What is Tetramine Toxicity?

Tetramethylenedisulfotetramine, also known as tetramine, is a type of rat poison that can seriously harm the nervous system. Although it’s banned globally, it’s still produced in some places. It’s especially prevalent in rural areas, with many cases of poisoning reported. This poison can be bought on the black market in numerous countries, usually at a low cost.

Tetramine can be particularly dangerous because it’s chemically stable, easy to make, and has no taste or smell. Furthermore, its toxic effects can come on quickly. Because of these factors, there’s been talk about its potential use as a chemical threat.

What Causes Tetramine Toxicity?

Tetramine is a type of poison used to control rodents, and it’s often sold at a low price outside the United States where it’s made. Because there are strict rules about producing, selling, and owning it, tetramine is sometimes bought from unauthorized dealers.

Risk Factors and Frequency for Tetramine Toxicity

The first record of tetramine synthesis was in Germany in 1949. Its harmful effects were initially discovered when workers who were exposed to flame retardant-infused fabric started to show symptoms like seizures. It was found that the flame retardants in the fabric formed tetramine. Due to its harmful effects and the absence of any antidote, it was banned internationally in the 1980s. Nonetheless, the manufacture of tetramine has continued illegally due to the easy availability of its ingredients.

The majority of cases involving tetramine are reported in China with over 14,000 instances between 1991 and 2010. After the Chinese government enforced stricter regulations regarding tetramine in 2003, reported cases declined. However, there are still reports of tetramine sales in China and other countries. There has been only one reported case in the United States, involving a 15-month-old girl in 2002.

There have been no documented cases of intentional poisoning with tetramine in the United States, but there have been cases in China. One instance involved a food vendor who poisoned his competitor’s food, leading to the poisoning of 300 customers and 42 deaths. Another case involved a student trying to poison a teacher at a school.

The use of tetramine in rural areas as a rodenticide has led to mass exposures, especially in the countryside. In one instance in 2001, about 200 individuals were exposed to tetramine in a rural area. Also, because tetramine can remain in water for six weeks, there are concerns that dogs consuming poisoned rats could have toxic levels of tetramine in their system.

Signs and Symptoms of Tetramine Toxicity

When a person might have ingested tetramine, a dangerous substance, it’s important for doctors to find out how much was consumed and when. It’s also crucial to check if the person might have ingested other harmful substances. Symptoms of tetramine poisoning often appear very quickly. As a result, the physical examination will mainly look for neurologic issues. However, the signs of tetramine poisoning might be quite vague. Some research on animals shows that tiredness and shaking may be early signs of poisoning.

Minor cases of tetramine poisoning can lead to symptoms such as:

Headache
Nausea
Vomiting
Dizziness
Hallucinations

In severe cases, people can experience:

Seizures
Uncontrollable seizures (status epilepticus)
Failure of multiple organs (often a result of uncontrollable seizures)
Death

Given how quickly these symptoms can develop, a person might arrive at the hospital experiencing uncontrollable seizures. Other symptoms might not be apparent when the person arrives at the hospital because the illness progresses so rapidly.

Testing for Tetramine Toxicity

Diagnosing tetramine poisoning primarily relies on the doctor’s evaluation of symptoms; hence, doctors need to be extremely vigilant for signs of this condition. Certain cases have reported changes in brain wave activity in children, which can be detected using a test called electroencephalography (EEG). Other symptoms that have been observed include an elevated white blood cell count (leukocytosis), muscle tissue breakdown (rhabdomyolysis), and a lower than normal platelet count (thrombocytopenia).

While there are advanced tests such as gas chromatography, which can detect the presence of tetramine, these tests are not always readily available in a typical clinical setting. This limits their usefulness in promptly diagnosing tetramine poisoning.

Imaging tests, like CT scans or MRI, unfortunately, do not reveal specific signs that can reliably confirm tetramine poisoning.

Post-mortem examinations have often shown lung swelling and congestion, alongside internal bleeding in most organs. In some cases, hemorrhaging beneath the protective layers covering the brain (subarachnoid hemorrhage) was noted. However, the underlying reason for these widespread internal bleeds remains uncertain and could possibly be due to continuous seizures, although this is not definitive.

Treatment Options for Tetramine Toxicity

Tetramine, a potentially toxic substance, is quickly absorbed into the body after someone swallows it. That’s why it’s important to start treatment as soon as possible. If you come into contact with tetramine, it may not affect you through your skin, unless you have a break or cut. In any case, healthcare professionals should always use protective measures to limit their exposure.

If someone has swallowed tetramine, doctors might perform a procedure known as gastric decontamination. In simple terms, they try to make sure that the body absorbs less of the harmful substance, which may help to reduce its toxicity. One method could be gastric lavage, where clinicians wash out the stomach. Despite being a commonly suggested treatment, there’s no solid proof that it routinely improves survival rates.

Activated charcoal is another tool doctors might use. Animal studies using rabbits showed that activated charcoal can help bind to the toxic substance, reducing its harmful effects. However, doctors have to be cautions as using activated charcoal might lead to seizures thus the patient’s airway should be safeguarded in these scenarios.

One of the significant features of tetramine toxicity is that it causes persistent seizures. Several different medicines might be used to manage these seizures, but they should be started quickly and increased as necessary. Some of these medications include midazolam and diazepam, which have demonstrated their usefulness in animal studies. But, it’s worth remembering that these results might not translate perfectly to human cases.

Phenobarbital, a type of medication that’s typically used to treat seizures, has also been proposed as beneficial in early animal studies. Similarly, propofol showed the same effectiveness as midazolam in blocking the harmful effects of tetramine.

In addition to the main treatments, there are other useful adjunct therapies. However, their efficacy is largely based on animal studies, and randomized controlled trials in humans are missing. One of these adjuncts is Pyridoxine, a form of Vitamin B6, which can be helpful as it can combine with other agents to decrease seizures. DMPS, a medication used to treat heavy metal poisoning, has also been suggested as it displayed potential benefits in animal studies.

Lastly, a few emerging treatments include neurosteroids, a type of mood-altering steroids that can interact with nerve cell receptors in the brain, thereby helping to manage the toxic effects of tetramine.

Extracorporeal removal, which involves removing the toxin from the body through external means such as filtering the blood, has been used in many cases of tetramine poisoning. However, the effectiveness of this treatment is a topic of debate among experts. Out of these methods, charcoal hemoperfusion, which involves using activated charcoal to filter the toxins out of the blood, has shown promising results. Still, this method’s availability could be an issue in some hospitals, affecting the treatment plan.

Lastly, it’s crucial to mention that the early start of treatments like charcoal hemoperfusion may decrease the recovery time. Thus, other treatments may also become more effective at removing tetramine from the body, further reducing the severity of symptoms. However, we’d need more studies to confirm these preliminary findings.

Some health conditions may show similar symptoms. These conditions include:

Sodium monofluoroacetate toxicity (a type of poisoning)
Stimulant abuse (misuse of drugs like cocaine or amphetamines)
Isoniazid toxicity (side effects from a tuberculosis medicine)
Organophosphate compound toxicity (poisoning due to chemicals often found in pesticides)
Serotonin toxicity (an excess of serotonin, a brain chemical)
Hydrazine toxicity (harmful effects from exposure to a chemical used in industrial applications)
Hypoglycemia (low blood sugar)
Severe electrolyte derangements (extreme imbalances in body salts)

It’s crucial for the doctors to correctly identify which one of these conditions a patient has, using careful testing and examination.

What to expect with Tetramine Toxicity

If severe tetramine poisoning is not treated, it’s almost always deadly. But with fast and aggressive treatment, the chances of survival increase significantly. One study in China, which observed cases from 2000 to 2012, saw 3526 cases and 225 deaths (which is a 6% death rate).

Possible Complications When Diagnosed with Tetramine Toxicity

: The main problems associated with tetramine toxicity are related to the nervous system. Research with children has shown long-term changes in brain wave patterns, as recorded by EEGs, even after treatment.

A common issue after the immediate toxic reaction is seizures. A study of 370 healthy individuals who had survived poisoning found that 55% had seizures when they were studied later. Most of those who did not have seizures at follow-up had initially been given anti-seizure medication. On average, they stopped having seizures without needing the medication after about 2.3 years. Of the 195 remaining patients who continued to have seizures, most experienced whole-body (tonic-clonic) seizures, with a smaller group (39 people) having partial seizures. A few patients had other long-term effects on the brain and nervous system, like difficulties with walking, thinking and memory problems, and hard-to-control epilepsy.

Interestingly, a few patients who showed minor toxicity, meaning their initial symptoms were not severe, still had long-term issues with seizures even though they did not have seizures when they were first poisoned. During the follow-up period in the previous study, these patients continued to have seizures.

Common Side Effects:

Long-term changes in brain wave patterns
Seizures after the acute phase of toxicity
Continued seizures despite initial treatment
Tonic-clonic (whole-body) seizures
Partial seizures
Difficulties with walking
Memory and thinking problems
Hard-to-control epilepsy
Seizures in patients with minor initial symptoms

Recovery from Tetramine Toxicity

When patients leave the hospital, it’s common for them to need regular check-ups and ongoing monitoring by a neurologist. This is because they might still experience seizures. A medication called Sodium valproate has been used in these situations to help control seizures. However, it’s important to note that there are no study results comparing Sodium valproate with other medications (known as antiepileptics) which could control aftermath of seizures in patients poisoned by tetramine.

Preventing Tetramine Toxicity

It’s very important to spread awareness and provide education to prevent poisoning from a harmful substance called tetramine. Tetramine is often used to control rodent populations because it works well, is cost-effective and stable. However, there are safer and legal alternatives available that should be used instead.