Table 2.
Studies Evaluating Inhaled Nitric Oxide Administration in Patients with Acute Respiratory Distress Syndrome or Severe Pneumonia Associated with Coronavirus Disease 2019
| Study name | Study type | Treatment group/study population | Control group | NO dose, ppm | Endpoint | Main results |
|---|---|---|---|---|---|---|
| Al Sulaiman et al.112 | Multicenter retrospective | 76 pts. receiving iNO | 1:2 propensity score matching | 40 | Change in PaO2, FiO2, PaO2/FiO2 ratio and oxygenation index 24 hours after iNO | Oxygenation parameters significantly improved |
| Poonam et al.109 | Retrospective | 41 pts. iNO started after no response to conventional treatment | N/A | 20–80 | Change in PaO2/FiO2 ratio after iNO | ns |
| Bonizzoli et al.110 | Prospective | 12 pts. iNO started after no response to conventional treatment | N/A | 40 | Right ventricle function, dimension, and PAP before and after iNO | ns |
| Lubinsky et al.103 | Retrospective | 84 pts. iNO started a median of 6 days after intubation, continued for a median of 106 hours | N/A | 10–40 | Change in PaO2/FiO2, OI, VR | ns |
| Laghlam et al.111 | Prospective | 12 pts. iNO for 30 minutes, then iNO+almitrine for 30 minutes, then almitrine for 30 minutes | N/A | 10 | Change in PaO2/FiO2 | ns |
| Lotz et al.100 | Retrospective | 7 pts. iNO administered for 15–30 minutes | N/A | 20 | Pulmonary vasoreactivity, pulmonary shunt fraction, arterial oxygenation | PaO2 from 78.2 to 105.0 after iNO (p = 0.03) |
| Ziehr et al.101 | Retrospective | 12 pts. iNO before prone session | N/A | 20–80 | Change in PaO2/FiO2 ratio, dead-space-to-tidal-volume ratio | PaO2/FiO2 ratio from 136 to 170 (p = 0.003) and dead-space-to-tidal-volume ratio from 0.54 to 0.46 (p = 0.001) after iNO |
| Longobardo et al.104 | Retrospective | 27 pts. | 20 pts. w/ARDS of other causes | 20 | Respiratory parameters | PaO2/FiO2 ratio change greater in control group than in treatment group (47% vs. 3%) |
| Abou-Arab et al.102 | Prospective | 34 pts. iNO administered for 30 minutes whether PaO2/FiO2 <150 | N/A | 10 | Respiratory parameters (PEEP, C,rs, driving pressure, FiO2, PaO2, PaCO2), cor pulmonale at cardiac ultrasound | 65% of pts responders, PaO2/FiO2 significantly lower in responders than nonresponders at baseline |
| Tavazzi et al.108 | Prospective | 16 pts. iNO for 30 minutes | N/A | 20–30 | PaO2/FiO2 increase >20% compared to baseline | 25% pts. responders |
| Cardinale et al.105 | Retrospective | 20 pts. iNO, or almitrine, or both of them | N/A | 10–20 | PaO2/FiO2 increase >20% compared with baseline | No responders in pts. receiving iNO alone or iNO+almitrine. 1 responder received almitrine alone |
| Ferrari et al.106 | Retrospective | 10 pts. iNO after 3.6 days of mechanical ventilation for 30 minutes | N/A | 20 | Improvement in arterial oxygenation | ns |
| Bagate et al.107 | Prospective | 10 pts. iNO alone after 1 prone session | 10 pts. iNO+almitrine for 30 minutes after 1 prone session | 10 | Change in PaO2/FiO2 ratio | PaO2/FiO2 ratio change ns after iNO alone. PaO2/FiO2 ratio from 102 to 180 after iNO+almitrine (p < 0.01) |
| DeGrado et al.140 | Retrospective | 11 pts. iNO in nonresponders to iEPO | N/A | 20–80 | Change in PaO2/FiO2 ratio | ns |
ARDS, acute respiratory distress syndrome; C,rs, compliance of the respiratory system; iEPO, inhaled epoprostenol; PaCO2, partial pressure of carbon dioxide; PAP, pulmonary artery pressure; VR, ventilatory ratio.