Is My Patient Drugged? Identifying Drugs of Abuse in the ED
James H. Nichols, PhD, DABCC, FACBProfessor of Pathology, Microbiology, and Immunology
Medical Director, Clinical ChemistryAssociate Medical Director of Clinical Operations
Vanderbilt University School of MedicineNashville, TN 37232‐5310
Objectives
• Identify common drugs of abuse• Describe laboratory methods for screening and confirmation of drugs of abuse
• Discuss DAU test cross‐reactivity and reasons for false‐positive or false‐negative results.
Case• 24 y/o male found lying on floor unresponsive. Family at scene tell EMT
that he may have used drugs.• BP 124/80, pulse 104, respiration 12 and shallow. Glascow coma score 3,
pupils constricted and non‐reactive. Skin cool and cyanotic. Glucose 55. IV dextrose and 5.2 mg Narcan started en route to hospital
• On triage in hospital, patient was alert and responsive. BP 117/88, temp 97.4, pulse 111, respiration 24. O2 Sat 98% on room air. Patient denied symptoms, not sure why he was brought to ED. Denied medical problems and couldn’t remember taking any medications.
• Later during exam by ED physician, admitted to accidentally “smoking too much” heroin! Denied suicidal ideations, normal neurologic and mentation. Urine tox screen positive for cocaine and opiates. Patient monitored for 5 hours, normal breathing, no dyspnea, discharged to wife who was bedside by this time.
American College of Emergency Physician’s Case
Audience Poll
• What opiate metabolite indicates heroin ingestion?A. BenzoylecgonineB. MethadoneC. 6‐MonoacetylmorphineD. Methamphetamine
The Obtunded Patient• Metabolic and toxic physiologic disturbances
– Acid‐base disequilibrium– Disorders of oxygen or glucose metabolism– Uremic and hepatic encephalopathy– Drug overdose and poison ingestion
• Epilepsy and post‐convulsive states• Cerebrovascular disorders (stroke, hemorrhage)• Infection (meningitis, encephalitis)• Head injury (including tumors)• Good H & P and lab testing can help sort differential
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Urine Drug Testing• Clinical – for patient management• Forensic – for legal purposes• Random urine sample, no additives• Sequential analysis
– Initial immunoassay “screen”– Confirmatory Mass Spectrometry “confirmation”
• Screening tests primarily immunoassays with broad spectrum antibodies to detect class of similar drugs
• Confirmatory testing is more specific and sensitive to isolate individual drugs – Typically GC/MS, HPLC/MS/MS
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Screening Immunoassays• Fast, inexpensive, can be run on random‐access, general chemistry analyzers
• Homogeneous IA – no separation of bound/free Abs• Subject to cross‐reactivity with drugs and other molecules of similar structure (may not even be related to target drug)
• Defined cutoff –– Positive above cutoff concentration, move on to confirmation– Negative below cutoff – end of testing
• Protein antibodies – can be denatured with adulterants like strong acids, bases, salts added to sample
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KIMS: Kinetic Interaction of Microparticles in SolutionPETINIA: Particle Enhanced Turbidimetric Inhibition
Immunoassay
+ =
+ + =
Negative - Light Scatter
Positive - Scatter Inhibited
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FPIA ‐ Fluorescence PolarizationImmunoassay
Negative - High Polarization
Positive - Low Polarization
+
+ +
=
=
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EMIT ‐ Enzyme Mediated Immunoassay Technique
+
+
Negative - Enzyme Inactive
Positive - Enzyme Active
+
=
=
Screening Test Cross‐Reactivity
• Cold medications may cross‐react with AMP screening tests due to similar drug structures
Manufacturer Package Insert
Confirmation Testing• Definitive mass spectrometry• Defensible – same technology used for forensic testing and legal evidence
• Total Ion Chromatogram – TIC – mass spec scans entire range of ion masses, searches library for matches based on ion ratio patterns – less sensitive, but detects everything at all retention times
• Select Ion Monitoring – SIC – mass spec skips between specific ions expected for a given drug confirmation –more sensitive, only detects selected ions
NAME : Methamphetamine
CHEMICAL NAME :(S)‐N,a‐Dimethylbenzene‐ethanamine; d‐N‐methylamphetamine;
Case Part II• 24 y/o male found unresponsive in home from previous case.
Admitted to accidentally smoking too much heroin.• Follow‐up after discharge from hospital, EMT called back to
house, 6 hrs after discharge. Patient found unresponsive in bed by family member. Paramedics arrived, patient in asystole, did not respond to advanced cardiac life support in field and terminated resuscitation attempts.
• Autopsy found needle marks with ecchymosis L forearm, L ventricular hypertrophy, congestion in lung, liver and kidneys. Blood tox positive for benzoylecgonine.
• Cause of death listed by the coroner as drug intoxication.
American College of Emergency Physician’s Case
Audience Poll
• Benzoylecgonine indicates ingestion of what drug?A. MethamphetamineB. HeroineC. CocaineD. Alcohol
Case• 25 y/o male in ED. Hx polysubstance abuse, was at party 2 days ago, had couple
beers and took what he thought may have been ecstasy. He felt terrible in the 24 hours after the party. He is having trouble sleeping. He felt anxious. Patient took another dose of the alleged ecstasy.
• In the following 24 hours, the patient started to see people crawling through the house, the people in his parent's car, feel his bed moving. He also saw all painting on the wall, move out of the wall towards him. He has never had this sensation before except for when he took LSD or other psychedelic drugs.
• Patient also endorses hearing voices giggling at him, denies suicidal ideation, homicidal ideation, depression. No pain, nausea, vomiting, chest pain, shortness of breath.
• Chief complaint: “I can't believe I am here. I was seeing things, but it is a misunderstanding.” Differential diagnosis includes drug‐induced psychosis versus acute psychotic break. Psychiatry pending. Given 1 dose of Xanax for anxiety.
• A 6404 for his been placed and patient will not be allowed to leave AGAINST MEDICAL ADVICE. A sitter is at his bedside.
• Toxicology: Positive for Amp, Methamp, BEG, oxazepam, nordiazepam, temazepam, alprazolam/met.
Audience Poll
• What is Xanax?A. AlprazolamB. OxycodoneC. NaloxoneD. Lithium
Xanax
Audience Poll
• What is the source of the other benzodiazepines (nordiazepam, temazepam, and oxazepam)?A. ValiumB. HeroinC. EcstasyD. Unknown
Audience Poll
• What screening test detects ecstasy?A. BEGB. CannabinoidsC. AmphetamineD. Oxycodone
Audience Poll
• Which of these drugs might cross‐react in an amphetamine screening test?A. OxycodoneB. MorphineC. SeligilineD. Ritalin
Amphetamine Cross‐Reactivity• Cold medications – IA structural similarity
– Sudafed (pseudoephedrine)– Ma Huang (ephedrine)– Phenylpropanolamine
• Diet Medications – IA structural similarity– Fenfluramine (phentermine – Fen Phen)
• True Cross‐Reactivity (IA and GC/MS as well)– Seligiline (Parkinson’s) metabolizes to methamp/amp– Adderall – (racemic amphetamine) – Vyvanse (lisdexamfetamine)– Dexedrine (dextroamphetamine)
• Drugs that will NOT cross react – either IA or MS– Ritalin (methylphenidate)
Case• 24 y/o man presents to ED with mother who reports he is confused and walking
funny• Hx of schizophrenia 3 yrs ago, in/out hospital since. Problems with drug abuse,
unstable housing situation. When “clean” he is allowed home, but typically only stays for 2 – 3 day stretches ea mo. Other times with friends. 2 wks ago, hospitalized with pneumonia after crack cocaine binge. Homeless, sleep deprived, undernourished. Found walking bus station, screaming that “people were after him”. In ED given IM haloperidol, lorazepam. Calmed down able to eat, shower, subsequently admitted to psych hospital with paranoia and auditory hallucinations decreased on haloperidol and fluoxetine. Compliant after discharge at home. Yesterday, complained of light‐headedness, flushed, nauseated.
• In ED more confused, glascow coma score 9, diaphoretic/tremulous. Temp 38.3C, BP 124/84, HR 124 bpm, resp 24/min. Appears ill and sedated. O2 sat 100% on room air. Labs pos for urine myoglobin, CK 15,125 (20 – 200 U/L), Tox: positive for THC.
• Diagnosed with neuroleptic malignant syndrome (NMS), admitted to IM service. After fluids, dantrolene and lorazepam, CK normalizes, fever decreases, and muscle tone improves. Haloperidol switched to risperidone and he is discharged with future monitoring for signs of NMS.
Audience Poll
• THC positivity indicates the ingestion of what drugs?A. MarijuanaB. CocaineC. OpiatesD. Amphetamine
• False positive IA:• Sustiva (antiretroviral)
false + in EMIT assay• True positive IA and MS:
• Marinol• Dronabinol• Recreational use in
food or smoking
The ED DAU Dilemma• Many toxicology experts agree that all DAU presumptive positive
screening tests should be confirmed before acted upon by clinicians• DAU screening tests give rapid results, but may have cross‐reactivity
and false‐pos as well as false‐neg results• Confirmation testing takes significantly longer – days later • Patient is discharged by time confirmation test results available• While confirmatory testing is definitive, ED physicians will treat and
act on preliminary results of presumptive positive/negative screening tests
• Is conducting more labor intensive confirmation of every positive screen efficient and productive in a hospital lab?
• Newer philosophy, allow physicians to choose whether they want or need confirmatory testing
Summary• Rapid drug‐of‐abuse testing can provide useful information
for clinical management of patients in the ED• Screening tests may be rapid, but suffer from cross‐reactivity
that leads to false‐positive and false‐negative test results• Confirmatory testing by mass spectrometry is both sensitive
and specific, but can take several days for result turnaround.• Clinicians should balance clinical history with screening results
and consider immediate and long‐term management goals when interpreting DAU screen‐only test results.
• Familiarity with metabolic pathways can assist clinical interpretation of urine DAU results.
Review Questions• What is the difference between heterogeneous and homogeneous immunoassays?
A – Heterogeneous requires extended incubation stepsB – With heterogeneous IA there is no mixing of reagentsC – Heterogeneous requires separation of bound and free antibody before detectionD – Heterogeneous runs on the same analyzer as chemistry tests
• What is the advantage of confirmation testing?A – Lower costB – SpecificityC – Using high tech equipmentD – Greater efficiency
• A patient is positive for 6‐monoacetyl morphine. This indicates ingestion of which drug?A – HeroinB – MethamphetamineC – CocaineD – Marijuana
• How would the laboratory director find the potential for a drug to cross‐react in an immunoassay?A – Defer to the clinicianB – Run an interference study on their assayC – Ask the patient what medications they ingestedD – Look in the package insert
