key: cord-0842127-halr93kb
authors: Taylor, Lauren J.; Jolley, Sarah E.; Ramani, Chintan; Mayer, Kirby P.; Etchill, Eric W.; Mart, Matthew F.; Fakhri, Shoaib; Peterson, Skyler; Colborn, Kathryn; Sevin, Carla M.; Kadl, Alexandra; Enfield, Kyle; Whitman, Glenn J.R.; Zwischenberger, Joseph B.; Rove, Jessica Y.; Montgomery-Yates, Ashley A.; Parker, Ann M.; Teman, Nicholas R.; Hoffman, Jordan; Bartels, Karsten; Kim, Bo Soo; Cho, Sung-Min; Hippensteel, Joseph A.
title: Early Post-Hospitalization Recovery after Extracorporeal Membrane Oxygenation in Survivors of COVID-19
date: 2022-03-14
journal: J Thorac Cardiovasc Surg
DOI: 10.1016/j.jtcvs.2021.11.099
sha: 55f0fbfa3d8cedda929aa5bb73dc3c7e2016748b
doc_id: 842127
cord_uid: halr93kb

Objective We sought to determine the impact of VV-ECMO on outcomes of mechanically ventilated patients with COVID-19 in the first 120 days after hospital discharge. Methods Five academic centers conducted a retrospective analysis of mechanically ventilated patients with COVID-19 admitted March through May 2020. Survivors had access to a multi-disciplinary post-intensive care recovery clinic. Physical, psychological, and cognitive deficits were measured using validated instruments and compared based on ECMO status. Results 262 mechanically ventilated patients were compared to 46 patients cannulated for VV-ECMO. ECMO patients were younger and travelled farther but there was no significant difference in gender, race, or BMI. ECMO patients were mechanically ventilated for longer durations (median 26 days IQR 19.5, 41 vs 13 days IQR 7, 20) and were more likely to receive inhaled pulmonary vasodilators, neuromuscular blockade, investigational COVID-19 therapies, blood transfusions and inotropes. ECMO patients experienced greater bleeding and clotting events (p<0.01). However, survival at discharge was similar (69.6% vs 70.6%). Of the 217 survivors, 65.0% had documented follow up within 120 days. Overall, 95.5% were residing at home, 25.7% had returned to work or usual activity and 23.1% were still using supplemental oxygen; these rates did not differ significantly based on ECMO status. Rates of physical, psychological and cognitive deficits were similar. Conclusions Our data suggest that COVID-19 survivors experience significant physical, psychological, and cognitive deficits following ICU admission. Despite a more complex critical illness course, longer average duration of mechanical ventilation and longer average length of stay, patients treated with VV-ECMO had similar survival at discharge and outcomes within 120 days of discharge.

Data from all sites were combined for analysis. Patient demographics and in-hospital 219 characteristics, including survival at discharge were compared based on ECMO status using chi-220 squared tests for categorical variables and t-tests or Kruskal Wallis tests for continuous variables. 221

For the subset of survivors who had available long-term outcomes data, the incidence of mental, 222 physical and cognitive dysfunction as well as place of residence and use of supplemental oxygen 223

were assessed using chi-squared tests based on ECMO status. The validated scales used to assess 224 cognitive and mental impairment were dichotomized into normal versus abnormal results 225 consistent with clinical practice. P-values of <0.05 were considered statistically significant. Due 226 to the small sample sizes in this observational cohort, we have interpreted any p-values greater 227 than 0.05 as inconclusive rather than non-significant. Analyses were performed using R software 228 Intubated and paralyzed, patients were unable to advocate for themselves. Family members were 286 prohibited to visit and over the phone they asked if it was realistic to hope that their family 287 member would regain meaningful quality of life. At the time, we could only confess that we did 288 not know for sure. Striving to find answers to these questions was the impetus for forming 289

In this retrospective, observational study, survivors of COVID-19 who required 291 mechanical ventilation experience significant deficits following ICU admission (Figure 3) . 292

Patients who failed mechanical ventilation and were also treated with VV-ECMO based on 293 ELSO guidelines during the first wave of the pandemic had a more complex critical illness 294 course, longer average duration of mechanical ventilation and longer average length of stay, but 295 similar survival at discharge and similar outcomes 120 days thereafter. While these findings are 296 encouraging, rates of PICS were high in all study patients; providers evaluating patient 297 candidacy for ECMO should be informed of post-hospitalization sequelae beyond mortality. 298

It is important to review our findings in the context of two multi-center randomized-299 controlled trials, CESAR and EOLIA, which offer pre-COVID mortality data for ECMO in 300 patients with severe ARDS. 24,25 The CESAR trial advocates for transfer to an ECMO center for 301 adults with severe but potentially reversible respiratory failure based on improved six-month 302 survival without severe disability (63 versus 47%). However, enthusiasm for these results has 303 been tempered by methodologic concerns including lack of control group standardization. 304 Subsequent investigation in the EOLIA trial failed to demonstrate a significant benefit in 60-day 305 mortality for patients supported with ECMO as compared to conventional mechanical ventilation 306 but there was significant crossover of patients into the ECMO group. Interestingly, a recent 307 meta-analysis combining data from these two trials demonstrated improved 90-day mortality 308 associated with ECMO (36% versus 48%, p=0.013). Furthermore, at 60 days post-309 randomization, ECMO was associated with increased number of days out of the ICU as well as 310 days without vasopressor support, renal replacement therapy or neurologic failure. 26 311 This is the largest multicenter analysis to date comparing post-hospitalization outcomes 312 of patients with COVID-19 requiring mechanical ventilation and VV-ECMO support. Of 313 survivors with documented follow up at four months, 95.5% were living at home, but in this 314 early post-hospitalization period only a quarter were back to work or usual activity and 315 significant impairments associated with PICS were identified. Over half of patients who 316 underwent cognitive assessment after mechanical ventilation and ECMO for COVID-19 317 associated ARDS reported cognitive dysfunction, with higher rates in the ECMO cohort. 318

Depression, anxiety or PTSD were less frequently screened for but present in a third of those 319 tested. ICU acquired weakness was present in half of survivors and nearly all of the survivors 320 who were assessed had an abnormal 6 minute walk distance. A quarter of patients still required 321 supplemental oxygen and nearly half of those tested had abnormal spirometry. These data help 322 providers, patients and families begin to understand the potential extended sequelae of this 323 critical illness. 324

We recall during the first COVID pandemic wave that several questioned the use of 325 ECMO because of increased manpower, equipment, and hospital bed utilization. Based on these 326 concerns ELSO issued a consensus of conservative guidelines for use. All five centers in this 327 study participate in ELSO and followed the early recommendations; as expected, the first wave 328 of ECMO patients were younger with few comorbidities. It is notable that despite a more 329 complex in-hospital course, patients who were selectively treated with ECMO and survived did 330 In summary, our study demonstrated significant physical, psychological, and cognitive 366 deficits at four months following COVID-19 associated critical illness. However, ECMO support 367 directed by early ELSO guidelines in specialized centers was not associated with worse survival 368 or post-hospitalization outcomes compared to other ICU survivors. As many are doing, these 369 data may prompt ongoing adjustments of cannulation criteria. However, further investigation 370 with a prospective trial is needed to better understand post-hospitalization outcomes and mitigate 371 the impact of PICS in survivors treated with ECMO. The ORACLE research collaborative is 372 actively working on gathering data for a larger cohort with extended follow up to one-year post 373 discharge. Post-ICU recovery clinics offer a unique opportunity for ongoing assessment of 374 critical illness survivors and may be harnessed to gather long-term data for a broader cohort of 375 cardiothoracic surgical patients while simultaneously offering coordinated multidisciplinary 376 evaluation and physical, psychological and cognitive therapies to maximize the recovery of 377 

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AATS 2021 Meeting Early Post-Hospitalization Recovery After Extracorporeal Membrane Oxygenation in Survivors

Thank you for your question. Yes, data collection is ongoing. We have these multidisciplinary post-ICU recovery clinics. They are at various states of, I'd say, thoroughness at various institutions. For example, at Vanderbilt, their clinics have been ongoing for quite some time before the pandemic. At our institution, University of Colorado, the pandemic was an impetus to get these clinics going. At this point, we're working on creating an actual in-person multidisciplinary clinic where we can have more of an organized data collection for these long-term outcomes for patients. Right now we're approaching the time where we can get the one-year follow-up for these patients