The value of toxicological analysis in acute poisoning patients with uncertain exposure histories: a retrospective and descriptive study from an institute of poisoning

Abstract

BACKGROUND:

In clinical practice, some patients might not be able or unwilling to provide a thorough history of medication and poison exposure. The aim of this study was to use toxicological analysis to examine the clinical characteristics of patients with acute poisoning whose exposure history was uncertain from a toxicological analysis perspective.

METHODS:

This was a retrospective and descriptive study from an institute of poisoning. Patient registration information and test reports spanning the period from April 1, 2020 to March 31, 2022, were obtained. Patients with uncertain exposure histories and who underwent toxicological analysis were included. Clinical manifestations and categories of toxics were analyzed.

RESULTS:

Among the 195 patients with positive toxicological analysis results, the main causes of uncertain exposure history was disturbance of consciousness (62.6%), unawareness (23.6%) and unwillingness or lack of cooperation (13.8%). The predominant clinical manifestations were disturbed consciousness (62.6%), followed by vomiting and nausea (14.4%) and liver function abnormalities (8.7%). A comparison of clinical manifestations between patients with positive and negative (n=99) toxicological analyses results revealed significantly different proportions of disturbances in consciousness (63% vs. 21%), dizziness (1.5% vs. 5.1%), multi-organ failure (1.5% vs. 7.1%), and local pain (0 vs 4%). The main categories of substances involved were psychiatric medications (23.1%), sedatives (20.5%), insecticides (13.8%), and herbicides (12.8%).

CONCLUSION:

The clinical manifestations of acute poisoning in patients with an uncertain exposure history are diverse and nonspecific, and toxicological analysis plays a pivotal role in the diagnosis and differential diagnosis of such patients.

INTRODUCTION

Acute poisoning is a significant public health concern and is among the most prevalent conditions encountered in emergency departments (EDs).[1,2] The risk of exposure to these poisons and drugs has increased in tandem with the rapid expansion of the chemical industry, the development of novel pharmaceuticals, and the greater accessibility of these substances to the general population.[3] Furthermore, there is no definitive boundary for poisons or drugs; the distinction lies in the dosage magnitude, where substances surpassing the appropriate dosage are categorized as poisons.[4] Due to the wide range and similarities of clinical manifestations among patients affected by poisoning, a thorough history of exposure, whether provided by the patient or by others (including relatives, friends, healthcare workers, or other bystanders), is an essential part of the diagnostic process for poisoning.[5-7] Nonetheless, clinicians may encounter challenges in obtaining precise exposure histories from certain patients.[6-8] There are no epidemiological data on these patients in China; however, a study in South Korea found that 21.7% (97/446) of patients visited the ED for unknown poisoning.[6]

Toxicological analysis plays a crucial role in diagnosis and treatment, particularly in patients with suspected poisoning and uncertain exposure history.[6,9-11] Nevertheless, the utilization of toxicological analysis in clinical practice remains uncommon due to a number of issues, including the high expense of testing, the difficulty of accessing testing facilities, the length of time required for the testing procedure, and the low number of samples that are submitted for analysis.[10,11] At present, establishing a dedicated toxicological analysis laboratory in each hospital is not feasible. Nonetheless, the creation of a regional toxicological analysis service would be suitable.[10] The toxicological analysis laboratory within the Institute of Poisoning at Nanjing Medical University operates as a regional center for toxicological analysis.[12,13] We noticed that the limited number of clinical studies on toxicological analysis. Consequently, the aim of this study was to examine the clinical characteristics of acute poisoning patients who presented uncertain exposure histories but showed positive toxicological results. This endeavor is intended to provide insights to guide the clinical diagnosis of these patients.

METHODS

Study design and setting

This was a retrospective and descriptive study from the Institute of Poisoning at Nanjing Medical University. Patient registration information and test reports spanning the period from April 1, 2020, to March 31, 2022, were obtained from the toxicological analysis laboratory. The samples, including blood and urine, utilized for toxicological analysis were obtained from patients in the EDs of different hospitals in this region.

Inclusion and exclusion criteria

The patients were included if they 1) had an uncertain exposure history; 2) underwent toxicological analysis; and 3) had poisoning events evaluated by toxicologists.

The patients were excluded if they had missing information and a definite exposure history.

Data collection

Demographic data and exposure information including sex, age, region, primary clinical manifestations, history of exposure, cause of exposure, exposure route, and toxicological analysis results were collected.

Equipment for the toxicological analysis

The toxicological analysis equipment includes: headspace-gas chromatography (7697A-7890B, Agilent Technologies, USA), gas chromatography-mass spectrometer (7890B-7000D, Agilent Technologies, USA) and liquid chromatography-mass spectrometer (XEVO TQS-Micro, Waters, USA).

Qualification for the toxicological analysis

The toxicological analysis laboratory of the Institute of Poisoning at Nanjing Medical University holds dual accreditations from China National Accreditation Service for Conformity Assessment (CNAS) and China Metrology Accreditation (CMA). This laboratory is authorized to test and identify toxic substances. Analytical methodologies have been established and tested to identify more than 300 common toxins in 7 different categories, including pharmaceuticals, rodenticides, herbicides, pesticides, gaseous toxins, volatile substances (e.g., methanol), plant toxins (e.g., aconitine) and animal toxins (e.g., tetrodotoxin). We conducted a non-targeted screening of these 7 categories for each patient with an uncertain exposure history.[12,13] The toxicological analysis laboratory can provide a test report within 24 h after receiving the sample.

Definitions

Positive toxicological analysis results refer to the identification of toxic substances in blood or urine samples. The poisoning of a prescription drug was defined as the concentrations of drugs in blood or urine exceeding the therapeutic range.

Based on the general information, clinical manifestations, toxicological analysis results (qualitative and quantitative), and clinical toxicologists assessment, a diagnosis of poisoning event would be made (Figure 1).

Figure 1.

Diagnostic flowchart for acute poisoning patients with ambiguous exposure histories.

Statistical analysis

The statistical analysis was performed using SPSS (version 23.0, IBM Corp, Chicago, USA). The categorical variables are expressed as numbers (percentage) and compared with a Chi-square test or Fischer’s exact test. Two-sided P-values <0.05 were considered as statistically significant.

RESULTS

Study population

A total of 758 patients were recorded. Of these, 464 cases with a definite history of exposure were excluded. Of the 294 cases with an uncertain history of exposure, 99 cases who had negative toxicological analysis results, and 195 cases with positive results (Figure 2). There were no instances of shared names among these cases, and each of the 195 cases corresponded to a distinct individual. In the 195 cases with positive results, the uncertainty of exposure history was attributed to various factors, including disturbance of consciousness (62.6%), unwillingness to share information or uncooperative behavior (13.8%), and lack of awareness regarding the poisoning (23.6%). During this period, the monthly count of such cases ranged from 1 to 22, with an average of 8 cases. Detailed demographic characteristics and exposure information are presented in Table 1.

Figure 2.

Flowchart of patient registration.

Table 1.

General characteristics of 195 acute poisoning patients with uncertain exposure histories and positive toxicological analysis results

Clinical manifestations

The primary clinical manifestations of the patients with positive results were disturbances of consciousness (62.6%), vomiting and nausea (14.4%), abnormal liver function (8.7%), coagulation abnormalities (5.6%), shortness of breath/dyspnea (5.6%), abdominal discomfort/abdominal pain (5.6%), and asthenia (5.1%) (Table 2). A comparison of clinical manifestations was conducted between the positive and negative toxicological analyses groups. The results revealed significant differences between the two groups in terms of disturbances of consciousness, dizziness, multiorgan failure, and local pain (Table 2).

Table 2.

Comparison of the primary clinical manifestations between patients with positive and negative results on toxicological analyses, n (%)

Categories of poisons and drugs

The toxicological analysis result identified only one poison or drug in 169 patients, and two or more poisons or drugs in the 26 patients. The most common category was psychiatric medications (23.1%), followed by sedatives (20.5%), insecticides (13.8%), and herbicides (12.8%) (Table 3).

Table 3.

Distribution of drug and poison species in acute poisoning patients with ambiguous exposure histories but positive toxicological analysis

DISCUSSION

Poisoning has diverse characteristics, sporadic occurrence, and regional specificity.[14-17] Furthermore, patients with acute poisoning may present uncooperative and aggressive behavior, disturbance of consciousness, intoxication with alcohol, or suffering from mental illness.[6,18,19] The identification and treatment of poisoned people can be extremely difficult in the absence of clinical experience.[6,20-22] Regional poison centers have been set up in a number of nations to address this problem and provide poisoned patients with expert care.[23-30] Poison centers have just recently been established in China. The Institute of Poisoning, Nanjing Medical University was established in 2021. As far as we know, this is one of the first regional poisoning center in China, with the primary goal to enhance the diagnosis and treatment of poisoning patients.[31-33]

In certain poisoning patients, the clinician may not get the whole history of toxic exposure at the initial diagnosis. Several factors contribute to this situation: the suicidal patients refuse to provide detailed information;[34] the patients with compromised consciousness are incapable of supplying relevant details;[19] some patients are uncooperative;[18] and some patients are unaware that they have been poisoned.[35] In this study, 76.4% of the patients had clues about poisoning, but obtaining more detailed information was hindered by factors such as unconsciousness, unwillingness, and uncooperation. Furthermore, 23.6% of patients were unaware of their poisoning status. The clinical manifestations of these patients cannot be explained by known disease, prompting the clinicians to consider the possibility of poisoning. Subsequent toxicological analysis confirmed this suspicion. When the patient’s history of toxic exposure is unknown, a Chinese expert consensus suggests considering the possibility of poisoning in certain situations, as described in Supplementary Table 1.[36] In patients with an uncertain history of toxic exposure, the toxicological analysis could help poisoning diagnosis, and similar findings have been reported in related literature (Supplementary Table 2).

The categories of toxic exposures among various age groups in the local population may provide indications in the initial screening of poisonings. A study conducted at the Australian Poisons Information Centers revealed that adults aged 20–74 years were frequently exposed to either psychiatric pharmaceuticals (17.8%) or painkillers (15.1%). In contrast, individuals over the age of 74 years were predominantly exposed to prescription errors involving cardiovascular (23.6%), anticoagulant (4.6%), or antidiabetic medications (4.1%).[29] In our study, among the patients with uncertain exposure histories, toxicological analysis revealed that the most prevalent poisons were psychiatric medications (23.1%), followed by sedatives (20.5%), insecticides (13.8%), and herbicides (12.8%), respectively. Pharmaceutical poisoning was more prevalent than pesticide poisoning, while other forms of poisoning occurred sporadically. Several studies indicated that medicine poisoning are the prevailing cause of poisonings in developed countries.[2,27,30]

This study revealed that acute poisoning patients with uncertain exposure histories but positive toxicological analysis results may occur in different age groups. When making a differential diagnosis, clinicians should always consider the possibility of poisoning in patients, regardless of age, and should order toxicological analysis when needed. A novel finding of this research is that accidents, rather than suicides, were more prevalent in these patients (76.1% vs. 23.1%). This differs from the typical scenario of acute poisoning, where the majority of cases are attributed to suicide.[21,28,30] The disparities among poisoning populations can account for this phenomenon.

Poisoning caused by different poisons and drugs can result in diverse clinical manifestations. Based on a report of 667 poisoning patients in the ED, the primary clinical manifestation was disturbance of consciousness in 44.8% of the patients, followed by tachycardia in 22.8%, abnormal electrocardiogram findings in 19.0%, and nausea and vomiting in 19.2%.[30] Our research revealed that clinical manifestations of the nervous system and digestive system were more prevalent in this population, and the most prevalent manifestation was disturbance of consciousness (62.6%), which was slightly higher than that reported in the literature;[30] however, these findings are consistent with the fact that these cases could not provide a comprehensive exposure history. Vomiting and nausea were the second-most common symptoms, according to our research, which was similar to the previous literature.[30,37] Additionally, we compared the clinical manifestations between the groups with positive and negative toxicological analysis, the results indicated significant differences in terms of disturbance of consciousness, dizziness, multiple organ failure, and local pain. Due to the limited sample size, caution should be exercised when interpreting these findings. Nevertheless, this study still reflects the complexity of the clinical presentation of poisoning cases and highlights the crucial role of toxicological analysis.

Diagnosing poisoning cases with an uncertain exposure history is challenging, and the following measures can help provide clues about the possibility of poisoning: a medical history of the patient, thorough physical examination, familiarity with the clinical manifestations of common poisonings, and knowledge of prevalent categories of exposures in the area.

The strength of this study resides in its exploration of a topic that has been overlooked yet is extremely important: poisoning with uncertain exposure history. Furthermore, the data were from a toxicological analysis laboratory, differentiating it from the majority of previous studies that have originated in EDs. This study has several limitations to acknowledge. First, the data were sourced from a regional toxicological analysis center, and the study design was retrospective, with a relatively small sample size. Second, access to additional information, such as routine laboratory test results for these patients, is restricted due to the diversity of medical institutions from which the patient samples were collected.

CONCLUSION

The clinical manifestations of acute poisoning in patients with an uncertain exposure history are diverse and nonspecific, and toxicological analysis plays a pivotal role in the diagnosis and differential diagnosis of these patients.