Patches, Needles, and Lollipops...

Transcription

1 Patches, Needles, and Lollipops... Jaime Lintemoot Los Angeles County Department of Coroner CAT - November Culver City

2 Objectives Fentanyl Routes of Administration Fentanyl Screening Methodologies 2 Year Fentanyl Study Results Conclusions

3 History of Fentanyl Synthesis Synthetic Opioid Belgium, Late 1950 s Janssen Pharmaceutica Use Clinical Use Surgical Anesthetic United States 1967 Schedule II Drug

4 Fentanyl Synthetic Narcotic Analgesic x more potent than Morphine Short Acting <30 Min Side Effects Severe Respiratory Depression Muscle Rigidity Seizures Hypotension Coma & Death Fentanyl C 22 H 28 N 2 O MW = Lethal Levels = 8-9 ng/ml *

5 The Needle Sublimaze Intravenous & Intramuscular Injection Anesthetic/Analgesic Dosage 50 ug/ml ampules ug administration Types of Abuse...

6 The Needle - Case Study #1 38-yo Male Unresponsive in Bathroom Hx of EtOH & Drug Abuse Fresh Trackmarks Syringe On Floor

7 The Needle - Case Study #1 Toxicology Results Fentanyl 10 ng/ml H. Blood Femoral 2.4 ng/ml EtOH 0.06 g% 0.06 g% Cause of Death Fentanyl Intoxication Mode of Death Accident

8 The Needle - Case Study #2 49-yo Female Nurse Anesthetist Unresponsive in Bed IV Left Arm Syringe Right Hand Recent Depression 1 Prior Suicide Attempt

9 The Needle - Case Study #2 Toxicology Results H. Blood Femoral Fentanyl 17 ng/ml 2.0 ng/ml Lidocaine 2.5 ug/ml 0.82 ug/ml Sertraline 0.31 ug/ml 0.18 ug/ml Norsertraline 1.7 ug/ml 0.35 ug/ml Morphine 0.87 ug/ml 0.22 ug/ml EtOH 0.14 g% 0.12 g% Laudanosine Present --- Medical Evidence Syringe Lidocaine Atracurium (Laudanosine) Cause /Mode of Death?

10 The Patch Duragesic Transdermal Delivery System Pain Management Dosage mg Patches ug/hr per 72 hrs Types of Abuse...

11 The Patch - Case Study #3 52-yo male Dr s Appointment 12/24/ hours Back Pain & Depression Fentanyl Patches Investigation 12/24/ hours Unresponsive Parking Lot of Dr s Office 2 of 10 Patches remaining

12 The Patch - Case Study #3 Toxicology Results H. Blood Femoral Fentanyl 115 ng/ml 36 ng/ml EtOH 0.09 g% 0.10 g% Clonazepam 21 ng/ml --- Hydrocodone 0.04 ug/ml --- Lorazepam 132 ng/ml --- Cause of Death Multiple Drug Intoxication Mode of Death Accident

13 Types of Abuse. Multiple Patches Intravenous Injection of Patch Material Application of Patch w/heat Previously Used Patches Frozen Patches - Chiclets??? Patch Abuse

14 The Lollipop Oralet Transmucosal Absorption Pre/Post Operative Dosage: ug minutes before procedure 5-15 ug/kg

15 The Lollipop Actiq Transmucosal Absorption Cancer Pain Dosage: ug Consume w/in 15 minutes 4 per day

16 The Lollipop - Case Study # 4 45-yo Male Unresponsive in Bathroom AIDS, Depression, Sinusitis & Severe Back Pain Bag w/ Lollipops in Adjacent Room

17 The Lollipop - Case Study #4 Medical Evidence 10 of 48 Lollipops Intact Toxicology Results Fentanyl Cocaine BE Hydrocodone Mirtazapine Cause of Death Coc/Fent/HC Use Mode of Death Accident H. Blood 1.7 ng/ml 0.33 ug/ml 0.50 ug/ml 0.03 ug/ml < 0.10 ug/ml

18 Illicit Fentanyl Use & Abuse Rx Drug Abuse Patches, Needles and Lollipops Hospital Administration Street Use & Manufacturing 10+ analogs Smoke, Snort & Inject The Toxicology Problem.

19 Fentanyl Screening Dr. s Request or Pharmaceutical Drug Screen Liquid/Liquid Extraction 3 ml Sample Size Deuterated Internal Standard Basic Shake Out with an Acid Back Extraction Evaporate & Reconstitute in MEOH GC/MS - SIM

20 Fentanyl Screening Problem L/L Extraction - Sensitivity - Inconsistencies ELISA Technology - 3 Months - All Toxicology Cases - Results???

21 Fentanyl Screening Case 40-yo Male Medical History of AIDS/HIV Unresponsive in Bed Transported to Hospital by Paramedics Unable to Revive Rx Meds: Epivir, Stauvudine, Atropine, Bactrim, Dilaudid, Pyrimethamine, Viramune, Catifluxalin, Paxil, Compazine, Hydroxyzine, Tagamet, Levofloxalin, Risperidal, Prevacid, and Ducusate

22 Fentanyl Screening Case Toxicology Results H. Blood Femoral Meperidine <0.10 ug/ml --- Normeperidine 0.13 ug/ml --- Norchlorcyclizine <0.10 ug/ml --- Paroxetine <0.10 ug/ml --- BE 0.19 ug/ml --- Hydromorphone ND 0.13 ug/ml Fentanyl 9.2 ng/ml 7.7 ng/ml Cause of Death Multiple Drug Intoxication Mode of Death Accident

23 Fentanyl Screening Revised Determination of Screening Procedures Practicality & Feasibility? The Study All Comprehensive Screens ( C ) 2 Years ELISA Technology for Screening L/L Extraction for Quantitation

24 Fentanyl Screening via ELISA Manual Set Up 100 ul Sample Negative Controls, & Positive Controls (1 2.5ng/ml) 900 ul Buffer Instrument Setup Tecan Minilyser Immunalysis FENTANYL Direct ELISA Kit

25 Fentanyl Screening via ELISA Automation 20 ul Sample into a 96- well plate 100 ul Conjugate Incubation 100 ul Color Reagent 100 ul Stop Solution Spectrophotometer

26 Fentanyl Screening Results December September 2003 Toxicology Cases = 9,402 C Screens = 3,495 ELISA (+) Fentanyl Cases = 170 Presumptive Positive Rate = 4.9% Confirmed Fentanyl Cases = 95 Confirmation Rate = 56% Fentanyl Positive Rate = 2.7%

27 (+) Fentanyl Statistics Modes of Death (95) 55 Accidents 3 Homicides 18 Naturals 8 Suicides 11 Und./Deferred Demographics Ages Average Age: 51 Years Gender 45 Male, 50 Female

28 (+) Fentanyl Statistics 95 Cases 20 Cases w/patches 2 Cases w/ Lollipops 4 Cases w/ Needles 3 Cases involving Nurses 49 Hospital Cases 23 Cases Undetermined Source

29 (+) Fentanyl Statistics 37 Cases (95): Cause of Death - Fentanyl Related H. Blood Ranges = ng/ml 26 Cases (95): Hospital Admin. Fentanyl - Not COD H. Blood Ranges = < ng/ml 47 Cases (95): Missed by Routine Screening Procedures 13 Cases (45): Cause of Death - Fentanyl Related H. Blood Ranges = < ng/ml, Ave = 7.7 ng/ml 49% of Fentanyl (+) Cases Missed by L/L Extraction 1.3% of All C Screens Missed by L/L Extraction

30 Conclusions Patches, Needles & Lollipops Sensitivity of Screening Procedures L/L Extraction ~ 7.7 ng/ml ELISA ~ 1.0 ng/ml 49% of (+) Fentanyl Cases Missed by L/L Extraction Confirmed Fentanyl Cases 2.7% of C Screens (+) for Fentanyl 35% of (+) Fentanyl Cases were Fentanyl Related COD

31 Where do we go from here? Laboratory Considerations... Fentanyl vs PCP Cost vs Relevance Other Approaches? Extended C Screens Looking into Case Histories New Abuse Problems? Illicit Fentanyl Detection?

32 Acknowledgements Los Angeles County Department of Coroner Forensic Toxicology Staff