Читать книгу Fundamentals of Analytical Toxicology - Robin Whelpton - Страница 29

The specialized nature of analytical toxicological investigations and the expense of modern equipment dictate that facilities are concentrated in centres that are often remote from the patient. Frequently, routine clinical chemical tests will be performed at one site, whilst more complex toxicological analysis will be performed by a different department, possibly at a different location. The toxicology laboratory will usually undertake a range of analyses in addition to emergency toxicology.

Despite physical separation, the importance of direct liaison between the physician treating the patient and the analytical toxicologist cannot be over-emphasized (Flanagan et al., 2013; Thompson et al., 2014). Ideally, this liaison should commence before any specimens are collected because some analytes, toxic metals for example, require special precautions in specimen collection (Section 21.2). At the other extreme, residues of samples held in a clinical chemistry laboratory or by other departments, for example in the emergency department refrigerator or in the histology department, can be invaluable if the possibility of poisoning is raised in retrospect (Vuori et al., 2013).

Toxicology screening is normally performed using immunoassays and/or temperature programmed capillary GC-MS or gradient elution LC-MS. Proponents of STA sometimes overstate the case for absolute reproducibility of retention data. In practice many factors (clinical and circumstantial evidence, availability of a particular poison, past medical history, occupation, number of peaks present on the chromatogram, selective detector responses, MS fragmentation patterns, and so on) are considered before reporting results. For example, Grapp et al. (2018) positively identified drugs by accurate mass measurement (±5 ppm for [M+H]⁺; ±10 ppm for [M-H]^–), LC retention time (±0.35 min), isotopic pattern match (less than 10 m/z root mean square error [RMS, ppm]), isotope match intensity (less than 20 % RMS) and the presence of at least two fragment ions.

The range of analyses that can be offered by specialized laboratories, sometimes on an emergency basis, usually encompasses several hundred poisons. ‘Poisons screens’ must use reasonable amounts of commonly available samples (20–30 mL urine, 2–5 mL plasma). If any tests are to influence immediate patient management, the (preliminary) results should be available within 2–3 h of receiving the specimens (ideally 1 h in the case of paracetamol). In some cases, the presence of more than one poison may complicate the analysis and examination of further specimens may be required.

A quantitative analysis carried out on whole blood or plasma is usually needed to confirm poisoning unequivocally, but this may not be possible if laboratory facilities are limited, or if the compound is particularly difficult to measure. It is important to discuss the scope and limitations of the tests performed with the clinician concerned and to maintain high standards of laboratory practice, especially when performing tests on an emergency basis. It may be better to offer no result rather than misleading data based on unreliable tests. Clinicians often treat poisoned patients on the basis of suspicion and history rather than await the results of a laboratory test, but may change their approach once they have the result. The treatment of paracetamol poisoning is an example.

Circumstantial evidence of the compound(s) involved in a poisoning episode is often ambiguous and thus, on the rare occasions when an analysis for ‘poisons’ is indicated, it is advisable to perform a ‘poisons screen’ routinely in all but the simplest cases. Similarly, the analysis should not end after the first positive finding because additional, hitherto unsuspected compounds may be present. An exception is sub-lethal carbon monoxide poisoning, which can be difficult to diagnose even if carboxyhaemoglobin measurements are available – circumstantial evidence of poisoning may prove invaluable in such cases. Of course, a positive result on a ‘poisons screen’ does not of itself confirm poisoning because such a result may arise from incidental or occupational exposure to the poison in question, or the use of drugs in treatment.

Blood is often the easiest specimen to obtain from an unconscious patient and is needed for any quantitative measurements. Urine is also a valuable specimen not only because relatively large volumes are often available, but also because it is by far the easiest specimen to obtain, especially from patients likely to have damaged veins. Moreover, some compounds may be detected in urine after they have been cleared from blood. In addition, human urine presents less of a hazard than blood to laboratory staff. However, some compounds such as many benzodiazepines are extensively metabolized prior to excretion and then blood plasma is the specimen of choice for detecting the parent compound. Quantitative measurements in urine are generally of little use in emergency toxicology.

All poisons screens have limitations (Table 1.7). Thus, of the drugs commonly used to treat depression, lithium has to be looked for specifically, whilst those monoamine oxidase inhibitors (MAOIs) that act irreversibly, such as phenelzine, have a prolonged action in the body even though plasma concentrations are very low after overdosage. Any drug that is not bound to the enzyme may be excreted rapidly and may be difficult to detect except in a urine specimen obtained soon after the event. Tricyclic antidepressants are very lipophilic hence urinary concentrations, even after fatal poisoning, may be below the LLoD of the analytical method if death has occurred relatively soon after the ingestion. Poisoning with endogenous substances such as sodium and potassium is likewise often very difficult to diagnose (Belsey & Flanagan, 2016).

Table 1.7 Some analytes not normally included in analytical toxicology screens

Anabolic steroids	Heavy/toxic metal ions (antimony, arsenic, cadmium, lead, mercury)
Anticoagulants (apixaban, dabigatran, rivaroxaban, warfarin)	γ-Hydroxybutyrate (GHB)
Baclofen	Hypoglycaemic agents (gliclazide, insulin, metformin)
Carboxyhaemoglobin	Iron salts
Chloral hydrate	Laxatives (phenolphthalein)
Digoxin and other Digitalis glycosides	Lithium ion
2,4-Dinitrophenol (DNP)	Organophosphorus and other pesticides
Diuretics (furosemide, chlortalidone)	Thallium ion
Ethylene glycol (1,2-ethanediol)	Volatile compounds (butane, nitrous oxide)
Fungal/plant toxins (α-amanitin)