Table 3.
Clinical trials of PDE inhibitors use in patients with ARDS or sepsis.
| Author (Year) | Diagnosis | Trial Design | Total No. of Patients | Treatment/Dose | Treatment Duration | Outcomes in the Treated Groups |
|---|---|---|---|---|---|---|
| Salari et al. (2005) | Early ARDS | Prospective clinical investigation | 30 (30 PDEI/0 placebo) | Aminophylline (NS-PDE-I) (3 mg/kg i.v. over 30 min., then 15 mg/h) | 8 h | Improvement in oxygenation and APACHE score, decrease in serum level of epidermal growth factor (EGF) |
| Bacher et al. (1997) | Sepsis | Prospective clinical investigation | 19 critically ill patients (12 septic, 7 non-septic, both groups treated by PDEI) | Pentoxifylline (NS-PDE-I) (5 mg/kg i.v.) | 3 h | In septic patients, increases in heart rate and cardiac index, decrease in systemic vascular resistance index and pulmonary vascular resistance index. No hemodynamic changes in non-septic patients. In both groups, increased oxygen transport (DO2) and oxygen uptake (VO2), in unchanged oxygen extraction ratio. |
| Maldonado et al. (2021) | COVID-19-induced moderate to severe ARDS | External pilot study | 38 (26 treated by PDEI, 12 controls) | Pentoxifylline (NS-PDE-I) (400 mg p.o. every 8 h) | from admission to discharge | Increased lymphocyte count, decreased serum LDH, a trend towards reduced hospitalization days, mortality, and proportion of patients requiring intubation. |
| The ARDS Network 2002 | ARDS | Prospective, randomized, placebo-controlled, multicenter study | 235 (116 treated by PDEI, 119 placebo) | Lisofylline (NS-PDE-I) (3 mg/kg with a maximum dose of 300 mg i.v. every 6 h) | 20 days or 48 h after unassisted breathing | Because of no evidence of beneficial effects, the trial was stopped. |
| Barton et al. (1996) | Pediatric non-hyperdynamic septic shock | Prospective, randomized, placebo-controlled, descriptive, interventional study. | 12 (12 treated by milrinone) | Milrinone (PDE3-I) (50 μg/kg i.v. followed by 0.5 μg/kg/min) or placebo for 2 h, then switch for next 2 h | 4 h | Increased cardiac index, stroke volume index, right and left ventricular stroke work index, and DO2. Decreased systemic vascular resistance index, pulmonary vascular resistance index, and mean pulmonary arterial pressure. |
| Wang et al. (2015) | Severe sepsis | Prospective randomized study | 90 (30 milrinone, 30 milrinone + β-blocker esmolol), 30 placebo) |
Milrinone (PDE3-I) (30 μg/kg i.v., maintained at 0.375–0.5 μg/kg/min by infusion |
96 h resp. 28 days | Milrinone plus esmolol improved cardiac function and 28-day survival rates, reduced heart rate, and inhibited inflammatory response. |
| Cornet et al. (2010) | Early ARDS (≤1 week from diagnosis), adults | Prospective, open-label, multicenter, interventional cohort study | 10 (10 PDEI/0 placebo) |
Sildenafil citrate (PDE5-I) (single dose of 50 mg, via nasogastric tube) | 1 day | Decrease in pulmonary artery pressure, systemic mean arterial pressure, no improvement in oxygenation, increased shunt fraction. |