Our miniscreen for drug abuse testing.

Our mini-screen for drug abuse testing

It was a familiar laboratory problem. We wanted more than we could have--specifically, 24-hour drug screening service without overburdening the toxicology staff or hiring more help.

The author and five other toxicologists actually had been providing 24-hour service, but we were overburdened. Besides working our day, evening, and weekend shifts, we took weekly turns on call for night testing. Stat drug screens ordered from the emergency room, from our 350-bed hospital's psychiatric annex, and from another local hospital cost us hours of sleep. In an average week, the on-call toxicology technologist made at least one or two early morning trips to the lab. Overtime expenses mounted, too.

The laboratory was minimally staffed at night, for Stat testing. Three technologists covered the blood bank, chemistry, hematology, coagulation, and urinalysis, and also processed bacteriology specimens. Although they acknowledged the value of round-the-clock drug testing, administrators at our hospital had trouble justifying the cost of an added toxicologist. Thus there was no one on the night shift who could perform the full range of toxicology testing, particularly thin-layer and gas chromatography.

Eventually, a solution dawned on us. The night technologists could perform several key drug tests by relatively simple, alternative methods. These tests might in many cases serve immediate medical needs, making it unnecessary to bring in a toxicologist for a full screen. In the morning, the toxicology staff would perform confirmatory tests.

I worked with our laboratory's Ph.D. consultant to determine what the nighttime Stat profile should include. We came up with 10 rapid tests for commonly abused drugs or drug families: ethanol, salicylate, ethclorvynol, phenothiazines, PCP (phencyclidine), sympathomimetic amines, barbiturates, benzodiazepines, cocaine, and opiates. Once the plan received approval, we trained the night staff to run the profile.

The Mini-Screen, as we called it, made its debut in the fall of 1982 and has since worked just as we had hoped it would. The procedures, several of them spot tests, can be completed in less than one hour, often in 30 minutes. The results usually give physicians a good indication of what treatment to order and whether a patient should be admitted. Toxicologists are still called in to test for suspected drugs not covered by the screen, but that doesn't happen too often.

The toxicology staff double-checks all Mini-Screen results the next morning, using a second method. The nighttime specimens are subjected to the standard daytime battery, which includes thin-layer and gas chromatography and gas chromatography/mass spectrometer testing. We seek to confirm all positive Mini-Screen results and to look for any additional, unreported drugs.

Follow-up daytime testing may pick up a trace of drug missed the night before. So in reporting results of the Mini-Screen, we avoid the term "negative" except when referring to controls. Instead, we say "none detected." This means there is no drug present at a level detected by our methods--or at a level sufficient to warrant treatment, since our methods are sensitive enough to detect overdoses.

Urine is the specimen of choice for our drug screens. It is fairly easy to process, gives us more of a drug than other specimens, and often yields both the parent drug and its metabolite, which is helpful in identification.

Gastric contents can provide a good specimen if ingestion is recent. We do serum alcohol testing, but we haven't developed Stat drug screening procedures for serum; it is screened for other drugs only when such infrequent cases as liver disease or renal shutdown bar use of urine specimens. There's usually a much smaller amount of drug in serum, and the procedures are more difficult than urine testing.

The entire Mini-Screen is performed on every Stat drug testing order--even during the day because it gives the physician rapid results. When a physician orders a Stat drug screen at night, a technologist enters the patient in the toxicology log book. The blood specimen is then centrifuged and the serum placed in a rubber-stoppered tube to prevent the evaporation of volatiles. An ethanol test is performed on a discrete analyzer in the chemistry department. The volatile screen by gas chromatography, which can detect ethanol, methanol, ispropanol, and acetone.

Next, the night technologists perform spot tests on the urine specimen for ethchlovynol, salicylate, and phenothiazines. If filtered gastric specimens are available, spot tests are also done on them.

In the spot test for urine ethchlovynol, that drug plus diphenylamine produces a pink color. Since phenothiazines can cause false-positive reactions, chloroform is added after the color reaction. In a true positive, the pink color extracts into the bottom chloroform layer. Of course, the technologist also runs a positive and a negative control with each spot test.

Salicylate plus ferric chloride produces a violet color. All positive urine salicylate results are verified by running a quantitative serum salicylate level.

In the presence of a suitable oxidizing agent, phenothiazines develop a color that matches the positive control. While this test may not pick up the drug in patients taking a prescribed dosage, it is a good indicator of gross overdosage.

Urine specimens are also tested by enzyme multiplied immunoassay for PCP, amphetamines, barbiturates, benzodiazepines, cocaine metabolite, and opiates. We use a modified spectrophotometer, and the results are qualitative.

To perform the test, the night technologist adds 3 ml of distilled water and 50 [mu]l of specimen to the patient vial. Next, 3 ml of distilled water and 50 [mu]l of calibrator are added to the calibrator vial. The calibrator contains measured amounts of all of the drugs being tested. The two vials are shaken immediately to mix the contents and inserted as a pair into the instrument.

The spectrophotometer, permanently set by the manufacturer at one wavelength, measures the rate change in each vial and prints the results on a special card 90 seconds later. If the rate of change of absorption for a patient specimen is greater than that of the calibrator, the report is positive for that particular drug. If the rate of changes is less, the presumptive report reads "none detected." The amount of drug in the calibrator defines the test sensitivity for that agent.

The results for all of the tests are reported on a Mini-Screen form and sent to the emergency room via a facsimile machine. The final report is issued the next morning after the toxicologists run their comprehensive drug screen. The following case studies detail typical results from the Mini-Screen:

* The history indicated that the patient passed out while drinking with his buddies. The ethanol level was 390 mg%. For the other nine analytes on the Mini-Screen, the report was "none detected" (Figure I). This told the physician that the patient's primary problem was ethanol intoxication. Indeed, follow-up thin-layer chromatography did not reveal any additional drugs.

* This patient felt "funny." She had no history of therapeutic drug use. The Mini-Screen did not detect ethanol but did find a positive urine salicylate. The night technologist performed a serum salicylate, which indicated a level of 9.4 mg/dl--a therapeutic level is less than 20 mg/dl. The only other positive finding was for the amphetamine family, which includes amphetamine, methamphetamine, ephedrine/pseudoephedrine, phentermine, and phenylpropanolamine (PPA). The last four drugs are typical over-the-counter cold preparations.

Thin-layer chromatography, performed the next day as part of the comprehensive drug screen, identified the sympathomimetic amine as PPA and also picked up the presence of acetaminophen. The patient's serum acetaminophen level was 10.4 [mu]g/ml, just within the therapeutic range of 10 to 20 [mu]g/ml. In this case, the patient had a cold and neglected to mention her medication.

* According to the history, this patient was taking Tylenol No. 3 (acetaminophen and codeine). The serum ethanol was 120 mg%, and the urine specimen was positive for benzodiazepines and opiates. Subsequent thin-layer chromatography indicated the presence of codeine and acetaminophen. The serum acetaminophen level was 11 [mu]g/ml, and the presence of codeine was confirmed by gas chromatography.

Evidently, this patient had neglected to mention that he was also taking either diazepam or chlordiazepoxide. (The toxicology staff was not able to further identify any parent benzodiazepines in this case.)

* This patient had a history of depression and tricyclic antidepressant use. The Mini-Screen showed only an ethanol level of 125 mg%. Other analytes were reported as "none detected." While the physician had cause for concern about the patient's alcohol consumption and tricyclic antidepressant use, he did not have to worry about potential alcohol interaction with any of the drugs in the Mini-Screen.

The doctor decided to call in a toxicologist to perform thin-layer chromatography, which in fact demonstrated the presence of a tricyclic antidepressant, amitriptyline. The toxicologist drew an adequate serum specimen (two clot tubes--minimum of 4 ml of serum) and went home. The next day, the toxicology staff performed a quantitation for amitriptyline and its active metabolite, nortriptyline. The procedure, which takes four to six hours, revealed serum levels that exceeded the therapeutic range.

In this case, it was wise to go beyond the Mini-Screen and bring a toxicologist into the laboratory. But the Mini-Screen did help rule out any possible problems with other drugs.

The Mini-Screen's advantages are clear. Its tests are fast and easy to perform. They enable emergency room physicians to start treatment within an hour of a Stat requisition because the laboratory work doesn't have to await the arrival of a toxicologist.

In addition, by allowing the toxicology staff to concentrate on its daytime responsibilities, the screen saves both the laboratory and the patient money. The lab is no longer saddled with heavy overtime, and patients aren't billed $57 for a toxicology consult. (There is no charge for phone consultations.)

Most of the disadvantages of the Mini-Screen have to do with the fact that it is not complete in itself. Additional testing is always performed.

If the screen's barbiturate test is positive, for example, a toxicologist must be called in for thin-layer chromatography to distinguish between phenobarbital and the short-acting barbiturates. These two classes of barbiturates call for different treatments.

The Mini-Screen will not pick up acetaminophen. When a physician suspects acetaminophen ingestion, he or she generally orders a serum test, which is performed at night on an automated instrument. The test is too expensive to be run routinely without a specific request. In any event, acetaminophen would be detected the next morning by thin-layer chromatography.

Tricyclic antidepressants also are not detected by the Mini-Screen. A physician who suspects one of these drugs will usually call in a toxicologist for thin-layer chromatography. Commonly encountered tricyclic antidepressants include amitriptyline, nortriptyline, imipramine, desipramine, and doxepin.

Finally, reagent costs are higher for the Mini-Screen than for a routine drug screen. Costs for the former use driven up by six enzyme multiplied immunoassays. On the routine screen, we use enzyme multiplied immunoassay reagents only for the benzodiazepine family and cocaine metabolite. Helping offset this higher cost for Stat testing at night is the labor saving--we do not have to pay a toxicologist overtime to come in and perform a drug screen.

In all, the Mini-Screen's advantages far outweigh the disadvantages. Our toxicologists are certainly better rested these days. We still have our on-call rotation, but we no longer get a late-night summons one or mre times per week--the frequency is more like once a month. Of course, we are awakened by phone calls when someone on the night shift has a question. That's a small price to pay.

I am glad we launched the Mini-Screen when we did, because business has really picked up. Our toxicology workload now includes Stat orders from a local reference laboratory that services the entire state. Volume has grown from just one or two drug screens to as many as 10 to 15 in a single 24-hour period. Without the Mini-Screen, on-call toxicologists would essentially pull double shifts, and additional staffing would be inevitable.

We recently trained the night shift at another hospital to do the Mini-Screen. The next morning, specimens are sent to our lab where we finish the screening and do the confirmation.

When an idea makes sense, it catches on.