Table 3.
Summary of study questions, measures and conclusions for studies with lung injury targeting or resulting in PaO2/FiO2s ≤ 100mmHg
| Author (y) | Question | Measures* | Conclusions† |
|---|---|---|---|
| Studies that compared an MV alone group with an ECMO group‡ | |||
| Plotz (1993) | Compared surfactant with positive pressure-controlled ventilation vs. with V-V ECMO with sighs | Weaning success, GasEx§, lung mechanics§, ventilator efficiency | Large volume surfactant instillation was possible with V-V ECMO and sighs |
| German (1996) | Compare effects of MV with NO vs with V-V ECMO on Hemos, GasEx and lung lymph drainage during | Hemos§, GasEx, lung lymph flow and protein concentration | NO reduced PVR and increased oxygenation and lung lymph flow; ECMO improved oxygenation more and removed CO2 |
| Iglesias (2008) | Compare conventional MV with 10-12mL/kg or 6mL/kg vs A-V ECMO with near-static ventilation | Weaning success, Hemos, GasEx, lung mechanics, LIS, lung IL-6, IL-8, TNFα, surfactant | A-V ECMO and near-static ventilation improved outcomes versus conventional MV |
| Araos (2016) | Compare the effects of V-V ECMO to MV alone | Survival, Hemos, GasEx, lung mechanics, LIS, W/D | ECMO rescued an MV refractory lung injury model and will allow testing of other V-V ECMO interventions |
| Huang (2022) | Investigate if V-V ECMO is protective and if Hippo/YAP signaling contributes to that protection | Oxygenation, LIS, W/D, AT2 cells, BAL and lung tissue IL-6, IL-8 and TNFα, Hippo/YAP signaling markers | V-V ECMO stimulated Hippo/YAP signaling aided recovery of injured alveolar epithelium |
| Studies that compared an MV alone group to two different ECMO groups | |||
| Yanos (1990) | Investigate whether V-V ECMO supported hypopnea would reduce lung edema | Hemos, GasEx, lung mechanics, W/D, lung H2O | V-V ECMO supported hypopnea decreased Paw and PAP and increased PaO2 but didn’t alter lung water and increased venous admixture |
| Johannes (2014) | Compare effects of reducing TV to 3mL/kg or apneic ventilation with A-V ECMO vs. MV with 6mL/kg alone | Hemos, GasEx, lung mechanics, regional LIS | A-V ECMO allowed TV decreases to 0mL and reduced upper lung hyperinflation but increased lower lung inflammation |
| Pilarczyk (2015) | Compare conventional V-V ECMO to a miniaturized oxygenator with rotary pump | Hemos, GasEx, CBC, LFTs, free Hb, pump characteristics | Miniaturized system supported Hemos and GasEx but increased hemolysis |
| Studies that compared differing ECMO groups | |||
| Hirschl (1995) | Investigate if liquid vs gas ventilation improves lung function during support with V-V ECMO | Hemos, GasEx, lung mechanics, histology | Liquid ventilation improved GasEx, lung compliance, and lung injury and inflammation |
| Hirschl (1996) | Investigate if total followed by partial liquid ventilation vs. gas ventilation improves lung function supported with V-V ECMO | Hemos, GasEx, lung mechanics, histology | Total followed by partial liquid ventilation improved GasEx, lung injury and inflammation but only total liquid ventilation improved compliance |
| Kopp (2009) | Investigate if a low resistance oxygenator without blood pump or an oxygenator with a miniaturized pump improves hemocompatibility vs. conventional V-V ECMO | Coagulation studies (ACT, PTT, PT, TAT, Fibrinogen, PLTs), thromboelastography, CBC, serum IL-8 and TNF, EM of filters | Both systems were hemocompatible but absence of a blood pump did not increase this |
| Kopp (2012) | Compare Hemos and GasEx with miniaturized V-V ECMO vs. A-V ECMO system | Hemos, GasEx and pump characteristics | Both systems facilitated LPV but A-V ECMO limited oxygenation and CO2 exchange and increased cardiac work |
| Araos (2019) | Compare nonprotective (10mL/kg), protective (6mL/kg) or near-apneic MV with V-V ECMO | Hemos, GasEx, lung mechanics, LIS, W/D, myofibroblast protein markers | ECMO supported near-apneic MV and reduced lung injury on histology and myofibroblast marker expression |
| Dubo (2020) | Investigate if low spontaneous breathing efforts worsens lung injury vs. controlled near-apneic ventilation during V-V ECMO | Hemos, GasEx, lung mechanics, vasopressors, fluid balance, lactate, LIS, W/D, lung cytokines | Low intensity spontaneous breathing with high RRs and low TVs did not worsen lung injury versus near-apneic controlled ventilation |
| Millar (2020) | Investigate safety and efficacy of mesenchymal stromal cell (MSC) administration with V-V ECMO | Hemos, GasEx, lung mechanics, LIS, W/D, BAL protein, ECMO characteristics | MSC diminished oxygenator function and did not improve oxygenation but reduced lung injury and inflammation on histology |
| Qaqish (2020) | Establish lung injury with V-V ECMO model with and without surfactant | Hemos, GasEx, lung mechanics, LIS, W/D, plasma and BAL inflammatory cytokines, BAL bile acid | A lung injury with V-V ECMO model developed and surfactant was tolerated but did not alter function |
| Araos (2021) | Compare PEEP 0, 10 and 20 levels during near-apneic ventilation with V-V ECMO | Hemos, GasEx, lung mechanics, LIS, W/D | V-V ECMO with PEEP = 10 limited lung injury, benefited GasEx, and did not worsen Hemos |
| Studies with a single group and serial measures | |||
| Booke (1995) | Investigate if percutaneous V-V ECMO can provide lung support | Hemo, GasEx | V-V ECMO maintained gas exchange even in paralyzed animals after ALI |
| Brederlau (2006) | Investigate A-V ECLA’s contribution to gas exchange with different gas flows | Hemo, GasEx | A-V ECLA removed CO2 but oxygenation was reduced during severe hypoxia by increased shunt fraction |
| Zick (2006) |
Test oxygenation with a pumpless interventional lung assist device (ILA) |
GasEx, oxygenator blood flow | ILA significantly increased oxygenation but the effect was small |
| Muellenbach (2009) | Investigate TV reductions with A-V ECMO and an open lung approach | Hemos, GasEx, lung mechanics | A-V ECMO and an open lung approach provided CO2 removal with TVs of 0-2mL/kg and maintained oxygenation increases |
| Langer (2014) | Investigate V-V ECMO during spontaneous ventilation with 6 different gas flows, before and then after lung injury | GasEx, lung mechanics, lung CT scans, plasma IL-1b, TNF, IL-8, IL-10 | V-V ECMO can control spontaneous ventilation in healthy sheep and ones with ARDS |
| Andresen (2018) | Investigate meropenem PKs and a rapid response PK biosensor during V-V ECMO supported | Meropenem PK measures | Biosensor provided reliable meropenem PK data which ECMO did not alter |
| Mendes (2022) | Investigate V-V ECMO effects on lung perfusion and Hemos during one-sided lung ventilation and lung collapse and lavage | Hemo, GasEx, lactate, Hb | ECMO decreased PAP and may have increased shunt, but did not alter lung perfusion distribution with varying V/Q mismatches |
ACT, activated thromboplastin time; ALI, acute lung injury; AT2, alveolar type 2 cells; AV, arterio-venous; BAL, bronchoalveolar lavage; BUN, blood urea nitrogen; CBC, complete blood count; CO2, carbon dioxide; CT, computerized tomography; ECLA, extracorporeal lung assist; ECMO, extracorporeal membrane oxygenations; EM, electron micrography; FiO2, fractional inspired oxygen concentration; GasEx, gas exchange; GP, group; H2O, water; Hb, hemoglobin; Hemos, hemodynamics; IL, interleukin; LFTs, liver function tests; LIS, lung injury score on histology; LPV, lung protective ventilation; MV, mechanical ventilation; NO, inhaled nitric oxide; O2, oxygen; PaO2, arterial oxygen pressure; PAP, pulmonary artery pressure; Paw, airways pressure; PEEP, positive end expiratory pressure; PK, pharmacokinetics; PLT -platelet; PTT, partial thromboplastin time; PT, prothrombin time; PVR, pulmonary vascular resistance; Rx, treatment; TAT, thrombin–antithrombin complexes; TNF, tumor necrosis factor; TV, tidal volume; V-A, veno-arterial; V/Q, ventilation/perfusion; V-V, veno-venous; W/D, wet to dry lung ratio;
*Listed measures may not include all those reported in a study
‡†Summarized from reports’ findings or conclusions
‡ALI is employed whether a study designated the model as an ALI or acute respiratory distress syndrome one
§depending on the study hemodynamics included systemic and/or pulmonary vascular measures, gas exchange included measures of oxygenation and/or carbon dioxide removal and lung mechanics included static lung compliance and/or airway pressures