Methaemoglobinaemia with G6PD deficiency: rare cause of persistently low saturations in neonates

We report a very rare case of methaemoglobinaemia associated with glucose 6 phosphate dehydrogenase (G6PD) deficiency, complicating a respiratory illness in a preterm neonate. This neonate had consistently low saturation readings despite being ventilated at moderately high pressures in 100% oxygen. An arterial blood gas confirmed a high methaemoglobin level and a high pO2, inconsistent with the saturations. In addition, the bilirubin increased to exchange levels and was difficult to control with quadruple phototherapy. A double volume exchange transfusion was performed, which reduced both bilirubin and methaemoglobin. The pulse oximetry then started to correlate well with pO2. G6PD deficiency was confirmed. CONCLUSION: Paediatricians should remember that methaemoglobinaemia is a rare but important cause of persistently low saturations, and exchange transfusion is a reliable treatment for this condition.     

Manejo anestésico del déficit de glucosa 6-fosfato deshidrogenasa

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 anesthesia for programmed low anterior resection of the rectum.     

Methaemoglobinaemia risk factors with inhaled nitric oxide therapy in newborn infants

Background: Inhaled nitric oxide (iNO), commonly used for hypoxic neonates, may react with haemoglobin to form methaemoglobin (MetHb). MetHb monitoring during iNO therapy has been questioned since low doses of iNO are used. Aim: To evaluate the incidence of and identify risk factors associated with elevated MetHb in neonates treated with iNO. Methods: Neonates who were treated with iNO and had at least one MetHb measurement were included. Demographic characteristics and methods of iNO administration (dosage, duration) at the time of each MetHb measurement were analysed. Results: Four hundred and fifty‐two MetHb measurements from 81 premature and 82 term and near‐term infants were analysed. MetHb was above 5% in one‐term infant, and between 2.5–5% in 16 infants. A higher maximum dose of iNO (22.7 vs 17.7 p.p.m.), but not gestational age, was a significant risk factor for elevated MetHb. Significantly higher oxygen levels (75.5% vs 51.7%) were associated with higher MetHb in term infants. Preterm infants had no risk for high MetHb when iNO was kept below 8 p.p.m. These data suggest the possibility of limiting blood withdrawal when low doses iNO are used. Conclusion: High MetHb is exceptional in neonates treated with low dose iNO. Associated risk factors are related to high iNO dose and the simultaneous use of high concentrations of oxygen.     

Toxicity of and biological monitoring for 1,3-diamino-2, 4, 6-trinitrobenzene and other nitro-amino derivatives of benzene and chlorobenzene

Summary Methaemoglobin-forming capacity of 1,3-diamino-2,4,6-trinitrobenzene (DATNB) was studied in vivo as well as in vitro and compared with those of aniline, phenylenediamine (o- and p-), nitroaniline (o-, m- and p-), nitrobenzene, dinitrobenzene (o-, m- and p-), 1,3,5-trinitrobenzene, chloroaniline (o-, m- and p-), chloronitrobenzene (o-, m- and p-), and 1-chloro-2,4-dinitrobenzene. m-Chloronitrobenzene and two isomers (m- and p-) of dinitrobenzene were the most potent methaemoglobin formers in vivo and it was p-dinitrobenzene when studied in vitro, while the capacity of DATNB was much lower both in vivo and in vitro, being comparable to those of aniline and nitrobenzene. The exposure monitoring by means of the urinalysis for diazo-positive metabolite(s) is applicable to all the compounds studied except DATNB and o-phenylenediamine; conversion of DATNB to the diazo-positive metabolite(s) in urine was very limited, indicating poor metabolism in vivo. Cumulative effects of DATNB was also discussed.This work was supported in part by a research grant from Environment Agency, the Government of Japan     

Severe chlorate poisoning: Report of a case

A case of severe sodium chlorate poisoning was observed within 5 h after suicidal ingestion of 150–200 g of the herbicide. Methaemoglobinaemia was the early symptom of the intoxication. Treatment with methylene blue and ascorbic acid could not prevent a massive haemolysis with disseminated intravascular coagulation. Hypercoagulation and hyperfibrinolysis could be treated successfully with exchange transfusions, heparin and fresh plasma. During the first hours, 70 mmol chlorate were excreted before complete renal failure occurred which required haemodialysis for several weeks. Clinical observations and in vitro experiments provide evidence that methylene blue is effective only in the very early stages of chlorate poisoning. Consequently, the following treatment is suggested: gastric lavage, exchange transfusion, bicarbonate infusion, haemodialysis, anticoagulation with heparin and substitution of clotting factors if necessary.Dedicated to Prof. Gustav Adolf Martini on occasion of his sixty-fifth birthdayA preliminary report has been given at the Spring Meeting of the German Pharmacological Society, Mainz, March 1981     

Acute oral toxicity of 4-dimethylaminophenol to the gastrointestinal tract,liver and kidney of the rat

Single oral doses up to 25 mg/kg body weight of the methaemoglobin-inducing cyanide antidote, 4-dimethylaminophenol (DMAP) did not result in any gross or histological abnormality in the gastrointestinal tract, liver and kidneys of rats killed up to 24 h after the dose. In animals kept for 7 days after the dose to abnormality was observed in the organs examined or in blood samples taken during the course of the experiment.     

NADH-diaphorase deficiency identified in a patient with congenital methaemoglobinaemia detected by pulse oximetry

We report on a young woman with congenital methaemoglobinaemia detected by a pulse oximeter during anaesthesia. Investigation of the patient and her family showed that the methaemoglobinaemia resulted from a recessive deficiency of NADH-diaphorase enzyme. A knowledge of the working principles and limitations of pulse oximetry is essential to determine appropriaie management in desaturation episodes during the perioperative period. Received: 17 December 1997 Accepted: 12 February 1998     

Methaemoglobin reductase deficiency in dogs

Erythrocyte methaemoglobin reductase deficiency is described in a toy Alaskan Eskimo dog, a miniature poodle dog and a cocker/poodle cross dog. Blood methaemoglobin contents ranged from 19% to 36% of total haemoglobin, with methaemoglobin reductase values between 13% and 33% of normal. There appeared to be a negative linear correlation between erythrocyte methaemoglobin content and methaemoglobin reductase activity. A single intravenous injection of methylene blue (1 mg/kg body weight) resulted in a dramatic decrease in methaemoglobin content within 1 hour when given to two of the deficient dogs in the present study. Following the disappearance of methylene blue from blood, methaemoglobin content increased linearly at 3.2% and 2.5% per day in these dogs, suggesting that about 3.0% of erythrocyte haemoglobin is normally oxidised to methaemoglobin each day in dogs, as has been estimated in humans. Oral riboflavin therapy was not effective in reducing blood methaemoglobin content in deficient dogs.     

Methaemoglobinaemia in young infants with diarrhoea

Seventeen infants under 2 months of age are described who presented with methaemoglobinaemia and acute diarrhoea during a period of 2 years. No infants beyond this age presented with such characteristics. In none of them was one of the known mechanisms of methaemoglobin formation found. All infants recovered with conventional therapy. Methacmoglobin associated with diarrhoea relapsed in three infants before they were 2 months old. Twenty-six similar cases have been reported in the literature. The mechanism of methaemoglobinaemia in these infants is unclear.     

Methaemoglobinaemia among neonates in a neonatal intensive care unit

After detection of a few clinical cases of methaemoglobinaemia (methb) in our NICU, a prospective clinical study was undertaken to determine the extent of the problem and to identify the causes. Consequently, during the following 8 months all haemoglobin tests included simultaneous measurements of methb on an OSM 3 hemoximeter (Radiometer): 8% (n= 33) of 415 neonates were found to be methb positive (denned as ≥6% methb). Mean methb was 19% (range 6.5–45.5%). Maximum methb concentrations were found on day 4–31 postpartum (mean 12 days) and the number of days with a positive methb sample ranged from 1 to 18 days (mean 6 days). About 40% of the neonates born at 25–30 weeks of gestation and 60%) with a birth weight < 1000 g were methb positive. Also, there was a negative correlation between the size of the methb positive concentration and gestational age (r=– 0.38,p= 0.02). Measurements of C–reactive protein and leucocytes, NADH reductase, pH, CI, nitrate and nitrite were carried out in methb positive patients. The tests were repeated 1 week after cessation of methb. The only significant difference was an increase in NADH reductase at the second measurement. Likewise, a wide range of clinical parameters were registered and they occurred with a higher frequency among the methb positive patients when compared with a methb negative control group matched with regard to gestational age and the closest possible birth weight. The mean birth weight of methb positive patients was 1170g and that of negative controls 1380g (p < 0.006). Epidemiological data and intervention studies indicated that para–chloraniline was the direct cause of the epidemic. The substance was derived from 0.02% chlorhexidine being inadvertently added to the humidifying fluid of the new incubators. Treatment of severe methb in premature neonates with 0.3–1.0mg methylene blue/kg body weight proved efficient. In conclusion, premature neonates developed severe methb when exposed to even small amounts of para–chloraniline. Immaturity, severe illness, the time exposed to para–chloraniline and low concentrations of NADH reductase probably played a part while other well known factors such as increased nitrite and nitrate concentrations, acidosis and hyperchloraemia did not seem to be significant.