LMPG: Laboratory Support
for Emergency Toxicology
A. Cyanide and Hydrogen Sulfide
Cyanide and hydrogen sulfide are chemical asphyxiants that disrupt cellular oxidative phosphorylation. These toxic gases are often produced as byproducts of heavy industrial combustion. Patients exposed to cyanide have non-specific symptoms of nausea, vomiting, abdominal pain, and upper gastrointestinal irritation (59).
Although rapid experimental assays have been developed (60,61), they have not been tested or implemented in an ED setting. In the case of cyanide and sulfide exposure, immediate application of the antidote is indicated if the patient has a history of possible exposure and rapid onset of symptoms of hypoxemia (gasping), oxygenated venous blood (non-cyanotic), wide anion gap, and tachycardia; frequently, the smell of bitter almonds is present if the patient can exhale. Treatment must be started immediately if therapy is to be successful (62). The ED cannot wait for the results of laboratory test to confirm cyanide or sulfide exposure.
However, it is useful to collect a blood sample for later testing to validate (or refute) exposure. In the event of a lethal cyanide exposure, the source of exposure or identify of the toxin may not be immediately obvious. Follow-up testing to identify presence of the toxin can be used to avoid future exposure to others.
Anticoagulants are used as rodenticides and act by inhibiting critical vitamin K-dependent coagulation factors, especially II, VII, IX, X, and proteins C and S, causing severe bleeding and eventual death. Most cases of rodenticide exposures do not require an ED visit, because there is residual vitamin K production by the bowel flora. In patients with suicidal ideation with rodenticides, the appropriate therapy is to provide an infusion of fresh frozen plasma and administer vitamin K after the patient has stabilized (63). Patients having prolonged bleeding times which are responsive for 2-3 days on vitamin K therapy, and return to a condition of prolonged bleeding times, should be evaluated for exposure to anticoagulants. This follow-up is not usually performed in the ED.
Lead is a toxin with major sequelae if left untreated and significant exposure opportunity; it is estimated that 3% of the population of the United States will experience some significant exposure at some time during life. Acute exposure to lead produces anemia and gastrointestinal distress, while chronic exposure interferes with mental development, bone growth, nerve function, and causes nephropathy. Young children are particularly sensitive to the effects of lead. Guidelines (63) published by the U.S. Centers for Disease Control and Prevention (CDC) in 1991 recommend screening of all children at the age of 2 years for low-level exposure.
Whole blood lead measurement has been identified by the CDC (64) as the best test to detect lead exposure. Persistent whole blood lead concentrations lower than 10 µg/dL are considered normal in children. Whole blood lead concentrations greater than 30 µg/dL in adults are indicative of significant exposure. Blood lead concentrations greater than 60 µg/dL represent serious exposure requiring chelation therapy.
The EPP test does not have the sensitivity for low–level lead exposure, but is a marker for overdose. An EPP concentration greater than 60 µg/dL is a significant indicator of acute lead exposure. Serum lead analysis has no clinical utility in cases of acute lead exposure because serum lead concentrations are abnormal only for a short period of time after exposure. Measurement of urine excretion rates either before or after chelation therapy has been used as an indicator of lead exposure, but this approach is not indicated in the ED practice. Since blood lead concentration has the strongest correlation with toxicity, this test is recommended for evaluation of lead exposure by the ED.
Excessive ingestion of iron-containing vitamins will cause toxicity; it is estimated there are 500 cases of iron poisonings per year in the U.S. Many garden pesticides and treated wood for outdoor use contain arsenic. Inappropriate handling of these commonly available products can cause exposure and toxicity. The patient presents with nonspecific symptoms of gastrointestinal distress, GI bleeding, and cardiac rhythm disturbance. The history and clinical examination in the ED are the keys to identifying these toxic agents. Excessive exposure to arsenic and iron occasionally occurs. Overexposed patients are likely to present to the ED with nonspecific symptoms, including severe gastrointestinal distress, GI bleeding, and cardiac rhythm disturbance. Serum iron analysis, readily available from most clinical laboratories, is useful to identify iron overdose.
Serum iron analysis, readily available from most clinical laboratories, is useful to identify iron overdose; serum iron > 350 m g/dL indicates significant exposure (65). Urine is the specimen of choice to identify arsenic (66). Tests for arsenic are not generally available from the clinical laboratory; these are test provided by reference laboratories. At this time, the evidence as to the significance of a general trace metals screen in asymptomatic subjects or those without a history of recent exposure is absent. The question of therapeutic protocols to manage these patients is also without adequate evidence. Testing of workers who have occupational exposures to heavy metals, however, may be appropriate (67).
Carbamates and organophosphates such as diazinon, chlorpyrifos, parathion and malathion are popular pesticides used in the agricultural industry (68). The carbamates and organophosphates inhibit cholinesterase at cholinergic synapses, thereby preventing the degradation of the neurotransmitter acetylcholine. Excess acetylcholine at neuroeffector (muscarinic), myoneural junctions, and autonomic ganglia (nicotinic) results in symptoms of bradycardia, lacrimation, salivation, emesis, diarrhea, and diaphoresis. Atropine is used to compete with acetylcholine for muscarinic receptors, thereby protecting the end organs from excess acetylcholine, while pralidoxime is effective in treating both muscarinic and nicotinic symptoms.
The Committee recognizes that most laboratories will not have the red blood cell cholinesterase test because it is a very difficult test to perform, and because of the infrequency of its need. Thus reference laboratories are the usual provider of red cell cholinesterase tests. In this case, results should be available within 24 hours. Reagents for serum pseudocholinesterase test are available and can be provided by clinical laboratories on a stat basis. However, due to low testing volumes, many small laboratories cannot justify the expense for providing this testing. While it is recognized that the pseudocholinesterase activity is an imperfect marker of anticholinergic agent exposure, the test is useful to address whether the patient has been exposed to an anticholinergic agent (70).
Inhalants are popular substances that are abused by children and adolescents. Aromatic hydrocarbons such as toluene are found in solvents, paint thinners, and plastic cements. These volatile compounds produce euphoria and hallucinations similar to other stimulants. There are a number of central nervous system manifestations to inhalant abuse including dizziness, blurred vision, violent behavior, tremors and convulsions (71). Long-term abuse can lead to learning deficits (72). Other organic solvents such as benzene, carbon tetrachloride, chloroform, xylene, acetonitrile, formaldehyde etc., can also produce toxicities, and are hazards to particular occupations.
ED personnel should be cognizant of signs of inhalant abuse. Clues to inhalant abuse include chronic sore throat, cough, and runny nose; unexplained listlessness, moodiness, weight loss, bloodshot eyes and/or blurred vision; chemical odors on breath, hair, bed linen, and clothes. Oral and nasal ulceration or a rash around the mouth ("glue sniffer’s rash") may be observed. Sometimes the products themselves may be discovered in the room of the abuser (73)
Toluene and benzene metabolizes principally to hippuric acid and phenol (74), respectively. Although analytical assays are available (75), they are not in routine use clinical laboratories. Thus samples must be sent to specialty laboratories where the turnaround time makes them impractical for critical care management. In addition, there are currently no guidelines for the interpretation of results. The presence of increased concentrations of hippuric acid is neither specific to inhalant abuse (e.g., certain food and beverages containing benzoate (76,77)), nor sensitive to the wide spectrum of potential inhalants.
As evidenced by the discussion in this document, most laboratories will not be able to meet all of the needs of an emergency department in their workup of intoxicated and overdosed patients. Some analytes require sophisticated methodologies that are expensive to acquire, or difficult to maintain and operate on a 24 hour-a-day basis. Many instruments (e.g., graphite furnace atomic absorption, gas chromatography/mass spectrometry, etc.), require very highly trained laboratory personnel. The low volume of testing does not justify the expense of providing the service. The lack of a commercial immunoassay for particular analytes (e.g., fentanyl, ketamine, GHB, etc) also limits the availability of testing. Even the largest hospital laboratories will have difficulty in providing testing needed for all clinical circumstances.
The success of a regional center will depend on good cooperation between facilities, and the proximity of the center to the clinical sites. To be useful in real time, it is important that samples be delivered, tested, and reported within a few hours after collection. Many reference laboratories have full-service toxicology capability and can serve as a regional center for the hospitals that are nearby. For areas where there are no reference laboratories in close proximity, a regional hospital toxicology laboratory would be desirable. To be economically viable, a commitment would be needed that all the regional toxicology testing is sent to this central facility, and that a reasonable reporting turnaround time (e.g., 4 h) is met. It would be the responsibility of laboratory and hospital administrators to establish the facility and maintain its viability. Area poison control centers may be helpful in publicizing and referring laboratory testing where appropriate, to the regional laboratories.