Abstract
Methemoglobinemia probably related to the ingestion of phenacetin and isosorbide dinitrate occurred in a 65-year old man who had been on chronic hemodialysis for four years. Although the withdrawal of the drugs and the administration of vitamin C lowered the concentration of methemoglobin from 22% to 2.6%, he died from heart failure soon after. The other hemodialyzed patients showed a normal concentration of methemoglobin (0.4-2.3%).
To examine whether the red blood cells of dialyzed patients are susceptible to the oxidant, the formation and reduction of methemoglobin were examined in vitro. Methemoglobin concentration was measured by the method described by Van Assendilft. When the washed cells from six normal and six dialyzed subjects were incubated in Krebs Ringer phosphate buffer containing 10mM glucose at 37°C in the presence of 0-6.75mM of NaNO2, a dose-and time-dependent formation of methemoglobin was observed. There was no difference in the velocity and magnitude of the reaction between the two groups. The reducing power of the red blood cells was examined by further incubation of the cells pretreated for 30 minutes with 2.25mM NaNO2 in the presence or absence of 10-5M methylene blue. Both the slow NADH-dependent reduction and rapid NADPH-dependent reduction induced by methylene blue were demonstrated to the same extent in normal and dailyzed subjects.
Thus, in the present experiment, by which the reaction of red blood cells was examined in vitro, no evidence was obtained to indicate that the cells of dialyzed patients themselves were particularly susceptible to the exidant and had decreased ability to reduce the formed methemoglobin. It is assumed that, in addition to the change in pharmacokinetics common to patients on hemodialysis, individual tendencies such as that to form more oxidative metabolites or a decreased reducing power of the red blood cells contributed to the onset of methemoglobinemia in the present patient.
