Hydrogen Sulphide (H2S) is a highly toxic, colorless gas that is recognized by a pungent odour reminiscent of ‘rotten eggs’. It is used in several industries and is a product of many industrial processes such as oil refining, mining and rayon manufacture . H2S originates mainly during breakdown of organic matter under anaerobic conditions. Following inhalation, H2S dissociates into free sulphide and hydrogen ions in the blood circulation. Sulphide binds to many macromolecules, including cytochrome oxidase thereby preventing oxidative phosphorylation. This causes reversible inhibition of aerobic metabolism leading to cellular anoxia [2, 3].
Accidental deaths following accidental H2S exposure is a known hazard amongst petroleum workers . H2S has also been implicated in deaths in farms following slurry or manure related accidents .
The development of seizures in case 1 is of considerable interest. It could be due to the seizure threshold being reached due to irritant effects of anoxia or due to effects of H2S itself. H2S has been known to characteristically cause sudden loss of consciousness which is colloquially termed 'knockdown' [3, 6]. Coma is often associated with severe poisonings by H2S . Recent studies have shown that neurons have relatively high H2S levels that act as messengers and therefore H2S is a neuromodulator . Animal studies indicate that this neuromodulation includes up-regulation and increased expression of gamma-aminobutyric acid B receptor subunits 1 (GABA(B)R1) and 2 (GABA(B)R2) . However, since GABA has inhibitory effects on neurons, one would not expect H2S to reduce the seizure threshold . Therefore our patient probably developed seizures as a consequence of the combination of hypoxic and histotoxic hypoxia in the background of a propensity for seizures, rather than a direct toxic effect of H2S.
Post-anoxic neurological sequelae have been reported . Survivors have been reported to exhibit neurobehavioral effects following acute, non-fatal H2S intoxication with proven reduction of cognitive capabilities, depressive symptoms and personality changes even though the results of neurological examination and neuroimaging techniques remained unremarkable . A case report detailing the sequelae following H2S exposure in a 27-year-old male with Glasgow Coma Score which improved from 3 to 15 over a 7 day period with hyperbaric oxygen therapy showed that though both CT and MRI of brain were unremarkable, PET scan 3 years later showed abnormally decreased metabolism bilaterally in the temporal, inferior parietal lobes, left thalamus and abnormal uptake in the striatum. Further cerebral perfusion studies showed bilaterally decreased flow in the putamen without cortical abnormalities. Neuropsychological and neurofunctional testing revealed microsmia, psychomotor slowing, extrapyramidal signs and deficits in memory and executive/planning functioning . The primary effects of H2S may be confounded by anoxia or head trauma . Persistent vegetative state is also a described phenomenon . Subclinical and clinical neuropsychiatric disorders have been documented to manifest in the long-term in cases with exposure without acute loss of consciousness . A recent study carried out in mice however demonstrated that when first put into a suspended animation-like state by a 20-min pretreatment with H2S followed by exposure to a hypoxic environment survival is prolonged with no apparent detrimental effects compared to mice which were not pretreated with H2S. Hence H2S also has a propensity to ameliorate hypoxic damage following exposure  Studies have also demonstrated that H2S can induce a hypometabolic, hibernation-like state in mammals when given in subtoxic concentrations which will reduce the demand for oxygen and minimize unavoidable hypoxia-induced injury such as ischemia/reperfusion injury during renal transplantation .
The features of central nervous system toxicity observed in the patient 1 overlaps with previously documented features and pathophysiology of neurotoxicity seen after hydrogen sulphide inhalation which are described above. New onset cerebellar dysfunction though unique to this patient could probably be explained by cytotoxic hypoxic injury to neurons. Despite the pre-existing neurofibromatosis and past history of seizures controlled by antiepileptics the temporal relationship to hydrogen sulphide exposure clearly establishes a cause and effect link between the abnormality and the toxic agent. PET scanning was not performed on our patient due to financial constraints despite literature evidence of studies showing abnormalities on PET imaging which were undetectable on MRI and CT scanning. Early administration of antidote and ventilation with 100% oxygen is likely to have minimized the severity of hypoxic damage. Persistent retrograde amnesia could either a post traumatic event or more likely the result of hypoxic damage to neurons involved in the complex tasks of processing memories.
The delayed onset respiratory failure seen in patient 2 is probably explained by a reactive airway dysfunction syndrome for which he probably could have had a predisposition as a result of asthma and chronic smoking. The absence of radiological evidence does not disprove the entity as the pathology is one of airways rather than gas exchange interface or alveolar parenchyma. Response to steroids and ventilator support with high FiO2 with complete reversibility and the temporal relationship to the exposure in this instance establish the relationship between the phenomenon and the toxic agent. Hypomagnesemia is a new observation hitherto unreported following hydrogen sulphide inhalation and is worthwhile looking for in future cases. Late onset perioral numbness reported in one of the cases was not substantiated by other clinical features of hypocalcemia or biochemical investigations to suggest a disturbance of calcium or magnesium homeostasis.
Animal studies following H2S poisoning have demonstrated respiratory and circulatory changes as early as 10–15 minutes with 100% involvement in 20–25 minutes in anaesthetized cats with severe respiratory disturbances and abrupt decrease of mean systemic arterial pressure and decreased cardiac output . Studies in rats have demonstrated morpho-functional alterations in the aero-hemic barrier and surfactant system of the lungs with resultant pulmonary oedema . Acute respiratory failure caused by an acute pulmonary oedema with left ventricular systolic dysfunction as a possible cause of this cardiorespiratory complication has been purported in medical literature . Exposure to higher concentrations increase the risk of pulmonary oedema . A late onset reactive airways dysfunction syndrome (RADS) after exposure to a high level of toxic gases mainly hydrogen sulphide has been described in a previously non-atopic man which had manifested with moderate, partially reversible, airway obstruction and increased responsiveness . Hemorrhagic bronchitis and pneumonitis have been demonstrated in postmortem studies and subacute lung injuries following long term exposure to hydrogen sulphide has also been postulated .
Hydrogen sulphide induced mucosal irritation may predominate at lower concentrations with a keratoconjunctivitis called 'gas eye'  Animal model studies using exfoliative cytology has yielded quantitative information of value in ocular irritation studies .
Blood sulphide levels are useful in the diagnosis of hydrogen sulphide toxicity and help to differentiate it from others with a similar presentation. Delta aminolaevulunic acid synthase and haem synthase levels are known to be decreased following exposure to hydrogen sulphide; however no correlate could be drawn to levels of blood sulphide in survivors .
Treatment following hydrogen sulphide toxicity is currently empirical, with a combination of nitrite and hyperbaric oxygen [3, 21, 22]. 4-dimethylaminophenol has also administered as an antidote, followed immediately by hyperbaric oxygen therapy .
The use of hyperbaric oxygen therapy (HBOT) for H2S poisoning remains controversial, but has a similar underlying rationale to that in carbon monoxide poisoning. HBOT may play a useful role in improving oxygenation and acid–base status quickly and counteracting the decrement in oxygen carriage caused by methaemoglobinaemia due to antidote administration .