key: cord-1038023-7aij0j2a authors: Aleva, F.E.; van Mourik, L.; Broeders, M.E.A.C.; Paling, A.J.; de Jager, C.P.C. title: COVID-19 in critically ill patients in North Brabant, the Netherlands: Patient characteristics and outcomes date: 2020-08-08 journal: J Crit Care DOI: 10.1016/j.jcrc.2020.08.001 sha: 00c4c4215a0b95d8eced47fb1b356281aaf46f7e doc_id: 1038023 cord_uid: 7aij0j2a PURPOSE: Since the SARS-CoV-2 pandemic, countries are overwhelmed by critically ill Coronavirus disease 2019 (COVID-19) patients. As ICU capacity becomes limited we characterized critically ill COVID-19 patients in the Netherlands. METHODS: In this case series, COVID-19 patients admitted to the ICU of the Jeroen Bosch Hospital were included from March 9 to April 7, 2020. COVID-19 was confirmed by a positive result by a RT-PCR of a specimen collected by nasopharyngeal swab. Clinical data were extracted from medical records. RESULTS: The mean age of the 50 consecutively included critically ill COVID-19 patients was 65 ± 10 years, the mean BMI was 29 ± 4.7 and 66% were men. Seventy-eight percent of patients had ≥1 comorbidity, 34% had hypertension. Ninety-six percent of patients required mechanical ventilation and 80% were ventilated in prone position. Venous thromboembolism was recognized in 36% of patients. Seventy-four percent of patients survived and were successfully discharged from the ICU, the remaining 26% died (median follow up 86 days). The length of invasive ventilation in survivors was 15 days (IQR 12–31). CONCLUSIONS: The survival rate of COVID-19 critically ill patients in our population is considerably better than previously reported. Thrombotic complications are commonly found and merit clinical attention. Trial registration number NL2020.07.04.01 Given its rapid global spread, over 10 million cases have been confirmed and COVID-19 has been responsible for at least 500,000 deaths by June 30, 2020. 3 COVID-19 represents a severe respiratory illness characterized by fever, dry cough and dyspnoea. 2 Although the most infected individuals experience mild complaints, infected patients are frequently admitted to hospitals. More importantly, a significant proportion of the admitted patients develop acute respiratory failure and require management in intensive care units (ICUs). 2, 4, 5 Several studies report prolonged treatment in ICU together with a high mortality in critically ill COVID-19 patients. [6] [7] [8] The need for prolonged intensive care treatment stresses health care facilities, as seen in China and the North of Italy. 2, 5 In the Netherlands, the first confirmed COVID-19 case was reported on the 27 th of February 2020 and was followed by an outbreak in the region of Noord-Brabant. 9 Dutch hospitals increased their intensive care capacity and a national coordination center allocates ICU patients to hospitals across the country. Investigators reviewed electronic medical records, laboratory results and radiological examinations. The demographical data concern admission date, age, gender, body mass index (BMI), ideal body weight (IBW), smoking status and comorbidities. Data on symptoms, vital parameters, laboratory parameters and radiographic findings were extracted, as well as the course of disease on the ICU (e.g. the need for mechanical ventilation, renal replacement therapy and complications such as VTE. Outcome parameters concern survival, discharge, days of mechanical ventilation, length of stay in hospital and length of stay in ICU. This observational case series aims to describe clinical characteristics and patient outcomes in Fifty critically ill COVID-19 patients were consecutively included from March 9, 2020 and followed up to June 20, 2020. The demographical and clinical characteristics are displayed in table 1. The mean age was 65 ± 10 (range 33 -82 years); 66% of patients were men and the mean BMI was 29 ± 4.7. Twenty-two percent of the patients had no relevant comorbidities. The most common comorbidities were hypertension (34%), type II diabetes (14%), obstructive sleep apnea (12%) and ischemic heart disease (10%) (see table 1 ). The mean duration of symptoms on admission to the hospital was 8.2 ± 3.5 days. The most common symptoms were shortness of breath (84%) and cough (82%). Upon presentation at the emergency department 53% of the patients had fever (see table 2 ). Bilateral pulmonary infiltrates were seen on 82% of the chest radiographs, see table 3 Also increased ferritin levels were observed, median 1200 ng/L (IQR 748 -1750) (see table 3 ). All patients were admitted to the ICU due to acute hypoxemic respiratory failure in absence of hemodynamic instability. Of the 50 admitted patients, 49 were in need of invasive or non-invasive respiratory support (98%)(see table 4 ). Endotracheal intubation and mechanical ventilation was The mortality rate observed in this study is considerably lower than previously reported. Yang et al. reported 61.5% mortality in a similar sized study performed in China. 7 Two studies performed in the United States report a mortality of 67% and 50%, respectively. 8 Italy showed a similar mortality rate of 26%, however, 58% of patients still received active treatment in ICU at the time of publication. 6 The mortality rates may be subject to various factors. First, countries that were affected early in the pandemic were overwhelmed by this previously unknown disease and may have experienced issues with allocation of healthcare resources. 2, 5 After early warnings from our colleagues, the level of preparedness in the Netherlands was high, shown by the increased ICU capacity on a national level and the Dutch system of patient allocation across the country. Second, in the Netherlands a stringent patient selection for ICU admission is generally applied, hence the data may be subject to patient selection. Patients with important comorbidities, a poor functional status or frailty are less frequently admitted to the ICU. 11 This is supported by data from the Dutch surveillance registry, National Intensive Care Evaluation (NICE). In their last report, the overall mortality of COVID-19 critically ill patients in the Netherlands was 31%, in a similar patient group in terms of age, gender and comorbidities. 12 In comparison to previous studies, our study has a significantly longer follow up and, additionally, prolonged ICU treatment may be pursued in patients with a better prognostic perspective. In the early stages of the pandemic little was known on the clinical course of the disease, whereas over time more became known and different treatment-and supportive strategies were proposed. Below, several factors that may have improved clinical outcome from a medical perspective are discussed. COVID-19 in critically ill patients is characterized by severe hypoxemia that has been attributed to the development of Acute Respiratory Distress Syndrome (ARDS). 6,13 A substantial proportion of our patients were ventilated in prone position according to our local protocol (based on the ARDSnet low tidal volume protocol). 13, 15 These lung-protective ventilatory strategies may improve patient survival in COVID-19, although this has not yet been formally established. Interestingly, most mechanically ventilated COVID-19 patients had a discrepantly good lung compliance. 16 Reports of pulmonary embolism in critically ill COVID-19 patients gained attention and during the study period VTE indeed were increasingly recognized. VTE were found in over a third of the critically ill COVID-19 patients and probably VTE have been overlooked in earlier cases. A recent publication that systematically investigated VTE in critically ill COVID-19 patients reports an incidence J o u r n a l P r e -p r o o f Journal Pre-proof of 31%. 17 Inflammation and coagulation are closely linked biological systems. 18, 19 The risk of VTE is higher during episodes of increased inflammation as has been shown in several clinical settings. [20] [21] [22] In critically ill COVID-19 patients, the risk for VTE is particularly high and more emphasis should be placed on the early recognition of thrombotic complications since VTE have important clinical consequences and may improve patient survival. Another explanation for the discrepantly compliant lung may be the development of bradykinindependent local lung angioedema. 23 Further research is needed to increase our understanding of the underlying mechanisms and to address the role of bradykinin in COVID-19. Lastly, it has been suggested that the administration of corticosteroids may be beneficial in critically ill COVID-19 patients. 24 In the late phase of our study several patients were treated with corticosteroids in the presence of a hyperinflammatory profile without signs of infection. There has been a long-standing questionable relationship with the use of corticosteroids in critically ill patients and well-designed studies are needed to address its role. Data are mean (SD) or n (%), unless otherwise specified. Data are mean (SD) or n/total n of patients with available data (%). J o u r n a l P r e -p r o o f Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy: Early Experience and Forecast During an Emergency Response Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State COVID-19; patient zero in the Netherlands Covid-19 in Critically Ill Patients in the Seattle Region -Case Series Should this elderly patient be admitted to the ICU? Nationale Intensive Care Evaluatie (NICE) COVID-19 in Dutch Intensive Care Units; patient characteristics and outcomes Acute respiratory distress syndrome: the Berlin Definition Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome Prone positioning in severe acute respiratory distress syndrome Respiratory mechanics to understand ARDS and guide mechanical ventilation Incidence of thrombotic complications in critically ill ICU patients with COVID-19 The interactions between inflammation and coagulation Inflammation as a cause of venous thromboembolism Prevalence and Localization of Pulmonary Embolism in Unexplained Acute Exacerbations of COPD: A Systematic Review and Meta-analysis Pneumonia and risk of venous thrombosis: results from the MEGA study Acute infection as a trigger for incident venous thromboembolism: Results from a population-based case-crossover study Kinins and Cytokines in COVID-19: A Comprehensive Pathophysiological Approach Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease Guarantor statement. F.A. and L.M. are the guarantors of the study and take responsibility for the integrity of the data and the accuracy of the data analysis.