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Semin Thromb Hemost 2018; 44(03): 276-286
DOI: 10.1055/s-0038-1636840
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Intracranial Hemorrhage and Early Mortality in Patients Receiving Extracorporeal Membrane Oxygenation for Severe Respiratory Failure

Deepa R.J. Arachchillage
1   Department of Haematology, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
2   Department of Haematology, Imperial College Healthcare NHS Trust and Imperial College London, London, United Kingdom
,
Maurizio Passariello
3   Adult Intensive Care Unit, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
,
Michael Laffan
2   Department of Haematology, Imperial College Healthcare NHS Trust and Imperial College London, London, United Kingdom
,
TC Aw
4   Department of Anaesthesia, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
,
Leah Owen
3   Adult Intensive Care Unit, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
,
Winston Banya
5   Department of Medical Statistics, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
,
Richard Trimlett
3   Adult Intensive Care Unit, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
,
Cliff Morgan
3   Adult Intensive Care Unit, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
,
Brijesh V. Patel
3   Adult Intensive Care Unit, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
6   Section of Anaesthesia, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom
,
John Pepper
7   Department of Cardiothoracic Surgery, National Heart and Lung Institute, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
,
Stephane Ledot
3   Adult Intensive Care Unit, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom
› Author Affiliations
Further Information

Publication History

Publication Date:
22 March 2018 (online)

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Abstract

Intracranial hemorrhage (ICH) is a serious complication in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) and is associated with high mortality. It is unknown whether ICH may be a consequence of the ECMO or of an underlying disease. The authors first aimed to assess the incidence of ICH at initiation and during the course of VV-ECMO and its associated mortality. The second aim was to identify clinical and laboratory measures that could predict the development of ICH in severe respiratory failure. Data were collected from a total number of 165 patients receiving VV-ECMO from January, 2012 to December, 2016 in a single tertiary center and treated according to a single protocol. Only patients who had a brain computed tomography within 24 hours of initiation of ECMO (n = 149) were included for analysis. The prevalence and incidence of ICH at initiation and during the course of VV-ECMO (at median 9 days) were 10.7% (16/149) and 5.2% (7/133), respectively. Thrombocytopenia and reduced creatinine clearance (CrCL) were independently associated with increased risk of ICH on admission; odds ratio (95% confidence interval): 22.6 (2.6–99.5), and 10.8 (5.6–16.2). Only 30-day (not 180-day) mortality was significantly higher in patients with ICH on admission versus those without (37.5% [6/16] vs 16.4% [22/133]; p = 0.03 and 43.7% [7/16] vs 26.3% [35/133]; p = 0.15, respectively). Reduced CrCL and thrombocytopenia were associated with ICH at initiation of VV-ECMO. The higher incidence of ICH at initiation suggests it is more closely related to the severity of the underlying lung injury than to the VV-ECMO itself. ICH at VV-ECMO initiation was associated with early mortality.

Keywords

extracorporeal membrane oxygenation - respiratory failure - intracranial hemorrhage - cerebral ischemic infarction - venous thrombosis - anticoagulation

Author contributions

D.R.J. Arachchillage was responsible for design of the study, acquiring data, some of the statistical analysis, interpretation of the data, and writing the first draft of the manuscript. M. Laffan, J. Pepper, and B. Patel critically evaluated the manuscript. M. Passariello, T.C. Aw, L. Owen, and S. Ledot collected the data. W. Banya performed statistically analysis. All authors commented and approved the final manuscript.


 

  • References

  • 1 Brogan TV, Thiagarajan RR, Rycus PT, Bartlett RH, Bratton SL. Extracorporeal membrane oxygenation in adults with severe respiratory failure: a multi-center database. Intensive Care Med 2009; 35 (12) 2105-2114
    CrossrefPubMedGoogle Scholar
  • 2 Allen S, Holena D, McCunn M, Kohl B, Sarani B. A review of the fundamental principles and evidence base in the use of extracorporeal membrane oxygenation (ECMO) in critically ill adult patients. J Intensive Care Med 2011; 26 (01) 13-26
    CrossrefPubMedGoogle Scholar
  • 3 Marasco SF, Vale M, Pellegrino V. , et al. Extracorporeal membrane oxygenation in primary graft failure after heart transplantation. Ann Thorac Surg 2010; 90 (05) 1541-1546
    CrossrefPubMedGoogle Scholar
  • 4 Combes A, Leprince P, Luyt CE. , et al. Outcomes and long-term quality-of-life of patients supported by extracorporeal membrane oxygenation for refractory cardiogenic shock. Crit Care Med 2008; 36 (05) 1404-1411
    CrossrefPubMedGoogle Scholar
  • 5 Camboni D, Philipp A, Lubnow M. , et al. Support time-dependent outcome analysis for veno-venous extracorporeal membrane oxygenation. Eur J Cardiothorac Surg 2011; 40 (06) 1341-1346 , discussion 1346–1347
    PubMedGoogle Scholar
  • 6 Lockie CJA, Gillon SA, Barrett NA, Taylor D, Mazumder A, Paramesh K, Rowland K, Daly K, Camporota L, Meadows CIS, Glover GW, Ioannou N, Langrish CJ, Tricklebank S, Retter A, Wyncoll DLA. Severe respiratory failure, extracorporeal membrane oxygenation, and intracranial hemorrhage. Crit Care Med 2017; DOI: 10.1097/. . [Epub ahead of print]
    CrossrefPubMedGoogle Scholar
  • 7 Aubron C, Cheng AC, Pilcher D. , et al. Factors associated with outcomes of patients on extracorporeal membrane oxygenation support: a 5-year cohort study. Crit Care 2013; 17 (02) R73
    CrossrefPubMedGoogle Scholar
  • 8 Marasco SF, Lukas G, McDonald M, McMillan J, Ihle B. Review of ECMO (extra corporeal membrane oxygenation) support in critically ill adult patients. Heart Lung Circ 2008; 17 (Suppl 4): S41-S47
    PubMedGoogle Scholar
  • 9 Murphy DA, Hockings LE, Andrews RK. , et al. Extracorporeal membrane oxygenation-hemostatic complications. Transfus Med Rev 2015; 29 (02) 90-101
    CrossrefPubMedGoogle Scholar
  • 10 Gattinoni L, Carlesso E, Langer T. Clinical review: extracorporeal membrane oxygenation. Crit Care 2011; 15 (06) 243
    CrossrefPubMedGoogle Scholar
  • 11 Luyt CE, Bréchot N, Demondion P. , et al. Brain injury during venovenous extracorporeal membrane oxygenation. Intensive Care Med 2016; 42 (05) 897-907
    CrossrefPubMedGoogle Scholar
  • 12 Kasirajan V, Smedira NG, McCarthy JF, Casselman F, Boparai N, McCarthy PM. Risk factors for intracranial hemorrhage in adults on extracorporeal membrane oxygenation. Eur J Cardiothorac Surg 1999; 15 (04) 508-514
    CrossrefPubMedGoogle Scholar
  • 13 Lorusso R, Gelsomino S, Parise O. , et al. Neurologic injury in adults supported with veno-venous extracorporeal membrane oxygenation for respiratory failure: findings from the extracorporeal life support organization database. Crit Care Med 2017; 45 (08) 1389-1397
    CrossrefPubMedGoogle Scholar
  • 14 Paden ML, Conrad SA, Rycus PT, Thiagarajan RR. ; ELSO Registry. Extracorporeal Life Support Organization Registry Report 2012. ASAIO J 2013; 59 (03) 202-210
    CrossrefPubMedGoogle Scholar
  • 15 Thiagarajan RR, Barbaro RP, Rycus PT. , et al; ELSO member centers. Extracorporeal Life Support Organization Registry International Report 2016. ASAIO J 2017; 63 (01) 60-67
    CrossrefPubMedGoogle Scholar
  • 16 Kalbhenn J, Wittau N, Schmutz A, Zieger B, Schmidt R. Identification of acquired coagulation disorders and effects of target-controlled coagulation factor substitution on the incidence and severity of spontaneous intracranial bleeding during veno-venous ECMO therapy. Perfusion 2015; 30 (08) 675-682
    CrossrefPubMedGoogle Scholar
  • 17 Nasr DM, Rabinstein AA. Neurologic complications of extracorporeal membrane oxygenation. J Clin Neurol 2015; 11 (04) 383-389
    CrossrefPubMedGoogle Scholar
  • 18 Lukito P, Wong A, Jing J. , et al. Mechanical circulatory support is associated with loss of platelet receptors glycoprotein Ibα and glycoprotein VI. J Thromb Haemost 2016; 14 (11) 2253-2260
    CrossrefPubMedGoogle Scholar
  • 19 Makdisi G, Wang IW. Extra corporeal membrane oxygenation (ECMO) review of a lifesaving technology. J Thorac Dis 2015; 7 (07) E166-E176
    PubMedGoogle Scholar
  • 20 Omar HR, Mirsaeidi M, Mangar D, Camporesi EM. Duration of ECMO is an independent predictor of intracranial hemorrhage occurring during ECMO support. ASAIO J 2016; 62 (05) 634-636
    CrossrefPubMedGoogle Scholar
  • 21 Schulman S, Kearon C. ; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
    CrossrefPubMedGoogle Scholar
  • 22 Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16 (01) 31-41
    CrossrefPubMedGoogle Scholar
  • 23 Kaatz S, Ahmad D, Spyropoulos AC, Schulman S. ; Subcommittee on Control of Anticoagulation. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost 2015; 13 (11) 2119-2126
    CrossrefPubMedGoogle Scholar
  • 24 Fletcher Sandersjöö A, Bartek Jr J, Thelin EP. , et al. Predictors of intracranial hemorrhage in adult patients on extracorporeal membrane oxygenation: an observational cohort study. J Intensive Care 2017; 5: 27
    CrossrefPubMedGoogle Scholar
  • 25 Arachchillage DRJ, Kamani F, Deplano S, Banya W, Laffan M. Should we abandon the APTT for monitoring unfractionated heparin?. Thromb Res 2017; 157: 157-161
    CrossrefPubMedGoogle Scholar
  • 26 Trudzinski FC, Minko P, Rapp D. , et al. Runtime and aPTT predict venous thrombosis and thromboembolism in patients on extracorporeal membrane oxygenation: a retrospective analysis. Ann Intensive Care 2016; 6 (01) 66-72
    CrossrefPubMedGoogle Scholar
  • 27 Cooper E, Burns J, Retter A. , et al. Prevalence of venous thrombosis following venovenous extracorporeal membrane oxygenation in patients with severe respiratory failure. Crit Care Med 2015; 43 (12) e581-e584
    CrossrefPubMedGoogle Scholar
  • 28 Zangrillo A, Biondi-Zoccai G, Landoni G. , et al. Extracorporeal membrane oxygenation (ECMO) in patients with H1N1 influenza infection: a systematic review and meta-analysis including 8 studies and 266 patients receiving ECMO. Crit Care 2013; 17 (01) R30
    CrossrefPubMedGoogle Scholar
  • 29 Eknoyan G, Wacksman SJ, Glueck HI, Will JJ. Platelet function in renal failure. N Engl J Med 1969; 280 (13) 677-681
    CrossrefPubMedGoogle Scholar
  • 30 Boccardo P, Remuzzi G, Galbusera M. Platelet dysfunction in renal failure. Semin Thromb Hemost 2004; 30 (05) 579-589
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Anton-Martin P, Raman L, Thatte N, Tweed J, Modem V, Journeycake J. Pre-ECMO coagulopathy does not increase the occurrence of hemorrhage during extracorporeal support. Int J Artif Organs 2017; 40 (05) 250-255
    CrossrefPubMedGoogle Scholar