SUBSTANCE
aIn decreasing order of frequency and based on 2,784,907 substances reported in 2,384,825 cases.
bData from reference 3.
aSome samples had multiple drugs identified.
In 2010, 4.1 million Americans (1.6% of the population) received treatment for a problem with the use of alcohol or illicit drugs.1 Of the 1.5 million people on parole and 5.4 million adults on probation in 2010, 27% to 30% were current illicit drug users and 37% to 38% were dependent or abusers of illicit drugs or alcohol.1 In a 2010 study of 8,300 arrestees in 10 U.S. sites, there was a high percentage of congruence between self-reporting of drug use and positive urine drug screening (82% marijuana, 61% methamphetamine, 45% cocaine, and 37% heroin).5
For eighth-, tenth-, and twelfth-grade students, the lifetime prevalence of the use of illicit drugs during 2011 was 20.1%, 37.7%, and 49.9%, respectively (Table 4-4).6 During 2009, 41,592 people died from poisoning or overdose with 99 deaths (0.2%) occurring in children under 5 years of age.7 Poisoning became the leading cause of injury-related death in the United States in 2008 with 89% of these deaths caused by drugs. The number of drug-related poisoning deaths has increased sixfold during the past three decades.8
There is no comprehensive tabulation of all incidents of substance abuse or poisoning, and the available databases have strengths and weaknesses.9,10 Nevertheless, substance abuse and poisoning are common problems facing healthcare professionals, law enforcement officials, employers, teachers, family members, and individuals throughout society. The detection and management of these incidents often involves laboratory testing and interpretation of the results. On a personal basis, healthcare professionals are asked by family members, acquaintances, and patients about drug testing and the potential impact on their lives. It is often prudent to refer the person to the testing laboratory or physician who ordered the test in question when pertinent facts are not available or when they are unable to be properly assessed. This chapter will focus on urine drug testing and serum drug concentration determinations as a means to aid in the management of substance abuse and poisoning.
URINE DRUG SCREENS
Objectives of Analysis
A drug screen provides a qualitative result based on the presence of a specific substance or group of substances. This determination is also called a toxicology screen or tox screen. Urine is the specimen of choice, and it is widely used for most situations requiring a drug screen. The collection of urine is generally noninvasive and can be collected following urinary catheterization in unresponsive patients. Adequate urine samples of 20–100 mL are easily collected. Most drugs and their metabolites are excreted and concentrated in urine. They are also stable in frozen urine allowing long-term storage for batched analyses or reanalysis. Urine is a relatively clean matrix for analysis due to the usual absence of protein and cellular components, thereby eliminating preparatory steps for analysis.11-16
A urine drug screen result does not provide an exact determination of how much of the substance is present in the urine. The concentration of the substance is actually measured by urine drug screen assays in the process of determining whether the drug is present in a significant amount to render the test as positive. For each substance, the test has performance standards established by the intrinsic specificity and sensitivity of the analytical process that are linked to regulatory or clinical thresholds, commonly called cutoff values. These thresholds are a balance of the actual analytical performance, likelihood for interfering substances, and the potential for false positives, which together suggest that the substance is actually present in the urine. Cutoff values may be set by an individual laboratory to meet regulatory or clinical needs or by purchasing immunoassay kits with the desired cutoff values.
Regulatory cutoff values are typically used to monitor people in the workplace or patients undergoing substance abuse therapy. The Substance Abuse and Mental Health Services Administration (SAMHSA) in the Department of Health and Human Services specifies cutoff values and requires that five categories be routinely included in urine screens (Table 4-5).17 In hospital and forensic settings, cutoff values are sometimes lowered relative to workplace values in order to detect more positive results, which can serve as an aid in verifying or detecting an overdose or poisoning.13-15,18 Reports of urine drug screen results will often list the cutoff value for a substance and whether the substance was detected at the specified value.
aStandards issued by Substance Abuse Mental Health Services Administration for urine specimens collected by federal agencies and by employers regulated by the Department of Transportation effective October 2010; check website for changes (http://workplace.samhsa.gov).
bSpecimen must also contain amphetamine at a concentration of 100 ng/mL or more.
cSame cutoff for 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxyethylamphetamine (MDEA).
dMetabolite as benzoylecgonine.
eMetabolite as delta-9-tetrahydrocannabinol-9-carboxylic acid.
fA metabolite specific to heroin.
General Analytical Techniques
There is no standardized urine drug screen that employs the same panel of tested drugs, analytical techniques, or turnaround times. Although there is some commonality among laboratories, tests differ by individual laboratory. Generally, urine drug screens are categorized by level of sensitivity of the analytical technique (preliminary versus confirmatory) and by the variety of drugs tested.12,15,18 Preliminary tests, also known as initial, provisional, or stat urine drug screens, typically employ one of six currently available immunoassays (EMIT, KIMS, CEDIA, RIA, FPIA, or ELISA). (See Chapter 2: Introduction to Common Laboratory Assays and Technology.)
Immunoassays can readily be performed on autoanalyzers that are available in most hospitals. These assays are available for many substances of abuse, and results can be reported within 1–2 hours.14,18 Many point-of-care tests (POCTs) also use an immunoassay technique, and results can be available within 5–15 minutes. Unfortunately, the result of an immunoassay is preliminary due to compromises in specificity that lead to cross-reactivity, particularly with amphetamines and opiates. A preliminary urine drug screen result cannot stand alone for medicolegal purposes and must be confirmed with another type of analysis that is more specific.11-13 For clinical purposes, some laboratories routinely confirm the results of preliminary drug screens, but others do so only on request of the physician. The need for confirming preliminary test results is based on several factors: whether the result would affect the patient’s care; whether the patient is expected to be discharged by the time the results are known; whether any legal actions are anticipated; and whether the cost justifies the possible outcome.
Reliability of Amphetamine Results
KISHA T., A 21-YEAR-OLD COLLEGE STUDENT, is brought to the ED by her family because of bizarre behavior. She is having visual hallucinations and is paranoid and jittery. She is clinically dehydrated, tachycardic, and delirious. A stat preliminary urine drug screen is positive for amphetamines.
Question: Is Kisha T. abusing amphetamine?
Discussion: Amphetamine abuse is possible, but alternative causes should be considered. Her parents report that she has just completed a week of final exams, is taking a full course load, and is working two part-time jobs. She is described as studious and a compulsive achiever. After 6 hours of supportive therapy, rest, and IV fluids, she is lucid and confesses to drinking more than a dozen “energy drinks” to stay awake in the past 2 days and taking two loratadine and pseudoephedrine combination 12-hour tablets 6 hours ago for allergy symptoms. A targeted confirmatory assay for amphetamines was negative for amphetamines and methamphetamine. Urine drug screens by immunoassay for amphetamines are subject to cross-reactivity with several sympathomimetic amine-type drugs (e.g., ephedrine and pseudoephedrine and their variants are often found in dietary supplements marketed for energy and weight loss and as decongestants), which would cause a false positive for amphetamines by immunoassay. Caffeine found in many energy drinks and dietary supplements for weight loss and energy is likely the principal cause of her symptoms. Caffeine was not detected in the urine screen because it was not on the testing panel of screened drugs.
The inclusion of a substance on a drug screen is also subject to individual laboratory discretion. Workplace and substance abuse monitoring programs are required to test for five categories of substances (marijuana metabolites, cocaine metabolites, opiate metabolites, PCP, and amphetamines) as specified by the “SAMHSA 5.” Most immunoassay manufacturers design the range of assays to meet this need and offer additional categories that a laboratory may choose to include.11,13 The expense of developing an immunoassay is balanced with the promise of economic recovery with widespread utilization. This economic reality precludes the development of a test for emerging substances of abuse, such as ketamine and gamma hydroxybutyrate, and life-threatening—albeit infrequent—overdoses, such as calcium channel antagonists and beta-adrenergic blockers.18 Techniques used for confirmatory tests would be required to detect many of the substances not included in the panel of the preliminary drug screen.
Confirmatory techniques are more specific than preliminary tests and utilize another analytical technique.12,15,18 These tests include high-performance liquid chromatography, gas chromatography, or mass spectrometry, depending on the substances being confirmed. The “gold standard” of confirmatory tests is the combination of gas chromatography and mass spectrometry, often referred to as GC mass spec or GC-MS. Compared to preliminary tests, these techniques are more time-consuming, more costly, require greater technical expertise, and require greater time for analysis—often several hours to days. Most hospital clinical laboratories do not have the capability to perform confirmatory tests and must send the specimen to a local reference laboratory or a regional laboratory. Transportation of the specimen will add to the delay in obtaining results. Confirmatory tests are routinely performed for workplace settings and forensic and medicolegal purposes, and the delay is often less critical than in clinical settings.11,13 (See Minicase 1.)
Common Applications
The purpose of a urine drug screen depends on the circumstances for its use, the condition of the patient, and the setting of the test. In an ED where a patient is being evaluated for a poisoning or overdose, the primary purposes are to verify substances claimed to be taken by the patient and to identify other toxins that could be likely causes of the poisoning or symptoms.14 This is particularly important when the patient has altered mental status and cannot give a clear history or is experiencing nondrug causes of coma, such as traumatic head injury or stroke. The value of routinely performing urine drug screens in the ED for patients who overdose has been questioned.19 The benefits include having objective evidence of the toxin’s presence to confirm the exposure; suggesting alternative toxins in the diagnosis; ruling out a toxin as a cause of symptoms of unknown etiology; and providing medicolegal documentation. The disadvantages include being misled by false-positive results; impractical delays in receiving the results that do not influence therapy; and limited practical value because many poisonings can be recognized by a collection of signs and symptoms.20
The American College of Emergency Physicians states in a clinical policy on the immediate treatment of poisonings that “qualitative toxicologic screening tests rarely assist the emergency physician in patient management.”21 Urine drug testing can be important with substances exhibiting delayed onset of toxic symptoms, such as sustained-release products, when patients ingest multiple agents, or when patients are found with multiple agents at the scene. Some trauma centers routinely perform urine drug screens on newly admitted patients, although the value of this practice has been questioned.22 Suicidal and substance-abusing patients are poor or misleading historians, whereby the amounts, number of substances, and routes of exposure can be exaggerated or downplayed. A urine drug screen may assist in identifying potential substances involved in these cases and lead to specific monitoring or treatment. (See Minicase 2.)
Drug Screens and Emergent Care
BOB C., A 26-YEAR-OLD MALE, is dropped off at an ED in the late evening after he became progressively more unresponsive in a hotel room. His acquaintances do not know his medical history, but eventually admit that he had swallowed some drugs. They promptly leave the area. Bob C. is unconscious with some response to painful stimuli and exhibits pinpoint pupils and depressed respirations at 12 breaths/min. His other vital signs are satisfactory. Oxygen administration and intravenous fluids are started. A bedside stat glucose determination yields a result of 60 mg/dL. A 50-mL intravenous bolus of dextrose 50% is administered with no change in his level of consciousness. Naloxone 0.8 mg is given IV push, and within minutes Bob C. awakens, begins talking, and exhibits an improved respiratory rate. He admits to drinking some whiskey and taking a handful of several combination tablets of hydrocodone and acetaminophen shortly before he was dropped off at the ED. In addition to routine laboratory assessment, a serum acetaminophen concentration is determined. During the next 24 hours, he receives supportive care in the critical care unit and requires two additional doses of naloxone. He is scheduled for a psychiatric evaluation to assess treatment options for his substance abuse, but he walks out of the hospital against medical advice on the second day. A urine drug screen by immunoassay that was obtained in the ED is reported as positive for opiates and marijuana on the morning of his second day of hospitalization. The serum acetaminophen concentration reported 2 hours after ED arrival was 60 mcg/mL, which was obtained approximately 6 hours after drug ingestion. Ethanol was not included in the drug screen panel.
Question: Was a urine drug screen necessary for the immediate care of Bob C.? How is a urine drug screen helpful in this type of situation?
Discussion: In emergent situations like this one that involve an apparent acute opiate overdose, the results of a urine drug screen are not necessary for immediate evaluation and effective treatment. The symptoms and history clearly indicate that an opiate overdose is very likely. The response to naloxone confirms that an opiate is responsible for the central nervous system (CNS) depressant effects. Since immediate treatment was necessary, waiting for the results of the preliminary drug screen, even if it was reported within hours, would not change the use of supportive care, glucose, and naloxone. The urine drug screen may be helpful to confirm the diagnosis for the record and to assist in guiding substance abuse treatment. Obtaining a serum acetaminophen concentration is important in cases of intentional drug use (suicide attempt and substance abuse). This practice is particularly important in situations of a multiple drug exposure, an unknown drug exposure, or when acetaminophen may be contained in a multiple-ingredient oral drug product (e.g., analgesics, cough and cold medicines, sleep aids, and nonprescription allergy medicines). A serum specimen is needed because acetaminophen is not part of routine urine drug screens, and serum assays on acetaminophen generally have a quick turnaround time so they can be used clinically to assess the potential severity of the exposure. In Bob C.’s case, the serum acetaminophen concentration did not indicate a risk for hepatotoxicity. Another benefit of obtaining a serum acetaminophen concentration in this case is that it indirectly confirms that an opioid combination product was involved and is consistent with the Bob C.’s response to naloxone.
In the workplace, the purpose of a urine drug screen may include pre-employment tests, monitoring during work, postaccident evaluation, and substance abuse treatment monitoring.11,13 Employers who conduct pre-employment urine drug tests will generally make hiring contingent on a negative test result. Many positions in the healthcare industry require pre-employment drug tests, and some employers perform random tests for employees in positions requiring safety or security as a means to deter drug use and abuse that could affect performance. In addition to random tests, some employers test individuals based on a reasonable suspicion of substance abuse such as evidence of use or possession, unusual or erratic behavior, or arrests for drug-related crimes. For employees involved in a serious accident, employers may test for substances when there is suspicion of use—to determine whether substance abuse was a factor—or as a necessity for legal or insurance purposes. Employees who return to work following treatment for substance abuse are often randomly tested as one of their conditions for continued employment or licensure. In the workplace setting, specific procedures must be followed to ensure that the rights of employees and employers are observed.
The Division of Workplace Programs of SAMHSA specifies guidelines for procedures, due process and the appeals process, and lists certified laboratories.11 Two critical elements of workplace drug testing include establishing a chain-of-custody and control for the specimen and involving a medical review officer (MRO) to interpret positive test results. The chain-of-custody starts with close observation of urine collection. Patients are required to empty their pockets, and they are placed in a collection room without running water and where blue dye has been added to the toilet water. These measures minimize the risk of adulteration or dilution of the urine sample. After the urine is placed in the container, the temperature is taken, the container is sealed, and the chain-of-custody documentation is completed. After the chain-of-custody form is completed by everyone in possession of the specimen, it reaches the laboratory where the seal is broken and further procedures are observed. Positive specimens are often frozen for 1 year or longer if requested by the client or if the results are contested by a court. Chain-of-custody procedures are time-consuming and are not typically considered in the clinical management of poisonings and overdoses, but they are important to sustain the validity of the sample and its result in a court of law.11
An MRO is typically a physician trained in this specialty who has responsibility to determine whether the result of the drug test is related to substance abuse.11,13,23 Duties involve interviewing the donor; reviewing their therapeutic drug regimen; reviewing possible extraneous causes of a positive result, such as a false-positive result from a prescribed medication or substance interfering with the analytical test; rendering an opinion on the validity of the test result; considering a retest of the donor or the same specimen; reporting the result to the employer; and maintaining confidential records. This individualized interpretation is not only critical because people’s careers, reputations, livelihood, and legal status can be affected, but also because it is a regulatory requirement.
Drug screening is also used in the criminal justice system for several purposes such as informing judges for bail-setting and sentencing, monitoring whether specified drug abstinence is being observed, and identifying individuals in need of treatment.5 For example, a positive drug test at the time of arrest may identify substance abusers who need medical treatment prior to incarceration, which may result in a pretrial release condition that incorporates periodic drug testing. If a defendant is being monitored while on parole or work release, a drug screen can verify that he or she is remaining drug-free. Drug tests in prisons can also assist in monitoring substance use in jail.
The impact of a drug screen result can be profound if it affects decisions of medical care, employment, legal importance, and a person’s reputation. In addition, several factors can affect the reliability and interpretation of drug screen results. These issues should be considered when evaluating a drug screen and are described in the following section.
Unique Considerations
When a urine drug screen is reported as negative, it does not mean that the drug was not present or not taken—it means that it was not detected. The drug in question may not be part of a testing panel of the particular drug screen (Table 4-6). For example, meperidine and pentazocine are not detected on current opioid immunoassays.13,14,18 Likewise, the urine may be too dilute for detection of the substance. This may be due to renal disease, intentional dilution to avoid detection, or administration of large volumes of intravenous fluids as part of a critically ill patient’s care. The urine may have been collected before the drug was excreted, but this is unlikely in symptomatic acute overdoses or poisonings. The time that an individual tests positive (i.e., the drug detection time) depends on pharmacologic factors including dose, route of administration, rates of metabolism and elimination, and analytical factors (e.g., sensitivity, specificity, and accuracy). In some cases, the urine sample may have been intentionally adulterated to mask or avoid detection.
Adulteration of a urine sample either intentionally or unintentionally can lead to negative or false-positive results through several means.11,13,24 A freshly voided urine sample may be replaced with a drug-free sample when urine collection is not directly observed. The ingestion of large volumes of water with or without a diuretic may dilute a drug in the urine, thereby reducing the concentration of the urine below the assay detection limit. Urine specimens for workplace testing will often be immediately tested for temperature and later tested for creatinine content and specific gravity in order to detect water dilution of the sample.
aThose without chemically similar drug counterparts are not detected on a drug screen.
bHeavy metals will require a special collection container, collection duration, and assay.
Adding a chemical to a urine sample may invalidate some test results. Adulteration products that are available through the Internet contain chemicals such as soaps, glutaraldehyde, nitrites, other oxidants, and hydrochloric acid. Depending on the assay method and test, these substances may interfere with absorbance rates or enzyme activity, produce false-positive or false-negative results, or oxidize metabolites that are measured in the immunoassay. For example, some chromate- and peroxidase-based oxidizers will degrade 9-carboxy-tetrahydrocannabinol, a principal metabolite of tetrahydrocannabinol, and lead to a negative result for marijuana.13,24 Taking large amounts of sustained-release niacin (2.5–5.5 g over 36–48 hours) has been promoted on the Internet as a means to rid the body of cocaine and marijuana and interfere with urine drug screens. This practice is unlikely to produce the desired outcome, but it has produced niacin poisonings ranging from skin flushing to life-threatening symptoms that required hospitalization.25 The effects of adulterants vary with the immunoassay technique and the specific test used by the laboratory; they are not reliable ways to mask drug use. Most adulterants do not affect the GC-MS analysis for drugs in urine, but such a confirmatory step would be ordered only if there was a high suspicion of adulteration. A positive immunoassay result is typically used to justify the use of a confirmatory GC-MS analysis.
aTime after which a drug screen remains positive after last use.
bSince performance characteristics may vary with the type of immunoassay, manufacturer, and lot, consult the laboratory technician and package insert for the particular test.
cData from references 12, 16, 26, and 27.
A positive drug test can show the presence of specific drugs in urine at the detectable level of the test. It does not indicate the dosage, when the drug was administered, how it was administered, or the degree of impairment. Many drugs can be detected in urine for up to 3 days after being taken and some up to 2 weeks or more (Table 4-7).12,14,26 It is possible for a legitimate substance in the urine to interact with the immunoassay and produce a false-positive result.13,14,27,28
Exposure to interfering substances can affect the results of an immunoassay urine drug screen (Table 4-7). A positive immunoassay result for opiates may result from the ingestion of pastries containing poppy seeds because they contain codeine and morphine in small, but sufficient, amounts to render the test positive. The result is a true positive but not a positive indicator of drug abuse. The immunoassay for amphetamines is prone to false-positive results from drugs with similar structures such as ephedrine, pseudoephedrine, and buproprion.13,14,27 Also, drugs seemingly dissimilar from the target of an immunoassay can cause false-positive results. For example, naproxen can produce false-positive results for marijuana and barbiturates and was found to do so in 1 in 14 volunteers tested.29 Most fluoroquinolone antibiotics can produce false-positive opiate results, but this interference varies with the fluoroquinolone and immunoassay.30 The immunoassay manufacturer’s package insert should be consulted for information on known interfering substances. In workplace settings, the MRO is obligated to assess whether a person’s legitimate drug therapy could interfere with the result. (See Minicase 3.)
Workplace Drug Screen Interpretations
JUAN G., A 45-YEAR-OLD PHARMACIST, applies for a position at a hospital pharmacy. As part of his pre-employment evaluation, he is asked to provide a urine specimen in a specially designed room for drug testing. His urine sample is positive for opiates and marijuana by immunoassay. His case is referred to the hospital’s MRO for a review of the findings. The physician orders a confirmatory test on the same urine specimen. The human resources department of the hospital learns from his current employer that he is an above average worker with no history of substance abuse. A criminal background check is negative for any criminal record. The MRO contacts Juan G. and learns that he was taking acetaminophen and codeine prescribed for pain from suturing of a laceration of his hand for 2 days prior to drug testing. He also routinely takes naproxen for arthritis in his knees. He had forgotten to list the recent use of these drugs on his employment application because his injured hand began to ache while writing.
Question: Has Juan G. used any drugs or substances that should prevent him from being considered for employment?
Discussion: Consideration of several factors is important in interpreting the urine drug screen result in this case. Juan G. has no obvious symptoms of intoxication and has a good employment record. It is likely that the codeine prescribed for pain control produced the positive opiate result. This drug is being used for a legitimate purpose with a valid prescription. The positive test for marijuana is likely from Juan G.’s use of naproxen causing a false-positive result. The confirmatory test by GC-MS was negative for marijuana, but it was positive for codeine and morphine. Codeine is metabolized in part to morphine. The MRO reviewing Juan G.’s case would likely conclude that the test results are not indicative of opioid abuse and the marijuana immunoassay result was a false positive. If there were concerns about his suitability for employment, Juan G. may be subjected to an unannounced drug test during his probationary employment period. Acetaminophen and naproxen were not reported as a result, because they were not on the routine assay panel.
The persistence of the substance in the urine is an important factor in the interpretation of the results (see Table 4-7).23 For lab results reported as negative, it may indicate that the specimen was obtained too early or too late after exposure to a chemical, thereby producing a urine specimen with insufficient concentration of the drug to lead to a positive result. Drugs with short half-lives, such as amphetamines, may not be detectable several hours after use. A common concern for individuals undergoing workplace testing is the length of time after use that the drug will still be detectable. This will vary with the sensitivity of the assay; whether the assay is directed to the parent drug or the metabolite; whether the drug or its metabolites exhibits extensive distribution to tissues that will affect its half-life; the dose of the drug taken; and whether the drug was used chronically or only once. For example, cocaine is rarely detected in a urine specimen because of its rapid metabolism. Immunoassays are directed to cocaine metabolites, such as benzoylecgonine, which are detected for up to 2–3 days after use and up to 8 days with heavy use. The major active component of marijuana, delta-9-tetrahydrocannabinol, is converted to several metabolites of which delta-9-tetrahydrocannabinol-9-carboxylic acid is the agent to which antibodies are directed in many immunoassays. This metabolite is distributed to tissues and can be detected for days to weeks after use.13,14 Chronic or heavy use can lead to detection up to a month or more after stopping use. (See Minicase 4.)
For clinical applications, the time it takes for the test result to be reported to the clinician after specimen collection, also known as turnaround time, can affect the utility of the drug screen.18 Many hospital laboratories can perform preliminary immunoassay urine drug screens using mechanized analytical technology, which is used for common clinical tests or using dedicated desktop analyzers. Results from in-hospital laboratories can often be returned within 2 hours of collection. For many urgent situations such as an acute overdose or poisoning, this delay is unlikely to influence the immediate therapy of the victim. The results may lead to later consideration of alternative or additional diagnoses. Most clinics, small hospitals, or specimen collection sites do not possess such capability and must rely on making the specimen a send out that is performed at a nearby or regional reference laboratory. The turnaround time from a reference laboratory varies with the laboratory and the need for urgency. Most results for clinical applications are reported within 24–48 hours. However, some results may take up to 3–7 days. In some situations, such as pre-employment workplace testing, this delay is acceptable. The turnaround time for confirmatory testing depends on the laboratory, transportation time from the collection site to the laboratory, the tests being performed or requested, and the need for urgency. The delay could be as short as 24 hours or as long as a month or more, particularly for postmortem samples. (See Minicase 5.)
SERUM CONCENTRATIONS
Objectives of Analysis
Quantitative assays determine the concentration of a substance in a biological specimen, typically this involves serum. The availability of serum concentrations for toxins is based on considerations of whether the concentration correlates with an effect; the outcome or need for therapy; the existing use of the assay for another application such as therapeutic drug monitoring; and technical ease of performing the assay. Serum is typically not used for drug screening purposes in clinical or workplace settings.
Many poisonings and overdoses can be adequately managed without quantitative analysis.10,13 A history of the exposure, signs and symptoms, and routinely available clinical tests—such as full blood count, electrolytes, glucose, international normalized ratio (INR), liver function tests, blood urea nitrogen, serum creatinine, anion gap, serum osmolality and osmolal gap, arterial blood gases, and creatinine kinase—can guide patient management decisions.
Differences Involving Opioids
DANNY W., A 23-YEAR-OLD ASSEMBLY LINE WORKER at a computer manufacturing facility, is examined by the company’s physician within an hour of being involved in a workplace accident. She observes a laceration on his left arm, pupil size of 1–2 mm, bilateral ptosis, and recent punctate lesions on the left antecubital fossa. The rest of the physical exam is unremarkable. Danny W. denies eating poppy seeds, taking any medication or dietary supplement, or having a neurological condition. He has no history of substance abuse in his files. The physician suspects heroin use and orders a focused urine drug test for opiates. Several days later, the laboratory report indicates positive results for morphine, codeine, and 6-acetylmorphine.
Question: Has Danny W. used a drug or substance that would impair his ability to work? What, if any, substance is likely?
Discussion: Danny W. has likely used heroin several hours before the accident and several symptoms are consistent with opiate intoxication. Heroin may not be present in sufficient amounts to be detected, in part, because it is metabolized to several compounds such as morphine and 6-acetylmorphine, which can be detected in the urine of heroin users. Since 6-acetylmorphine is only found in urine following heroin use, its presence confirms heroin but other opioids could also contribute to Danny W.’s symptoms. The presence of small amounts of codeine in heroin abusers is likely from contamination of the heroin with codeine and is not a metabolic byproduct (or he had consumed codeine).
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