Tox and Hound – Not All Gas Is Funny

by Jeanna Marraffa

It’s 4:30 in the morning and the emergency department (ED) calls the poison center about multiple patients. A car was found disabled on the highway. When police arrived on scene, they found an unresponsive female in the front seat. Obstructing their view was a sign on the window stating – “Toxic Gas. Do Not Enter. ” The police officer broke the front window to extract the patient. EMS is en route to the ED with the extracted patient, and three police officers who complain of feeling dizzy. . .

Suicide clusters and suicide contagion have long been recognized, and are well described in the literature.^​1,2​ Teenagers and adolescents appear to be the most vulnerable to increases in suicide rates and attempted suicides secondary to media reports.^​1​ Exposure to suicide methods through media reports have been shown to encourage vulnerable individuals to imitate it.^​3​ When Netflix released the show “13 Reasons Why’’ in 2017, there was significant concern for suicide contagion and outcry from numerous organizations. Despite these concerns, the show was released.

Chemical suicides first became popular in Japan. Known as detergent suicides, these cases involved using a mixture of a bath additive plus toilet cleaner to create hydrogen sulfide. From March through June 2008, there were 220 suicides by this method reported in Japan, with the mortality rate an astonishing 95%.^​4​ After the first cases were reported, due to suicide contagion, this method of suicide began to spread to other parts of the world.^​5​ In the US, gas inhalation comprises only 4% of suicides, but is growing. Between 2005 to 2012 cases increased from 15 to 40%.^​6​ In one study looking at data from State Health Departments participating in the Agency for Toxic Substances and Disease Registry’s National Toxic Substance Incidents Program (ATSDR-NTSIP), there were 22 incidents from 2011 through 2013, with 43 victims. Similar to Japanese cases, there was a high case mortality rate of 68% (15/22).^​7​ This emerging problem needs to be recognized not only to manage the poisoned patient, but also to educate providers.

Hydrogen Sulfide

The most common cause of detergent suicide involve hydrogen sulfide. Hydrogen sulfide poisoning is a significant contributor to occupational poisoning with often fatal outcomes.^​8​ Proteins are decomposed by bacteria, generating hydrogen sulfide. Decay of sulfur-containing products, including sewage and manure, also produces hydrogen sulfide. When used as a chemical suicide agent, a sulfur containing insecticide is mixed with an acid to create hydrogen sulfide.^​9​ Classic stories of exposure to this rapid knockdown agent include scenarios in which people are in confined spaces like sewers or manure pits. There are catastrophic cases of entire family members succumbing to hydrogen sulfide. A father enters the manure pit, and after a few minutes, his son knows something is wrong because his father isn’t out. The son goes in to rescue his father. The other brother tells his mother to call 911 because now, both father and son haven’t come out of the pit. The other brother attempts to rescue his father and brother. When EMS arrives, all 3 have not emerged from the manure pit. They are extricated but resuscitative efforts are unsuccessful for all of them. Kind of like the “lemming effect”, an innate psychological phenomenon, present in most mammals. Lemmings are small rodents known to follow each other as they charge to their deaths into raging rivers, or off of cliffs.

via GIPHY

Similar to cyanide, hydrogen sulfide is a potent inhibitor of cytochrome oxidase resulting in rapid inhibition of oxidative phosphorylation. And luckily, I don’t have to recreate the wheel and try to explain oxidative phosphorylation because Dr. Curry already did. Symptom onset after large exposure is typically abrupt, leading to it being referred to as a “rapid knockdown agent”. The effects on the electron transport chain do not fully explain this effect and there is increasing evidence that hydrogen sulfide causes considerably more oxidative stress than cyanide. The exact mechanisms for this are currently under investigation.^​10​ H₂S causes a reduction in oxygen consumption due to its inhibition of complex IV of the electron transport chain. Additionally, it increases cellular acid production likely due to a switch to anaerobic metabolism and subsequently an increased lactate production. There is also emerging research that hydrogen sulfide is a brain stem toxin.^​10,11​

via GIPHY

Hydrogen sulfide has the irritating odor of rotten eggs. The rotten egg smell occurs at very low concentrations of 0.1 to 0.3 parts per million (ppm) with the notable strong intense odor occurring at 20 – 30 ppm. It is irritating to mucous membranes, and causes eye irritation at concentrations between 20 – 100 ppm. At concentrations higher than 100 to 150 ppm, it causes olfactory nerve paralysis. This leads the unknowing victim to have a false sense of security . . . if they don’t smell it, they must be safe. At concentrations of greater than 500 ppm, it leads to rapid cardiac arrest.

Treatment is largely supportive, with removal from the source, and aggressive supportive care. Unlike cyanide, the administration of antidotal therapy is not as clearly indicated after hydrogen sulfide poisoning. There are animal models showing that methemoglobin is protective against toxicity, and because of this, it is not unreasonable to give sodium nitrite to severely poisoned patients.^​12​ Additionally, hydroxocobalamin and cobinamide are being studied for their potential benefits.^​10​ Cobinamide (IV or IM) has been shown to be effective against lethal IV hydrogen sulfide exposures in both rabbits and pigs.^​11​ Methylene blue is also being investigated as an antidote.^​13,14​ There are several postulated mechanisms suggesting the beneficial effects of methylene blue including: direct oxidation of free sulfide; increasing the pool of trapped hydrogen sulfide in red cells; a restoration of the mitochondria substrate-level phosphorylation and rescue of the electron transport chain.^​13,14​ This research is still evolving, and definitive conclusions regarding their efficacy cannot be stated.

Carbon Monoxide

We have all heard the stories of carbon monoxide poisoning. Running a car in the garage; a hose from the exhaust pipe into the window; a charcoal grill in an enclosed space. But, did you know that people can create carbon monoxide in a chemical reaction by mixing two relatively common ingredients? Carbon monoxide is formed when sulfuric acid and formic acid are combined. How much CO is formed? Enough that carboxyhemoglobin levels have been reported to be greater than 30% in the victims.^​15,16​

This isn’t a post on carbon monoxide toxicity, and certainly not a post about the role of hyperbaric oxygen treatment. But remember, having high concentrations of carboxyhemoglobin results in a shift of the oxygen dissociation curve to the left, and less oxygen delivered to tissues. Certainly, the toxic effects can’t be explained purely by this mechanism and there are other pathophysiologic mechanisms. Some of which are known and some of which remain unknown. Inactivation of cytochrome oxidase results in inflammatory processes that result in ischemic reperfusion after CO exposure and during recovery, white blood cells adhere to the microvasculature. This results in delayed lipid peroxidation which then activates excitatory amino acids which are ultimately responsible for neuronal cell loss.^​17​

Treatment includes administration of 100% oxygen immediately, either by non-rebreather or endotracheal tube. IV normal saline and/or vasopressors should be administered for hypotension. Hyperbaric oxygen should be considered in patients with syncope, persistent altered mental status, or CO levels greater than 25%. ECMO may play a role in severely poisoned patients with cardiogenic shock.^​18​

Secondary Contamination and Decontamination

Are we all doomed to be exposed and become ill when taking care of the victims of chemical suicide? Do all of these cases turn into a mass casualty incident? How can our colleagues that work in prehospital medicine protect themselves?

The substances used are usually liquid products. The most important component of these scenarios is rapid recognition. Many times, the victim places signs on their vehicle, or on the outside of an enclosed space with sayings such as “Toxic Gas: Do not Enter”. If there is a victim in a vehicle, the windows should be broken from the farthest point away from the patient to allow for the gas to dissipate. If there is a victim in an enclosed space other than a vehicle, standard self contained breathing apparatus is sufficient, or Level B PPE. One of the most important take home points is to NOT GO INTO AN ENCLOSED SPACE WITHOUT RESPIRATORY PROTECTION UNDER ANY CIRCUMSTANCES. Standard precautions, including gloves and gowns, will protect you from topical exposure to the chemicals.

Ocular and dermal decontamination of the victims is often necessary due to exposure to liquid products during mixing. However, gas exposures carry no risk of secondary contamination to healthcare workers and therefore, larger decontamination efforts are not needed.^​19​ Decontamination should largely be done prehospital, but in the event that a patient is brought in to the ED without being decontaminated, removal of their clothes is imperative. Removal of clothing removes an estimated 75 to 90% of the exposure.^​19​ Once their clothes have been removed, they should be placed in a plastic bag and sealed. If there are any solid materials on the skin, unlikely in this scenario, they should be brushed off, followed by decontamination with water and soap, if available.

Don’t forget the eyes! Acids burn. Acids in the eye cause chemical burns via coagulative necrosis. Decontamination should be started immediately and the eyes should be flushed for a minimum of 15 minutes with water or normal saline until neutral pH. Thereafter, care is supportive.

Summary

Despite the concerns surrounding “13 Reasons Why”, the show was released. Netflix did add a warning to viewers about the theme of the show. Additionally, in July 2019, the suicide scene in the first season’s final episode was edited out. But, sadly, the warnings and removal of the suicide scene did not impact the suicide contagion. The concerns of suicide contagion were valid. A recent retrospective review utilizing data from the Centers for Disease Control (CDC) Wide-ranging Online Data for Epidemiologic research database (WONDER) confirms that suicide rates among both males and females between the ages of 10 and 19 years of age increased during the times when the show was trending on social media sites. This data also showed that there was an increase in suicides by hanging, which was the method used in the series.^​1​

We have seen this trend of suicide contagion in chemical suicides and this will likely continue with increased media reports of the ease of these methods. Nearly 90% of suicide victims have a significant psychiatric illness at the time of their death, which may be undiagnosed, untreated or both.^​20​ It is imperative that we attempt to identify at risk populations. The National Suicide Prevention Lifeline at 1-800-273-TALK (8255) is an invaluable resource.

Approach to these Patients

• Removal from the source is imperative
• Aggressive supportive care and ACLS as needed
• Removal of clothes and decontamination of skin and eyes of the victims
• Consider sodium nitrite and/or hydroxocobalamin in patients with suspected hydrogen sulfide that remain symptomatic after initial supportive care
• Hyperbaric oxygen therapy in severely poisoned CO patients