Combined effects of inhaled nitric oxide (iNO) and oxidant agents on the production of methemoglobinemia in newborn piglets.
OBJECTIVE
To investigate the effects of the association of inhaled nitric oxide (iNO) and oxidant drugs (acetaminophen, phytomenadione, and EMLA cream) on methemoglobinemia during the neonatal period.


METHODS
Prospective, randomized, experimental study.


METHODS
University Experimental Pharmacology laboratory.


METHODS
Sixty newborn piglets weighing 1.5-2.0 Kg.


METHODS
Twelve groups of five piglets were anaesthetized, mechanically ventilated, and studied for 3 hrs. Eight groups received iNO (40 ppm or 80 ppm) alone or in association with a single intravenous dose of acetaminophen (120 mg/kg propacetamol), phytomenadione (5 mg vitamin K1) or EMLA cream (2.5 g) applied to the ventral lower abdomen for 3 hrs. Three other groups received, respectively, acetaminophen, phytomenadione, or EMLA cream without iNO. The last group (control group) received neither drugs nor iNO.


RESULTS
Methemoglobinemia was measured before the beginning of each experiment, 30 mins later, and every hour for 3 hrs. There was no significant difference in methemoglobinemia at any time between groups receiving acetaminophen (0.90%+/-0.12%), phytomenadione (0.88%+/-0.11%), or EMLA cream alone (0.97%+/-0.11%) and the control group (0.92%+/-0.12%). At 3 hrs, methemoglobinemia was slightly but significantly increased in group receiving iNO alone (1.04%+/-0.17% at 40 ppm iNO and 1.14%+/-0.16% at 80 ppm iNO; p < .05). Conversely, methemoglobinemia increased as a function of time in groups in which iNO was associated to drug administration and was significantly greater than the control group at 3 hrs (80 ppm iNO + acetaminophen, 2.80%+/-0.47%; 80 ppm iNO + phytomenadione, 2.38%+/-0.45%; 80 ppm iNO + EMLA cream, 2.33%+/-046%; p < .001).


CONCLUSIONS
These results demonstrate that if oxidant drugs (acetaminophen, phytomenadione, or EMLA cream) did not increase blood methemoglobinemia in neonatal piglets, their association with iNO caused an increase in methemoglobin. Special care should be taken to monitor methemoglobinemia when iNO is combined to such drugs in newborn infants.
Riou
Y
Y
Department of Respiratory Physiology, Centre Hospitalier Régional et Universitaire, Lille, France.
Storme
L
L
Klosowski
S
S
Rakza
T
T
Kongolo
G
G
Zerimech
F
F
Martin-Ponthieu
A
A
Lequien
P
P
D000082:Acetaminophen / Q000008:administration & dosage* / Q000009:adverse effects; D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D008012:Lidocaine / Q000008:administration & dosage* / Q000009:adverse effects; D000077442:Lidocaine, Prilocaine Drug Combination; D008706:Methemoglobin / Q000032:analysis / Q000187:drug effects; D008708:Methemoglobinemia / Q000097:blood / Q000139:chemically induced*; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000009:adverse effects; D009824:Ointments; D016877:Oxidants / Q000008:administration & dosage* / Q000009:adverse effects; D011318:Prilocaine / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D011897:Random Allocation; D013552:Swine; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D010837:Vitamin K 1 / Q000008:administration & dosage* / Q000009:adverse effects
D000077442:Lidocaine, Prilocaine Drug Combination; D009824:Ointments; D016877:Oxidants; D014665:Vasodilator Agents; D011318:Prilocaine; D009569:Nitric Oxide; D000082:Acetaminophen; D010837:Vitamin K 1; D008706:Methemoglobin; D008012:Lidocaine