The Structure Of Clinical Toxicology Testing

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It has been argued above that random screening is not an effective approach to the problem of laboratory involvement in care of the overdosed patient. What tests should be included in a hospital's repertoire and how rapidly should the laboratory provide such testing results? Three knowledgeable sources have published responses to this question and they provide the lists shown here for STAT (i.e., immediate) testing in the context of possible drug overdose:

LIST 17

LIST 28

LIST 39

Iron

Iron

Acetaminophen

Acetaminophen

Acetaminophen

Methanol

Methanol

Methanol

Methemoglobin

Methemoglobin

Methemoglobin

Carboxyhemoglobin

Carboxyhemoglobin

Carboxyhemoglobin

Salicylates

Salicylates

Salicylates

Ethylene glycol

Ethylene glycol

Theophylline

Theophylline

Lithium

Lithium

Arsenic

Iron binding capacity

Barbiturates

Digoxin

Lead

Ethanol

Osmolality

The lists above may be regarded as compilations of the most important toxicology tests, and those tests should be provided locally. Results from them should ordinarily be reported in 1 hour or less. A review of the above recommendations shows a high degree of agreement among these experts but some surprising vari ability. For example, one opinion supports lead and arsenic as critical analytes that should be eligible for STAT testing, but other experts do not agree. Also, only one of the three experts believes that iron binding capacity, digoxin, ethanol, and osmo-lality should be included in this critical grouping.

What are the criteria to be considered when making a decision about the importance of offering a particular test within one's laboratory? A critical principle in laboratory medicine must be kept in mind here. If a test result alters therapy in a critical way, then that test is, by necessity, a critical one. Another factor is lethality of the toxin. If exposure to a substance causes only minor symptoms then we can feel free to exclude that test from our menu. A second consideration is the availability of an antidote. If an effective antidote or other treatment is available, then the knowledge that a patient's symptoms are due to a specific toxin is of great value because it directly guides the physician's intervention. A third factor is the relative informational content supplied by the patient's presentation. This refers to the ability of the history, physical examination, etc. to guide the patient's care without any help from the laboratory. If the patient has a severe cardiac arrhythmia, for example, and a specific medication would always be given to counter this arrhythmia, then the laboratory identification of the toxin is irrelevant to the subsequent steps taken by the treating physician. On the other hand, if the patient's presentation is misleading, the laboratory might be quite helpful. For example, acetaminophen may cause mild symptoms such as nausea. A finding of high amounts of acetaminophen in the blood of a nauseous patient changes the treatment plan totally. A fourth factor is the presence or absence of a pharmacokinetic relationship between the laboratory finding and its clinical significance. By this we mean that a positive drug finding may be coincidental to a patient's presentation. A positive urine screen result for antidepres-sants can be due to normal therapeutic use of antidepressants and may not explain symptoms that the patient is currently manifesting. A high serum level of a phe-nothiazine may be due to the patient's tolerance to these drugs and may not be associated with some problem that the patient is currently experiencing. A fifth factor is the frequency with which a particular toxin is ordered for testing. For example, if a laboratory is asked to test for ethylene glycol 2 or 3 times a year, then it probably makes no sense to do the test in house. Even if rapid results are needed, the laboratory is not likely to conduct this test in a competent manner because its personnel lack sufficient experience in doing the test.

Why were the specific tests listed here selected for inclusion? Iron is chosen because it is common in overdose and because the clinical presentation is likely to overstate the severity of the poisoning. Intense GI irritation and hypotension occur, which collectively often suggest that the patient's situation is worse than it really is. Nevertheless, iron toxicity is often life-threatening. A quantitative serum level can help to sort things out. Acetaminophen is selected for the opposite reason. Severe overdose may appear to be mild when first observed but there is a risk of hepatic failure if antidotal therapy is not begun. Methanol is dangerous because its toxicity is due more from its metabolites than from methanol itself. Thus, the most critical symptoms are delayed and laboratory help in recognizing a severe overdose is likely to be beneficial. Methemoglobin must be confirmed by a laboratory test in order to distinguish this cause of cyanosis from other causes. Serum concentrations of sali-

cylate are critical because salicylate poisoning is a common occurrence and early symptoms do not correlate well with prognosis. Theophylline levels are valuable because there is a narrow margin between a safe dose and a toxic dose and a patient may have minor symptoms that can abruptly escalate to major problems such as respiratory and cardiac arrest. A high level is sometimes a major prognostic factor for severe toxicity. Carboxyhemoglobin must be measured because carbon monoxide is a relatively common toxin and CO concentration is suggestive of the severity of exposure.

The testing opinions of several experts have been presented above. The present author suggests still a fourth set of tests and rules for the ideal use of the toxicology laboratory. The following list is intended to meet almost all of the needs of the attending physician and at the same time be realistic in regard to the economic and technical limitations placed on the laboratory:

Screens that should be STAT eligible

Urine: marijuana metabolite, cocaine metabolite, amphetamines, opiates, phencyclidine, benzodiazepines, and barbiturates Serum: acetaminophen, salicylates, ethanol Therapeutic drug levels that should be STAT eligible

Phenytoin, digoxin, theophylline, lithium Therapeutic drug levels that should be offered but not STAT

Aminoglycosides, anticonvulsants (except phenytoin), antiarrhythmics Miscellaneous tests that should be STAT

Carboxyhemoglobin, methemoglobin, iron Tests that should be sent to commercial laboratories Methanol, ethylene glycol, isopropanol

How is this last list justified? The drugs of abuse and over-the-counter analgesics that are recommended for STAT testing are very common in overdose situations. Many fatalities have been seen with these drugs. Therapeutic drugs that are often measured in the serum are potentially very toxic, especially those listed here for STAT service. Carboxyhemoglobin, methemoglobin, and iron are common enough and of proven clinical value. They can be done by highly automated and inexpensive test methods. Finally, alcohols other than ethanol should be sent to outside laboratories unless the hospital laboratory is located in an area where these substances are commonly found. That is rarely the case. Because the tests are rarely ordered and difficult to conduct it makes sense to send them to a laboratory accustomed to this type of analysis. Some contend that physicians need immediate results in order to decide whether a patient should be started on hemodialysis. The fact is, however, that a decision to dialyze is best based on the overall condition of the patient, not merely on a laboratory number.

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