key: cord-1029582-munccwld authors: Monti, Giacomo; Leggieri, Carlo; Fominskiy, Evgeny; Scandroglio, Anna Mara; Colombo, Sergio; Tozzi, Margherita; Moizo, Elena; Mucci, Milena; Crivellari, Martina; Pieri, Marina; Guzzo, Francesca; Piemontese, Simona; De Lorenzo, Rebecca; Da Prat, Valentina; Fedrizzi, Monica; Faustini, Carolina; Di Piazza, Martina; Conte, Francesca; Lembo, Rosalba; Esposito, Antonio; Dagna, Lorenzo; Landoni, Giovanni; Zangrillo, Alberto title: Two‐months quality of life of COVID‐19 invasively ventilated survivors; an Italian single‐center study date: 2021-03-15 journal: Acta Anaesthesiol Scand DOI: 10.1111/aas.13812 sha: 125645041eff506d3e434dd8664ad8b355f83156 doc_id: 1029582 cord_uid: munccwld BACKGROUND: COVID‐19 disease can lead to severe functional impairments after discharge. We assessed the quality of life of invasively ventilated COVID‐19 ARDS survivors. METHODS: We carried out a prospective follow‐up study of the patients admitted to the Intensive Care Units (ICUs) of a teaching hospital. Patients affected by COVID‐19 ARDS who required invasive ventilation and were successfully discharged home were assessed through the telephone administration of validated tests. We explored survival, functional outcomes, return to work, quality of life, cognitive and psychological sequelae. The main variables of interest were the following: demographics, severity scores, laboratory values, comorbidities, schooling, working status, treatments received during ICU stay, complications, and psychological, cognitive, functional outcomes. RESULTS: Out of 116 consecutive invasively ventilated patients, overall survival was 65/116 (56%) with no death occurring after hospital discharge. Forty‐two patients were already discharged home with a median follow‐up time of 61 (51‐71) days after ICU discharge and 39 of them accepted to be interviewed. Only one patient (1/39) experienced cognitive decline. The vast majority of patients reported no difficulty in walking (32/35:82%), self‐care (33/39:85%), and usual activities (30/39:78%). All patients were either malnourished (15/39:38%) or at risk for malnutrition (24/39:62%). Exertional dyspnea was present in 20/39 (51%) patients. 19/39 (49%) reported alterations in senses of smell and/or taste either before or after hospitalization. CONCLUSIONS: Invasively ventilated COVID‐19 ARDS survivors have an overall good recovery at a 2‐months follow‐up which is better than what was previously reported in non‐COVID‐19 ARDS patients. The Coronavirus Disease 2019 (COVID-19) pandemic led to a dramatic number of Intensive Care Unit (ICU) admissions. In Italy, as of November 7th, 2020, 902,490 people were diagnosed with SARS-CoV-2 infection, 1 and 41,063 died. COVID-19 is in most cases a self-limited lower respiratory tract illness, but in some patients, it may cause acute respiratory distress syndrome (ARDS), shock, and multi-organ failure. [2] [3] [4] Long-term clinical outcomes of ARDS survivors is a topic of high interest 5 ; over the years, ARDS mortality declined but its incidence increased, and a growing number of ARDS survivors present functional, psychological, and cognitive consequences persisting for years. 6 Longterm follow-up of survivors of Severe Acute Respiratory Syndrome (SARS-CoV-1) and Middle East Respiratory Syndrome (MERS) showed a high prevalence of post-traumatic stress disorder (PTSD) (39%), depression (33%), anxiety (30%), and reduced quality of life. 7 Up to one-third of general ICU patients develop the so-called Post-Intensive Care Syndrome (PICS), 8 which includes cognitive, physical, and psychological sequelae, occurring independently of the reason for ICU admission. PICS leads to significant burden and costs for patients, caregivers, and society. It reduces patients' quality of life, due to an impaired physical and cognitive functioning and a delay or inability to return to work. Follow-up ICU of patients can facilitate prompt recognition and treatment of PICS and improve long-term physical, psychological, and cognitive outcomes. 9 The short-term mortality of invasively ventilated COVID-19 ARDS patients is extremely high, in the range of 80%-90%, 10, 11 and the middle-term outcome and quality of life of survivors is unknown. COVID-19 is severe and multifactorial, and it involves several organs and systems. 12 In the hypothesis that COVID-19 disease can lead to severe functional impairments after discharge, the primary aim of this study was to assess the quality of life of invasively ventilated COVID-19 ARDS survivors. This study is part of the COVID-BioB study, an observational investigation performed at San Raffaele Scientific Institute-a 1,350-bed university hospital in Milan, Italy. The study was approved by the hospital Ethics Committee (protocol No. 34/int/2020) and was registered on ClinicalTrials.gov (NCT04318366). All the authors reviewed the manuscript and vouch for the accuracy and completeness of the data and adherence to the study protocol. Our hospital was immediately involved in the management of the COVID-19 surge. Since the beginning, a reorganization of large areas of the hospital took place, in order to admit COVID-19 patients, and elective surgical activity was rapidly reduced and then stopped. 2, 3, 13 The emergency department admitted simultaneously up to 70 patients requiring oxygen therapy or non-invasive ventilation (NIV). In a few days, we had a total of 279 general ward beds dedicated to COVID-19 patients; moreover, the ICU beds were also increased from 28 to 72 (54 of them dedicated to critical COVID-19 patients). Healthcare staff was rapidly trained in order to use personal protective equipment and deliver care to critically ill patients. We were able to have a nurse ratio of at least 1:3 (one nurse for three patients) in our ICUs, therefore, ensuring high standards of care. We included all adult patients with COVID-19 ARDS admitted to an ICU of San Raffaele Scientific Institute during the study period (February 25th, 2020 -April 27th, 2020), who received at least one day of invasive ventilation, and were already discharged home on June 3rd. Patients aged 18 years or over admitted to an ICU at San Raffaele Scientific Institute, affected by confirmed SARS-CoV-2 infection (defined as positive real-time reverse-transcriptase polymerase chain reaction from a nasal and/or throat swab together with signs, symptoms, and radiological findings suggestive of COVID-19 pneumonia), were included in the study. Anesthesiologists and intensivists managed patients in the ICUs, while internal medicine and infectious diseases specialists managed the general wards, supported by intensivists for deteriorating patients. General ward patients could receive non-invasive ventilation, usually continuous positive airway pressure (CPAP) and, in selected cases, some were treated with prone positioning while receiving non-invasive ventilation (NIV). Prone position in the main ward was suggested in case of poor response to NIV, and if the first hour of treatment showed improvement it was continued. 14, 15 We were fully aware of the theoretical risk of aerosolization during NIV, exposing staff and patients to an increased risk of infection, but during In this prospective follow-up of survivors after severe COVID-19 ARDS, 39 of 42 patients discharged to their homes were assessed. There was an overall good recovery 2 months after discharge, with reduced body weight and exertional dyspnea being the main complaints. such a pandemic, the number of ICU beds for mechanical ventilation through tracheal intubation could rapidly become insufficient, whereas NIV can be offered also outside the ICU. 16 A management protocol for patients with COVID-19 respiratory failure was implemented in our hospital. 2 If the partial pressure of arterial oxygen (PaO2) was less than 8 kPa (60 mm Hg) or saturation of peripheral oxygen (SpO2) was less than 90%, while breathing room air, physicians would increase the fraction of inspired oxygen (FiO2) up to 70-80% via non-rebreathing mask with an O2 flow up to 15 L/min, and the target SpO2 would be >94%. If SpO2 was stable above 94%, the indication was to continue the treatment and monitor for deterioration. If SpO2 < 94% despite 15 L/min O2 via nonrebreathing mask, the physicians would start CPAP (initial parameters FiO2 0.5, PEEP 7.5cmH2O), with target SpO2 > 94% and recommended blood gas analysis after 1 hour, with the possibility to increase the PEEP up to 12 cmH2O if SpO2 < 94%. Intubation was considered if SpO2 < 94% and/ or PaO2/FiO2 < 26.7 kPa (200 mm Hg) and respiratory rate (RR) > 25-30 after 1 hour. For mechanically ventilated patients in the ICU, we adopted current recommendations for mechanical ventilation in patients with ARDS. Study methodology has been previously described. 2 We prospectively collected data on medical history, comorbidities, the Simplified Acute Physiology Score II (SAPS II), 17 ARDS severity according to the Berlin Definition, 18 major organ support, and outcome. To assess mid-term follow-up, discharged patients were contacted by phone by a trained investigator after a median of 61 days from ICU discharge. The follow-up questionnaire is described in detail in the Supplemental Digital Content. Data were progressively recorded in a dedicated database during the phone interview. For this study, we present the follow-up data as of June 3rd, 2020. We evaluated multidimensional outcomes through the phone administration of various tests. 33 We also explored patients' smoking habit, basal working status and return to work, alterations in senses of smell and taste. We also asked the patients to report any form of discrimination that they (or their families) may have endured because of the disease. Baseline data of consecutive COVID-19 patients who died during or after ICU stay were collected as well. 25th -75th percentiles) or as means with standard deviation (SD). Means and SD were used with normally distributed variables, while medians and IQR were used with non-normally distributed variables. Categorical and dichotomous variables were presented as absolute number and percentages (%). No data imputation for missing data was performed. Among invasively ventilated COVID-19 ARDS patients admitted to our ICUs in the study period, all the first 42 discharged home were contacted after a median follow-up of 61 (51-71) days after ICU discharge ( Figure 1 ): 39 accepted to reply (adherence rate 93%: one patient was abroad; one had a psychiatric illness; and one was confirmed alive by the general practitioner but did not answer). The mean age of our cohort of patients was 56 ± 10.5 years at ICU admission (six were >70 y), and 35 (90%) were males. Twentyeight (72%) had a job, two patients (5.1%) were current smokers, and the most frequent comorbidity was hypertension (49%). Mean SAPS II score was 31 ± 8.7, while the PaO2/FiO2 mean ratio was 16.7 ± 8.2 kPa (125 ± 61.8 mm Hg). Patients were on mechanical ventilation for a median of 9 (6-14) days. At the time of evaluations for the start of mechanical ventilation, according to the Berlin criteria, 18 Table 1 and Table S1 , and results of midterm follow-up questionnaires are presented in Table 2 and Table 3 . After a median of 61 (51-71) days after ICU discharge, only one patient (2.6%) had cognitive impairment at the Itel-MMSE scale. The overall quality of life explored through the administration of the EQ5D-3L test showed no difficulty in walking (32/39:82%), self-care (33/39:85%), and usual activities (30/39:78%), with only eight (21%) patients reporting moderate anxiety or depression. Psychological tests confirmed low rates of anxiety, depression, PTSD, and insomnia. Before the onset of the disease, 28 out of 39 patients (72%) were working. At 2 months after discharge, despite a good recovery, only eight patients (21%) had returned to their usual job, while one patient (2.6%) returned with different tasks due to the disease. Eleven out of 39 patients (28%) were unemployed or retired as before the COVID-19 disease, but 19 patients (49%) were not working because of COVID-19 disease-dependent reasons. Only two studies investigated the quality of life of COVID-19 ICU patients so far, and the majority of them focused on the need for a post-ICU follow-up of COVID-19 critical patients, due to the wellknown PICS. 34 Our patients were relatively young, a vast majority were males and overweight with few comorbidities, consistent with literature data reported so far. 40 We found that the number of active smokers was extremely low. This finding is surprising and counterintuitive. We had already noticed this finding when presenting the short-term reported in previous studies. 44, 45 Interestingly, although patients reported a good recovery, few of them returned to work. This is consistent with what has been previously reported for non-COVID-19 ARDS. 5 Percentage may not total 100 because of rounding. (Continues) Of note, our mid-term mortality was 44%. This is in the lower range of short-term mortality data from other groups in February-March 2020, 47,48 but far more encouraging when compared to early reports of short-term mortality which was in the range of 80%-90% for invasively ventilated patients with COVID-19 ARDS. 10, 11 Interestingly, mortality in our cohort was higher-than-expected as calculated by the SAPS II score, but in line with ARDS predicted mortality based on PaO2/FiO2 ratio. Due to improvement in short-term survival, there is now increasing awareness toward long-term sequelae of critical illness survivors. Ensuring good long-term quality of life, rather than simply survive an acute event, is now becoming the major goal of intensive care medicine. The strengths of our study are the well-defined and detailed characterization of the cohort of COVID-19 survivors and our high-rate of response to follow-up. Even for the three patients that did not Percentage may not total 100 because of rounding. complete the interview, we were able to assess survival status by other strategies. We had very few missing data in the questionnaire, mainly due to language issues (2 patients were foreigners, although Italian speaking) in the administration of slightly more complex tests (HADS, PCL-5, ISI, Itel-MMSE). Outcomes are deeply influenced by age and frailty as testified by the baseline data of the first 39 invasively ventilated COVID-19 ARDS ICU patients who died (Table S1) . A limitation of the study is the limited sample size and the short follow-up time. Moreover, it is proved that the depth of patient's insights is strongly influenced by means of communication: questionnaires administered by telephone do not have the same degree of reliability as tests administered face to face. Another limitation is the different rehabilitation interventions received by patients, which may influence the reported outcomes. All patients were offered a period of rehabilitation, and almost all had an in-hospital rehabilitation, while very few were the ones that showed a level of recovery good enough to be discharged home immediately after their general ward stay. Our data are limited to ICU survivors from a single-center, and may not be generalizable to all COVID-19 patients. In consideration of the exercise limitations reported by our patients, future studies should involve objective measures of pulmonary functioning through the administration of tests such as the 6-minutes walking test (6MWT), Spirometry, and CT-scan. Also, the role of current or previous smoking in the course of the disease should be addressed in the future. Pain is a field that should be as well adequately explored: nearly 50% of our COVID-19 ARDS survivors report pain to some extent, and further studies should investigate its quality and characteristics. In summary, in a cohort of consecutive COVID-19 invasively ventilated ARDS patients we found a 56% survival rate at 2 months after ICU discharge. The overall quality of life in survivors was good, and cognitive and psychological outcomes showed no impairment at the 2 months follow-up, suggesting that recovery in COVID-19 patients with ARDS could be better than previously published in non-COVID-19 patients. All the authors have disclosed that they do NOT have any conflicts of interest or source of funding. We thank all healthcare personnel of our Institute for the care provided to COVID-19 patients during the pandemic. All the authors equally contributed to the manuscript. All the authors approved the final version of the paper for publication. 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