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Selective pulmonary vasodilation by NOi results from inactivation of NO by hemoglobin. This phenomenon leads to its oxidation in methemoglobin (MetHb). The aim of the study was to investigate the effect of NOi combined with 3 different agents known to be able to induce methemoglobin: EMLA cream, paracetamol, or vitamin K1. Forty newborn piglets (1.5±0.7 days, 1.4±0.2 kg) were sedated (ketamine=20mg/kg), intubated and mechanically ventilated (FiO2=0.3; RR=15/mn; PIP=15cmH2O; PEEP=3cmH2O; Babylog HF1 Draeger®). A peripheral venous catheter was inserted. Animals were randomly assigned to one of the following groups (each group = 5 piglets). Four groups were treated by 80 ppm NO delivered in the inspiratory limb of the breathing circuit during 3 hours: no additional drug was given in the group NO; a single dose of paracetamol (120 mg/kg, prodaffalgan Upsa®) and Vit K1 (5mg, Roche®) were intravenously infused in respectively the group NO+Parac and NO+Vit, and EMLA cream (Astra®) was applied to the ventral lower abdomen (2.5 g) and covered with a semipermeable polyurethane dressing(Tegaderm®) during 3 hours in the group NO+EMLA. Four other groups were not treated by NOi and received respectively paracetamol, Vit K1, EMLA cream, or no drug (respectively group Parac, group Vit, group EMLA and Group Control). MetHb was measured on venous blood samples before drugs and/or iNO administration and at 3 hrs (OSM 3 Radiometer®). Results are summarized in the table (*; p < 0.05 versus control group). In groups NO, Parac, Vit, and EMLA, MetHb were not significantly different from the control group. Conversely, MetHb concentration increased significantly in groups in which iNO was associated to drug administration (groups NO+Parac, NO+Vit, NO+EMLA) as compared to control group or to NO group. These results suggest that the MetHb reductase may be overloaded when iNO is administered with other MetHb-inducing agents. Special care should be taken to monitor MetHb level when iNO is combined with such drugs.

Combined Effect of Inhaled Nitric Oxide (iNO) and Drug-Induced Methemoglobin on Methemoglobinemia 1732