Download A. Urine Drug Testing Interpretation Basics

Urine screen interpretation basics
Michael E.M. Larson, Ph.D.
Pain Management
Marshfield Clinic Minocqua Center
Continuing Medical Education (CME) Disclosure
Urine screen interpretation basic.
Michael Larson, PhD,
June 14, 2016
I, Michael E M Larson, PhD, do have a relevant financial interest or
other relationship with a commercial entity producing health-care
related product and or services:
Affiliation/Financial Interest Name of Corporate Organization(s)
Grant/Research Support:
Ameritox Ltd
Other Financial or Material Support
Ameritox Ltd
Objectives
• Review basics elements of urine screens.
• Discuss advanced methods of analyses using urine
creatinine and statistical analyses.
• Specific review of urine screen evaluation of marijuana.
• Specific review of urine screen evaluation of
buprenorphine.
Expertise Disclosure
I am a psychologist, not a toxicologist!
Oversight of the Opioid Medication Management Team for MQA Pain Mgt for past 14
years.
Asked many questions:
● Over 300 saved emails from Drs. Grinstead and Flanagan (real toxicologists!),
many more have been discarded.
● Took many provider questions (well over a 4,000 by my count) that required me
to think, review and learn.
● Talked with other providers (Drs. Studt, Carpenter etc.) who had interest in urine.
Clinical Research Database (LAR30104):
● Documented over 29,000 urine screens connected to medication list. Had to
connect findings to a specific substance or medication.
Member – Team of providers and administrators that developed the Scheduled
Medication Policy.
SAFETY TIP
• Urine screens are one piece of data and should not
be used in a vacuum!!!!
•
They are NOT perfect and we do not have a screen
that can perfectly identify with complete certainty
that the person is taking the medication as
prescribed.
•
They are a TOOL to ADD TO clinical judgment, refill
data, outside report, etc. to help make decisions.
•
They should NEVER and are NEVER the sole reason
for a change in a person’s treatment plan.
Urine Testing 101
Why use urine screens?
● They provide objective data of recent use
● Unbelievably accurate. Hard to argue with the accuracy.
● Depending on type of testing performed, learn:
● Use of the prescribed medication.
● Use of non-prescribed medications.
● Use of illicit substances.
Why people don’t use them
● Sometimes they are difficult to interpret
● Difficult to ask people to submit a sample. Easier if you prompt them
when signing the agreement.
Urine Test Basics (1)
From Lab News Article per J. Flanagan PhD
Step 1: First step in a urine test is:
● Screening based on antibody-antigen immunoassay.
● This cross-reacts with structurally similar compounds.
● If positive, really is called “presumptive positive”.
● Can be a “false positive”. Only way to confirm that it is a
“true positive” move to step two.
● Can be also a “false negative” due to the THRESHOLD
element.
● Remember that a positive without confirmation can
potentially impact pt care, BE CAREFUL. Also remember the
false negative.
Urine Test Basics (2)
From Lab News Article per J. Flanagan PhD
Step 2: confirmation and quantification:
● This occurs by Gas Chromatography and Mass Spectrometry
(GC/MS) which is very reliable.
● My simplistic explanation of GC/MS:
● Gas chromatography maps the various compounds.
● Mass Spectrometry evaluates the mass (chemical structure) of the
compounds.
● Very specific and reliable.
● Provides you with confirmation that the specific metabolite was
present AND
● Provides how much of the metabolites were present in the urine
(quantification).
What is the purpose of urine testing?
PURPOSE OF URINE TEST:
●
●
●
●
●
Confirm patient is taking the prescribed opioid or Medication
Assisted Treatment (MAT) such as buprenorphine;
Monitor abuse of other prescription medications (e.g., opioids,
benzodiazepines and psychostimulants);
Confirm that they are avoiding any illicit substance use;
Confirm that they are not abusing ethanol in the context of opioid
medication use.
If patient is only taking low dose or PRN medication may be
negative (see negative drug screen results spreadsheet).
What type of urine screen should I order?
Use of Controlled Substances for Long Term Tx Plan Policy
URINE TEST TYPE: Pain Clinic Survey with Confirmation (PCS10)
or a similar type of SURVEY that covers multiple substances.
●
Want to cover opioids (i.e., methadone, oxycodone,
morphine, hydrocodone, hydromorphone, codeine)
along with benzodiazepines, amphetamines (except
methyphenidate), THCA, Cocaine, ethanol and
BUPRENORPHINE
●
Add fentanyl or tramadol GC-MS if patient also on those
medications
Can consider PCS-Mini (with / without conf) but this
would NOT be appropriate for MAT patients.
Safety Tip regarding urine screens
• Know what the type of screen you are order is going to show
• Document in your note how the patient has been taking
medications the previous 24-48 hours for comparison
• Don’t just focus on opioids, look at benzodiazepines and
psychostimulants that may give you additional information on
patient’s overall compliance
• Check with the experts when it is not a clear and consistent
result ([email protected])
• Patients are EXPERTS with street knowledge of urine screen
interpretation and sometimes professional knowledge.
Our method developed at the Minocqua Center
•
Use Urine Creatinine to adjust for sample hydration.
•
•
•
•
•
•
Urine creatinine (UC) is a by-product of muscle metabolism and
excretes thru the urine at a relatively constant rate.
Allows for use to understand how hydrated (watery vs dense) the
urine sample provided is.
If urine is watery, UC is low. If UC is high, then urine is more dense or
has less water in it. Avg UC is around 100 mg/dL.
The level of metabolites or analytes in the urine will COVARY with the
UC level.
If UC is LOW, then the amount of metabolites in the urine from the
ingested drug will also be LOW.
If UC is HIGH, then the amount of metabolites in the urine from the
ingested drug will also be HIGH.
Our research history
2009 Article (Larson & Richards, Clinical Medicine & Research) showed:
1.
●
●
●
UC dramatically improved connection of drug dose to urine metabolite levels
for individuals on methadone.
Use of UC allowed statistical analysis of urine screen thru the use of
comparison to another group of individuals on the same medication and
dose.
We were able to successfully identify individuals who were overusing,
underusing and appropriately using methadone.
2015 Article (Larson, Berg & Flanagan, Journal of Opioid Management)
showed:
2.
●
UC also relevant for Morphine and Oxycodone products.
●
Drug dose and UC are highly statistically significant to drug
metabolites level shown in the urine.
Additional background
US Patent on this method granted in August 2009 (US Patent No. 7,585,680
M. Larson and T. Richards). Patent covers the statistical comparison of an
individual urine sample with the use of UC to correct for hydration to a normative
database.
Patent has been exclusively licensed for use outside of Marshfield Clinic (MC)
to Ameritox Ltd.
1. This means that I can only interpret urine screens using the statistical analyses
when urine screen is ordered by a MC provider.
2. An understanding with Ameritox Ltd does allow me to statistically analyze urine
screens if they use the Ameritox Ltd service outside of MC for GRANT PATIENTS
ONLY. There is no payment associated with this understanding.
3. Royalties are paid to MC on a yearly basis at a constant rate and do NOT change
regardless of any use factors. Please note that my royalties are NOT impacted by
the above use or non-use with grant patients. There is NOT a conflict of interest
given that there is NO CHANGE regardless of how many samples are interpreted or
whether the method is used or not.
Example of PCS10
Urine Screen was "Clean and
Appropriate" per Larson-Richards
Protocol, findings:
(*) Ratio Z-score of -0.63 for OxyContin /
oxycodone (male dose norms) is
appropriate.
(*) Negative for any illicit substances or
other problematic medications.
Urine Screen was reviewed per LarsonRichards Protocol, findings:
(*) CONCERN: Ratio Z-score of -1.15 for
OxyContin / oxycodone (male dose norms) is
LOWER than expected given that the pt had
actually reported using a few more of the
oxycodone than prescribed. This is UNUSUAL.
(*) CONCERN: Positive for LOW LEVEL of
THCA with ratio of 0.11. This is likely passive
inhalation but this has been an issue with this
pt in the past.
Cocaine Example
Urine Screen was reviewed per LarsonRichards Protocol, findings:
(*) APPROPRIATE: Ratio Z-score of -1.11 for
oxycodone, on low end of expected range.
(*) APPROPRIATE: Ratio Z-score of -1.06 for
temazepam.
(*) PROBLEMATIC: Positive for THCA at a
very low level with ratio of 0.20, which could
represent passive inhalation.
(*) PROBLEMATIC: Positive for COCAINE at
very low level with ratio of 0.95.
Interpretation guidelines for Marijuana
Use of Urine Creatinine
1.
2.
3.
4.
5.
6.
Rules for Marijuana (THCA) interpretation:
Divide the THCA level by Urine Creatinine (example 100 / 50.0 = 2).
Identify that ratio and locate in table below.
If THCA / Urine Creatinine ratio is LESS THAN 0.5, this may be due to PASSIVE INHALATION
(e.g., being in a closed space with other smoking marijuana and you are passively inhaling that
smoke). This could also suggest a very infrequent user or a person who has not used for a
several weeks and the THCA is excreting out of the system.
If THCA / Urine Creatinine ratio is 0.5 OR HIGHER, then we can accurately identify that the
person has had ACTIVE INHALATION at some point in the recent past (e.g., 1-30 days or so).
CAUTION: Individuals with kidney dysfunction may show higher levels due to kidney problems,
so if person has those known problems (e.g., recent low eGFR) the some caution may be
indicated.
Low
0.0 to
0.5 to
High
0.49
3.0
3.0 to
7.0
7.0 to
10.0 or
10.0
Above
Comment
Possible PASSIVE INHALATION or remote use or very low level use.
ACTIVE INHALATION CONFIRMED but likely fairly low level use (e.g., 1 x per
week or less).
Active inhalation but likely more frequent. This may be in the several
times a week user.
DAILY USERS will fall in this category. Likely chronic users.
MULTIPLE TIMES PER DAY USERS. Likely CHRONIC AND CONSISTENT
USERS.
Buprenorphine specifics.
Buprenorphine when ingested leads to two analytes that will be present
in a urine screen:
1.
●
Buprenorphine: This is the parent drug.
●
Norbuprenorphine: This is due to the body’s metabolism of the buprenorphine, this is
an active metabolite in the body.
If the person is taking the medication in a STEADY STATE or consistently
we will see:
2.
●
Norbuprenorphine > (greater than) buprenorphine.
●
Usually the ratio will be 2 to 1 or more (e.g., norbuprenorphine will be 2 x higher than
buprenorphine generally) but there is a fairly broad range.
This ratio allows analysis of the following:
3.
●
Steady state use.
●
Loading Dose, where Buprenorphine is higher than Norbuprenorphine.
●
Weaning Dose, where Norbuprenorphine is significantly higher than Buprenorphine.
●
FILM DIPPING, where ONLY buprenorphine is present because the body has not shown
any metabolism.
Buprenorphine specifics #2.
1.
The combination of the two metabolites, when added together provide a great
deal of stability and consistency with dose ingested
2.
So – We can simply ADD the buprenorphine level in the urine to the
norbuprenorphine in the urine together to get a TOTAL BUPRENORPHINE
METABOLITES.
When we then CORRECT the Total Buprenorphine Metabolites with UC (simply
divide the Total Buprenorphine Metabolites by UC) we get a TOTAL
BUPRENORPHINE METABOLITES RATIO.
3.
4.
5.
We then statistically COMPARE this ratio to other individuals (adjusted for liver /
kidney function if present and gender, possibly age) to a Normative Dataset of
people on the same dose that have been ASSESSED TO BE ADHERENT.
The results of this statistical comparison is what we call a Ratio Z-score, where
roughly 66% should be between +/-1.00 and 95% should be between +/-2.0. We
adjust our scale due to our inclusion of the actual sample in the distribution
(which intentionally broadens our variability to be assured of adjustment for
individual characteristics, such as fast or slow metabolizers).
Steady State User
Pt currently on buprenorphine or Suboxone therapy, urine screen was
review per Larson-Richards Protocol, findings:
(***) LEVEL ANALYSIS: Buprenorphine Total Metabolites Ratio Z-score
of -0.88 (female dose norms) is appropriate.
(***) STEADY STATE ANALYSIS: NorB to Bup Ratio Z-score of -0.67
suggests steady state use.
(*) Remainder of urine screen was negative for problematic substances.
This is considered a "CLEAN AND APPROPRIATE" urine screen.
Buprenorphine example of Loading Dose and Overuse
Pt currently on buprenorphine or Suboxone
therapy, urine screen was review per LarsonRichards Protocol, findings:
(***) LEVEL ANALYSIS: Buprenorphine Total
Metabolites Ratio Z-score of -0.57 (female dose
norms) is appropriate.
(***) CONCERN - STEADY STATE ANALYSIS:
NorB to Bup Ratio Z-score of -1.94 suggests a
PARTIAL LOADING DOSE. The NorB to Bup
ratio is IN THE OPPOSITE DIRECTION and is a
substantial concern. This is also VERY
INCONSISTENT with her prior ratios on an
INTRAINDIVIDUAL ANALYSIS.
Pt currently on buprenorphine or Suboxone therapy,
urine screen was review per Larson-Richards
Protocol, findings:
(***) CONCERN - LEVEL ANALYSIS: Buprenorphine
Total Metabolites Ratio Z-score of 2.94 (female dose
specific norms) is VERY ELEVATED strongly
suggesting some level of OVERUSE.
(***) STEADY STATE ANALYSIS: NorB to Bup Ratio
Z-score of 0.99 suggests steady state use at a higher
dose.
Pt's level was most consistent (estimate) with 14-16
mg total use per day. She is prescribed 8 mg total
per day.
Buprenorphine example of FILM DIPPING
Pt currently on buprenorphine or Suboxone therapy.
(*) Findings:
(***) Buprenorphine: 16886 ratio of 219 (ratio Z-score for this dose 2.67, which is elevated).
(***) Norbuprenorphine: NEGATIVE which is INCONSISTENT with steady state / consistent use.
(***) This is most consistent with a LOADING DOSE (i.e., taking large amount of medication day or
evening prior to urine screen. Given that the pt had about 18 hrs prior to submitting the urine screen,
this provided him time to perform the loading dose.
This pt now receiving Suboxone from another provider in
Stevens Point with NO confirmatory testing performed.
Buprenorphine Weaning Dose
Pt currently on buprenorphine or Suboxone therapy, urine screen was review per
Larson-Richards Protocol, findings:
(***) LEVEL ANALYSIS: Buprenorphine Total Metabolites Ratio Z-score of -0.51
(male norms) appears appropriate.
(***) CONCERN - STEADY STATE ANALYSIS: NorB to Bup Ratio Z-score of 2.16 is
in the correct direction but very high. This may suggest reduced use prior the urine
screen or even running out prior to urine screen.
REPEAT SAFETY TIP
• Urine screens are one piece of data and should not
be used in a vacuum!!!!
•
They are NOT perfect and we do not have a screen
that can perfectly identify with complete certainty
that the person is taking the medication as
prescribed.
•
They are a TOOL to ADD TO clinical judgment, refill
data, outside report, etc. to help make decisions.
•
They should NEVER and are NEVER the sole reason
for a change in a person’s treatment plan.
Conclusions
•
•
•
•
•
Urine screens can be used to help us understand use
patterns, especially with buprenorphine.
The use of Urine Creatinine and statistical analyses /
comparisons can be helpful.
At times people do have unique metabolism and in those
cases we can statistically analyze their new urine with their
past urines to provide understanding of adherence.
The use of urine screens can provide information about
aberrant use or tip us off to overuse, underuse, loading
doses, weaning doses or dipping a film.
If you have questions, please contact me.
[email protected]
Michael Larson PhD
Marshfield Clinic – Minocqua Center
Please contact with any specific questions or for
any of the handouts.