Comparing SARS-CoV-2 and influenza A(H1N1)pdm09-infected patients requiring ECMO – A single-centre, retrospective observational cohort experience
Authors: Matthew Charlton, Susan Dashey, Abigail Stubbs, Florence YL Lai, Paul W Bird, Vinay Badhwar, Julian W Tang
Journal: Journal of Infection (2020)

We read with interest the recent report from Fiore and colleagues,1Fiore A. de Roux Q. Daami N. et al.Clinical feedback from experience with COVID-19: specific considerations for extracorporeal membrane oxygenation.J Infect. 2020; 81: e59-e60https://doi.org/10.1016/j.jinf.2020.06.050Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar describing their experience with ECMO on COVID-19 cases. Here we share our own ECMO COVID-19 experience, and compare this with our previous experience of ECMO use in influenza patients.2Charlton M. Dunn C. Dashey S. Lai F.Y. Tang J.W Severe influenza a cases requiring extra-corporeal membrane oxygenation (ECMO) therapy, 2018-2019.J Infect. 2020; 80: 469-496https://doi.org/10.1016/j.jinf.2019.12.009Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar ECMO is a resource-intensive, highly specialised, and expensive form of life support with the potential for significant complications with unknown benefits, in the management of COVID-19. Thus its clinical utility during the current pandemic has been uncertain.3MacLaren G., Fisher D., Brodie D. Preparing for the most critically ill patients with COVID-19: the potential role of extracorporeal membrane oxygenation JAMA. 2020;10.1001/jama.2020.2342. doi:10.1001/jama.2020.2342.Google Scholar An early retrospective case series from China described the role of ECMO in COVID-19 as 'unpromising', with nearly half of patients treated with ECMO dying from septic shock and multiple organ failure.4Zeng Y. Cai Z. Xianyu Y. Yang B.X. Song T. Yan Q Prognosis when using extracorporeal membrane oxygenation (ECMO) for critically ill COVID-19 patients in China: a retrospective case series.Crit Care. 2020; 24 (Published 2020 Apr 15): 148https://doi.org/10.1186/s13054-020-2840-8Crossref PubMed Scopus (81) Google Scholar To investigate this further, we describe the clinical characteristics and outcomes of 34 patients presenting with severe COVID-19 pneumonitis who received respiratory ECMO support during the COVID-19 pandemic to one of the commissioned UK respiratory ECMO centres. Single-centre, retrospective data collection was performed for all patients receiving respiratory ECMO support for severe respiratory failure secondary to SARS-CoV-2 infection during the peak of the UK pandemic (1st April to 31st May 2020). Various ECMO-related and laboratory parameters were extracted and statistically compared between patients who died (n = 18) and those who survived (n = 16) using the t-test or Mann-Whitney test for continuous variables and the Fisher-exact test for categorical variables. Correlation between duration on ECMO and laboratory parameters was assessed using Spearman's rank correlation coefficient. A total of 268 patients were referred for consideration of respiratory ECMO support in Leicester (patient eligible criteria are shown in Fig. S1). Of the 268 referrals, 38 were retrieved for consideration of ECMO. Thirty-four went on to receive ECMO support, with 4 patients managed with advanced conventional ventilatory support as part of the Severe Acute Respiratory Failure (SARF) pathway (Table S1). The mean age of the 34 patients receiving ECMO support was 46 years (range: 28–58). The majority were male (27/34, 79%), with a mean body mass index (BMI) of 31.9 (range: 22.4–45), and most patients (88%) had at least one comorbidity (hypertension, diabetes or obesity). The most frequently occurring COVID-19 symptoms in this patient group included fever (26/34, 76%), cough (25/34, 74%) and myalgia (10/34, 29%). Anosmia was a relatively uncommon finding, being recognised in only 2 patients (6%). Black and Minority Ethnic (BAME) groups accounted for 59% (20/34) of patients, with 38% (13/34) of the cohort being healthcare workers. Co-morbid conditions were present in the majority of patients (30/34, 88%), with the most common being: obesity (23/34, 68%), hypertension (8/34, 24%) and diabetes (4/34, 12%). The majority of patients had a dual-lumen cannula configuration of the right internal jugular vein (28/34, 82%), as is routine practice for our unit. Renal replacement therapy was initiated in 26% (9/34) of patients. The mean duration of ventilation prior to initiation of ECMO was 4.9 days (range: 2–8), and the mean duration of ECMO support was 13.2 days (range: 4–26). The survival to discharge in this cohort of patients was 53% (18/34). Table 1 compares COVID-19 patients who survived (18/34, 52.9%) versus those who died (16/34, 47.1%), with both groups being evenly matched with respect to demographic data and medical history. White cell count (p = 0.027) and neutrophil count (p = 0.035) were both significantly lower in those patients who died (10.5 vs. 14.1 and 9.1 vs. 12.3, respectively). The duration of ECMO was also significant, 11.1 days (survivors) versus 15.6 days (deaths). The slight differences in Na/K concentrations between the two groups, though just statistically significant (p<0.05), were of little clinical significance.Table 1Demographic and clinical characteristics of the COVID-19 patients on ECMO.SurvivorDiedp-valueDemographics(n = 18)(n = 16)Age (years)45.6 (6.7)47.0 (8.4)0.596Sex - M15 (83%)12 (75%)0.682EthnicityAsian8 (44%)8 (50%)0.893Black2 (11%)2 (13%)White8 (44%)6 (38%)HCW6 (33%)7 (44%)0.725Medical historyAny comorbidity17 (94%)13 (81%)0.323Hypertension6 (33%)2 (13%)0.233Diabetes3 (17%)1 (6%)0.604Obese15 (83%)8 (50%)0.066Haematology and biochemistry parametersWhite cell count (109/L)14.1 (5.7)10.5 (2.9)0.027Neutrophils (109/L)12.3 (5.4)9.1 (2.9)0.035Lymphocytes (109/L)1.1 (0.4)0.9 (0.5)0.220C-reactive protein (mg/L)195.4 (113.0)260.6 (95.5)0.080Haemoglobin (g/L)105.3 (11.2)103.4 (11.8)0.623LDH (IU/L)656.4 (277.2)603.5 (243.7)0.684ALT (IU/L)51 (35 - 73)47.5 (34 - 79)0.931GGT (IU/L)154.5 (78.5 - 251)104 (73 - 156)0.097AST (IU/L)74 (59.5 - 85)69 (65 - 94)0.728Total bilirubin (µmol/L)13 (8 - 31)10.5 (7 - 17.5)0.284Urea (mmol/L)9.4 (6.7 - 13)10.3 (7.4 - 15)0.504Na (mmol/L)143.0 (4.6)146.2 (4.2)0.043K (mmol/L)5.3 (0.7)4.8 (0.5)0.045Creatinine (µmol/L)74.5 (52 - 190)68 (45.5 - 124)0.704Troponin (ng/L)15 (4 - 41)29 (17 - 83)0.142BNP (pg/mL)384 (253 - 566)532 (341 - 1127)0.365D-dimers (ng/mL)7.9 (3.3 - 9.6)6.2 (3.5 - 18)0.772ECMO parametersPaO2:FiO2 ratio9.0 (7.3 - 10)8.3 (7 - 9.8)0.398PEEP (cm H20)12.8 (3.5)13.8 (3.2)0.373Tidal volume (mL)476.5 (78.3)476.1 (154.6)0.992Respiratory rate (RR, bpm)20.4 (4.3)19.3 (5.3)0.498Peak RR (bpm)32.9 (3.7)32.3 (3.6)0.612pH7.3 (0.1)7.3 (0.1)0.823PaO2 (kPa)7.9 (1.2)8.0 (1.2)0.689PaCO2 (kPa)7.7 (1.9)9.6 (4.3)0.112Base excess (mmol/L)2.4 (4.5)3.0 (2.9)0.702Lactate (mmol/L)1.5 (0.6)1.5 (0.5)0.911Bicarbonate (HCO3, mmol/L)27.2 (4.8)28.7 (4.3)0.409MAP (mm Hg)79.6 (12.1)77.3 (10.7)0.553Days ventilated pre-ECMO5.2 (1.8)4.6 (1.7)0.278Days on ECMO11.1 (4.9)15.6 (5.6)0.017LDH - lactate dehydrogenase; ALT – alanine aminotransferase; GGT – gamma glutamyl transferase; AST – aspartate aminotransferase; BNP - brain natriuretic peptide; PEEP – positive end expiratory pressure; H2O – water; bpm - breaths per minute; PaO2/PaCO2 – partial pressure of arterial oxygen/carbon dioxide; MAP – mean arterial pressure; ECMO – extra-corporeal membrane oxygenation. Open table in a new tab LDH - lactate dehydrogenase; ALT – alanine aminotransferase; GGT – gamma glutamyl transferase; AST – aspartate aminotransferase; BNP - brain natriuretic peptide; PEEP – positive end expiratory pressure; H2O – water; bpm - breaths per minute; PaO2/PaCO2 – partial pressure of arterial oxygen/carbon dioxide; MAP – mean arterial pressure; ECMO – extra-corporeal membrane oxygenation. When comparing this COVID-19 cohort to a previous cohort presenting for ECMO support with influenza A(H1N1)pdm09 during the 2018–2019 season (Table 2), a number of significant differences were noted. Most significantly, severe influenza requiring ECMO support occurred more frequently in ethnically white (Caucasian) compared to the COVID-19 patients (p ≤ 0.001). White cell count also appears significantly lower in the influenza cohort (5.8 vs. 12.4, p ≤ 0.001). A significant proportion of the patients in the influenza group required renal replacement therapy (24/26, 92%), which was not seen in the COVID-19 patients. The number of days ventilated prior to initiation of ECMO was also significantly shorter in the influenza group (2.4 vs. 4.9, p ≤ 0.001). More deaths were recognised in the COVID-19 group (47% vs. 31%), although this did not reach statistical significance.Table 2Comparison of demographic and clinical characteristics of COVID-19 (2020) and influenza (2018–2019) patients on ECMO.COVID-19A(H1N1)pdm09p-value(n = 34)(n = 26)DemographicsAge (yrs)46.3 (7.5)43.1 (8.7)0.133Sex - male27 (79%)18 (69%)0.386Ethnic White14 (41%)24 (92%)<0.001Body-mass index (BMI)31.9 (6.0)30.6 (7.8)0.475Medical historyComorbidity30 (88%)18 (69%)0.104Hypertension8 (24%)5 (19%)0.760Diabetes4 (12%)2 (8%)0.689Obese23 (68%)12 (46%)0.118Haematology and biochemistry parametersWhite cell count (109/L)12.4 (4.9)5.8 (4.6)<0.001C-reactive protein (mg/L)226.1 (108.7)259.4 (140.3)0.323Haemoglobin (g/L)104.4 (11.3)129.7 (23.0)<0.001ALT (IU/L)47.5 (35 - 78)57 (31 - 78)0.883Total bilirubin (µmol/L)11.5 (8 - 22)18 (9 - 30)0.702Urea (mmol/L)10.2 (7.1 - 13)9.05 (4.9 - 15.1)0.405ECMO parametersCreatinine (µmol/L)70.5 (51 - 149)100 (71 - 181)0.070PaO2:FiO2 ratio8.6 (7.3 - 9.9)8.3 (7.2 - 10.1)0.994PEEP (cm H20)13.3 (3.3)12.8 (3.3)0.657Tidal volume (mL)476.3 (118.4)495.0 (108.6)0.548Respiratory rate (RR, bpm)19.9 (4.8)20.0 (6.9)0.954Peak RR (bpm)32.6 (3.6)30.3 (5.2)0.058pH7.3 (0.1)7.3 (0.2)0.337PaO2 (kPa)7.9 (1.2)8.1 (1.8)0.722PaCO2 (kPa)8.6 (3.3)7.8 (3.0)0.361Base excess (mmol/L)2.7 (3.8)−0.8 (6.6)0.023Lactate (mmol/L)1.5 (0.6)2.2 (1.4)0.023Bicarbonate (HCO3, mmol/L)27.8 (4.6)23.7 (5.4)0.004MAP (mm Hg)78.5 (11.4)72.4 (11.8)0.048Days ventilated pre-ECMO4.9 (1.7)2.4 (2.5)<0.001OutcomesDays on ECMO13.2 (5.6)12.3 (8.0)0.601RRT9 (26%)24 (92%)<0.001Death16 (47%)8 (31%)0.288ALT – alanine aminotransferase; PEEP – positive end expiratory pressure; H2O – water; bpm - breaths per minute; PaO2/PaCO2 – partial pressure of arterial oxygen/carbon dioxide; MAP – mean arterial pressure; ECMO – extra-corporeal membrane oxygenation; RRT – renal replacement therapy. Open table in a new tab ALT – alanine aminotransferase; PEEP – positive end expiratory pressure; H2O – water; bpm - breaths per minute; PaO2/PaCO2 – partial pressure of arterial oxygen/carbon dioxide; MAP – mean arterial pressure; ECMO – extra-corporeal membrane oxygenation; RRT – renal replacement therapy. In this single-site, retrospective observational cohort study, we present the data from 34 patients admitted to one of the six UK severe respiratory failure centres who received ECMO support for COVID-19 pneumonitis. Earlier speculation by some teams about the potential application of ECMO suggested that it may be useful in severe cases of COVID-19, though this would depend very much on case selection. This speculation has since been borne out by more recent reports on single5Zhan W.Q. Li M.D. Xu M. Lu Y.B Successful treatment of COVID-19 using extracorporeal membrane oxygenation, a case report.Eur Rev Med Pharmacol Sci. 2020; 24: 3385-3389https://doi.org/10.26355/eurrev_202003_20705Crossref PubMed Scopus (28) Google Scholar,6Hu D. Liu K. Li B. Hu Z Large intracardiac thrombus in a COVID-19 patient treated with prolonged extracorporeal membrane oxygenation implantation.Eur Heart J. 2020; (ehaa524)https://doi.org/10.1093/eurheartj/ehaa524Crossref Scopus (13) Google Scholar, small7Yang Y. Rali A.S. Inchaustegui C. et al.Extracorporeal membrane oxygenation in coronavirus disease 2019-associated acute respiratory distress syndrome: an initial US experience at a high-volume centre.Card Fail Rev. 2020; 6 (Published 2020 Jun 26): e17https://doi.org/10.15420/cfr.2020.16Crossref PubMed Scopus (8) Google Scholar and larger8Mustafa A.K. Alexander P.J. Joshi D.J. et al.Extracorporeal membrane oxygenation for patients with COVID-19 in severe respiratory failure.JAMA Surg. 2020 Aug 11; (e203950)https://doi.org/10.1001/jamasurg.2020.3950Crossref PubMed Scopus (139) Google Scholar,9Schmidt M. Hajage D. Lebreton G. et al.Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with COVID-19: a retrospective cohort study.Lancet Respir Med. 2020; (S2213-2600(20)30328-3)https://doi.org/10.1016/S2213-2600(20)30328-3Abstract Full Text Full Text PDF Scopus (311) Google Scholar case series of patients with severe COVID-19, where the authors have been cautious about the potential benefits of ECMO in such patients, emphasising the limited capacity for this complex treatment. A recent ECMO consensus document10Shekar K. Badulak J. Peek G. et al.Extracorporeal life support organization coronavirus disease 2019 interim guidelines: a consensus document from an international group of interdisciplinary extracorporeal membrane oxygenation providers.ASAIO J. 2020; 66: 707-721https://doi.org/10.1097/MAT.0000000000001193Crossref PubMed Scopus (255) Google Scholar states this succinctly as: "ECMO is a highly technical therapy and is resource intensive. Although the distribution of this therapy should be as equitable as possible, during a pandemic such as COVID-19, distribution should focus on optimal candidates for recovery." In our case series presented here, it is difficult to conclude exactly how much the ECMO therapy contributed to the survival of these severely ill COVID-19 patients versus if they only had standard intensive care unit (ICU) support, as it was not possible for each patient to act as his/her own control in this comparison. However, as per our previous experience reported on seasonal influenza patients requiring ECMO2Charlton M. Dunn C. Dashey S. Lai F.Y. Tang J.W Severe influenza a cases requiring extra-corporeal membrane oxygenation (ECMO) therapy, 2018-2019.J Infect. 2020; 80: 469-496https://doi.org/10.1016/j.jinf.2019.12.009Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar it is likely that ECMO was more beneficial than not in this highly selected patient cohort. Download .docx (.23 MB) Help with docx files Download .docx (.02 MB) Help with docx files