COVID-19 Related Acute Respiratory Distress Research Articles

Evolution of the oxyhemoglobin dissociation curve in COVID-19 related ARDS patients

IntroductionSevere hypoxemia is the leading cause of admission in intensive care (ICU) in patients with COVID-19 related acute respiratory distress syndrome (ARDS). In these patients, several studies reported a left shift of the oxyhemoglobin dissociation curve associated with a lower mortality. However, these results are conflicting, as these studies include few patients and often no control groups. Moreover, the calculation of P50, representing the PaO2 value at which 50% of hemoglobin is saturated, is not corrected for factors known to influence it (pH, PaCO2 or temperature). For all of these reasons, we compared the corrected P50 between ICU patients with severe COVID-19 related ARDS on mechanical ventilation or not, and ARDS from other causes. We investigated the evolution of the corrected P50 during the first 3 days of ICU and its relationship with ICU mortality.Methods and PatientsWe retrospectively calculated the corrected P50 in three groups of patients: intubated and mechanically ventilated COVID-19 related ARDS, non-intubated COVID-19 related ARDS and intubated patients with ARDS due to other infectious causes. The corrected P50 was calculated, on the worst blood gas analysis on days 1 and 3 of ICU admission, by the formula of Hill but modified by Dash et al., controlled for pH, PaCO2 and temperature. We collected ICU mortality.Results463 blood gas analysis at days 1 and 3 from 214 ICU COVID-19 related ARDS patients (114 with intubation and 100 without) and 35 ICU patients with ARDS from other causes were analyzed. All patients were severely hypoxemic: PaO2/FiO2 of 76 [58-108] mmHg for intubated COVID-19, 79 [60-108] mmHg for non-intubated COVID-19 and 142 [78-197] mmHg for the third group (p < 0.001). The mortality rate was higher in intubated COVID-19 related ARDS patients (44.7 versus 14 versus 37% in ARDS from other causes; p < 0.001). The corrected P50 was significantly lower in COVID-19 patients, especially in non- intubated patients (21.2 [18.8–25.2] mmHg vs. 25.5 [19.2–30.3] mmHg in intubated patients; compared to ARDS from other causes: 27.2 [23.3-35.4] mmHg; p < 0.001. The corrected P50 does not change over the first 3 days, except for the non intubated COVID-19 related ARDS and is not correlated with ICU mortality (odds ratio = 0.98 [0.95-1.03]; p = 0.51), in contrast of PaO2/FiO2 and ICU gravity scores.ConclusionThe oxyhemoglobin dissociation curve at ICU admission was left shifting in severe COVID-19 related ARDS patients regardless of the type of ventilation. This deviation increases the third day only in non-intubated COVID-19 related ARDS and was not related to the outcome.

Lung Transplantation in the United States for COVID-19 Related Lung Disease During the Pandemic.

Lung transplantation (LTx) is a potential intervention for end-stage COVID-19 lung disease. Current literature is sparse regarding the outcomes of LTx for COVID-19 related acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF). This study aims to characterize outcomes and patterns of LTx for COVID-19 related lung disease throughout the pandemic. Patients who underwent LTx during the pandemic for COVID-19 related lung disease were retrospectively identified using the UNOS registry. Demographics, as well as outcomes measures and nationwide patterns of care were collected and analyzed. A total of 510 adult cases of LTx for COVID-19 (259 ARDS, 251 PF) were compared to 4,031 without COVID-19 (3,994 PF, 37 ARDS). Patients who received LTx for COVID-19 ARDS did not differ in 2-year survival when compared to those with COVID-19 PF (81.9% vs 77.2%, p = 0.4428). Compared to non-COVID-19 etiologies, COVID-19 ARDS patients had higher rates of stroke (2.3% vs 0%, p = 0.0005), lower rates of graft failure (12.8% vs 36.1%, p = 0.0003) and post-transplant ECMO (29.6% vs 41.7%, p = 0.0002), and improved 2-year survival following LTx (81.9% vs 61.7%, p = 0.0064). No difference in 2-year survival following LTx was observed between patients with COVID-19 and non-COVID-19 PF (77.2% vs 71.8%, p = 0.34). Rates of LTx spiked with variant emergence and declined with rounds of vaccination. Our results are consistent with early reports of survival outcomes following LTx for COVID-19 ARDS and PF while providing an increased layer of granularity. LTx may be considered as a safe and effective intervention for COVID-19 lung disease.

Duration of Invasive Mechanical Ventilation before Veno-Venous ExtraCorporeal Membrane Oxygenation for Covid-19 related Acute Respiratory Distress Syndrome: The experience of a tertiary care center

BackgroundVeno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) is an efficient ventilatory support in patients with refractory Covid-19-related Acute Respiratory Distress Syndrome (ARDS), however the duration of invasive mechanical ventilation (IMV) before ECMO initiation as a contraindication is still controversial. The aim of this study was to investigate the impact of prolonged IMV prior to VV-ECMO in patients suffering from refractory Covid-19-related ARDS. MethodsThis single-center retrospective study included all patients treated with VV-ECMO for refractory Covid-19-related ARDS between January 1, 2020 and May 31, 2022. The impact of IMV duration was investigated by comparing patients on VV-ECMO during the 7 days (and 10 days) following IMV with those assisted after 7 days (and 10 days). The primary endpoint was in-hospital mortality. ResultsSixty-four patients were hospitalized in the ICU for Covid-19-related refractory ARDS requiring VV-ECMO. Global in-hospital mortality was 55 %. Median duration of IMV was 4 [2; 8] days before VV-ECMO initiation. There was no significant difference in in-hospital mortality between patients assisted with IMV pre-VV-ECMO for a duration of ≤7 days (≤10 days) and those assisted after 7 days (and 10 days) ((p = 0.59 and p = 0.45). ConclusionThis study suggests that patients assisted with VV-ECMO after prolonged IMV had the same prognosis than those assisted earlier in refractory Covid-19-related ARDS. Therefore, prolonged mechanical ventilation of more than 7–10 days should not contraindicate VV-ECMO support. An individual approach is necessary to balance the risks and benefits of ECMO in this population.

Echocardiographic assessment of right ventricular performance in COVID-19 related acute respiratory distress syndrome: the importance of systo-diastolic interaction.

The cardiac manifestations of COVID-19 have been described in patients with acute respiratory distress syndrome (ARDS) admitted to intensive care unit (ICU). The presence and impact of right ventricular (RV) diastolic function and performance has not been studied in this population yet. We describe the prevalence of RV diastolic dysfunction, assessed by the pulmonary valve pre-ejection A wave (PV A wave), and the RV systo-diastolic interaction, using the RV total isovolumic time (t-IVT), in COVID-19 ARDS. Prospective observational study enrolling patients with moderate to severe COVID-19 ARDS admitted to ICU who underwent a transthoracic echocardiogram within 24h of ICU admission and at least a second one during the ICU stay. Respiratory, hemodynamic and biochemistry parameters were collected. 163 patients (age 61.0 ± 9.3years, 72% males) were enrolled. 36 patients (22.1%) had RV dysfunction, 45 (27.1%) LV systolic dysfunction. 73 patients (44.7%) had PV A wave. The RV t-IVT correlated with TAPSE at ICU admission (p < 0.002; r -0.61), presence of PV A wave (p < 0.001; r 0.78), peak inspiratory pressure (PIP) (p < 0.001; r 0.42), PEEP (p < 0.001; r 0.68), dynamic driving pressure (DDP) (p < 0.001; r 0.58), and PaO2/FiO2 ratio (p < 0.01; r -0.35). The presence of PV A wave was associated with higher PIP (p < 0.001; r 0.45), higher PEEP (p < 0.001; r 0.56), higher DDP (p < 0.01, r 0.51), and lower PaO2/FiO2 ratio (p < 0.001; r -0.49). RV t-IVT and the presence of PV A wave are non-invasive means to describe a significant RV diastolic dysfunction and may be consider descriptive signs of RV performance in COVID-19 ARDS.

Oral beta-hydroxybutyrate alleviates COVID-19 related acute respiratory distress syndrome: A randomized, single-blind, placebo-controlled trial

BackgroundAcute respiratory distress syndrome (ARDS) is a lung complication of COVID-19 that requires intensive care and ventilation. Beta-hydroxybutyrate (BHB) is a ketone body that can modulate metabolism and inflammation in immune cells and lung tissues. We hypothesized that oral BHB could alleviate COVID-19 related ARDS by reducing pro-inflammatory cytokines and increasing anti-inflammatory cytokines. MethodsWe randomized 75 patients with mild (as per Berlin criteria) ARDS symptoms to receive oral 25 g twice daily or placebo for five days. The primary outcome was the change in pro-inflammatory cytokines (Interleukin-1β, Interleukin-6, interleukin-18, tumour necrosis factor-alpha) and anti-inflammatory cytokine (interleukin-10) from baseline to day 5. The secondary outcomes were the change in BHB levels from baseline to day 5, the number of hospitalization days, and the occurrence of adverse events. ResultsTreatment with formulated BHB resulted in a significant decrease in pro-inflammatory cytokines; Interleukin-1β (p = 0.0204), Interleukin-6 (p = 0.0309), interleukin-18 (p = 0.0116), tumour necrosis factor-alpha (p = 0.0489) and increase in interleukin-10 (p = 0.0246) compared treatment with placebo. Importantly, higher BHB levels (p = 0.0001) were observed after supplementation; additionally, patients who underwent this approach were hospitalized for fewer days. No serious adverse events were reported. ConclusionBeta-hydroxybutyrate, an oral adjunct therapy, has shown promising results in ameliorating symptoms of ARDS. This includes reduced inflammation, oxidative stress, and decreased patient fatigue levels. Further study with a large sample size is warranted to assess the potential of BHB therapy's effectiveness in reducing the development of severe illness. Clinical trial registration(http://ctri.nic.in/CTRI/2021/03/031790)

Quantitative Computed Tomography and Response to Pronation in COVID-19 ARDS.

The use of prone position (PP) has been widespread during the COVID-19 pandemic. Whereas it has demonstrated benefits, including improved oxygenation and lung aeration, the factors influencing the response in terms of gas exchange to PP remain unclear. In particular, the association between baseline quantitative computed tomography (CT) scan results and gas exchange response to PP in invasively ventilated subjects with COVID-19 ARDS is unknown. The present study aimed to compare baseline quantitative CT results between subjects responding to PP in terms of oxygenation or CO2 clearance and those who did not. This was a single-center, retrospective observational study including critically ill, invasively ventilated subjects with COVID-19-related ARDS admitted to the ICUs of Niguarda Hospital between March 2020-November 2021. Blood gas samples were collected before and after PP. Subjects in whom the PaO2 /FIO2 increase was ≥ 20 mm Hg after PP were defined as oxygen responders. CO2 responders were defined when the ventilatory ratio (VR) decreased during PP. Automated quantitative CT analyses were performed to obtain tissue mass and density of the lungs. One hundred twenty-five subjects were enrolled, of which 116 (93%) were O2 responders and 51 (41%) CO2 responders. No difference in quantitative CT characteristics and oxygen were observed between responders and non-responders (tissue mass 1,532 ± 396 g vs 1,654 ± 304 g, P = .28; density -544 ± 109 HU vs -562 ± 58 HU P = .42). Similar findings were observed when dividing the population according to CO2 response (tissue mass 1,551 ± 412 g vs 1,534 ± 377 g, P = .89; density -545 ± 123 HU vs -546 ± 94 HU, P = .99). Most subjects with COVID-19-related ARDS improved their oxygenation at the first pronation cycle. The study suggests that baseline quantitative CT scan data were not associated with the response to PP in oxygenation or CO2 in mechanically ventilated subjects with COVID-19-related ARDS.

Association between a low-risk COVID-19 extracorporeal membrane oxygenation criteria and mortality: A retrospective study.

Our study aimed to compare the outcomes of COVID-19 patients who met a low-risk inclusion criteria for veno-venous extra corporeal membrane oxygenation (VV ECMO) with those who did not meet criteria due to higher risk but were subsequently cannulated. This was a retrospective observational cohort study that included adult patients who were placed on VV ECMO for COVID-19 related acute respiratory distress syndrome (ARDS) at a tertiary care academic medical center. The primary outcome was the association between the low-risk criteria and mortality. The patients met the criteria if they met EOLIA severe ARDS criteria, no absolute contraindications (age > 60 years, BMI > 55 kg/m2, mechanical ventilation (MV) duration >7 days, irreversible neurologic damage, chronic lung disease, active malignancy, or advanced multiorgan dysfunction), and had three or less relative contraindications (age > 50 years, BMI > 45 kg/m2, comorbidities, MV duration > 4 days, acute kidney injury, receiving vasopressors, hospital LOS > 14 days, or COVID-19 diagnosis > 4 weeks). Sixty-five patients were included from March 2020 through March 2022. Patients were stratified into low-risk or high-risk categories. The median Sequential Organ Failure Assessment score was 7 and the median PaO2/FiO2 ratio was 44 at the time of ECMO cannulation. The in-hospital mortality was 47.8% in the low-risk group and 69.0% in the high-risk group (p = 0.096). There was not a statistically significant difference in survival between low-risk patients and high-risk patients; however, there was a trend toward higher survival in the lower-risk group.

Impact of prone position on dead-space fraction in COVID-19 related acute respiratory distress syndrome

IntroductionCOVID-19 Related Acute Respiratory Syndrome (C-ARDS) is characterized by a mismatch between respiratory mechanics and hypoxemia, suggesting increased dead-space fraction (DSF). Prone position is a cornerstone treatment of ARDS under invasive mechanical ventilation reducing mortality. We sought to investigate the impact of prone position on DSF in C-ARDS in a cohort of patients receiving invasive mechanical ventilation.Methodswe retrospectively analysed data from 85 invasively mechanically ventilated patients with C-ARDS in supine and in prone positions, hospitalized in Intensive Care Unit (Reims University Hospital), between November, 1st 2020 and November, 1st 2022. DSF was estimated via 3 formulas usable at patients’ bedside, based on partial pressure of carbon dioxide (PaCO2) and end-tidal carbon dioxide (EtCO2).Resultsthere was no difference of DSF between supine and prone position, using the 3 formulas. According to Enghoff, Frankenfield and Gattinoni equations, DSF in supine vs. prone position was in median respectively [IQR]: 0.29 [0.13–0.45] vs. 0.31 [0.19–0.51] (p = 0.37), 0.5 [0.48–0.52] vs. 0.51 [0.49–0.53] (p = 0.43), and 0.71 [0.55–0.87] vs. 0.69 [0.57–0.81], (p = 0.32).Conclusionprone position did not change DSF in C-ARDS.

Functional Capacity in COVID-19 related Acute Respiratory Distress Syndrome Survivors

Background/Purpose:: The aim of this retrospective study is to determine the functional capacity, global muscle weakness and quality of life in COVID-19 survivors. Acute respiratory distress syndrome survivors frequently develop impaired physical function, quality of life, and muscle weakness.&#x0D; Methods: Acute respiratory distress syndrome survivors related to COVID-19 underwent standardized physical clinical evaluation, Medical Research Council-sumscore, hand-grip strength, 6-minute walk test, 5 repetition-chair-stand test, timed up and go test and Short form-36 evaluation following 4-6 weeks after hospital discharge in Physical Medicine and Rehabilitation Outpatient Clinic.&#x0D; Results: Fifteen patients (10 men, 5 women) with median age 69 years and length of intensive care unit stay 10 days were analyzed. There were impairments in 6-minute walk test, 5 repetition-chair-stand test, hand-grip strength and, Role-physical, Role-emotional and Social functioning domains of Short form-36. 6-minute walk distance was negatively correlated with timed up and go. SF-physical functioning was positively correlated with hand-grip strength, Medical Research Council-sumscore and 5 repetition-chair-stand. SF-general health was positively correlated with hand-grip strength.&#x0D; Conclusion: There were varying degrees of functional impairment in survivors. Therefore, it could add advantage to assess these patients after nearly 4-6 weeks following discharge in order to ascertain rehabilitation needs and giving appropriate therapies.

Failing categorization of severe COVID-19 ARDS into ventilatory subphenotypes studied via the clinical-histopathologic relationship

BackgroundCategorization of severe COVID-19 related acute respiratory distress syndrome (CARDS) into subphenotypes does not consider the trajectories of respiratory mechanoelastic features and histopathologic patterns. This study aimed to assess the correlation between mechanoelastic ventilatory features and lung histopathologic findings in critically ill patients who died because of CARDS. MethodsMechanically ventilated patients with severe CARDS who had daily ventilatory data were considered. The histopathologic assessment was performed through full autopsy of deceased patients. Patients were categorized into two groups according to the median worst respiratory system compliance during ICU stay (CrsICU). ResultsEighty-seven patients admitted to ICU had daily ventilatory data. Fifty-one (58.6%) died in ICU, 41 (80.4%) underwent full autopsy and were considered for the clinical-histopathological correlation analysis. Respiratory system compliance at ICU admission and its trajectory were not different in survivors and non-survivors. Median CrsICU in the deceased patients was 22.9 ml/cmH2O. An inverse correlation was found between the CrsICU and late-proliferative diffuse alveolar damage (DAD) (r = −0.381, p = 0.026). Late proliferative DAD was more extensive (p = 0.042), and the probability of stay in ICU was higher (p = 0.004) in the “low” compared to the “high” CrsICU group. Cluster analysis further endorsed these findings. ConclusionsIn critically ill mechanically ventilated patients, worsening of the respiratory system compliance correlated pathologically with the transition from early damage to late fibroproliferative patterns in non-survivors of CARDS. Categorization of CARDS into ventilatory subphenotypes by mechanoelastic properties at ICU admission does not account for the complexity of the histopathologic features.

Infiltrative monocyte derived adenosine deaminase 2 is associated with COVID-19 related acute respiratory distress syndrome

Abstract Acute respiratory distress syndrome (ARDS) is a severe complication of COVID-19 characterized by immune dysregulation. The pathogenesis for this, particularly the involvement of infiltrative monocytes, is poorly understood. Extracellular ATP released during inflammation and hypoxia is rapidly scavenged into adenosine, which is further converted into inosine by adenosine deaminase (ADA). ADA2 is an extracellular isoform of ADA secreted by activated monocytes and expressed by infiltrated CD16 +CXCR3 +monocytes. Herein, we aim to study the impact of monocyte-derived ADA2 in the pathogenesis of COVID-19 associated ARDS. Critically ill COVID-19 patients were assigned to the ARDS group based on Berlin criteria, while the non-ARDS group included COVID-19 patients without any or with low-flow oxygen therapy. We observed elevated ADA activity in the serum of ARDS patients, reflecting increased level of the secreted ADA2 protein, when compared to the non-ARDS group. ARDS patients exhibited high level of circulating IL-6, CXCL8 and CXCL10. Notably, correlation analysis revealed a significant association between circulating ADA activity and CXCL10, a chemokine for CXCR3 +monocytes. Post-mortem bulk RNAseq analysis of lung tissues showed increased expression of the ADA2 gene, CECR1, along with CXCL10 suggesting intrapulmonary accumulation of ADA2 positive macrophages. These observations were further supported by the analysis of single-nuclear and spatial transcriptomic atlas of lung tissues of severe COVID-19 patients, which demonstrated a strong expression of ADA2 in CD16 +monocytes. In summary, our data suggest a potential role of infiltrative monocyte-derived ADA2 in modulating the immune response in COVID-19 related ARDS. Supported by the German Center for Infection Research (TI 07.005 to STH)

Prevalence of pulmonary hypertension in patients with COVID-19 related lung disease listed for lung transplantation: A UNOS registry analysis.

COVID-19 related lung disease (CRLD) has emerged as an indication for lung transplantation (LT) in highly select patients. The prevalence and prognostic implication of coexisting pulmonary hypertension (PH) in patients with CRLD listed for LT is not known. Adult patients in the United Network for Organ Sharing database listed for LT for COVID-19 related acute respiratory distress syndrome or fibrosis through March 2022 were identified. The prevalence and impact of precapillary PH on pre- and posttransplantation survival was determined. Time-to-event analysis was used to compare outcomes between those with and without precapillary PH. We identified 245 patients listed for LT for CRLD who had right heart catheterization data available at the time of registry listing. Median age of the cohort was 54 years (interquartile range [IQR]: 46, 60), 56 (22.9%) were female, and the median lung allocation score was 81.3 (IQR: 53.3, 89.4). The prevalence of precapillary PH at the time of transplant listing was 27.9%. There was no significant difference in pretransplant mortality in patients with and without precapillary PH (sHR: 0.5; 95% confidence interval [CI]: 0.1-1.7, p = 0.261). A total of 187 patients ultimately underwent LT; of those, 60 (31.0%) were identified as having precapillary PH during the waitlist period. Posttransplantation survival was similar between patients with and without pretransplant precapillary PH (hazard ratio: 0.96; 95% CI: 0.2-3.7, p = 0.953). We observed a high rate of concomitant precapillary PH in patients listed for LT for CRLD. Though common, coexisting precapillary PH was not associated with a significant difference in either pre- or post-transplantation outcomes.

Worse survival in patients with right ventricular dysfunction and COVID-19–associated acute respiratory distress requiring extracorporeal membrane oxygenation: A multicenter study from the ORACLE Group

ObjectiveWe sought to determine the impact of right ventricular dysfunction on the outcomes of mechanically ventilated patients with COVID-19 requiring veno-venous extracorporeal membrane oxygenation. MethodsSix academic centers conducted a retrospective analysis of mechanically ventilated patients with COVID-19 stratified by support with veno-venous extracorporeal membrane oxygenation during the first wave of the pandemic (March to August 2020). Echocardiograms performed for clinical indications were reviewed for right and left ventricular function. Baseline characteristics, hospitalization characteristics, and survival were compared. ResultsThe cohort included 424 mechanically ventilated patients with COVID-19, 126 of whom were cannulated for veno-venous extracorporeal membrane oxygenation. Right ventricular dysfunction was observed in 38.1% of patients who received extracorporeal membrane oxygenation and 27.4% of patients who did not receive extracorporeal membrane oxygenation with an echocardiogram. Biventricular dysfunction was observed in 5.5% of patients who received extracorporeal membrane oxygenation. Baseline patient characteristics were similar in both the extracorporeal membrane oxygenation and non–extracorporeal membrane oxygenation cohorts stratified by the presence of right ventricular dysfunction. In the extracorporeal membrane oxygenation cohort, right ventricular dysfunction was associated with increased inotrope use (66.7% vs 24.4%, P < .001), bleeding complications (77.1% vs 53.8%, P = .015), and worse survival independent of left ventricular dysfunction (39.6% vs 64.1%, P = .012). There was no significant difference in days ventilated before extracorporeal membrane oxygenation, length of hospital stay, hours on extracorporeal membrane oxygenation, duration of mechanical ventilation, vasopressor use, inhaled pulmonary vasodilator use, infectious complications, clotting complications, or stroke. The cohort without extracorporeal membrane oxygenation cohort demonstrated no statistically significant differences in in-hospital outcomes. ConclusionsThe presence of right ventricular dysfunction in patients with COVID-19–related acute respiratory distress syndrome supported with veno-venous extracorporeal membrane oxygenation was associated with increased in-hospital mortality. Additional studies are required to determine if mitigating right ventricular dysfunction in patients requiring veno-venous extracorporeal membrane oxygenation improves mortality.

Feasibility and outcomes with subclavian vein access for crescent jugular dual lumen catheter for venovenous extracorporeal membrane oxygenation in COVID-19 related acute respiratory distress syndrome.

Femoral-femoral Veno-Venous ExtraCorporeal Life Support (V-V ECLS) has been associated with higher infections rates, vascular site bleeding complications, and restricted patient mobility. Jugular or bicaval dual lumen V-V ECLS conceptually overcomes some of these adverse factors, but experience has shown that jugular vein cannulation still limits mobility and has increased bleeding complications. Technique and outcomes of subclavian vein single-cannulation with Crescent jugular dual-lumen V-V ECLS is described. five patients with COVID-19 related acute respiratory distress syndrome (ARDS) underwent right subclavian vein V-V ECLS placement with the Crescent 32 French jugular dual-lumen V-V ECLS catheter. A standardized percutaneous technique was developed that allowed efficient insertion without need for any specialized imaging (i.e. transesophageal echocardiogram) and outcomes assessed. Mean age of the five patients was 41.2years, all obese with an average basal mass index of 45.2kg/m2 and mean days to decannulation of 24.2days. Outcomes discovered included; improved patient mobility allowing physical rehabilitation, no vascular access site related complications requiring surgery or endovascular intervention, and none had evidence of superior vena cava syndrome. One patient had subclavian/axillary vein thrombosis with resolution after 3months of direct-acting oral anticoagulants, and one patient had blood cultures positive at day 37, nearing decannulation. Subclavian vein access for crescent jugular dual lumen V-V ECLS catheter appears to be safe and feasible with added benefits of decreased bleeding and increased mobility over jugular or femoral-femoral access site for long term V-V ECLS support in COVID-19 related ARDS patients.

Extracorporeal membrane oxygenation circuits in parallel for refractory hypoxemia in patients with COVID-19

ObjectivesRefractory hypoxemia can occur in patients with acute respiratory distress syndrome from COVID-19 despite support with venovenous (VV) extracorporeal membrane oxygenation (ECMO). Parallel ECMO circuits can be used to increase physiologic support. We report our clinical experience using ECMO circuits in parallel for select patients with persistent severe hypoxemia despite the use of a single ECMO circuit. MethodsWe performed a retrospective cohort study of all patients with COVID–19-related acute respiratory distress syndrome who received VV-ECMO with an additional circuit in parallel at Vanderbilt University Medical Center between March 1, 2020, and March 1, 2022. We report demographic characteristics and clinical characteristics including ECMO settings, mechanical ventilator settings, use of adjunctive therapies, and arterial blood gas results after initial cannulation, before and after receipt of a second ECMO circuit in parallel, and before removal of the circuit in parallel, and outcomes. ResultsOf 84 patients with COVID-19 who received VV-ECMO during the study period, 22 patients (26.2%) received a circuit in parallel. The median duration of ECMO was 40.0 days (interquartile range, 31.6-53.1 days), of which 19.0 days (interquartile range, 13.0-33.0 days) were spent with a circuit in parallel. Of the 22 patients who received a circuit in parallel, 16 (72.7%) survived to hospital discharge and 6 (27.3%) died before discharge. ConclusionsIn select patients, the additional use of an ECMO circuit in parallel can increase ECMO blood flow and improve oxygenation while allowing for lung-protective mechanical ventilation and excellent outcomes.

Feasibility of a New Lung Ultrasound Protocol to Determine the Extent of Lung Injury in COVID-19 Pneumonia

BackgroundLung ultrasound (LUS) is useful to diagnose and assess the severity of pulmonary lesions during CoViD-19 related acute respiratory distress syndrome (CoARDS). A conventional LUS score is proposed to measure the loss of aeration during CoARDS. However, this score was validated during the pre-COVID-19 era in ARDS patients in intensive care and does not consider the differences with CoARDS. An alternative LUS method is based on grading the percentage of extension of the typical signs of COVID-19 pneumonia on the lung surface (LUSext).Research questionIs LUSext feasible in COVID-19 patients at onset of disease and does it correlate with the volumetric measure of severity of COVID-19 pneumonia lesions at computed tomography (CTvol)?Study design and methodThis observational study enrolled a convenience sampling of patients in the emergency department with confirmed COVID-19 and demonstration of pneumonia at bedside LUS and CT scan. LUSext was visually quantified. All CT studies were retrospectively analyzed by a specifically designed software to calculate the CTvol. The correlation between LUSext and CTvol, and the correlations of each score with PaO2/FiO2 ratio (P/F) were calculated.ResultsWe analyzed data from 179 patients. Feasibility of LUSext was 100%. Time to perform LUS scan was 5 + 1.5 mins. LUSext and CTvol were positively correlated, with R = 0.67, P < 0.0001. Both LUSext and CTvol showed negative correlation with P/F, respectively with R = -0.66 and R = -0.54; P <0.0001.InterpretationLUSext is a valid measure of the severity of the lesions when compared to CT scan. Not only are LUSext and CTvol correlated, but they also have similar inverse correlation with the severity of respiratory failure. LUSext is a practical and simple bedside measure of the severity of pneumonia in CoARDS, whose clinical and prognostic impact need to be further investigated.

Clinical decision analysis of elective delivery vs expectant management for pregnant individuals with COVID-19–related acute respiratory distress syndrome

BACKGROUNDPregnant individuals are vulnerable to COVID-19–related acute respiratory distress syndrome. There is a lack of high-quality evidence on whether elective delivery or expectant management leads to better maternal and neonatal outcomes.OBJECTIVEThis study aimed to determine whether elective delivery or expectant management are associated with higher quality-adjusted life expectancy for pregnant individuals with COVID-19-related acute respiratory distress syndrome and their neonates.STUDY DESIGNWe performed a clinical decision analysis using a patient-level model in which we simulatedpregnant individuals and their unborn children. We used a patient-level model with parallel open-cohort structure, daily cycle length, continuous discounting, lifetime horizon, sensitivity analyses for key parameter values, and 1000 iterations for quantification of uncertainty. We simulated pregnant individuals at 32 weeks of gestation, invasively ventilated because of COVID-19–related acute respiratory distress syndrome. In the elective delivery strategy, pregnant individuals received immediate cesarean delivery. In the expectant management strategy, pregnancies continued until spontaneous labor or obstetrical decision to deliver. For both pregnant individuals and neonates, model outputs were hospital or perinatal survival, life expectancy, and quality-adjusted life expectancy denominated in years, summarized by the mean and 95% credible interval. Maternal utilities incorporated neonatal outcomes in accordance with best practices in perinatal decision analysis.RESULTSModel outputs for pregnant individuals were similar when comparing elective delivery at 32 weeks’ gestation with expectant management, including hospital survival (87.1% vs 87.4%), life-years (difference, −0.1; 95% credible interval, −1.4 to 1.1), and quality-adjusted life expectancy denominated in years (difference, −0.1; 95% credible interval, −1.3 to 1.1). For neonates, elective delivery at 32 weeks’ gestation was estimated to lead to a higher perinatal survival (98.4% vs 93.2%; difference, 5.2%; 95% credible interval, 3.5–7), similar life-years (difference, 0.9; 95% credible interval, −0.9 to 2.8), and higher quality-adjusted life expectancy denominated in years (difference, 1.3; 95% credible interval, 0.4–2.2). For pregnant individuals, elective delivery was not superior to expectant management across a range of scenarios between 28 and 34 weeks of gestation. Elective delivery in cases where intrauterine death or maternal mortality were more likely resulted in higher neonatal quality-adjusted life expectancy, as did elective delivery at 30 weeks' gestation (difference, 1.1 years; 95% credible interval, 0.1 – 2.1) despite higher long-term complications (4.3% vs 0.5%; difference, 3.7%; 95% credible interval, 2.4–5.1), and in cases where intrauterine death or maternal acute respiratory distress syndrome mortality were more likely.CONCLUSIONThe decision to pursue elective delivery vs expectant management in pregnant individuals with COVID-19–related acute respiratory distress syndrome should be guided by gestational age, risk of intrauterine death, and maternal acute respiratory distress syndrome severity. For the pregnant individual, elective delivery is comparable but not superior to expectant management for gestational ages from 28 to 34 weeks. For neonates, elective delivery was superior if gestational age was ≥30 weeks and if the rate of intrauterine death or maternal mortality risk were high. We recommend basing the decision for elective delivery vs expectant management in a pregnant individual with COVID-19–related acute respiratory distress syndrome on gestational age and likelihood of intrauterine or maternal death.

Hyperinflammation Reduces Midazolam Metabolism in Critically Ill Adults with COVID-19.

Background and ObjectiveMany patients treated for COVID-19 related acute respiratory distress syndrome in the intensive care unit are sedated with the benzodiazepine midazolam. Midazolam undergoes extensive metabolism by CYP3A enzymes, which may be inhibited by hyperinflammation. Therefore, an exaggerated proinflammatory response, as often observed in COVID-19, may decrease midazolam clearance. To develop a population pharmacokinetic model for midazolam in adult intensive care unit patients infected with COVID-19 and to assess the effect of inflammation, reflected by IL-6, on the pharmacokinetics of midazolam.MethodsMidazolam blood samples were collected once a week between March 31 and April 30 2020. Patients were excluded if they concomitantly received CYP3A4 inhibitors, CYP3A4 inducers and/or continuous renal replacement therapy. Midazolam and metabolites were analyzed with an ultra-performance liquid chromatography–tandem mass spectrometry method. A population pharmacokinetic model was developed, using nonlinear mixed effects modelling. IL-6 and CRP, markers of inflammation, were analyzed as covariates.ResultsThe data were described by a one-compartment model for midazolam and the metabolites 1-OH-midazolam and 1-OH-midazolam-glucuronide. The population mean estimate for midazolam clearance was 6.7 L/h (4.8–8.5 L/h). Midazolam clearance was reduced by increased IL-6 and IL-6 explained more of the variability within our patients than CRP. The midazolam clearance was reduced by 24% (6.7–5.1 L/h) when IL-6 increases from population median 116 to 300 pg/mL.ConclusionsInflammation, reflected by high IL-6, reduces midazolam clearance in critically ill patients with COVID-19. This knowledge may help avoid oversedation, but further research is warranted.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-022-01122-5.

Changes in Therapy Outcome of Veno-Venous Extracorporeal Membrane Oxygenation for Therapy-Refractory COVID-19 Infections Throughout the Pandemic

PurposeSince the beginning of the current pandemic in late 2019, three accumulations of severe COVID-19 infections (so-called infective waves) caused a fulminant increase in hospitalization. In therapy-refractory patients, veno-venous extracorporeal membrane oxygenation (vv-ECMO) was used since the early beginning. However, potential developments in vv-EMCO therapy still need to be proven.MethodsBetween 2020 and 2021 a total of n=60 patients were treated with vv-ECMO for severe COVID-19 related acute respiratory distress syndrome in our department. The patients were prospectively enrolled into an institutional database, followed-up and subsequent retrospectively reviewed. Patients were divided concerning the date of vv-ECMO onset into three groups (03/2020-09/2020: 1. wave, n=11; 10/2020-02/2021: 2. wave, n=23; 03/2021-08/2021: 3. wave, n=26).ResultsFrom the first to the third wave, patients seemed to be younger, more likely to be female as well as more likely obese. While patients of the first wave regularly developed acute kidney failure (81.3 %), these adverse event was seldom in the second (21.7) and third wave (15.4 5)(p=0.01). In contrast to that, other device-related complications such as stroke, bleeding or visceral ischemia did not differ between the three waves. Most apparent changes during the pandemic were prolonged ECMO support duration (1. wave: 8.5 ± 2.1, 2. wave: 54.0 ± 122.7, 3. wave: 28.0 ± 18.6), ECMO weaning rate (1. wave: 18.2 %, 2. wave: 39.1, 3. wave: 44.0 %) and in-hospital mortality (1. wave: 81.8 %, 2. wave: 69.6, 3. wave: 56.0 %), although none of these effects reached statistical significance.ConclusionAlthough our data cover only a small study population, we observed clear trends towards younger and heavier patients during the pandemic. Most likely, due to a learning effect, support duration of ECMO patients distinctly increased during the pandemic. Subsequently, weaning and survival also increased. However, differences in patient selection could act as a major confounder for these results.

Bedside Selection of Positive End Expiratory Pressure by Electrical Impedance Tomography in Patients Undergoing Veno-Venous Extracorporeal Membrane Oxygenation Support: A Comparison between COVID-19 ARDS and ARDS from Other Etiologies.

Background: The interest in protective ventilation strategies and individualized approaches for patients with severe illness on veno venous extracorporeal support has increased in recent years. Wide heterogeneity exists among patients with COVID-19 related acute respiratory distress syndrome (C-ARDS) and ARDS from other etiologies (NC-ARDS). EIT is a useful tool for the accurate analysis of regional lung volume distribution and allows for a tailored ventilatory setting. The aim of this work is to retrospectively describe the results of EIT assessments performed in patients C-ARDS and NC-ARDS undergoing V-V ECMO support. Methods: A clinical EIT-guided decremental PEEP trail was conducted for all patients included in the study and mechanically ventilated. Results: 12 patients with C-ARDS and 12 patients with NC-ARDS were included in the study for a total of 13 and 18 EIT evaluations, respectively. No significant differences in arterial blood gas, respiratory parameters, and regional ventilation before and after the EIT exam were recorded. The subset of patients with NC-ARDS whose EIT exam led to PEEP modification was characterized by a lower baseline compliance compared with the C-ARDS group: 18 (16–28) vs. 27 (24–30) (p = 0.04). Overdistension significantly increased at higher steps only for the NC-ARDS group. A higher percentage of overdistension was described in patients with NC-ARDS when compared with patients with C-ARDS. Conclusions: EIT is feasible in patients with COVID-19-associated ARDS on veno-venous extracorporeal support and may help in tailoring the PEEP setting. Overall, severe COVID-19-related ARDS presents respiratory characteristics similar to severe “classical” NC-ARDS. However, C-ARDS is associated with a lower risk of overdistension at a higher PEEP level compared with NC-ARDS.