Background: Inhalation of NO as a selective, short acting vasodilator is been administered at a
concentration of up to 80 ppm for use in infants with pulmonary hypertension. Experimental higher dose of NO has a broad range of antimicrobial and antiviral activity as shown in vitro, ex vivo, and in animal models. Inhalation of 160 ppm NO for 30 minutes, 5 times daily, for 5 consecutive days, was shown to be safe and well tolerated in healthy individuals. We hypothesized that intermittent high-dose inhaled NO is safe and tolerable for the treatment of hospitalized infants 2-12 months with acute viral bronchiolitis.
Methods: A prospective, double-blind, randomized controlled study. Patients were assigned to receive NO + standard treatment (NO+SdTx) or SdTx only. High-dose inhaled NO (160ppm) was given 5 times a day, for 30 minutes each time, by a face mask (maximum 25 treatments). Preterm infants and those with genetic syndromes, chronic heart or lung diseases were excluded. Nitrogen
dioxide (NO2), NO, and inhaled FiO2 were continuously monitored at the face mask, along with continuous monitoring of Met-Hemoglobin percentage (%MetHb), Oxygen saturation (SaO2), and end-tidal CO2 (EtCO2). Vital signs were closely monitored before, during and after each treatment. Multiplex PCR was used to detect respiratory viruses from nasal washes.
Results: 24 infants (15 males, mean age 5.3 months), all with RSV bronchiolitis, were included. A total of 87 NO inhalations were given (mean number of NO treatments per infant 7.3 (range: 2-16)). None of the 24 infants prematurely discontinued treatment due to side effects. Two infants from each study group experienced serious adverse events: 2 with pneumonia (one from each
group), 1 with otitis media and 1 with gastroenteritis (1 of each group), all completely recovered. There were no differences in heart and respiratory rate, oxygen saturation, and EtCO2 during treatments between the NO+SdTx and the SdTx groups. Base-line mean MetHb level was similar in NO+SdTx vs. SDTx: 0.82% (range: 0.1-1.4) and 0.75% (range: 0.2-1.1), respectively (p=0.65). Mean peak MetHb during first NO treatment was 3.1% (range 3.1 - 5.1). In 3/87 (3.4%) of the NO+SdTx maximal level of MetHb was >5%, once in each infant: 5.1%, 5.2%, 5.6%. NO2 level was >5ppm during one treatment episode (5.1ppm). Mean maximal NO2 level during inhalation was 1.6 ppm (range: 1.5 - 1.8).
Conclusion: Intermittent high-dose (160ppm) inhaled nitric-oxide is safe and tolerable in young infants with acute RSV bronchiolitis.
