3/8/2018. Reasons for Doing UDT. UDT: A Tool in Risk Assessment. Faculty/Presenter Disclosure. Urine Drug Testing in Chronic Pain Management
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1 Urine Drug Testing in Chronic Pain Management March 8, 2018 Faculty/Presenter Disclosure Faculty: Andrew J Smith, MDCM Relationships with commercial interests: None to report Andrew J Smith, MDCM Staff Physician, Pain and Addiction Medicine Clinical Lead, Interprofessional Pain and Addiction Recovery Clinic Centre for Addiction and Mental Health 1 2 Urine Drug Testing: Learning Objectives 1. Describe the clinical guidelines on appropriate use of UDT as part of the management of patients with chronic pain 2. Formulate practice strategies to determine the appropriate test to order 3. Interpret UDT results accurately. Reasons for Doing UDT Clinical Baseline measure of substance use may help assess risk for addiction Ongoing monitoring of a patient prescribed opiates to measure adherence 3 4 Pillar 1 (cont): Risk Assessment Universal Precautions history (Gourlay et al, 2005) Current and previous pain treatment Aberrant drug-related behaviours Previous drug and alcohol use Family history of drug or alcohol use History of other addictions History of physical, sexual or emotional trauma Depression, anxiety, and other mental health issues Urinary drug screen and identification Identify the individuals with the greatest risk of aberrant behaviour NOT to stigmatize, but to improve care UDT: A Tool in Risk Assessment UDS can be helpful in establishing the reliability of a patient s reported substance use. UDS should be used routinely to establish baseline information regardless how well the patient is known to the prescriber. Universal approach destigmatizes testing Increases prescriber confidence in using opioids 5 6 1
2 UDT: A Tool in Adherence Monitoring Identification of Aberrant Drug Seeking Behaviors During opioid trial, UDS can be useful in detecting unauthorized drug use, non-compliance, and diversion No compelling evidence to guide physicians on identifying CNCP patients who should have UDS or how often In deciding whether to order a baseline UDS, and how often to use screening to monitor patients, consider: patient s risk for opioid misuse and addiction aberrant drug-related behaviours availability of UDS Eminence-Based Medicine The medical literature is filled with various definitions of "aberrant" behavior Providers typically under-identify aberrant behaviors: Study: Physicians identified 13.9% of patients on chronic opiates as demonstrating aberrant behaviors, despite 50% of their patients having positive drug screens for illicit substances, and 8.7% having no evidence of prescribed opiates in their urine. Wasan, et al. Clinical Journal of Pain, 2007;23: Predicting Aberrant Use In one prospective study, 32 % of patients in an academic chronic pain practice were identified by UDT as engaging in aberrant use UDT: Risk Assessment & Management Aberrancy 62 (31.6%) of N=196 Stimulants (cocaine or amphetamines) 25 (40.3%) Negative urines 15 (21.2%) Doctor collecting 10 (16.1%) Inconsistent urines (other opioids) 9 (14.5%) Prescription forgery 2 (3.2%) Diversion 1 (1.6%) TOTAL 62 (100%) Urine drug testing reduces illicit drug use in chronic pain patients receiving opioids Illicit drug use reduced by 50% in a group with urine testing compared to previous data 9% of patients had accessed controlled substances from sources other than the prescribing physician Manchikanti L et al.. Pain Physician Jan;9(1): BMC Health Serv Res Apr 4;6: Canadian Guidelines for Opioids and Chronic Non-Cancer Pain 2017 Canadian Guidelines for Opioids and Chronic Non-Cancer Pain Expert Guidance (not a guideline) for Risk Mitigation A baseline urine drug screen may be useful for patients currently receiving or being considered for a trial of opioids. Clinicians may repeat urine drug screening on an annual basis and more frequently if the patient is at elevated risk or in the presence of any aberrant drug-related behaviours. Expert Guidance (not a guideline) for Risk Mitigation Evidence ~30% of UDS will show aberrancy: mostly non-detection of prescribed opioids and presence of THC Only 1 abstract report large retrospective cohort study that found no difference in rates of opioid overdose for those who did or did not receive baseline UDT (BUT VERY LOW QUALITY EVIDENCE) 2017 Canadian Guideline for Opioids for Chronic Non-Cancer Pain Canadian Guideline for Opioids for Chronic Non-Cancer Pain 11 Saunders K et al. Chronic Opioid UDT in Primary Care: Prevalence and Predictors of Aberrant Results. J Gen Int Med. 29 (12): Larochelle M et al : Association of urine drug test screening during initiation of chronic opioid therapy with risk of opioid overdose. Abstract presented at the 2016 Society of General Internal Medicine Annual Meeting; May 11-14, 2016; Hollywood, FL.. J Gen Int Med. 2016;31(2 Suppl):S
3 2017 Canadian Guidelines for Opioids and Chronic Non-Cancer Pain Expert Guidance (not a guideline) for Risk Mitigation When ordering a urine drug screen, clinicians should ask patients about all medications/drugs recently taken, and be aware of local resources to assist them in assessing for potential false positive and false negative results. Different immunoassay testing kits have different response characteristics, and may require confirmation with other testing (gas chromatography/mass spectrometry for example). On site, point-of-care testing, though less accurate than delayed in lab testing, may be preferable as one can discuss the results with the patient and make an immediate decision regarding the safety of opioid prescribing Canadian Guidelines for Opioids and Chronic Non-Cancer Pain In one study only 8% of physicians utilized UDS (Adams 2001). Another study found only 7% used UDS before initiating opioids and 15% used UDS once patients initiated were on long-term treatment (Bhamb 2006) Canadian Guideline for Opioids for Chronic Non-Cancer Pain Clinical Process Why am I doing this test? If the results won t change what you are planning clinically Consider not running the test What will I do with an unexpected result? Conducting Urine Drug Testing Take a detailed history of the patient s medication use for the preceding 7 days. Inform patients that the UDT is not meant to catch or punish patients but to improve the safety and effectiveness of long term opioid therapy Tell the patient what results are expected from appropriate opioid use and ask the patient if anything else might show up. If using a treatment agreement, add the requirement of UDT to the treatment agreement UDT: Immunoassay - Screening Test Of Opiates and Opioids Uses antibodies to detect specific substance or class VERY SENSITIVE DETECTION TIME 3-5 days NB CROSS-REACTIVITY LOW FOR COCAINE HIGH FPR AMPHETAMINES Does not distinguish between codeine and morphine LOW SENSITIVITY FOR SEMI-SYNTHETIC OPIOIDS NOT SENSITIVE FOR SYNTHETIC OPIOIDS unless specified Cheap, Rapid, Point-Of-Care NEED TO CONFIRM ABNORMALS
4 UDT: Gas Chromatography/Mass Spectroscopy (GCMS) Confirmatory Test Sensitivity depends on cut-off criteria MUCH MORE SPECIFIC Occasional False + for Amphetamines Often used as confirmatory testing Distinguishes molecules among a class Can detect semi- and synthetic opioids Expensive Must be sent to lab Detection Time 1-2 days Sample Control Need to ensure the sample belongs to the patient Urine TEMP : C / F Urine specific gravity >= ph U Creatinine < 2-3 mmol/l Nonphysiological <4.5mmol/L Dilute (<1% of population) Eliminating water sources Removing outer garments and extraneous belongings Patient hand-washing Direct observation Urine Tampering Substitution Dilution = Most common form of tampering Pre-Collection Hydration, water loading, diuretics Post-Collection Add water or fluid NB: CHECK CREATININE Adulteration = Adding foreign substances to mask drug ph shift: vinegar, bleach, ammonia, lemon, drano Disrupt testing chemistry: salt, methanol, detergent Urine Tampering Toxicology is Part of The Team Know what drugs the lab actually tests for Is the test an Immunoassay or GCMS? Many do Immunoassay GCMS only to confirm positives on IMMUNO What is the CUT-OFF selection? Typical Cutoff Levels screening & confirmation Amphetamines 1000 ng/ml 500 ng/ml Benzodiazepines 300 ng/ml variable Cannabinoids 50 ng/ml 15 ng/ml Cocaine (crack) 300 ng/ml 150 ng/ml Opiates (heroin) 10) 300*/2000 ng/ml (MS 2000; MAM Phencyclidine (PCP) 25 ng/ml 25 ng/ml Alcohol 20 mg/dl 10 mg/dl NB Poppy seeds Lower Cut-Off = Longer Detection Window
5 Opioid Metabolism Opiate Metabolism Opiate Metabolism Review Heroin shows up as morphine Codeine codeine, morphine, hydrocodone Morphine morphine, (hydromorphone) Synthetics won t appear on IMMUNO Benzos often metabolize to other benzos Cocaine cocaine if recently used Drug Detection Time Windows Alcohol Substance Length of Time Detected 2-12 hours* Ethylglucuronide 3-5 days Morphine IMMUNO 2-4 days GCMS 1-2 days Heroin 6-monoacetylmorphine (MAM) Methadone 2-ethylene-1,5-dimethyl 3,3- diphenylpyrrolidine (EDDP) Minutes < 12 hours (on GCMS) 1-4 days EDDP detected on GCMS Drug Detection Time Windows Substance Cocaine Benzoylecgonine D9-THC Benzos Length of Time Detected Few hours (only GCMS) 3-5 days (on IMMUNO or GCMS) 2-7 days (light use) 1-2 months (heavy) Days or weeks depending on t1/2 IMMUNO doesn t distinguish Short-acting = poor sensitivity and often undetected Results Patient USING substance Patient NOT USING Positive Result True Positive False Positive Negative Result False Negative True Negative True Positive Adherence to therapy for prescribed drugs Use of non-prescribed drugs True Negative Patient is not adherent to treatment Patient is not using substances tested for
6 True Positives NOT QUANTITATIVE : CAN T TELL HOW MUCH CAN T TELL EXACTLY WHEN SUBSTANCE USED CAN T TELL HOW INGESTED WON T PICK UP BINGE BEHAVIOUR UNLESS TESTED IMMEDIATELY AFTER A BINGE False Positives Most reports of false positives based on case reports Opiates Poppy seeds, quinoloneabx, DM, diphen Amphetamines bupropion, trazodone, ranitidine Barbs NSAIDS (0.4% false + rate) Cannabinoids NSAIDS (O.4%), pantoprazole (1 case report), nabiximols PCP venlafaxine, DM, tramadol, ibuprofen Unexpected Results Scenario Patient prescribed oxycodonecontrolled release 10mg TID for 2 months Patient reports adherence UDT NEGATIVE! Possibilites False negative. Non-compliance. Diversion Repeat test using GCMS ask for the drug of interest (e.g. oxycodone often missed by immunoassay) Take a detailed history of the patient s medication use for the preceding 7 days (e.g., could learn that patient ran out several days prior to test) Ask patient if they ve given the drug to others. Monitor compliance with pill counts. UDT Mythology Will second-hand exposure to cannabis smoke produce positive drug test? 6 smokers and 6 non-smokers in a sealed chamber seated in an alternating manner THC Concentration Session 1 5.3% No Session % No Session % Yes Ventilation Passive cocaine Poppy seeds Alcohol 33 Cone EJ et al. Non-Smoker Exposure to Secondhand Cannabis Smoke. I. Urine Screening and Confirmation Results. J Anal Toxicol Jan; 39(1): doi: /jat/bku Passive Exposure to Cannabis Smoke Approaching Unexpected Results A single positive test at 50ng/mL cut off Multiple positives at 20ng/mL NB Higher potency Lack of ventilation Extreme smoke exposure can produce positive tests at lower cutoff concentrations, but not generally at the higher initial test cutoff concentration in general use. Is it true, false? Confirm the result (GCMS, ask patient,meds) What will an abnormal result mean Non-adherence Substance use?disorder Presence of risk eg benzos, EtOH Normalize difficult conversations, acknowledge fears Remember stigma Check-in with self around process, anger, etc Make changes in therapy about the result NOT the patient Cone EJ et al. Non-Smoker Exposure to Secondhand Cannabis Smoke. I. Urine Screening and Confirmation Results. J Anal Toxicol Jan; 39(1): doi: /jat/bku
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