Incidence of Subclinical Methemoglobinemia in Infants With Diarrhea

Pollack, Emily S.; Pollack, Charles V.

doi:10.1016/s0196-0644(94)70275-6

Cited by 34 publications

(12 citation statements)

References 18 publications

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“…In contrast, the relation between methemoglobinemia and diarrhea is well known 10,20 with or without some degree of metabolic acidosis in infants, particularly in those with weight at or below the 10th percentile for age. 8,9 However, none of these circumstances occurred in our patients.…”

Section: Discussioncontrasting

confidence: 56%

Methemoglobinemia and Consumption of Vegetables in Infants

Benito²,

2001

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ABSTRACT. Objective. To assess clinical and epidemiologic data of 7 infants diagnosed with acquired methemoglobinemia at the pediatric emergency department between 1993 and 1998. All cases were attributed to the consumption of mixed vegetables.Methods. Medical records were reviewed to collect anamnestic data; history of food ingestion; and results of physical examination, pulse oximetry, gasometry, cooximetry, urinalysis, and outcome. Local health authorities provided information on nitrate concentration in running water and in vegetables of common consumption in the area.Results. The mean age of the patients was 8.14 months (range: 7-13). None of the infants was undernourished, had diarrhea, or was given any drug. Drinking water showed a nitrate concentration of 3 to 6 ppm. All were fed homemade purée of mixed vegetables, prepared in advance and kept in the refrigerator for 12 to 27 hours. Silver beets were a common ingredient. No case showed metabolic acidosis. Methemoglobin level ranged between 10% and 58%. Three cases had nitrituria. Silver beets in our area were the vegetables with the highest nitrate concentration (mean: 3200 mg/kg).Conclusions. Consumption of silver beets and incorrect storage of homemade purées of mixed vegetables were potential causes of methemoglobinemia in this series. The disease may occur in children older than 6 months of age. Nitrituria in a cyanotic infant may suggest the diagnosis of methemoglobinemia. Pediatrics 2001; 107:1024 -1028; methemoglobinemia, nitrates, nitrites, food analysis, infant food, food preservation.ABBREVIATIONS. Sao 2 , oxygen saturation; Hb, hemoglobin. M ethemoglobinemia is a rare cause of cyanosis in pediatric patients. Methemoglobin, a derivative of hemoglobin in which the iron component has been oxidized from the Fe 2ϩ to the Fe 3ϩ state, imparts a characteristic brownish color to blood and is unable to transport oxygen. 1,2 Under physiologic conditions, methemoglobin reduction is accomplished primarily by red cell reduced nicotinamide adenine dinucleotide reductase so efficiently that there is Ͻ1% of methemoglobin in the circulating blood. Hereditary methemoglobinemia is attributable either to deficiency of erythrocyte methemoglobin reductase or to the presence of one of the M hemoglobins. Acquired methemoglobinemia is induced by oxidizing agents, particularly chlorates and inorganic and organic nitrites, or by exposure to certain drugs or their metabolites.The most common sources of nitrate exposure are well water, which is mixed with infant formula, consumption of some vegetables with high nitrate concentration, administration of oxidant drugs, and the presence of diarrheal episodes. After ingestion, nitrates are converted to nitrites by fecal organisms, rapidly absorbed from the intestine by passive diffusion reaching the systemic circulation without undergoing first-pass metabolism in the liver (extrahepatic metabolism). Nitrites are potent oxidant agents of ferrohemoglobin. Infants younger than 6 months old are particularly susceptible to nitrate-...

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Section: Discussioncontrasting

confidence: 56%

Methemoglobinemia and Consumption of Vegetables in Infants

Benito²,

2001

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“…First, children with impaired perfusion and acidosis (vomiting, delayed capillary refill, and elevated lactate) had significantly higher odds of methemoglobinemia after controlling for a set of potential confounders. These findings are consistent with previous studies in infants where methemoglobinemia was reported in the context of metabolic acidosis secondary to diarrhea and dehydration [31, 32]. In our cohort, we observed increased odds of methemoglobinemia associated with vomiting, but not diarrhea.…”

Section: Discussionsupporting

confidence: 93%

Methemoglobin and nitric oxide therapy in Ugandan children hospitalized for febrile illness: results from a prospective cohort study and randomized double-blind placebo-controlled trial

et al. 2016

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BackgroundExposure of red blood cells to oxidants increases production of methemoglobin (MHb) resulting in impaired oxygen delivery to tissues. There are no reliable estimates of methemoglobinemia in low resource clinical settings. Our objectives were to: i) evaluate risk factors for methemoglobinemia in Ugandan children hospitalized with fever (study 1); and ii) investigate MHb responses in critically ill Ugandan children with severe malaria treated with inhaled nitric oxide (iNO), an oxidant that induces MHb in a dose-dependent manner (study 2).MethodsTwo prospective studies were conducted at Jinja Regional Referral Hospital in Uganda between 2011 and 2013. Study 1, a prospective cohort study of children admitted to hospital with fever (fever cohort, n = 2089 children 2 months to 5 years). Study 2, a randomized double-blind placebo-controlled parallel arm trial of room air placebo vs. 80 ppm iNO as an adjunctive therapy for children with severe malaria (RCT, n = 180 children 1–10 years receiving intravenous artesunate and 72 h of study gas). The primary outcomes were: i) masimo pulse co-oximetry elevated MHb levels at admission (>2 %, fever cohort); ii) four hourly MHb levels in the RCT.ResultsIn the fever cohort, 34 % of children admitted with fever had elevated MHb at admission. Children with a history of vomiting, delayed capillary refill, elevated lactate, severe anemia, malaria, or hemoglobinopathies had increased odds of methemoglobinemia (p < 0.05 in a multivariate model). MHb levels at admission were higher in children who died (n = 89) compared to those who survived (n = 1964), p = 0.008. Among children enrolled in the iNO RCT, MHb levels typically plateaued within 12–24 h of starting study gas. MHb levels were higher in children receiving iNO compared to placebo, and MHb > 10 % occurred in 5.7 % of children receiving iNO. There were no differences in rates of study gas discontinuation between trial arms.ConclusionsHospitalized children with evidence of impaired oxygen delivery, metabolic acidosis, anemia, or malaria were at risk of methemoglobinemia. However, we demonstrated high-dose iNO could be safely administered to critically ill children with severe malaria with appropriate MHb monitoring.Trial registrationClinicalTrials.gov Identifier: NCT01255215 (Date registered: December 5, 2010).

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“…Although this is a common bacterial species, it is not necessarily known for its pathogenicity. A prospective study of infantile diarrheal cases in Arizona examined the methemoglobin levels of infants and found elevated levels of methemoglobin (42). In particular, these investigators found an association between the child's ranking in weight for age and the incidence of methemoglobin in the blood above the physiologic normal value of 1% (42).…”

mentioning

confidence: 99%

“…A prospective study of infantile diarrheal cases in Arizona examined the methemoglobin levels of infants and found elevated levels of methemoglobin (42). In particular, these investigators found an association between the child's ranking in weight for age and the incidence of methemoglobin in the blood above the physiologic normal value of 1% (42). Data concerning children in the lower 10th percentile of weight for their age exhibited an analysis of variance (ANOVA) f factor of 0.039 for low weight and incidence of elevated methemoglobin level (42).…”

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confidence: 99%

A nested case-control study of methemoglobinemia risk factors in children of Transylvania, Romania.

Zeman

Kross

Vlad

2002

Environ Health Perspect

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In this nested case-control study, we investigated the risk factors for methemoglobinemia (MHG) in 71 children in the Transylvania region of Romania. This study was unique in that the exposures for cases and controls were calculated as continuous values and were reported in milligrams per kilogram per day of nitrate/nitrite based on careful dietary reconstruction and environmental sampling. This procedure allowed us to compare point estimates of nitrate/nitrite exposure with other continuous, categoric, and ranked risk factors such as the presence or absence of diarrheal disease, reported severity of diarrheal disease, the use of vitamin supplements, the presence, absence, and/or duration of breast-feeding, and whether or not first-generation relatives experienced MHG. Analysis of these factors and exposure levels using both univariate and multivariate whole-model tests was performed to understand the relative significance of risk factors at varying levels of exposure to the development of MHG. Univariate and multifactorial analysis of risk factors for MHG underscored that, for this population, MHG is most strongly associated with nitrate/nitrite exposure through the dietary route (p = 0.0318), via feeding of formula and tea made with water containing high levels of nitrates, and that breast-feeding protects infants younger than 6 months of age (p = 0.0244). Our findings also raise questions about the role of diarrheal disease in the development of MHG, as likelihood ratios (likelihood 4.323, p = 0.0376) and multifactorial analysis indicated a significant role for diarrheal disease for some individuals.

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Incidence of Subclinical Methemoglobinemia in Infants With Diarrhea

Cited by 34 publications

References 18 publications

Methemoglobinemia and Consumption of Vegetables in Infants

Methemoglobinemia and Consumption of Vegetables in Infants

Methemoglobin and nitric oxide therapy in Ugandan children hospitalized for febrile illness: results from a prospective cohort study and randomized double-blind placebo-controlled trial

A nested case-control study of methemoglobinemia risk factors in children of Transylvania, Romania.

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