Table of Contents

A. Immunoassays
B. Tiered Testing
C. Broad Spectrum Testing
D. Selectivity of Testing
E. Drug Panels by "Toxidromes"
F. "Universal" Acetaminophen Screening

LMPG: Laboratory Support for Emergency Toxicology
(Draft Guidelines)

Part I. Recommendations for Drug Testing to Support Emergency Department Toxicology

A. Immunoassays

Immunoassays, which have become the mainstay of stat urine drug testing, have significant limitations in sensitivity and specificity.  Many emergency physicians are unaware of these limitations, and will order all available immunoassay tests for every patients suspected of drug use, irrespective of the presenting signs and symptoms, lack of clinical significance for some drugs, availability of management measures, and local prevalence for use and abuse of that drug.  Given the degree of cross-reactivities that many of these drug assays have, the accuracy of testing for a drug with a low prevalence can be very poor.  The limited number of available immunoassays to drug classes also limits the utility of this approach.  Furthermore, many clinicians are not even aware of what their own laboratory drug panel might cover (5). 

Recommendations throughout are shown in boxes.

Recommendation:  Optimum use of urine drug testing assays for ED patients requires an understanding of the limitations of existing commercial immunoassays for drugs of abuse.  A close relationship between the clinical laboratory and emergency department staffs is necessary.


The Committee feels that it is the joint responsibility of the emergency department and clinical laboratories to provide initial education on the limitations of drug testing to new house officers and to maintain a continuous medical education program to existing practitioners.  It is clear that this knowledge is not adequately taught at the undergraduate level, and it is inappropriate to expect that senior residents will have sufficient understanding of these limitations to effectively educate their junior house staff.  The laboratory must inform the ED staff when there are changes made to the specificity and performance of commercial drugs-of-abuse immunoassays.  They should also discuss the availability of new drug assays or assay platforms (e.g., point-of-care devices), and the appropriateness of implementing such assays in that institution.  On the other hand, ED physicians must inform the laboratory staff of changing drug utilization patterns, the appearance of new drugs or analogs such as designer drugs (6,7), or testing and reporting needs that are not currently being met.

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B. Tiered Testing

Due to significant limitations in resources and existing technology, it is impossible for any clinical laboratory to provide a full spectrum of toxicologic analyses for the impaired or overdosed patient in real time.  Given this limitation, it is appropriate to make recommendations as to which serum and urine tests have the greatest impact on patient management, and can be realistically delivered.

Recommendation:  The clinical laboratory should provide two tiers of drug testing.  The first tier includes stat testing of selected target analytes in serum and urine, with a turnaround time of 1 h or less.  Table 2 lists the group of tests that fit in this first category.  If the initial screen is negative and the patient is in no acute distress, additional toxicology testing may be unnecessary. There is no role for the testing of gastric contents.

Table 2. Stat Toxicology Assays Required to Support an Emergency Departmenta

Quantitative assays, serum

Ethyl alcohol

Phenobarbital (if urine barbiturates positive)

Methyl alcohol
Ethylene glycol

Qualitative assays, urine

Tricyclic antidepressants
Amphetamines (regionally-dependent)


aTurnaround time of 1 h or less.

Recommendation: The second tier of drug tests is for patients admitted to the hospital who remain intoxicated, obtunded, or comatose, where a broad spectrum (“comprehensive”) screening panel is necessary to cover drugs and substances that may have clinical significance, and are not attributed to the findings of the first tier of lab tests.  The turnaround time goal for reporting results is 24 hours.  Laboratorians should work closely with intensivists to determine the appropriate menu of tests that are necessary.


A two-tiered mechanism allows a laboratory to put the majority of their resources in providing for the needs of the sick ED patient.  The Committee has excluded certain drugs from the first tier of testing because they do not contribute to significant toxicities, or, are difficult to measure on a stat basis.  Some of these include the phenothiazines, calcium channel blockers, beta blockers, hypnotics and tranquilizers (chloral hydrate, ethchlorvynol, glutethimide), some anticholinergic drugs (e.g., atropine), muscle relaxants (carisoprodol, cyclobenzaprine), some antidepressants (e.g., fluoxetine), behavorial drugs (clonidine, methylphenidate), date rape drugs (gamma-hydroxybutyrate, flunitrazepam), certain anesthetics (e.g., ketamine), and analgesics (fentanyl and analogs).  Many of these drugs will be detected on the broad-spectrum tier of testing.

Once the patient has stabilized, and if the etiology of the original clinical problem is still unknown, it may be appropriate for the laboratory to perform additional tests.  In this situation, the turnaround time may not be as critical as for the tests in the first tier.  Techniques for a comprehensive urine drug screen profile include thin-layer chromatography (8), liquid chromatography with rapid scanning spectrophotometric detection (9), gas chromatography (GC), GC with mass spectrophotometry (10), and liquid chromatography/tandem mass spectrophotometry (11).  (A comparison of the advantages and disadvantages of each technique is beyond the scope of these guidelines.)  Hospitals that do not have adequate resources to perform a broad-spectrum screening panel can elect to send these specimens to a reference laboratory or regional toxicology laboratory.  In this situation, laboratory personnel should determine the reference laboratory’s methodologies used, expected turnaround time, and assay limitations, and communicate this information to the attending physician, as this may have impact on the interpretation of results.

It is important to note that the list of tests shown in Table 2 are analytes the laboratory should make available on a stat basis, so that when a patient who presents with signs and symptoms suggesting exposure to one or more of these drugs, the causative agent can be identified.  Table 2 does not imply an ED panel of the tests that should be ordered on all patients.  The ED physician and toxicologist must decide on the most appropriate plan of action based on the clinical presentation on a case-by-case basis.

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C. Broad Spectrum Testing

General screening for a broad spectrum of toxins is not indicated in the ED.  Stat testing for the toxins listed in Table 2 is adequate to support evaluation of acute toxicity carried out in the ED.

Recommendation:  Testing for toxins beyond those outlined in Table 2 should be performed only after the patient is stabilized and has received a thorough evaluation by a specialist trained in clinical toxicology.


The toxins identified in Table 2 represent the common agents that will cause a patient to experience adverse effects to the extent that it leads to an ED visit.  Table 2 represent those agents that can be readily recognized by experienced ED staff, supported by stat testing provided by the clinical laboratory, for which a specific therapy or antidote is available.  In the event that a patient presents either in coma or with bizarre behavior that cannot be explained by one of these toxins, further evaluation by a trained clinical toxicologist is indicated.  These evaluations usually occur outside the ED setting.  The clinical toxicologist may select from among a broader assortment of tests for toxicants and tests that are usually provided by a reference or regional laboratory.

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 D. Selectivity of Testing

It is not appropriate for the clinical laboratory to provide test results for all classes of drugs, simply because an automated and inexpensive immunoassay is available.  Certain tests may not be indicated because they do not contribute to significant toxicological sequelae, or have little or no prevalence in that particular geographic location. There is an additional problem of diagnostic inaccuracy if used on a general drug screen panel (particularly with PCP and tricyclic antidepressants, TCAs) because existing immunoassays exhibit significant cross-reactivity towards other drugs (e.g., dextromethorphan, diphenhydramine and sertraline for PCP (12) and phenothiazines, cyclobenzaprine, diphenhydramine for TCAs (13)).  As shown in Figure 1, even if the assay has an accuracy of 99%, when it is tested on a population of subjects where the prevalence is 0.1%, the rate of false positive findings exceeds the rate of true positive findings by 10-fold. 


10,000 Subjects




Negative Screen


True Negative


False Negative

Positive Screen


False Positive


True Positive




Fig. 1. The diagnostic outcome of a test that has an accuracy of 99% and is used on a population with a prevalence of 0.1%.  Of 10,000 subjects screened, there will be 10 subjects who abuse the drug in question, and all 10 will have a positive result for the assay (99% accuracy).  Of the remaining 9990 non-drug abusing individuals, 100 will have a falsely positive result (99% accuracy).  Given these pretest assumptions, only 9.1% of positive drug screen results (10 out of 110) will be from an individual who abuses the drug in question.

Recommendation:  Stat testing for the following drugs is not recommended for ED patients presenting with acute symptoms: tetrahydrocannabinol, lysergic acid diethylamide (LSD), methaqualone, ibuprofen, and cotinine (nicotine metabolite).  Testing for PCP should be conducted in areas where this drug exhibits notable prevalence.


The prevalence of methaqualone and phencyclidine (PCP) abuse is very minimal in the U.S. today.   In one recent study of drugs used in cases of alleged sexual assault, ElSohly et al. found no cases of methaqualone and PCP use among 1179 submitted urine samples (14).  A very low incidence of these drugs was also reported by 877 homosexual men (15).   While tetrahydrocannabinol (marijuana) and lysergic acid diethylamide (LSD) are more widely abused, many clinical toxicologists do not want to know if a patient is positive for this drug because they do not contribute to major acute clinical problems (16).  THC testing may be useful in drug compliance and rehabilitation programs that are outside the usual objectives of ED testing.

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 E. Drug Panels by “Toxidromes”

Patients who are drug intoxicated or overdosed often present to the ED with a collection of physical findings and symptoms that are consistent with a particular drug or class of agents.  Recognition of these “toxidromes” can be important in the effective clinical management of that patient while in the ED (17).  Proper identification of a particular toxidrome could be used to exclude some drug classes as the cause of the symptoms without performing the urine drug testing.  Drug testing panels can be established that link specific symptoms to a particular menu of tests (e.g., sympathetic: cocaine, amphetamines; sedative: benzodiazepines, tranquilizers, barbiturates; hallucinogenic: marijuana, lysergic acid diethylamide, phencyclidine).  Although implementation of such an approach could reduce the unnecessary utilization of laboratory tests, the opportunity of identifying the causative agent could be missed if the initial clinical impressions were made in error.

Recommendation:  Clinical laboratories should not set up specific drug testing panels based on toxidromes.  The failure to recognize a particular toxidrome may lead to the failure to order an important drug test.  Availability of the spectrum of tests defined in Table 2 is recommended.


Although the clinical laboratories are under tremendous pressure to reduce
costs and utilization of laboratory services, elimination of a few drug tests that are already available (i.e., regularly calibrated and quality controlled) on the menu of tests on an automated testing platform on urine collected and sent to the laboratory will not greatly impact the cost of delivering laboratory services.  On the other hand, a delay in the triage and management of the overdosed patient due to inappropriate laboratory orders can greatly affect the cost for treating that patient, and may have an adverse effect on patient outcomes.  There has been at least one study that examined the potential success of linking toxidromes to particular ED drug screening patterns (18).  When ED nurses, clinical pharmacists and medical residents were asked to choose among eight toxidromes, the diagnostic accuracy ranged from 79-88%, with the medical residents scoring the lowest of the group.  Although these figures indicate a reasonable degree of performance, the critical question is what would the clinical and fiscal impact be for the 12-21% of patients incorrectly diagnosed, if the toxicological causes of these cases were not identified.  The inaccuracies in the assessment of toxidromes may be due to presence of polydrug overdoses, delayed-onset toxicities (19), or clinical inexperience.  The importance of clinical experience in the ED is a major factor in the success of toxidrome accuracy and the potential use of specific drug panels.  In a study of periodicity of drug overdose presentations, Raymond et al. concluded that EDs are most likely to encounter overdosed patients in the early evening (20).  This is also a time of peak activity in the EDs, when both resident supervision and tolerance of delays in patient management may be critical.

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F. “Universal” Acetaminophen Screening

Acetaminophen overdose is a common clinical problem, with over 111,000 exposures reported to U.S. poison control centers and 40,000 associated ED cases per year.  Following therapeutic dosages, the majority of acetaminophen is detoxified by conjugation and excreted in the urine.  Toxic ingestion of acetaminophen results in more of the drug being metabolized by the CYP2E1 isoenzyme of cytochrome P450 to N-acetyl-p-benzoquinone imine, a highly reactive intermediate (21).  Accumulation of this metabolite leads to fulminant hepatic failure.  Therapy with N-acetylcysteine is most effective when initiated within 8-12 hours after ingestion.  Unfortunately, the early stages of acetaminophen toxicity are usually asymptomatic or when present, are nonspecific, and can be easily missed (22).  Determination of serum acetaminophen concentration will confirm ingestion and with Rumack-Matthews nomogram, allows for the initiation of appropriate therapy (23).  Once the first signs of hepatic injury become apparent, (right upper quadrant pain and tenderness, and increases in the concentration of serum aminotransferases), treatment may be less effective.  With the eventual development of fulminant liver failure occurs, orthotopic transplantation may be the only remaining therapeutic option.

Recommendation: All emergency department patients who present with intentional drug ingestions, and chronic overuse secondary to chronic pain, should be screened with a quantitative serum acetaminophen assay.


In the absence of specific symptoms to suggest the presence of a disorder, the introduction of a screening test for a particular population requires careful consideration before implementation.  In the case of acetaminophen screening, the cost of testing many patients to identify a small number of acetaminophen-overdosed patients must be weighed against the cost of treating missed acetaminophen ingestions that progresses to fulminant liver failure.  The incidence of detectable acetaminophen in blood of patients with suicidal ingestions or mental status changes ranges from 6-11%.   There have been a few studies conducted to determine the number of patients who deny ingestion of acetaminophen and yet had a potentially hepatotoxic acetaminophen concentration.   In the study of Sporer et al. (24), only 5 out of 1820 patients (0.3%) had a negative history and an acetaminophen concentration of >50 mg/L. On the other hand, Ashbourne et al. (25) found 7 of 365 (1.9%) of patients with occult acetaminophen ingestion at potentially toxic concentrations.  While both studies suggest that routine screening is warranted, there have been no outcomes studies to show that this approach is cost effective or provides medical benefit.  Nevertheless, the Committee felt that assessment of acetaminophen concentrations was appropriate in any circumstance of suicidal ingestion or repeated overuse.
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