Table 1.
Summary of the studies included in systematic review and meta-analysis
| Reference | Region | Patients (heparin/control) | Design | Agent (dosage) | Physiological endpoints | Clinical endpoints (heparin/control) |
|---|---|---|---|---|---|---|
| Holt (2008) [21] |
Salt Lake City, Utah, USA | 62/88 children or adults | Retrospective study using historical controls | Hep (5000 U，Q4h) + NAC + salbutamol，7 d | PaO2/FiO2, optimal PaO2 = | Mortality (15/18), DOMV (18.2 ± 22.2/17.2 ± 18.1), LOHS (31.0 ± 22.2/31.9 ± 18.1), unplanned reintubation (9/7), pneumonia (39/44) = |
| Yip (2011) [22] |
Singapore City, Singapore | 52/11 adults | Retrospective study using historical controls | Hep (5000 U，Q4h) + NAC + salbutamol，7 d | APTT, PT, platelet count = | Mortality (19/6), DOMV (5.0 ± 20.0/9.0 ± 3.9), LOIC (6.0 ± 13.1/7.0 ± 3.5), pneumonia (9/2), bleeding (37/9) = |
| Sharma (2005) [23] |
Indore, Madhya Pradesh, India | 50/50 adults | Prospective study (single-center, double-blind) | Hep (5000 U，Q4h) + NAC + salbutamol，7 d | NR | Mortality (28/38), pneumonia (4/10) = |
| Desai (1998) [24] |
Galveston, Texas, USA | 43/47 children | Retrospective study using historical controls | Hep (5000 U，Q2h) + NAC，7 d | NR | Mortality (2/8), unplanned reintubation (3/12), LOHS (36.0 ± 21/48 ± 36.0), DOMV (3.4 ± 3.9/7.9 ± 3.3), pneumonia (20/30)↓ |
| McIntire (2018) [25] | Birmingham, UK | 36/36 adults | Retrospective study using historical controls | Hep (10,000 U，Q4h) + NAC + Salbutamol，28 d | NR | DOMV(7.0 ± 2.6/14.5 ± 4.3)↓,mortality (1/1), LOHS (17.0 ± 4.5/22.0 ± 6.2), pneumonia (23/26), bleeding (23/23) = |
| McGinn (2019) [26] | Auburn, Alabama, USA | 22/26 adults | Retrospective study using historical controls | Hep (5000 U，Q4h) + NAC + salbutamol，5 d | NR | DOMV(3.0 ± 1.8/6.5 ± 3.6)↓, mortality (5/6), LOHS (12.4 ± 6.4/18.5 ± 9.0), unplanned reintubation (4/3), pneumonia (4/0) = |
| Miller (2009) [27] | Brooklyn, New York, USA | 16/14 adults | Retrospective study using historical controls | Hep (10,000 U，Q4h) + NAC + salbutamol，7 d | Lung injury ↓ | Mortality (1/6)↓ |
| Kashefi (2014) [28] | Lubbock, Texas, USA | 20/20 adults | Retrospective study using historical controls | Hep (5000 U，Q4h) + NAC + salbutamol，7 d | NR | Mortality (6/4), DOMV (8.5 ± 7.7/8.9 ± 11.2), LOHS (15.3 ± 10.8/16.3 ± 16.6) =, pneumonia (9/2) ↑ |
| Rivero (2007) [29] | Tampa, Florida, USA | 9/7 adults | Retrospective study using historical controls | Hep (10,000 U，Q4h) + NAC，7 d | Lung injury ↓ | Mortality (1/3) ↓ |
↓ decrease, ↑ increase, = no difference
Counting data (n): mortality, unplanned reintubation, pneumonia, bleeding; measurement data (days): DOMV, LOHS, LOIC
Since physiological endpoints are dynamic indicators, we cannot provide specific numerical results. Lung injury included PaO2/FiO2, PaO2, PEEP, chest roentgenogram, respiratory resistance and compliance etc
Hep heparin, NAC N-acetylcysteine, DOMV duration of mechanical ventilation, LOHS length of hospital stay, LOIC length of intensive care, APTT activated partial thromboplastin time, PT prothrombin time, PaO2 arterial oxygen tension, PaO2/FiO2 arterial oxygen tension to inspired oxygen concentration ratio, PEEP positive end-expiratory pressure, NR no report