Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD)

Comb the med list first - Screen every drug you plan to give against the G6PD avoid list: antimalarials, sulfonamides, nitrofurantoin, and local anesthetics all appear on it. The Italian G6PD Deficiency Association maintains the comprehensive list at g6pd.org — check it rather than working from memory.

No methylene blue, ever - Methylene blue is reduced to leucomethylene blue by an NADPH-dependent mechanism. The G6PD patient lacks the NADPH to do it, so the unreduced dye drives further oxidative damage, hemolysis, and death. This applies to known and suspected deficiency alike.

Methemoglobinemia without the usual antidote - Suspect it when central cyanosis and hypoxia persist despite supplemental oxygen. Symptoms begin around a methemoglobin level of 10% and death can occur above 50%. Since methylene blue is off the table, the alternatives are packed red blood cell transfusion or hyperbaric oxygen — know which is available at your facility before you need it.

Infection is the biggest trigger - Infection is the most likely offending agent, because inflammation floods the red cell with free radicals it cannot detoxify. Treat infection as indicated by history and exam, and expect a lower threshold for hemolysis in the septic patient.

Watch for hemolysis intraoperatively - The tells are dark urine from hemoglobinuria, jaundice or icterus, a falling hematocrit, tachycardia, dyspnea, and hypotension. Send a CBC and bilirubin, and ask for a peripheral smear — Heinz bodies and bite cells confirm oxidative injury.

Know the baseline oxygen-carrying reserve - Get a hemoglobin before the case. Chronic hemolysis brings bilirubin gallstones and iron overload, and the anemic patient has less margin when a crisis strips more red cells intraoperatively.

Crisis management is subtraction plus support - There is no antidote for oxidative erythrocyte damage. Stop and avoid the offending agent, support the patient, and transfuse for severe hemolysis.

Neonates are a separate problem - In the newborn the concern is jaundice and preventing kernicterus. Check the bilirubin trend before an elective neonatal case and coordinate with the team managing it.

Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the rate-limiting first step of the pentose phosphate pathway, converting NADP to NADPH. NADPH keeps glutathione reduced, which is how the red cell converts hydrogen peroxide to water and protects its membrane from reactive oxygen species. Mature erythrocytes cannot replace damaged proteins, so when NADPH runs short, oxidant stress denatures hemoglobin into Heinz bodies, damages the cell membrane, and produces acute hemolysis with hemoglobinuria and jaundice. Inheritance is X-linked, so men are more commonly affected; it is the most common human enzyme defect, affecting upward of 400 million people, and is most prevalent in patients of African, Mediterranean, or Asian descent.

Crises are triggered by infection, oxidant foods such as fava beans, and oxidant drugs — antimalarials are the classic offenders. Perioperatively that makes the medication list and any intercurrent infection the two levers you control.