Tocilizumab Initiation based on Indicator in Patients Infected by Coronavirus-19 to Prevent Intubation

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has created severe medical and economic consequences worldwide since 2019. Tocilizumab is one of the therapies considered capable of improving the condition of patients with COVID-19. However, there is not much information about the best time to give tocilizumab. METHOD(S): This was an analytical study with a retrospective cohort design, using the data of 125 patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with signs of acute respiratory distress syndrome in Dr. Moewardi Hospital, Surakarta, from March to August 2020. We analyzed various available clinical data to see which factors into clinical improvement with tocilizumab therapy. RESULT(S): Most patients showed clinical improvement after administration of tocilizumab. During the follow-up period, 21 patients died despite tocilizumab therapy. Significant risk factors associated with the need for intubation were heart rate, neutrophil, lymphocyte, pH, PaCO2, and PO2. The most influential variable on the need for intubation without being associated with other risk factors was PaO2 (p = 0.003, Confidence Intervals 95%). CONCLUSION(S): Tocilizumab has a role in treating patients infected by SARS-CoV-2, preventing the need for intubation when given to patients in good saturation condition with oxygen supplementation without positive pressure (PaO2 >65mmHg;SpO2 >93%).Copyright © 2023 Septian Adi Permana, Adhrie Sugiarto, Sidharta Kusuma Manggala, Muhammad Husni Thamrin, Purwoko Purwoko, Handayu Ganitafuri.

Early prone positioning under VV-ECMO in SARS- CoV-2-induced acute respiratory distress syndrome - a retrospective cohort study

Objectives: The effectiveness of prone positioning (PP) under VV-ECMO for severe COVID-19 still be unclear. Until now, PP under VV-ECMO was often performed as the trump card for refractory hypoxemia and weaning off ECMO. On the other hand, PP has the effect of promoting homogenization of Lung aeration and leading to prevention of VILI. Combine use of early prone positioning together VV-ECMO may have synergy effects of ultra-lung protective strategy. In this study, we analyzed early PP cases under VV-ECMO for severe COVID-19 in our hospital and examined their efficacy and feasibility. Method(s): We performed a retrospective study of patients with SARS-CoV-2-induced ARDS submitted to early PP during VV-ECMO. During VVECMO, PP was considered in case of "Type-H transition in imaging findings (CT / LUS) " and cases that the physician deemed necessary. The lung aeration is evaluated by LUS before and after each PP. If there is a finding that the dorsal collapsed lung is improved through PP, it is implemented as effective, and it continued. Result(s): From April 2021 to August 2021, there were a total of 10 early PP cases under ECMO, and the age was (average) 56 years. ECMO was implanted with P/F 98 and Murray score 3.3 points, and PP was started 14 hours after the ECMO implantation. The average PP duration is 17.4 hours and PP performed 5.8 times per patient. Comparing blood gas and respiratory mechanics before and after PP showed a significant difference in PaCO2 (before: 46 +/- 8 vs after: 42 +/- 9, p = 0.02). Finally, there were 10 ECMO successful weaning (100%) and 8 surviving discharges (80%). No major complications were observed. Conclusion(s): Early PP under VV-ECMO for severe COVID-19 can be safely performed, and it is suggested that the synergy effect of ultra-lung protective strategy may be associated with a reduction of hospital mortality.

Characteristics, management and outcomes of thirty COVID-19 ARDS patients supported with veno-venous extracorporeal membrane oxygenation at Rikshospitalet, Oslo University Hospital

Background: We reviewed patients with COVID-19 ARDS managed with VV-ECMO support at our center from March 2020 until February 2022. Material(s) and Method(s): We extracted data from electronic health records (Metavision and DIPS). We registered premorbid health status, ventilator-settings before initiation of ECMO, the time-course, and hospital mortality. Result(s): Thirty patients were managed at our hospital, with a median age of 57.2 years (28-65) and median BMI 28 (22-40). No patient had any serious comorbidity. Twenty-two patients received non-invasive ventilation prior to intubation (1-10 days). The median time on ventilator were 8.0 days (1-19) prior to ECMO and median tidal volume was 5.8 mL/kg PBW (3.1-7.5). Hypoxemia (median PaO2-FiO2 ratio 8 kPa, range 6-12 kPa) and hypercapnia (median PaCO2 11.9 kPa, range 4.2-18.5) [SEP1] despite lung protective ventilation were the main indications for VV-ECMO. Two patients had severe respiratory acidosis without hypoxemia. 18 patients developed serious complications while managed with ECMO (acute renal failure, clinically significant bleeding, sepsis, right ventricular heart failure, dislocation of cannulae). Seven patients received renal replacement therapy. Sixteen patients (53%) died. Thirteen patients (43%) died on ECMO, three (10%) after weaning, Twelve (40%) were discharged from hospital, two are currently in ICU (7%). The median duration of ECMO and ventilator treatment, was 27 (6-50) and 37 (9-78) days, respectively. Conclusion(s): Management of patients with COVID-19 ARDS with VV-ECMO is very resource-intensive, and accompanied by serious complications and high mortality. In-hospital mortality in our cohort was 53%, which is comparable with reports from other centers. However, the duration of ECMO, and pre-ECMO mechanical ventilation, were longer than typically reported.

The impact of prone episodes on oxygenation in COVID-19 mechanically ventilated patients

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.

Predictive value of central venous-to-arterial carbon dioxide tension in patients with ARDS treated with veno - venous extracorporeal membrane oxygenation (ECMO)

Introduction: Central venous-to-arterial carbon dioxide tension ( PvaCO2) can be useful for monitoring adequacy of tissue perfusion in patients with ARDS supported with veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO). However, in theory, the unavoidable mixing of venous blood with blood after the oxygenator can affect PvaCO2 values by increasing central venous oxygen saturation and substantially decreasing CO2 concentration. This study aimed to evaluate acute changes in PvaCO2 after VV-ECMO installation and determine its association with patient outcomes. Method(s): Retrospectively evaluated coronavirus disease 2019 (COVID-19) ARDS patients with at least one concurrent arterial and central venous blood gas analysis before and after VV-ECMO installation as standard care. The primary outcome was intensive care unit (ICU) mortality at 28 days. Result(s): 29 patients were enrolled in the study. All the patients had a 25 F drainage multistage femoral cannula and a 21 F internal jugular infusion cannula. The median distance between the central venous sampling point and the tip of the infusion cannula was 39 [23-73] mm. No statistically significant changes in PvaCO2frelative changes calculated. After were observed 24-48 h after VV-ECMO installation (5 [4-7] mmHg to 6.5 [5-8.2] mmHg, p = 0.12). Hemoglobin concentration decreased 24 to 48 h after VVECMO installation (10.7 [9.5-12.7] g/dl to 9.6 [8.8-11.6] g/dl, p < 0.01) but neither central venous (75 [70-81]% to 73 [67-78]%, p = 0.46) nor arterial oxygen saturation (95 [92-97]% to 95 [93-96]%, p = 0.81) changed significantly. Elevated PvaCO2 after VV-ECMO installation had a good predictive value for 28 day ICU mortality (calculated area under the ROC curve 0.81) (Fig. 1 veno-venous). Conclusion(s): VV-ECMO support appears to have little effect on the PvaCO2 calculation. PvaCO2 can be used to evaluate patients with ARDS supported with VV-ECMO, as persistently elevated values can be associated with poor outcomes.

Increased shunt and dead space in recovered COVID-19 pneumonitis patients

Introduction/Aim: We previously reported impaired pulmonary gas exchange in acute COVID-19 patients resulting from both increased intrapulmonary shunt (SH) and increased alveolar dead space (AD) 1 . The present study quantifies gas exchange in recovered patients. Method(s): Unvaccinated patients diagnosed with acute COVID-19 infection (March-December 2020) were studied 15 to 403 days post first SARS-CoV-2 positive PCR test. Demographic, anthropometric, acute disease severity and comorbidity data were collected. Breathing room air, steady-state exhaled gas concentrations were measured simultaneously with arterial blood gases. Alveolar CO 2 and O 2 (P A CO 2 and P A O 2 ;mid-exhaled volume) determined;AaPO2, aAPCO2, SH% and AD% calculated. 2 Results: We studied 59 patients (33 males, Age: 52[38-61] years, BMI: 28.8[25.3-33.6] kg/m 2 ;median[IQR]). Co-morbibities included asthma (n = 2), cardiovascular disease (n = 3), hypertension (n = 12), and diabetes (n = 9);14 subjects smoked;44 had experienced mild-moderate COVID-19 (NIH category 1-2), 15 severe-critical disease (NIH category 3-5). PaCO 2 was 39.4[35.6-41.1] mmHg, PaO 2 92.1[87.1-98.2] mmHg;P A CO 2 32.8[28.6-35.3] mmHg, P A O 2 112.9[109.4-117.0] mmHg, AaPO 2 18.8[12.6-26.8] mmHg, aAPCO 2 5.9[4.3-8.0] mmHg, SH 4.3 [2.1-5.9]% and AD 16.6 [12.6-24.4]%. 14% of patients had normal SH (<5%) and AD (<10%);1% abnormal SH and normal AD;36% both abnormal SH and AD;49% normal shunt and abnormal AD. Previous severe-critical disease was a strong independent predictor for increased SH (OR 14.8[2.28-96], [95% CI], p < 0.01), increasing age weakly predicted increased AD (OR 1.18[1.01, 1.37], p < 0.04). Time since infection, BMI and comorbidities were not significant predictors (all p > 0.11). Conclusion(s): Prior COVID-19 was associated with increased intrapulmonary shunt and/or increased alveolar dead space in 86% of this cohort up to ~13 months post infection, with those with more severe acute disease, and older patients, at greater risk. Increased intrapulmonary shunt suggests persistent alveolar damage, while increased alveolar dead space may indicate persistent pulmonary vascular occlusion.

Relationship between blood gases and inflammatory markers with clinical outcomes in critically ill patients with COVID-19

Introduction: SARS - CoV mainly affects the airways and, although most cases of COVID-19 are mild or moderate, up to 30% of patients may have the severe form of the disease and be hospitalized due to the cytokine storm in response to viral infection (Milovanovic, L. et al. BMJ Open. 2021;11(1):e042008). Of these, up to a quarter need an Intensive Care Unit (ICU) and in this unit, data on partial pressure of oxygen (PaO2), carbon dioxide (PaCO2) and inflammatory markers are collected daily to assess respiratory function and assist in decision making. Aim(s): To analyze how these blood gas and inflammatory data are related to a greater need for invasive support and mortality in the ICU. Method(s): 79 patients admitted to an Intensive Care Unit with a mean age of 60 years, of whom 50 required invasive support and 44 died. Result(s): After comparing the groups, it was observed that the need for invasive ventilatory support and death were related to higher values of PaCO2 (p<0.001;p<0.001) and C-Reactive Protein (p=0.004;p=0.006), which did not occur with those with lower PaO2 levels (p=0.339;p=0.580). Furthermore, the inflammatory activity marker CRP correlated significantly and positively with PaCO2 (p=0.007;0.378), which did not happen with PaO2 (p=0.406;-0.121). Conclusion(s): Although the respiratory involvement caused by COVID-19 has hypoxemic characteristics, it is observed that, in critically ill patients, the assessment of CRP and carbon dioxide levels are more decisive for the clinical outcome, having more relevance for patient decisions and evaluations. serious hospitalized with COVID-19.

SARS-CoV-2 infection, lung involvement and vitamin D-driven immune endocrine reactivity a Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology

Vitamin D is a hormone rather than a vitamin in the strict sense. In fact, the active form 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] exerts several effects on the inflammatory response of autoimmune rheumatic and infectious diseases. Low serum concentrations (less than 20 ng/ml) of 25-hydroxyvitamin D3 [25(OH)D3], the precursor of 1,25(OH)2D3, are common in COVID-19 patients and are associated with an impairment of the innate (neutrophils, monocytes/macrophages, dendritic cells) and adaptive (T and B lymphocytes, antibodies production) immune responses. Respiratory parameters (partial pressure of arterial oxygen-PaO2, partial pressure of arterial carbon dioxide-PaCO2, pressure of arterial oxygen to fractional inspired oxygen concentration-PaO2/FiO2), radiological pulmonary involvement, and serum concentrations of 25(OH)D3 were evaluated in sixty-five hospitalized COVID-19 patients (mean age 76 +/- 13 years) and sixty-five sex- and age-matched control subjects (CNT). COVID-19 patients showed significant lower 25(OH)D3 serum concentrations than CNT (median 8 ng/ml vs 16 ng/ml, p=0.001). 25(OH)D3 serum concentrations correlated positively with PaO2 (p=0.03) and PaO2/FiO2 (p=0.02). Moreover, 25(OH)D3 serum concentrations were significantly lower in COVID-19 patients with diffuse/severe radiological lung involvement (p=0.05) or multiple lung consolidations (p=0.0001) than in those with mild radiological lung involvement. Finally, significantly lower 25(OH)D3 serum concentrations were found in COVID-19 patients who died during hospitalization, compared to those who survived (p=0.05). In conclusion, vitamin D deficiency is associated with a more severe lung involvement and a higher risk of death in old COVID-19 patients.

Impact of Active Cycle of Breathing Technique on Selected Pulmonary Outcomes in Post-COVID Syndrome Patients

Background Worldwide, the 2019 coronavirus disease (COVID-19) pandemic has imposed a substantial burden. A large number of post-Covid-19 patients have long-lasting symptoms like fatigue and exercise intolerance. This condition been labelled 'post-acute sequelae of Covid-19' (PASC). Pulmonary rehabilitation is a comprehensive treatment that is based on a thorough assessment of the patient and is meant to improve the health of people with respiratory disease. Purpose To determine how active cycle breathing affects specific pulmonary outcomes in patients having post-COVID syndrome. Materials and methods 60 patients of both sexes (29 men and 31 women) took part. Their age was ranging from 40-50 years. Patients were randomized into 2 groups of the same size. Variables were assessed before and after training and statistically analyzed: Arterial blood gas analysis (ABG), the six-minute walk test (6MWT) and fatigue level Results: The mixed MANOVA statistical analysis results indicated no substantial change in any outcome measures between the two groups prior to treatment (p > 0.05). After treatment, comparisons across the groups showed that Group A had significantly increased (6MWT 11.09%, PaO2 3.5%, SaO2 2.7%) (Decrease fatigue 35.92% PaCO2 4.35%). Group B: (6MWT 21.61%, PaO2 12.41%, SaO2 6.43%) (Decrease fatigue 61.05%, PaCO2 10.75). Conclusion ABG parameters, fatigue level and six-minute walk test (6MWT) for post-COVID syndrome patients were all positively impacted by the active cycle of breathing technique, which is an efficient modality that may be incorporated into conventional physical therapy protocols. Copyright © 2023 Authors. All rights reserved.

Prognostic Markers of Geriatric Patients in the Icu with Respiratory Failure Secondary to Covid-19

INTRODUCTION: SARS-CoV-2 (COVID-19) has continued to be a public health emergency, affecting almost 450 million people worldwide, with a disproportionate significant disease burden in the elderly community. Our objective is to provide population specific prognostic markers upon description of demographic factors, clinical characteristics, diagnostic variables, treatment characteristics and outcome variables in critically ill geriatric patients with acute hypoxic respiratory failure due to COVID-19 infection. METHOD(S): This is a retrospective chart review of 165 patients admitted to a single institution's medical and cardiovascular intensive care unit between the dates of March 01, 2020 and December 31, 2020. Inclusion criteria was patients age greater than or equal to 65 years, documented positive COVID-19 polymerase chain reaction test result and a diagnosis of acute hypoxic respiratory failure. Our primary end point evaluated the rate of mortality in relation to multiple variables during intensive care unit admission. RESULT(S): Of 165 patients, 45 patients were excluded. Of the remaining 120 patients, 41 were females and 79 were males. Four independent risk factors are significantly associated with higher odds of mortality for the concerned population: presence of solid tumor (AOR: 0.002, 95% CI: < 0.001, 0.31), maximum value of PaCO2 (AOR: 1.094, 95% CI: 1.029, 1.163), Charlson comorbidity index (AOR: 2.962, 95% CI: 1.59, 5.52), and use of diuretics (AOR: 0.015, 95% CI: < 0.001, 0.49). CONCLUSION(S): It was to our surprise that the mortality rate among those intubated was not statistically significant. However, it has been shown in prior research, which is in alignment with our results, that mechanical ventilation does not necessarily result in increased mortality. Certain factors were found to be poor prognostic markers during intensive care unit admission, which may predict a higher rate of mortality in those patient populations.

Effect Of Prone Position On Respiratory Parameters And Mortality Rate Among Mechanical Ventilated Covid-19 Patients

Background: SARS-CoV-2 virus causes a pneumonia that was identified through fever, dyspnea, and acute respiratory symptoms and named COVID-19. This disease exacerbates in a number of patients and causes pulmonary edema, multi-organ failure, and acute respiratory distress syndrome (ARDS). Concerning the new management modality of ARDS patients, prone position can be used as an adjuvant therapy for improving ventilation in these patients. Purpose(s): The study purposed to evaluate the effect of prone position on respiratory parameters and mortality rate among mechanical ventilated covid-19 patients Methods: Experimental prospective study including a convenience 50 patients were recruited from governmental hospital in Al-Jouf to evaluate the effect of prone position on oxygenation parameters in patients with Coronavirus Disease 2019 (COVID-19). Result(s): The results showed that PaO2 mm Hg is statistically significant higher in study group (average 86.48) compared to the control group average of PaO2 mm Hg (51.18). In addition, PaCO2 mm Hg level is seemed to be significantly higher in the control group which arrived 46.57. Conclusion(s): Prone position improve respiratory function in the vast majority of patients with ARDS due to COVID-19 which reducing the injurious effects of mechanical ventilation. In addition, improve oxygenation in patient with moderate to severe acute respiratory distress syndrome and there is no effect of the prone position on the mortality rate. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Retrospective Analysis of Arterial Carbon Dioxide Level and Arterial pH Level at the Time of Initiation of Respiratory ECMO and Outcome

Introduction Respiratory extracorporeal membrane oxygenation (ECMO) is well established and its popularity has increased during coronavirus disease 2019 (COVID-19) time. The efficacy of ECMO has been proved in refractory respiratory failure with varied etiology. More than 85,000 respiratory ECMO cases (neonatal, pediatric, adult) registered as per Extracorporeal Life support Organization (ELSO) statistics April 2022 report, with survived to discharge or transfer ranging from 58 to 73%. Early initiation of ECMO is usually associated with shorter ECMO run and better outcome. Many patient factors have been associated with mortality while on ECMO. Pre-ECMO patient pH and arterial partial pressure of carbon dioxide (paCO2) have been associated with poor outcome. We designed a retrospective study from a single tertiary care center and analyzed our data of all respiratory ECMO (neonatal, pediatric, and adult) to understand the effect of pre ECMO, paCO2, and arterial pH to ECMO outcome. Methods It is a retrospective analysis of data collected of patients with acute respiratory failure managed on ECMO from January 2010 to December 2021. Pre-ECMO (1-6 hours before initiation), paCO2, and arterial pH level were noted and analyzed with primary and secondary outcome. Primary outcome goal was survivor and discharged home versus nonsurvivor, while secondary goal was the number of ECMO days and incidence of neurological complications. The statistical analysis was done for primary outcome and incidences of neurological complications and p-value obtained by using chi-squared method. Meta-analysis was done by classifying the respiratory ECMO cases in three major category-COVID-19, H1N1 non-COVID-19, and H1N1 respiratory failure. Results The total 256 patients of respiratory failure were treated with ECMO during specified period by Riddhi Vinayak Multispecialty Hospital ECMO team. Data analysis of 251 patients (5 patients were transferred for lung transplant, hence been not included in study) done. Patients were divided on the basis of pH level less than 7.2 and more than 7.2 and analyzed for primary and secondary outcome. Similarly, patients were divided on the basis of paCO2 level of less than 45 and more than 45. Patient with pre-ECMO pH level more than 7.2 has statistically better survived extracorporeal life support (ECLS) (p-value: 0.008) and survival to discharge home (p-value: 0.038) chances. Pre-ECMO paCO2 level of less than 45 also showed better survival chance of survived ECLS (46.67 vs. 36.02) and survived to discharge home (42.22 vs. 31.06) but not statistically significant (p-value: 0.15 and 0.18, respectively). There was no significant difference in average number of ECMO days in patient survived to discharge home with paCO2 less than 45 and more than 45 (15.7 vs. 11.1 days), and also in pH more than 7.2 and pH less than 7.2 (15.8 vs. 11.6). The incidence of neurological complications was also found lower in patient with pH more than 7.2 (7.5 vs. 17.3%, p-value: 0.034) and in paCO2 level of less than 45 (4.4 vs. 12.65, p-value: 0.15). Conclusion Pre-ECMO arterial pH of more than 7.2 (statistically significant) and paCO2 of less than 45 (statistically not significant) have definitely better survival chances and have lesser incidences of neurological complications. There was no significance difference in the number of ECMO days in either group. Authors recommends early initiation of ECMO for mortality and morbidity benefits.

COMPARATIVE EFFECTIVENESS OF INHALED NITRIC OXIDE IN ARDS AND VIRAL PNEUMONIA WITH AND WITHOUT COVID-19

SESSION TITLE: ECMO and ARDS in COVID-19 Infections SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/17/2022 12:15 pm - 1:15 pm PURPOSE: Inhaled nitric oxide (iNO) is a potent vasodilator of pulmonary vasculature improving perfusion to ventilated alveoli in ARDS and other lung pathologies. During the pandemic, intensivists turned to iNO as “salvage” therapy in COVID-19 patients. Rationale was driven by vasodilatory effect and antiviral properties despite lack of evidence of clear benefit even in patients without COVID. We hypothesized that iNO would provide reduced increases in pulmonary perfusion and subsequent gas exchange improvement in COVID-19 patients due to extensive endothelial damage and coagulopathy throughout the pulmonary vasculature. METHODS: Our IRB exempt analysis examined patients hospitalized with and without COVID-19 from January 2020 to September 2021 who received at least 24h of invasive mechanical ventilation with iNO (15-20ppm). Effectiveness outcomes were PaO2/FIO2 ratio(PFR), PEEP/CPAP level, and PaCO2 serially measured and observed up to 24 hours prior to initiation of iNO and for up to 120h post iNO administration. Data were statistically controlled for age, sex, race, time to initiation of therapy and COVID-19 directed treatment. RESULTS: From January 2020 and September 2021, 42 patients were admitted to the ICU and received invasive mechanical ventilation and iNO. Results are sequenced as ARDS COVID-negative, ARDS COVID-positive, viral pneumonia COVID-negative, viral-pneumonia COVID-positive. Patient n = 8/14/6/14. Median age was 56/55/63/62 years. Demographics split 64-62% male vs 36-38% female in ARDS without/with COVID, 50%/83% male vs 50%/17% female in viral pneumonia without/with COVID. Racial distribution resulted 75%/93%/86%/83% White vs 25%/0%/17%/14% Black. Other races constituted less than 7% of patient total in any category. PFR delta from -24h to +120h post-iNO = +35/+35/+41/+22. PEEP/CPAP delta from -24h to +120h = -4/-1/-3/-2. PaCO2 delta mmHg from -24h to +120h = -21/-23/-9/-13. Median Hospital LOS = 26/26.5/17/19 days. Median ICU LOS = 15.8/19.0/13.8/17.6 days. Hospital mortality = 100% across all 4 subgroups. CONCLUSIONS: ARDS patients with or without COVID showed similar rates of PFR response to iNO, however viral pneumonia patients with COVID exhibited a blunted PFR response vs those without COVID. No statistically significant difference was observed with respect to PEEP/CPAP levels, PaCO2 mmHg, hospital or ICU LOS, or mortality. CLINICAL IMPLICATIONS: Our findings suggest that the presence of COVID-19 did not significantly inhibit response to iNO in ARDS or other viral pneumonia patients. Further evaluation of other indirect markers of gas exchange could provide further evidence of responsiveness. DISCLOSURES: No relevant relationships by Katherine Burns No relevant relationships by Karen Hamad No relevant relationships by Bobby Malik No relevant relationships by Richard Walo Jr No relevant relationships by Wilhelmine Wiese-Rometsch No relevant relationships by Stephanie Williams

LUCINACTANT, A SYNTHETIC SURFACTANT FOR TREATMENT OF COVID-19-ASSOCIATED ARDS

SESSION TITLE: ECMO and ARDS in COVID-19 Infections SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/17/2022 12:15 pm - 1:15 pm PURPOSE: The SARS-CoV-2 virus preferentially attacks alveolar Type 2 cells that have the membrane ACE2 receptors. Type 2 cells are the surfactant producing cells in the lung. Damage to Type 2 cells can result in decreased/abnormal surfactant production leading to ARDS and respiratory failure. Surfactant is further inactivated by inflammatory proteins during ARDS. We sought to evaluate the feasibility, safety and tolerability of surfactant therapy in COVID-19 associated ARDS using a synthetic surfactant, lucinactant. METHODS: Open-label, single arm, multicenter study (NCT04389671) in adults with COVID-19 associated ARDS, who have been intubated and on mechanical ventilation (MV) with a P/F ratio <= 300. COVID-19 infection was confirmed by PCR. Lucinactant at a dose of 160 ml (∼80 mg TPL/kg lean body weight) was delivered intratracheally within 7 days of intubation. Retreatment was allowed at >= 6-hour intervals if subjects remained on MV. Assessments included time to deliver the dose, physiologic parameters of oxygenation (P/F, OI, PaO2), FiO2, PaCO2, lung compliance (CL) from baseline (pre-dosing) through day 5 post-dosing. Safety parameters included peri-dosing (PD) events (bradycardia, desaturation, hypotension, regurgitation) and adverse events through 30 days post dosing. RESULTS: 20 subjects were enrolled and 19 received at least one dose. Five subjects received 2 doses of lucinactant. The mean age of subjects was 49 years, 80% were male, 60% were white. The mean time to administer the dose was 31 minutes. FiO2 requirements, PaO2 and PCO2 remained stable throughout the 5-day period post dosing. Baseline mean P/F ratio and standard deviation (SD) was 196 (68), 179 (57) at 12 hours and 193 (61) at day 1 post-dosing, followed by a gradual increase to 223 (105) at day 5. Mean CL increased from 40.5 (16) at baseline to 49.8 (23) at day 5. Seven subjects (37%) died, 6 due to secondary infection and sepsis > 13 days after dosing. Two subjects experienced transient PD events (desaturation, regurgitation). Lucinactant administration in severe ARDS due to COVID-19 was safe and generally well tolerated. The incidence of PD events was low. Stable to improved physiologic parameters of oxygenation were observed post dosing. Increasing the dose and number of administrations may provide additional benefit. CLINICAL IMPLICATIONS: The data support continued study of lucinactant in ARDS patients. DISCLOSURES: Consultant relationship with Windtree Therapeutics Please note: August 2000 Added 03/31/2022 by Carlos Guardia, value=Consulting fee Consultant relationship with Windtree Therapeutics Inc. Please note: August 2000 Added 03/31/2022 by Carlos Guardia, value=Consulting fee Removed 03/31/2022 by Carlos Guardia Advisory Committee Member relationship with Windtree, inc Please note: 4/2021-2/2022 Added 04/04/2022 by Yuh-Chin Huang, value=Grant/Research No relevant relationships Added 04/04/2022 by Peter Morris, value=Consulting fee Removed 04/04/2022 by Peter Morris Employee relationship with Windtree Therapeutics, Inc. Please note: 2008-2022 Added 04/04/2022 by Phillip Simmons, value=Salary Employee relationship with Windtree Therapeutics Please note: 2014 to present Added 04/14/2022 by Steven Simonson, value=Salary

Parameters that affect the outcome in ICU patients with critical COVID -19 infection

Introduction: COVID -19 pandemic continues to affect millions worldwide, while the critical form of the disease requires ICU hospitalization to manage not only respiratory failure but multiple organ dysfunctions as well. Objectives: Our retrospective observational study aimed to test the hypothesis that there is a difference in mean values of indexes pointing to organ dysfunction on ICU admission day, like BUN over Creatinine ratio, BUN over Albumin ratio, and PaCO2 over HCO3 ratio among patients with confirmed critical COVID -19 infection who died and patients who survived ICU. Methods: During late 2020 to 2021, 69 patients indicated with the diagnosis of critical COVID -19 disease admitted to ICU. The patients were separated into two groups. Group A involved all patients who survived ICU and group B all patients who died in ICU. We looked for statistically significant differences between the medians values of two groups according to BUN/Cr, BUN/Alb, PaCO2/HCO3 ratios on the ICU admission day, performing unpaired t-test or Mann-Whitney Test according to equal S.D.s assumption. Results: (Table) Conclusions: According to our data, there was a strong statistically significant difference detected between the two groups according to BUN/Alb and PaCO2/HCO3, while the BUN/Cr ratio had no statistically significant difference. Our data suggest that prerenal disorder took place early and was already present on ICU admission day, although not statistically greater in group B. However, a renal disorder associated with albumin levels was greater in group B, and acute type II respiratory failure was by far greater in patients that died in the ICU, pointing that oxygenation disorder was not the only impact of COVID -19 infection on the ICU admission day.

Nutritional adequacy and accuracy in long-stay critically ill patients as measured by indirect calorimetry

Introduction: Nutritional optimisation is recognised as having significant impact on clinical and functional outcomes of critically ill patients.1 Clinical recommendations suggest use of indirect calorimetry guided nutrition in the intensive care unit (ICU),2 and a recent systematic review demonstrated improved outcomes from its use.3 The COVID-19 pandemic has seen a greater proportion of patients with prolonged critical illness, a cohort for whom nutritional optimisation is a key unmet need.4 Objectives: To assess rates of over and underfeeding in a tertiary centre ICU and how these relate to markers of catabolism and persistent critical illness. Methods: Serial measurements of REE (resting energy expenditure) and RQ (respiratory quotient) by indirect calorimetry were performed using Q-NRG+ device (COSMED, Rome, Italy). Nutritional intake and estimations of requirements were recorded concurrently together with routine clinical observations, and markers of critical illness, catabolism and over or underfeeding. Results: Across 30 patients, REE was lower than estimated energy requirements, 24.2 (IQR 20.0-28.1) kcal/ day/kg IBW vs. 29.1(IQR 25.4-33.1) kcal/day/kg IBW, p<0.001. 41.8% of measurements showed overfeeding (actual calorie intake >110% of REE), and 23.3% showed underfeeding (actual calorie intake <85% of REE). Obese patients (n=15) were underfed (-98kcal/day deficit) compared to non-obese patients (n=15), who were on average overfed (+256kcal/day surplus), p=0.021. Overfeeding was also associated with greater length of ICU admission (R2 0.159, p<0.005). Median day of ICU admission in overfed patients was 39 days (IQR 24-56), and in underfed patients 21.5 (IQR 7.5-45.25). However, there was no significant association between calorie surplus or deficit, and other markers of overfeeding PaCO2, insulin use, ureacreatinine-ratio. Conclusion: This service evaluation recorded measurements of REE and RQ in critically ill patients with high lengths of ICU stay (up to 66 days). We observed increased rates of overfeeding with increased duration of ICU admission, and increased overfeeding in non-obese patients.

Negative Pressure Ventilation for Acute and Acute-on-Chronic Respiratory Failure: A systematic review and meta-analysis

Introduction: Respiratory failure is the most common organ failure seen in the intensive care unit1 and is managed with non-invasive or invasive positive pressure ventilation (PPV). Negative pressure ventilation (NPV) could offer a safe and effective alternative, however existing devices, such as the iron lung, are heavy and access to the patient for ongoing care is a limitation. The COVID-19 pandemic necessitated intense focus on the rapid design and manufacture of new ventilators,2 most of which were positive pressure ventilators. However, new, light-weight negative pressure ventilators were also designed and appeared to be safe and effective in an early trial in healthy human volunteers.3 These devices have the potential to offer patients an alternative to PPV, without the limitations associated with the early negative pressure devices. They are cheaper to manufacture, and importantly, do not require a pressurised gas supply, which may be of particular benefit to countries with less well-resourced healthcare facilities in which acute and acute-onchronic respiratory failure continue to cause significant morbidity and mortality.4 Objectives: To address whether acute or acute-onchronic respiratory failure in hospitalised adults can be safely and effectively managed with NPV. Methods: This systematic review was registered with the international prospective register of systematic reviews (ID CRD420200220881). MEDLINE, EMBASE, CENTRAL, medRxiv, bioRxiv and Trip databases were searched (from inception to 22nd April 2021). Eligible studies included non-intubated hospitalised adults who received NPV in the management of acute or acute on chronic respiratory failure. We included randomised controlled trials, non-randomised studies of intervention and case series. Risk of bias was assessed using three separate tools due to differing study designs. Results: 575 unique citations were screened with 14 meeting inclusion criteria. 1032 acute episodes (888 patients) of respiratory failure were managed with NPV, with 234 receiving PPV as a comparator. The majority (n=845, 66.7%) were treated for an acute exacerbation of COPD. 417 patients from four studies were included in the meta-analysis. The effect of NPV on PaCO2, pH and PaO2/FiO2 was similar to PPV with a mean difference -0.39kPa (95% confidence interval (CI): -0.95, 0.18), 0.01 (95% CI: 0.00, 0.02), and -0.16 (95% CI: -1.98, 1.66) respectively. Of those studies not included in the meta-analysis six showed a statistically significantly increase in PaO2 with the use of NPV and 5 showed a statistically significant improvement in PaCO2. Rates of complications were similar with NPV in those studies that compared it to PPV, and NPV appeared to be well tolerated by patients. This systematic review study was limited by a wide range of study designs. Conclusions: NPV appears to be a safe and effective alternative to PPV in the management of acute exacerbation of COPD. Evidence for its use in other forms of respiratory failure is limited but warrants further investigation.

Real-World Use of Extracorporeal CO2 Removal (ECCO2R) to Correct Respiratory Acidosis: Analysis of the Hemolung Registry

Hypercapnia and respiratory acidosis lead to increased morbidity and mortality in critically ill patients. Extracorporeal CO2 removal (ECCO2R) can rapidly correct pH and PaCO2 as a treatment for refractory, hypercapnic respiratory failure. Current clinical evidence for the benefits of ECCO2R is primarily limited to case series and single-center studies. The Hemolung (ALung Technologies, Inc., Pittsburgh, PA) is the only FDA cleared ECCO2R system and has been utilized to treat greater than 1,000 patients world-wide. The purpose of this study was to evaluate real-world evidence of the Hemolung ECCO2R system for the treatment of hypercapnic respiratory failure across a range of primary diagnoses. Methods: The Hemolung Registry was queried for patients with a baseline, pre-Hemolung pH < 7.35. Patients receiving either noninvasive or invasive ventilation were included in the analysis. Physiological benefits of Hemolung therapy were evaluated using a mixed model for repeated measures based on changes in pH and PaCO2 after 4-6 hrs and 16-35 hrs of Hemolung therapy compared to the baseline value. The model was used to calculate two-sided 95% confidence intervals and associated nominal p-values. Additional markers of clinical improvement included avoidance of intubation, survival to decannulation, and Hemolung CO2 removal rate and duration of use. Adverse events were also analyzed based on patient harm. Results: 176 Hemolung patients were included in the analysis. Multiple primary diagnoses were represented: 31% ARDS, 22% COPD exacerbation, 32% COVID-19, and 15% Other. Median CO2 removal by the Hemolung during the first day of therapy was 88 mL/min and resulted in a concomitant correction of pH from a median of 7.20 to 7.35 (p<0.001) and median PaCO2 correction of 81.7 to 57.0 mmHg (p<0.001). Correction of respiratory acidosis was independent of primary diagnosis, age, and BMI. 69% (112/162) of patients survived to de-cannulation. 86% (19/22) of patients failing NIV avoided intubation. There were no unanticipated complications, and the majority of adverse events did not require medical intervention or discontinuation of Hemolung therapy. 3 deaths associated with Hemolung therapy occurred. Conclusion: These data represent the largest reported analysis of ECCO2R therapy to treat a diverse population of hypercapnic respiratory failure patients. The results demonstrate significant correction of pH and PaCO2 within the first day of Hemolung therapy without significant adverse events. Data from forthcoming RCTs will shed further light on whether these physiologic benefits translate to improved outcomes compared to current standard of care.

Early Awake Proning in COVID-19 Patients to Reduce Invasive Ventilation: A Prospective Interventional Study ABS0264)

Aim: To prevent endotracheal intubations in the COVID wards with early awake proning, allowing time for lung to recover, and decrease mortality in COVID-19 patients. Objectives: 1. To assess the effect of prone positioning on the requirement for invasive mechanical ventilation. 2. To calculate PaO2/FiO2 before prone position. 3. To measure PaO2/FiO2 after prone position. 4. To assess how much increase in PaO2 during prone. 5. To assess the length of time tolerating prone positioning. Materials and methods: Inclusion criteria: (1) Age >18 years. (2) Patient with confirmed COVID with or without chest X-ray infiltrates. (3) Isolated hypoxemic respiratory failure without substantial dyspnea (the paradoxically well appearing hypoxemic patient). Requiring >2 L of O2 to maintain SpO2 >92%. A reasonable candidate might meet the following criteria: • not in multi-organ failure, • expectation that patient has a fairly reversible lung injury and may avoid intubation, • no hypercapnia or substantial dyspnea, • normal mental status, able to communicate distress, • no anticipation of difficult airway. (4) Patients who do not wish to be intubated (DNI). The main risk of awake proning is that it could cause excessive delays in intubation. In the DNI patient who is failing other modes of ventilation, there is little to be lost by trialing awake proning. Exclusion criteria: (1) Signs of respiratory fatigue (RR > 40/minute, PaCO2 > 50 mm Hg/pH< 7.30, and obvious accessory respiratory muscle use), (2) immediate need for intubation (PaO2/FiO2 < 50 mm Hg, unable to protect airway or change of mental status), (3) unstable hemodynamic status, and (4) inability to collaborate with prone position with agitation or refusal. Also, it is observed that the mean O2 requirement is slightly higher in females (Baseline-7.74 L) as compared to males (Baseline-6.06 L), however, this difference is not statistically significant when observed using an independent sample t test (t value = -1.728, df = 48, p > 0.05). The mean reduction of O2 requirement from baseline to Day 3 post proning amongst male patients is 4.53 L, while in females it is 5.16 L. There is no statistically significant mean reduction of O2 requirement in males and females which was observed using independent sample t-test (t value = -0.675, df = 47, p > 0.05). SpaO2 increase after awake proning Overall, a total of 21 patients were followed up until Day 3 post proning and an increase in SpaO2 was observed in these patients. It is seen that the Mean Baseline SpaO2 in these 21 patients was 68.43 ± 2 (14.172) and after 3 days of awake proning it increased to 77.24 + 2 (17.023). However, this difference is not statistically significant using the paired sample t-test (t value = -1.819, df = 20, p > 0.05). Conclusion: It can be concluded from the study that 3 out of 50 patients (6.0%) required NIV or intubation after giving awake proning. The SpaO2 increases after awake proning but the increase is not statistically significant. However, the O2 requirement is reduced 4 to 6 times after awake proning and this reduction is statistically very highly significant. Thus, awake proning significantly helps in the reduction of the requirement of O2.

A study of NT PRO-BNP and ETCO2 in Patients Presenting with Acute Dyspnea

Introduction: Common diagnoses amongst patients presenting with acute dyspnoea in Emergency Department are Decompensated Heart Failure, Chronic Obstructive Pulmonary Disease, ARDS, and others like pulmonary embolism, etc. Differentiating these is essential for proper management. Objectives: 1. To measure NT-PRO-BNP and ETCO2 in patients presenting with dyspnea. 2. To evaluate the levels of NT-PRO-BNP and ETCO2 in patients with Heart Failure, COPD, and ARDS. Materials and methods: This is a cross-sectional, observational study in patients admitted to the Medicine ICU with Dyspnoea. A total of 72 hypoxic (COVID Negative) patients requiring ventilatory support were evaluated and further categorized into three groups: 1. Heart failure (n = 44). 2. Pulmonary (COPD-13 and PE-2). 3. Sepsis with ARDS (n = 13). All patients were evaluated clinically and NT pro-BNP, ETCO2, ABG, Chest X-ray, Lung Ultrasound, 2D Echocardiography, and other basic laboratory testing were carried out. Results: The mean NT Pro-BNP and ETCO2 in the study subjects was 9872.69 pg/mL ± 10223.83 and 31.52 +13.83 mm Hg, respectively. Mean NT pro-BNP value was found to be more in cardiac group (13,835.04 pg/mL + 9868.87, CI 10,834.63 to 16,835.45) as compared to respiratory group (785.92 pg/mL + 1129.16, CI 103.6 to 1468.24) and sepsis with ARDS group (4890.6 pg/mL ± 9583.78, CI 900.81 to 10,682.03). This result was statistically significant with p value < 0.05. The difference between mean values of NT pro-BNP in the respiratory and sepsis group was NOT statistically significant (p value > 0.05). Mean ETCO2 value was found to be maximum in respiratory group (49.89 ± 7.26 mm Hg, CI 45.5 to 54.28), followed by the cardiac group (30.88 ± 10.78 mm Hg, CI 27.61 to 34.17) followed by sepsis group (19.46 ± 12.15 mm Hg, CI 12.12 to 26.8) and all three were statistically significant (p value < 0.05). Two patients with pulmonary embolism had mean NT pro-BNP value of 13,649 pg/mL and mean ETCO2 value of 29 mm Hg. Mean PaCO2-ETCO2 value was found to be maximum in sepsis group (16.78 ± 6.97 mm Hg, CI 12.57 to 21) followed by the respiratory group (8.15± 3.32 mm Hg, CI 6.14 to 10.16) followed by cardiac group (5.55 ± 2.04 mm Hg, CI 4.93 to 6.17). This was found to be statistically significant. The difference between mean values of PaCO2-ETCO2 in the respiratory and cardiac group was NOT statistically significant. The lung ultrasound comet-tail sign had 93.02% sensitivity, 100% specificity, 90.62% negative predictive value (NPV), 100% positive predictive value (PPV), and 95.83% accuracy for the diagnosis of heart failure. Conclusion: High NT-pro BNP and lower ETCO2 were found in acute HF-related dyspnea as compared to COPD. Mean PaCO2-ETCO2 value was found significantly higher in patients of ARDS. Hence, NT pro-BNP, ETCO2, and PaCO2-ETCO2 can be used together in evaluating patients presenting with acute dyspnea in emergency settings.