Methaemoglobinaemia and the radical curative efficacy of 8-aminoquinoline antimalarials.

Methaemoglobin results from the oxidation of ferrous to ferric iron in the centre of the haem moiety of haemoglobin. The production of dose-dependent methaemoglobinaemia by 8-aminoquinoline antimalarial drugs appears to be associated with, but is not directly linked to, therapeutic efficacy against latent Plasmodium vivax and Plasmodium ovale malarias (radical cure). Iatrogenic methaemoglobinaemia may be a useful pharmacodynamic measure in 8-aminoquinoline drug and dose optimization.

Cyanide poisoning in patients with inhalation injury - the phantom menace.

Inhalation injury is a serious complication in patients with burns that dramatically increases their morbidity and mortality. These patients are always suspected of having inhalation injury with potential intoxication. We usually encounter carbon monoxide intoxication, but it is necessary to think about the possibility of poisoning by other combustion products. Cyanide intoxications are less common, but their diagnosis and treatment are more complicated. The diagnosis can only be based on the history, clinical findings, and indirect laboratory signs. Direct determination of plasma cyanide levels is not generally adopted in routine clinical practice. Nowadays, several specific antidotes with different mechanisms of action are available. There are no clear guidelines on the antidote of choice, as the evidence base is limited by a lack of randomised controlled trials in humans. In two mini case reports, we present our experience with the diagnosis and therapy of patients with suspected cyanide poisoning.

Poppers regulation for public sale: No measure in France yet.

AIM: Poppers have become legal in France since June 2013. Is their liberalisation associated with an increase of severe side effects observed? METHODS: To identify elevated methaemoglobinaemia related to poppers abuse, we reviewed all methaemoglobin concentrations measured in Nantes university hospital, during 12 months. RESULTS: Methaemoglobin concentrations were superior to 25% in three cases of poppers consumption that occurred after the legalisation. CONCLUSION: Evaluating the prevalence of elevated methaemoglobinaemia could help to monitor severe complications of poppers use in France.

Detection of methaemoglobinaemia and its application in 'poppers' abuse: maintaining the right balance between reduction and autooxidation during storage.

In our study, we analysed the effect of a variety of storage conditions on the methaemoglobin (MetHb) content of blood samples obtained from altogether 110 deceased subjects with diverse causes of death, including three 'poppers'-related fatalities. The obtained results were compared to data from blood samples of six living, healthy subjects. Results obtained from the spectrophotometric measurement of blood MetHb content suggest that storage at room temperature (RT) and storage at -20 °C result in either highly fluctuating values, as was the case for the RT samples, or values much higher than the initial MetHb concentrations when stored at -20 °C. Blood samples at 4 °C showed more stable MetHb levels, which, however, increased with up to 4 % of the initial value after only 3 weeks of storage. These factors pose a problem in forensic toxicology, especially in nitrite abuse cases, where the involvement of such substance abuse is often unknown at the time of blood sampling and thus often requires longer storage times. Nevertheless, even after the storage of blood samples over several months at 4 and -20 °C, 'poppers' cases still show a significantly higher MetHb concentration as compared to non-'poppers' samples that were stored for the same time period under identical conditions.

Rebound methaemoglobinaemia secondary to intentional sodium nitrite ingestion.

We report a case of rebounding severe methaemoglobinaemia secondary to sodium nitrite ingestion, despite several administrations of methylene blue. The patient's clinical course was characterised by a series of alternating improvements and deteriorations and proved challenging for treating clinicians. On discussion with poisoning experts, it was hypothesised that a small amount of sodium nitrite remained in the gastrointestinal tract leading to prolonged absorption of the causative agent. Methaemoglobin levels returned to normal following the administration of multi-dose activated charcoal via a nasogastric tube 30 h after the initial presentation to hospital.

Acquired methaemoglobinaemia in infancy associated with acute diarrhoea: A case series.

Acute diarrhoeal illness remains a common medical problem in children with nearly 1.7 billion cases globally every year. We report five infants who, following severe diarrhoea, developed methaemoglobinemia. This is an altered state of haemoglobin presenting with cyanosis and can pose a diagnostic dilemma. It should be suspected in young infants without cyanotic heart disease presenting with severe diarrhoea, sepsis and cyanosis disproportionate to their clinical status. Its outcome depends on prompt treatment, the severity of underlying sepsis and co-morbidity.

Acalypha indica induced acute oxidative haemolysis and methaemoglobinaemia: two case reports.

BACKGROUND: Herbal products and traditional remedies are commonly used by individuals worldwide for the management of common ailments, even though most are not without risks. Acalypha indica is a popular medicinal plant consumed in some Asian countries. CASE PRESENTATION: This case report presents a 40-year-old previously unevaluated Sri Lankan female and her 8-year-old son who presented with severe glucose-6-phosphate dehydrogenase (G6PD) deficiency related acute intravascular oxidative haemolysis and methaemoglobinaemia precipitated by Acalypha indica consumption, successfully managed with supportive care and blood transfusion. CONCLUSIONS: This case highlights the potential hemolytic and methaemoglobinaemic effects of ingesting oxidant herbal products and the importance of considering such exposures in patients presenting with hemolysis and multiorgan involvement, particularly in communities where herbal product intake is popular. Healthcare providers should be aware of the risks associated with traditional remedies and maintain a high index of suspicion to ensure prompt recognition and appropriate management.

Anesthetic management of glucose 6-phosphate dehydrogenase deficiency.

Glucose 6-phosphate dehydrogenase deficiency is the most common enzyme disease of red blood cells, with around 400 million people suffering from it throughout the world and linked to the X chromosome inheritance, thus it predominantly affects men. Glucose 6-phosphate-dehydrogenase participates in the pentose-phosphate pathway, being responsible for cellular metabolism and the production of antioxidants. A deficiency of this enzyme alters its ability to protect red blood cells from oxidative stress caused by certain drugs, metabolic conditions, infections and food. Specific anesthetic considerations are required to reduce the morbidity and mortality associated with medical-surgical interventions in patients with this disease. This article presents the case of a 45-year-old man with glucose 6-phosphate dehydrogenase deficiency who underwent combined general anaesthesia for programmed low anterior resection of the rectum.

The use of sodium nitrite for deliberate self-harm, and the online suicide market: Should we care?

Sodium nitrite is a common household product with a variety of uses such as curing meat, food additive, colouring agent, anti-freezing agent and disinfectant. We report a case of sodium nitrite intoxication for deliberate self-harm and discuss the increasing number of such cases in recent times.

Two cases of methaemoglobinaemia and haemolysis due to poisoning after skin absorption of 4-chloro-1-nitrobenzene.

INTRODUCTION: While 4-chloro-1-nitrobenzene has oxidising properties and can lead to methaemoglobinaemia and haemolysis, such reports are rare. We herein describe two cases of 4-chloro-1-nitrobenzene poisoning after skin exposure and detail relevant clinical characteristics and treatment outcomes. CASE PRESENTATION: A 45-year-old man and his 32-year-old male co-worker presented at our department shortly after skin exposure to 4-chloro-1-nitrobenzene. They developed similar symptoms, including dizziness, dyspnoea, excessive fatigue, and coma. Patients' chest inspection yielded normal findings. Despite maximal oxygen supplementation, neither patient exhibited improvements in the following clinical parameters: diffuse cyanosis, chocolate-coloured blood, and decreased pulse oximetry. For patients 1 and 2, methaemoglobin levels at admission were 78.6% and 63.6%, and 4-chloro-1-nitrobenzene concentrations were 4.12 µg/mL and 2.89 µg/mL, respectively. Their symptoms and methaemoglobin levels improved after we cautiously administered methylene blue; we subsequently detected oxidative haemolysis (confirmed by peripheral blood smears) that later resolved without further aggravation. No further episodes of anaemia were documented via telephone follow-up for eight months after hospital discharge for either patient. DISCUSSION: Typical features of methaemoglobinaemia included diffuse cyanosis, dark chocolate-coloured blood, elevated partial pressure of oxygen, and decreased pulse oximetry saturation. Haemolysis likely occurred secondary to the toxic effects of 4-chloro-1-nitrobenzene.

Phenazopyridine-Induced Methaemoglobinaemia The Aftermath of Dysuria Treatment.

Introduction: Phenazopyridine is an over-the-counter urinary analgesic commonly used to alleviate the burning and urgency associated with lower urinary tract infections. Methaemoglobinaemia is an uncommon adverse effect of phenazopyridine use. We report a case of methaemoglobinaemia in a patient prescribed daily phenazopyridine to treat urethral and bladder irritation caused by a chronic indwelling Foley catheter. Case description: A 55-year-old female resident of a long-term acute care facility with a chronic Foley, tracheostomy and ventilator-dependent respiratory failure was observed to have generalized dusky skin and hypoxia. Pulse oximetry was reading in the high 80s despite administration of 100% FiO2. ABG revealed paO2 of 451, oxyhaemoglobin level 75% and methaemoglobin level 22%. Medication review indicated that the patient was prescribed phenazopyridine 400 mg TID for the previous 2 months. This medication was discontinued. Considering she was chronically taking mirtazapine, she can increase risk of serotonin syndrome should she be administered first-line treatment with methylene blue. Vitamin C was thus instead administered as a second-line agent. Serial ABGs showed a rapid decline in methaemoglobin levels and an increase in oxyhaemoglobin within 2 days. Discussion: Acquired methaemoglobinaemia is a rare adverse effect of treatment with phenazopyridine. This risk increases when drug dosage and duration exceed manufacturer specifications. Treatment typically includes cessation of the offending drug and administration of methylene blue in severe cases. A thorough medication reconciliation should be performed prior to methylene blue initiation, as patients taking serotonergic medications (for example, MAOIs, SSRIs, SNRIs, TCAs) are at increased risk of serotonin toxicity with co-administration of methylene blue. In these instances, ascorbic acid/vitamin C can be chosen as an alternative treatment agent. Conclusion: Work-up of refractory hypoxia should involve a thorough review of medications as even some over-the-counter drugs can cause the fatal side effect of methaemoglobinaemia. Treatment with vitamin C should be considered over methylene blue if serotonergic medications have been recently prescribed in order to avoid risk of serotonin syndrome. LEARNING POINTS: Methaemoglobinaemia is an uncommon, life-threatening adverse effect of phenazopyridine use. Presentation depends on the severity of the disorder, ranging from headache, weakness, lightheadedness and dyspnoea, to arrhythmias, confusion, seizures and multiorgan failure.Workup of refractory hypoxia should involve a comprehensive medication review as even some over-the-counter drugs can cause methaemoglobinaemia.Management of methaemoglobinaemia involves cessation of the offending drug, administration of supplemental oxygen and treatment with methylene blue (1-2 mg/kg) if MetHb >30%, or for symptomatic patients with MetHb >20%. Vitamin C can be used as an alternative agent if there is a contraindication to methylene blue (for example, with patients simultaneously receiving serotonergic medications and/or those with G6PD deficiency).

Poppers Use and High Methaemoglobinaemia: 'Dangerous Liaisons'.

Poppers are legal and largely used in France despite severe side effects, such as methaemoglobinaemia (MetHbia). Our work aimed to assess the prevalence of poppers consumers among patients with a MetHbia higher than or equal to 5% in French university hospitals and its evolution before and after the legalization of poppers in France. We conducted a national multicentre observational retrospective study. All patients for whom at least one MetHbia measurement was performed from 2012 to 2017 in university hospitals where the French addictovigilance network (FAN) is implanted were included. For each MetHbia measurement exceeding or equal to 5%, a return to the clinical file was made by the FAN to assess poppers consumption. We calculated the prevalence of MetHbia exceeding or equal to 5% and 25% and the prevalence of poppers consumption before and after the legalization. A total of 239 (0.14%) patients had a MetHbia level exceeding or equal to 5% with 25 (10.46%) cases of poppers consumption. Poppers consumption represented 68.4% (13 out of 19) of cases with MetHbia greater than or equal to 25%. Poppers consumption among patients with MetHbia exceeding or equal to 5% increased after the legalization from 4.76% to 11.67% (prevalence ratio PR = 2.45, 95% CI = [0.98-8.37], p-value = 0.190). The proportion of patients with a MetHbia level of 25% or more increased after the legalization from 4.76% to 8.63% (PR = 1.81, 95% CI = [0.68-6.82], p-value = 0.374). The use of poppers is very frequently reported by patients with MetHbia greater than or equal to 25%.

Methaemoglobinaemia Can Complicate Normothermic Machine Perfusion of Human Livers.

Background: Although liver normothermic machine perfusion is increasingly used clinically, there are few reports of complications or adverse events. Many centers perform liver NMP to viability test suboptimal grafts, often for prolonged periods. In addition, several researchers are investigating NMP as a drug delivery platform, which usually necessitates prolonged perfusion of otherwise non-viable liver grafts. We describe two instances of methaemoglobinaemia during NMP of suboptimal livers. Methods: The NMP of eight human livers rejected for transplantation is described. Methaemoglobinaeima developed in two; one perfused using generic Medtronic™ perfusion equipment and one using the OrganOx Metra®. Results: The first liver (53 years DBD) developed methaemoglobinaemia (metHb = 2.4%) after 13 h of NMP, increasing to metHb = 19% at 16 h. Another liver (45 years DBD) developed methaemoglobinaemia at 25 h (metHb = 2.8%), which increased to metHb = 28.2% at 38 h. Development of methaemoglobinaemia was associated with large reductions in oxygen delivery and oxygen extraction. Both livers were steatotic and showed several suboptimal features on viability testing. Delivery of methylene blue failed to reverse the methaemoglobinaemia. Compared to a matched cohort of steatotic organs, livers which developed methaemoglobinaemia showed significantly higher levels of hemolysis at 12 h (prior to development of methaemoglobinaemia). Conclusions: Methaemglobinaemia is a complication of NMP of suboptimal liver grafts, not limited to a single machine or perfusion protocol. It can occur within 13 h (a timepoint frequently surpassed when NMP is used clinically) and renders further perfusion futile. Therefore, metHb should be monitored during NMP visually and using blood gas analysis.

The mystery of 'saturation gap' and falsely normal G6PD: a case of primaquine-induced haemolysis in Plasmodium vivax malaria infection.

Eradication therapy in Plasmodium vivax in variants of glucose-6-phosphate dehydrogenase (G6PD) deficiency individuals remains a clinical challenge. We present a case of primaquine-induced methaemoglobinaemia and haemolytic anaemia in a patient with falsely normal qualitative G6PD result during initial presentation, which was complicated with clinical sequelae of thrombosis. Further investigations showed moderate degree of G6PD deficiency. Our patient responded well to vitamin C and a modified weekly regimen of primaquine with no evidence of malaria relapse.

Methemoglobinemia caused by volatile nitrites derivates ('poppers') / Illékony nitritszármazékok ("popperek") által okozott methaemoglobinaemia.

Összefoglaló. A methaemoglobinaemia az oxigén szállítására képtelen methemoglobin szintjének kóros emelkedését jelenti a vérben, ami jelentos szöveti oxigénhiányt okozhat, súlyos, akár életveszélyes tünetekhez vezethet. Methaemoglobinaemiát számos, oxidáló hatású exogén anyag idézhet elo, ezek közé tartoznak a partidrogként használt alkil-nitritek, az ún. "popperek" is. A "poppereket" korábban "alacsony rizikójú" drogként tartották számon, azonban számos esetet közöltek, amikor súlyos, idonként fatális kimenetelu methaemoglobinaemiát okoztak. A folyadékok gozének belélegzése euforizáló, szexuálisvágy-fokozó és simaizom-lazító hatású, ezért a "popperek" igen népszeruek a homo- és biszexuális férfiak körében, de fiatal felnottek és tinédzserek is használják. A folyadékok szájon át való fogyasztása különösen veszélyes. A szerzok két esetet ismertetnek, amelyekben a "popperek" használatát követoen methaemoglobinaemia alakult ki. Mindkét betegnél, a jó általános állapot mellett, centrális és perifériás cyanosis tüneteit észlelték. Az alkalmazás módja (inhaláció/lenyelés), a methaemoglobinaemia súlyossága (16,4% és 57%) és a terápia eltéro volt a két betegnél. Az elso beteg oxigén adása és tüneti kezelés mellett gyógyult, a másodiknál antidotum (metilénkék) adására is szükség volt. Mindketten panaszmentesen távoztak a kórházból. A szerzok célja az volt, hogy felhívják a figyelmet az illékony alkil-nitrit-származékok által okozott methaemoglobinaemiára, annak felismerésére, kezelésére, és bemutassák azok kevésbé ismert szövodményeit is. Orv Hetil. 2021; 162(8): 306-313. Summary. Methemoglobinemia means the abnormally elevated level of methemoglobin in the blood, which is incapable of oxygen transport, accordingly it can cause significant tissue hypoxia, leading to severe or even life-threatening clinical symptoms. Several exogen oxidative agents can induce methemoglobinemia, including alkyl-nitrites which are also used as party drugs, the so-called 'poppers'. The 'poppers' were previously considered 'low-risk' drugs, however, several cases have been published when they caused severe, sometimes fatal methemoglobinemia. Inhaling vapours from liquids has euphoric, smooth-muscle relaxing and aphrodisiac effects, therefore 'poppers' are extremely popular among gay and bisexual men but also used by young adults and teenagers. Oral consumption of the fluids is particularly dangerous. The authors present two cases when methemoglobinemia developed after 'poppers' usage. Both patients were in good general condition and symptoms of central and peripheral cyanosis were detected. The method of application (inhalation/ ingestion), the severity of methemoglobinemia (16,4% and 57%) and the treatment were different in the two patients. The first patient recovered with inhalation of oxygen and symptomatic treatment; the second patient required administration of antidote (methylene blue). Both patients left the hospital without complaints. The authors' aim was to attract attention to methemoglobinemia caused by volatile alkyl-nitrites, its recognition, treatment and to present their lesser-known complications. Orv Hetil. 2021; 12(8): 306-313.

A case of dapsone-induced methaemoglobinaemia.

Methaemoglobinaemia is an uncommon but potentially serious condition. It can be caused by congenital or acquired cause. Drug-induced methaemoglobinaemia is the commonest cause of acquired methaemoglobinaemia. The clinical signs and symptoms of methaemoglobinaemia include dyspnoea, desaturation, presence of saturation gap, headache, nausea and seizures depending on level of serum methaemoglobinaemia. We illustrate a case of dapsone-induced methaemoglobinaemia and its successful treatment by intravenous methylene blue.

Lessons of the month 3: Intravenous poppers abuse: case report, management and possible complications.

BACKGROUND: Poppers are nitrite-containing liquids, which are inhaled for their aphrodisiac and hallucinogenic effects. Despite some cases of severe poisonings, poppers are often perceived as harmless by consumers. Inhalation and ingestion of poppers are well known, but, according to our literature review, intravenous abuse has not been reported before. CASE PRESENTATION: A 34-year-old man injected poppers intravenously for recreational purposes. He then suffered from dyspnoea and general discomfort. Upon arrival of emergency medical services, the patient was dyspnoeic with blue-grey skin colour and oxygen saturation was 82% on ambient air. Non-invasive ventilation was necessary, and he was transferred to the intensive care unit. Toluidine blue was administered because of a methaemoglobinaemia of 40% and methaemoglobin levels dropped to 0.4%. He was discharged home after a 24-hour observation. We additionally analysed the contents of the poppers bottle: isopropyl nitrite, isopropanol and acetone were detected. Possible complications and the treatment regarding intravenous administration of poppers are discussed. CONCLUSION: We present the first published case of intravenous poppers abuse. Our patient suffered from methaemoglobinaemia and was rapidly discharged after treatment with toluidine blue. No specific treatment regarding the contents of the poppers bottle, apart from isopropyl nitrite, was necessary.

A bolt from the blue; A case report of an unusual asthma exacerbation.

BACKGROUND: We describe this case of a young gentleman presenting with acute dyspnoea on a background history of known, long-standing asthma. His dramatic presentation, notable for profound hypoxia and cyanosis, led to an unexpected additional diagnosis of type one congenital methaemoglobinaemia. CASE PRESENTATION: A 26-year-old Irish gentleman was transferred urgently to the emergency department resuscitation room with marked cyanosis and tachypnoea. His oxygen saturation was 70% on 100% high flow oxygen. His arterial blood gas (On Fi02 90%) demonstrated a PaO2 = 76.8 kPa, SpO2 = 99%, pCO2 = 3 kPa and pH = 7.51. A saturation gap was evident and on further analysing the arterial blood gas, the methaemoglobin level was noted to be 28%. No contributing drugs were identified. Our patient was diagnosed with type one congenital methaemoglobinaemia. He recovered well from this admission, however, has had recurrent presentations to hospital since with high methaemoglobin levels noted on each occasion. DISCUSSION: Congenital methemoglobinemia is a rare, often overlooked differential diagnosis in patients presenting with cyanosis and dyspnoea. This is the only case, to our knowledge, of a patient with both asthma and congenital methaemoglobinaemia. Congenital methaemoglobinaemia was first described in 1943 by Dr Deeny who described two siblings as suffering from 'Familial Idiopathic Methaemoglobinaemia'. The case we present is the first reported Irish case of congenital methaemoglobinaemia, we are aware of, since 1943.Current treatment strategies include high-flow oxygen, methylene blue infusion (contraindicated in glucose-6-phosphate-dehydrogenase deficiency) and red cell exchange transfusions in the emergency setting whilst oral ascorbic acid and riboflavin are preventative.

Fatal acute haemolysis and methaemoglobinaemia in a man with renal failure and Alkaptonuria - Is nitisinone the solution?

Haemolysis and methaemoglobinaemia (MetHb) are rare metabolic complications that can occur in Alkaptonuria (AKU), for which there is no curative treatment. Presented is a case of a man who had AKU, and serves as a reminder of life-threatening complications that can occur with haemolysis and MetHb. This case presents an opportunity to revisit important considerations relating to the investigation and treatment of haemolysis and MetHb with a view to raising awareness, and in doing so hopefully reducing the uniformly fatal outcome. Additionally it is proposed that treatment of haemolysis and MetHb with nitisinone is considered as a potentially lifesaving treatment as it is believed that reducing the concentration of circulating homogentisic acid will reduce oxidative stress.