Definitions for the degree of consensus (A or B) are provided at the end of the "Major Recommendations" field.
General Principles for Drug Testing to Support Emergency Department (ED) Toxicology
Tier I Toxicology Testing
Guideline 1.
The clinical laboratory should provide two tiers of drug testing. The first tier includes stat testing of selected target quantitative tests in serum or plasma (see Table 1 below) and qualitative tests in urine (see Table 2 below). If the patient is in no acute distress, additional or even most initial toxicology testing may be unnecessary.
Degree of consensus: A for the analytes listed in Table 1, B for the analytes listed in Table 2.
Table 1. Stat quantitative serum toxicology assays required to support an ED*
- Acetaminophen (paracetamol)
- Lithium
- Salicylate
- Co-oximetry for oxygen saturation, carboxyhemoglobin, and methemoglobin
- Theophylline
- Valproic acid
- Carbamazepine
- Digoxin
- Phenobarbital (if urine barbiturates are positive)
- Iron
- Transferrin (or unsaturated iron-binding capacity [UIBC] assay if transferrin is not available)
- Ethyl alcohol
- Methyl alcohol**
- Ethylene glycol**
*Turnaround time (TAT) of 1 hour or less.
**More realistic TATs for these assays are 2-4 hours. These tests are largely unnecessary in countries where these agents are not widely available.
Table 2. Stat qualitative urine toxicology assays required to support an ED*
- Cocaine
- Opiates
- Barbiturates
- Amphetamines**
- Propoxyphene**
- Phencyclidine (PCP**)
- Tricyclic antidepressants (TCAs***)
*In general, urine toxicology screens such as these have a lower urgency and utility than do serum assays. They do not correlate well with clinical effects and suffer from problems with sensitivity and specificity, as discussed in the text. Although widely available, these assays (with the exception of that for the cocaine metabolite) require clinical interpretation.
**Need for these assays may be based on prevalence of drug use, which may vary from region to region. Regular review of drug usage is important.
***Recommended only if the clinical staff fully understands the specificity limitations of this assay (i.e., results are used in conjunction with the electrocardiograph to support a clinical suspicion of TCA toxicity, but not in cases where a positive urine drug test is the sole evidence for this suspicion.)
Assay Turnaround Times for Tier I Tests
Guideline 2.
The ideal TAT for Tier 1 toxicology tests is 1 hour or less except where noted on Table 2.
Degree of consensus: B
Tier II Testing: Comprehensive or Board-spectrum Testing
Guideline 3.
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 and would not be identified based on the findings of the first tier of laboratory tests. Results of these tests might be used for more long-term management and/or counseling of patients. Laboratorians should work closely with intensive care providers to determine the appropriate menu of tests and TATs that are necessary.
Degree of consensus: B is necessary to cover drugs and substances that may have clinical significance
Guideline 4.
Testing for toxins beyond those outlined in Tables 1 and 2 should be performed only after the patient is stabilized and the attending physician has received toxicology input from a poison control center or, preferably, bedside evaluation by personnel trained in medical toxicology.
Degree of consensus: A
Selectivity of Testing
Guideline 5.
Stat testing for the following drugs is not recommended for ED patients presenting with acute symptoms: tetrahydrocannabinol (THC; marijuana), lysergic acid diethylamide (LSD), methaqualone, ibuprofen, and cotinine (nicotine metabolite). Testing for some other drugs, such as amphetamines, PCP, and propoxyphene, should be conducted in areas where these drugs exhibit notable prevalence.
Degree of consensus: B
Drug Panel by "Toxidromes"
Guideline 6.
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.
Degree of consensus: A
Gastric Samples
Guideline 7.
There is no role for the testing of gastric contents in clinical management, although premortem collection and specimen retention may be important for cases with medico-legal considerations.
Degree of consensus: A
"Chain-of-Custody" for Clinical Specimens
Guideline 8.
Maintenance of chain-of-custody documentation is unnecessary for samples collected for clinical toxicology purposes, and such practice should be discouraged. As with any laboratory specimen, proper procedures for collection, transport, results reporting, and storage are necessary.
Degree of consensus: A
Recommendations of Analytical and Reporting Issues for Drug-of-Abuse Testing by Immunoassays
Immunoassays
Guideline 9.
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 ED staffs is necessary. The laboratory should clearly communicate to the ED staff the extent of the toxicology services available to them, such as the menu, target TATs, cross-reactivity data, and contact information for consultations.
Degree of consensus: A
Listing of Cross-Reacting Substances on Immunoassays
Guideline 10.
When immunoassays are used, the laboratory should list the major cross-reacting substances for each drug class when a positive result is reported. It may also be appropriate to indicate in a final report (e.g., in the "notes" section) that a negative urine drug result does not indicate absence of all drugs of abuse.
Degree of consensus: A
Immunoassay Cutoffs
Guideline 11.
Cutoff concentrations optimized for workplace drug testing are not necessarily appropriate for clinical toxicology. Although a true-positive result indicates use, it does not presume impairment or intoxication of the patient at the time of specimen collection.
Degree of consensus: A
Inadequate Spectrum of Benzodiazepine Detection by Immunoassays
Guideline 12.
Some immunoassays for testing benzodiazepines are inadequate. Antibodies in optimum assays should be targeted toward the parent compound and principal conjugated metabolites or should utilize an online hydrolysis procedure to convert the conjugated metabolites to the unconjugated forms.
Degree of consensus: A
Guideline 13.
Antibodies for benzodiazepines should be updated to identify the newer drugs in this class as they become approved and available for clinical use.
Degree of consensus: A
Opiate versus Opioid Detection by Immunoassay
Guideline 14.
Immunoassays should detect most opioids (e.g., oxycodone, hydromorphone, meperidine, tramadol, buprenorphine, propoxyphene, and pentacozine) and not just codeine and morphine.
Degree of consensus: B
Immunoassays for Amphetamines versus Sympathomimetic Drug Class
Guideline 15.
The optimum immunoassays to test for amphetamines in ED patients are those directed toward a broad spectrum of amines as a class, rather than assays that are directed specifically toward the illicit amines. An assay directed toward phenylethyl amines would largely cover this class. The name of the test should be changed from "amphetamines" to "sympathomimetic amines" or "stimulant amines."
Degree of consensus: A
Confirmation of Positive Immunoassays
Guideline 16.
When reporting results of immunoassay screening, there must be proper notation given that the assay used is considered as a "screening test'' and that any positive results are to be considered as "presumptive''.
Degree of consensus: A
Guideline 17.
The laboratory should not routinely perform confirmative analyses on positive screening results.
Degree of consensus: A
Guideline 18.
When confirmation is needed, the laboratory should store these specimens for an indefinite period or until the case is resolved. The laboratory should consult with the hospital's risk management department for further guidance.
Degree of consensus: B
Recommendations for Specific Analysis of Ethyl Alcohol and Other Toxic Alcohols
Need for a Breath Alcohol Quality-Assurance/Quality-Control Program
Guideline 19.
Clinical breath alcohol testing is point-of-care (POC) testing and must meet the same quality-assurance (QA)/quality-control (QC) requirements as any POC test. As a part of the laboratory's ongoing QA effort, a program must be in place to monitor and evaluate policy, protocols, and the total testing process so that breath alcohol results are accurate and reliable. The clinical laboratory should be involved in the design, implementation, and monitoring of the quality assurance program.
Degree of consensus: A
Selection and Validation of Breath Alcohol Analysis
Guideline 20.
The laboratory should be involved in the selection, validation, and deployment of the breath alcohol devices used.
Degree of consensus: A
Reporting Units for Ethyl Alcohol
Guideline 21.
Alcohol concentrations should be reported in units clearly defined by the laboratory, with a notation as to the sample matrix that was tested (serum or plasma, urine, whole blood, breath) and methodology.
Degree of consensus: A
Assays for Methanol and Ethylene Glycol
Guideline 22.
Clinical laboratories should provide direct measurements for methanol and ethylene glycol in serum or plasma. If gas chromatography (GC), the assay should target glycolic acid, the toxic metabolite, in addition to the parent intoxicant, ethylene glycol.
Degree of consensus: B
Osmolality Measurement for Toxic Alcohol Surveillance
Guideline 23.
Inherent problems with the measured osmolality and calculation of the osmolal gap reduce the reliability of these measurements in the differential diagnosis of volatile and ethylene glycol alcohol intoxication in patients. A very high osmolal gap (e.g., > 50 mOsm/kg) requires investigation of a toxic alcohol or other agents that can increase the osmolality.
Degree of consensus: B
Isopropyl Alcohol, Propylene Glycol Intoxication and Acetoacetic Acid
Guideline 24.
Quantification of isopropyl alcohol and propylene glycol by GC is the preferred approach to their identification. Measurement of lactate is appropriate for monitoring patients exposed to propylene glycol because this is the major metabolite.
Degree of consensus: A
Guideline 25.
Because propylene glycol is used as a vehicle in some drug preparations and there can be inadvertent exposure, this alcohol should not be used as an internal standard for the GC analysis of volatile alcohols.
Degree of consensus: A
Guideline 26.
In the absence of GC testing for isopropanol, the "Acetest" may be used as an insensitive surrogate because there is some reactivity of this reagent toward acetone. However, the name of the test should be listed as "acetoacetic acid" and not "ketones," "ketone bodies," or "acetone," as this test has the highest sensitivity toward acetoacetic acid.
Degree of consensus: A
Recommendations on Laboratory Assays for Other Toxicants as Causes of Poisonings
"Universal" Acetaminophen and Salicylate Screening
Guideline 27.
All ED patients who present with intentional drug ingestion and chronic overuse secondary to chronic pain should be screened with a quantitative serum or plasma acetaminophen assay.
Degree of consensus: A for quantitative serum or plasma screen.
Guideline 28.
Screening for the presence of salicylate can be guided by clinical findings or acid-base abnormalities.
Degree of consensus: A
Cyanide and Hydrogen Sulfide
Guideline 29.
The ED must rely on history and physical examination to determine whether treatment with cyanide antidote is appropriate. Collection of a blood sample for later cyanide and sulfide testing may be useful to document exposure.
Degree of consensus: A
Anticoagulants
Guideline 30.
Patients who intentionally ingest anticoagulants, particularly the long-acting formulations, should be monitored for coagulation status by the prothrombin time (PT) test. Samples should be collected at 24-36 hours after exposure to monitor anticoagulation effects without prophylactic vitamin K administration. There is no stat clinical need for determining the identity or concentration of the specific anticoagulant taken.
Degree of consensus: A
Lead Poisoning
Guideline 31.
Emergency testing for lead is not required to support ED practice. The ED should be prepared to collect heparinized blood samples for lead testing when lead exposure is suspected; however, specific treatment is usually not initiated in the ED. Because lead is ubiquitous in the environment, needles and collection and transfer tubes need to be free of lead contamination (<5 micrograms/L). Next-day availability of the blood lead result is adequate to ensure appropriate follow-up. Collection of serum or plasma for lead evaluation is not appropriate. The erythrocyte protoporphyrin (EPP) test is not useful for detecting low-level exposure.
Degree of consensus: A
Testing for Iron Toxicity
Guideline 32.
The clinical laboratory should be prepared to provide serum or plasma iron results on a stat basis to aid in the diagnosis of iron overdose. Because of analytical limitations, heterogeneous assays for the total iron-binding capacity (TIBC) cannot be used to determine the absence of free iron and toxicity. Serum or plasma transferring is a more reliable marker for estimating free and potentially toxic iron. If this assay is not available on a stat basis, the homogeneous unsaturated iron-binding capacity (UIBC) assay is more useful than TIBC assays that require a pretreatment step.
Degree of consensus: A
Arsenic and Mercury
Guideline 33.
A 12- or 24-hour timed urine collection in a metal-free container (use opaque plastics with no metal caps) is the best sample for arsenic and mercury analysis and falls outside the realm of ED practices. Results of urine testing should be available within 48 hours of specimen collection.
Degree of consensus: A
Broad-Spectrum Screening for Trace Elements and Environmental Pollutants
Guideline 34.
In the absence of probable cause, such as occupational and/or accidental environmental exposure, broad-spectrum screening for trace elements or other analytes is inappropriate and would rarely be indicated in the ED or any general office practice. These tests have not been sufficiently validated in a general patient population, nor have the implications of clinical decisions based on one-time measurements been discussed sufficiently to warrant any use other than research and biomonitoring for occupational exposure.
Degree of consensus: B
Pesticides
Guideline 35.
Clinical laboratories should provide access to stat pseudocholinesterase testing to screen for exposure to cholinergic agents and not for monitoring of therapy.
Degree of consensus: B
Inhalants
Guideline 36.
Because of a lack of stat availability, there are no clinical laboratory tests that are currently appropriate for monitoring acute inhalant abuse or solvent exposure.
Degree of consensus: A
Methemoglobinemia
Guideline 37.
For patients suspected of having methemoglobinemia, measurement of the fraction of oxyhemoglobin (oxygen saturation) should be performed with a co-oximeter and not a pulse oximeter, as the latter overestimates the actual O2 saturation. If a request for oxygen saturation is received, all results of a four-part co-oximetry panel should be reported even if the specific requests for carboxyhemoglobin and methemoglobin are not received. Laboratories should not charge separately for the inclusion of these additional results.
Degree of consensus: A
Regional Toxicology Centers
Guideline 38.
A cooperative effort should be made to establish regional toxicology centers where specialized methods can be made available to service the toxicologic needs of a larger community of medical centers.
Degree of consensus: A
Definitions:
Degree of consensus:
A - indicates general consensus by most participants
B - indicates either no consensus or that the recommendation was not applicable to all situations
