Emergency Toxicology Testing

Question 1

What is the glasgow coma scale range, and what are the levels?

Answer 1

mild: 13-15
moderate: 9-12
severe: 3-8 (intubate)

Question 2

What are the specimens for ESSENTIAL lab tests? What are the tests done

Answer 2

Blood and urine
- CBC
- ABG
- Electrolytes (anion gap)
- Glucose
- Bicarb
- Urea/creatinine
- osmolality (osmolar gap)
- PTT
- Liver function tests
- urinalysis

Question 3

What are the specimens for emergency toxicology? describe the benefits

Answer 3

Blood and urine
- blood: best change for correlating symptoms with drug concentration
- urine: non-invasive and easy sample collection; higher concentrations than serum

Question 4

How do you calculate the anion gap?

Answer 4

anion gap= (Na + K) - ( HCO3 + Cl)

Question 5

How do you calculate the osmolar gap?

Answer 5

Osmolar gap = measured - calculated osmolality

calculated osmolality = glucose + urea + (ethanol * 1.2 ) + (Na * 2)

Question 6

What can cause Anion gap metabolic acidosis?

Answer 6

2 mnemonics
MUDPILES: methanol, uremia, diabetic ketoacidosis, Phenformin, iron+ ibuprofen, lactic acidosis (eg. cyanide) , ethylene glycol, salicylates

GOLDMARK: glycol (ethylene and propylene), oxoproline, L-lactic-acidosis, d-lactic-acidosis (caused by fermenting gut bacteria), methanol, aspirin, renal failure, ketones

Question 7

What causes osmolar gap?

Answer 7

MEDIE: methanol, ethanol, diuretics, isopropanol, ethylene glycol

Question 8

Why should we perform emergency toxicology testing?

Answer 8

• support treatment decisions
• help physicians diagnose patients suffering from accidental or intentional poisonings (useful if patient is unable/unwilling to admit ingestion)

Question 9

What are the two tiers of emergency toxicology testing?

Answer 9

tier 1: select serum quantitative tests, and urine qualitative tests (available 24/7, <1 hr)
tier 2: detects additional drugs, may require reference lab testing (hrs to days)

Question 10

What are the considerations for choosing tier 1 toxicology testing?

Answer 10

• consult the ED physicians
• local drug abuse patterns
• significant toxicities
• immediate impact on subsequent treatment decisions (therapy or antidote available)
• ability of lab to meet turn around time req (24/7 <1hr)

Question 11

What are 3 important tier 1 drugs in plasma

Answer 11

• acetaminophen
• salicylates
• ethanol

Question 12

What are some important tier 1 drugs in urine

Answer 12

note urine is qualitative, just looking for presence
typically looking for illicit drugs:
- amphetamines
- fentanyl
- opioids
- cocaine
- benzodiazepines

Question 13

What drugs are found in tier 2 toxicology testing? what are some considerations?

Answer 13

anything not in tier 1
-methods are less automated (often mass spec based)
- specimen type can vary

Question 14

What are the methods used in essential lab testing?

Answer 14

blood gas analyzer
osmometer
urinalysis
spectrophotometer

Question 15

What are the methods used in toxicology testing?

Answer 15

immunoassay
gc
gc-ms
lc tandem mass spec

Question 16

What are the 3 use cases for urine drug testing

Answer 16

1. urgent care setting (intoxicated patient)
2. forensic urine drug testing (workplace drug test, substance abuse during pregnancy)
3. patient centered clinical urine drug testing (chronic opioid therapy for pain; addiction clinics; psychiatric clinic) -> used to minimize risk of unintentional overdose (monitor adherence to therapy; detect drug diversion; detect illicit drug use)

Question 17

What drugs are tested for in urine test

Answer 17

Typical illicit drugs: amphetamines, cannabinoids, cocaine, opioids
Pain-medication: opioids, benzodiazepines (also used in psychiatric)
Opioid addiction medication: methadone, buprenorphine

Question 18

What are 4 urine drug testing methods

Answer 18

immunoassays:
- instrument based IA analyzer
- point of care testing device

Specific drug identification:
- GC MS
- LC tandem mass spec

Question 19

How does the homogenous immunoassay EMIT work?

Answer 19

If urine sample contains the target drug above the cutoff, the antibody will release from the enzyme (G-6-P dehydrogenase) that initially already was bound to some of the drug. The enzyme will then be able to activate and produce the product from the substrates G-6-P and NAD -> phosphogluconolactone and NADH thereby producing a detectable signal. If the drug in the urine is not above the cutoff, the antibody will remain bound to the enzyme, preventing it from activating, thereby not producing a signal

Question 20

How does the homogenous immunoassay CEDIA work?

Answer 20

In the Cedia assay, the enzyme (beta galactosidase) is fragmented into an enzyme acceptor, and an enzyme donor that is conjugated to the target drug. The antibody is initially bound to the enzyme donor + drug fragment. If the urine sample contains enough drug to pass the cutoff, the antibodies then bind to the drugs in the urine, release the enzyme donor allowing it to activate with the enzyme acceptor and form the functional enzyme unit. They then catalyze the substrate into the red product that can be detected.

Question 21

how does the POC microparticle capture immunoassay work?

Answer 21

The microparticle capture immunoassay has a capture zone with the drug of interest and a control zone with antibodies. When the sample is first input in sample well, it picks up coloured beads with antibodies and it flows along the test strip. If there is drug in the sample, the antibodies on the beads will bind to the drugs, and so when it flows past the capture zone, it cannot bind to the capture zone. It will then flow to the control zone where the antibodies in the control zone bind to the antibodies in the sample, producing a line. In a positive test only 1 line is visible. In the case that the sample is negative, the antibodies carried by the sample will bind to the capture zone and the control zone, producing 2 lines.

Question 22

What are the limitations of urine drug testing by immunoassays

Answer 22

Sensitivity: false negatives
- does not indicate absence of drug
- oxycodone for EMIT
- POCT opioid test for hydrocodone, hydromorphone, oxycodone

specificity: false positives
- other medications with similar structures (sometimes even structurally unrelated)
- amphetamines are highly cross-reactive; can detect OTC meds
- tests for opioids (can cross reacts with structurally similar such as some antibiotics)

Question 23

Describe the performance of immunoassays for cocaine, amphetamines, opioids, benzodiazepines, methadone, fentanyl, and tricyclic antidepressants

Answer 23

cocaine: very good, detects its metabolite with low cross-reactivity to other things
amphetamines: false neg with MDMA, false pos when taking OTC meds
opioids: false neg with oxycodone, false pos with some antibiotics
benzos: false negative
methadone: false positives with antipsychotic drugs
fentanyl: false positives with antipsychotic drugs
TCA: false positive with benadryl, gravol