Course (34 y/o male) Day 1, at ER Day 1, in ICU Intubation with mechanical ventilator support N/S challenge, Norepinephrine run 30 µg/min Give amyl nitrite 1pc inhalation and 3% sodium nitrite 10ml iv drip for 20 mins Brain CT: no evidence of ICH or structural lesions Day 2, in ICU Consciousness: confused and disoriented GaGa
Course (34 y/o male) Day 4, in ICU Day 5, at ordinary ward Aspiration pneumonia => give empiric antibiotics: Ceftazidime 2g q8h Day 16, at ordinary ward Consciousness clear Discharge Extubation EEG: diffuse cortical dysfunction
Introduction Hydrogen sulfide (H2S) is a colorless toxic gas that has strong odor of “rotten eggs” H2S poisoning usually occurs by inhalation Discussion ~ Woodall GM et al, Inhal Toxicol. 2005;17:593-639
Source Organic 1. Incomplete oxidation of sulfur compounds 2. Bacterial degradation of sulfur compounds Inorganic, mainly industrial 1. Petroleum industry -- contamination or by-product 2. Chemical industry -- reactant for production of chemicals 3. Production of heavy water 4. Metal refining ~ Tee L. Guidotti, International Journal of Toxicology. 2010, 29:569-581
Knock down !! Apnea !! ~ Doujaiji B et al, Ann Saudi Med. 2010;30:76-80
Symptoms 0.05 ppm (airbone concentration) Pungent smell mimicking “rotten egg” 0.1 ppmAnosmia 50-150 ppmParalysis, conjunctivitis 250 ppmPhotophobia, pulmonary edema 250-500 ppmHeadache, nausea, vomiting, confusion, tachycardia, hypotension 500-750 ppmRespiratory arrest 750-1000 ppmKnocked down (central neurotoxicity) > 1000 ppmDying immediately within a breath ~ Tee L. Guidotti, International Journal of Toxicology. 2010, 29:569-581
Diagnosis Measurement of blood sulfide in acute emergencies is of little clinical value. History of hydrogen sulfide exposure Odor of hydrogen sulfide Serum BUN, Cr, electrolyte, glucose, CPK, blood gas & serum lactate ECG & Chest X-ray CT scan ~ Milby HT et al, American Journal of Industrial Medicine. 1999, 35:192-195
Treatment ~ Gregorakos L et al, Angiology. 1995, 46:1123-1131
Antidote – Nitrite Salt Nitrite salt oxidizes the Fe2+ of hemoglobin to Fe3+, deriving Met-Hb Met-Hb competes with the Fe3+ of cytochrome oxidase and protects it from oxidization by H2S Keep the Met-Hb level < 25% with a concern of hypoxemia from methemoglobinemia Oxy-Hb Met-Hb Sulfa-MetHb Oxy-Hb + SO2 H2S Amyl nitrite, Sodium nitrite cyt c 2+ cyt c 3+ cyt a 2+ cyt a 3+ cyt a 3 2+ cyt a 3 3+ H2O2 + 2H + 2H2O ~ Smith RP et al, Ann Rev Toxicol. 1976, 16:189 Mitochondria Blood
Nitrite Kit Amyl nitrite If spontaneous breathing remains, give amyl nitrite inhalation every 3 min until sodium nitrite is ready Sodium nitrite Dissolve 0.6g sodium nitrite to 20 ml of water ( 3% solution) IV 10ml of the 3% sodium nitrite solution > 20 mins ~ Morii et al, Journal of Occupational Medicine and Toxicology. 2010, 5:28
Investigation of death Autopsy findings : pulmonary edema and greenish discoloration of viscera. The presence of sulfide ion in blood or major organs at toxic concentrations (usually in excess of 1.0 mg/L or mg/kg) the demonstration of potentially lethal levels of sulfide (1 – 5 mg/L or mg/kg) in blood, lung, and skeletal muscle will provide the best corroboration of a ruling of death due to acute hydrogen sulfide intoxication.
Conclusion Certain neurotoxic effects of exposure are probably due to a direct toxic effect on the brain, while others are almost certainly a result of hypoxia secondary to H2S-induced respiratory insuffıciency. pulmonary edema is a common consequence of poisoning and there is suggestive evidence of hyperactive airway responses in some individuals following brief H2S-induced unconsciousness (knockdown)
criteria for acceptable community levels are very different than those governing occupational standards urinary thiosulfate determinations can be useful for monitoring occupational exposure. determination of sulfide ion concentrations in blood or major organs can be useful in corroborating a diagnosis of fatal H2S toxicity, but there are many pitfalls in collecting, storing, and analyzing tissue and fluid samples.
LABORATORY TESTING Biological Monitoring for Chronic Industrial Exposure. Diagnosis of Acute Poisoning
Chronic Industrial Exposure measurement of urinary thiosulfate one study : 29 unexposed healthy men had urinary thiosulfate values of 0.4 – 5.4 umol/mmol creatinine a volunteer exposed to 18 ppm hydrogen sulfide for 30 minutes exhibited urinary thiosulfate concentrations that increased to a peak of 30 umol/mmol creatinine at 15 hours, before declining to a normal value by 17 hours. Ingestion of food or water high in sulfur content can dramatically increase urinary thiosulfate concentration.
Chronic Industrial Exposure not routinely performed : paucity of studies correlating air concentrations with urinary excretion data, as well as the potential complications in interpretation of such data.
Special concern Paramedics and caregivers were also reported to have become injured secondarily Undressing, dry decontamination, water decontamination in an airy space Mouth-to-mouth resuscitation is not indicated When transferring a patient with H2S poisoning by an ambulance, all windows should be opened
Clarification 1) Certain neurotoxic effects of exposure are probably due to a direct toxic effect on the brain, while others are almost certainly a result of hypoxia secondary to H2S-induced respiratory insufficiency 2) pulmonary edema is a common consequence of poisoning and there is suggestive evidence of hyperactive airway responses in some individuals following brief H2S-induced unconsciousness (knockdown);
Clarification 3) criteria for acceptable community levels are very different than those governing occupational standards; 4) urinary thiosulfate determinations can be useful for monitoring occupational exposure; 5) determination of sulfide ion concentrations in blood or major organs can be useful in corroborating a diagnosis of fatal H2S toxicity, but there are many pitfalls in collecting, storing, and analyzing tissue and fluid samples.