Early physical rehabilitation dosage in the Intensive Care Unit predicts hospital outcomes after critical COVID-19.

Objective : to examine the relationship between physical rehabilitation parameters including a novel approach to quantifying dosage with hospital outcomes for patients with critical COVID-19. Design: Retrospective practice analysis from March 5, 2020, to April 15, 2021. Setting: Intensive care units (ICU) at four medical institutions Patients: n = 3,780 adults with ICU admission and diagnosis of COVID-19 Interventions: We measured the physical rehabilitation treatment delivered in ICU and patient outcomes: 1) mortality; 2) discharge disposition; and 3) physical function at hospital discharge measured by the Activity Measure-Post Acute Care (AM-PAC) "6-Clicks" (6-24, 24=greater functional independence). Physical rehabilitation dosage was defined as the average mobility level scores in the first three sessions (a surrogate measure of intensity) multiplied by the rehabilitation frequency (PT + OT frequency in hospital). Measurements and Main Results: The cohort was a mean 64 ± 16 years old, 41% female, mean BMI of 32 ± 9 kg/m 2 and 46% (n=1739) required mechanical ventilation. For 2191 patients with complete data, rehabilitation dosage and AM-PAC at discharge were moderately, positively associated (Spearman's rho [r] = 0.484, p < 0.001). Multivariate linear regression (model adjusted R 2 = 0.68, p <0.001) demonstrates mechanical ventilation (ß = -0.86, p = 0.001), average mobility score in first three sessions (ß = 2.6, p <0.001) and physical rehabilitation dosage (ß = 0.22, p = 0.001) were predictive of AM-PAC scores at discharge when controlling for age, sex, BMI, and ICU LOS. Conclusions: Greater physical rehabilitation exposure early in the ICU is associated with physical function at hospital discharge.

Construct and criterion validity of muscle ultrasonography for assessment of skeletal muscle in patients recovering from COVID-19.

Background: The purpose was to investigate the content, construct, and criterion validity of muscle ultrasound in a mixed cohort of participants recovering from mild and critical COVID-19. Methods: A secondary analysis of a prospective cross-sectional study was conducted on data obtained from a battery of muscle and physical function assessments including a muscle biopsy and muscle ultrasonography (US). Rectus femoris (RF) muscle thickness (mT), quadricep complex (QC) mT, RF muscle cross-sectional area (CSA) using 2D freeform trace and estimated from Feret's diameter, and RF echo intensity (EI) were assessed with US. Muscle fiber CSA, fiber type, protein content in muscle fibers, extracellular matrix content (ECM; wheat-germ agglutin), and percent area of collagen in ECM (picrosirius red) were examined from vastus lateralis muscle biopsies. Spearman rho correlations (r) were performed to assess validity of ultrasound parameters. Results: Thirty-three individuals participated including 11 patients surviving critical COVID-19, 15 individuals recovering from mild-COVID, and 7 controls. There were several significant correlations between RF mT, QC mT, RF CSA, and RF EI with age, comorbid burden, body-mass index, and measures of muscle strength, muscle power, and physical function (range r = 0.35-0.83). RF Feret's CSA correlated to CSA of type II muscle fibers (r = 0.41, p = 0.022) and the average size of all muscle fibers (r = 0.39, p = 0.031). RF EI was correlated with collagen in muscle ECM (r = 0.53, p = 0.003) and protein content in muscle tissue (r = -0.52, p = 0.012). Conclusion: Muscle size and quality measured using US has moderate content and construct validity, and to lesser extent, fair to moderate criterion validity in a mixed cohort of individuals recovering from COVID. Muscle ultrasound quality (EI) appears to be sensitive at detecting muscle dysfunction as it is associated with strength, power, physical function, and collagen distribution in a mixed group of individuals recovering from COVID-19.

Nutrition in the intensive care unit and early recovery influence functional outcomes for survivors of critical illness: A prospective cohort study.

BACKGROUND: Patients who are critically ill may receive suboptimal nutrition that leads to weight loss and increased risk of functional deficits. METHODS: Our overarching hypothesis is that nutrition in the intensive care unit (ICU) and the early recovery phase associates with functional outcomes at short-term follow-up. We enrolled adult patients who attended the University of Kentucky ICU recovery clinic (ICU-RC) from November 2021 to June 2022. Patients participated in muscle and functional assessments. Nutrition intake and status during the ICU stay were analyzed. The Subjective Global Assessment and a nutrition questionnaire were used to identify changes in intake, ongoing gastrointestinal symptoms, and patient's access to food at the ICU-RC appointment. RESULTS: Forty-one patients enrolled with a median hospital length of stay (LOS) of 23 days. Patients with 0 days of nil per os (NPO) status throughout hospitalization had a shorter LOS (P = 0.05), were able to complete the five times sit-to-stand test (P = 0.02), and were less likely to experience ICU-acquired weakness (P = 0.04) at short-term follow-up compared with patients with ≥1 day of NPO status. Twenty (48%) patients reported changes in nutrition intake in early recovery compared with before hospitalization. Eight (20%) patients reported symptoms leading to decreased intake and four (10%) reported access to food as a barrier to intake. CONCLUSION: Barriers to nutrition exist during critical illness and persist after discharge, with almost half of patients reporting a change in intake. Inpatient nutrition intake is associated with functional outcomes and warrants further exploration.

Post-intensive care syndrome and pulmonary fibrosis in patients surviving ARDS-pneumonia of COVID-19 and non-COVID-19 etiologies.

The purpose was to examine patient-centered outcomes and the occurrence of lung fibrotic changes on Chest computed tomography (CT) imaging following pneumonia-related acute respiratory distress syndrome (ARDS). We sought to investigate outpatient clinic chest CT imaging in survivors of COVID19-related ARDS and non-COVID-related ARDS, to determine group differences and explore relationships between lung fibrotic changes and functional outcomes. A retrospective practice analysis of electronic health records at an ICU Recovery Clinic in a tertiary academic medical center was performed in adult patients surviving ARDS due to COVID-19 and non-COVID etiologies. Ninety-four patients with mean age 53 ± 13 and 51% male were included (n = 64 COVID-19 and n = 30 non-COVID groups). There were no differences for age, sex, hospital length of stay, ICU length of stay, mechanical ventilation duration, or sequential organ failure assessment (SOFA) scores between the two groups. Fibrotic changes visualized on CT imaging occurred in a higher proportion of COVID-19 survivors (70%) compared to the non-COVID group (43%, p < 0.001). Across both groups, patients with fibrotic changes (n = 58) were older, had a lower BMI, longer hospital and ICU LOS, lower mean RASS scores, longer total duration of supplemental oxygen. While not statistically different, patients with fibrotic changes did have reduced respiratory function, worse performance on the six-minute walk test, and had high occurrences of anxiety, depression, emotional distress, and mild cognitive impairment regardless of initial presenting diagnosis. Patients surviving pneumonia-ARDS are at high risk of impairments in physical, emotional, and cognitive health related to Post-Intensive Care Syndrome. Of clinical importance, pulmonary fibrotic changes on chest CT occurred in a higher proportion in COVID-ARDS group; however, no functional differences were measured in spirometry or physical assessments at ICU follow-up. Whether COVID infection imparts a unique recovery is not evident from these data but suggest that long-term follow up is necessary for all survivors of ARDS.

Meeting the Challenges of Establishing Intensive Care Unit Follow-up Clinics.

Intensive care unit follow-up clinics are becoming an increasingly widespread intervention to facilitate the physical, cognitive, psychiatric, and social rehabilitation of survivors of critical illness who have post-intensive care syndrome. Developing and sustaining intensive care unit follow-up clinics can pose significant challenges, and clinics need to be tailored to the physical, personnel, and financial resources available at a given institution. Although no standard recipe guarantees a successful intensive care unit aftercare program, emerging clinics will need to address a common set of hurdles, including securing an adequate space; assembling an invested, multidisciplinary staff; procuring the necessary financial, information technology, and physical stuff; using the proper screening tools to identify patients most likely to benefit and to accurately identify disabilities during the visit; and selling it to colleagues, hospital administrators, and the community at large.

Patients Surviving Critical COVID-19 have Impairments in Dual-task Performance Related to Post-intensive Care Syndrome.

OBJECTIVE: The purpose was to examine Dual Task (DT) performance in patients surviving severe and critical COVID-19 compared to patients with chronic lung disease (CLD). Secondarily, we aimed to determine the psychometric properties of the Timed Up and Go (TUG) test in patients surviving COVID-19. DESIGN: Prospective, cross-sectional, observational study. SETTING: Academic medical center within United States. PATIENTS: Ninety-two patients including 36 survivors of critical COVID-19 that required mechanical ventilation (critical-COVID), 20 patients recovering from COVID-19 that required supplemental oxygen with hospitalization (severe-COVID), and 36 patients with CLD serving as a control group. MEASUREMENTS AND MAIN RESULTS: Patients completed the TUG, DT-TUG, Short Physical Performance Battery (SPPB), and Six Minute Walk Test (6MWT) 1-month after hospital discharge. A subset of patients returned at 3-months and repeated testing to determine the minimal detectable change (MDC). Critical-COVID group (16.8 ± 7.3) performed the DT-TUG in significantly slower than CLD group (13.9 ± 4.8 s; P = .024) and Severe-COVID group (13.1 ± 5.1 s; P = .025). Within-subject difference between TUG and DT-TUG was also significantly worse in critical-COVID group (-21%) compared to CLD (-10%; P = .012), even despite CLD patients having a higher comorbid burden (P < .003) and older age (P < .001). TUG and DT-TUG demonstrated strong to excellent construct validity to the chair rise test, gait speed, and 6MWT for both COVID-19 groups (r = -0.84to 0.73, P < .05). One- and 3-months after hospital discharge there was a floor effect of 14% (n = 5/36) and 5.2% (n = 1/19), respectively for patients in the critical-COVID group. Ceiling effects were noted in four (11%) critical-COVID, six (30%) severe-COVID patients for the TUG and DT-TUG at 1-month. CONCLUSION: The ability to maintain mobility performance in the presence of a cognitive DT is grossly impaired in patients surviving critical COVID-19. DT performance may subserve the understanding of impairments related to Post-intensive care syndrome (PICS) for survivors of critical illness.

Feasibility of Contrasting Brain Connectivity Patterns in Cognitive and Motor Cerebral Networks to Clinical Outcomes in Patients Surviving Acute Respiratory Failure: A Pilot Study.

BACKGROUND: There is a paucity of research regarding the feasibility and association of cerebral cortex function to patient outcomes after acute respiratory failure (ARF). PURPOSE: To determine the feasibility of functional connectivity measures and examine the association of functional connectivity to a multifaceted battery of outcomes in survivors of ARF. METHODS: Eight ARF patients (age:58±3.7, ICU days:10.4±8.6) completed functional magnetic resonance imaging (fMRI), cognitive, physical-function, anxiety, depression, and driving simulator tests at one month post-hospital discharge. Pearson's correlations assessed the relationship between functional connectivity within the default mode network (FPN), sensorimotor network (SMN), and frontoparietal network (FPN) to outcomes. RESULTS: Low physical-function (r=0.75, p=0.03) and divided-attention (r=-0.86, p=0.03) during the driving simulator task correlated with low FPN connectivity. Low SMN connectivity demonstrated relationships to slower gait speed (r=0.82, p=0.01) and low short physical performance battery (SPPB) scores (r=0.81, p=0.01). CONCLUSIONS: fMRI is feasible to assess ARF patients' post-ICU limitations, as low post-ARF brain connectivity may be linked to low physical function, providing potential development of therapeutic interventions.

Safety and Feasibility of an Interdisciplinary Treatment Approach to Optimize Recovery From Critical Coronavirus Disease 2019.

OBJECTIVES: Examine the safety and feasibility of a multimodal in-person or telehealth treatment program, administered in acute recovery phase for patients surviving critical coronavirus disease 2019. DESIGN: Pragmatic, pre-post, nonrandomized controlled trial with patients electing enrollment into one of the two recovery pathways. SETTING: ICU Recovery Clinic in an academic medical center. PATIENTS: Adult patients surviving acute respiratory failure due to critical coronavirus disease 2019. INTERVENTIONS: Patients participated in combined ICU Recovery clinic and 8 weeks of physical rehabilitation delivered: 1) in-person or 2) telehealth. Patients received medical care by an ICU Recovery Clinic interdisciplinary team and physical rehabilitation focused on aerobic, resistance, and respiratory muscle training. MEASUREMENTS AND MAIN RESULTS: Thirty-two patients enrolled with mean age 57 ± 12, 62% were male, and the median Sequential Organ Failure Assessment score was 9.5. There were no differences between the two groups except patients in telehealth pathway (n = 10) lived further from clinic than face-to-face patients (162 ± 60 vs 31 ± 47 kilometers, t = 6.06, p < 0.001). Four safety events occurred: one minor adverse event in the telehealth group, two minor adverse events, and one major adverse event in the in-person group. Three patients did not complete the study (two in-person and one telehealth). Six-minute walk distance increased to 101 ± 91 meters from pre to post (n = 29, t = 6.93, p < 0.0001), which was similar between the two groups (110 vs 80 meters, t = 1.34, p = 0.19). Self-reported levels of anxiety, depression, and distress were high in both groups with similar self-report quality of life. CONCLUSIONS: A multimodal treatment program combining care from an interdisciplinary team in an ICU Recovery Clinic with physical rehabilitation is safe and feasible in patients surviving the ICU for coronavirus disease 2019 acute respiratory failure.

Physical Therapy Management of an Individual With Post-COVID Syndrome: A Case Report.

OBJECTIVE: The purpose of this case report is to provide the clinical presentation and physical therapist management for a patient with post-COVID syndrome. Secondarily, the report highlights the importance of assessing cognitive and emotional health in patients with post-COVID syndrome. METHODS (CASE DESCRIPTION): A 37-year-old woman tested positive for SARS-CoV-2 and developed mild COVID-19 disease but did not require supplemental oxygen or hospitalization. The patient experienced persistent symptoms, including dyspnea, headaches, and cognitive fog. On day 62, they participated in an outpatient physical therapist evaluation that revealed deficits in exercise capacity, obtaining 50% of their age-predicted 6-minute walk distance. They had minor reductions in muscle strength and cognitive function. Self-reported quality of life was 50, and they scored above established cut-off scores for provisional diagnosis of posttraumatic stress disorder (PTSD). RESULTS: The patient participated in biweekly physical therapist sessions for 8 weeks, which included aerobic training, strengthening exercises, diaphragmatic breathing techniques, and mindfulness training. Metabolic equivalent for task levels increased with variability over the course of the program. The patient's muscle strength, physical function, and exercise capacity improved. 6-Minute walk distance increased by 199 m, equating to 80% of their age-predicted distance. Quality of life and PTSD scores did not improve. At evaluation after physical therapy, the patient was still experiencing migraines, dyspnea, fatigue, and cognitive dysfunction. CONCLUSION: This case report described the clinical presentation and physical therapist management of a person with post-COVID syndrome, a novel health condition for which little evidence exists to guide rehabilitation examination and interventions. Physical therapists should consider cognitive function and emotional health in their plan of care for patients with post-COVID syndromes. IMPACT: This case alerts physical therapists to post-COVID syndrome-which can include debilitating symptoms of decreased aerobic tolerance, anxiety, PTSD, and cognitive dysfunction-and to the role that therapists can play in assessing these symptoms and managing these patients.

Muscle Power is Related to Physical Function in Patients Surviving Acute Respiratory Failure: A Prospective Observational Study.

BACKGROUND: Up to 66% of patients admitted to the intensive care unit (ICU) for acute respiratory failure (ARF) develop ICU-acquired weakness, which is diagnosed by muscle strength testing. Muscle power, different from strength, is an important determinant of function that is not a common focus in patients surviving critical illness. Therefore, the purpose of this study is to assess muscle power in survivors of ARF. METHODS: A cross-sectional observational study performed with survivors of ARF. Muscle power, strength and physical function were assessed 4-8 weeks post-hospital discharge. Cross sectional area and echogenicity of rectus femoris and tibialis anterior muscles were assessed using ultrasonography. Healthy community-dwelling adults were included for comparison. RESULTS: 12 survivors of ARF mean age of 55.6 ± 17.1 (66% male) and 12 healthy adults mean age of 51.6.1 ± 10.3 (66% male) participated in this study. Patients in the post-ARF group had a mean muscle power of 9.9 ± 3.5 W and 63.7 ± 31.6 W for 2-lb and 10% of body-weight loads, respectively. Compared to matched controls, power in ARF group was reduced by 43%. Muscle power in post-ARF group had moderate correlations with 5-times sit-to-stand testing (r = -0.644, P = 0.024), 4-m habitual gait speed (-0.780, P = 0.002), and 6-min walk distance (r = 0.589, P = 0.044). CONCLUSIONS: Muscle power is significantly reduced in survivors of critical illness and associated with deficits in physical function. These preliminary findings may support therapeutic interventions aimed at improving muscle power to potentially increase functional benefit.

Acute skeletal muscle wasting and dysfunction predict physical disability at hospital discharge in patients with critical illness.

BACKGROUND: Patients surviving critical illness develop muscle weakness and impairments in physical function; however, the relationship between early skeletal muscle alterations and physical function at hospital discharge remains unclear. The primary purpose of this study was to determine whether changes in muscle size, strength and power assessed in the intensive care unit (ICU) predict physical function at hospital discharge. METHODS: Study design is a single-center, prospective, observational study in patients admitted to the medicine or cardiothoracic ICU with diagnosis of sepsis or acute respiratory failure. Rectus femoris (RF) and tibialis anterior (TA) muscle ultrasound images were obtained day one of ICU admission, repeated serially and assessed for muscle cross-sectional area (CSA), layer thickness (mT) and echointensity (EI). Muscle strength, as measured by Medical Research Council-sum score, and muscle power (lower-extremity leg press) were assessed prior to ICU discharge. Physical function was assessed with performance on 5-times sit-to-stand (5STS) at hospital discharge. RESULTS: Forty-one patients with median age of 61 years (IQR 55-68), 56% male and sequential organ failure assessment score of 8.1 ± 4.8 were enrolled. RF muscle CSA decreased significantly a median percent change of 18.5% from day 1 to 7 (F = 26.6, p = 0.0253). RF EI increased at a mean percent change of 10.5 ± 21% in the first 7 days (F = 3.28, p = 0.081). At hospital discharge 25.7% of patients (9/35) met criteria for ICU-acquired weakness. Change in RF EI in first 7 days of ICU admission and muscle power measured prior to ICU were strong predictors of ICU-AW at hospital discharge (AUC = 0.912). Muscle power at ICU discharge, age and ICU length of stay were predictive of performance on 5STS at hospital discharge. CONCLUSION: ICU-assessed muscle alterations, specifically RF EI and muscle power, are predictors of diagnosis of ICU-AW and physical function assessed by 5x-STS at hospital discharge in patients surviving critical illness.

ICU Recovery Clinic Attendance, Attrition, and Patient Outcomes: The Impact of Severity of Illness, Gender, and Rurality.

OBJECTIVES: The primary purpose is to characterize patients attending ICU recovery clinic and then describe their trajectory of cognitive and emotional health in 1 year. DESIGN: Retrospective observational study to assess attendance, attrition, and patient outcomes. SETTING: ICU Recovery Clinic. PATIENTS: Adult patients recently admitted to ICU for sepsis or acute respiratory failure and who were referred to clinic. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-eight patients (63%) attended ICU recovery clinic with a mean age of 53.2 ± 16 years (range, 20-82 yr), 42% female and mean Sequential Organ Failure Assessment scores at an ICU admission of 9.4 ± 2.9 participated in outcomes. Twelve patients (32%) were lost to follow up and 12 patients (32%) were transferred to different providers before the end of 1 year. Sequential Organ Failure Assessment scores were negatively associated with health-related quality of life at baseline (r = -0.41; p = 0.033; n = 28) and short term (r = -0.40; p = 0.037; n = 27). Male patients had higher Sequential Organ Failure Assessment scores (mean difference = 2.4; t = 2.779; p = 0.008) and longer hospital length of stay (mean difference = 9.3; t = 2.27; p = 0.029). Female patients had higher scores on Hospital Anxiety and Depression Scale (mean difference = 7.2; t = 2.74; p = 0.01) and Impact of Events Scale-Revised (mean difference = 18.9; t = 2.74; p = 0.011) at the initial follow-up visit. Patients never attending clinic were more likely to live further away, have a tracheotomy, and spent longer time in the ICU. CONCLUSIONS: Attendance and attrition in ICU recovery clinic are related to patient factors (living in rural area) and ICU factors. Data suggest different recovery trajectories exist based on gender, severity of illness, and self-reported outcomes.

Recovery from COVID-19 and acute respiratory distress syndrome: the potential role of an intensive care unit recovery clinic: a case report.

BACKGROUND: In this case report, we describe the trajectory of recovery of a young, healthy patient diagnosed with coronavirus disease 2019 who developed acute respiratory distress syndrome. The purpose of this case report is to highlight the potential role of intensive care unit recovery or follow-up clinics for patients surviving acute hospitalization for coronavirus disease 2019. CASE PRESENTATION: Our patient was a 27-year-old Caucasian woman with a past medical history of asthma transferred from a community hospital to our medical intensive care unit for acute hypoxic respiratory failure due to bilateral pneumonia requiring mechanical ventilation (ratio of arterial oxygen partial pressure to fraction of inspired oxygen, 180). On day 2 of her intensive care unit admission, reverse transcription-polymerase chain reaction confirmed coronavirus disease 2019. Her clinical status gradually improved, and she was extubated on intensive care unit day 5. She had a negative test result for coronavirus disease 2019 twice with repeated reverse transcription-polymerase chain reaction before being discharged to home after 10 days in the intensive care unit. Two weeks after intensive care unit discharge, the patient returned to our outpatient intensive care unit recovery clinic. At follow-up, the patient endorsed significant fatigue and exhaustion with difficulty walking, minor issues with sleep disruption, and periods of memory loss. She scored 10/12 on the short performance physical battery, indicating good physical function. She did not have signs of anxiety, depression, or post-traumatic stress disorder through self-report questionnaires. Clinically, she was considered at low risk of developing post-intensive care syndrome, but she required follow-up services to assist in navigating the healthcare system, addressing remaining symptoms, and promoting return to her pre-coronavirus disease 2019 societal role. CONCLUSION: We present this case report to suggest that patients surviving coronavirus disease 2019 with subsequent development of acute respiratory distress syndrome will require more intense intensive care unit recovery follow-up. Patients with a higher degree of acute illness who also have pre-existing comorbidities and those of older age who survive mechanical ventilation for coronavirus disease 2019 will require substantial post-intensive care unit care to mitigate and treat post-intensive care syndrome, promote reintegration into the community, and improve quality of life.

Procalcitonin: A promising tool or just another overhyped test?

Sepsis is the leading cause of death worldwide. Timely administration of antibiotics is recognized as the cornerstone in the management of sepsis. However, inappropriate use of antibiotics may lead to adverse effects and the selection of drug-resistant pathogens. Microbiological cultures remain the gold standard to diagnose infection despite their low sensitivity and the intrinsic delay to obtain the results. Certain biomarkers have the benefit of rapid turnover, potentially providing an advantage in timely diagnosis leading to accurate treatment. Over the last few decades, there is an ongoing quest for the ideal biomarker in sepsis. Procalcitonin (PCT), when used alone or alongside additional clinical information, has shown to be a promising tool to aid in the diagnosis and management of patients with sepsis. In February 2017, the Food and Drug Administration (FDA) approved the use of PCT to guide antibiotic treatment in lower respiratory tract infections and sepsis. Despite a good negative predictive value for bacterial infection, the utility of PCT-guided antibiotic initiation is conflicting at best. On the other hand, the use of PCT-guided antibiotic discontinuation has shown to reduce the duration of antibiotic use, the associated adverse effects, and to decrease the overall mortality. The current review discusses the history and pathophysiology of procalcitonin, synthesizes its utility in the diagnosis and management of sepsis, highlights its limitations and compares it with other biomarkers in sepsis.