Not 100% effective so failures with IN naloxone need to be followed with IV naloxone