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Introduction: Prone positions have been used extensively to improve oxygenation in patients with acute respiratory distress syndrome (ARDS). During the COVID-19 pandemic there was widespread adoption of proning in patients with acute severe hypoxic respiratory failure. Few studies explore the use of prone positioning in mechanically ventilated COVID-19 patients. Method(s): This study was part of the REACT COVID observational study at University Hospital Southampton (UHS) [1]. Eligibility included admission to UHS with a positive COVID-19 RT-PCR between 03/2020 and 03/2022. Data was collected from all available electronic clinical data sources using semi-automated and manual data extraction. Result(s): 184 patients received invasive mechanical ventilation with documented evidence for 931 prone episodes. We performed detailed analysis for 763 prone episodes. The rest were excluded due to insufficient data. The median duration of each cycle was 16 h (IQR 15-17 h). 459 cycles were done within 7 days of intubation (early), 202 in 7-14 days (intermediate) and 102 after 14 days (late). The change in oxygenation defined as delta PaO2/ FiO2 ratio (DELTAPF) for early, intermediate, and late cycles were 2.4 +/- 5.2 kPa, 1.6 +/- 3.7 kPa and 1.4 +/- 4.0 kPa, (p = 0.03) respectively. The overall DELTAPF for all groups after a cycle was 2.1 +/- 4.7 kPa. There was an increase in PaCO2 following proning with an overall change of 0.30 +/- 1.0, however, this was not statistically significant (p = 0.30). Conclusion(s): Following proning, there was significant improvement in oxygenation. Cycles lasted for 16 h consistent with current ARDS guidelines [2]. Although the results suggest a diminishing response in those proned at later times, the DELTAPF ratio was still significant. Overall, this suggests a beneficial effect on oxygenation. However, findings cannot be translated into survival benefit. Further research including randomised controlled trials is recommended.
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Introduction: Pulmonary embolism (PE) is a major cause of intensive care unit (ICU) mortality and morbidity [1]. Optimal venous thromboembolism preventive strategy in COVID-19 patients remains a controversial issue. Therapeutic anticoagulation in the context of severe COVID-19 without a formal indication does not appear to offer a survival advantage and was associated with increased risk of major bleeding episodes. Locally, we adopted an enhanced anticoagulation (enoxaparin twice a day) pathway guided by anti-Xa levels. Method(s): This is a retrospective cross-sectional single-center study between March 2020 and March 2021. All patients admitted to the intensive care unit at University Hospital Southampton with diagnosis of COVID-19 confirmed via a reverse-transcriptase-polymerase-chain reaction (RT-PCR) test were included in this study. Result(s): There were 292 admissions included in the study with a mean age of 60 (+/- 15). 67.1% received enhanced anticoagulation titrated according to anti-Xa levels. The median day 7 trough and peak anti-Xa levels were 0.33 (IQR 0.18-0.41) and 0.54 (IQR 0.33-0.68) respectively. 62 patients had CTPA for clinical suspicion of pulmonary embolism and 11 were positive. The overall incidence of PE was 3.8%. The distribution of PE was mostly bilateral segmental or unilateral segmental. There were no lobar or main pulmonary artery pulmonary embolism. There were 9 major bleeding episodes in those received enhanced anticoagulation. Conclusion(s): For critically ill COVID-19 patients, anti-Xa guided enhanced anticoagulation protocol proved to be associated with lower than anticipated incidence of PE with minimal clot burden. Randomised controlled trials are required to explore this concept further.
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S44 Table 1Summary of significant medical events, thoracic computed tomography (CT) and pulmonary function tests (PFTs) in ORBCEL-C and placebo groups at 1 year follow upORBCEL-C Placebo Number of patients followed up 20 21 Significant medical events Number of patients with SMEs 6/20 9/21 Total SME events 7 11 Classification Respiratory,thoracic and mediastinal disorders 4 6 Neoplasm - benign, malignant, unspecified 1 0 Infections and infestations 1 1 Cardiac disorders 1 0 Metabolism and nutrition disorders 0 1 Injury, poisoning and procedural complications 0 1 Renal and urinary disorders 0 1 Gastrointestinal disorders 0 1 Thoracic CT Number of CTs available 5 8 Time to CT (Median, IQR) 181 (157–198) 203 (95–233) Evidence of ILD on CT 4 6 PFTs Number of PFTs available 10 8 Time to PFTs (Median, IQR) 184.5 (117.5–292.75) 203.5 (118.25–242.5) FEV1 (Mean, SD) 84.9 (13.6) 80.5 (13.3) FEV1 <80% predicted (n,%) 4/10 (44%) 4/8 (50%) FVC (Mean, SD) 78.4 (13.2) 79.3 (16.5) FVC <80% predicted (n,%) 5/10 (55%) 5/8 (62.5%) FEV1/FVC ratio (Mean, SD, n) 0.88 (0.12) N=8 0.76 (0.05) N=5 FEV1/FVC <0.7 (n,%) 0 (0%) 0 (0%) TLCO (Mean, SD, n) 78.9 (14.8) N=9 61.9 (13.4) N=7 TLCO <80% (n,%) 6/9 (66.7%) 7/7 (100%) ConclusionsOne year follow up supports the safety of ORBCEL-C MSCs in patients with moderate to severe ARDS due to COVID-19. A similar incidence of pulmonary dysfunction is reported in both groups at long term follow up.Please refer to page A?? for declarations of interest related to this .
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Introduction: There have been over 200 million cases and 4.4 million deaths from Covid-19 worldwide. In the UK over half a million have required hospitalisation, with over 130,000 deaths. Although most experience a mild illness the mortality can be over 50% for those requiring mechanical ventilation.1 One potential treatment for severe hypoxaemia is inhaled pulmonary vasodilator (IPVD) therapy, either as nitric oxide (NO) or prostaglandin analogues. Despite the lack of robust evidence IPVDs are often considered recue treatments for refractory hypoxaemia.2,3 Given the disease severity in COVID-19 we implemented a protocol for the use of IPVDs on a compassionate basis for patients with severe hypoxaemia receiving otherwise maximal support. In this study we detail our findings and assess differences between survivors and non-survivors. Objectives: The primary outcome of this study was percentage changes in PaO2/FiO2 (PF) ratio and Alveolararterial (A-a) gradient at 2, 6, 12, 24, 48 and 72 hours following initiation of IPVD therapy. Secondary outcomes were differences in characteristics and response to therapy between survivors and non-survivors who received an IPVD. Methods: Data from a prospectively maintained research database of patients with SARS-CoV-2 admitted to the ICU at a large teaching hospital were analysed for the time period 14 March 2020 -11 February 2021. Patients aged 18 years or older who received an IPVD during their admission were eligible for inclusion. An IPVD was considered if the PF ratio was less than 13.3kPa despite rescue therapies (prone positioning, neuromuscular blockade, airway pressure release ventilation). Nitric oxide was commenced at 20ppm and titrated to response. If oxygenation improved Iloprost nebulisers were commenced at 10-30mcg four hourly and NO weaned. Results: Three-hundred eight patients with SARS-Cov-2 were admitted during the study period of whom 59 (19.2%) received IPVD therapy. Patients receiving an IPVD had a lower PF ratio (14.37 vs. 16.37kPa, p=0.002) and higher APACHE-II score (17 vs. 13, p=0.028) at admission compared to those who did not. Survival to ICU discharge was lower in patients receiving an IPVD (55.9% vs. 81.9%, p<0.001). The median PF ratio at commencing IPVD therapy was 11.33kPa (9.93-12.91) with a median of 6 days from admission to receiving an IPVD. At 72 hours the median improvement in PF ratio was 33.9% (-4.3-84.1). In patients receiving IPVDs there were no differences in other therapies received (steroids, prone ventilation, ECMO) between survivors (n=33) and non-survivors (n=26), with the exception of renal replacement therapy. At 72 hours changes in PF ratio (70.8 vs. -4.1%) and reduction in A-a gradient (44.7 vs. 14.8%) differed significantly between survivors and non-survivors (both p <0.001). Conclusion: The response to the compassionate use of IPVDs for patients with acute hypoxic respiratory failure due to Covid-19 differs significantly between survivors and non-survivors. Both NO and inhaled prostaglandins may offer therapeutic options for severe hypoxaemia due to COVID-19, with prostaglandins particularly attractive as they do not require specialist delivery systems. The use of inhaled prostaglandins, and NO where feasible, should be studied in both isolation and combination in adequately powered prospective randomised trials.
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Introduction: COVID-19 has presented as a wide spectrum of severity, from asymptomatic transmission to acute hypoxic respiratory failure (AHRF). Non-invasive ventilation (NIV) has been increasingly used during the pandemic, partially driven due to resource constraints. There has, however, been varying opinions of the best strategy managing the acute hypoxic respiratory failure, of immediate versus delayed intubation, and the role of NIV. Objectives: With this trial we aimed to explore noninvasive ventilation as a primary ventilation strategy with its outcomes. Also, looking at duration of therapy and associated patient characteristics which may help predict NIV success or failure. Method: This was a single-centre retrospective observational study (REC reference 17/NW/0632) between 19/3/20 and 12/3/21. Patients managed with NIV only or NIV prior to invasive mechanical ventilation (IMV) were included. Patients receiving only NIV outside ICU and NIV as part of weaning from IMV were excluded. The term NIV is used to include both continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP). Data was taken from electronic health records used in the ICU. NIV was applied via a full facemask or a facemask covering the nose and mouth. NIV failure was defined by the need for intubation and IMV or death during hospital stay. Results: Between 19/3/20 and 12/3/21 309 patients were admitted to ICU with confirmed Covid-19 and AHRF. Of these 250 (80.9%) were initially managed with NIV and 59 (19.1%) were intubated immediately. Of those managed with NIV, 137 (54.8%) received NIV only, and 113 (42.5%) were subsequently intubated. 18 patients managed purely on NIV did not survive, with NIV their ceiling of treatment. Therefore 119 (47.6%) patients were successfully managed with NIV. NIV success patients were termed Group 1, NIV failure requiring IMV as Group 2. Group 2 was subdivided based on duration of NIV therapy prior to intubation. Within Group 2, 36 (31.9%) were intubated within 24 hours (2a), 37 (32.8%) within 24-96 hours (2b) and 40 (35.4%) after more than 96 hours (2c) of NIV. The hospital mortality for groups 2a, 2b, 2c were 19.4%, 35.1% and 47.5% respectively. Multivariate analysis showed the APACHE II score (OR 1.25, 95% CI 1.11-1.14, p<0.001) and PaO 2 /FiO 2 ratio< 13.3kPa (OR 4.73, 95% CI 1.82-13.2, p = 0.002) predicted the need for intubation and invasive mechanical ventilation. Conclusion: Almost half the patients of the NIV cohort required eventual intubation. A high APACHE II or SOFA score and hypoxaemia on admission were significant in this group. Of note despite worse APACHE II and SOFA scores the patients who were intubated <24 hours after failing NIV had a better survival rate than those intubated later. We were unable to comment if the poorer outcomes were due to disease progression regardless of intervention or delayed mechanical ventilation. However, nearly 50% of patients with AHRF due to Covid-19 improved without IMV and with better outcomes. While further trials are needed comparing NIV and IMV it appears that NIV can play a definite role in the management of acute hypoxaemic respiratory failure secondary to Covid-19 (Figure 2).
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Introduction: Hypoxic respiratory failure, a hallmark of severe COVID-19, often requires oxygen therapy.1 Mechanical ventilation carries a high mortality.2 We evaluate trends in oxygen indices (PaO2/FiO2 ratio, CaO2, O2ER) in COVID-19 patients throughout an intensive care admission and correlation with clinical outcomes. Objectives: To establish the trends in oxygen indices in mechanically ventilated adult COVID-19 patients throughout an intensive care admission. Methods: We performed a retrospective observational cohort study in a UK university hospital (ethics through REACT COVID-193), including all adult COVID-19 patients requiring mechanical ventilation between 01/03/20 and 31/ 03/21. We collected baseline characteristics, clinical outcomes and oxygen parameters. Results: 184 patients met inclusion criteria, providing 34592 blood gas data points over 30-days. The median age was 59.5 (IQR 51, 67), and median BMI 30 (IQR 25.8, 35.5). The majority were men (62.5%) of white ethnicity (70.1%). Median mechanical ventilation duration was 15-days (IQR 8, 25) and 133 patients (72.3%) survived 30-days. Oxygen indices are presented in Table 1. Non-survivors exhibited lower oxygen extraction;there was an averaged mean difference in O2ER of -0.06 (95% CI -0.09, -0.03) across days one to seven and -0.09 (95% CI -0.10, -0.07) across days one to 30. While both survivors and non-survivors had sub-physiological CaO2 (which trended down throughout their ICU admission), non-survivors tended to exhibit higher values;there is an averaged mean difference of 0.23 (95% CI 0.13, 0.34) across day one to day seven and 0.28 (95% CI 0.21, 0.35) across days one to 30. Conclusions: As a novel cause of respiratory failure, COVID-19 offers a unique opportunity to study a homogenous cohort. In mechanically ventilated adult COVID-19 patients, oxygen indices are abnormal. Despite having similar CaO2 values, oxygen extraction differs significantly between survivors and non-survivors, suggesting COVID-19 causes impaired oxygen utilisation. Urgent further evaluation is warranted.
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Background: Patients with COVID-19 present severe respiratory symptoms progressing to acute respiratory distress syndrome (ARDS). Upon infection, SARS-CoV-2 destroys cells expressing the ACE2 receptor including alveolar type II cells (AT2). These cells are found in the alveolar-capillary barrier which normally secrete pulmonary surfactant, a complex of lipid and surfactant proteins (SPA, SP-B, SP-C, SP-D). Exogenous surfactant therapy (mainly composed of phospholipids, SP-B, and SP-C) has been successful in treating neonatal respiratory distress syndrome (nRDS) caused by surfactant deficiency in preterm babies.Plasma SP-D has been proposed as a marker of lung injury in COVID-19 but so far, no reports have evaluated sequential SP-D levels in both airway and plasma. As part of a clinical trial repurposing surfactant therapy to treat adult ventilated COVID-19 patients, we hypothesized that plasma SP-D levels may reflect decreased lung integrity and that SP-D degradation in plasma and airway samples from COVID-19 patients may reflect disease progression and severity. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to quantify SP-D concentration in patient plasma and tracheal aspirate samples. Western Blotting was used to identify any protein degradation. Sequential daily plasma and airway samples were analysed. Results: SP-D concentration in serum was 10-20 times higher in patients ventilated for COVID-19 than in healthy volunteers. Additionally, the concentration of SP-D in plasma has shown to be 10-100-fold higher than in tracheal aspirates. Furthermore, degraded fragments of SP-D were detected at a higher ratio than intact SP-D in plasma of ventilated patients. This ratio decreased with administration of surfactant therapy (containing phospholipids and SP-B and SP-C but no SPA or SP-D). Conclusions: Increased serum SP-D and decreased tracheal aspirate SP-D from ventilated COVID-19 patients suggested leakage of pulmonary surfactant into the bloodstream caused by damage to the alveolar-capillary barrier in diseased lungs. The ratio of degraded vs. intact SP-D found in the plasma was compared before and after therapeutic surfactant administration. The results indicated that levels of SP-D in plasma and tracheal aspirates together with the ratio of degraded and intact SP-D in the plasma may be useful indicators of the severity of COVID-19 lung disease progression.
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BACKGROUND: Acute kidney injury (AKI) is a common manifestation among patients critically ill with SARS-CoV-2 infection (Coronavirus 2019) and is associated with significant morbidity and mortality. The pathophysiology of renal failure in this context is not fully understood, but likely to be multifactorial. The intensive care unit outcomes of patients following COVID-19 acute critical illness with associated AKI have not been fully explored. We conducted a cohort study to investigate the risk factors for acute kidney injury in patients admitted to and intensive care unit with COVID-19, its incidence and associated outcomes. METHODS: We reviewed the medical records of all patients admitted to our adult intensive care unit suffering from SARS-CoV-2 infection from 14th March 2020 until 12th May 2020. Acute kidney injury was defined using the Kidney Disease Improving Global Outcome (KDIGO) criteria. The outcome analysis was assessed up to date as 3rd of September 2020. RESULTS: A total of 81 patients admitted during this period. All patients had acute hypoxic respiratory failure and needed either noninvasive or invasive mechanical ventilatory support. Thirty-six patients (44%) had evidence of AKI (Stage I-33%, Stage II-22%, Renal Replacement Therapy (RRT)-44%). All patients with AKI stage III had RRT. Age, diabetes mellitus, immunosuppression, lymphopenia, high D-Dimer levels, increased APACHE II and SOFA scores, invasive mechanical ventilation and use of inotropic or vasopressor support were significantly associated with AKI. The peak AKI was at day 4 and mean duration of RRT was 12.5 days. The mortality was 25% for the AKI group compared to 6.7% in those without AKI. Among those received RRT and survived their illness, the renal function recovery is complete and back to baseline in all patients. CONCLUSION: Acute kidney injury and renal replacement therapy is common in critically ill patients presenting with COVID-19. It is associated with increased severity of illness on admission to ICU, increased mortality and prolonged ICU and hospital length of stay. Recovery of renal function was complete in all survived patients.