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Abstract
Previous experience has shown that transporting patients on extracorporeal membrane
oxygenation (ECMO) is a safe and effective mode of transferring critically ill patients
requiring maximum mechanical ventilator support to a quaternary care center. The coronavirus
disease 2019 (COVID-19) pandemic posed new challenges. This is a multicenter, retrospective
study of 113 patients with confirmed severe acute respiratory syndrome coronavirus
2, cannulated at an outside hospital and transported on ECMO to an ECMO center. This
was performed by a multidisciplinary mobile ECMO team consisting of physicians for
cannulation, critical care nurses, and an ECMO specialist or perfusionist, along with
a driver or pilot. Teams practised strict airborne contact precautions with eyewear
while caring for the patient and were in standard Personal Protective Equipment. The
primary mode of transportation was ground. Ten patients were transported by air. The
average distance traveled was 40 miles (SD ±56). The average duration of transport
was 133 minutes (SD ±92). When stratified by mode of transport, the average distance
traveled for ground transports was 36 miles (SD ±52) and duration was 136 minutes
(SD ±93). For air, the average distance traveled was 66 miles (SD ±82) and duration
was 104 minutes (SD ±70). There were no instances of transport-related adverse events
including pump failures, cannulation complications at outside hospital, or accidental
decannulations or dislodgements in transit. There were no instances of the transport
team members contracting COVID-19 infection within 21 days after transport. By adhering
to best practices and ACE precautions, patients with COVID-19 can be safely cannulated
at an outside hospital and transported to a quaternary care center without increased
risk to the transport team.
Summary Background An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3–11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. Interpretation The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Funding None.
Background Multiple major health organisations recommend the use of extracorporeal membrane oxygenation (ECMO) support for COVID-19-related acute hypoxaemic respiratory failure. However, initial reports of ECMO use in patients with COVID-19 described very high mortality and there have been no large, international cohort studies of ECMO for COVID-19 reported to date. Methods We used data from the Extracorporeal Life Support Organization (ELSO) Registry to characterise the epidemiology, hospital course, and outcomes of patients aged 16 years or older with confirmed COVID-19 who had ECMO support initiated between Jan 16 and May 1, 2020, at 213 hospitals in 36 countries. The primary outcome was in-hospital death in a time-to-event analysis assessed at 90 days after ECMO initiation. We applied a multivariable Cox model to examine whether patient and hospital factors were associated with in-hospital mortality. Findings Data for 1035 patients with COVID-19 who received ECMO support were included in this study. Of these, 67 (6%) remained hospitalised, 311 (30%) were discharged home or to an acute rehabilitation centre, 101 (10%) were discharged to a long-term acute care centre or unspecified location, 176 (17%) were discharged to another hospital, and 380 (37%) died. The estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 37·4% (95% CI 34·4–40·4). Mortality was 39% (380 of 968) in patients with a final disposition of death or hospital discharge. The use of ECMO for circulatory support was independently associated with higher in-hospital mortality (hazard ratio 1·89, 95% CI 1·20–2·97). In the subset of patients with COVID-19 receiving respiratory (venovenous) ECMO and characterised as having acute respiratory distress syndrome, the estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 38·0% (95% CI 34·6–41·5). Interpretation In patients with COVID-19 who received ECMO, both estimated mortality 90 days after ECMO and mortality in those with a final disposition of death or discharge were less than 40%. These data from 213 hospitals worldwide provide a generalisable estimate of ECMO mortality in the setting of COVID-19. Funding None.
To the Editor: With the dramatic increase of confirmed cases of coronavirus disease (COVID-19) and the increasing death toll in China, timely and effective management of severely and critically ill patients appears to be particularly important. Previous studies on COVID-19 mainly described the general features of patients (1). However, little attention has been paid to clinical characteristics and outcomes of intensive care patients, data on whom are scarce but are of paramount importance to reduce mortality. Some of the results of these studies have been previously reported in the form of an abstract (2). Methods This study enrolled 344 severely and critically ill patients (intensive care patients) who were diagnosed with COVID-19 according to World Health Organization interim guidance by positive result of an RT-PCR assay of nasal and/or throat-swab specimens, and were hospitalized in eight intensive care wards (totaling approximately 330 beds) in Tongji hospital from January 25, 2020, through February 25, 2020. The intensive care wards staff intensivists and specialist nurses in intensive care and were equipped with continuous vital signs monitoring and respiratory support, including noninvasive and invasive ventilators, high-flow nasal cannula (HFNC) oxygen therapy, and extracorporeal membrane oxygenation. We collected demographic, clinical, laboratory, and radiologic findings, and treatment and outcome data from electronic medical records. The illness severity of COVID-19 was defined according to the Chinese management guideline for COVID-19 (version 6.0) (3). Cytokines were measured by a chemiluminescent immunometric assay (Immulite 1000; Diagnostic Products). Acute respiratory distress syndrome (ARDS) was diagnosed according to the Berlin definition, and septic shock was defined according to the 2016 Third International Consensus definition (4, 5). Disseminated intravascular coagulation was defined per the International Society of Thrombosis and Haemostasis, and acute kidney injury was diagnosed according to the Kidney Disease Improving Global Outcomes clinical practice guidelines (6). Myocardial damage was diagnosed according to the serum levels of cardiac biomarkers or new abnormalities in electrocardiography and echocardiography. Liver injury was diagnosed according to elevation of bilirubin and aminotransferase. Rhabdomyolysis was diagnosed on the basis of the serum level of creatine kinase and myoglobin. Survival endpoint was 28-day mortality after admission to the intensive care ward. The Ethics Commission of Tongji hospital approved this study, with a waiver of informed consent. Continuous variables are presented as median (interquartile range [IQR]), whereas categorical variables were expressed as frequencies (%). Statistical analyses were conducted with R3.6.2 (https://www.r-project.org/) using a Fisher’s exact test for categorical data and Mann-Whitney test for continuous data; Kaplan-Meier estimator and Cox regression were used for survival analysis. Correlations were measured by Spearman’s method (ρ). For unadjusted comparisons, a two-sided P less than 0.05 was considered statistically significant. Results Characteristics and treatment Of the 344 intensive care patients (Table 1), nonsurvivors are generally older than survivors, with a higher proportion aged over 60 years, and every 10-year increase in age was associated with a 58% additional risk (hazard ratio [HR], 1.58; 95% confidence interval [CI], 1.38–1.81; P 60 194 (56.4) 93 (44.1) 101 (75.9) Sex, M 179 (52.0) 105 (49.8) 74 (55.6) 0.341 Signs and symptoms Fever 301 (87.5) 186 (88.2) 115 (86.5) 0.770 Dry cough 233 (67.7) 137 (64.9) 96 (72.2) 0.200 Dyspnea 208 (60.5) 108 (51.2) 100 (75.2) 90), ml/min/1.73 m2 87 (70–101) 93 (78–107) 74 (55–91) <0.001 Glu (3.9–6.1), mmol/L 6.8 (5.7–9.0) 6.1 (5.2–7.8) 8.2 (6.6–11.4) <0.001 Radiologic manifestation <0.001 GGO 164 (47.7) 101 (50.8) 63 (54.8) Local patchy opacities 38 (11.0) 35 (17.6) 3 (2.6) Bilateral patchy opacities 110 (32.0) 61 (30.7) 49 (42.6) Organ function injury ARDS 145 (42.2) 17 (8.1) 128 (97.0) <0.001 Septic shock 114 (33.1) 2 (0.9) 112 (84.2) <0.001 DIC 71 (20.6) 1 (0.5) 70 (52.6) <0.001 AKI 86 (25.0) 6 (2.8) 80 (60.2) <0.001 Myocardial damage 111 (32.3) 4 (1.9) 107 (80.5) <0.001 Liver injury 54 (15.7) 9 (4.3) 45 (33.8) <0.001 Rhabdomyolysis 9 (2.6) 0 (0) 9 (6.9) <0.001 Ventilatory support throughout the course HFNC oxygen therapy 35 (10.2) 7 (3.3) 28 (21.1) <0.001 NIV 34 (9.9) 7 (3.3) 27 (20.3) <0.001 IV 100 (29.1) 3 (1.4) 97 (72.9) <0.001 Definition of abbreviations: ACE = angiotensin-converting enzyme; AKI = acute kidney injury; ALT = alanine transaminase; ARDS = acute respiratory distress syndrome; AST = aspartate transaminase; BUN = blood urea nitrogen; CK = creatine kinase; CK-MB = creatine kinase, MB form; COPD = chronic obstructive pulmonary disease; COVID-19 = coronavirus disease; Cr = serum creatinine; DIC = disseminated intravascular coagulation; e-GFR = estimated glomerular filtration rate; GGO = ground-glass opacity; Glu = fasting blood glucose; HFNC = high-flow nasal cannula; hs-CRP = high-sensitivity C-reactive protein; INR = international normalized ratio; IV = invasive ventilation; LDH = lactate dehydrogenase; Myo = myoglobin; NIV = noninvasive ventilation; PCT = procalcitonin; SpO 2 = oxygen saturation as measured by pulse oximetry; TBIL = total bilirubin; TNF-α = tumor necrosis factor α. All records were measured at admission to intensive care wards unless otherwise indicated. Data are shown as n (%) or median (interquartile range). * The percentages represent the frequency divided by the total cohort size (N = 344), whereas percentages in subgroups were calculated according to contingency table, with missing data removed first. † Normal ranges of listed biochemical parameters are indicated in parentheses. Ventilatory support A total of 35 (10.2%) patients were treated with HFNC, of whom 23 (65.7%) also received invasive ventilation. Of the 12 patients who received HFNC only, 7 (58.3%) died at or before 28 days. A total of 134 (40.6%) patients were treated with mechanical ventilation (either noninvasive or invasive), of whom 34 received treatment of noninvasive ventilation only, and 27 (79.4%) died at or before 28 days, whereas invasive ventilation was given to 100 patients, with 97 (97%) deaths at or before 28 days. Median duration from admission to invasive ventilation was 5 (IQR, 1–8) days, and median duration of invasive ventilation was 4 (IQR, 3–8) days. Of the 145 patients who developed ARDS, 100 (69.0%) were treated with invasive ventilation. Clinical course and outcomes A total of 133 (38.7%) patients died at or before 28 days, with a median survival of 25 days (Figure 1). For nonsurvivors, median duration from admission to death was 10 (IQR, 6–15) days. Of the 211 survivors, 185 (87.7%) were discharged. Median duration from onset of symptoms to laboratory confirmation of infection by RT-PCR was 8 (IQR, 5–11) days. In survivors, median duration from positive to negative RT-PCR result was 12 (IQR, 9–15) days, whereas, in nonsurvivors, median duration from infection confirmation to death was 15 (IQR, 10–19) days (Figure 1). Figure 1. (Left panel) Kaplan-Meier curve showing a 28-day median survival of 312 intensive care patients in this cohort (32 out of 344 patients lack records of survival time). (Right panel) Timeline showing the time span from symptoms onset (median) to three important events. IQR = interquartile range. Discussion This report, to our knowledge, is the largest case series of patients with COVID-19 in intensive care, with informative laboratory characteristics, detailed clinical course, and outcome. In our cohort, nonsurvivors were older than survivors, which is consistent with an earlier study (7). We did not observe survival differences in regard to sex, but this is inconsistent with the results of a previous study (8). Compared with survivors, nonsurvivors presented more commonly with dyspnea and a higher respiratory rate, indicating that more attention should be paid to changes in vital signs with respect to respiratory rate for intensive care patients. A previous study revealed that original comorbidities were potential risk factors (8), and we observed that hypertension is significantly differentially distributed between nonsurvivors (69 [52.3%]) and survivors (72 [34.1%]), and 62 out of 141 (44.0%) patients with hypertension had a medication history of taking ACE (angiotensin-converting enzyme) inhibitors. Given that ACE2 plays a dual role of vasopeptidase and severe acute respiratory syndrome (SARS) virus receptor, we speculated that patients with hypertension with COVID-19 might be more likely to become critically ill (9). In addition, S/F may be a useful and noninvasive predictive marker, which was defined by the Kigali modification of the Berlin definition and had good correlation with the diagnosis of ARDS (10). Given a large patient flow during epidemic conditions, this indicator could be flexibly used for screening and monitoring. Lymphocytopenia occurred in almost 70% and was predominant in nonsurvivors, which contradicts a previous study with a relatively small sample size (8). Lymphocytopenia is a prominent feature of critically ill patients with SARS (11) and Middle East respiratory syndrome, which is the result of apoptosis of lymphocytes (12); thus, lymphocyte depletion could be harmful, and lymphocyte count might serve as another prognostic factor for SARS–coronavirus 2 (SARS-CoV-2). In addition, we observed a higher level of hs-CRP (high-sensitivity C-reactive protein), along with other inflammatory markers, which is consistent with relevant reports of SARS and Middle East respiratory syndrome (13). Unexpectedly, however, nonsurvivors showed a higher level of IL-2R. Highly expressed IL-2R initiates autoreactive cytotoxic CD8+ T-cell–mediated autoimmunity. Meanwhile, IL-2 stimulates the proliferation of natural killer cells that highly express IL-2R, promoting the release of cytokines, further inducing the lethal “cytokine storm” (14). We also observed that factors, such as red blood cell distribution width, lactate dehydrogenase, and coagulation index, were upregulated in nonsurvivors, which was probably due to their active participation in inflammatory response. It has been reported that chest computed tomography imaging can be more sensitive diagnostically compared with RT-PCR (15), and we reasoned that computed tomography might even show guiding significance in the critical stage of COVID-19. The high mortality rate of patients who received mechanical ventilation may have been due, in part, to the centralized admission of a large number of intensive care patients in February and the fact that patients were sometimes transferred late to the hospital. These conditions made us question the effectiveness of noninvasive ventilation treatment or HFNC in the first line, and whether the early use of invasive ventilation would improve prognosis. Both questions may be worth further study in a larger cohort. In summary, in this single-center case series study, older patients with comorbidities are at dramatically increased risk of mortality. Real-time monitoring of S/F and regular measurements of lymphocyte count and inflammatory markers may be essential to disease management.
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