Lung transplantation (LT) has emerged as a crucial life-saving option for critically ill patients with severe coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) or irreversible lung injury.[1] Intensive care unit-acquired weakness (ICU-AW) is a prevalent complication in critically ill patients.[2] The recovery of recipients undergoing LT for COVID-19-related respiratory failure may face impediments due to ICU-AW, which negatively affects early mobilization and functional improvement. This study describes two cases of successful bilateral LT for severe COVID-19-related ARDS with the occurrence of ICU-AW and subsequent successful discharge.
The first patient, a 59-year-old man, was positive for COVID-19 test and his condition gradually worsened. The details of the clinical characteristics and timeline are shown in Table 1 and supplementary Figure 1. On day 15, with a sudden drop in oxygen and unconsciousness, the patient was urgently intubated and transferred to the ICU. The next day, he developed cardiac arrest and was given cardiopulmonary resuscitation (CPR). Through the evaluation, veno-arterial extracorporeal membrane oxygenation (V-A ECMO) support was initiated. Following consultation and evaluation by a specialized team, the patient was recommended to undergo LT. Four months later, the patient was transferred to our hospital for LT. At the time of admission, the patient’s Medical Research Council (MRC) score was only 18, indicating the presence of ICU-AW. His trachea was incised, and ventilation was used to assist breathing intermittently. He was conscious and able to respond. A computed tomography (CT) scan revealed significant fibrosis in both lungs. Preoperative evaluation showed no significant abnormalities in the patient’s cardiac function, and we changed the patient’s V-A ECMO to veno-venous ECMO (V-V ECMO). When the matched donated lung was allocated by the organ allocation system, the patient underwent bilateral LT. Following surgery, ECMO removal occurred on day 1, and successful weaning from the ventilator was achieved on day 5. The chest X-rays and CT scans displayed the improvement in both lungs following surgery (Figure 1). During the postoperative care, bronchoscopy was periodically employed to maintain airway clearance. An invasive ventilation bridge with high-flow respiratory humidifier oxygen therapy was utilized, complemented by intensified respiratory function exercises. The patient’s daily nutrition and caloric supply were meticulously maintained. The rehabilitation protocol included an upright seated position, upper and lower extremity function exercises (mobility and muscle strength training), mobilization training (sitting the edge of the bed, standing, moving between surfaces [e.g., seat, wheelchair], and progressively walking longer with decreasing levels of assistance). Two months after surgery, the patient underwent replacement of the metal tracheostomy tube, which was subsequently sealed two days later. He was transferred out of the ICU to the ward on day 125 after LT. Following a period of rehabilitation, he fully recovered and was ultimately discharged from the hospital 144 d after LT.
Table 1. Clinical characteristics of two cases with lung transplantation for COVID-19-related respiratory failure
| Clinical characteristics | Patient 1 | Patient 2 |
|---|---|---|
| Gender | Male | Male |
| Age, years | 59 | 61 |
| Body Mass Index | 22.5 | 23.3 |
| Charlson Comorbidity Index score | 4 | 3 |
| Primary disease | Severe pneumonia | Severe pneumonia |
| Transplant type | Bilateral | Bilateral |
| Duration of supportive therapy | ||
| MV duration, d | 136 | 23 |
| MV duration before lung transplantation, d | 131 | 15 |
| ECMO duration, d | 131 | 16 |
| ECMO duration before lung transplantation, d | 130 | 15 |
| Drugs | ||
| Glucocorticoid (duration a, d) | Yes (146) | Yes (57) |
| Norepinephrine | Yes | Yes |
| Adrenaline | Yes | No |
| NMBAs | Yes | Yes |
| Time and depth of sedationa | ||
| Sedation duration, h | 670.5 | 291.5 |
| Deep sedation duration, h | 9.5 | 192.5 |
| Light sedation duration, h | 661 | 99 |
| Blood glucose range a, mmol/L | 5.4-24.1 | 5.3-13.0 |
| Duration of ICU-AW a, d | 112 | 34 |
| APACHE II score | 18 | 23 |
| Medical Research Council score | 18 | 24 |
| Length of ICU stay, d | 256 | 45 |
| Length of hospital stay, d | 290 | 84 |
| Donor | DBD | DBD |
| Ischemic time of left lung, h | 7.38 | 6.33 |
| Ischemic time of right lung, h | 6.48 | 4.78 |
MV: mechanical ventilation; ECMO: extracorporeal membrane oxygenation; NMBAs: neuromuscular blocking agents; APACHE II: Acute Physiology and Chronic Health Evaluation II; ICU-AW: ICU-acquired weakness; DBD: donation after brain death; a: treatment details of patients after transfer to our hospital.
Figure 1.
Figure 1.
Chest imaging changes in patient 1. A and B: CT scans of the chest before LT (A) and on day 9 after LT (B); C, D, and E: chest X-rays before LT (C), on day 1 (D), and on day 9 (E) after LT. CT: computed tomography; LT: lung transplantation.
The second patient, a 61-year-old male, initially presented with fever, chills, cough, and sputum production, testing positive for COVID-19. Despite glucocorticoid and antibiotic therapy, the patient was transferred to the ICU due to worsening conditions on day 4 of hospitalization, followed by endotracheal intubation and V-V ECMO. A chest CT revealed diffuse exudation and fibrosis in both lungs. After consultation and evaluation by a multidisciplinary team, LT was recommended. He was listed on the waiting list. When the donated matched donor lung was allocated by the organ allocation system, the patient underwent successful bilateral LT. Postoperatively, comprehensive treatment, including anti-infection, anti-rejection, and rehabilitation exercises, was administered. The patient was successfully weaned from ECMO on day 1 after surgery, and the tracheal tube was removed on day 8 (supplementary Figure 1). The chest X-rays and chest CT scans revealed marked improvement following transplantation (Figure 2). However, on the second day after surgery, the muscle strength of the patient significantly decreased after he was awake, and the MRC score was 24. The patient developed ICU-AW. He subsequently received comprehensive and multidisciplinary rehabilitation interventions involving pulmonary rehabilitation, nutritional support and exercise-based rehabilitation. These included passive and active limb exercise training, joint motion training, and respiratory muscle training, such as cough exercises, ball blowing exercises, upright seated positions, bed bicycle exercises, and standing and mobilization exercises. After rehabilitation exercise treatment, the ICU-AW improved. The patient was transferred out of the ICU on day 22 after LT and entered the ward. His upper and lower limb strength improved. The patient was discharged home for rehabilitation on the 57th postoperative day without oxygen inhalation.
Figure 2.
Figure 2.
Chest imaging changes in patient 2. A and B: CT scans of the chest before LT (A) and on day 5 after LT (B); C, D, and E: chest X-rays before LT (C), on day 1 (D), and on day 5 (E) after LT. CT: computed tomography; LT: lung transplantation.
Critically ill COVID-19 patients might rapidly progress to severe ARDS or irreversible acute lung injury, and LT could become a life-saving option for those who cannot be salvaged by other treatment methods. A multicenter study analyzed 12 patients who underwent LT for severe COVID-19 infection and revealed that the pathology of the explanted lungs revealed extensive and ongoing acute lung injury, with characteristics indicative of lung fibrosis.[3] For critically ill non-transplant patients who survived from COVID-19 infection, a prospective study also conducted a 6-month follow-up of patients.[4] The results indicated that more than one-third of severe COVID-19 pneumonia survivors exhibited pulmonary fibrosis-like changes. Notably, the lung injury caused by COVID-19 might lead to progressive pulmonary fibrosis and even multiple organ failure. Given the lack of suitable antifibrotic medications, COVID-19-related pulmonary fibrosis remains a significant challenge. Few reports have described ICU-AW in LT recipients for COVID-19. However, it is a recognized complication in critically ill patients. In the present cases, the patients underwent successful bilateral LT. This salvaging lung transplant surgery significantly improved the unfavorable prognosis and prolonged survival. However, perioperative management based on LT is challenging. Both patients experienced ICU-AW, leading to decreased limb muscle strength and weakness, substantially hindering autonomous exercise, rehabilitation, and organ function recovery. The factors contributing to ICU-AW included prolonged immobilization, extended ICU hospitalization, prolonged MV, and the administration of sedatives, neuromuscular blockers, and corticosteroids. Furthermore, hyperglycemia was identified as a risk factor for ICU-AW. It is recommended that blood glucose be tightly controlled to prevent hyperglycemia and thereby reduce risk.[5] Additionally, ECMO provides extracorporeal support for refractory cardiopulmonary failure and bridge options for lung transplants.[6,7] A prior retrospective study reported an 80% prevalence of ICU-AW in the ECMO population, confirming the presence of these risk factors in the discussed cases and their potential contribution to ICU-AW development.[8] ICU-AW has been associated with adverse outcomes, including an elevated risk of ICU and in-hospital mortality.[9] Hence, prioritizing early rehabilitation for posttransplant recipients is critical in ICU management. The evidence supports the safety and benefits of early rehabilitation in improving muscle strength, long-term cognitive function, and health-related quality of life in critically ill patients.[10] Furthermore, given the detrimental impact of ICU-AW, emphasizing its management during the perioperative period or long-term intensive care after LT is imperative to mitigate potential risks.
In conclusion, this study demonstrates that successful LT may significantly improve poor prognosis and extend survival in recipients with COVID-19-related ARDS, despite being complicated by ICU-AW.
Funding: This work was supported by a grant from the National Natural Science Foundation of China (82072201).
Ethical approval: This study was approved by the Research Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (2023-1203).
Conflicts of interest: The authors have no conflicts of interest.
Contributors: JC and BQY contributed to the conception and design of this case report. JC was responsible for collecting the data. JC and BQY wrote the first draft of the manuscript. MH and JYC revised and supervised all aspects of the development of the manuscript. All the authors read and approved the final manuscript.
All supplementary files in this paper are available at http://wjem.com.cn.
Reference
Lung transplants for COVID-19 similarly successful
Intensive care unit-acquired muscle weakness in COVID-19 patients
Intensive Care Med.
Early outcomes after lung transplantation for severe COVID-19: a series of the first consecutive cases from four countries
DOI:10.1016/S2213-2600(21)00077-1
PMID:33811829
[Cited within: 1]
Lung transplantation is a life-saving treatment for patients with end-stage lung disease; however, it is infrequently considered for patients with acute respiratory distress syndrome (ARDS) attributable to infectious causes. We aimed to describe the course of disease and early post-transplantation outcomes in critically ill patients with COVID-19 who failed to show lung recovery despite optimal medical management and were deemed to be at imminent risk of dying due to pulmonary complications.We established a multi-institutional case series that included the first consecutive transplants for severe COVID-19-associated ARDS known to us in the USA, Italy, Austria, and India. De-identified data from participating centres-including information relating to patient demographics and pre-COVID-19 characteristics, pretransplantation disease course, perioperative challenges, pathology of explanted lungs, and post-transplantation outcomes-were collected by Northwestern University (Chicago, IL, USA) and analysed.Between May 1 and Sept 30, 2020, 12 patients with COVID-19-associated ARDS underwent bilateral lung transplantation at six high-volume transplant centres in the USA (eight recipients at three centres), Italy (two recipients at one centre), Austria (one recipient), and India (one recipient). The median age of recipients was 48 years (IQR 41-51); three of the 12 patients were female. Chest imaging before transplantation showed severe lung damage that did not improve despite prolonged mechanical ventilation and extracorporeal membrane oxygenation. The lung transplant procedure was technically challenging, with severe pleural adhesions, hilar lymphadenopathy, and increased intraoperative transfusion requirements. Pathology of the explanted lungs showed extensive, ongoing acute lung injury with features of lung fibrosis. There was no recurrence of SARS-CoV-2 in the allografts. All patients with COVID-19 could be weaned off extracorporeal support and showed short-term survival similar to that of transplant recipients without COVID-19.The findings from our report show that lung transplantation is the only option for survival in some patients with severe, unresolving COVID-19-associated ARDS, and that the procedure can be done successfully, with good early post-transplantation outcomes, in carefully selected patients.National Institutes of Health. VIDEO ABSTRACT.Copyright © 2021 Elsevier Ltd. All rights reserved.
Six-month follow-up chest CT findings after severe COVID-19 pneumonia
Intensive care unit-acquired weakness: recent insights
Lung transplantation in pulmonary fibrosis secondary to influenza A pneumonia
Use of veno-arterial extracorporeal membrane oxygenation ian the first successful combined lung-liver transplantation patient in China
DOI:10.5847/wjem.j.1920-8642.2022.090 PMID:36119762 [Cited within: 1]
Intensive care unit-acquired weakness in patients with extracorporeal membrane oxygenation support: frequency and clinical characteristics
ICU-acquired weakness
DOI:10.1007/s00134-020-05944-4
PMID:32076765
[Cited within: 1]
Critically ill patients often acquire neuropathy and/or myopathy labeled ICU-acquired weakness. The current insights into incidence, pathophysiology, diagnostic tools, risk factors, short- and long-term consequences and management of ICU-acquired weakness are narratively reviewed. PubMed was searched for combinations of "neuropathy", "myopathy", "neuromyopathy", or "weakness" with "critical illness", "critically ill", "ICU", "PICU", "sepsis" or "burn". ICU-acquired weakness affects limb and respiratory muscles with a widely varying prevalence depending on the study population. Pathophysiology remains incompletely understood but comprises complex structural/functional alterations within myofibers and neurons. Clinical and electrophysiological tools are used for diagnosis, each with advantages and limitations. Risk factors include age, weight, comorbidities, illness severity, organ failure, exposure to drugs negatively affecting myofibers and neurons, immobility and other intensive care-related factors. ICU-acquired weakness increases risk of in-ICU, in-hospital and long-term mortality, duration of mechanical ventilation and of hospitalization and augments healthcare-related costs, increases likelihood of prolonged care in rehabilitation centers and reduces physical function and quality of life in the long term. RCTs have shown preventive impact of avoiding hyperglycemia, of omitting early parenteral nutrition use and of minimizing sedation. Results of studies investigating the impact of early mobilization, neuromuscular electrical stimulation and of pharmacological interventions were inconsistent, with recent systematic reviews/meta-analyses revealing no or only low-quality evidence for benefit. ICU-acquired weakness predisposes to adverse short- and long-term outcomes. Only a few preventive, but no therapeutic, strategies exist. Further mechanistic research is needed to identify new targets for interventions to be tested in adequately powered RCTs.
Effect of early mobilisation on long-term cognitive impairment in critical illness in the USA: a randomised controlled trial
DOI:10.1016/S2213-2600(22)00489-1
PMID:36693400
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Patients who have received mechanical ventilation can have prolonged cognitive impairment for which there is no known treatment. We aimed to establish whether early mobilisation could reduce the rates of cognitive impairment and other aspects of disability 1 year after critical illness.In this single-centre, parallel, randomised controlled trial, patients admitted to the adult medical-surgical intensive-care unit (ICU), at the University of Chicago (IL, USA), were recruited. Inclusion criteria were adult patients (aged ≥18 years) who were functionally independent and mechanically ventilated at baseline and within the first 96 h of mechanical ventilation, and expected to continue for at least 24 h. Patients were randomly assigned (1:1) via computer-generated permuted balanced block randomisation to early physical and occupational therapy (early mobilisation) or usual care. An investigator designated each assignment in consecutively numbered, sealed, opaque envelopes; they had no further involvement in the trial. Only the assessors were masked to group assignment. The primary outcome was cognitive impairment 1 year after hospital discharge, measured with a Montreal Cognitive Assessment. Patients were assessed for cognitive impairment, neuromuscular weakness, institution-free days, functional independence, and quality of life at hospital discharge and 1 year. Analysis was by intention to treat. This trial was registered with ClinicalTrials.gov, number NCT01777035, and is now completed.Between Aug 11, 2011, and Oct 24, 2019, 1222 patients were screened, 200 were enrolled (usual care n=100, intervention n=100), and one patient withdrew from the study in each group; thus 99 patients in each group were included in the intention-to-treat analysis (113 [57%] men and 85 [43%] women). 65 (88%) of 74 in the usual care group and 62 (89%) of 70 in the intervention group underwent testing for cognitive impairment at 1 year. The rate of cognitive impairment at 1 year with early mobilisation was 24% (24 of 99 patients) compared with 43% (43 of 99) with usual care (absolute difference -19·2%, 95% CI -32·1 to -6·3%; p=0·0043). Cognitive impairment was lower at hospital discharge in the intervention group (53 [54%] 99 patients vs 68 [69%] 99 patients; -15·2%, -28·6 to -1·7; p=0·029). At 1 year, the intervention group had fewer ICU-acquired weaknesses (none [0%] of 99 patients vs 14 [14%] of 99 patients; -14·1%; -21·0 to -7·3; p=0·0001) and higher physical component scores on quality-of-life testing than did the usual care group (median 52·4 [IQR 45·3-56·8] vs median 41·1 [31·8-49·4]; p<0·0001). There was no difference in the rates of functional independence (64 [65%] of 99 patients vs 61 [62%] of 99 patients; 3%, -10·4 to 16·5%; p=0·66) or mental component scores (median 55·9 [50·2-58·9] vs median 55·2 [49·5-59·7]; p=0·98) between the intervention and usual care groups at 1 year. Seven adverse events (haemodynamic changes [n=3], arterial catheter removal [n=1], rectal tube dislodgement [n=1], and respiratory distress [n=2]) were reported in six (6%) of 99 patients in the intervention group and in none of the patients in the usual care group (p=0·029).Early mobilisation might be the first known intervention to improve long-term cognitive impairment in ICU survivors after mechanical ventilation. These findings clearly emphasise the importance of avoiding delays in initiating mobilisation. However, the increased adverse events in the intervention group warrants further investigation to replicate these findings.None.Copyright © 2023 Elsevier Ltd. All rights reserved.
