Multicenter randomized controlled trial of the effects of inhaled nitric oxide therapy on gas exchange in children with acute hypoxemic respiratory failure,☆☆,

https://doi.org/10.1016/S0022-3476(99)70196-4Get rights and content

Abstract

Objectives and background: To determine whether inhaled nitric oxide (iNO) therapy can attenuate the progression of lung disease in acute hypoxemic respiratory failure, we performed a multicenter, randomized, masked, controlled study of the effects of prolonged iNO therapy on oxygenation. We hypothesized that iNO therapy would improve oxygenation in an acute manner, slow the rate of decline in gas exchange, and decrease the number of patients who meet pre-established oxygenation failure criteria. Study design: A total of 108 children (median age 2.5 years) with severe acute hypoxemic respiratory failure from 7 centers were enrolled. After consent was obtained, patients were randomized to treatment with iNO (10 ppm) or mechanical ventilation alone for at least 72 hours. Patients with an oxygenation index ≥40 for 3 hours or ≥25 for 6 hours were considered treatment failures and exited the study. Results: Patient age, primary diagnosis, pediatric risk of mortality score, mode of ventilation, and median oxygenation index (35 ± 22 vs 30 ± 15; iNO vs control; mean ± SEM) were not different between groups at study entry. Comparisons of oxygenation indexes during the first 12 hours demonstrated an acute improvement in oxygenation in the iNO group at 4 hours (-10.2 vs -2.7, mean values; P < .014) and at 12 hours (-9.2 vs -2.8; P < .007). At 12 hours 36% of the control group met failure criteria in contrast with 16% in the iNO group (P < .05). During prolonged therapy the failure rate was reduced in the iNO group in patients whose entry oxygenation index was ≥25 (P < .04) and in immunocompromised patients (P < .03). Conclusions: We conclude that iNO causes an acute improvement in oxygenation in children with severe AHRF. Two subgroups (immunocompromised and an entry oxygen index ≥25) appear to have a more sustained improvement in oxygenation, and we speculate that these subgroups may benefit from prolonged therapy. (J Pediatr 1999;134:406-12)

Section snippets

Patients

The study protocol was approved by the Institutional Review Committee at each participating center based on Food and Drug Administration approval of an Investigational New Drug exemption. Any pediatric patient admitted to 1 of the participating pediatric intensive care units with AHRF of sufficient severity to require intubation and mechanical ventilation was eligible for enrollment pending parental consent. Acute hypoxemic respiratory failure was defined as an OI (mean airway pressure × FiO2 ×

RESULTS

Patients enrolled into this study (n = 108) were randomized to the control group (n = 55) and to the iNO group (n = 53). Age, sex, mode of ventilation, duration of mechanical ventilation before enrollment, Murray score, and pediatric risk of mortality scores were similar between groups at enrollment (Table I). No difference was seen in assignment of patients with each primary diagnostic categories between the control and iNO groups (Table I).

Ventilator settings (FiO2 , PEEP, and mean airway

DISCUSSION

We report the results of a prospective, multicenter, randomized, masked trial of iNO in the management of pediatric AHRF. We found that iNO therapy improved oxygenation in an acute manner in children with severe AHRF as reflected by an increase in the PaO2 /FiO2 ratio and a decrease in the OI in the iNO group early in treatment. Although no difference occurred in the proportion of responders between groups after 72 hours of treatment, 2 subgroups appeared to benefit from iNO treatment. The

Acknowledgements

We acknowledge the support and contributions of Jayvant Deshpande, MD, Ole Georg Vinorum, MD, Thore Henrichsen, MD,Joel E Barbato, Michelle Holecek, RN, MSN, Jade Forlidas, RN, MS, Lori Roberts, RN, Rocky Stone, RCP, RRT, Christine Cassaw, RRT, RCP, IV, Cherry Smith, RRT, Gary R Cutter, PhD, Wendy Dortch, and Todd MacKenzie, PhD.

Cited by (0)

Supported by in part by National Institutes of Health SCOR grant (P50HL57144) and the General Clinical Research Centers Program, National Centers for Research Resources (M01 RR00069).

☆☆

Reprint requests: Emily L. Dobyns, MD, Section of Pediatric Critical Care Medicine B530, The Children’s Hospital, 1056 E. 19th Ave, Denver, CO 80218.

0022-3476/99/$8.00 + 0  9/21/96518

View full text