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Brain injury during venovenous extracorporeal membrane oxygenation

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Abstract

Purpose

The frequency of neurological events and their impact on patients receiving venovenous extracorporeal membrane oxygenation (VV-ECMO) are unknown. We therefore study the epidemiology, risk factors, and impact of cerebral complications occurring in VV-ECMO patients.

Methods

Observational study conducted in a tertiary referral center (2006–2012) on patients developing a neurological complication (ischemic stroke or intracranial bleeding) while on VV-ECMO versus those who did not, and a systematic review on this topic.

Results

Among 135 consecutive patients who had received VV-ECMO, 18 (15 assessable) developed cerebral complications on ECMO: cerebral bleeding in 10 (7.5 %), ischemic stroke in 3 (2 %), or diffuse microbleeds in 2 (2 %), occurring after respective medians (IQR) of 3 (1–11), 21 (10–26), and 36 (8–63) days post-ECMO onset. Intracranial bleeding was independently associated with renal failure at intensive care unit admission and rapid PaCO2 decrease at ECMO initiation, but not with age, comorbidities, or hemostasis disorders. Seven (70 %) patients with intracranial bleeding and one (33 %) with ischemic stroke died versus 40 % of patients without neurological event. A systematic review found comparable intracranial bleeding rates (5 %).

Conclusions

Neurological events occurred frequently in patients on VV-ECMO. Intracranial bleeding, the most frequent, occurred early and was associated with higher mortality. Because it was independently associated with rapid hypercapnia decrease, the latter should be avoided at ECMO onset, but its exact role remains to be determined. These findings may have major implications for the care of patients requiring VV-ECMO.

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References

  1. Luyt CE, Combes A, Becquemin MH, Beigelman-Aubry C, Hatem S, Brun AL, Zraik N, Carrat F, Grenier PA, Richard JC, Mercat A, Brochard L, Brun-Buisson C, Chastre J (2012) Long-term outcomes of pandemic 2009 influenza A (H1N1)-associated severe acute respiratory distress syndrome. Chest 142:583–592

    Article  CAS  PubMed  Google Scholar 

  2. Combes A, Brodie D, Bartlett R, Brochard L, Brower R, Conrad S, De Backer D, Fan E, Ferguson N, Fortenberry J, Fraser J, Gattinoni L, Lynch W, MacLaren G, Mercat A, Mueller T, Ogino M, Peek G, Pellegrino V, Pesenti A, Ranieri M, Slutsky A, Vuylsteke A (2014) Position paper for the organization of extracorporeal membrane oxygenation programs for acute respiratory failure in adult patients. Am J Respir Crit Care Med 190:488–496

    Article  PubMed  Google Scholar 

  3. Davies A, Jones D, Bailey M, Beca J, Bellomo R, Blackwell N, Forrest P, Gattas D, Granger E, Herkes R, Jackson A, McGuinness S, Nair P, Pellegrino V, Pettila V, Plunkett B, Pye R, Torzillo P, Webb S, Wilson M, Ziegenfuss M (2009) Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) acute respiratory distress syndrome. JAMA 302:1888–1895

    Article  CAS  PubMed  Google Scholar 

  4. Kasirajan V, Smedira NG, McCarthy JF, Casselman F, Boparai N, McCarthy PM (1999) Risk factors for intracranial hemorrhage in adults on extracorporeal membrane oxygenation. Eur J Cardiothorac Surg 15:508–514

    Article  CAS  PubMed  Google Scholar 

  5. Mateen FJ, Muralidharan R, Shinohara RT, Parisi JE, Schears GJ, Wijdicks EF (2011) Neurological injury in adults treated with extracorporeal membrane oxygenation. Arch Neurol 68:1543–1549

    Article  PubMed  Google Scholar 

  6. Chow FC, Edlow BL, Frosch MP, Copen WA, Greer DM (2011) Outcome in patients with H1N1 influenza and cerebrovascular injury treated with extracorporeal membrane oxygenation. Neurocrit Care 15:156–160

    Article  PubMed  Google Scholar 

  7. Le Guennec L, Bertrand A, Laurent C, Roze H, Chastre J, Combes A, Luyt CE (2015) Diffuse cerebral microbleeds after extracorporeal membrane oxygenation support. Am J Respir Crit Care Med 191:594–596

    Article  PubMed  Google Scholar 

  8. Nasr DM, Rabinstein AA (2015) Neurologic complications of extracorporeal membrane oxygenation. J Clin Neurol 11:383–389

    Article  PubMed  PubMed Central  Google Scholar 

  9. Heilmann C, Geisen U, Beyersdorf F, Nakamura L, Benk C, Trummer G, Berchtold-Herz M, Schlensak C, Zieger B (2012) Acquired von Willebrand syndrome in patients with extracorporeal life support (ECLS). Intensive Care Med 38:62–68

    Article  PubMed  Google Scholar 

  10. Schmidt M, Tachon G, Devilliers C, Muller G, Hekimian G, Brechot N, Merceron S, Luyt CE, Trouillet JL, Chastre J, Leprince P, Combes A (2013) Blood oxygenation and decarboxylation determinants during venovenous ECMO for respiratory failure in adults. Intensive Care Med 39:838–846

    Article  CAS  PubMed  Google Scholar 

  11. Schmidt M, Pellegrino V, Combes A, Scheinkestel C, Cooper DJ, Hodgson C (2014) Mechanical ventilation during extracorporeal membrane oxygenation. Crit Care 18:203

    Article  PubMed  PubMed Central  Google Scholar 

  12. Lassen NA, Christensen MS (1976) Physiology of cerebral blood flow. Br J Anaesth 48:719–734

    Article  CAS  PubMed  Google Scholar 

  13. Meng L, Gelb AW (2014) Regulation of cerebral autoregulation by carbon dioxide. Anesthesiology 122:196–205

    Article  Google Scholar 

  14. Muellenbach RM, Kilgenstein C, Kranke P, Kustermann J, Kredel M, Roewer N, Ernestus RI, Westermaier T (2014) Effects of venovenous extracorporeal membrane oxygenation on cerebral oxygenation in hypercapnic ARDS. Perfusion 29:139–141

    Article  CAS  PubMed  Google Scholar 

  15. Kredel M, Lubnow M, Westermaier T, Muller T, Philipp A, Lotz C, Kilgenstein C, Kustermann J, Roewer N, Muellenbach RM (2014) Cerebral tissue oxygenation during the initiation of venovenous ECMO. ASAIO J 60:694–700

    Article  CAS  PubMed  Google Scholar 

  16. Repesse X, Au SM, Brechot N, Trouillet JL, Leprince P, Chastre J, Combes A, Luyt CE (2013) Recombinant factor VIIa for uncontrollable bleeding in patients with extracorporeal membrane oxygenation: report on 15 cases and literature review. Crit Care 17:R55

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kolla S, Awad SS, Rich PB, Schreiner RJ, Hirschl RB, Bartlett RH (1997) Extracorporeal life support for 100 adult patients with severe respiratory failure. Ann Surg 226:544–564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Linden V, Palmer K, Reinhard J, Westman R, Ehren H, Granholm T, Frenckner B (2000) High survival in adult patients with acute respiratory distress syndrome treated by extracorporeal membrane oxygenation, minimal sedation, and pressure supported ventilation. Intensive Care Med 26:1630–1637

    Article  CAS  PubMed  Google Scholar 

  19. Mols G, Loop T, Geiger K, Farthmann E, Benzing A (2000) Extracorporeal membrane oxygenation: a ten-year experience. Am J Surg 180:144–154

    Article  CAS  PubMed  Google Scholar 

  20. Hemmila MR, Rowe SA, Boules TN, Miskulin J, McGillicuddy JW, Schuerer DJ, Haft JW, Swaniker F, Arbabi S, Hirschl RB, Bartlett RH (2004) Extracorporeal life support for severe acute respiratory distress syndrome in adults. Ann Surg 240:595–605

    PubMed  PubMed Central  Google Scholar 

  21. Brogan TV, Thiagarajan RR, Rycus PT, Bartlett RH, Bratton SL (2009) Extracorporeal membrane oxygenation in adults with severe respiratory failure: a multi-center database. Intensive Care Med 35:2105–2114

    Article  CAS  PubMed  Google Scholar 

  22. Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, Hibbert CL, Truesdale A, Clemens F, Cooper N, Firmin RK, Elbourne D (2009) Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 374:1351–1363

    Article  PubMed  Google Scholar 

  23. Noah MA, Peek GJ, Finney SJ, Griffiths MJ, Harrison DA, Grieve R, Sadique MZ, Sekhon JS, McAuley DF, Firmin RK, Harvey C, Cordingley JJ, Price S, Vuylsteke A, Jenkins DP, Noble DW, Bloomfield R, Walsh TS, Perkins GD, Menon D, Taylor BL, Rowan KM (2011) Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1). JAMA 306:1659–1668

    Article  CAS  PubMed  Google Scholar 

  24. Patroniti N, Zangrillo A, Pappalardo F, Peris A, Cianchi G, Braschi A, Iotti GA, Arcadipane A, Panarello G, Ranieri VM, Terragni P, Antonelli M, Gattinoni L, Oleari F, Pesenti A (2011) The Italian ECMO network experience during the 2009 influenza A(H1N1) pandemic: preparation for severe respiratory emergency outbreaks. Intensive Care Med 37:1447–1457

    Article  PubMed  Google Scholar 

  25. Pham T, Combes A, Roze H, Chevret S, Mercat A, Roch A, Mourvillier B, Ara-Somohano C, Bastien O, Zogheib E, Clavel M, Constan A, Marie Richard JC, Brun-Buisson C, Brochard L (2013) Extracorporeal membrane oxygenation for pandemic influenza A(H1N1)-induced acute respiratory distress syndrome: a cohort study and propensity-matched analysis. Am J Respir Crit Care Med 187:276–285

    Article  CAS  PubMed  Google Scholar 

  26. Lindskov C, Jensen RH, Sprogoe P, Klaaborg KE, Kirkegaard H, Severinsen IK, Lorentsen AG, Folkersen L, Ilkjaer S, Pedersen CM (2013) Extracorporeal membrane oxygenation in adult patients with severe acute respiratory failure. Acta Anaesthesiol Scand 57:303–311

    Article  CAS  PubMed  Google Scholar 

  27. Michaels AJ, Hill JG, Bliss D, Sperley BP, Young BP, Quint P, Shanks TR, Dalthorp J, Long WB, Morgan LJ (2013) Pandemic flu and the sudden demand for ECMO resources: a mature trauma program can provide surge capacity in acute critical care crises. J Trauma Acute Care Surg 74:1493–1497

    Article  PubMed  Google Scholar 

  28. Roch A, Hraiech S, Masson E, Grisoli D, Forel JM, Boucekine M, Morera P, Guervilly C, Adda M, Dizier S, Toesca R, Collart F, Papazian L (2014) Outcome of acute respiratory distress syndrome patients treated with extracorporeal membrane oxygenation and brought to a referral center. Intensive Care Med 40:74–83

    Article  CAS  PubMed  Google Scholar 

  29. Ng GW, Leung AK, Sin KC, Au SY, Chan SC, Chan OP, Wu HH (2014) Three-year experience of using venovenous extracorporeal membrane oxygenation for patients with severe respiratory failure. Hong Kong Med J 20:407–412

    PubMed  Google Scholar 

  30. Kon ZN, Dahi S, Evans CF, Byrnes KA, Bittle GJ, Wehman B, Rector RP, McCormick BM, Herr DL, Sanchez PG, Pham SM, Griffith BP (2015) Long-term venovenous extracorporeal membrane oxygenation support for acute respiratory distress syndrome. Ann Thorac Surg 100:2059–2063

    Article  PubMed  Google Scholar 

  31. Gray BW, Haft JW, Hirsch JC, Annich GM, Hirschl RB, Bartlett RH (2015) Extracorporeal life support: experience with 2,000 patients. ASAIO J 61:2–7

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors thank Janet Jacobson for editorial assistance in revising the manuscript and Marguerite Guiguet for statistical assistance.

Author information

Authors and Affiliations

  1. Service de Réanimation, Institut de Cardiologie, ICAN, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 47–83, Boulevard de l’Hôpital, 75651, Paris Cedex 13, France

    Charles-Edouard Luyt, Nicolas Bréchot, Tamara Jovanovic, Guillaume Hékimian, Ania Nieszkowska, Matthieu Schmidt, Jean-Louis Trouillet, Jean Chastre & Alain Combes

  2. Sorbonne Universités, UPMC Université Paris 06, INSERM, UMRS-1166, ICAN Institute of Cardiometabolism and Nutrition, Paris, France

    Charles-Edouard Luyt, Nicolas Bréchot, Guillaume Hékimian, Ania Nieszkowska, Matthieu Schmidt, Jean-Louis Trouillet, Jean Chastre & Alain Combes

  3. Service de Chirurgie Thoracique et Cardiovasculaire, Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France

    Pierre Demondion, Guillaume Lebreton & Pascal Leprince

Authors
  1. Charles-Edouard Luyt
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  2. Nicolas Bréchot
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  3. Pierre Demondion
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  4. Tamara Jovanovic
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  5. Guillaume Hékimian
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  6. Guillaume Lebreton
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  7. Ania Nieszkowska
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  8. Matthieu Schmidt
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  9. Jean-Louis Trouillet
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  10. Pascal Leprince
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  11. Jean Chastre
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  12. Alain Combes
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Corresponding author

Correspondence to Charles-Edouard Luyt.

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Conflicts of interest

Alain Combes is the primary investigator of the EOLIA, NCT07470703, a randomized trial of VV-ECMO supported in part by Maquet. Alain Combes has received honoraria for lectures by Maquet, Baxter, and ALung. Other authors declare that they have no conflict of interest related to the purpose of this manuscript.

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Additional information

Take-home message: Cerebral bleeding frequency in patients on venovenous ECMO is 5–6 %, occurs early during the ECMO course, and is associated with a high mortality rate, whereas other neurological complications are rare. Rapid correction of hypercapnia at ECMO initiation seems to be associated with cerebral bleeding. Hence, slow correction of hypercapnia at ECMO initiation might be a way to prevent this complication.

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Luyt, CE., Bréchot, N., Demondion, P. et al. Brain injury during venovenous extracorporeal membrane oxygenation. Intensive Care Med 42, 897–907 (2016). https://doi.org/10.1007/s00134-016-4318-3

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  • DOI: https://doi.org/10.1007/s00134-016-4318-3

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