Low sensitivity of toxicological analysis in daily practice of acute poisonings: An endless rupture in spite of modern technology

Abstract

The diagnosis in clinical toxicology is based on the collection of information on: – the substance, the dose, and the route of administration; – signs and symptoms that have to fit the supposed ingested drug (SID), and; – toxicological analysis (TA) which is expected to provide the definitive diagnosis. However, in the past, the development of methods based on immuno-enzymology provided information on the class rather the substance by itself with questionable ability to quantify exposure. Consequently, routinely used TA was progressively disgarded. TA was recommended in only a few number of toxicants and in conditions were SID does not explain major signs and symptoms. However, over the past decade, modern TA using various modes of mass spectrometry was developed meanwhile analysts claimed they were able to address all toxicological concerns of attending physicians. From a theoretical viewpoint this assumption was sounded. However, the translational to practice has not been assessed to our knowledge. The aim of this retrospective study performed in a medical polyvalent intensive care unit (MPICU) was to test the hypothesis more especially as the MPICU has unlimited access to facilities provided by three University Toxicology Laboratory (Tox Lab). Patients: included patients were adult patients admitted for suspicion of poisoning ranging from moderate to severe in our MPICU from the 1st of January 2014 until April 2015. This period of time corresponded to the period of time at which the MPICU has unlimited access to the three Tox Lab. Toxicology analyses: according to our current practice blood and urine specimens were collected at the time of admission and sent to the different ToxLab owing to the facilities provided by each, including the local hospital for a limited of toxicants, the ToxLab on duty in our institution allowing screening and dosing, and The ToxLab of the forensic department of our Institution. The two latters have facilities of modern apparatus including mass spectrometry in various modes as well as separative process (gas and liquid). The ToxLab were blinded regarding the aim of the study. Expression of results: in each patient's results from the different laboratory were gathered one positive detection/quantitification of an SID was considered SID+,TA+; lack of SID with positive TA: SID-,TA+, a SID+ with negative TA was considered SID+,TA-. Unfortunately there was no SID6,TA- as there were no need to ask for the presence of a drug to Toxlab knowing is was absent in a study done in current practice. Assessment of severity of exposure: severity of exposure as assessed only for drugs and alcohol using the maximum daily recommended for drugs (a therapeutic index > 1 deontes an intoxication) and a blood alcohol level (BAL) of 0.4 g/lg (a BAL > 0.4 g/L was considered toxic). Over the study period there were 224 occurrences concerning 90 SID (a number of multiple occurrences of the same drug) in 70 patients (a number of patients reported multiple drug ingestions). An SID+, TA+ was recorded in only 33% of the 224 occurrences; however, the TI was > 1 in 45% of the dosed drugs. In addition, in the group of SSI-, TA+, the TA added in 15% of patients with SID-. However, in 79% of the SID-, TA+, the TI was less than 1. This finding suggests the detection was that of drugs prescribed or used by the patient therapeutically or recreatively in this class of patients SID6, TA+. In the sixties, toxicological analysis was considered the gold standard to definitively assume the role of a substance in a poisoning. Suprisingly, while the methods used in analytical toxicology resulted in a manifold increase in sensitivity and specificity allowing to screen hundreds of substances in 10 microliter of whole blood, the added value of analytical toxicology is fairly low as shown by evidencing the SID in only 33% of the occurrences. We can question about the accuracy of the SID. However, until the toxicological analysis does not currently assume the substance is not present, the analytical result is subject to caution. The question is open to know whether high-resolution mass spectrometer can actually increase the added value of TA. Furthermore, closer collaboration regarding the actual needs of the clinicic and may help analysts in defining the lists of toxicants of interest, providing an regular update of this list of toxicants. Gathering facilities provided by three University Tox Lab using modern technology resulted in a low added value of toxicological analysis in acute poisonings daily presenting in ICU. Improving the gap might be helped by high-resolution mass spectrometry. However, a close collaboration between toxicologists and analysts should result in filling the gap.