Introduction
Drug screening facilitates the accurate assessment of the presence or absence of common xenobiotics in vivo. No drug screening methodology can or should replace the meticulous history, the physical examination, and the experience and judgment of a seasoned clinician. Still, appropriate drug screening can help answer important questions about drug exposure in the realm of child safety and can be used as an informative tool for large-scale screening to guide targeted interventions.
The term drug screening refers to a number of testing methods used to identify the presence or absence of medications, illicit drugs, and environmental substances in a variety of clinical situations. No single screening method can identify all substances, and each institution or facility will have its own menu of testing options and availability. It is essential for clinicians to become acquainted with the range of testing available in their clinical setting. It is equally important for clinicians to recognize that many types of new testing methods are being developed, and locally endemic drugs often necessitate acquisition of rapid testing for a particular target (e.g., methamphetamine, ketamine, or gamma-hydroxybutyrate). This can be accomplished through consultation with on-site laboratory and toxicology personnel.
The rationale for drug screening for child safety focuses on identifying drug exposure in specific populations of neonates, children, and adolescents. Often women self-report drug use during pregnancy, and many of these drugs have significant consequences for neonatal and child health and development. Concerns about stigmatization, custody issues, and forced rehabilitation may prompt pregnant women to conceal their substance abuse from medical providers. Maternal self-report has been repeatedly documented to underestimate prevalence of in utero drug exposure, with estimates of prenatal substance abuse ranging from 0.4% to 27% in various populations. , The consequences of maternal drug use during pregnancy are sometimes severe, including preterm labor, intrauterine growth restriction, congenital abnormalities, stillbirths, and neonatal abstinence syndromes. Targeted drug screening protocols can help identify high risk infants and allow early intervention for possible sequelae; common criteria for targeted drug screening include a history of maternal substance abuse, prior preterm labor or placental abruption, minimal or no prenatal care, and a history of births outside of a hospital.
In children, drug screening can help to identify supervisory neglect resulting in accidental exposures, the presence of illicit substances in the home, medical child abuse, or willful and unwarranted medication of children for purposes such as sedation or drug-facilitated sexual assault. (See Chapter 15, “Drug-Facilitated Sexual Assault.” ) These same issues can be identified in the adolescent population, as well as further elements of addiction and risk-taking behaviors.
The interpretation of drug screening results can be complex and challenging and relies on several factors, including patient history and presentation, the testing methodology, the specific target drug, and the source of the fluid tested. Knowledge about detectable toxins and turnaround times can further facilitate choosing the most appropriate test for each clinical setting.
Drug Testing Methodologies
There are many testing strategies that provide information on both qualitative (absence or presence) and quantitative (level of drug present in serum or blood) data for thousands of common and unusual xenobiotics. In child protection, the two most common testing methods are the immunoassay for drug screening and chromatography/spectroscopy for confirmation and quantitation of drugs of abuse.
Immunoassays and Rapid Drug Screening
Several strategies are used as initial methods in drug screening, including enzyme immunoassay, fluorescence polarization immunoassay, radioimmunoassay, and enzyme-linked immunosorbent assay. Immunoassays are the most common testing methods used in the rapid drug screening found in most clinical settings and emergency departments. These antibody-based assays generally demonstrate high sensitivity and high specificity for target drugs. The ease and relative inexpense of immunoassay use (similar to home pregnancy tests) lead to rapid turnaround times and wide availability. However, problems can exist with cross-reactivity (a positive test for a substance other than the target, particularly among substances with similar structures). For example, in older assays, therapeutic use of pseudoephedrine could trigger a positive methamphetamine screen due to cross-reactivity. Newer generations of immunoassays are much more specific, with far less cross-reactivity; for the newest generation of testing, only a truly massive overdose of pseudoephedrine would interfere with the methamphetamine assay. Every laboratory will have specifications about the particular testing methodology in use, and the likelihood of cross-reaction with common drugs. Specific questions about cross-reactivity require knowledge of the exact method in use and should be answered in consultation with on-site laboratory personnel.
Chromatography
Although rapid drug screening techniques have become more specific, most laboratories still use confirmatory testing with a second method to reveal any false positives, especially given the medical, legal, and possible criminal implications of a positive drug screen. Confirmatory testing is traditionally done via chromatography and spectroscopy. Chromatography and spectroscopy are highly specific processes used to physically separate individual compounds and to then identify them. In addition, these techniques can be used to obtain quantitative serum levels of many drugs. Quantitative levels can be used to help determine the time of exposure, monitor changes in concentration over time, predict toxicity, and determine treatment. Techniques like thin-layer chromatography (TLC), gas chromatography/mass spectroscopy (GC/MS) and liquid chromatography/mass spectroscopy (LC/MS) are frequently used to confirm the qualitative results obtained through immunoassays. By separating and identifying individual substances, these techniques provide reliable and accurate detection. The widespread use of chromatography is limited by its cost, as well as by the time and expertise required to perform the tests.
Biological Matrices
Several sources of tissue and fluid can be used for drug screening. Urine is the most commonly-used source fluid in drug screening. The preference for urine as a testing sample stems from its ease of collection and the minimal preparation required for its analysis. Drug screening on urine, however, is generally qualitative, and little information can be obtained regarding the time of exposure beyond the window of detection in positive samples. With the exception of marijuana, few drugs of abuse are found in urine more than 72 hours after exposure (see Table 58-1 for representative intervals). Considerable time and effort have been spent in finding ways to foil the standard urine drug screen, including using another individual’s urine to fill the specimen cup, dilution techniques, and addition of adulterants. Although these methods are rarely successful, professional drug testing services will use indices such as specific gravity and urine temperature to prevent fraud.
| Drug | Interval |
|---|---|
| Amphetamine | 2-3 days |
| Cocaine metabolite (benzoylecgonine) | 2-3 days |
| Opiates | |
| Buprenorphine | 48-56 hr |
| Codeine | 24 hr |
| 6-MAM (heroin metabolite) | 2-4 hr |
| Methadone | 7-9 days |
| Morphine | 48 hr |
| Marijuana metabolite (tetrahydrocannabinol) | 2-5 days; up to 10 days in heavy users |
| Methamphetamine | 2 days |
Serum or blood sampling is another common source fluid. Most quantitative testing is done on serum, and certain drugs, such as alcohols, can only be accurately identified through serum sampling. One clear benefit of serum sampling is that results follow a well-defined dose response curve for many drugs, and conclusions regarding timing and intensity of exposure can be drawn in many cases, particularly with serial samples. However, obtaining blood requires expertise in phlebotomy, appropriate resources, and increased costs. In addition, the risk of needlestick and bloodborne pathogen exposure is higher for healthcare providers who draw blood.
Meconium represents a very important source fluid for drug screening in the neonatal population. Meconium is the combined debris of lanugo, desquamated alimentary tract, amniotic fluid and intestinal secretions that begins to form during the second trimester (after 16 weeks). As such, any drugs that are encountered by the mother and fetus can accumulate in meconium from the second trimester onward, and are stored until meconium is passed at or shortly after birth. Typically, 4 to 5 g of meconium is preferred for laboratory analysis, but some laboratories will be able to perform testing with as little as 2 g. The advantages of meconium as a source for testing includes greater sensitivity for illicit drug screening caused by the greater window of exposure. In one study, meconium was twice as sensitive for detecting prenatal cocaine exposure compared with neonatal urine screening; this might represent a period of maternal abstention from drug use in the days prior to delivery. In addition, meconium can be collected easily; however, it becomes increasingly mixed with stool after birth, producing a limited collection time of approximately 24 hours after delivery. Commercial laboratories are capable of performing large-scale meconium screening. Familiarity with the substances tested for, confirmatory methods, and identification of any unusual or specific testing issues requires consultation with the specific laboratory used.
Hair testing has been used to identify neonatal and childhood exposure to illicit drugs. Between 2 and 5 mg of hair are required for most assays, and frequently hair must be washed as part of the preparation for laboratory analysis to remove any external contaminants. Specimens of hair are collected and subjected to mechanical disruption and extraction in various organic solvents. In contrast to meconium testing, detection of cocaine in neonatal hair identifies exposure occurring during the third trimester of pregnancy. This may have important ramifications from a child protection standpoint, since the vast majority of pregnancies would be apparent to the mother during this interval. The advantages of hair testing include ease of collection and its potential to remain positive for as much as 3 months after delivery. This window can be very helpful in infants who manifest delayed symptoms suggestive of drug exposure. The disadvantages of hair testing include susceptibility to external contamination and lack of standardization of testing methods among laboratories. Radioimmunoassay or ELISA protocols can detect benzoylecgonine (the primary metabolite of cocaine) at very low limits (0.02 ng/g) in neonatal hair, with a sensitivity of 84%.
Comparison of meconium and hair testing has shown that meconium testing is associated with superior sensitivity for identification of illicit drugs. One study demonstrated detection of cocaine metabolites in 95% of meconium samples, compared with 78% of hair samples from the same patients. Cannabis was identified in 95% of meconium samples, compared with 71% of hair, and the same frequency (87%) was found for opiates in matched specimens. This difference may reflect the longer window for drug detection seen with meconium testing (second trimester onward, compared with third trimester for hair).
Specific Drugs
Amphetamine
Because of the ease with which it can be synthesized from readily available consumer products, methamphetamine abuse in the United States saw a dramatic surge during the 1990s. The use of methamphetamine among women of child-bearing age appears to be greater than that of cocaine, with as many as 5% of U.S. pregnancies exposed to methamphetamine. Other members of the phenylethylamine class, such as amphetamine, dextroamphetamine, and ephedrine, have been used clinically and/or abused for much of the twentieth century; clinical uses of methamphetamine include therapy for ADHD, obesity, and narcolepsy.
Also known as “ice,” “crystal,” and “speed,” methamphetamine is rapidly absorbed after smoking, nasal insufflation, intravenous injection, or ingestion. The characteristic clinical effects of methamphetamine occur as a result of the widespread release of dopamine, serotonin, and norepinephrine from presynaptic neurons, as well as the inhibition of monoamine oxidase. Effects include euphoria, increased alertness, hallucinations, CNS excitation, diminished appetite, tachycardia, hypertension, and seizures.
The bulk of illegal methamphetamine used in the United States is manufactured in clandestine home laboratories, which pose added hazards to children living in the home, including burns caused by explosive reagents, exposure to lead salts, and caustic injuries from concentrated acids and organic solvents. In addition, neglect may occur during methamphetamine binges, when parents are unable to provide meals or supervise younger children. The practice of sedating children during these binges also has been reported. In addition, children can be exposed to weapons, pornography, and sexual exploitation in the setting of clandestine methamphetamine laboratories.
Methamphetamine readily crosses the placenta and has been linked to intrauterine growth retardation, placental abruption, and premature labor. The low birth weight and other complications seen with gestational exposure to methamphetamine are likely compounded by the appetite-suppressing effects of the drug when taken regularly by pregnant women. Methamphetamine screening can be performed on meconium as well as on urine or serum.
The laboratory confirmation of exposure to methamphetamine is plagued by the problem of forensically false-positive results from licit amphetamine derivatives found in common decongestants, appetite suppressants, and CNS stimulants. The anti-parkinsonian medication selegiline is metabolized to d -methamphetamine (identical to the illegal form), and the common atypical antidepressant, bupropion, can also cause false-positive methamphetamine assays. In addition, commonly prescribed nasal inhalers (e.g., Vicks) may contain l -methamphetamine and cause false-positive methamphetamine screening results. Even gas chromatography and mass spectrometry analysis can confuse these substances, and more sophisticated methods, such as negative-ion chemical ionization mode-GC-MS testing, can be required to further differentiate these medications from illicit methamphetamine.
Marijuana
Marijuana (“weed”, “pot”) is the most commonly abused illicit drug in the United States. It is usually smoked as cigarettes or via a water pipe (“bong”). Hashish refers to the more resinous and concentrated form of the drug. Marijuana is currently a schedule I drug and is illegal to possess or cultivate according to federal law; certain state and local statutes, however, allow the use of marijuana for medical purposes. The active compound in marijuana, delta-9-tetrahydrocannabinol (THC), is responsible for its effects, including euphoria and anxiolysis. Among adolescents, marijuana use is extensive. In 2005, one study reported that 16.3% of eighth graders and 44.8% of high school seniors had used marijuana.
Approximately 5% of pregnant women report smoking marijuana while pregnant. Considerable controversy exists as to the effects of marijuana use during pregnancy; however, multiple studies suggest that antenatal exposure to marijuana can lead to lower birth weight regardless of gestational age and can increase the risk of preterm delivery. Other reports suggest long-term cognitive effects after prenatal marijuana exposure and a possible increased risk of marijuana use in adolescence.
Essentially any source fluid can be used for marijuana testing; screening has been conducted on urine, blood, saliva, meconium, hair, and nails. Marijuana is stored in adipose tissue and persists in urine up to 7 to 10 days in heavy users. Screening for marijuana use during pregnancy is typically conducted on meconium passed by the newborn.
Cocaine
Cocaine in its various forms is one of the most prevalent illicit substances in use in the United States. According to the 2007 National Survey on Drug Use and Health, 2.4 million Americans reported using cocaine in the previous month, with an additional 700,000 reporting use of crack cocaine. Among pregnant women the prevalence of cocaine use ranges from 2.6% to 11% and appears to vary with race, socioeconomic status, and geographical setting, but is inaccurately assessed by maternal self-report. ,
The use of cocaine by pregnant women can have consequences that are both unique and potentially devastating to the developing fetus. Chronic increases in vasomotor tone can impair placental perfusion and result in intrauterine growth retardation and low birth weight. Likewise, the catecholamine excess caused by cocaine can trigger placental abruption and preterm labor. Infants born after repeated exposure to cocaine can display a unique neonatal abstinence syndrome marked by poor sucking, feeding problems, irritability, hypertonia, yawning, and sneezing.
In contrast to other substances with high potential for abuse such as heroin and methamphetamine, cocaine is classified as a Schedule II substance by the U.S. Controlled Substances Act. This allows for the continued medicinal use of cocaine as a topical agent for anesthesia and vasoconstriction of mucous membranes, chiefly in otorhinolaryngologic procedures. Although used with less frequency than in decades past, its continued role in clinical medicine provide both opportunities for drug diversion as well as for positive screening test results following legitimate exposure.
Powdered cocaine represents the hydrochloride salt of the naturally occurring alkaloid benzoylmethylecgonine. The leaves of the coca plant ( Erythroxylum coca ) are harvested and extracted in a solvent such as sulfuric acid or benzene before being converted to the purified form. Crack cocaine is formed by dissolving the hydrochloride salt in a solution of sodium bicarbonate and extracting the resultant base. Cocaine can be used alone or in combination with opioids or other drugs via nasal insufflation, oral ingestion, mucosal absorption, intravenous injection, or smoking. The packaging of cocaine into well-made packets for concealment within the human body for trafficking purposes presents unique diagnostic and management challenges.
Cocaine is rapidly absorbed following administration by all routes, and metabolism proceeds by three chief pathways. Approximately 5% of absorbed cocaine undergoes demethylation in the liver to produce the active metabolite norcocaine, which is capable of crossing the blood–brain barrier and producing cocaine’s characteristic effects. The remainder of the absorbed dose is hydrolyzed chemically and enzymatically by plasmacholinesterase to the inactive metabolites benzoylecgonine and ecgonine methyl ester. Although these compounds have little or no clinical effect, they persist in biological fluids and tissues longer than native cocaine and thus are a more reliable target for drug testing.
Rapid drug screening methods for cocaine identify benzoylecgonine at a detection limit of 200 to 300 ng/ml, a range comparable to that of GC/MS techniques. In contrast to assays for other drugs of abuse such as opioids, cannabinoids, and amphetamines, false-positive results for cocaine are exceedingly rare. Cocaine metabolites are detectable in urine, blood, hair, nails, and meconium. Radioimmunoassay screening and GC/MS confirmation methods detect benzoylecgonine in meconium at limits of 50 ng/g with a sensitivity of approximately 96%.
Ethanol
Alcohol plays a complicating role in a wide variety of child protection cases. In neonates, fetal alcohol spectrum disorder represents one of the most common preventable causes of birth defects. The prevalence of fetal alcohol spectrum disorder has been estimated as 0.5 to 2/1000 births, with an estimated cost of up to $9.7 billion per year. , Fetal alcohol syndrome refers to the more severe constellation of characteristic facial abnormalities, restricted growth, and CNS impairment seen in children exposed to heavy and chronic alcohol in utero. , Fetal alcohol spectrum disorder describes a broader range of neurodevelopmental findings seen in children exposed to prenatal alcohol, but lacking the classic facial findings. Clinicians may be alerted to prenatal alcohol exposure through maternal self-report, maternal intoxication during provider contacts or blood alcohol testing performed on the mother within hours of alcohol ingestion. Screening for maternal alcohol exposure using maternal blood or breathalyzer testing is of limited utility, given the rapid and complete elimination of alcohol in adults. In addition, many infants without the classic facies of fetal alcohol syndrome are not diagnosed for months, making testing for fetal alcohol syndrome, or the broader diagnosis of fetal alcohol spectrum disorder, challenging. Specific biomarkers can be used to assess for fetal exposure to alcohol during the prenatal period.
Fatty acid esters (FAE) are nonoxidative metabolites of ethanol that accumulate in meconium and have been used as indicators of prenatal alcohol exposure. At least one study has demonstrated a link between elevated meconium FAE levels, and limited neurodevelopmental outcomes. Several FAEs are detectable using GC/MS.
One unique and concerning feature of alcohol exposure in infants and small children is the potential for life-threatening hypoglycemia. All infants and small children with a documented ethanol exposure require serial glucose measurements, as well as close examination of supervisory issues.
Alcohol use during adolescence has been linked to negative consequences including injury, suicide, unsafe sexual activity, and date rape. In addition, early age of onset of drinking correlates with risk of alcoholism. Although screening for alcohol use among adolescents is imperative during clinical encounters, drug testing for alcohol has limited utility outside of those patients with evidence of clinical intoxication. In intoxicated adolescents, serum alcohol levels can provide a quantitative alcohol level that correlates with clinical features of intoxication ( Table 58-2 ). This correlation is altered by chronic alcohol use and tolerance. Alcohol is generally eliminated at rates of 15-30 mg/dL/hr. Minors should be observed until they have an undetectable alcohol level, or until adult supervision is available, and the patients are deemed clinically sober enough to be evaluated and are safe for discharge. All intoxicated adolescents should be referred for alcohol abuse counseling.
