[Sulfhemoglobinemia secondary to the use of zopiclone. Report of two cases]. / Sulfohemoglobinemia secundaria a zopiclona. Casos clínicos.

Sulfhemoglobin (SulfHb) is formed by hemoglobin (Hb) oxidation by sulfur compounds. Sulfhemoglobinemia is mainly associated with drugs or intestinal bacterial overgrowth. Patients present with central cyanosis, an abnormal pulse oximetry and normal arterial oxygen partial pressure. These features are shared with methemoglobinemia (MetHb) whose diagnosis requires an arterial co-oximetry. Depending on the device used, SulfHb may produce interference with this technique. We report two females aged 31 and 43 years, consulting at the emergency room with cyanosis. Both had a history of acute and chronic, high dose zopiclone ingestion. Pulse oximetry showed desaturation but with normal arterial oxygen partial pressure. Cardiac and pulmonary diseases were ruled out. Co-oximetry in two different analyzers showed interference or normal MetHb percentages. No other complications ensued, and cyanosis decreased over days. Since MetHb was discarded among other causes of cyanosis in a compatible clinical context, the diagnosis of sulfhemoglobinemia was made. The confirmatory method is not available in Chile. The presence of SulfHb is difficult to diagnose, confirmatory tests are not readily available, and it frequently interferes with arterial co-oximetry. This is attributed to a similar absorbance peak of both pigments in arterial blood. Venous co-oximetry can be useful in this context. SulfHb is a self-limited condition in most cases, however it must be differentiated from methemoglobinemia to avoid inappropriate treatments like methylene blue.

Case Report: Phenazopyridine-Induced Sulfhemoglobinemia in an 83-Year-Old Presenting with Dyspnea.

BACKGROUND: Sulfhemoglobinemia is a rare dyshemoglobinemia that presents similarly to methemoglobinemia. CASE REPORT: An 83-year-old woman with stage IV ovarian cancer presented to the Emergency Department after a near syncopal spell and was found to be cyanotic with a pulse oximetry reading of 71%. Pulse oximetry improved to only the mid-80s range with administration of high-flow oxygen. Her arterial blood gas on supplemental high-flow oxygen demonstrated a PaO2 of 413 mm Hg and methemoglobin of 1.2%, but also noted the interference of the co-oximetry with sulfhemoglobinemia. Further history revealed that the patient had recently been started on phenazopyridine. The phenazopyridine was stopped, an exchange transfusion was offered but declined, and the patient was discharged to home hospice. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The diagnosis of sulfhemoglobinemia can be challenging given that routine co-oximetry does not identify it. The clue to the diagnosis is that the cyanotic-appearing patient has a normal or elevated PaO2 and seems to be less ill than expected, given the degree of cyanosis. Sulfhemoglobinemia does not reverse with the administration of methylene blue.

A Case of Sulfhemoglobinemia Secondary to a Urinary Tract Infection.

Sulfhemoglobinemia (SulfHb) is a rare dyshemoglobinemia that can present with cyanosis in the absence of respiratory distress. It has been reported secondary to drug ingestion and chronic constipation. We present a case of SulfHb in an adolescent female with spina bifida and neurogenic bladder in the setting of an Escherichia coli urinary tract infection. An arterial blood gas differentiated a dyshemoglobinemia from other causes of hypoxemia. The resolution was achieved with antibiotics and red cell transfusion. Here we review the pathophysiology of SulfHb and contribute a unique case report to the limited body of literature on this topic.

Sulfhemoglobin under the spotlight - Detection and characterization of SHb and HbFeIII-SH.

Sulfhemoglobinemia is an incurable disease caused by an overdose of sulfur-containing drugs with oxidizing properties. Its diagnosis remains hindered due to the similarity of symptoms to other pathological state - methemoglobinemia, as well as contradictory information on the structure and characteristics of sulfhemoglobin. Herein, we present sulfhemoglobinemia model on living functional human erythrocytes, designed to recreate processes which could take place in a patient body in order to complement missing information and highlight distinctiveness of two hemoglobin (Hb) adducts formed after interaction with sulfur donors. Employed techniques, UV-Vis absorption, Raman, Fourier transformed infrared (FT-IR) and electronic circular dichroism (ECD) spectroscopies, allowed to distinguish and characterize Hb adduct with sulfur atom bounded directly to the iron ion (HbFeIII-SH), and irreversibly connected to the porphyrin ring (SHb - sulfhemoglobin). Presented herein results provided also new evidence on formation of both these hemoglobin adducts inside functional erythrocytes under oxidative conditions and during sulfur-containing drug presence, what can be further translated into future physiological studies. Moreover, we found that sulfur attachment to the porphyrin ring altered Hb structure and lead to changes in protein packing inside RBCs, eventually. Interestingly, measurement of blood drop smear by Raman spectroscopy occurred the most accurate method to differentiate HbFeIII-SH and SHb, indicating potential of this technique in sulfhemoglobinemia diagnosis.

Interpreting sulfhemoglobin and methemoglobin in patients with cyanosis: An overview of patients with M-hemoglobin variants.

INTRODUCTION: Methemoglobin (MetHb) and sulfhemoglobin (SHb) measurements are useful in the evaluation of cyanosis. When one or both values are elevated, additional analysis is important to establish the etiology of the disorder. Methemoglobinemia occurs from acquired or hereditary causes with diverse treatment considerations, while true sulfhemoglobinemia is only acquired and treatment is restricted to toxin removal. Some toxic exposures can result in a dual increase in MetHb and SHb. Hereditary conditions, such as M-Hemoglobin variants (M-Hbs), can result in increased MetHb and/or SHb values but are clinically compensated and do not require treatment if they are cyanotic but otherwise clinically well. METHODS: Herein, we report 53 hemoglobin variant cases that have associated MetHb and SHb levels measured by an adapted Evelyn-Malloy laboratory assay method. RESULTS: Our data indicate M-Hbs cause variable patterns of MetHb and SHb elevation in a fairly reproducible pattern for the particular variant. In particular, α globin chain M-Hbs can mimic acquired sulfhemoglobinemia due to an isolated increased SHb value. CONCLUSION: If the patient appears clinically well other than cyanosis, M-Hbs should be considered early in the evaluation process to differentiate from acquired conditions to avoid unnecessary testing and treatment regimens and prompt genetic counseling.

Acrocyanosis from phenazopyridine-induced sulfhemoglobinemia mistaken for Raynaud phenomenon.

Rheumatologists are often asked to evaluate patients with Raynaud phenomenon. Occasionally, an alternate explanation is revealed such as acrocyanosis. Methemoglobinemia and sulfhemoglobinemia are rare causes of cyanosis that can be medication-induced. Both are known complications of therapy with phenazopyridine. We report an unusual case of a 45-year-old woman in whom sulfhemoglobinemia from chronic therapy with phenazopyridine was misdiagnosed as due to Raynaud phenomenon and limited scleroderma. This case illustrates the importance of taking into account medication-related adverse events when evaluating patients with Raynaud-like phenomenon.

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.

Identification of sulfhemoglobinemia after surgical polypectomy.

Sulfhemoglobinemia (SHb) is an uncommon cause of cyanosis that is predominantly drug-induced in adults. We report an unusual case of sodium sulfate-induced sulfhemoglobinemia in a 61-year-old woman after surgical polypectomy. Fractional hemoglobin derivates were assayed by spectrophotometry and high-performance liquid chromatography. The SHb ratio was 8.6% in the first sample and 3.77% a month later measured by spectrophotometry. In the blood hemolysate, a new peak was identified as SHb with high-performance liquid chromatography (HPLC). HPLC showed the presence of 9.37% SHb in the first sample and 4.88% a month later. After removing the suspected toxic agent the cyanosis decreased significantly. The findings underline the importance of routine SHb detection in cyanosis of unknown origin especially in emergency cases.

Three-wavelength method for the optical differentiation of methemoglobin and sulfhemoglobin in oxygenated blood.

Methemoglobinemia and sulfhemoglobinemia are rare, but potentially life threatening, diseases that refer to an abnormal amount of methemoglobin or sulfhemoglobin in the blood, respectively. Unfortunately, blood samples containing abnormal quantities of methemoglobin or sulfhemoglobin have similar spectral characteristics. This makes it difficult to optically differentiate them and, hence, difficult to diagnose a patient with either disease. However, performing treatments for one of the diseases without a correct diagnosis can introduce increased risk to the patient. In this paper, we propose a method for differentiating the presence of methemoglobin and sulfhemoglobin in blood, under several conditions, using reflectance values measured at three wavelengths. In order to validate our method, we perform in silico experiments considering various levels of methemoglobin and sulfhemoglobin. These experiments employ a cell-based light interaction model, known as CLBlood, which accounts for the orientation and distribution of red blood cells. We then discuss the reflectance curves produced by the experiments and evaluate the efficacy of our method. In particular, we consider various experimental conditions by modifying the flow rate, hemolysis level and incident light direction.

Sulfohemoglobinemia secundaria a zopiclona. Casos clínicos / Sulfhemoglobinemia secondary to the use of zopiclone. Report of two cases

Sulfhemoglobin (SulfHb) is formed by hemoglobin (Hb) oxidation by sulfur compounds. Sulfhemoglobinemia is mainly associated with drugs or intestinal bacterial overgrowth. Patients present with central cyanosis, an abnormal pulse oximetry and normal arterial oxygen partial pressure. These features are shared with methemoglobinemia (MetHb) whose diagnosis requires an arterial co-oximetry. Depending on the device used, SulfHb may produce interference with this technique. We report two females aged 31 and 43 years, consulting at the emergency room with cyanosis. Both had a history of acute and chronic, high dose zopiclone ingestion. Pulse oximetry showed desaturation but with normal arterial oxygen partial pressure. Cardiac and pulmonary diseases were ruled out. Co-oximetry in two different analyzers showed interference or normal MetHb percentages. No other complications ensued, and cyanosis decreased over days. Since MetHb was discarded among other causes of cyanosis in a compatible clinical context, the diagnosis of sulfhemoglobinemia was made. The confirmatory method is not available in Chile. The presence of SulfHb is difficult to diagnose, confirmatory tests are not readily available, and it frequently interferes with arterial co-oximetry. This is attributed to a similar absorbance peak of both pigments in arterial blood. Venous co-oximetry can be useful in this context. SulfHb is a self-limited condition in most cases, however it must be differentiated from methemoglobinemia to avoid inappropriate treatments like methylene blue.

Neonatal Sulfhemoglobinemia and Hemolytic Anemia Associated With Intestinal Morganella morganii.

Sulfhemoglobinemia is a rare disorder characterized by the presence of sulfhemoglobin in the blood. It is typically drug-induced and may cause hypoxia, end-organ damage, and death through oxygen deprivation. We present here a case of non-drug-induced sulfhemoglobinemia in a 7-day-old preterm infant complicated by hemolytic anemia. Microbiota compositional analysis of fecal samples to investigate the origin of hydrogen sulphide revealed the presence of Morganella morganii at a relative abundance of 38% of the total fecal microbiota at the time of diagnosis. M morganii was not detected in the fecal samples of 40 age-matched control preterm infants. M morganii is an opportunistic pathogen that can cause serious infection, particularly in immunocompromised hosts such as neonates. Strains of M morganii are capable of producing hydrogen sulphide, and virulence factors include the production of a diffusible α-hemolysin. The infant in this case survived intact through empirical oral and intravenous antibiotic therapy, probiotic administration, and red blood cell transfusions. This coincided with a reduction in the relative abundance of M morganii to 3%. Neonatologists should have a high index of suspicion for intestinal pathogens in cases of non-drug-induced sulfhemoglobinemia and consider empirical treatment of the intestinal microbiota in this potentially lethal condition.

Pseudomethemoglobinemia: a case report and review of sulfhemoglobinemia.

OBJECTIVES: To see if methemoglobin could potentially be misdiagnosed and the limitation of present cooximeters. PATIENT: A 17-year-old girl who overingested a combination of cimetidine, acetaminophen, ibuprofen, and naproxen in a suicide attempt. METHOD: Use of pulse co-oximeters to aid in the diagnosis of suspected sulfhemoglobinemia. RESULTS: Diagnosis of sulfhemoglobinemia achieved with final confirmation made with gas chromatography. Patient steadily improved with supportive care. CONCLUSIONS: There is a potential for the diagnosis of methemoglobin with some of the limitations of present co-oximeters. The laboratory diagnosis of sulfhemoglobinemia can be difficult to make.

Oxidative stress and antioxidative status of plasma and erythrocytes in patients with vivax malaria.

OBJECTIVES: To investigate the oxidative stress and antioxidative status of plasma and erythrocytes in patients with vivax malaria and healthy persons. DESIGN AND METHODS: Activities of antioxidative enzymes, rates of pathways of hexose monophosphate shunt and purine salvage, levels of lipid peroxidation, reduced glutathione, methemoglobin and sulfhemoglobin of erythrocytes were determined. Lipid peroxidation and levels of antioxidant substances were measured. RESULTS: Antioxidants levels and antioxidative enzymes activities were lower and lipid peroxidation, purine salvage rate were higher in patients group than controls. Erythrocyte glucose-6 phosphate dehydrogenase (G-6-PD) activity was not different from that of healthy subjects. CONCLUSIONS: Oxidative mechanisms were observed to be dominant compared with antioxidative mechanisms in patients with vivax malaria. Therefore, oxidative stress may be produced and maintained by the host defense mechanisms against malarial infection.

Oxygen toxicity and hemoglobinemia in subjects from a highly polluted town.

Red blood cell activities of superoxide dismutase and glutathione peroxidase, two key enzymes responsible for the control of the concentrations of activated oxygen species, were approximately two-fold higher in residents of Vila Parisi (Cubatão, Brazil)--a higher polluted neighborhood--than in a population sample from São Paulo City. The catalase levels were the same in both samples. A concurrent high concentration of methemoglobinemia and sulfhemoglobinemia was encountered in the blood of Vila Parisi residents. These data raise the possibility that the increased rate of oxyhemoglobin oxidation yielding O-.2 and H2O2 may be relevant to mutagenesis induced by HO. radicals.

Congenital sulfhemoglobin and transient methemoglobinemia secondary to diarrhoea.

Sulfhemoglobinemia and Methemoglobinemia are common causes of cyanosis arising due to accumulation of abnormal heme pigment. We present an unusual case of congenital sulfhemoglobinemia along with diarrhoea induced methemo-globinemia in a neonate. A high index of suspicion and a proper diagnostic approach is needed to determine the true frequency of their occurrence together.

[Fatal calcium polysulfide overdose presenting corrosive chemical injury of esophagus and sulf-hemoglobinemia].

A-79-year-old woman ingested a cup of unknown violet agricultural solution intentionally. She was vomiting and smelt of sulfur. Arterial blood gas showed metabolic acidosis and marked cyanosis regardless of relatively high PaO2, caused by sulfhemoglobinemia. A nasogastric tube could not be inserted because of marked stenosis caused by endoscopically proven severe corrosive chemical injury (burn) of esophagus. Considering the smell and the clinical presentation, we concluded that the causative agent was calcium polysulfide or lime-sulphur solution, a common agricultural product used as a fungicide. Despite supportive therapy including infusion of NaNO2, the patient expired 4.5 hours after ingestion. Calcium polysulfide ingestions cause direct injury to the upper gastrointestinal tract, and react with gastric HCl producing poisonous H2S gas, which interferes cytochrome oxidase activity, developing tissue hypoxia, shock, and metabolic acidosis. Sulfhemoglobin is also produced causing severe cyanosis.

[Measurement of sulfhemoglobin (S-Hb) blood levels to determine individual hydrogen sulfide exposure in thermal baths in Italy]. / La concentrazione di solfo-emoglobina presente nel sangue è una misura affidabile dell'esposizione individuale a vapori solfurei: il caso degli stabilimenti idrotermali in Italia.

Significant exposure to hydrogen sulfide may occur in workers at sulphureous thermal baths. Work-related exposure to hydrogen sulfide may be shown by measuring sulfhemoglobin (S-Hb) blood levels. In this study we measured S-Hb blood levels in two groups of workers at two different thermal baths and compared these with hydrogen sulfide concentrations in the air of the two work environments. Our results show that blood S-Hb levels can be considered a reliable measure of individual exposure to hydrogen sulfide.

[Preoperative care and accumulation of non-active hemoglobin derivatives in blood of patients]. / Predoperatsionnaia podgotovka i nakoplenie neaktivnykh derivatov gemoglobina v krovi bol'nykh.

A study of the concentration of met- and sulfhemoglobine in patients on admission to the clinic and at the end of the preoperative management and treatment was carried out upon 35 surgical cases. The medicamentous therapy included the drugs favouring the restoration of methemoglobin (10.20% and 40% glucose solutions, ascorbic acid etc.). Therewith the concentration of non-active hemoglobine derivatives dropped at the end of the preoperative management and treatment.