Methemoglobinemia Induced by Prilocaine in a Child With Noonan Syndrome.

Limited information is currently available on methemoglobinemia caused by the administration of prilocaine in children undergoing dental procedures in Japan. This case report presents the development of methemoglobinemia due to prilocaine overdose. The patient was a female aged 5 years 8 months with Noonan syndrome who also had pulmonary valve stenosis and hypertrophic cardiomyopathy. She presented with severe dental caries affecting 12 total teeth and required general anesthesia due to a lack of cooperation during dental treatment. General anesthesia was performed, during which 3% prilocaine with 0.03 IU/mL felypressin was administered intraoperatively via infiltration. Her SpO2 gradually decreased after 30 minutes, and cyanosis was observed postoperatively. Several assessments including a 12-lead electrocardiogram, an anteroposterior chest radiograph, and venous blood gas analysis were performed to identify potential causes. However, there were no indications of acute respiratory or cardiovascular abnormalities. It was noted that a total of 192 mg prilocaine was administered during the procedure, and methemoglobinemia was suspected to have developed because of overdose. Further testing revealed an elevated serum methemoglobin of 6.9%, supporting methemoglobinemia as the cause of her decreased SpO2. In dental procedures that require the use of prilocaine to treat multiple teeth, particularly for pediatric patients, it is important to carefully manage prilocaine dosing, as an overdose may lead to methemoglobinemia.

[A Case of Methemoglobinemia Caused by Toluidine Revelation with Dyspnea and Cyanosis].

Toluidine is a known cause of bladder cancer, but it is less widely recognized as a cause of methemoglobinemia because methemoglobinemia is rare. We herein report a case of methemoglobinemia caused by toluidine in a 50-year-old man. A solution of toluidine overflowed from its container during transportation and adhered to the man's clothes, but he drove to his workplace 100 km away without changing his clothes or undergoing decontamination. Before arriving at his workplace, he developed dyspnea and called emergency services, and he was then transported to a local hospital. He had significant cyanosis upon arrival, and arterial blood gas analysis revealed a high methemoglobin level of 44%. He was diagnosed with toluidine-induced methemoglobinemia and was transported to our hospital, where he was admitted to the intensive care unit. Treatment for methemoglobinemia was started immediately after hospitalization, and the patient's symptoms and methemoglobin level improved. Methemoglobinemia should be considered in workers who handle toluidine and develop cyanosis and dyspnea.

A Case Report of Hypotension and Methemoglobinemia Associated With Gunshot Residue Poisoning: Nitrite-Induced Methemoglobinemia.

A patient with gunshots within inches of the skin developed intraoperative vasodilatory hypotension and methemoglobinemia, both recognized consequences of nitrite poisoning. A 1- mg/kg dose of methylene blue transiently and partially reversed methemoglobinemia, but the color of the methylene blue faded rapidly, consistent with bleaching of methylene blue by nitrite in vivo. Methylene blue did not raise blood pressure, consistent with inhibition of nitric oxide (NO) synthase. Because NO production from nitrite uses an NO synthase (NOS)-independent pathway, methylene blue is expected to have little effect on reversing hypotension from nitrite poisoning. Consider nitrite toxicity in gunshot patients with refractory vasodilatory hypotension and elevated methemoglobin.

Utility of routine methemoglobin laboratory assays in critically ill pediatric subjects receiving inhaled nitric oxide.

PURPOSE: Inhaled nitric oxide (iNO) has been associated with safety risks including reports of methemoglobinemia. While standard of care recommends routine monitoring of methemoglobin in subjects on iNO therapy, the utility of this practice remains unknown. MATERIALS AND METHODS: This retrospective chart review aimed to determine the frequency of methemoglobinemia in pediatric patients receiving iNO. Included subjects were under 18 years of age receiving iNO therapy with at least one methemoglobin concentration measured from 10/18/2014 to 11/18/2016. RESULTS: In total, 1809 methemoglobin concentrations were collected in 247 subjects during the study period. Median age was 0.33 (0.04-0.83) years. The mean methemoglobin concentration was 1.33% (±0.42) while receiving a mean iNO dose of 11.71 ppm (±7.97). Twenty-nine subjects had a total of 131 methemoglobin concentrations analyzed while receiving iNO doses above 20 ppm which were similar to the entire cohort at 1.33% (±0.42); (p = .95). CONCLUSIONS: Pediatric patients receiving iNO at doses below 40 ppm have minimal risk of developing clinically significant methemoglobinemia. Routine, ongoing monitoring of metHb levels in all pediatric subjects receiving iNO therapy at doses <40 ppm without the presence of risk factors predisposing the subject to increased risk of methemoglobinemia is unnecessary and should be avoided.

Mujer de 18 años con metahemoglobinemia tras utilización de crema anestésica tópica / An 18 year old female with methaemoglinaemia after using EMLA(R) topical anaesthetic cream

La metahemoglobinemia es una entidad poco frecuente, cuyo diagnóstico se basa en la aparición de niveles elevados de metahemoglobina en sangre, tanto en adultos como en niños. Es una de las causas importantes de cianosis, y en ocasiones la severidad de su presentación puede requerir el ingreso en Unidades de Cuidado Intensivo. Las causas pueden ser adquiridas o congénitas, siendo ésta última debida a mutación en el gen de la hemoglobina reductasa dependiente de NADPH. La forma adquirida o metahemoglobinemia tóxica se produce cuando los hematíes son expuestos a sustancias químicas oxidantes que aumentan la producción de metahemoglobina, sobrepasando los mecanismos reductores de protección que actúan normalmente. Se presenta el caso de una mujer de 18 años, con cuadro de cianosis de aparición súbita diagnosticada de metahemoglobinemia tóxica tras utilización de crema anestésica tópica EMLA(R) (mezcla de anestésicos locales, lidocaína y prilocaína(AU)

Methaemoglobinaemia is a very uncommon disorder, with its diagnosis being based on the appearance of high levels of methaemoglobin in the blood, both in adults and children. It is an important cause of cyanosis, and occasionally its severity of its presentation may require admission to an Intensive Care Unit. It may be acquired or hereditary; the latter being due to a mutation of the NADPH-dependent haemoglobin reductase gene. The acquired form or toxic methaemoglobinaemia is produced when red cells are exposed to oxidising chemicals that increase methaemoglobin production, overwhelming the regulatory mechanisms that function normally (AU)

Gaseous nitric oxide bactericidal activity retained during intermittent high-dose short duration exposure.

Previously, we have shown that gaseous Nitric oxide (gNO) has great potential as an effective topical anti-infective agent for non-healing wounds due to its non-specific antimicrobial properties. These same antimicrobial attributes may be useful for pulmonary infections. However, gNO would have limited usefulness as an inhaled antimicrobial agent as continuous exposure to the concentration required for a bactericidal effect (160-200 ppm) leads to methemoglobinemia. To overcome this problem, we investigated whether a thirty minute exposure of 160 ppm every four hours would retain the same antimicrobial effect as continuous delivery. In vitro, exposure of clinical multi-drug resistant Staphylococcus aureus and Escherichia coli strains isolated from the lungs of nosocomial pneumonia patients and a lethal antibiotic-resistant strain of Pseudomonas aeruginosa, isolated from a deceased cystic fibrosis patient resulted in over a 5 log(10) reduction in bacterial load after multiple thirty minute treatments (4 cycles) every four hours to 160 ppm gNO. The intermittent regimen required 320 (SD=0)ppm h for 100% lethality whereas the continuous exposure required 800 (SD=160)ppm h. We have also shown that selection for a gNO resistant phenotype did not lead to decrease sensitivity to gNO therapy (p>0.05). In addition, no host cellular toxicity was observed in human THP-1 monocytes and macrophages following intermittent delivery of a high concentration of gNO, and the proliferation and migration of pulmonary epithelial cells was not adversely affected by the administration of intermittent high-dose gNO. These results justify further studies that should focus on whether intermittent delivery of 160 ppm of gNO every four hours can technically be administered while keeping inhaled NO(2) levels less than 2 ppm and methemoglobin saturation less than 2.5 percent.

Polyethylene glycol conjugated bovine hemoglobin containing 15% MetHb plays approving effect in exchange transfusion rabbit model.

PEG-bHb was developed by Kaizheng Biotech (Beijing, China), and pre-clinical research was completed. The objective of this study was to investigate the safe concentration of MetHb in PEG-bHb. The study was accomplished by examining the effects of PEG-bHb containing 5%, 8%, 15%, and 25% methemoglobin (MetHb), respectively, on cardiovascular system, blood chemistry, pathology of liver and kidney in rabbits following a 50% exchange transfusion. The results showed that PEG-bHb containing 5%, 8%, 15%, and 25% MetHb could keep four groups of experimental rabbits (5/5) alive until the 8th day after 50% exchange infusion as autologous whole blood did, and were superior to dextran 40 (2/5). MetHb concentration in PEG-bHb, no more than 25%, did not affect the PEG-bHb function on resuscitation of hemorrhaged rabbits by physiological measurements and blood chemistry assays. Histology study using optic and electron microscopy showed that there were slight pathological changes in hepatocytes and renal tubule epithelia in rabbits, which were infused by PEG-bHb containing 5%, 8%, and 15% MetHb. Partial organelles collapse was observed in rabbits resuscitated by PEG-bHb containing 25% MetHb. In conclusion, PEG-bHb is safe and effective when the MetHb concentration is at or below 15%.

Effects of hemoglobin and its breakdown products on synaptic transmission in rat hippocampal CA1 neurons.

During head injuries and hemorrhagic stroke, blood is released into the extravascular space. The pooled erythrocytes get lysed and hemoglobin is released into the intracranial cavities. Therefore, neurons may be exposed to hemoglobin and/or its breakdown products, hemin and iron, for long periods of time. In this study, the electrophysiological actions of these agents on synaptic transmission in rat hippocampal CA1 pyramidal neurons were studied using extracellular field- and whole cell patch-recordings. Previously our laboratory reported that commercially available hemoglobin produced a dose dependent suppression of synaptic transmission in hippocampal CA1 neurons. In the present study, however, we found that this depression was caused by impurities present in the hemoglobin samples. Commercially available hemoglobin and methemoglobin did not have a significant effect on synaptic transmission. Although, reduced-hemoglobin prepared using a method described by Martin et al. [J. Pharm. Exp. Ther. 232 (1985) 708], produced a significant depression of synaptic transients, these effects were due to contamination with bisulfite that was present due to the reducing procedure. Therefore, the technique of Martin et al. was inadequate in removing the reducing agents or their breakdown products. A number of studies in literature used commercial samples of hemoglobin or reduced hemoglobin prepared using the method of Martin et al. Our observations indicate that it would be important to determine if contaminants, rather than hemoglobin, are responsible for the observed effects in these studies. Unlike hemoglobin, its breakdown products, ferrous chloride and hemin, produced an irreversible and significant depression of field excitatory postsynaptic potentials. The relevance of these effects in neurological complications that follow head injuries and hemorrhagic stroke awaits further investigation.