Methemoglobinemia Associated with Late-Onset Neonatal Sepsis: A Single-Center Experience

Abstract

Objective Methemoglobinemia (MetHb) is a rare congenital or acquired cause of infantile cyanosis. We examined the role of MetHb in a neonatal intensive care unit (NICU). Study Design A retrospective observational study was conducted reviewing blood gas analyses of hospitalized newborns over a 2-year period. MetHb-positive patients (MetHb >1.8%) were matched with a control group for gestational age, weight, disease, and illness severity at admission. Maternal, neonatal, clinical, and laboratory parameters were collected and analyzed in both groups. Results MetHb incidence was 6%. The mean MetHb in the case group was 7.2%, and the first positive samples were observed at a mean of 22 days of life, 6 days prior to clinical or culture-proven sepsis. We identified low maternal age (31 vs. 34 years; p = 0.038), sepsis (90 vs. 45%; p = 0.022), and protracted parenteral nutrition (46 vs. 23 days; p = 0.013) as risk factors for MetHb, and early minimal enteral feeding as protective factor (12th vs. 9th day; p = 0.038). Conclusion MetHb has a high occurrence in NICU and can be a helpful prognostic indicator of an infectious process. Understanding and prompt identification of MetHb can allow pediatricians to implement a life-saving therapy.

Circulating Methemoblogin Fraction in Dogs With Sepsis

“…Methemoglobinemia describes a state where the iron component of heme within hemoglobin is oxidized from the ferrous to the ferric state. Methemoglobin is unable to bind oxygen, and its overproduction leads to impaired aerobic cellular metabolism, hypoxia, chocolate-brown colored blood and mucous membranes, cyanosis, and death (1)(2)(3)(4). Low levels of methemoglobin are normally produced by auto-oxidation of hemoglobin in vivo.…”

“…In steady state conditions, however, methemoglobin is rapidly recycled back to hemoglobin by methemoglobin-reducing enzymes, so that normal methemoglobin concentrations are usually kept <0.5-3% of total hemoglobin in humans and dogs (1,3,4). Both congenital and acquired forms of abnormal methemoglobinemia have been reported in human and veterinary literature (1,2). In small animals, clinically significant methemoglobinemia usually arises from exposure to toxicants or chemicals able to induce hemoglobin oxidation (e.g., aniline, sulfonamides, nitrates, acetaminophen, hydroxicarbamide, tetracaine) (5)(6)(7).…”

“…In humans, sepsis is considered a differential diagnosis among the endogenous causes of methemoglobinemia both in adult and pediatric patients (2,8,9). Inflammatory cytokines and bacterial lipopolysaccharides in sepsis activate endothelial cells and stimulate the production of an inducible form of nitric oxide synthase (iNOS) (2,8,10). As a result, nitric oxide (NO) is produced, contributing to vasodilation and distributive shock.…”

“…NO acts as a cytostatic and cytotoxic molecule against microorganisms and host cells, and interacts with hemoglobin forming methemoglobin and nitrates. Nitrates can be converted into nitrite, and to further methemoglobin and NO in the presence of nitrate-producing bacteria through a vicious cycle (1,2,8,10). Thus, the high methemoglobin levels reported in sepsis are thought to reflect such iNOS and NO overproduction, and might be a marker of sepsis severity (11).…”

“…Additional causes of methemoglobinemia in sepsis include reduced activity of methemoglobin-reducing enzymes or lack of energy substrate for these enzymes (8). Risk factors or concurrent conditions such as anemia, acidosis, cardiocirculatory failure, dysbiosis, and slow intestinal transit may further contribute to superoxide radicals and NO formation, leading to methemoglobin overproduction (1,2).…”