PALICC-2 Section 8 – ECMO

(1)

PALICC-2

Section 8 – ECMO

Supplemental Table S1. Search Strategy...2

Supplemental Figure S1: Study flow diagram according to the PRISMA protocol recommendations...3

Supplemental Table S2. Evidence to Decision Framework Table for Recommendation 8.1.1...4

APPENDIX 1. Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) Group...10

(2)

Supplemental Table S1. Search Strategy

PALICC-2 Group 8: ECMO

Initial search: 1/14/2021 Search update (4/6/2022)

PubMed:

("ARDS"[all] OR "respiratory distress syndrome, adult"[Mesh] OR "respiratory distress syndrome, adult"[all]

OR "adult respiratory distress syndrome"[all] OR "adult respiratory distress syndromes"[all] OR "acute respiratory distress syndrome"[all] OR "acute respiratory distress syndromes"[all] OR "shock lung"[all] OR

"shock lungs"[all] OR "acute lung injury"[mesh] OR "acute lung injury"[all] OR "acute lung injuries"[all] OR

"acute hypoxemic respiratory failure"[all] OR "acute hypoxemic respiratory failures"[all] OR "AHRF"[all] OR

"idiopathic respiratory distress syndrome"[all] OR "idiopathic respiratory distress syndromes"[all] OR

"PARDS"[all] OR "pediatric respiratory distress syndrome"[all] OR "pediatric respiratory distress syndromes"[all] OR "paediatric respiratory distress syndrome"[all] OR "paediatric respiratory distress syndromes"[all])

AND

("extracorporeal membrane oxygenation"[mh] OR (("extracorporeal"[all] OR "extra-corporeal"[all] OR "extra corporeal"[all]) AND "membrane"[all] AND "oxygenation"[all]) OR "extracorporeal membrane

oxygenation"[all] OR "ECMO"[all] OR "extracorporeal life support"[all] OR "ECLS"[all] OR "extracorporeal oxygenation"[all] OR "extrapulmonary oxygenation"[all] OR "extra corporeal oxygenation"[all] OR "extra corporeal membrane oxygenation"[all] OR "extra-corporeal oxygenation"[all] OR "extra-corporeal membrane oxygenation"[all] OR "extra corporeal life support"[all] OR "extra-corporeal life support"[all]) NOT "case reports"[pt] NOT (“animals”[mesh] NOT (“animals”[mesh] AND “humans”[mesh])) AND 2013:2021[dp] AND English[la]

Updated "respiratory distress syndrome, adult"[mh] to "respiratory distress syndrome"[mh]

https://www.ncbi.nlm.nih.gov/mesh/68012128 Embase:

('ARDS' OR 'adult respiratory distress syndrome'/exp OR 'respiratory distress syndrome, adult' OR 'adult respiratory distress syndrome' OR 'adult respiratory distress syndromes' OR 'acute respiratory distress syndrome' OR 'acute respiratory distress syndromes' OR 'shock lung' OR 'shock lungs' OR 'acute lung injury'/exp OR 'acute lung injury' OR 'acute lung injuries' OR 'acute hypoxemic respiratory failure' OR 'acute hypoxemic respiratory failures' OR 'AHRF' OR 'idiopathic respiratory distress syndrome' OR 'idiopathic respiratory distress syndromes' OR 'PARDS' OR 'pediatric respiratory distress syndrome' OR 'pediatric respiratory distress syndromes' OR 'paediatric respiratory distress syndrome' OR 'paediatric respiratory distress syndromes')

AND

('extracorporeal oxygenation'/exp OR (('extracorporeal' OR 'extra-corporeal' OR 'extra corporeal') AND 'membrane' AND 'oxygenation') OR 'extracorporeal membrane oxygenation' OR 'ECMO' OR 'extracorporeal life support' OR 'ECLS' OR 'extracorporeal oxygenation' OR 'extrapulmonary oxygenation' OR 'extra

corporeal oxygenation' OR 'extra corporeal membrane oxygenation' OR 'extra-corporeal oxygenation' OR 'extra-corporeal membrane oxygenation' OR 'extra corporeal life support' OR 'extra-corporeal life support') AND [english]/lim AND [2013-2020]/py NOT ('animal'/exp NOT ('animal'/exp AND 'human'/exp)) NOT ('conference abstract'/it OR 'editorial'/it OR 'letter'/it OR 'note'/it OR 'case report'/exp)

Removed date limit from search and limited to records added 1/1/2021-4/6/2022

2

(3)

(4)

Supplemental Table S2. Evidence to Decision Framework Table for Recommendation 8.1.1

Recommendations

Recommendation 8.1.1. We suggest that patients with a potentially reversible cause of severe PARDS should be evaluated for ECMO when lung protective strategies result in inadequate gas exchange.

(Conditional recommendation, very low certainty of evidence, 96% agreement).

Remarks: There is no evidence to support strict criteria for the selection of patients who will benefit from ECMO in PARDS.

AREA JUDGEM

ENT

RESEARCH EVIDENCE Desirable

Effects Moderate

Appropriate ECMO use may improve survival and reduce exposure to ventilator settings that may lead to ventilator induced injury or hypoxemic induced organ. Appropriate use also avoids unnecessary ECMO and ECMO associated complications. Multiple prior reports have noted that following serial measures such as Oxygenation Index, p/f ratio, changes in mechanical ventilation status and occurrence of secondary organ failure may be helpful in predicting outcome from ARDS or candidacy for ECMO.

Undesirable

Effects Varies

ECMO-supported children have been observed to suffer bleeding and thrombotic complications including stroke and intracranial hemorrhage.

The required cannulation and anticoagulation needed for ECMO support provides a scientific rationale to attribute these to ECMO, but in the absence of clinical trials for ECMO in PARDS it is not possible to discern which complications are the result of ECMO and which are the result of critical illness.

Overuse of ECMO, exposes patients to the risk of ECMO when it is not required, and underuse or delays in ECMO may increase exposure to ventilator settings that may lead to ventilator induced injury, hypoxemic induced organ or death.

Certainty of evidence

Very low No randomized trials exist for PARDS specific ECMO support.

Randomized clinical trials in perinatal lung disease and ARDS provide evidence for ECMO support in acute respiratory failure.

Balance of Effects

Don’t know

Likely supports use of ECMO support in PARDS when the cause of respiratory failure is reversible. There is absence of PARDS-specific evidence for a threshold to initiate ECMO support. However, evidence in perinatal lung disease and ARDS suggest there may be a threshold beyond which ECMO support increases the likelihood of survival in PARDS.

Value Pediatric evidence is weak as only one study is available on mechanical power and one on driving pressure (13). Higher mechanical power is associated with fewer 28-day ventilator-free days in children with pediatric acute respiratory distress syndrome. This association is strongest in children <2-years-old in whom there are notable differences in mechanical ventilation management (14).

Resources required

Don’t know

Randomized clinical trials performed in the United Kingdom in perinatal lung disease and ARDS found ECMO support to have significant expense 4

(5)

Developing and performing studies to answer questions as to what lung protective strategies are optimal and feasible are needed.

Equity Probably

yes

ECMO support is a high resource and high-cost technology that may not be available to patients in lower resourced settings.

Implementation Probably yes

ECMO availability is increasing, and with advances in technology it is becoming easier to apply and increasingly healthcare providers have training in its application. However, ECMO support is expensive and resource intensive and often low volume. At present this likely means that some centers will have ability to provide ECMO support and others will have referral relationships with an ECMO center.

Serial evaluation of the efficacy and safety of invasive mechanical

ventilation need to be performed before transitioning to ECMO support for severe PARDS. Neonatal and adult evidence would suggest considering initiating ECMO if the OI is 40 or a pH <7.25 with a PaCO2 of 60 mm Hg or more and a plateau pressure of 32 cm of water or less.

(6)

Supplemental Table S3. Evidence to Decision Framework Table for Recommendation 8.1.4

Recommendations

Recommendation 8.1.4. We suggest the use of veno-venous ECMO over veno-arterial ECMO in

patients with PARDS who have adequate cardiac function. (Conditional recommendation, low certainty of evidence, 94% agreement).

AREA JUDGEMENT RESEARCH EVIDENCE

Desirable

Effects Moderate

Avoidance of carotid arterial cannulation and associated complications possibly including carotid occlusion, cerebral ischemia and embolic stroke.

Undesirable

Effects Low

Bicaval dual lumen ECMO cannula (cannula that most traverse the superior and inferior vena cava) can be more technically difficult to place than VA cannulation for ECMO support. Likely occlusion of the common femoral vein or engorgement of the limb distal to cannula placement

Balance of Effects

Favors the intervention

Avoidance of carotid artery cannulation likely reduces neurologic injury.

Equity Probably no Availability to dual lumen cannula could be limited in developing countries, although multi-site cannulation is also effective.

Implementatio n

Yes Dual lumen right arterial cannuals have been able to be safely placed bedside without fluoroscopy or echocardiogram which complicate deployment.

6

(7)

Recommendations

Recommendation 8.3.1a. We suggest maintaining normal PaO2 as compared to hyperoxia in patients with PARDS supported on ECMO. (Conditional recommendation, very low certainty of evidence, 96%

agreement).

Recommendation 8.3.1b. We suggest slow decrease in PaCO2 as compared to rapid decrease of PaCO2

in patients with PARDS supported on ECMO. (Conditional recommendation, very low certainty of evidence, 88% agreement).

AREA JUDGEME

NT

RESEARCH EVIDENCE Desirable

Effects Small/

Moderate

- Low grade-retrospective observational study on 204 subjects. 3-d ventilator FIO2 average on ECMO is associated with worst outcome 1.38 (1.09–1.75) (30)

- In a large retrospective study using the ELSO database, Friedman et al analyzed 1022 children who had invasive mechanical ventilation during ECMO. Higher ventilator FiO2 (odds ratio:1.13 per 0.1 increase, 95% confidence interval:1.04, 1.23), independent of arterial oxygen saturation, was associated with mortality.

- In a retrospective study on 484 children who underwent ECMO, Cashen et al. (32) found that hyperoxia and hypocapnia during the first 48 hours of ECMO were associated with decreased survival. Hyperoxic patients had higher mortality than patients without hyperoxia (167 [50.5%] vs 48 [31.4%]; p < 0.001), hypocapnic patients were more likely to have a neurologic event (49 [50.0%] vs 143 (37.0%]; p = 0.021) or hepatic dysfunction (49 [50.0%] vs 121 [31.3%]; p < 0.001) than patients without hypocapnia.

- A large relative decrease in PaCO2 was independently associated with neurological complications after controlling for previously described risk factors (odds ratio, 1.7; 95% confidence interval, 1.3 to 2.3; P < 0.001) (34).

- Patients with worse neurologic outcome experienced longer durations of mild (adjusted odds ratio, 1.10; 95% CI, 1.01-1.19; p

= 0.02), moderate (adjusted odds ratio, 1.12; 95% CI, 1.04-1.22; p

= 0.002), and severe (adjusted odds ratio, 1.19; 95% CI, 1.06- 1.35; p = 0.003) hyperoxia (33).

Undesirable

Effects Trivial

The risk of avoiding hyperoxia or early rapid change of PaCO2 are trivial.

Very low Few studies exist from which to extrapolate data. (30–32).

Balance of Effects

Favors the comparison

Close monitoring techniques for PaO2 and PaCO2 are available using common techniques such as blood gas analysis, following end-tidal CO2, pulse oximetry.

(8)

Resources required

Don’t know Developing studies evaluating the impact of gases exchanges during the first hours of ECMO is feasible and may lead to a better outcomes and avoidance of complications.

Equity Don’t know Ability to monitor gas exchange, pulse oximetry is common in many units throughout the world.

Implementation Yes Gas monitoring is easy to implement with devices such as transcutaneous monitoring of PaCO2 , pulse oximetry or blood gas analysis.

8

(9)

Recommendations

Recommendation 8.3.2. In patients with PARDS supported by ECMO, we suggest mechanical ventilator pressures comply with the lung protective limits previously identified, as compared to exceeding these limits, to avoid additional lung injury. (Conditional recommendation, low certainty of evidence, 98%

agreement).

AREA JUDGEMENT RESEARCH EVIDENCE

Desirable

Effects Small/

Moderate

- Low grade-retrospective observational study on 204 subjects.

3-d ventilator FIO2 average on ECMO is associated with worst outcome 1.38 (1.09–1.75) (30)

- A large retrospective study using the ELSO database analyzed 1022 children who had invasive mechanical ventilation during ECMO. Higher ventilator FiO2 (odds ratio: 1.13 per 0.1 increase, 95% confidence interval:1.04, 1.23), independent of arterial oxygen saturation, was associated with mortality.

- Adult study

LIFEGUARD study (37): multicenter observational study on 350 VV ECMO. Significant association between delta pressure and 6-months mortality (1.03 for one cmH20, CI 95% 1.01 – 1.07, p: 0.03).

Undesirable

Effects Trivial

Limiting invasive ventilatory pressure may be responsible for lung atelectasis. This could increase ventilation/perfusion mismatch and hypoxia. Moreover, the re-opening of the collapsed lung can be challenging. The best protective invasive ventilation under ECMO still remains unknow.

low Pediatric evidence is very weak two observational studies with potential for bias

Balance of Effects

Favors the comparison

Even if lung function recovery is a multifactorial process, controlling ventilatory pressure during ECMO for refractory P-ARDS may limit the occurrence of ventilator induced lung injury, decrease risk for airleak and be beneficial to lung recovery.

Resources required

Don’t know Developing studies evaluating the impact of several kind of protective invasive ventilation ECMO is feasible and may lead to a better care during first hours of ECMO Run. Multicenter data should be recorded with specific study goals and consistent definitions of data fields.

Equity Don’t know The use of invasive ventilation during ECMO is common and available in all centers providing ECMO.

Implementation Yes Clinicians are able to implement ventilator settings if guidance for optimal modes and measures are provided.

(10)

APPENDIX 1. Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) Group

Co-Chairs – Guillaume Emeriaud, Yolanda M López-Fernández, Robinder G Khemani

Methodologists: Narayan Prabhu Iyer, Melania Bembea, Steven Kwasi Korang, Katherine M. Steffen Experts

Section 1 (Definition, Incidence and Epidemiology) Nadir Yehya, Lincoln Smith, Neal J. Thomas, Jerry J.

Zimmerman, Simon J. Erickson, Steven L. Shein

Section 2 (Pathobiology, Severity, and Risk Stratification) Jocelyn R. Grunwell, Mary K. Dahmer, Anil Sapru, Michael W. Quasney, Heidi R Flori.

Section 3 (Ventilatory Support) Analia Fernandez, Vicent Modesto i Alapont, Peter Rimensberger, Ira Cheifetz.

Section 4 (Pulmonary Specific Ancillary Treatment) Courtney Rowan, Adrienne G. Randolph, Martin Kneyber.

Section 5 (Non pulmonary treatment) Stacey Valentine, Sapna Kudchadkar, Shan Ward, Vinay Nadkarni, Martha A.Q. Curley.

Section 6 (Monitoring) Anoopindar Bhalla, Florent Baudin, Muneyuki Takeuchi, Pablo Cruces.

Section 7 (Noninvasive support) Christopher L Carroll, Natalie Napolitano, Marti Pons-Odena, Sandrine Essouri.

Section 8 (Extracorporeal Support) Jérome Rambaud, Ryan Barbaro, Duncan Macrae, Heidi Dalton.

Section 9 (Morbidity and Long-Term Outcomes) Elizabeth Killien, Aline Maddux, Sze Man Tse, Scott Watson.

Section 10 (Clinical Informatics and Data Science) L. Nelson Sanchez-Pinto, Michaël Sauthier, Prakadeshwari Rajapreyar, Philippe Jouvet, Christopher Newth.

Section 11 (Resource-Limited Settings) Brenda Morrow, Asya Agulnik, Werther Brunow de Carvalho, Mohamod Chisti, Jan Hau Lee.

Librarians: Katie Lobner, Lynn Kysh, Alix Pincivy, Philippe Dodin

10