Recovery of skeletal muscle strength and physical function in a patient with (post) COVID-19 requiring extra-corporeal membrane oxygenation

ABSTRACT

Background

The ongoing coronavirus-19 disease (COVID-19) has taught us that early mobilization is essential for functional recovery during and after prolonged intensive care unit (ICU) stay. This especially applies for patients receiving a challenging combination of prolonged invasive treatments such as mechanical ventilation (MV) and extra-corporeal membrane oxygenation (ECMO). This case report describes the recovery of skeletal muscle strength and physical function in a patient (post) COVID-19 during ICU stay.

Case Description

A 54 year old female patient was diagnosed with COVID-19 pneumonia, and ultimately needed ICU treatment with MV and ECMO for 69 days during which she received physiotherapy treatment.

Outcomes

The patient recovered from intensive care acquired muscle weakness (ICUAW) at day 53, resulting in the ability to walk at day 62. She was discharged from the ICU after 69 days with the ability to walk 20 meters with support of one person and a mobility aid. No evident adverse events were noted during or after physiotherapy sessions.

Discussion

Early mobilization is feasible and safe in a patient (post) COVID-19 with prolonged ECMO treatment and facilitates functional recovery during ICU stay. This single case observation should be handled with caution and needs further validation.

KEYWORDS:

• Early mobilization
• critical illness
• muscle weakness
• ambulation

Background

The ongoing coronavirus-19 disease (COVID-19) pandemic has taught us that a COVID-19 infection has a substantial impact on functional status post-COVID (Nalbandian et al., 2021), especially in the post-intensive care unit (ICU) patients (Huang et al., 2021; Parker et al., 2021). About a quarter of the patients with COVID-19 admitted to the hospital require medical treatment at the ICU of which about 6% ultimately require rescue therapies such as extra-corporeal membrane oxygenation (ECMO) (Ñamendys-Silva, 2020; Parker et al., 2021).

Approximately three-quarters of those admitted to ICU with COVID-19 require infusion with neuromuscular blocking agents (Parker et al., 2021). In the authors’ opinion the use of neuromuscular blocking agents is expected to be even higher in patients with COVID-19 on ECMO. However, the sedation and chemical paralytic infusion levels are comparable to non-COVID-19 patients on ECMO (Bohman et al, 2022). Still the use of neuromuscular blocking agents adds cumulatively to known risk factors for the development of ICU acquired muscle weakness (ICUAW) such as the use of glucocorticoids, physical inactivity and critical illness (Kress and Hall, 2014). This effect even seems to be exaggerated in patients with COVID-19 (de Andrade-Junior et al., 2021).

As a consequence about half of the patients (post) COVID-19 who survived ICU treatment developed ICUAW at ICU discharge (Van Aerde et al., 2020) of which a quarter persisted at hospital discharge (Van Aerde et al., 2020) even in patients without any prior functional limitation (Paneroni et al., 2021). Thereby, the incidence of ICUAW at variable time-points seems to exceed the incidence of ICUAW in patients without COVID-19 in previous ICU cohorts (Hermans and Van den Berghe, 2015).

Especially for critically ill patients with COVID-19 who developed ICUAW during ECMO treatment early mobilization (i.e. passive and/or active mobilization at the earliest opportunity) is challenging, but of evident clinical importance to regain skeletal muscle strength (Zhang et al., 2019) and to enhance weaning from the ventilator and physical recovery (Parker et al., 2021; Polastri, Swol, Loforte, and Dell’Amore, 2022). The purpose of this case report is to describe the recovery of skeletal muscle strength and physical function of a patient with (post) COVID-19 during and after ECMO support. The multidisciplinary approach and strategies which facilitated early mobilization are particularly highlighted.

Case description

Procedures concerning this case report (i.e. informed consent, privacy, and data handling) meet the regulations concerning case reports developed by the department of Good Research Practice of the Leiden University Medical Center, Leiden, Netherlands. Written patient informed consent for use of anonymized data, publication of the manuscript, and use of the photograph was obtained and administered after the patient had been given the opportunity to read the manuscript. No Medical Ethical approval was necessary.

Medical treatment

The case was a 54 year old female patient not fully vaccinated against COVID-19 with a medical history of asthma, hypertension, obesity, obstructive sleep apnea syndrome, and fibromyalgia, without any prior physical dysfunction who presented to the emergency room of a regional hospital. She was diagnosed with COVID-19 pneumonia, 90% of lung-tissue affected (evaluated with computed tomography (CT) of the chest) without pulmonary embolism. She was admitted to the general ward, but after 3 days she was transferred to the ICU because of hypoxemia for which she was intubated and mechanically ventilated. At ICU admission she was treated with Dexamethasone 6 mg every day and received a single dose of 520 mg of anti-interleukin-6 (IL-6) receptor monoclonal antibodies (Tocilizumab). During the first 7 ICU days she was deeply sedated as operationalized with a score “-5” on the Richmond Agitation-Sedation Scale (RASS) (Sessler et al., 2002) with an average of 40 mg/hour of midazolam and received 25 micrograms/hour of sufentanyl. Furthermore, she received several days of neuromuscular blocking agents with an average of 20 mg/hour of rocuronium titrated to a train-of-four of 0 and prone positioning.

Hypoxemia remained refractory to maximal ventilatory support (pressure controlled), high fractions of inspired oxygen (FiO₂) (i.e. FiO₂ 80%) and periods of prone positioning and therefore she was referred to a tertiary center for veno-venous (V–V) ECMO consideration. She was eventually treated with V–V ECMO using a 28Fr Crescent jugular dual-lumen catheter (Medtronic, USA) placed in the right internal jugular vein under fluoroscopy and trans-thoracic echo-cardiography guidance in the catheterization laboratory and connected to a Cardiohelp device (Getinge) with an HLS set advanced 7.0 set (Getinge). At the start of the ECMO-run she received high doses of methylprednisolone of 1000 mg every day for three days followed by 75 mg of prednisolone every day tapered off over 6 weeks. The patient was on ECMO in two runs deviated by 4 days in which the second run was necessary due to recurrent acute respiratory distress syndrome (ARDS) which was refractory to pronation.

Overall she had been on ECMO for a total duration of 54 days and a total ICU length of stay of 69 days during which she also received a tracheal cannula to facilitate weaning from MV. In the first 7 days the patient was deeply sedated and received neuromuscular blockers. Thereafter, the level and intensity of sedation were gradually reduced and the patient received only dexmedetomidine (preserving respiratory drive), and low doses of midazolam and sufentanil. This allowed for a transition from pressure-controlled mandatory ventilation (P-CMV) to a pressure support ventilation mode (SPONT).

After 67 days the tracheal cannula could be removed and she only needed 1 to 2 L/min standard oxygen (O₂) therapy via a nasal cannula during rest and exercise, respectively. Meanwhile, the patient was considered negative for COVID after 23 days at the ICU whereafter the use of full personal protective equipment for caregivers was stopped.

Physiotherapy treatment

During medical treatment for critical illness at the ICU, physiotherapy was involved on a daily base from day one according to best practice based on current Dutch COVID-specific ICU recommendations (Felten-Barentsz et al., 2020) and a general ICU evidence statement (Sommers et al., 2015). Generally, the physiotherapy interventions on the COVID-ICU were divided into two phases: 1) phase A, when the patient is (fully) sedated; and 2) phase B, when the sedation is stopped). However, there is a gradual transition between these two phases.

Physiotherapy at the (full) sedation phase

Overall in this phase A the patient is (fully) sedated. The primary focus is the prevention of contractures in the absence of neuromuscular blocking. During pronation and when under neuromuscular blocking, no physiotherapist was involved as the risk of contractures is considered negligible while under neuromuscular blocking (Felten-Barentsz et al., 2020). No active mobilization is possible.

Physiotherapy at the awakening phase

In this phase sedation is stopped or decreased and active mobilization is possible. Patients in both phases could still be on MV. Physiotherapy interventions concerning mobilizations were merely described in terms of in- and out-bed activities. Exercise therapy was started in the absence of general ICU-related (relative) contraindications for active mobilization as screened by the involved physiotherapist (Sommers et al., 2015). Before commencing supported standing and walking core stability and strength of the lower extremities were checked by the physiotherapist. Sitting core stability should be adequate to remain stable with minimal support of one person and strength of the knee extension muscles should be at least enough to overcome gravity. Additionally, the perfusionist checked the adequate position of the cannula, which was secured with a headband (Eden et al., 2017). Second, the perfusionist’s criteria to permit enhanced levels of out-bed mobilization were: 1) a resting venous oxygen saturation (SvO₂) > 65% to account for additional oxygen consumption during exercise; 2) ECMO system inlet pressures > 30 mmHg to allow adequate circulation in vertical position; and 3) a sweep gas flow < 10 L/min to preserve adequate CO₂ wash-out in rest, which provides some reserve to increase sweep gas flow during mobilization (Abrams et al., 2014; Polastri, Loforte, Dell’Amore, and Nava, 2016). Physiotherapy was postponed or canceled if the perfusionist’s criteria deviated from recommended levels. For safety a wheelchair was available to be able to put the patient in a seated position immediately at all time.

Outcomes

As insight in the trend of parameters of functional recovery (i.e. skeletal muscle strength and physical function) is essential to coordinate and prioritize multidisciplinary team efforts, the physiotherapist is responsible for monitoring of these parameters. Follow-up of skeletal muscle strength and detection of ICUAW were performed by the involved physiotherapists with assessment of handgrip strength (HGS) and the Medical Research Council (MRC) sum-score according to the protocol and strategy of Parry et al. (2015).

Physical function was measured and monitored by the involved physiotherapists with the Chelsea Critical Care Physical Assessment tool (CPAx) which is a composite measure of ten components of physical function varying from complete dependence to independence (i.e. breathing, airway clearance, transfers in and out bed, standing, walking, skeletal muscle strength) (Corner et al., 2013).

Both measurements are part of usual care follow-up and are standardly conducted at baseline when the physiotherapist decides that the patient is sufficiently responsive and cooperative based on both the RASS (between −2 and +2) and the Standardized Five Questions [(S5Q) ≥ 3] (Sommers et al., 2015) respectively, and in the absence of (relative) contraindications for active mobilization as previously mentioned. Furthermore, assessments are regularly repeated at ICU discharge and preceding events and milestones such as extubation, liberation from ECMO, or first out of bed transfer. All primary ICU physiotherapists are experienced and trained in the conduction of both measurements, and calibration sessions between colleagues revealed negligible differences in outcomes.

As presented in Table 1 during the initial phase while under sedation and various periods of neuromuscular blocking and in the absence of contraindications such as minimal handling the primary aim on the domain of the physiotherapy was the prevention of contractures as these could hamper physical recovery when the patient starts being awake and able to exercise. After that initial phase of 41 days the patient started being awake and cooperative. At day 42 in-bed chair positioning was started which could be increased to out-bed chair positioning [Sara Combilyzer® (Arjo Huntleigh)] at day 45 and standing in a tilt table (Sara Combilyzer®) at day 47. Physical activities such as in bed strength training and in-bed cycling were further increased under continuous monitoring by the physiotherapist of the adequacy of physiological response using specific general ICU-related stopping criteria such as: hemodynamical instability (mean arterial pressure < 65 mmHg; > 110 mmHg); deoxygenation (peripheral oxygen saturation (SpO₂) < 90%); inadequate or disproportional response of heart rate (< 40 beats per minute; > 130 beats per minute); and irregularity of heart rate (signs of arrhythmia) (Sommers et al., 2015). Ultimately after 49 days the patient was able to stand with a standing aid and at day 62 the patient could start walking while still on the mobile ECMO circuit. For walking she needed a mobility aid and support of two persons (Figure 1) while on continuous monitoring of the parameters and their responses as mentioned above, with additional ECMO-related criteria such as presence of bleeding around the cannula (Braune et al., 2020) and ECMO flow and negative inlet pressures. The physiotherapist and ICU nurse were responsible for monitoring of the general safety criteria, whereas the perfusionist (ECMO specialist) was responsible for the ECMO parameters. At ICU discharge, she was able to walk 20 m with mobility aid and minor support of one person.

Figure 1. Ambulation with support of a multidisciplinary team while on ECMO.

The ECMO specialist (depicted on the right) monitors ECMO parameters and security of the cannulas during exercise, while the physical therapist (depicted on the left) focusses on providing support during walking and monitoring of fatigue and safety issues concerning walking ability. An ICU nurse follows (not depicted) with a chair and monitors security of the lines at the back.

Table 1. Clinical course of physical function recovery milestones.

ICU Phase		Physical therapy intervention
Phase A: Day 1–41	MV (P-CMV and SPONT), V–V ECMO	PROM
		Prevention of contractures
Phase B: Day 42–65	MV (SPONT, P-CMV and APV (volume targeted)), High Flow during weaning, V–V ECMO	In-bed positioning
		In-bed cycling
		Out of bed in-chair (passive transfer)
		Passive standing (tilt)
		Active standing
		Active transfer bed-chair
		In-chair exercises
		Ambulation (~2-10 m) with mobility aid and 2 persons
Phase B: Day 66	MV (SPONT), High Flow during weaning, V–V ECMO decannulation	In chair exercises
Phase B: Day 67	High Flow	Ambulation (2x 10 m) with mobility aid and 1 person
		In-chair exercises
Phase B: Day 68	standard oxygen therapy (1 L) nasal canula	Airway Clearance Techniques
Phase B: Day 69 ICU discharge	Weaning from standard oxygen therapy in rest, 2 L add O2 during exercise	Ambulation (~10 meters) with mobility aid and 1 person
		In-chair exercises

APV = Adaptive Pressure Ventilation; ECMO = extracorporeal membrane oxygenation; MV = mechanical ventilation; P-CMV = pressure supported continuous mandatory ventilation; Phase A: patient is unconscious; Phase B: patient is conscious and able to cooperate; PROM = passive range of motion; SPONT = pressure supported spontaneous breathing; V–V ECMO = veno-venous ECMO

The mode of the MV during ICU stay was modified from P-CMV to SPONT in which the patient triggers and controls respiratory rate and inspiratory time, which merely reflected pulmonary recovery and decreasing levels of sedation, as did the increasing level of mobility. In other words, the switch in ventilation mode was not modified deliberately to accommodate respiratory demands during mobilization, but was modified as a covariate of clinical improvement which preceded increasing mobility levels.

In line with the more narrative description of the functional recovery above skeletal muscle strength parameters (i.e. MRC sum-score and HGS) increased continuously as did the physical function as measured with the CPAx (Figure 2). Initially, after 45 days, at the first assessment of skeletal muscle strength when being fully eligible for testing (i.e. absence of contraindications for active mobilization and being sufficiently awake and cooperative) MRC sum-score and HGS were scored as 42/60 and 6 kg, respectively. As the patient was already awake and cooperative at day 41 and in a bed chair position at day 42, this was relatively late. Overall, during first mobilization milestones we choose not to stress the patient extra as we do with a full, strenuous, relatively time-consuming MRC procedure to prevent exhaustion. However, both values were below international cutoff values for ICUAW (i.e. < 48/60 and ≤ 7 kg for the MRC sum-score and HGS, respectively) (Parry et al., 2015) which confirmed the urge for starting active mobilization to prevent any further decrease in skeletal muscle strength and physical function. As presented in Figure 2, already at day 53 (i.e. eleven days after starting being awake and cooperative) she scored above the cutoff values for ICUAW on the MRC sum-score and HGS (49/60 and 12 kg, respectively) which further increased from 14 kg HGS on day 59, and an MRC sum-score of 50/60 at day 60 to 18 kg HGS and an MRC sum-score of 52/60 at day 69 just before ICU discharge. Likewise physical function recovery showed a similar trend from initial assessment at day 45 (CPAx score 8/50) to CPAx score 22/50 at day 53, CPAx score 27/50 at day 59, to CPAx score 38/50 ultimately at ICU discharge (Figure 2). During and after physiotherapy and mobilization sessions no relevant adverse events were noted and reported, and no ECMO nor hemodynamic alarms occurred. Only one day of physiotherapy and out of bed mobilization interruption was registered due to a period of asymptomatic transient hypotension based on a relative intravascular hypovolemia which was resolved by intravenous fluid suppletion. This event was not associated with nor induced by postural changes or exercise therapy.

Figure 2. Skeletal muscle strength and physical function parameters recovery.

The dotted horizontal line shows the cutoff value for ICUAW on the MRC sum-score; Vertical dotted lines indicate the dates when the patient started out-bed chair positioning (A), standing (B) and walking (C)

Discussion

This case shows that in a multidisciplinary approach, provided that the patient is awake and cooperative, active mobilization in and out of bed and even walking are feasible and safe in a critically ill patient with (post) COVID-19 during prolonged V–V ECMO treatment. This is of evident clinical importance as specifically patients with (post) COVID-19 on ECMO are at risk for the development of long-lasting ICUAW which highlights the necessity for active mobilization at the earliest opportunity. The multidisciplinary approach in this case enhanced recovery of initial ICUAW and facilitated functional recovery up to ICU discharge after a total of 54 days on ECMO. However, as this observation is only based on one case, implementation of this insight should be handled with strong caution and needs further validation.

Recovery of skeletal muscle strength and physical function

The recovery trend of the skeletal muscle strength is in line with previous COVID findings by Van Aerde et al. (2020) in which ICUAW was present in 72% of the patients at awakening and in 52% at ICU discharge. However, these patients with comparable duration of ICU stay have been treated “only” with MV and not with ECMO. The rate of physical function recovery in terms of the ability to stand was comparable to a similar case requiring comparable ECMO treatment duration (49 days) (Oh et al., 2021). These specific patient characteristics of this patient in relation to other reports highlight the benefit of early mobilization and its’ correlation to physical recovery.

Lessons learned

Although about 77% of patients on ECMO support do receive physiotherapy the ultimate transfer to walking while on ECMO is relatively rare at about 5% of patients (Wells et al., 2018) and has not been extensively reported in literature in patients (post) COVID-19. This highlights the successful strategy followed in this particular patient. Hence in this particular case mobilization in the form of walking was facilitated a priori by three factors: 1) a stable clinical condition; 2) the absence of delirium and the patient being fully awake and cooperative; and 3) the use of a single dual-lumen catheter in the right jugular vein. The latter factor is associated with higher levels of mobilization while on ECMO in patients with COVID-19 and greatly facilitated the onset, variety in type, and intensity of out-bed mobilizations compared to other cases with double (femoral-femoral/femoral-jugular) cannulation sites (Polastri, Swol, Loforte, and Dell’Amore, 2022). However, ambulation can still be accomplished in the presence of bifemoral cannulation (Ferreira et al., 2019; Wells et al., 2018).

Moreover as previously described regular coordination and communication between involved specialisms (i.e. intensivist, clinical perfusionist (ECMO specialist), ICU nurse, and physical therapist) were essential in providing a safe framework for active mobilization and functional recovery in this patient on ECMO support (Ferreira et al., 2019; Polastri, Loforte, Dell’Amore, and Nava, 2016). This collaborative model was applied by weekly multi-disciplinary deliberation in which primary targets and focusses of that week were determined. As the center did not have considerable expertise in mobilization and ambulation of patients on ECMO to date it is recommended to set up a multidisciplinary team for similar cases in the future to formally define roles and responsibilities for each specialty involved. However, as insights from systematic reviews concerning physiotherapy and ambulation in patients on ECMO are merely based on case reports and small numbered retrospective studies, these lessons and approach cannot be generalized to all patients on ECMO (Polastri, Loforte, Dell’Amore, and Nava, 2016) although emerging evidence is promising (Ferreira et al., 2019; Wells et al., 2018).

Conclusion

This report showed that active mobilization in and out of bed and even walking are feasible and safe in a critically ill patient with (post) COVID-19 during prolonged V–V ECMO treatment. This was highly facilitated by the multidisciplinary collaborative model and the single dual-lumen catheter site.

Acknowledgments

We thank Dr. H. Vermeulen (Head of Department of Physiotherapy, Leiden University Medical Center, Leiden, the Netherlands) and colleagues at the Department of Physiotherapy for providing the necessary time for this project.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.