[Sargassum seaweed assaults the French West Indies]. / Algues sargasses à l'assaut des Antilles.

SARGASSUM SEAWEED AS SAULTS THE FRENCH WEST INDIES. Since 2011, Martinique and the islands of Guadeloupe have been affected by repeated groundings, culminating in an exceptional wave in 2018. While the sargassum ( Sargassum natans and S. fluitans ) involved in these phenomena are neither toxic nor urticating, indirect toxicity linked to the presence of microorganisms and heavy metals (arsenic, mercury, etc.) in sargassum clusters has been described. Similarly, after a 24 to 48 hours stay on the shore, sargassum algae enter a putrefaction cycle responsible to produce hydrogen sulfide (H2S) and ammonia (NH3). The acute toxicity of these gases is well known. However, very few data are available on the clinical effects of prolonged exposure to low doses of H2S and NH3. Our team has recently described the syndromic features of chronic exposure, supposing for deleterious effects on the cardiovascular, respiratory and neurological systems.

ALGUES SARGASSES À L'ASSAUT DES ANTILLES. Depuis 2011, la Martinique et les îles de la Guadeloupe sont touchées par des échouements à répétition d'algues sargasses qui ont culminé avec une vague exceptionnelle en 2018. Si les sargasses (Sargassum natans et S. fluitans) impliquées dans ces phénomènes ne sont ni toxiques ni urticantes, une toxicité indirecte liée à la présence de micro-organismes et de métaux lourds (arsenic, mercure…) dans les amas de sargasses est décrite. De même, après un séjour de vingt-quatre à quarante-huit heures sur le littoral, les algues sargasses entrent dans un cycle de putréfaction responsable de la production d'hydrogène sulfuré (H2S) et d'ammoniac (NH3). La toxicité aiguë de ces gaz est bien connue. Il existe en revanche très peu de données disponibles sur les effets cliniques d'une exposition prolongée à de faibles doses d'H2S ou NH3. Notre équipe a récemment décrit le tableau syndromique de l'exposition chronique et suppose des effets délétères sur le système cardiovasculaire, respiratoire et neurologique.

Basin-scale reconstruction of euxinia and Late Devonian mass extinctions.

The Devonian-Carboniferous transition marks a fundamental shift in the surface environment primarily related to changes in ocean-atmosphere oxidation states1,2, resulting from the continued proliferation of vascular land plants that stimulated the hydrological cycle and continental weathering3,4, glacioeustasy5,6, eutrophication and anoxic expansion in epicontinental seas3,4, and mass extinction events2,7,8. Here we present a comprehensive spatial and temporal compilation of geochemical data from 90 cores across the entire Bakken Shale (Williston Basin, North America). Our dataset allows for the detailed documentation of stepwise transgressions of toxic euxinic waters into the shallow oceans that drove a series of Late Devonian extinction events. Other Phanerozoic extinctions have also been related to the expansion of shallow-water euxinia, indicating that hydrogen sulfide toxicity was a key driver of Phanerozoic biodiversity.

Novel treatment of dihydrogen sulfide inhalation using hyperbaric oxygen during mass casualty.

Hydrogen sulfide (H2S) is a toxic gas produced via breakdown of organic matter. Hydrogen sulfide exposure can cause symptoms ranging in severity from mild effects (dizziness, headache, nausea) to severe lactic acidosis, respiratory failure, pulmonary edema, cardiac arrhythmias and death. Treatment modalities include oral countermeasures and 100% FiO2 with supportive therapy. However, case studies utilizing hyperbaric oxygen (HBO2) therapy have been reported with general benefit seen in severe cases of toxicity. In this report, cases of mild to moderate H2S toxicity occurred aboard a U.S. Navy ship, resulting in a mass casualty incident of more than 30 patients. Patient symptoms included dizziness, headaches, nausea, vomiting, and one patient with altered mental status. Most patients' symptoms resolved after several hours of supportive therapy, but six patients had symptoms refractory to 100% FiO2 at 1 atm. These six patients received HBO2 therapy with a USN Treatment Table 9 after consultation with the local emergency room and hyperbaric assets. Four separate chambers were utilized, including two chambers onboard USN ships and the local explosive ordnance disposal (EOD) chamber. Complete resolution of symptoms in all six patients was achieved within the first breathing period. Patients were monitored after treatment aboard the USN ship medical department. No patients required emergency department care. These cases demonstrate an expanded use of HBO2 to include moderate cases of H2S toxicity refractory to first-line therapy.

Fatal poisoning of four workers in a farm: Distribution of hydrogen sulfide and thiosulfate in 10 different biological matrices.

We evaluate the distribution of sulfide and thiosulfate (TS) in biological samples of four dairy farmers died inside a pit connected to a manure lagoon. Autopsies were performed 4 days later. Toxicological analyses of sulfide and TS were made using an extractive alkylation technique combined with gas chromatography/mass spectrometry (GC/MS). Autopsies revealed: multiorgan congestion; pulmonary edema; manure inside distal airways of three of the four victims. Sulfide concentrations were cardiac blood: 0.5-3.0 µg/mL, femoral blood: 0.5-1.2 µg/mL, bile: <0.1-2.2 µg/mL; liver 2.8-8.3 µg/g, lung: 5.0-9.4 µg/g, brain: 2.7-13.9 µg/g, spleen: 3.3-6.3 µg/g, fat: <0.1-1.5 µg/g, muscle: 2.6-3.5 µg/g. TS concentrations were cardiac blood: 2.1-4.9 µg/mL, femoral blood: 2.1-2.3 µg/mL, bile: 2.5-4.4 µg/mL, urine: <0.5-1.8 µg/mL; liver <0.5-2.6, lung: 2.8-5.4 µg/g, brain: <0.5-1.9 µg/g, spleen: 1.2-2.9 µg/g, muscle: <0.5-5.6 µg/g. The cause of death was assessed to be acute poisoning by hydrogen sulfide (H2S) for all the victims. Manure inhalation contributed to the death of three subjects. The measurement of sulfide and TS concentrations in biological samples contributed to better understand the sequence of the events. Subjects 3 provided the highest concentration of sulfide in brain, thus, supporting the hypothesis of a rapid loss of consciousness and respiratory depression. One by one, the other farmers entered the pit in attempts to rescue the coworkers but collapsed. Despite the rapid death, subject 3 was the only one with TS detectable in urine. This could be due to differences in metabolism of H2S.

Acute myocardial injury following hydrogen sulfide poisoning.

BACKGROUND: Hydrogen sulfide poisoning can cause severe myocardial injury, but the damage is subtle and can be easily misdiagnosed. This report presents the dynamic observation of myocardial injury associated with hydrogen sulfide poisoning. CASE REPORT: Two young men presented with symptoms of "lightning-like" death immediately after entering a tank. They were found and rescued in 20 min at a time when they were already in a coma. Case 1 had no spontaneous breathing and pulse, while case 2 had spontaneous breathing and a pulse. Upon transfer to a local hospital, case 1 received continuous cardiopulmonary resuscitation which led to the recovery of his heart rate 3 min after arriving at the hospital. However, the patient remained in a Glasgow coma scale of 3. He was transferred to our hospital where he, unfortunately, died on the seventh day due to multiple organ failure. Case 2 was also transferred to the intensive care unit in our hospital and on the fourth day of hospitalization, the patient presented ST-segment elevation and dynamic changes in markers of myocardial injury. Changes in electrocardiogram and markers of myocardial injury were monitored and examination improved through conventional echocardiography, coronary artery CT, radionuclide myocardial perfusion imaging, and two-dimensional speckle tracking imaging strain. The treatment gradually improved the patient's myocardial injury and was discharged from the hospital. CONCLUSION: Hydrogen sulfide poisoning can cause damage to myocardial function and the damage can be more insidious in nature and with a delayed onset. Recovery from myocardial damage can be very slow.

Sample preparation method with ultrafiltration for whole blood thiosulfate measurement.

Quantitative analysis of thiosulfate is useful for diagnosing hydrogen sulfide poisoning. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) enables more rapid and sensitive measurements than previous methodologies. As simple measurements of blood thiosulfate concentration are affected by the blood matrix, blood is used as the solvent to prepare the standard solution for calibration curve generation. Thus, a large amount of blood devoid of thiosulfate is required. We developed a preparation method by incorporating an ultrafiltration step to overcome this limitation and generate a calibration curve using a standard solution prepared with pure water. We used this improved method to investigate the stability of thiosulfate in refrigerated samples. To compare the effects of refrigeration, blood samples were prepared using the following two methods: one sample was treated with a 50-kDa exclusion ultrafiltration membrane and the other was not treated. The samples were stored at 4 °C, and then measured at 0, 3, 6, 24, 48, and 96 h. The incorporation of the ultrafiltration step in the measurement procedure enabled the quantification of thiosulfate, by plotting a calibration curve using a standard of pure water; it did not require a blood standard. Additionally, the reduction in whole blood thiosulfate concentration was within 10% during 2 days of refrigeration. Thus, the need for a large amount of blood to prepare the standard solution was resolved by the ultrafiltration step in test sample preparation. This method is useful to measure thiosulfate concentration and is not hindered by sample refrigeration for a few days.

Intramuscular aminotetrazole cobinamide as a treatment for inhaled hydrogen sulfide poisoning in a large swine model.

Hydrogen sulfide (H2 S), a high-threat chemical agent, occurs naturally in a variety of settings. Despite multiple incidents of exposures and deaths, no FDA-approved antidote exists. A rapid-acting, easy to administer antidote is needed. We conducted a randomized control trial in swine comparing intramuscular administration of aminotetrazole cobinamide (2.9 mL, 18 mg/kg) to no treatment following inhalation of H2 S gas. We found that aminotetrazole cobinamide administered 2 min after the onset of respiratory depression-defined as a tidal volume of less than 3 mL/kg for 2 consecutive minutes-yielded 100% survival, while all control animals died. Respiratory depression resolved in the treatment group within 3.6 ± 1.5 min (mean ± SD) of cobinamide administration, whereas control animals had intermittent gasping until death. Blood pressure and arterial oxygen saturation (SO2 ) returned to baseline values within 5 and 10 min, respectively, of cobinamide treatment, and plasma lactate concentration decreased to less than 50% of the highest value by the end of the experiment. In control animals, plasma lactate rose continuously until death. We conclude that intramuscular aminotetrazole cobinamide is effective in a large animal, inhalational model of acute, severe H2 S poisoning.

Lethal Hydrogen Sulfide poisoning in open space: An atypical case of asphyxiation of two workers.

Hydrogen sulfide is one of the most dangerous toxic gases that has led to the deaths in confined spaces of many workers. We report an atypical case of a fatal accident of H2S poisoning in an open space when two workers died during the opening of a hatch on a tanker truck filled with leachate water. Despite being outdoors, the two workers, were suddenly and quickly overwhelmed by a lethal cloud of H2S, which escaped like a geyser from the hatch and hovered over the top of the tanker making it impossible for them to survive. The first operator was engulfed by the sudden flow of lethal gas near the hatch while the second worker, who came to his aid, immediately lost consciousness and fell off the tanker onto the ground. Environmental toxicological analyses were carried out on the air near the hatch and inside the tanker 2h, 20 days and 70 days after the accident. Toxicological analyses on the blood were also carried out but unfortunately, no urine sample was available. The thiosulfate, detected by GC/MS analysis after derivatization of PFBBr, was found to be 0.01 and 0.04mM/L. These values are included in the medium-low lethal values of occupational fatalities involving H2S reported in the literature.

[Characteristics analysis and control countermeasures of acute hydrogen sulfide poisoning in fishing boats in a city from 2009 to 2018].

Objective: To conduct a characteristic analysis of the case of acute hydrogen sulfide poisoning in fishing boats for nearly ten years in a city, and to research on prevention and control measures, so as to provide scientific basis for formulating prevention strategies. Methods: In July 2018, collecting the data of acute hydrogen sulfide poisoning in fishing boats recorded by the Oceanic and Fishery Department & Health Sector from January 1, 2009 to June 30, 2018, the accident characteristics of acute hydrogen sulfide poisoning in fishing boats was analyzed, and compared the differences of hydrogen sulfide poisoning under different classification statistics. Results: In the past ten years, there were 14 acute poisonings in the city, 34 people were poisoned and 12 deaths (the case fatality rate was 35.3%) . According to the types of fishing vessels, the majority number of acute hydrogen sulfide poisoning incidents, poisoned persons and deaths occurred on fishing boats, accounted for 71.4% (10/14) , 76.5% (26/34) and 75.0% (9/12) respectively. From the location of the accident, 85.7% (12/14) of the acute hydrogen sulfide poisoning incidents occurred outside the fishing port. Fisher's exact test showed that the case fatality rate in within the fishing port was higher than that outside the fishing port (P=0.008) . From the cause of direct poisoning, the first three reasons were enter the fish room to rescue, enter the fish room to move fresh catch, to clean the fish room. The poisoning showed seasonal changes, Fisher's exact test showed that the fatality rate in summer was significantly higher than that in spring (P=0.044) , but there was no statistical significance in other seasons (P>0.05) . Conclusion: The acute hydrogen sulfide poisoning of fishing boats in this city has a high case fatality rate, frequent collective poisoning, and showed seasonal changes. Blind rescue, incomplete facilities, and inadequate system are important factors leading to poisoning, so daily measures and rescue measures should be strengthened to reduce the occurrence of poisoning and casualties.

Toxicological investigations in a fatal and non-fatal accident due to hydrogen sulphide (H2S) poisoning.

Hydrogen sulphide (H2S) is one of the most toxic natural gas and represents a not rare cause of fatal events in workplaces. We report here a serious accidental poisoning by hydrogen sulphide inhalation involving six sailors. Three of them died while the other three survived and were transported to the emergency room. No greenish discolouration of the body, that could be a feature of these type of deaths, was observed at autopsy. Given that blood and/or urine H2S detection does not allow to discriminate if it is related to inhalation or to putrefactive processes, the determination of thiosulphate, H2S main metabolite, is decisive. The succession of fatal events reported here can be rebuilt by toxicological data interpretation: the subject 1 died after a longer interval of time as demonstrated by the highest blood and urine thiosulfate concentrations; the subject 2 died after a short interval of time as showed by a lower blood and urine thiosulfate concentrations than subject 1; the subject 3 died almost immediately after H2S inhalation since he showed the lowest blood thiosulfate concentration, and no trace of sulphide and thiosulfate was found in the urine.

Fatal inhalation of volcanic gases in three tourists of a geothermal area.

The study reports the environmental, toxicological and histopathological forensic investigations applied on three victims of accidental death (father, mother and son), due to the fall in a volcanic pothole, during the touristic visit of the "Solfatara park", near Naples (Italy). At autopsy greenish skin discolouration was observed and all bodies showed the classical signs of asphyxial deaths, such as cyanosis and hemorrhagic pulmonary edema. Focal micro-hemorrhages were found in the brain at intracranial and subpial levels. The hemogasanalysis and spectrophotometric test on blood for Methemoglobin (MetHb), Carboxyhemoglobin (HbCO) and Sulfhemoglobin (SHb) showed pCO2, SHb and MetHb above the physiological levels. On biological specimens, toxicological analyses performed by GC/MS revealed high concentrations of hydrogen sulfide (H2S) and of thiosulfate (TS), its main metabolite. The monitoring of toxic gases on the death scene showed an unsafe environment, into the pothole, able to cause the sudden loss of consciousness of the victims with subsequent asphyxiation (knockdown effect). In particular, at the bottom of the hole, the maximum levels of H2S and carbon dioxide (CO2) were 2200 ppm and 98% respectively. For the family members, the cause of the death was assessed as acute poisoning by H2S and CO2. The fatalities, happened in quick succession as for a domino effect, were pretty similar to the asphyxial deaths by confined spaces, frequently observed in occupational setting. Fatalities secondary to accidental volcanic gases inhalation, such as H2S and CO2 in geothermal areas, have been already described but often without a forensic approach. To the best of our knowledge this is the first case that reports the accidental poisoning by volcanic gases involving three people, with different caracteristic of age and sex, allowing the correlation between toxicological and pathological results with the true levels of asphyxiating gas, measured on the death scene.

Methylene Blue Administration During and After Life-Threatening Intoxication by Hydrogen Sulfide: Efficacy Studies in Adult Sheep and Mechanisms of Action.

Exposure to toxic levels of hydrogen sulfide (H2S) produces an acute cardiac depression that can be rapidly fatal. We sought to characterize the time course of the cardiac effects produced by the toxicity of H2S in sheep, a human sized mammal, and to describe the in vivo and in vitro antidotal properties of methylene blue (MB), which has shown efficacy in sulfide intoxicated rats. Infusing NaHS (720 mg) in anesthetized adult sheep produced a rapid dilation of the left ventricular with a decrease in contractility, which was lethal within about 10 min by pulseless electrical activity. MB (7 mg/kg), administered during sulfide exposure, maintained cardiac contractility and allowed all of the treated animals to recover. At a dose of 350 mg NaHS, we were able to produce an intoxication, which led to a persistent decrease in ventricular function for at least 1 h in nontreated animals. Administration of MB, 3 or 30 min after the end of exposure, whereas all free H2S had already vanished, restored cardiac contractility and the pyruvate/lactate (P/L) ratio. We found that MB exerts its antidotal effects through at least 4 different mechanisms: (1) a direct oxidation of free sulfide; (2) an increase in the pool of "trapped" H2S in red cells; (3) a restoration of the mitochondrial substrate-level phosphorylation; and (4) a rescue of the mitochondrial electron chain. In conclusion, H2S intoxication produces acute and long persisting alteration in cardiac function in large mammals even after all free H2S has vanished. MB exerts its antidotal effects against life-threatening sulfide intoxication via multifarious properties, some of them unrelated to any direct interaction with free H2S.

Intramuscular cobinamide versus saline for treatment of severe hydrogen sulfide toxicity in swine.

INTRODUCTION: Hydrogen sulfide (H2S) is found in petroleum, natural gas, and decaying organic matter. Terrorist groups have attempted to use it in enclosed spaces as a chemical weapon. Mass casualty scenarios have occurred from industrial accidents and release from oil field sites. There is no FDA approved antidote for sulfide poisoning. We have previously reported that intravenous cobinamide is effective for sulfide poisoning. A rapid-acting antidote that is easy to administer intramuscularly (IM) would be ideal for use in a prehospital setting. In this study, we assessed survival in sulfide-poisoned swine treated with IM cobinamide. METHODS: Eleven swine (45-55 kg) were anesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring. After stabilization, anesthesia was adjusted such that animals ventilated spontaneously with a FiO2 of 0.21. Sodium hydrosulfide (NaHS, 8 mg/mL) was infused intravenously at 0.9 mg/kg.min until apnea or severe hypotension. Animals were randomly assigned to receive cobinamide (4 mg/kg), or no treatment at the apnea/hypotension trigger. The NaHS infusion rate was sustained for 1.5 min post trigger, decreased to 0.2 mg/kg.min for 10 min, and then discontinued. RESULTS: The amount of NaHS required to produce apnea or hypotension was not statistically different in both groups (cobinamide: 9.0 mg/kg ±6.1; saline: 5.9 mg/kg ±5.5; mean difference: -3.1, 95% CI: -11.3, 5.0). All of the cobinamide treated animals survived (5/5), none of the control (0/6) animals survived (p < .01). Mean time to return to spontaneous ventilation in the cobinamide treated animals was 3.2 (±1.1) min. Time to return to baseline systolic blood pressure (±5%) in cobinamide-treated animals was 5 min. CONCLUSION: Intramuscular cobinamide was effective in improving survival in this large swine model of severe hydrogen sulfide toxicity.

Midazolam Efficacy Against Acute Hydrogen Sulfide-Induced Mortality and Neurotoxicity.

Hydrogen sulfide (H2S) is a colorless, highly neurotoxic gas. It is not only an occupational and environmental hazard but also of concern to the Department of Homeland Security for potential nefarious use. Acute high-dose H2S exposure causes death, while survivors may develop neurological sequelae. Currently, there is no suitable antidote for treatment of acute H2S-induced neurotoxicity. Midazolam (MDZ), an anti-convulsant drug recommended for treatment of nerve agent intoxications, could also be of value in treating acute H2S intoxication. In this study, we tested the hypothesis that MDZ is effective in preventing/treating acute H2S-induced neurotoxicity. This proof-of-concept study had two objectives: to determine whether MDZ prevents/reduces H2S-induced mortality and to test whether MDZ prevents H2S-induced neurological sequelae. MDZ (4 mg/kg) was administered IM in mice, 5 min pre-exposure to a high concentration of H2S at 1000 ppm or 12 min post-exposure to 1000 ppm H2S followed by 30 min of continuous exposure. A separate experiment tested whether MDZ pre-treatment prevented neurological sequelae. Endpoints monitored included assessment of clinical signs, mortality, behavioral changes, and brain histopathological changes. MDZ significantly reduced H2S-induced lethality, seizures, knockdown, and behavioral deficits (p < 0.01). MDZ also significantly prevented H2S-induced neurological sequelae, including weight loss, behavior deficits, neuroinflammation, and histopathologic lesions (p < 0.01). Overall, our findings show that MDZ is a promising drug for reducing H2S-induced acute mortality, neurotoxicity, and neurological sequelae.

Investigation of a Worker Death While Agitating Manure in a Non-enclosed Storage.

An in-depth investigation of an unusual, non-enclosed manure storage hydrogen sulfide-induced fatality on a Holstein beef production operation is presented. The case involved several factors that likely played a role in the young farmer's death. These included zero wind movement, a reported temperature inversion in the area, relatively cool late summer outdoor temperatures on the morning of the incident, higher outdoor temperatures the week prior, and a high by-product steer ration containing ingredients that contributed significant sulfur content to the stored manure. Recommendations are offered for future research to determine the combinations of conditions and inputs that have potential to increase human and animal risk around manure storage structures. Based on this case and others recently documented showing unsafe levels of hydrogen sulfide being released from similar outdoor storages, it is critical that agricultural industry experts and input suppliers continue to analyze risk and consequences associated with new management practices, processes, inputs (including feed ingredients and animal bedding), machines, and other technology developed to support animal agriculture. Production practice and educational guidance are also offered based on this case and published literature.

[An investigation of an accident of occupational acute hydrogen sulfide poisoning].

Objective: To investigate an accident of occupational acute hydrogen sulfide poisoning, and to analyze related clinical data. Methods: An investigation was performed for an accident of occupational acute hydrogen sulfide poisoning in a place in Shandong, China, in July 2016, and related clinical data were summarized. Results: This was a typical accident of occupational acute hydrogen sulfide poisoning, and a lack of occupational protection and illegal operation were the major causes of this accident. Of all five patients, four experienced coma, toxic encephalopathy, and respiratory failure and were cured at last, and one had cortical syndrome after long-term treatment and died of pulmonary infection seven months later. Conclusions: In case of occupational acute hydrogen sulfide poisoning, rescuers should help the persons who are poisoned reasonably and meanwhile ensure their own safety.

Hydrogen sulfide gas poisoning in fish garbage room: A report of a fisherman.

We report the case of a fisherman who was exposed to high concentrations of hydrogen sulfide (H2S) gas from the fish garbage room. The patient survived and was discharged with full recovery from the hospital. H2S is a colourless, foul smelling and highly toxic gas next to carbon monoxide, which causes inhalation death. It is a by-product of various industrial processes particularly involves exposure from agriculture, petrochemical industry and organic matter decomposition from sewage processing. It is a by-product of H2S has been referred as the "knock down gas" because inhalation of high concentrations can cause immediate loss of consciousness and death. Although early use of amyl nitrate and hyperbaric oxygen shows some benefit in literature, supportive care remains the mainstay of treatment. Emergency physicians and pre-hospital care personnel are not very familiar with such exposure due to its rarity. This becomes more relevant in the developing world settings where there are rising concerns about the unsafe exposure to hazardous chemicals and its impact on human health. Emergency physicians working in Pakistan should be aware of this entity especially in regard to fishermen presenting to the Emergency Department with such a clinical presentation and its toxic manifestations. This incident also illustrates the need of enforcement of health and safety regulations in the fishing industry.

Efficacy of Intravenous Cobinamide Versus Hydroxocobalamin or Saline for Treatment of Severe Hydrogen Sulfide Toxicity in a Swine (Sus scrofa) Model.

BACKGROUND: Hydrogen sulfide (H2 S) is a potentially deadly gas that naturally occurs in petroleum and natural gas. The Occupational Health and Safety Administration cites H2 S as a leading cause of workplace gas inhalation deaths. Mass casualties of H2 S toxicity may be caused by exposure from industrial accidents or release from oil field sites. H2 S is also an attractive terrorism tool because of its high toxicity and ease with which it can be produced. Several potential antidotes have been proposed for hydrogen sulfide poisoning but none have been completely successful. OBJECTIVE: The objective was to compare treatment response assessed by the time to spontaneous ventilation among groups of swine with acute H2 S-induced apnea treated with intravenous (IV) cobinamide (4 mg/kg in 0.8 mL of 225 mmol/L solution), IV hydroxocobalamin (4 mg/kg in 5 mL of saline), or saline alone. METHODS: Twenty-four swine (45-55 kg) were anesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring. After stabilization, anesthesia was adjusted such that animals would spontaneously ventilate with an FiO2 of 0.21. Sodium hydrosulfide (NaHS; concentration of 8 mg/mL) was begun at 1 mg/kg/min until apnea was confirmed for 20 seconds by capnography. This infusion rate was sustained for 1.5 minutes postapnea and then decreased to a maintenance rate for the remainder of the study to replicate sustained clinical exposure. Animals were randomly assigned to receive cobinamide (4 mg/kg), hydroxocobalamin (4 mg/kg), or saline and monitored for 60 minutes beginning 1 minute postapnea. G* power analysis using the Z-test determined that equal group sizes of eight animals were needed to achieve a power of 80% in detecting a 50% difference in return to spontaneous ventilations at α = 0.05. RESULTS: There were no significant differences in baseline variables. Moreover, there were no significant differences in the mg/kg dose of NaHS (5.6 mg/kg; p = 0.45) required to produce apnea. Whereas all of the cobinamide-treated animals survived (8/8), none of the control (0/8) or hydroxocobalamin (0/8)-treated animals survived. Mean (±SD) time to spontaneous ventilation in the cobinamide-treated animals was 3.2 (±1.1) minutes. CONCLUSIONS: Cobinamide successfully rescued the severely NaHS-poisoned swine from apnea in the absence of assisted ventilation.