Intensive care, right ventricular support and lung transplantation in patients with pulmonary hypertension

Authors, Journal, Affiliations, Type, DOI

• Marius M. Hoeper, Raymond L. Benza, Paul Corris, Marc de Perrot, Elie Fadel, Anne M. Keogh, Christian Kühn, Laurent Savale, Walter Klepetko
• European Respiratory Journal 2019; 53: 1801906
• Hannover Medical School (Hoeper/Kühn), Allegheny General Hospital (Benza), Newcastle University (Corris), Toronto General Hospital (de Perrot), Hôpital Marie Lannelongue (Fadel/Savale), St Vincent's Public Hospital Sydney (Keogh), Medical University of Vienna (Klepetko)
• Expert consensus article — Series: Proceedings of the 6th World Symposium on Pulmonary Hypertension
• DOI: https://doi.org/10.1183/13993003.01906-2018

Overview

This 6th World Symposium on Pulmonary Hypertension (WSPH 2018) expert consensus addresses three domains where robust RCT data are absent: ICU management of PH/PAH with right-sided heart failure; extracorporeal life support (ECLS/ECMO) for mechanical RV support; and lung transplantation including timing, perioperative strategy, and outcomes. ICU care focuses on precipitant treatment, careful fluid management, and afterload reduction with IV prostacyclins. ECLS (primarily VA-ECMO) is established only as bridge to transplant in fully evaluated candidates; awake/non-intubated ECMO is preferred. Bilateral lung transplantation achieves 1-year survival >90% in expert centres when extended perioperative ECMO prevents early graft dysfunction. All recommendations are based on clinical experience and expert consensus rather than scientific evidence from large clinical trials.

Keywords

Pulmonary hypertension, right heart failure, intensive care, extracorporeal membrane oxygenation, ECMO, extracorporeal life support, lung transplantation, right ventricular support, bridge to transplant

Key Takeaways

Pathophysiology of Right-Sided Heart Failure

• RV failure: defined as low cardiac output and/or elevated right-sided filling pressures from systolic and/or diastolic RV dysfunction
• Severe: if leading to secondary dysfunction of liver, kidneys, or gut
• RV hypertrophies then dilates → spherical shape → wall stress ↑, contractility ↓, TR ↑ → reduced effective CO
• Ventricular interdependence: dilated RV impairs LV filling and function via septal shift
• Congestion-mediated organ damage: bowel wall permeability ↑ → bacterial translocation → systemic inflammation/sepsis (common terminal event)
• Key warning signs of imminent death: ↓ ScvO₂ + ↑ lactate + ↓ urine output

ICU Monitoring

• Central venous line mandatory: provides CVP and ScvO₂ (correlates with CO)
• CVP measurement important in RV failure (unlike most ICU patients) to track elevated filling pressures
• RHC: not always necessary; consider in severe/complex cases for comprehensive haemodynamic assessment
• Regular echocardiography: RV/LV function, valve function, pericardial effusion, rule out tamponade
• Biomarkers: NT-proBNP/BNP, troponin; renal function (eGFR/BUN/uric acid); liver function (AST/bilirubin); lactate

ICU Treatment of Severe RV Failure

• Treat precipitants first: arrhythmia (restore sinus rhythm rapidly for atrial flutter/AF), infection (broad-spectrum antibiotics; consider bowel translocation source), anaemia, thyroid dysfunction, non-adherence
• Avoid intubation when possible: General anaesthesia + increased RV afterload = high risk of death; if unavoidable, maintain stable blood pressure
• Supplemental oxygen: maintain SpO₂ >90%; non-invasive ventilation for hypercapnia with caution (may worsen RV function)
• Fluid management: Most RV failure patients have elevated filling pressures — fluid administration worsens septal shift, TR, and LV filling; target negative fluid balance with IV loop diuretics or haemofiltration
• Afterload reduction: All approved PAH drugs may be used; IV prostacyclin analogues preferred (rapid onset); upfront triple combination (IV epoprostenol + PDE5i + ERA) reported with excellent short/mid-term results in newly diagnosed PAH with RV failure
• Inotropes: Dobutamine/milrinone most used; levosimendan more effective in animal models but lacks reliable clinical data in this setting
• Vasopressors: Norepinephrine and vasopressin preferred; vasopressin may have pulmonary vasodilator properties (low-dose) but clinical relevance uncertain
• Treat at expert centres capable of providing all options (medical, ECLS, transplantation)

Mechanical Support — Technical Principles

Peripheral Veno-Arterial ECMO (VA-ECMO)

• Most widely used ECLS strategy; usually via femoral vessels (upper body approach for ambulation)
• Flow 2.5–4 L/min achieves effective RV unloading while maintaining perfusion; avoids excessive LV afterload increase
• ECMO watershed: Opposing aortic blood flows (heart vs ECMO) create a watershed affecting differential oxygenation; upper body (brain, coronary) supplied by native heart; lower body by ECMO
• Upper body oxygenation can be impaired when LV output is hypoxic → monitor with right forearm SpO₂; regular troponin and echocardiography mandatory

PA-LA Approach (Pumpless Membrane Oxygenator)

• Membrane oxygenator placed between pulmonary artery and left atrium (no pump needed in PH due to high native pressure gradient)
• Requires sternotomy or anterolateral thoracotomy; temporary ECMO often needed pre-anaesthesia
• Advantages: ambulation feasible; oxygenated blood enters entire systemic circulation; LV preloading "primes" for post-transplant haemodynamics
• PA-LA preferred for longer expected bridging duration or in children with small femoral arteries

RVAD

• Isolated RVAD support in PAH: only sporadic case reports; no successful long-term use reported
• Risks: pulmonary vascular remodelling aggravation, pulmonary bleeding, LV diastolic dysfunction → pulmonary oedema
• Isolated RVAD should not be used in PAH (or used with utmost caution)

ECLS Indications, Contraindications, and Timing

• Established indication: Bridge to transplant in fully evaluated and accepted candidates
• Potential indications (selected cases):
  • Bridge to transplant decision (not yet fully evaluated but potentially eligible)
  • Bridge to recovery: reversible cause of RV failure (arrhythmia, infection) or hitherto untreated/undertreated PAH
• Contraindication: End-stage disease without realistic chance of recovery or transplantation (futility)
• Timing: When clinical course suggests imminent terminal RV failure or secondary organ failure despite optimised medical therapy; ECLS during CPR rarely results in good outcomes
• Awake ECMO preferred: avoids risks of general anaesthesia, ventilator-associated pneumonia, muscle deconditioning; feasible for weeks; associated with better outcomes than intubated bridging strategies
• All ECLS forms have potentially life-threatening complications — use only when less invasive options exhausted
• Transplanting centres performing lung Tx in PAH should have an established ECLS programme

Published Bridge-to-Transplant Outcomes (Table 3 Summary)

• 11 series; 81 total patients (66 ECMO, 15 PA-LA); 77 bridged to transplant
• Bridged to transplant: 94% (72/77)
• Discharged from hospital: 78% (56/72)
• Best outcomes with VA-ECMO and PA-LA; mixed VV-ECMO results

Lung Transplantation in PH

When to Refer

• Referral when: ESC/ERS intermediate or high risk OR REVEAL risk score >7 on appropriate PAH medication; progressive disease or recent hospitalisation; need for IV/SC prostacyclin; known/suspected high-risk variants (PVOD, PCH, scleroderma, large pulmonary artery aneurysms); secondary liver/kidney dysfunction or recurrent haemoptysis
• Early referral critical: allows full evaluation and optimal timing; avoids rushed listing when rapidly deteriorating
• Referral ≠ immediate listing; completed evaluation allows rapid listing if clinical deterioration occurs

When to List

• Listing when: ESC/ERS high risk OR REVEAL risk score ≥10 on optimised medical therapy (usually including IV/SC prostacyclins); progressive hypoxaemia (especially PVOD/PCH); progressive (not end-stage) liver/kidney dysfunction; life-threatening haemoptysis
• Expected 1-year mortality on high-risk medical therapy: >20% (registry data); 1-year post-Tx mortality in expert centres: ~10% → survival benefit is expected
• LAS score underestimates PAH disease severity; modified LAS (2015) adds RAP ≥14 mmHg and 6MWD ≤300 m as additional mortality predictors
• Pre-transplant rehabilitation programmes recommended
• No degree of RV dysfunction precludes bilateral lung transplantation in PAH (RV recovers within weeks post-transplant regardless of pre-operative severity)

Procedure and Perioperative Management

• Bilateral lung transplantation: method of choice for most patients with PH
• Intraoperative VA-ECMO has almost completely replaced conventional cardiopulmonary bypass — associated with fewer peri-operative complications (renal failure, transfusions) and potentially better survival
• Pre-anaesthesia VA-ECMO established in patients with severe PH and RV failure to prevent haemodynamic instability
• Post-transplant extended ECMO: Prevents primary graft dysfunction driven by LV failure ("unconditioned" small LV exposed to normal/high preload after transplantation → diastolic dysfunction → pulmonary oedema)
  • Strategy 1: Extubation first + continue ECMO support 3–7 days (Hannover approach) — 1-year survival >90%
  • Strategy 2: Brief post-operative ECMO in intubated patients until haemodynamic stabilisation + fluid balance normalisation — 1-year survival >90%
• RV recovery after transplantation: Almost any RV recovers within weeks post-transplant regardless of pre-transplant dilatation/dysfunction or degree of TR
• Combined heart-lung transplantation: historically used for severe PH with "unconditioned LV"; now superseded by bilateral Tx + extended ECMO
• Low-volume/high-risk procedure → should be concentrated in specialised centres

Ethical Considerations

• ECLS warranted when clear treatment objective exists (recovery or transplantation)
• If recovery and transplantation are not achievable → ECLS is futile; best supportive care is appropriate
• Discuss end-of-life matters proactively and early; patient preferences may change with disease progression

Limitations of the Document

• Expert consensus only; explicitly states most recommendations are based on clinical experience rather than large clinical trial evidence
• ECLS and lung transplantation data from small, largely single-centre series (largest published bridge-to-transplant series is 18 patients)
• Survival benefits of specific ECLS strategies not formally compared in RCTs
• Post-transplant extended ECMO strategies described from two centres' experience; no head-to-head comparison

Key Concepts Mentioned

• concepts/Right-Ventricular-Failure — ICU management framework, precipitant treatment, fluid management
• concepts/ECLS-in-PH — VA-ECMO, PA-LA, RVAD, indications/contraindications/timing
• concepts/Lung-Transplantation-PAH — referral/listing criteria, perioperative ECMO strategy, outcomes
• concepts/Pulmonary-Hypertension — PAH natural history, treatment context, transplant role

Key Entities Mentioned

• entities/Dobutamine — inotrope for RV failure; most widely used
• entities/Milrinone — PDE3 inhibitor; alternative inotrope
• entities/Levosimendan — animal model data more favourable than dobutamine; clinical data lacking in PH-specific setting
• entities/Vasopressin — preferred vasopressor; pulmonary vasodilatory properties at low doses

Wiki Pages Updated

• wiki/sources/PHT-RVsupport-WSPH-2019.md — created
• wiki/concepts/ECLS-in-PH.md — created
• wiki/concepts/Lung-Transplantation-PAH.md — created
• wiki/concepts/Right-Ventricular-Failure.md — updated ICU treatment and ECLS sections
• wiki/concepts/Pulmonary-Hypertension.md — updated transplant referral/listing criteria section
• wiki/sourceindex.md — updated
• wiki/wikiindex.md — updated