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Lactate Dehydrogenase and Hemorrhagic Stroke During Extracorporeal Membrane Oxygenation for COVID-19

  • ECMO in COVID-19
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Abstract

Purpose

Hemorrhagic stroke (HS) is a devastating complication during extracorporeal membrane oxygenation (ECMO) but markers of risk stratification during COVID-19 are unknown. Lactate dehydrogenase (LDH) is a readily available biomarker of cell injury and permeability. We sought to determine whether an elevated LDH before ECMO placement is related to the occurrence of HS during ECMO for COVID-19.

Methods

Adult patients with COVID-19 requiring ECMO between March 2020 and February 2022 were included. LDH values prior to ECMO placement were captured. Patients were categorized into high (> 750 U/L) or low (≤ 750 U/L) LDH groups. Multivariable regression modeling was used to determine the association between LDH and HS during ECMO.

Results

There were 520 patients that underwent ECMO placement in 17 centers and 384 had an available LDH. Of whom, 122 (32%) had a high LDH. The overall incidence of HS was 10.9%, and patients with high LDH had a higher incidence of HS than those with low LDH level (17% vs 8%, p = 0.007). At 100 days, the probability of a HS was 40% in the high LDH group and 23% in those with a low LDH, p = 0.002. After adjustment for clinical covariates, high LDH remained associated with subsequent HS (aHR: 2.64, 95% CI 1.39–4.92). Findings were similar when restricting to patients supported by venovenous ECMO only.

Conclusion

Elevated LDH prior to ECMO cannulation is associated with a higher incidence of HS during device support. LDH can risk stratify cases for impending cerebral bleeding during ECMO.

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Abbreviations

ECMO:

Extracorporeal membrane oxygenation

ARDS:

Acute respiratory distress syndrome

HS:

Hemorrhagic stroke

LDH:

Lactate dehydrogenase

References

  1. Saeed O, Tatooles AJ, Farooq M et al (2022) Characteristics and outcomes of patients with COVID-19 supported by extracorporeal membrane oxygenation: a retrospective multicenter study. J Thorac Cardiovasc Surg 163:2107-2116.e6. https://doi.org/10.1016/j.jtcvs.2021.04.089

    Article  PubMed  Google Scholar 

  2. Badulak J, Antonini MV, Stead CM et al (2021) Extracorporeal membrane oxygenation for COVID-19: updated 2021 guidelines from the extracorporeal life support organization. ASAIO J 67:485–495. https://doi.org/10.1097/MAT.0000000000001422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Shaefi S, Brenner SK, Gupta S et al (2021) Extracorporeal membrane oxygenation in patients with severe respiratory failure from COVID-19. Intensive Care Med 47:208–221. https://doi.org/10.1007/s00134-020-06331-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ling RR, Ramanathan K, Sim JJL et al (2022) Evolving outcomes of extracorporeal membrane oxygenation during the first 2 years of the COVID-19 pandemic: a systematic review and meta-analysis. Crit Care 26:147. https://doi.org/10.1186/s13054-022-04011-2

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ramanathan K, Shekar K, Ling RR et al (2021) Extracorporeal membrane oxygenation for COVID-19: a systematic review and meta-analysis. Crit Care 25:211. https://doi.org/10.1186/s13054-021-03634-1

    Article  PubMed  PubMed Central  Google Scholar 

  6. Schmidt M, Langouet E, Hajage D et al (2021) Evolving outcomes of extracorporeal membrane oxygenation support for severe COVID-19 ARDS in sorbonne hospitals. Paris Crit Care 25:355. https://doi.org/10.1186/s13054-021-03780-6

    Article  PubMed  Google Scholar 

  7. Lebreton G, Schmidt M, Ponnaiah M et al (2021) Extracorporeal membrane oxygenation network organisation and clinical outcomes during the COVID-19 pandemic in Greater Paris, France: a multicentre cohort study. Lancet Respir Med 9:851–862. https://doi.org/10.1016/S2213-2600(21)00096-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bertini P, Guarracino F, Falcone M et al (2022) ECMO in COVID-19 patients: a systematic review and meta-analysis. J Cardiothorac Vasc Anesth 36:2700–2706. https://doi.org/10.1053/j.jvca.2021.11.006

    Article  CAS  PubMed  Google Scholar 

  9. Chung M, Cabezas FR, Nunez JI et al (2020) Hemocompatibility-related adverse events and survival on venoarterial extracorporeal life support: an ELSO registry analysis. JACC Heart Fail. https://doi.org/10.1016/j.jchf.2020.09.004

    Article  PubMed  PubMed Central  Google Scholar 

  10. Nunez JI, Gosling AF, O’Gara B et al (2022) Bleeding and thrombotic events in adults supported with venovenous extracorporeal membrane oxygenation: an ELSO registry analysis. Intensive Care Med. https://doi.org/10.1007/s00134-021-06593-x

    Article  PubMed  PubMed Central  Google Scholar 

  11. Schmidt M, Hajage D, Lebreton G et al (2020) Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with COVID-19: a retrospective cohort study. Lancet Respir Med 8:1121–1131. https://doi.org/10.1016/S2213-2600(20)30328-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Mansour A, Flecher E, Schmidt M et al (2022) Bleeding and thrombotic events in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study. Intensive Care Med 48:1039–1052. https://doi.org/10.1007/s00134-022-06794-y

    Article  CAS  PubMed  Google Scholar 

  13. Kannapadi N, v, Jami M, Premraj L, et al (2022) Neurological complications in COVID-19 patients With ECMO support: a systematic review and meta-analysis. Heart Lung Circ 31:292–298. https://doi.org/10.1016/j.hlc.2021.10.007

    Article  PubMed  Google Scholar 

  14. Lang CN, Dettinger JS, Berchtold-Herz M et al (2021) Intracerebral hemorrhage in COVID-19 patients with pulmonary failure: a propensity score-matched registry study. Neurocrit Care 34:739–747. https://doi.org/10.1007/s12028-021-01202-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  16. Ippolito A, Urban H, Ghoroghi K et al (2022) Prevalence of acute neurological complications and pathological neuroimaging findings in critically ill COVID-19 patients with and without VV-ECMO treatment. Sci Rep 12:17423. https://doi.org/10.1038/s41598-022-21475-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Arachchillage DRJ, Passariello M, Laffan M et al (2018) Intracranial hemorrhage and early mortality in patients receiving extracorporeal membrane oxygenation for severe respiratory failure. Semin Thromb Hemost 44:276–286. https://doi.org/10.1055/s-0038-1636840

    Article  PubMed  Google Scholar 

  18. Cho S-M, Canner J, Caturegli G et al (2021) Risk factors of ischemic and hemorrhagic strokes during venovenous extracorporeal membrane oxygenation: analysis of data from the extracorporeal life support organization registry. Crit Care Med 49:91–101. https://doi.org/10.1097/CCM.0000000000004707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Seeliger B, Doebler M, Hofmaenner DA et al (2022) Intracranial hemorrhages on extracorporeal membrane oxygenation: differences between COVID-19 and other viral acute respiratory distress syndrome. Crit Care Med 50:e526–e538. https://doi.org/10.1097/CCM.0000000000005441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ghahramani S, Tabrizi R, Lankarani KB et al (2020) Laboratory features of severe vs. Non-severe COVID-19 patients in Asian populations: a systematic review and meta-analysis. Eur J Med Res. https://doi.org/10.1186/s40001-020-00432-3

    Article  PubMed  PubMed Central  Google Scholar 

  21. Motawea KR, Varney J, Talat NE et al (2022) Lactate dehydrogenase can be considered a predictive marker of severity and mortality of Covid-19 in diabetic and non-diabetic patients. A Case Series Am Heart J 254:246–247. https://doi.org/10.1016/J.AHJ.2022.10.040

    Article  Google Scholar 

  22. Martha JW, Wibowo A, Pranata R (2022) Prognostic value of elevated lactate dehydrogenase in patients with COVID-19: a systematic review and meta-analysis. Postgrad Med J 98:422–427. https://doi.org/10.1136/postgradmedj-2020-139542

    Article  PubMed  Google Scholar 

  23. Silina E, v, Rumyantceva SA, Stupin VA, et al (2021) Early predictive blood markers of hemorrhagic stroke - influence of cytoflavin therapy. Can J Physiol Pharmacol 99:72–79. https://doi.org/10.1139/cjpp-2020-0277

    Article  CAS  PubMed  Google Scholar 

  24. Wang A, Tian X, Zuo Y et al (2021) High lactate dehydrogenase was associated with adverse outcomes in patients with acute ischemic stroke or transient ischemic attack. Ann Palliat Med 10:10185–10195. https://doi.org/10.21037/apm-21-2195

    Article  PubMed  Google Scholar 

  25. Jin H, Bi R, Hu J et al (2022) Elevated serum lactate dehydrogenase predicts unfavorable outcomes after rt-PA thrombolysis in ischemic stroke patients. Front Neurol 13:816216. https://doi.org/10.3389/fneur.2022.816216

    Article  PubMed  PubMed Central  Google Scholar 

  26. Chu H, Huang C, Dong J et al (2019) Lactate dehydrogenase predicts early hematoma expansion and poor outcomes in intracerebral hemorrhage patients. Transl Stroke Res 10:620–629. https://doi.org/10.1007/s12975-019-0686-7

    Article  CAS  PubMed  Google Scholar 

  27. Wang C-Y, Zhang Y-B, Wang J-Q et al (2022) Association between serum lactate dehydrogenase level and hematoma expansion in patients with primary intracerebral hemorrhage: a propensity-matched analysis. World Neurosurg 160:e579–e590. https://doi.org/10.1016/j.wneu.2022.01.080

    Article  PubMed  Google Scholar 

  28. Jin XX, Fang MD, Hu LL et al (2022) Elevated lactate dehydrogenase predicts poor prognosis of acute ischemic stroke. PLoS One 17:e0275651. https://doi.org/10.1371/journal.pone.0275651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Saeed O, Silvestry S (2021) Extracorporeal membrane oxygenation support during the coronavirus disease 2019 pandemic: outcomes and technical considerations. JTCVS open 8:77–82. https://doi.org/10.1016/j.xjon.2021.09.022

    Article  PubMed  PubMed Central  Google Scholar 

  30. Jin Y, Zhang Y, Liu J (2022) Ischemic stroke and intracranial hemorrhage in extracorporeal membrane oxygenation for COVID-19: a systematic review and meta-analysis. Perfusion. https://doi.org/10.1177/02676591221130886

    Article  PubMed  PubMed Central  Google Scholar 

  31. Cavayas YA, Munshi L, del Sorbo L, Fan E (2020) The early change in PaCO2 after extracorporeal membrane oxygenation initiation is associated with neurological complications. Am J Respir Crit Care Med 201:1525–1535. https://doi.org/10.1164/rccm.202001-0023OC

    Article  CAS  PubMed  Google Scholar 

  32. Lüsebrink E, Zimmer S, Schrage B et al (2022) Intracranial haemorrhage in adult patients on venoarterial extracorporeal membrane oxygenation. Eur Heart J Acute Cardiovasc Care 11:303–311. https://doi.org/10.1093/ehjacc/zuac018

    Article  PubMed  Google Scholar 

  33. Bermea RS, Raz Y, Sertic F et al (2021) Increased intracranial hemorrhage amid elevated inflammatory markers in those with COVID-19 supported with extracorporeal membrane oxygenation. Shock 56:206–214. https://doi.org/10.1097/SHK.0000000000001730

    Article  CAS  PubMed  Google Scholar 

  34. Cho S-M, Premraj L, Fanning J et al (2021) Ischemic and hemorrhagic stroke among critically Ill patients with coronavirus disease 2019: an international multicenter coronavirus disease 2019 critical care consortium study. Crit Care Med 49:e1223–e1233. https://doi.org/10.1097/CCM.0000000000005209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Henry BM, Aggarwal G, Wong J et al (2020) Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: a pooled analysis. Am J Emerg Med 38:1722–1726. https://doi.org/10.1016/j.ajem.2020.05.073

    Article  PubMed  PubMed Central  Google Scholar 

  36. Zhang D, Shi L (2021) Serum lactate dehydrogenase level is associated with in-hospital mortality in critically Ill patients with acute kidney injury. Int Urol Nephrol 53:2341–2348. https://doi.org/10.1007/s11255-021-02792-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Erez A, Shental O, Tchebiner JZ et al (2014) Diagnostic and prognostic value of very high serum lactate dehydrogenase in admitted medical patients. Isr Med Assoc J 16:439–443

    PubMed  Google Scholar 

  38. Lampl Y, Paniri Y, Eshel Y, Sarova-Pinhas I (1990) Cerebrospinal fluid lactate dehydrogenase levels in early stroke and transient ischemic attacks. Stroke 21:854–857. https://doi.org/10.1161/01.STR.21.6.854

    Article  CAS  PubMed  Google Scholar 

  39. Zan X, Deng H, Zhang Y et al (2022) Lactate dehydrogenase predicting mortality in patients with aneurysmal subarachnoid hemorrhage. Ann Clin Transl Neurol 9:1565–1573. https://doi.org/10.1002/acn3.51650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. McAlpine LS, Zubair AS, Maran I et al (2021) Ischemic stroke, inflammation, and endotheliopathy in COVID-19 patients. Stroke 52:e233–e238. https://doi.org/10.1161/STROKEAHA.120.031971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Merad M, Subramanian A, Wang TT (2021) An aberrant inflammatory response in severe COVID-19. Cell Host Microbe 29:1043–1047. https://doi.org/10.1016/j.chom.2021.06.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Fajgenbaum DC, June CH (2020) Cytokine storm. N Engl J Med 383:2255–2273. https://doi.org/10.1056/NEJMra2026131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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The production of this manuscript was made without any source of funding.

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Authors and Affiliations

  1. Department of Medicine, Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA

    Jose I. Nunez, Ulrich Jorde & Omar Saeed

  2. Departments of Cardiothoracic and Vascular Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA

    Mayuko Uehara, Nicholas Mellas, Justin E. Ashley, Stephen J. Forest & Daniel Goldstein

  3. Department of Medicine, Division of Critical Care Medicine and Pulmonology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA

    Amira Mohamed, Marjan Rahmanian & Anthony Carlese

  4. Department of Medicine, Division of Cardiovascular Medicine, Montefiore Medical Center, Albert Einstein College Of Medicine, Bronx, NY, USA

    Omar Saeed

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OS, UJ created the study protocol. JN and OS wrote the manuscript and created the figures. All authors reviewed the manuscript

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Correspondence to Omar Saeed.

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Nunez, J.I., Uehara, M., Mohamed, A. et al. Lactate Dehydrogenase and Hemorrhagic Stroke During Extracorporeal Membrane Oxygenation for COVID-19. Lung 201, 397–406 (2023). https://doi.org/10.1007/s00408-023-00630-w

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