laboratory challenges in clinical toxicology of pain management by michael (rusty) nicar & marc...
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Laboratory Challenges in Clinical Toxicology of Pain Management
By Michael (Rusty) Nicar &
Marc McCain
Clinical Tandem Mass Spectrometry:Cutting Edge Technology for the Clinical Lab
Children’s Medical Center October 2010
Texas Medical Board Rules 2010
What is Chronic Pain: “a state in which pain persists beyond the natural course of an acute disease or healing of an injury.”
Appropriate drug therapy: “recognized by consensus.”
“A physician may require laboratory tests fordrug levels upon request.”
How Many Patients Have Chronic Pain?
1 out of 4 Americans have recurrent pain
1 out of 10 have pain of at least 1 yr duration
Treatment of Choice for Chronic Pain
CHRONIC OPIOID Rx
Hydrocodone is the most prescribed drug in the USA. Others used for pain:morphine, codeine, fentanyl, oxycodone, hydromorphone, oxymorphone, meperidine, methadone.
Why Do Pain Doctors Drug Test
Concerns: Drug Diversion
(majority of overdose deaths in W. Virginia were due todiversion of opioids, JAMA 2008 300:2613)
Taking non-prescribed or illegal drugs
Taking more than the prescribed dose
Overdose
Estimated Number of Emergency Department Visits in 2006:
Opioids – 250,000Acetaminophen – 50,000NSAIDS – 35,000
What Medications Do Pain Patients Take
What Are Patients Taking
CT: Cymbalta, Lyrica, Fentanyl, Hydrocodone
GG: Flexeril, Rozerem, Lortab, Allegra, Relafen
TK: Duragesic, Percocet, Ambien
RT: Lyrica, Norco
LV: Zantac, Carisoprodol, Wellbutrin, Topamax, Ambien,Hydrocodone, Celebrex, Flomax, Lexapro, Morphine,Baclofen
What Are Patients Taking
RR: Oxycontin, Percocet, Topamax, Metformin, Foltix, Lasix, Singulair, HCTZ, Nifedapine, Diovan, Premarin, Zetia, Omega 3
ML: Sirolimus, Cellcept, Metoprolol, Methadone,Effexor, Synthroid, Norvasc, Lisinopril,Allegra, ASA
OP: Skelaxin, Robaxin, Norco, Methadone
FH: Fentanyl, Tramadol
Why Do Pain Doctors Drug Test
State regulators require physicians to test patients during pain management.
Testing improves the Quality of Care.
Testing is the Standard Of Care for pain management.
Pain Physician 11:S5-S62, 2008.Journal of Pain 10:113-130, 2009.
Laboratory Monitoring
“Standard of Practice” for laboratory monitoring of pain patients is urine drug testing.
Because it was readily available, rapid, non-invasive, and inexpensive.
Not because it is the best scientifically.
Urine Drug Positives
Study from Johns Hopkins in 11,000 chronic pain patients confirmed positives in theiurine specimens (JAT 2008):
Amphetamines 2% Barbiturates 3% Benzodiazapines 22%
Cannabis 9% Carisoprodol 3% Cocaine 3%
Fentanyl 4% Meperidine 1% Methadone 11%
Opiates 82% Propoxyphene 4%
Drug Screen Results in Dallas
At CHOICE Laboratory, I see the following distribution on AU urine drug screens:
Negative – 25%Opiate – 50%
Opiate + Oxycodone – 16%
Illicit Drug Use Among Pain Patients
Patients must also be tested for illicit drug use.
A study in Kentucky reported the followingpercentage of pain patients using:
Marijuana – 11% (13% of females, 7% of males)Cocaine – 5%Methamphetamine – 2%
Pain Physician 9:215-226, 2006
Illicit Drug Use in Dallas Patients
At Choice Labs:
Marijuana (THC positives confirmed) – 8% *
Cocaine – 2% *
Methamphetamine – 1%
*no false positives by AU immunoassay screen
Limitations of Immunoassays
Crossreactivity of the antibody
Can’t identify specific drugsOpiate = morphine + codeine + hydrocodone
Cut-offs (Qualitative)Commercial assays come with cut-offs
Limitations of Immunoassays
False Positives due to crossreactivity:
Cannabinoids – Protonix, Daypro
Methadone – diphenhydramine, propoxyphene
PCP – meperidine, dextromethorphan
Oxycodone - Oxymorphone
Instrumentation
Immunoassays for single drugs can be quantitative and the Beckman Olympus AU has a semi-quantitative mode for drug classes (ie Opiates, Benzos) – but these assay still use antibodies and have limitations.
Confirmation instrument of choice for pain management labs:
LC-MS/MS
Why LC-MS/MS
SPECIMEN PREPARATION:
LC-MS/MS requires significantly less specimen prep than GC/MS
GC/MS – treatment and derivatization
LC-MS/MS – little or no treatment andno derivatization“Dilute & Shoot”
Why LC-MS/MS
SPECIMEN VOLUME:
LC-MS/MS requires significantly less specimen than GC/MS
GC/MS – 2-5 mLs
LC-MS/MS – 0.2-1 mL
Why LC-MS/MS
SENSITIVITY
LC-MS/MS requires dilution of specimens while GC/MS requires specimen concentration
GC/MS Opiate LOD = 100 ng/mL
LC-MS/MS Opiate LOD = 25 ng/mL
Why LC-MS/MS
Single scan determination of many drugs in minutes.
But…..CPT codes are for “assays” andMedicare pays for each assay – not for each drug measured.
The Pain Drug Screen
Amphetamine Barbiturates Benzodiazepines
Cannabinoids Cocaine MDMA
Methadone Opiates PCP
Propoxyphene Oxycodone TCAs
Creatinine Alcohol Cotinine
Buprenorphine Adulterants
The Pain Drug Confirmations
Amphetamine, Methamphetamine, MDA, MDMA, MDEA
Buprenorphine, Norbuprenorphine
7-aminoclonazepam, Hydroxyalprazolam, Oxazepam, Lorazepam, Nordiazepam, Tamazepam
Carisoprodol, Meprobamate
Benzoylecgonine
Methadone, EDDP
Propoxyphene, Norpropoxyphene
The Pain Drug Confirmations, cont
Morphine, Codeine, Hydrocodone, Hydromorphone Oxycodone, Oxymorphone, 6-MAM
Amitriptyline, Nortriptyline, Imipramine, Desipramine, Doxepin, Desmethyldoxepin, Cyclobenzaprine,
Clomipramine, Norclomipramine
Fentanyl
Tramadol, Meperidine, Normeperidine
Amobarbital, Butabarbital, Pentobarbital, Phenobarbital, Butalbital, Secobarbital
THC-COOH
Children’s Medical Center 2010
Thank You.