Hydrogen sulfide is a highly flammable, colorless, and toxic gas found naturally in sewage, swamps, manure gas, hot springs, geysers, and volcanoes. It is found in the oil and gas industries and is used in activities such as food processing, paper mills, and tanneries. It is also found in some homemade cleaning mixtures that are occasionally employed in suicide attempts.[1][2][3][4][5][6][7]
Hydrogen sulfide toxicity typically results from gaseous exposure and acts as an irritant initially and later acts by inhibiting mitochondrial respiration. Inhalation is the most common route of administration for the toxic substance to enter the bloodstream though it can be absorbed through the skin as well.[2]
The combustible nature of the gas increases the risk of explosions and burns as another mechanism of injury. Hydrogen sulfide is heavier than air and therefore tends to accumulate and concentrate near the floors of poorly ventilated rooms rather than disperse into the air.[1][8]
Hydrogen sulfide toxicity results mostly from unintentional exposure. Cases have steadily increased in the United States from the 1990s to 2019. After being popularized as a method of suicide in Japan in 2007, suicides increased significantly before strongly trending downward. Approximately 80% of suicide attempts have ensued in toxicity of first responders and civilians near the scene. Most cases occur in those greater than 20 years of age. Less than 1% of unintentional cases result in death, while the mortality rate in intentional cases exceeds 50%.[9][10][11][12][13][14][15][16]
Hydrogen sulfide results in direct irritation to the eyes, causing conjunctival injection initially and corneal injury eventually. When inhaled, it leads to pulmonary injury presenting as hemorrhagic pulmonary edema. Once it enters the bloodstream and passes the blood-brain barrier, neurotoxic effects can be seen, namely dizziness, seizure, coma, and ultimately death.[2][17][18] In brief, hydrogen sulfide is a known pulmonary irritant and asphyxiant that primarily causes respiratory and neurological clinical manifestations when inhaled.[19]
The mechanism of action of hydrogen sulfide toxicity is similar to that of cyanide. Oxidative phosphorylation in the electron transport chain during aerobic glucose metabolism is disrupted via inhibition of cytochrome c oxidase. Cells, therefore, largely are diverted to anaerobic metabolism, producing a metabolic acidosis due to lactate accumulation.[2][17][18]
As many toxic gases overlap in terms of toxic effects, history is imperative to help determine the specific gas causing the toxicity. Occupational history and recent local travel history will help to differentiate, i.e., working in a petroleum plant or as a sewage inspector, or travel to a natural hot spring or volcano. Patients may typically report a strong “rotten egg” smell. However, it is important to note that hydrogen sulfide rapidly desensitizes olfactory nerves, and after prolonged exposure, patients may fail to recall the malodorous scent. Lack of malodor should not be relied upon as a definitive exclusion of hydrogen sulfide toxicity.
Clinical examination findings include signs of irritation at low doses: conjunctival injection/pain, and cough and some shortness of breath as hydrogen sulfide is a pulmonary irritant. At higher doses, pulmonary edema, hemoptysis (hemorrhagic pulmonary edema), and delayed corneal injury may occur. Higher doses may also induce neurological symptoms of seizure, coma, and ultimately death.[2][6][7][17][18][21]
The diagnostic workup is largely negative. However, in cases of pulmonary edema, this can be seen on X-ray of the chest or on bedside ultrasound. Elevated lactate is another finding. However, this should be considered in conjunction with the history and clinical examination findings as elevated lactate has numerous causes. Arterial blood gas (ABG) analysis or venous blood gas (VBG) analysis shows metabolic acidosis secondary to the lactate. An electrocardiogram (ECG) should be obtained to assess for myocardial ischemia and/or infarction.[17][18][22]
Initial treatment in an awake patient includes removal from exposure, including removal of clothing, and administration of high flow oxygen. In higher toxic doses where a patient may be altered or in severe respiratory distress secondary to pulmonary edema, treatment consists of sodium nitrite administration of 300mg IV given over 2-4minutes. Sodium nitrite causes methemoglobin to accumulate at low levels. This promotes the conversion of the sulfide to sulfmethemoglobin, which is less toxic than the sulfide. This medication is most effective if given within minutes, as hydrogen sulfide toxicity escalates rapidly. After treatment with sodium nitrite, levels of methemoglobin should be checked within 30-60 minutes, with ideal levels below 30%. If levels of methemoglobin become concerning, methylene blue may be administered. Other than sodium nitrite administration for the treatment of hydrogen sulfide, there is some evidence to suggest hyperbaric oxygen can help improve the delivery of oxygen to end organs. Another medication, cobinamide, has shown promise in animal models for hydrogen sulfide and cyanide toxicity.[17][18][22][23][24][25][26]
Other gaseous toxicities can present with similar symptoms. Hydrocarbons commonly cause dyspnea and cough and may lead to respiratory distress. Infiltrates can be seen on a chest X-ray. CNS depression and myocardial dysfunction can also occur.[27]
Cyanide has a similar mechanism of action as hydrogen sulfide, and patients may also have an overlap of some symptoms, including seizures, tachypnea, and coma. Cyanide, however, is more likely to also present with headache, nausea, vomiting, arrhythmias, cyanosis, and renal and hepatic failure. Cyanide classically has a smell of almonds rather than the rotten egg smell of hydrogen sulfide.[28]
Patients with carbon monoxide poisoning and methemoglobinemia can also present with headache, dyspnea, and confusion but are also more likely to have symptoms of chest pain, nausea, and vomiting. Context is key when differentiating many of these toxic gases with overlapping symptoms. Co-oximetry can help rule out carbon monoxide poisoning and methemoglobinemia.[29][30][31]
The main form of deterrence is to avoid areas known to contain hydrogen sulfide, such as volcanoes, sewers, swamps, and other areas of natural gas.[2][25] In industries where employees are expected to work around the toxic substances, proper personal protective equipment (PPE) should be donned to avoid toxicity. Chief among these is to wear a respirator mask to avoid inhalation, which is the most frequent and direct way for severe toxicity to occur.[25][33]
Hydrogen sulfide toxicity can be difficult to diagnose as it is a colorless gas with a rapidly desensitizing scent. Symptoms can overlap with other toxic gaseous exposures. It is important that first-responders obtain a thorough history so as to clue clinicians into the likely diagnosis upon arrival to the emergency department. Once the patient arrives, an astute clinician will look for keys to diagnosis such as the location of toxicity, work environment, the possible scent of rotten egg, and assess these clues in conjunction with patient symptoms and/or signs.[25]
It is imperative the patient is decontaminated so as not to affect other staff, and treatment should begin promptly as hydrogen sulfide toxicity can be rapidly decompensating and ultimately ensue in death. The poison control center should be notified immediately for greater expertise in diagnosing and treating this rare condition.[12] The patient should immediately be given supplemental oxygen for any signs of respiratory distress or hypoxia, and the clinical pharmacist may aid in the dosing of appropriate medical management.[22] [Level 5]
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