In the fifth part of this article series, our focus is on investigating the toxicology of poisonous gases and the laboratory procedures used to identify them. Additionally, we will address the management and treatment of victims poisoned by unknown gases in emergency units.
It is worth emphasizing that at IIPHA, we intend to investigate and study potential factors involved in Iranian students’ mass poisoning based on evidence and reports received from victims and health workers. Due to a lack of direct access to lab examinations and contact with patients, these reports are purely based on available scientific sources regarding the use of known/identified gases and other related poisonous factors/chemicals to date.
- Analytical Report of Serial Poisoning of Iranian Students (Part 1: Introduction)
- Analytical Report Of Serial Poisoning Of Iranian Students (Part 2: Plausible Candidates)
- Analytical Report Of Serial Poisoning Of Iranian Students (Part 3: Unknown chemicals exposure: Signs and Symptoms, Coping Strategies & Seeking Medical Assistance)
- Analytical Report Of Serial Poisoning Of Iranian Students (Part 4: Laboratory Findings for Diagnosis of Chemical Poisoning)
Toxicology Examinations (or Forensic Toxicology Tests) are the most accurate techniques to identify possible ways of dealing with unknown chemical substances. Although patient symptoms enable physicians to diagnose various types of poisoning fairly, toxicology examinations are essential to identify, confirm, and authenticate the specific type of each. These examinations are particularly crucial when the poisoning could potentially result from a combination of gases or other unknown chemicals.
The Pharmacokinetics (PK) behaviour of an element plays a crucial role in analysing drugs and chemical substances used in toxicology. PK is the study of how the body interacts with administered substances or prescribed medications for the entire duration of exposure. PK analyses are critical since they help experts understand how drugs behave in the body and how it reacts to drugs.
The pharmacokinetic behaviour of a substance depends on its physical and chemical characteristics as well as living parameters, especially in the form of a gas. Some vital chemical and physical parameters include the volume of distribution (Vd), metabolic yielding, absorption ability, vapour pressure, and protein binding. In the study of toxicology and pharmacology, important living parameters include age, sex, body weight, level of physical activity, organ blood flow anatomy, organ volume and status, and breathing. It is worth mentioning that the level of vulnerability is linked to both the chemical and physical characteristics of a substance and living parameters.
In order to respond to the following question “What types of examinations are required to identify chemical substances?”, we shall initially identify potential candidates based on the preliminary diagnosis and then decide on the course of action and type of examination required. For instance, no specific toxicology test is required when we come across respiratory stimulants i.e. ammonia or chlorine compounds. The influential process of such gases is through mucus, causing eye irritation, severe coughing, and stimulation of the respiratory tract. Since these substances are not absorbed into the bloodstream, toxicology tests that rely on blood and urine samples are not very useful.
In cases where there is a possibility of cyanide compound intoxication (also known as cyanide poisoning/toxication), measuring the level of cyanide in the blood or red blood cells is recommended *. For other types of exposure, various specialized examinations/tests are required based on the type of chemical substance involved. These tests involve taking blood, urine, and skin samples and utilizing research methods to identify potential specific types of toxins**.
In addition, spectrometry approaches, gas chromatography-mass spectrometry, and ion mobility spectroscopy are utilized in specialized examinations/tests for the rapid analysis and measurement of the level of contamination by chemical gases, particularly chemical warfare agents including nerve gases (also referred to as nerve agents)***.
*Plasma cholinesterase and RBC Acetylcholinesterase (RBC AChE) Activity
**Gas Chromatography (GC), High-Performance Liquid Chromatography (HPLC), Mass Spectrometry (Ms) and Liquid Chromatography-Tandem Mass Spectrometry (HPLC–Ms/Ms)
***Optical Methods, Gas Chromatography, Mass Spectrometry and Ion Mobility Spectroscopy
The table below shows identification methods used to detect nerve agents along with the time post-exposure in which the tests are most effective (window of detection).
As previously mentioned, if someone is contaminated with chemical substances, it is essential to take blood, urine, and other tissue samples to investigate, analyse, and diagnose the specific type and extent of poison. However, most contaminants are excreted shortly after absorption, and identifying them using stated approaches may not be possible. For example, the chances of finding nerve agents in blood, urine, and skin decrease a few days after the contamination, but hairs can be used as a reference source for identifying various types of contamination for months, and even years.
When an individual is exposed to nerve agents or other toxic gases, nerve agent metabolites within the bloodstream are transferred to the hair cells formed in the hair follicle which is nourished by capillary blood vessels. Once the cells are keratinized, the metabolite is tightly bound at the centre of the growing hair shaft, protecting it from further metabolism. After the segment of the hair shaft containing the agent or metabolite grows above the skin, the hair can be sampled, extracted, and analysed to verify a past exposure. Hair analysis was first used to detect heavy metals, followed by opiates and other drugs of abuse.
A robust analytical technique called liquid chromatography with tandem mass spectrometry (LC-MS/MS) is utilized to investigate the presence of nerve agents in hair. Liquid chromatography is an analytical chemistry technique used to separate a sample into its distinctive components to identify and measure each one. In this technique, each molecule is separated based on its weight and characteristics, allowing scientists to identify specific types of molecules accordingly. In cases where nerve agent exposure is possible, specialists can analyse hair strands by dissolving them in special solvents and then using LC-MS/MS technique to detect nerve agents.
The following image shows the results of analysing hair contaminated with a nerve agent after 5.5 years, compared to uncontaminated hair, using the LC method.
Management and treatment of contamination with unknown poisonous gases in emergency units
In the third part of this article series, we at IIPHA have explored possible strategies for confronting and managing after poisoning caused by unknown gases. As previously mentioned, in cases of contamination by low-to-mid density toxic gases, there is a slight possibility for chemical substances to remain on the skin surface and clothing. However, the likelihood of passing such substances to other individuals or healthcare workers and causing secondary poisoning is very low.
In contrast, exposure to high-density poisonous gases or chemical liquids increases the risk of chemical contamination on clothing, skin and potential transmission to others. In such cases, immediate decontamination is essential.
Decontamination is crucial in case of contamination with poisonous gases. If you suspect you have been contaminated, you should remove your clothing and other wearables, such as watches, jewellery, hair accessories, purses, wallets, keys, etc., place these items in a double-layered plastic bag and seal it tightly. Then you should wash any contaminated parts of the body with a significant amount of water for at least 3-5 minutes to prevent spreading the chemical contamination. If the contamination involves oil compounds, you should use soap and water for washing. When facing oil compounds, you should use soap and water. If the eyes are contaminated, you should flush your eye with water for at least 5 minutes. If a chemical splashes into your eye, use clean, lukewarm tap water for at least 20 minutes. Contact lenses should be removed immediately and not reused, but glasses are usable after thorough washing.
We need to emphasize that decontamination is explicitly mandatory for individuals exposed to high-volume gas exposure.
Primary Therapeutic Procedures
The first step in treating patients exposed to poisonous gases is to ensure their vital signs, such as airway, breathing, and circulation (ABC), are stable. If needed, cardiopulmonary resuscitation (CPR) should be performed. Oxygen therapy using inhaler masks should be given if the patient shows signs of low blood oxygen or other respiratory issues. In cases where there is a risk of low blood pressure or other concerning symptoms, IV access or serum therapy is crucial. Inhaled bronchodilators, also known as “Rescue Inhalers,” should be used for bronchospasm.
Specific Therapeutic Procedures
Certain gases require more advanced treatments to cure toxication. Pralidoxime is often used in combination with Atropine (2PAM; 2-pyridine aldoxime methyl chloride, a muscarinic antagonist) to treat the parasympathetic effects of organophosphate poisoning.
The recommended initial dose of Atropine in cases of moderate to severe symptoms is 2 to 5 mg given as an intravenous infusion for adults, and for children, it is 0.5 mg per kg of their body weight. If the patient does not respond to the initial treatment, the dose should be doubled every 3-5 minutes until clinical improvement is observed. Oxygen therapy is not necessary before administering Atropine.
For the treatment of Nicotine symptoms and, where applicable, Pralidoxime can be used. Scientific sources recommend using this compound for the existence of Cholinergic signs/symptoms, nervous and muscle functioning disorders, or when facing Delayed Neuropathy compounds.
The recommended dosage of Pralidoxime is 30mg for adults and 25-50 mg for children per kg of body weight as an intravenous infusion over 30 minutes. For adults, the same process can be repeated with an 8mg dosage after 1 hour if symptoms persist and where required. For children, the dosage will be 10-30mg per kg of body weight and can be repeated as an intravenous infusion every hour.
If Pralidoxime therapy is required, it should not be injected prior to Atropine, and it is advisable to use it in line with Atropine (both at the same time).
The information on this topic is subject to change as new evidence emerges, and the report will be updated accordingly.