Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has been used to treat acute respiratory distress syndrome (ARDS) in a total of > 3000 patients with COVID-19 in over 200 hospitals in Germany (1). At up to 68%, the mortality of these patients is very high compared with international registry data (1). Many of them required long-term VV-ECMO (> 30 days). Owing to the extended duration of extracorporeal support and the associated complications, which may lead to considerable mental stress for the treatment team and the relatives, this group of patients represent a particular challenge. Evidence on survival, functional status after discharge from hospital, and complications during intensive care treatment of these patients is sparse.
Table 2. Complications during intensive care treatment.
| Survivors (n = 26) | Deceased (n = 26) | |
| Acute kidney injury (KDIGO)* | 11 (42%) | 20 (77%) |
| Renal replacement therapy | 4 (15%) | 10 (38%) |
| Pulmonary embolism | 9 (35%) | 12 (46%) |
| Intracranial hemorrhage | 2 (8%) | 6 (23%) |
| Ischemic stroke | 1 (4%) | 3 (12%) |
| Major bleeding | 17 (65%) | 17 (65%) |
| Confirmed SSC | 0 | 5 (19%) |
* Acute kidney injury as defined by KDIGO
No patient underwent dialysis prior to extracorporeal membrane oxygenation.
KDIGO, Kidney Disease: Improving Global Outcomes; SSC, secondary sclerosing cholangitis
Acknowledgments
Translated from the original German by David Roseveare.
Footnotes
Conflict of interest statement
M. Malfertheiner has received consultancy fees from Eurosets and Medtronic. B. Salzberger was involved in the compilation of the DGIM guidelines on the treatment of COVID-19. F. Hitzenbichler has had travel costs and congress registration charges reimbursed by Gilead Sciences. F. Hanses is a member of the advisory boards of Sobi and GlaxoSmithKline. The remaining authors declare that no conflict of interest exists.
Methods
A retrospective study of the 137 patients who underwent VV-ECMO for the treatment of ARDS in COVID-19 at University Hospital Regensburg between March 2020 and March 2022.
Results
Survival, complications, functional status after discharge
Fifty-two patients (38%) required long-term VV-ECMO (median 49 days). Twenty-six (50%) of these patients were discharged from the hospital. There were no differences between those who died and those who survived at the beginning of the ECMO treatment (table 1). The complications that occurred during the patients’ time in the intensive care unit are summarized in Table 2.The median duration of follow-up was 4.4 months (IQR 1.5–12.5); one patient died after hospital discharge. Fifty percent of the patients who survived were transferred to a weaning center before their rehabilitation. The seven patients in rehabilitation can move around independently. With the exception of one man who needs a home respirator and dialysis, all patients who were discharged could be weaned off use of a tracheal cannula. The Karnofsky Index (KI) after rehabilitation was 70 (IQR 57.5–82.5). The patients’ median persisting stress dyspnea was WHO class 2 (IQR 1–3). Twelve of the 18 patients discharged from rehabilitation have a satisfactory self-rated quality of life; six patients’ quality of life was subjectively impaired. Four patients need routine daily nursing support. Four patients report symptoms of depression or anxiety; nevertheless, by their own criteria they are content with their life situation as it is. Two further patients were diagnosed with secondary sclerosing cholangitis (SSC) during the follow-up period.
Table 1. Patient characteristics at the beginning of VV-ECMO treatment.
| Parameter | Survivors with COVID-19 (n = 26) | Deceased with COVID-19 (n = 26) |
| General, previous illnesses, and disease course | ||
| Age (years) | 56.9 (48.8–61.8) | 59.9 (52.7–63.2) |
| Male sex n (%) | 21 (81) | 24 (92) |
| Body mass index (kg/m2) | 27.8 (26.4–33.0) | 29.4 (26.7–32.0) |
| Diabetes mellitus n (%) | 5 (19) | 3 (12) |
| Arterial hypertension n (%) | 8 (31) | 11 (42) |
| Prev. rheumatic disease n (%) | 2 (4) | 3 (12) |
| COPD n (%) | 1 (4) | 1 (4) |
| Active smoking n (%) | 3 (12) | 5 (19) |
| Days on VV-ECMO | 49 (37–65) | 44 (35–65) |
| SOFA score | 9 (8–10) | 9 (8–11) |
| Days of intubation beforestarting VV-ECMO | 5 (2–10) | 4 (1–12) |
| Days from symptom onset to VV-ECMO initiation | 14 (6–20) | 16 (11–20) |
| Virus variants and specific COVID-19 treatment | ||
| Wild-type variant n (%) | 10 (39) | 12 (46) |
| Alpha variant n (%) | 5 (19) | 7 (27) |
| Delta variant n (%) | 11 (42) | 7 (27) |
| Glucocorticoids n (%) | 26 (100) | 26 (100) |
| Reconvalescent plasma n (%) | 6 (23) | 7 (27) |
| Casivirimab, Imdevimab n (%) | 4 (15) | 0 |
| Remdesivir n (%) | 4 (15) | 7 (27) |
| Tocilizumab n (%) | 3 (12) | 2 (8) |
| Baricitinib n (%) | 3 (12) | 0 |
| Ventilation parameters, blood gas analysis, liver function tests | ||
| Peak pressure (mbar) | 32 (30–34) | 30 (29–35) |
| Pos. endexsp. pressure (mbar) | 15.0 (12.0–16.0) | 15.0 (13.0–15.5) |
| Dynamic pulmonarycompliance (mL/mbar) | 25 (18–32) | 29 (25–35) |
| PaO2/FiO2 ratio (mmHg) | 66 (56–89) | 68 (50–89) |
| PaCO2 (mmHg) | 62 (51–69) | 61 (52–78) |
| pH | 7.30 (7.26–7.36) | 7.28 (7.22–7.35) |
| Creatinine (mg/dL) | 0.8 (0.6–1.1) | 0.8 (0.6–1.1) |
| ALAT (U/L) | 48 (38–65) | 51 (34–83) |
| Bilirubin (mg/dL) | 0.7 (0.4–1) | 0.6 (0.4–0.9) |
| C-Reactive protein (mg/dL) | 130 (43–252) | 145 (24–258) |
| D-dimers (mg/L) | 4.5 (2–9) | 4 (2.75–12.5) |
| Interleukin 6 (pg/mL) | 70 (31–664) | 89 (44–490) |
| Interleukin 8 (ng/L) | 52.5 (29.5–80.5) | 46.0 (35.0–90.0) |
Continuous parameters are expressed as median and interquartile range, categorical parameters as absolute number and percentage. Longest treatment duration: 113 days in a patient who died, 93 days in a survivor. All patients were put in prone position at least once before starting ECMO. Thirty-one patients (60 %) were intubated by the ECMO team of University Hospital Regensburg (UHR) at other hospitals and then transported to UHR. ALAT, Alanine aminotransferase; FiO 2, inspiratory oxygen fraction; PaCo 2, carbon dioxide partial pressure; PaO 2, oxygen partial pressure; SOFA, Sequential Organ Failure Assessment; VV-ECMO, veno-venous extracorporeal membrane oxygenation
Specific characteristics of the patients who died
In the first 30 days of ECMO, the following characteristics were found exclusively in the patients who died: repeated (at least 2 ×) serum concentrations of interleukin (IL)-8 > 150 ng/L (n = 6), bilirubin > 5mg/dL for more than 7 days (n = 4), dynamic pulmonary compliance < 10 mL/mbar for more than 14 days (n = 5), ALAT > 400 U/L (n = 8). At least one of the first three of these criteria was found in 12 (46%) of the 26 patients who later died.
Discussion
Our case series, describing 50% survival with subjectively satisfactory quality of life and functionality (70%) after long-term ECMO treatment in patients with COVID-19, suggests that selected patients benefit from extended extracorporeal support of lung function. The survival rate is comparable to (2) or higher than (3) that reported in large studies from Germany and other countries. Care was taken to ensure that ECMO was indicated; retrospective analysis showed that none of the patients displayed any of the proposed contraindications (4). The previous illnesses and disease course are comparable with the findings described in other publications (2, 3).
The fact that only one patient died after discharge underscores the critical importance of weaning centers and rehabilitation in the post-intensive phase. The majority of patients were subjectively satisfied with their quality of life and their ability to participate in routine general activities.
In view of the enormous burden that long-term VV-ECMO places on physicians, nurses, relatives, and patients, it is essential to identify those patients who show an unfavorable course and may not benefit from continuation of this treatment regime. Because the groups did not differ in terms of their basic characteristics at the beginning of ECMO, we looked to see what clinical characteristics emerged in the first 30 days on VV-ECMO. Due to the complexity and dynamics of the illness, we took account only of characteristics that persisted or occurred repeatedly. Persistent hyperbilirubinemia—a sign of persistent liver function disorder—persistent severe pulmonary restriction, and persistence of pronounced symptoms of inflammation despite treatment, as described above, seem to point to an unfavorable course. These symptoms were identified during the first 30 days on ECMO in 46% of the patients who later died; they occurred exclusively in patients who did not survive. Given the low number of patients and the retrospective, single-center design, further research into predictors of an unfavorable outcome in patients on long-term ECMO is vital. The quality of life was not assessed with validated instruments.
Extended extracorporeal pulmonary support may be useful in patients with COVID-19 and may subsequently lead to subjectively satisfactory quality of life and functionality in the majority of cases, but owing to the serious risk of complications it should preferably be carried out in experienced centers. Predictors of the prognosis of patients on long-term VV-ECMO must be investigated in prospective studies.
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