Opiate overdose can occur from drugs extracted from the poppy plant or synthetic opioids. Symptoms include decreased breathing, sedation, small pupils, and decreased heart rate and blood pressure. Evaluation involves checking vitals, lung exam, and neurological exam. Treatment is with naloxone to reverse respiratory depression and intubation if needed to protect the airway. Naloxone may need to be continued as an infusion if respiratory depression recurs, and patients can typically be discharged once breathing and mental status have normalized without further naloxone for 2-3 hours.

1. Opiate OverdoseOpiate Overdose
Dr. Hein Yarzar AungDr. Hein Yarzar Aung
Consultant PhysicianConsultant Physician
Medical Unit 1Medical Unit 1
Yangon General HospitalYangon General Hospital

2. Papaver somniferumPapaver somniferum , Opium poppy, common poppy, Opium poppy, common poppy

3. Opiate OverviewOpiate Overview
 Opiates are extracted from the poppy plantOpiates are extracted from the poppy plant
Papaver somniferumPapaver somniferum..
 Opiates belong to a larger class of drugs, theOpiates belong to a larger class of drugs, the
opioids, which include synthetic and semi-opioids, which include synthetic and semi-
synthetic drugssynthetic drugs
 Opioid pharmaceuticals are analagous to theOpioid pharmaceuticals are analagous to the
three families of endogenous opioid peptides:three families of endogenous opioid peptides:
enkephalins, endorphins, and dynorphinenkephalins, endorphins, and dynorphin
 There are three major classes of opioidThere are three major classes of opioid
receptor, with several minor classes (receptor, with several minor classes (μμ,, κκ,, δδ,,
nociceptin/orphanin)nociceptin/orphanin)

4. Opiate OverviewOpiate Overview
 Receptors in CNS and PNS; linked to variety ofReceptors in CNS and PNS; linked to variety of
neurotransmittersneurotransmitters
 Analgesic effectAnalgesic effect
 Inhibition of nociceptive information at points ofInhibition of nociceptive information at points of
transmission from peripheral nerve to spinal cord totransmission from peripheral nerve to spinal cord to
brainbrain
 Euphoric effectEuphoric effect
 From increased dopamine released in mesolimbicFrom increased dopamine released in mesolimbic
systemsystem
 Anxiolysis EffectAnxiolysis Effect
 From effect of noradrenergic neurons in locusFrom effect of noradrenergic neurons in locus
ceruleusceruleus

5. Opiate kineticsOpiate kinetics
 Variable protein binding (89% methadone, 7.1%Variable protein binding (89% methadone, 7.1%
hydrocodone)hydrocodone)
 Given volume of distribution, difficult to remove viaGiven volume of distribution, difficult to remove via
hemodialysishemodialysis
 Most are renally eliminatedMost are renally eliminated
 Many metabolized in liver to active metabolitesMany metabolized in liver to active metabolites
 Hydrocodone metabolized to hydromorphone by CYP2D6Hydrocodone metabolized to hydromorphone by CYP2D6
 Morphine metabolized to morphine-6-glucuronideMorphine metabolized to morphine-6-glucuronide
 Overdose issuesOverdose issues
 If multiple tablets are taken, dissolution and absorption will beIf multiple tablets are taken, dissolution and absorption will be
delayed, prolonging the apparent half-life.delayed, prolonging the apparent half-life.
 Duration of action may be shortened in overdoseDuration of action may be shortened in overdose
 Ex: when sustained release formulation of oxycodone isEx: when sustained release formulation of oxycodone is
crushed before ingestion, the drug is rapidly absorbed.crushed before ingestion, the drug is rapidly absorbed.

6. Opioid IssuesOpioid Issues
 NaturalNatural
 Morphine (1.9h), codeine (2.9h)Morphine (1.9h), codeine (2.9h)
 Metabolized to active drug morphine in liverMetabolized to active drug morphine in liver
 Semi-syntheticSemi-synthetic
 Hydromorphone (2.4h), oxycodone (2.6h), hydrocodone (4.24h),Hydromorphone (2.4h), oxycodone (2.6h), hydrocodone (4.24h),
diacetylmorphine (heroin)diacetylmorphine (heroin)
 SyntheticSynthetic
 Meperidine (3.2h)Meperidine (3.2h)
 Excitatory neurotoxicity may occur when the renally excreted metabolite,Excitatory neurotoxicity may occur when the renally excreted metabolite,
normeperidine, accumulates. Seizures and serotonin syndrome.normeperidine, accumulates. Seizures and serotonin syndrome.
 Methadone (27h)Methadone (27h)
 Very long acting; may cause QT prolongation, torsades de pointesVery long acting; may cause QT prolongation, torsades de pointes
 PropoxyphenePropoxyphene
 Seizures, IA antidysrhythmic properties (leads to widened QRS and negativeSeizures, IA antidysrhythmic properties (leads to widened QRS and negative
inotropy)inotropy)
 Tramadol (5.5h)Tramadol (5.5h)
 Effects not completely revered by naloxone, seizuresEffects not completely revered by naloxone, seizures
 Fentanyl (3.7h)Fentanyl (3.7h)
 Ultrashort actingUltrashort acting

7. The Physical ExamThe Physical Exam
 VitalsVitals
 HR decreased or unchangedHR decreased or unchanged
 BP decreased or unchangedBP decreased or unchanged
 RR decreased (decreased tidal volume)RR decreased (decreased tidal volume)
 Temp decreased or unchangedTemp decreased or unchanged
 GIGI
 Decreased bowel soundsDecreased bowel sounds
 NeurologicalNeurological
 Sedation or comaSedation or coma
 Seizure (meperidine, propoxyphene, tramadol, or 2/2 hypoxia)Seizure (meperidine, propoxyphene, tramadol, or 2/2 hypoxia)
 OphthalmologicOphthalmologic
 miosismiosis

8. PE Points to PonderPE Points to Ponder
 Users of meperidine and propoxyphene may have nl pupils, andUsers of meperidine and propoxyphene may have nl pupils, and
presence of coingestants (sympathomimetics or anticholinergics)presence of coingestants (sympathomimetics or anticholinergics)
may make pupils normal or large.may make pupils normal or large.
 Best predictor of opioid poisoning is RR<12 (predicted responseBest predictor of opioid poisoning is RR<12 (predicted response
to naloxone in one study)to naloxone in one study)
 Mild hypotension (from histamine release) may be presentMild hypotension (from histamine release) may be present
 Hypothermia results from combination of environmental exposureHypothermia results from combination of environmental exposure
and impaired thermogenesis may be presentand impaired thermogenesis may be present
 In severely obtunded patients, room temperature may produceIn severely obtunded patients, room temperature may produce
significant hypothermiasignificant hypothermia
 Elevated temperature may suggest early aspiration pneumonia orElevated temperature may suggest early aspiration pneumonia or
complications if IVDU (endocarditis)complications if IVDU (endocarditis)
 Rales may indicate the presence of aspiration or acute lung injuryRales may indicate the presence of aspiration or acute lung injury
 Examine the skin for medication patches that must be removed,Examine the skin for medication patches that must be removed,
track marks, or soft tissue infectionstrack marks, or soft tissue infections

9. Opiate OverdoseOpiate Overdose
 LabsLabs
 Check serum glucoseCheck serum glucose
 Serum APAP levelSerum APAP level
 Salicylate level (consider if tachypnea or incr anion gap)Salicylate level (consider if tachypnea or incr anion gap)
 CK (to exclude rhabo in setting of prolonged immobilization)CK (to exclude rhabo in setting of prolonged immobilization)
 Serum creatinineSerum creatinine
 ElectrolytesElectrolytes
 Urine toxicology screenUrine toxicology screen
 Should not be routinely obtainedShould not be routinely obtained
 Positive test can indicate recent use but not current intoxication, or may represent false negativePositive test can indicate recent use but not current intoxication, or may represent false negative
 Many opioids (especially synthetics) will produce false negative results in commonly availableMany opioids (especially synthetics) will produce false negative results in commonly available
urine screensurine screens
 EKGEKG
 Propoxyphene can produce prolongation of QRS and is responsive to sodiumPropoxyphene can produce prolongation of QRS and is responsive to sodium
bicarbonatebicarbonate
 Methadone can cause prolonged QTc and TorsadesMethadone can cause prolonged QTc and Torsades
 CXRCXR
 Reserved for those patients with adventitious lung sounds or hypoxia that does notReserved for those patients with adventitious lung sounds or hypoxia that does not
correct when ventilation is addressed.correct when ventilation is addressed.
 May eval for body packing and stuffingMay eval for body packing and stuffing

10. MgmtMgmt
 Initial focus on airway and breathingInitial focus on airway and breathing
 Administer IV naloxoneAdminister IV naloxone
 Apneic pts and pts with extremely low RR should be ventilatedApneic pts and pts with extremely low RR should be ventilated
by bag-valve mask attached to O2 to reduce ALI.by bag-valve mask attached to O2 to reduce ALI.
 Apneic pts should receive 0.2-1mgApneic pts should receive 0.2-1mg
 Pts in cardiopulmonary arrest should be given minimum ofPts in cardiopulmonary arrest should be given minimum of
2mg2mg
 When spontaneous ventilations are present, give initial dose ofWhen spontaneous ventilations are present, give initial dose of
0.05mg and titrate upward every few minutes until RR >12.0.05mg and titrate upward every few minutes until RR >12.
 The goal of naloxone is NOT a nl level of consciousness,The goal of naloxone is NOT a nl level of consciousness,
but adequate ventilation.but adequate ventilation.
 In the absence of signs of opioid withdrawal, there is noIn the absence of signs of opioid withdrawal, there is no
maximum safe dose; if clinical effect does not occur after 5-maximum safe dose; if clinical effect does not occur after 5-
10mg, reconsider your diagnosis.10mg, reconsider your diagnosis.

11.  Naloxone InfusionNaloxone Infusion
 If hypoventilation recurs following initial bolus, give additionalIf hypoventilation recurs following initial bolus, give additional
boluses to restore adequate ventilation.boluses to restore adequate ventilation.
 When ventilation is adequate, an infusion may be initiated at aWhen ventilation is adequate, an infusion may be initiated at a
rate of 2/3 the total dose of naloxone needed to restorerate of 2/3 the total dose of naloxone needed to restore
breathing, delivered every hourbreathing, delivered every hour
 If respiratory depression develops despite an infusion,If respiratory depression develops despite an infusion,
administer naloxone bolus (using ½ the original bolus dose)administer naloxone bolus (using ½ the original bolus dose)
and repeat if necessary until adequate ventilation returns, thenand repeat if necessary until adequate ventilation returns, then
increase the infusion rateincrease the infusion rate

12. MgmtMgmt
 Activated charcoal and gastric emptying are almostActivated charcoal and gastric emptying are almost
never indicated in opioid poisoningnever indicated in opioid poisoning
 The large volume of distribution of opioids precludesThe large volume of distribution of opioids precludes
removal of a significant quantity of drug byremoval of a significant quantity of drug by
hemodialysishemodialysis
 In most cases, the pt may be discharged or transferredIn most cases, the pt may be discharged or transferred
for psychiatric evaluation once respiration and mentalfor psychiatric evaluation once respiration and mental
status are normal and naloxone has not beenstatus are normal and naloxone has not been
administered for 2-3 hrsadministered for 2-3 hrs

13.  Thank youThank you