Common Toxicology and TDM Calls

1. Emergency Department Critical Drug Values. - a technologist has probably already called the result to an ED attending and/or nurse - report the value to the resident/attending taking care of the patient - offer any needed assistance in interpretation of the value or further laboratory evaluation in the case - express interest in the clinical situation and try to obtain some information for your notebook and for future discussion in rounds, with attendings, etc. 2. In-patient critical values, unusual situations, problems, concerns, etc. - technologists do not routinely call critical drug values on in-patients to the lab. med. resident (LMR) - however, whenever there is an unusual situation, problem or reason for concern they may call/page the LMR for assistance or for follow-up with the physician - response is clearly tailored to the situation 3. Requests for send-outs (tests which we dont offer and we refer to Quest, Mayo, NMS, etc.). - although the LMR is called on nearly all requests, many can be approved without follow-up - our primary role in reviewing these requests is NOT to screen indicated versus non-indicated tests (or, even less so, to perform a cost-benefit analysis) although, if a test is clearly inappropriate we should attempt to clearly communicate this to the physician. - instead, we should assess whether (1) if the test is possible (where to send it, correct sample, etc.), (2) if this is the best test for the clinical situation (i.e. maybe an alternative or additional test should be ordered) and (3) what interpretative value the test will provide (and offer assistance to the physician if needed). In the case of drug levels, this involves determining if a reference range exists for the drug and how well that range correlates with efficacy/toxicity of the drug. As well, we must make sure that proper attention has been paid to pharmacokinetics when ordering the drug (trough vs. peak, time to steady state, etc.). - should know all about the send-out desk and location of our card catalogue and reference books 4. How long is it positive? - difficult to answer, depends on many factors - will attempt to cover details in lectures - bottom line (but not sufficient for answer): most drugs are negative in 1-5 days (rare exceptions for 10-14 days), except for cannabanoids which can be positive for weeks (rare exceptions for months). - see article included in the Resident Education web page 5. Which tube should I draw? - unfortunately commonly get referred to LMR because of worry over need for clinical judgement - most of the time, just look it up in the spinning manual or find answer at the send-out desk - take the opportunity to proactively address possibility of follow-up due to #3, above 6. In this anuric patient, can we detect drugs of abuse in serum (or, sometimes, other bodily fluids such as breast milk or stomach contents)? - yes, but it is a lot of work and the interpretation can be tricky - refer all of these to Dr. Hodsdon or other laboratory director 7. Questions about potential cross-reactivities/interferences with immunoassays. - very important role of LMR

- information is found in multiple locations: lecture handouts (part of resident manual), laboratory procedure for the test and the package insert (occasionally may need to do a medline search). - stress role of confirmatory testing to resolve issue, although answer is usually delayed by days - a few tests are not routinely confirmed (benzodiazepines and cannabinoids), but we can offer sendout confirmation whenever requested - immunoassay for serum tricyclic antidepressants (TCAs) are a big problem, details in handout and in laboratory procedure manual; communication by the LMR to the physician is critical - a related, common question is whether we can prove that a positive opiate immunoassay is due to heroin and not due to other sources of morphine and codeine (such as poppy seeds) - there is a common interference with the amphetamine immunoassay requiring a send-out; LMR should call physician to see if necessary - spironolactone (and other chemically related drugs) cause a potential negative interference with our digoxin immunoassay (see paper with procedure) 8. Requests for detection of ethylene glycol in blood. - no requirement for LMR approval, test should be done directly without delay - LMR is called for clinical consultation as all positive results are considered a critical value - remember that a normal osmolal gap does NOT exclude a potentially fatal glycol or alcohol poisoning 9. My patient is taking a drug, but the drugs of abuse, urine panel is negative. - most often a problem with opiate and benzodiazepine immunoassay - we can offer GC/MS detection of oxycodone and hydrocodone - for benzodiazepines, we send the sample out to a referral lab for a panel done by either HPLC, GC/MS or LC/MS/MS. 10. Off-hours request for drug levels. - some tests are available 24-hours/day and others are only performed once/day or 1-3 times/week - there will be a specific cutoff point (time and day) for accepting new samples for scheduled tests - frequently, drug levels are requested off-hours or after the cutoff point - the LMR should explain to the physician the situation (emphasize that scheduled tests are generally performed manually and take many hours to complete) and confirm that an off-schedule test is actually desired (often they simply realize that they can wait until the next scheduled run) - once confirmed, then the LMR should inquire about the clinical situation and assess the need for the test in collaboration with the physician caring for the patient; i.e. a dialogue should ensue where a consensus is reached, not a simple approval/disapproval. - sometimes alternative arrangements can be arranged which satisfy the clinical need and minimize adverse impact on other patient services provided by the laboratory - feel free to contact a laboratory director for consultation in handling these requests; in general, a technologist should not be called in from home to perform a test without approval from director 11. Requests for free phenytoin levels, their interpretation and other problems. - interpretation of free phenytoin is best covered in the pharmacokinetic lectures - they used to be done on as-needed basis dependent on LMR approval - now, we offer them daily M-F without LMR approval - however, off-hours requests (rare) require approval - as well, the technologists monitor the use of the free phenytoin level by physicians and will alert the LMR with concerns about appropriate use and interpretation

12. Requests for cannabanoids on non-YPI (Yale Psych. Inst.) patients. - cannabanoids not included in routine DAU panel, except for YPI - this is because of low clinical significance of a positive result, in most cases - when requested, we will provide cannabanoid testing on other YNHH patients, but the LMR is contacted to provide clinical consultation (caveats for interpretation) and also to inquire about the need for send-out confirmatory testing 13. Vancomycin levels. - complex situation where physicians are not allowed to order vancomycin levels directly; they must get approval from the pharmacy and if they disagree with the ruling of the pharmacy they page the chief of service representative (an MD, generally an ID fellow, basically the same person who approves non-formulary antibiotics) for a 2nd ruling. - this policy was instituted by the Pharmacy and Therapeutics Committee and is NOT a laboratory medicine policy - we should support the policy and refer any requests for vancomycin levels to the pharmacy - however, should a dispute arise, the LMR is free to approve a vancomycin level, but should refer the event to a chemistry director for further discussion with the pharmacy, et al. 14. Antibiotic levels in CSF. - occasionally a physician will want to measure an antibiotic level in CSF and this requires LMR approval - there is not good data correlating CSF antibiotic levels to efficacy, problems such as variable penetration of the blood-brain barrier exist; all the trials for establishment of clinical efficacy based on blood levels - when the antibiotic is given intrathecally, the physician has no choice but to monitor CSF; they get automatic approval and should only have to call once (put the name up on the white board in the spinning room). - primary concern is that a patient receiving IV (or PO) antibiotics for meningitis (or other CNS infection) will only have antibiotic levels monitored in CSF (i.e. physician wont also follow blood levels). - therefore, make sure that physician will continue monitoring of blood levels and is aware of their primary importance - otherwise, dont deny the CSF antibiotic level, just provide clinical consultation on interpretation and further use 15. Digoxin levels in patients on spironolactone (and other related molecules). - spironolactone, canrenone and other related steroids negatively interfere with our digoxin assay (see article and commentary from Clinical Chemistry on the Resident Education web page). - biggest effect is when they are given by IV at relatively high doses, often used to treat ascites; in such cases measured digoxin levels might be less than one-half of the true level. - spironolactone is frequently used for CHF at doses of 12.5 50 mg PO qd; this translates into only about a 10% inhibition of the digoxin level - best advice for the physician is to measure the digoxin level when spironolactone is at its trough, i.e. just before the next dose; of course, if spironolactone is being given IV, this isnt an option. 16. Can poppy seed ingestion cause a positive urine opiate immunoassay? - yes, actually very common

- guidelines have been established by the NIDA for distinguishing heroin abuse from poppy seed ingestion; any of the following are supposed to rule-out poppy seed ingestion as the likely cause of a positive urine opiate assay: 1) Any amount of 6-monoacetylmorphine 2) Total morphine concentration > 5,000 ng/ml (maybe should be raised to > 10,000 ng/ml) 3) Total codeine concentration > 300 ng/ml 4) Ratio of morphine:codeine concentrations < 2.0 5) Combination of NO codeine and total morphine concentration > 1,000 ng/ml - see related article on Resident Education web page