Use of inhaled nitric oxide in ICU - When is a therapy trial enough?

ABSTRACT

Introduction: Inhaled nitric oxide (iNO) can be utilized as a rescue treatment option in refractory hypoxaemia and in the potential reversal of pulmonary vascular resistance by pulmonary vasodilation.1 Its use remains controversial due to limited evidence regarding efficacy and potential side effects.2 Furthermore, it requires additional equipment and consumables and its infrequent use means staff may be relatively unfamiliar with the treatment. Objectives: Investigate use of iNO within our adult critical care unit in order to identify potential quality improvements that could be made to the delivery of this therapy. Clarify the proportion of patients who demonstrated a favourable PaO2/FiO2 (PF) response to iNO. Methods: We conducted a single-centre retrospective analysis of consecutive patients treated with iNO on the General & Cardiac Intensive Care Unit at Manchester Royal Infirmary between 01/01/2018 and 25/06/2021. Data was extracted from electronic patient records on patient characteristics, indication for iNO, starting dose, ventilatory characteristics, change in PF ratio and ICU outcome. Results were recorded at iNO initiation, 2, 6, 12 and 24 hours. A responder was defined by improvement in the PF ratio of ≥20% at any point up to 6 hours after initiation. Results: 37 patients were identified, mean age 51 years (SD 14). 84% were male and 16% were female. 27 patients (73%) had a diagnosis of COVID-19 pneumonitis (Figure 1). Primary indication for iNO was acute respiratory failure (ARF) in32 (86%) and right ventricular failure in 5 (14%)patients. Prior to iNO, patients had been in ICU for 11 days (SD 11) and had received invasive mechanical ventilation for 163 hours (SD 188). PF ratios at initiation were 12.8kPa (SD 5.0), in keeping with severe ARDS and 13 (39%) were already proned at initiation. Median troponin result prior to therapy was 21[IQR 14-81]. 12 patients (32%) had ECHO evidence of raised pulmonary artery pressures. A starting dose of 20ppm iNO was observed for each patient. By 6 hours, 14/37 patients (37%) were classified as positive responders. There was a significant increase in PF ratios at 6 hours compared to baseline in responders (15.9kPa vs 12.0kPa, p=0.04) but no significant difference at any other time point. There was no difference in the duration of therapy in responders vs non responders (76 vs 85 hours, p=0.72). Conclusion: iNO therapy may offer short-term improvement in oxygenation in <40% of patients at 6 hours. Duration of therapy was similar regardless of response. This may suggest reluctance to discontinue therapy once started possibly through fear of precipitating deterioration, belief that iNO has halted decline or reluctance to recognize futility when there are few other therapeutic options. iNO is typically commenced when patients have already been invasively ventilated for several days. It is unknown whether earlier initiation would affect response. Use of iNO has increased markedly since the start of the COVID-19 pandemic which should prompt units to evaluate their own practice with this therapy.