Abstract
Background
Patients with critical COVID-19 often require invasive mechanical ventilation (IMV) and admission to the intensive care unit (ICU), resulting in a higher incidence of ICU-acquired weakness (ICU-AW) and functional decline.
Objective
This study aimed to examine the causes of ICU-AW and functional outcomes in critically ill patients with COVID-19 who required IMV.
Methods
This prospective, single-center, observational study included COVID-19 patients who required IMV for ≥48 h in the ICU between July 2020 and July 2021. ICU-AW was defined as a Medical Research Council sum score <48 points. The primary outcome was functional independence during hospitalization, defined as an ICU mobility score ≥9 points.
Results
A total of 157 patients (age: 68 [59–73] years, men: 72.6%) were divided into two groups (ICU-AW group; n = 80 versus non-ICU-AW; n = 77). Older age (adjusted odds ratio [95% confidence interval]: 1.05 [1.01–1.11], p = 0.036), administration of neuromuscular blocking agents (7.79 [2.87–23.3], p < 0.001), pulse steroid therapy (3.78 [1.49–10.1], p = 0.006), and sepsis (7.79 [2.87–24.0], p < 0.001) were significantly associated with ICU-AW development. In addition, patients with ICU-AW had significantly longer time to functional independence than those without ICU-AW (41 [30–54] vs 19 [17–23] days, p < 0.001). The development of ICU-AW was associated with delayed time to functional independence (adjusted hazard ratio: 6.08; 95% CI: 3.05–12.1; p < 0.001).
Conclusions
Approximately half of the patients with COVID-19 requiring IMV developed ICU-AW, which was associated with delayed functional independence during hospitalization.
Keywords: Coronavirus disease 2019, Intensive care unit, Respiratory distress syndrome, Rehabilitation, Muscle weakness, Functional decline
Introduction
The increasing number of coronavirus disease 2019 (COVID-19) patients has led to acute challenges in caring for critically ill patients who may have marked disability even post-discharge, with reduced activities of daily living and quality of life.1 Previous studies have reported that 17% of the patients with COVID-19 were admitted to intensive care unit (ICU),2 and the prevalence of ICU-acquired weakness (ICU-AW) after developing COVID-19 -related acute respiratory distress syndrome (ARDS) was as high as 70–100%.3 , 4 In addition, patients with critical COVID-19 may have long-term effects on functional disability, similar to those with ARDS.5 Previous studies have shown that several years are required for patients with ARDS to recover from functional disabilities, known as post-intensive care syndrome (PICS).6 , 7 In a report, 74% of patients with critical COVID-19 who were treated in the ICU were diagnosed as PICS at 1-year after ICU treatment.8 However, there was scarce data regarding risk factors for the development of ICU-AW and the effect of ICU-AW on the post-discharge functional decline in patients with critical COVID-19.
The aim of our study was to elucidate the factors related to the development of ICU-AW, and functional decline after discharge in critical COVID-19 patients who required invasive mechanical ventilation (IMV) in the ICU.
Material and methods
Study design, setting, and participants
This single-center, prospective, non-interventional, observational study was conducted at the Kobe City Medical Center General Hospital, a referral acute care hospital, from July 2020 to July 2021. Our hospital is located in Kobe, Japan and has 768 beds. This study was approved by the Institutional Ethics Committee of the Kobe City Medical Center General Hospital (Approval no. zn200709) on June 10, 2020 and was conducted in accordance with the principles of the Declaration of Helsinki regarding human investigations. All participants provided written informed consent in accordance with the ethical standards of the Declaration of Helsinki.
During the study period, consecutive patients with COVID-19 who were ≥ 18 years of age were included. Patients were excluded if they were not admitted to the ICU or did not require IMV > 48 h, did not get assessed for ICU-AW due to a communication disorder during hospitalization, or had a mobility disorder defined as a clinical frailty scale (CFS) >6 points before admission.
The COVID-19-dedicated ward at our hospital had a diverse team of doctors from the emergency, anesthesia, infectious diseases, and respiratory medicine departments. The COVID-19 rehabilitation team comprised physical therapists, nurses, and physicians who were experienced in the rehabilitation of critically ill patients. Rehabilitation prescription was provided as soon as the patients were admitted to the ICU in all patients who required IMV in our institution. Furthermore, the rehabilitation team shared information on the patient's condition and the previous day's rehabilitation progress and decided a rehabilitation program for the day. Patients with COVID-19 in the ICU received rehabilitation programs on each weekday, and also received usual rehabilitation after discharge from the ICU or COVID-19-dedicated ward during hospitalization.
ICU-AW
The primary outcome measure was the development of ICU-AW, which was assessed according to the following criteria9; (1) generalized weakness developing after the onset of critical illness, (2) weakness is diffuse (involving both proximal and distal muscles), symmetric, flaccid, and generally spares cranial nerves, (3) Medical Research Council (MRC) sum score of <48 points, (4) dependence on mechanical ventilation, and (5) causes of weakness not related to the underlying critical illness were excluded. The limb muscle strength was assessed using the MRC score immediately after intubated patients gained consciousness in the ICU. The MRC score comprises the strength of the six muscle groups that assess the arm abduction, forearm flexion, wrist extension, leg flexion, knee extension, and foot dorsal flexion. Each test was scored from 0 to 5, and the total score for all three tests ranged from 0 (paralysis) to 60 (normal strength).10 All the scores were evaluated by the experienced physical therapists.
Data collection
Data were collected prospectively using electronic medical records, and all outcome measures were collected as part of standard care. Baseline data, including demographics, the acute physiology and chronic health evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, CFS, smoking history, Charlson comorbidity index (CCI), pharmacologic treatments for COVID-19, duration of stay at both the ICU and hospital, and mortality, were obtained. Moreover, clinical data regarding various aspects of ICU therapy, including the use of continuous renal replacement therapy (CRRT), prone position management, use of high-flow nasal cannula (HFNC), duration of ventilation, tracheostomy, reintubation, administration of neuromuscular blocking agents (NMBAs), administration of sedatives, pulse steroid therapy, and complications at any point on ICU admission were collected. Pulse steroid therapy was defined as treatment with more than 250 mg intravenous methylprednisolone per day for three days.
APACHE II score and SOFA score were assessed as the severity of illness in ICU and widely used as of most validated and reliable scoring systems. APACHE II score consists of three components; twelve physiological variables along with the previous state of the patient's health and age.11 The maximum score is 71, and a higher score indicates severe status. The SOFA score is based on six different scores, one each for respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems.12
The CCI was utilized to assess the prognostic burden of comorbid diseases.13 The index assigns integer weights to specific diseases, and the total score is calculated by adding the integer weights for all comorbid conditions. CCI is the most widely used comorbidity index, and higher scores indicate poorer medical conditions.
The CFS is a validated scale to assess frailty using multidimensional domains, including mobility function, basic activities of daily living (ADLs), instrumental ADL, assistance for personal care, comorbidities, and cognition.14 The CFS determines frailty status using a nine-point scale ranging from 1 (very fit) to 9 (terminally ill). The CFS is also used for assessing critically ill patients, and frailty before admission is defined as CFS >4.14 , 15
Complications included sepsis, ventilator-associated pneumonia (VAP), and delirium after admission to the ICU. Sepsis was diagnosed according to the guideline criteria.16 VAP was diagnosed based on exacerbation of respiratory status and identification of the causative microorganism. Delirium was assessed using the Confusion Assessment method for the ICU.17 All complications were based on the diagnosis in the medical record and were adjudicated by the study physician. The discharge destination was assessed as: discharge to home, discharge to hospital, or death in hospital. The first mobilization was defined as sitting on the edge of the bed and standing on the floor.
Functional independence, as measured by experienced physical therapists using the ICU mobility score (IMS). The IMS was developed as a validated scale for measuring the highest level of mobility for patients in the ICU.18 The IMS grades the patient's mobility capabilities from 0 (bedridden) to 10 (walking independently without a gait aid); higher scores indicate better mobility function. In the present study, IMS ≥9 was defined as functional independence, and patients who died in the hospital were assigned 0 points for IMS at discharge.
Statistical analysis
Continuous variables are expressed as medians (interquartile ranges), whereas qualitative variables are expressed as n (%). Participants were divided into ICU-AW and non-ICU-AW groups according to the cutoff points of the MRC <48 points. The Mann-Whitney U test and chi-squared test were used to compare patient characteristics and clinical parameters between the two groups. Time to functional independence was analyzed using Kaplan–Meier analysis and compared between groups by using the log-rank tests. Observations of patients who were lost during follow-up were censored at the date of the last follow-up.
Factors related to ICU-AW were assessed using a logistic regression model according to age, sex, APACHE II, CCI, CFS, administration of NMBAs, pulse steroid therapy, development of sepsis, and development of VAP. Moreover, factors related to time to functional independence were assessed using the Cox proportional hazards model according to age, sex, APACHE II, CCI, CFS, NMBAs, pulse steroid therapy, sepsis, VAP, and ICU-AW. These variables were selected based on biological plausibility and preexisting knowledge in previous study.5
All statistical analyses were performed using R software (version 3.6.1; The R Foundation for Statistical Computing, Vienna, Austria). A p < 0.05 was considered to be statistically significant.
Results
During the study period, a total of 688 consecutive patients with COVID-19 were admitted to our institution. Among them, 157 patients who were intubated and admitted to the ICU were included in the final analysis. Fig. 1 illustrates a flowchart describing the inclusion of patients in this study.
Fig. 1.
Flowchart for patient selection. IMV: Invasive mechanical ventilation; ICU-AW: intensive care unit-acquired weakness; CFS: Clinical frailty scale.
Demographic data are summarized in Table 1 . A majority of the participants were older adults (median age: 68 years; interquartile range [IQR]: 59–73 years), men (72.6%), had hypertension (54.8%), and had diabetes mellitus (30.6%) with a median CCI of 1 (IQR: 0–2). Patients with ICU-AW were significantly older (70 [62–74] vs. 67 [57–72] years; p = 0.023) and had higher severity scores, including APACHE II (20 [17–24] vs. 17 [14–20] points; p < 0.001), SOFA (8 [6–9] vs. 6 [5–8] points; p < 0.001). Almost all patients were administered steroids (99.4%), including dexamethasone (98.1%), methylprednisolone (63.1%), and pulse steroid therapy (49.0%). Patients with ICU-AW used less methylprednisolone (45.5 vs. 80.0%) and more pulse steroid therapy (66.3 vs. 28.5%) than non-ICU-AW. However, there were no significant differences between the two groups in terms of CFS, comorbidities, and other pharmacotherapy.
Table 1.
Clinical characteristics of participants.
| All (n = 157) | Non-ICU-AW (n = 77) | ICU-AW (n = 80) | P-Value | |
|---|---|---|---|---|
| DEMOGRAPHIC CHARACTERISTICS | ||||
| Age (years) | 68 (59–73) | 67 (57–72) | 70 (62–74) | 0.023 |
| Male (n,%) | 114 (72.6) | 56 (72.7) | 58 (72.5) | 0.999 |
| BMI (kg/m2) a | 24.6 (22.6–26.9) | 24.7 (23.0–26.8) | 24.2 (22.4–27.0) | 0.557 |
| APACHE II (points) | 18 (16–22) | 17 (14–20) | 20 (17–24) | <0.001 |
| SOFA (points) | 7 (5–8) | 6 (5–8) | 8 (6–9) | <0.001 |
| CFS before admission (points) | 3 (3–3) | 3 (3–3) | 3 (3–3) | 0.215 |
| Frailty before admission (n,%) b | 2 (1.3) | 2 (1.3) | 2 (1.2) | 0.999 |
| Smoking history (n,%) | 0.241 | |||
| Never | 63 (40.1) | 31 (40.3) | 32 (40.0) | |
| Past | 86 (54.1) | 44 (57.1) | 41 (51.2) | |
| Current | 9 (5.7) | 2 (2.6) | 7 (8.8) | |
| CCI (points) | 1 (0–2) | 1 (0–2) | 1 (0–2) | 0.702 |
| COMORBIDITIES (n,%) | ||||
| Hypertension | 86 (54.8) | 37 (48.1) | 49 (61.3) | 0.133 |
| Diabetes mellitus | 48 (30.6) | 25 (32.5) | 23 (28.7) | 0.740 |
| Chronic heart failure | 5 (3.2) | 3 (3.9) | 2 (2.5) | 0.965 |
| Malignancy | 17 (10.8) | 5 (6.5) | 12 (15.0) | 0.145 |
| Cerebrovascular disease | 10 (6.4) | 6 (7.8) | 4 (5.0) | 0.697 |
| Chronic kidney disease | 5 (3.2) | 1 (1.3) | 4 (5.0) | 0.387 |
| Chronic respiratory disease | 26 (16.7) | 12 (15.8) | 14 (17.5) | 0.943 |
| PHARMACOTHERAPIES (n,%) | ||||
| Steroid | 156 (99.4) | 76 (98.7) | 80 (100.0) | 0.985 |
| Tocilizumab | 113 (72.0) | 52 (67.5) | 61 (76.2) | 0.299 |
| Remdesivir | 81 (51.6) | 47 (61.0) | 34 (42.5) | 0.03 |
| Favipiravir | 10 (6.4) | 7 (9.1) | 3 (3.8) | 0.297 |
| Baricitinib | 6 (3.8) | 3 (3.9) | 3 (3.8) | 0.999 |
Data are presented as medians (interquartile ranges) or numbers (percentages).
Mann-Whitney U and chi-square tests are used for quantitative and qualitative analyses, respectively.
a) BMI is assessed in 139 patients.
b) Frailty was defined as CFS > 4.
Abbreviations: BMI: body mass index; APACHE II: acute physiology and chronic health evaluation 2 score; SOFA: Sequential Organ Failure Assessment; CFS: clinical frailty scale; CCI: Charlson comorbidity index.
The ICU therapy management and clinical outcomes are summarized in Table 2 . All patients required IMV for a median duration of 8 days (IQR: 5–25 days). A tracheostomy was performed in 24.8% of the patients, all of whom were in the ICU-AW group. Almost all patients were sedated (98.7%) for a median duration of 8 days (IQR: 4–17 days).
Table 2.
ICU therapy managements and clinical outcomes.
| All (n = 157) | Non-ICU-AW (n = 77) | ICU-AW (n = 80) | P-Value | |
|---|---|---|---|---|
| TREATMENTS RECEIVED | ||||
| ECMO (n,%) | 0 (0) | 0 (0) | 0 (0) | 0.999 |
| CRRT (n,%) | 9 (5.7) | 1 (1.3) | 8 (10.0) | 0.045 |
| Prone position (n,%) | 60 (38.2) | 11 (14.3) | 49 (61.3) | <0.001 |
| HFNC (n,%) | 138 (87.9) | 66 (85.7) | 72 (90.0) | 0.563 |
| Mechanically ventilation | ||||
| Duration of ventilation (days) | 8 (5–25) | 5 (3–7) | 25 (13–40) | <0.001 |
| Extubation (n,%) | 149 (94.9) | 75 (97.4) | 74 (92.5) | 0.301 |
| Re-intubation (n,%) | 13 (8.3) | 4 (5.2) | 9 (11.2) | 0.277 |
| Tracheostomy (n,%) | 39 (24.8) | 0 (0) | 39 (48.8) | <0.001 |
| Neuromuscular blockade (n,%) | 66 (42.0) | 12 (15.6) | 54 (67.5) | <0.001 |
| Duration of blockade (days) | 1 (1–2) | 1 (1–2) | 1.5 (1–2) | 0.258 |
| Sedation (n,%) | 155 (98.7) | 75 (97.4) | 80 (100) | 0.460 |
| Duration of sedation (days) | 8 (4–17) | 4 (2–7) | 16 (10–22) | <0.001 |
| OUTCOMES | ||||
| Length of stay in the ICU (days) | 11 (6–19) | 6 (4–11) | 18 (11–26) | <0.001 |
| Death in the ICU (n,%) | 3 (1.9) | 0 (0) | 3 (3.8) | 0.257 |
| Complications (n,%) | ||||
| Sepsis | 49 (31.2) | 6 (7.8) | 43 (53.8) | <0.001 |
| VAP | 103 (65.6) | 35 (45.5) | 68 (85.0) | <0.001 |
| Delirium | 54 (34.4) | 21 (27.3) | 33 (41.2) | 0.094 |
| Time to first mobilization (days) | ||||
| Sitting on the edge of bed | 7 (4–11) | 6 (4–8) | 9 (5–16) | <0.001 |
| Standing at the bed side | 11 (7–19) | 8 (6–12) | 19 (14–28) | <0.001 |
| ICU-MS (points) | ||||
| ICU discharge | 3 (1–3) | 3 (1–3) | 3 (3, 3) | 0.837 |
| Hospital discharge | 9 (5–10) | 10 (9–10) | 7 (0–9) | <0.001 |
| ICU-MS >9 at discharge (n,%) | 86 (54.8) | 64 (83.1) | 22 (27.5) | <0.001 |
| Time to functional independence a (days) | 21 (18–29) | 19 (17–23) | 41 (30–54) | <0.001 |
| Length of stay in hospital (days) | 26 (17–42) | 18 (14–25) | 41 (29–53) | <0.001 |
| Discharge destination (n,%) | <0.001 | |||
| Home | 47 (29.9) | 44 (57.1) | 3 (3.8) | |
| Hospital | 79 (50.3) | 29 (37.7) | 50 (62.5) | |
| Death in hospital | 31 (19.7) | 4 (5.2) | 27 (33.8) |
Data are presented as medians (interquartile ranges) or numbers (percentages).
*Defined as ICU-MS>9. Mann-Whitney U and chi-square tests are used for quantitative and qualitative analyses, respectively.
Abbreviations: ICU-AW: intensive care unit-acquired weakness; ECMO: extracorporeal membrane oxygenation; CRRT: continuous renal replacement therapy; HFNC: high-flow nasal cannula; VAP: ventilator associated pneumonia; ICU-MS: intensive care unit mobility scale.
ICU-AW was diagnosed after gaining consciousness in 80 (51.0%) patients according to their MRC scores; based on this, participants were divided into ICU-AW (n = 80) group and non-ICU-AW (n = 77) group. Patients with ICU-AW had a significantly higher prevalence of requiring CRRT (10.0% vs. 1.3%; p = 0.045), placed in the prone position (61.3% vs. 14.3%; p < 0.001), administering NMBAs (67.5% vs. 15.6%, p <0.001), and a longer sedation time (16 vs. 4 days; p < 0.001) than patients with non-ICU-AW. The ICU-AW group showed significantly delayed first mobilization than non-ICU-AW group, including sitting on the edge of the bed (9 vs. 6 days; p < 0.001) and standing (19 vs. 8 days; p < 0.001). At discharge from the ICU, there were no significant differences in the IMS (3 vs. 3 points; p = 0.837), but the IMS (7 vs. 10 points; p < 0.001) and prevalence of functional independence (27.5% vs. 83.1%; p < 0.001) at hospital discharge were significantly lower in the ICU-AW group than in the non-ICU-AW group. The Kaplan–Meier analysis revealed that the ICU-AW group had a significantly delayed functional independence during hospitalization than the non-ICU-AW group (hazard ratio [HR]: 14.1; 95% confidence interval [CI]: 7.82–25.4, p < 0.001; Fig. 2 ). Moreover, as per the Cox proportional hazards model, ICU-AW (adjusted HR: 6.08; 95% CI: 3.05–12.1; p < 0.001) were significantly associated with a delayed time to functional independence.
Fig. 2.
Kaplan–Meier analysis plot for time to mobility independence stratified based on ICU-AW. ICU-AW: intensive care unit-acquired weakness.
The results of multivariate analysis are presented in Table 3 . As per the logistic regression model, age (adjusted odds ratio [OR]: 1.05; 95% CI: 1.01–1.11; p = 0.036), administration of NMBAs (adjusted OR: 7.79; 95% CI: 2.87–23.3; p < 0.001), pulse steroid therapy (adjusted OR: 3.78; 95% CI: 1.49–10.1; p = 0.006), and development of sepsis (adjusted OR: 6.94; 95% CI: 2.33–24.0; p < 0.001) were significantly associated with development of ICU-AW.
Table 3.
Association with ICU-AW.
| OR | 95% CI | p | |
|---|---|---|---|
| VARIABLES | |||
| Age, years | 1.05 | 1.01–1.11 | 0.036 |
| Men | 1.61 | 0.58–4.71 | 0.370 |
| APACHE II, points | 1.08 | 0.98–1.20 | 0.141 |
| CCI, points | 0.85 | 0.58–1.24 | 0.5394 |
| CFS, points | 1.02 | 0.31–4.58 | 0.977 |
| Neuromuscular blockade | 7.79 | 2.87–23.3 | <0.001 |
| Pulse steroid therapy | 3.78 | 1.49–10.1 | 0.006 |
| Sepsis | 6.94 | 2.33–24.0 | <0.001 |
| VAP | 2.50 | 0.92–7.00 | 0.074 |
Abbreviations: ICU-AW: intensive care unit-acquired weakness; APACHE II: acute physiology and chronic health evaluation 2 score; CCI: Charlson comorbidity index; CFS: clinical frailty scale; VAP: Ventilator associated pneumonia.
Discussion
This study reported risk factors of ICU-AW in patients with COVID-19 who required IMV in ICU. The major findings of this study are follows; (i) older age, administration of NMBAs, pulse steroid therapy, and sepsis were associated with the development of ICU-AW; and (ii) development of ICU-AW were associated with delayed functional recovery; (iii) both of these findings were similar to those reported in critically ill patients due to other causes of COVID-19, such as ARDS. Our results suggest that more attention should be paid to functional decline after ICU-AW in patients with critical COVID-19.
ICU-AW is a critical problem in critically ill patients treated in ICU. The prevalence of ICU-AW in critically ill patients with non-COVID-19 conditions has been reported to be 40%–50%,19., 20., 21. while the prevalence of ICU-AW in patients with COVID-19 was reported to be as high as 70–100%.3 , 4 However, ICU-AW was observed in 51% of patients in the present study. As compared to the previous COVID-19 reports, the severity of COVID-19 was comparable, but the duration of NMBA administration, IMV and hospital stays were shorter than the previous studies.22 These differences may explain the lower rate of ICU-AW in our study. Although patients were older in our study than the previous studies,21 , 22 it was similar to a multicenter ICU Japanese study included patients with COVID-19 with a median age of 68 years and a median APACHE II score of 16.23
The use of NMBAs were reported to be associated with ICU-AW development,24 which was consistent in our study. NMBAs are administered to avoid lung injury from spontaneous breathing under sedation in patients with severe ARDS,25 and many cases of COVID-19 may have been used NMBAs for similar reasons. Therefore, some patients with COVID-19 with severe ARDS, especially those requiring NMBAs, may not be entirely prevented developing ICU-AW during ICU management. Such patients need appropriate assessment of ICU-AW, prediction of prognosis for ICU-AW, a rehabilitation program after their condition stabilizes, and seamless rehabilitation through community collaboration after discharge from an acute care hospital.
Pulse steroid therapy was also associated with ICU-AW development in our results. Although corticosteroid therapy is sometimes used for selected critically ill patients such as ARDS, it can cause changes in specific gene expression to indicate the inhibition of protein synthesis, leading to muscle wasting.26 In previous studies, the use of corticosteroids was associated with ICU-AW in patients who required IMV with COVID-19 and non-COVID-19.27 , 28 However, it has been reported that early and low-dose corticosteroid therapy was associated with reduced mortality in sepsis patients with the highest severity of illness.29 Therefore, low-dose and short-term corticosteroid therapy may improve the prognosis without increasing the risk of ICU-AW in ICU patients. In the present study, where most of the subjects received steroids, pulse steroid therapy with higher doses may have been extracted as a risk for the development of ICU-AW. Moreover, a previous study reported that an APACHE II score ≥15 points is a risk factor for ICU-AW,24 however, not APACHE II but sepsis was associated with ICU-AW in participants in the present study. This may be explained by the inclusion of subjects who had a higher risk, more severe risk, with a median APACHE II score of 18 points.
In the present study, functional independence was associated with ICU-AW, and the rate of functional independence, defined as IMS ≥9, was 54.8%. Previous studies have reported the ADL dependence rate of approximately 50% at discharge from hospital in critical patients without COVID-19 in ICU.21 , 30 In patients with COVID-19, ADL dependence at the hospital discharge was reported to be 50–80%,3 , 31 a higher rate than in patients without COVID-19. Reasons for this may include pharmacotherapy, infection management, and the susceptibility to severe disease in patients with COVID-19. Similar to our results, critically ill patients, including those with COVID-19, often experience long-term physical symptoms or exercise intolerance6 , 8 , 32 and may require long-term follow-up. At first, it is important to prevent ICU-AW by adjusting medications for disease management and early mobilization. It is considered necessary to screen high-risk patients and a system that allows long-term follow-up and rehabilitation after the onset of ICU-AW. Moreover, future research is needed on prevention and intervention for ICU-AW in COVID-19 patients.
The present study included some limitations. First, this was a single-center, prospective, observational study with a small sample size. Therefore, there was a risk of sampling bias, and the generalization of the data may be limited. Second, patients who could not access ICU-AW were excluded from the analysis. Patients with more severe diseases may have lower consciousness levels, and the study findings are applicable only to patients who can communicate; thus, the associations may represent a biased sample of those admitted to the ICU. Third, during the observation period, the treatment and medical conditions for COVID-19 at our hospital may have changed due to the pandemic, which may have affected the results. Moreover, coordinating the transfer of patients to subacute hospitals during the early stages of the pandemic was difficult.
In conclusion, ICU-AW was diagnosed in approximately half of the COVID-19 patients who required IMV, and older age, administration of NMBAs, pulse steroid therapy, and sepsis were associated with the progression of ICU-AW. In addition, ADL dependence is higher in critically ill patients with COVID-19 who have generally more severe conditions compared to those without COVID-19. Further studies are needed to determine the differences between COVID-19 and non-COVID-19. Given the high prevalence of ICU-AW, rehabilitation interventions and careful follow-up for the functional decline after discharge should be needed.
Authors' contributions
All authors contributed to the conception and design of the study. KY, HN, TI, RY, YI, and TS prepared the materials and collected the data. KY performed data analysis and prepared the first draft of the manuscript. TK revised the manuscript for critical content. All authors participated in data interpretation, commented on the previous versions of the manuscript, and read and approved the final manuscript.
Conflicts of interest and source of funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of Competing Interest
All authors have nothing to disclose.
Acknowledgments
None.
References
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