Long-term support of COVID-19 patients with veno-venous extracorporeal membrane oxygenation: Complications, predictors of mortality and long-term outcome

Objectives: Treatment of severe respiratory distress syndrome (ARDS) due to COVID-19 by veno-venous extracorporeal membrane oxygenation (VV-ECMO) had a mortality of up to 70% in Germany. Many patients with COVID-19 need VV-ECMO support longer than 28 days (long-term VV-ECMO). Evidence on mortality, complications during intensive care, functional status after discharge and mortality-predictors for patients supported with long-term VV-ECMO is lacking. Method(s): Retrospective study of 137 consecutive patients treated with VV-ECMO for ARDS due to COVID-19 at University Hospital Regensburg from March 2020 to March 2022. Result(s): 38% (n=52;87% male) of patients needed longterm VV-ECMO support. In these, SOFA score (median [IQR]) at ECMO initiation was 9 [8-11], age 58.2 [50.6- 62.5] years, PaO2/FiO2-ratio 67 [52-88] mmHg, pCO262 [52-74] mmHg, Murray-Score 3.3 [3.0-3.6] and PEEP 15 [13 - 16] cmH2O. Duration of long-term support was 45 [35-65] days. 26 (50%) patients were discharged from the ICU. Only one patient died after hospital discharge. At VVECMO initiation, baseline characteristics did not differ between deceased and survivors. Complications were frequent (acute kidney injury: 31/52, renal replacement therapy: 14/52, pulmonary embolism: 21/52, intracranial hemorrhage 8/52, major bleeding 34/52 and secondary sclerosing cholangitis: 5/52) and more frequent in the deceased. Karnofsky index (normal 100) after rehabilitation was 70 [57.5-82.5]. Twelve of the 18 patients discharged from rehabilitation had a satisfactory quality of life according to their own subjective assessment. Four patients required nursing support. Mortality-predictors within the first 30 days on VV-ECMO only observed in those who deceased later, were: Bilirubin >5mg/dl for > 7 days, pulmonary compliance <10ml/mbar for >14 days, and repeated serum concentrations of interleukin 8 >150ng/L. Conclusion(s): Long-term extracorporeal lung support in patients with COVID-19 resulted in 50 % survival and subsequently lead to a satisfactory quality of life and functionality in the majority of patients. It should preferably be performed in experienced centers because of a high incidence of complications. Several findings during the early course were associated with late mortality but need validation in large prospective studies.

Two-year outcome of extracorporeal membrane oxygenation in COVID-19 related severe respiratory failure

Objectives: We sought to evaluate 2-year outcome of V-V ECMO support for COVID-19 related severe respiratory failure in our center. Method(s): Retrospective analysis of 41 consecutive patients (73% male, mean age 51.6+/-14.2 years, mean BMI 35.1+/-12.5 kg/m2) with critical hypoxemic and/or hypercapnic refractory respiratory failure (mean P/F ratio 67.9+/-14.3 mmHg, mean pCO2 77.6.0+/-185.7 mmHg, Murray Score 3.71+/-0.4) on V-V ECMO support from October 2020 to January 2022 Results: With mean support duration of 234.4+/-63.2 hours, 29 patients (70.7%) were successfully weaned off. Finally, 19 of them (46.3%) were discharged home with good neurological outcome (CPC 1,2). During followup, 30-day, 6-, 12-, and 24 -month survival rate was 61.3%, 46.2%, 41.9%, and 41,9% respectively. In survivor group shorter symptoms onset to respiratory failure time (4+/-4.7 vs. 7+/-6.7 days, p=0.04), higher P/F ration (86+/-41.5 vs. 65+/-37.5 mmHg, p=0.04) and norepinephrine support (0.03+/-0.06 vs. 0.09+/-0.12 ug/kg/min, p=0.04), and lower IL-6 level (12.3+/-7.5 vs. 25.9+/-8.8 ng/l, p=0.03) p=0.01) were analysed before cannulation. Mean in-ICU stay and in-hospital stay in survivors;groups reached 32.5+/-27.7 days and 42.6+/-35.8 days, respectively. All long-term survivors (17 patients) complained about slight functional health limitation only with normal 6MWT (542.6+/- 89.2 min), near to normal spirometry parameters (FEV/VC 87+/-7.4%, DLCO 63.1+/-13.7%, KCO 82.,1+/-19.4%) and minimal neurological disability (CPC 1-2) Conclusion(s): 2-year outcome of V-V ECMO support in COVID-19 severe respiratory failure is acceptable even in the scope of low-volume ECMO centre. Reported functional status of long-term survivors was good despite the complicated and prolonged in-hospital stay. (Table Presented).

Echocardiographic findings in critically Ill patients with COVID-19 treated with and without extracorporeal membrane oxygenation

Objectives: There is a paucity of data on echocardiographic findings in patients with COVID-19 supported with Venovenous Extracorporeal Membrane Oxygenation (VV ECMO). This study aimed to compare baseline echocardiographic characteristics of mechanically ventilated patients for acute respiratory distress syndrome (ARDS) due to COVID-19 infection with and without VV ECMO support and to describe the incidence of new echocardiographic abnormalities in these patients. Method(s): Single-center, retrospective cohort study of patients admitted from March 2020 to June 2021 with COVID-19 infection, that required mechanical ventilation, and had an available echocardiogram within 72 hours of admission. Follow-up echocardiograms during ICU stay were reviewed. Result(s): A total of 242 patients were included in the study. One-hundred and forty-five (60%) patients were supported with VV ECMO. Median (IQR) PaO2/ FiO2 was 76 (65-95) and 98 (85-140) in the VV ECMO and non-ECMO patients, respectively (P = < 0.001). On the admission echocardiograms, the prevalence of left ventricular (LV) systolic dysfunction (10% vs 15%, P= 0.31) and right ventricular (RV) systolic dysfunction (38% vs. 27%, P = 0.27) was not significantly different in the ECMO and non-ECMO groups. However, there was a higher proportion of acute cor pulmonale (41% vs. 26 %, P = 0.02) in the ECMO group. During their ICU stay, echocardiographic RV systolic function worsened in 44 (36%) patients in the ECMO group compared with six (10%) patients in the non-ECMO group (P< 0.001). The overall odds ratio for death for patients with worsening RV systolic function was 1.8 (95% confidence interval 0.95-3.37). Conclusion(s): Echocardiographic findings suggested that the presence of RV systolic dysfunction in COVIDECMO patients was comparable to the non-ECMO group on admission. However, a higher percentage of patients on ECMO developed worsening RV systolic function during follow-up.

Liver dysfunction as a respiratory prognostic factor in covid-19 patients.

Respiratory dysfunction is a main clinical symptom of COVID-19. Liver dysfunction is also frequently reported in patients with COVID-19 and considered to be related to a poor prognosis. However, the precise mechanisms behind these findings remain unclear. We investigated the clinical features and prognostic factors related to liver dysfunction in 26 COVID-19 pa-tients. The patients with liver dysfunction had markedly higher WBC, neutrophils, CRP, and frequency of oxygen administration and markedly lower PaO2/FIO2 ratios. The patients with liver dysfunction had longer mean hospital stays. In conclusion, liver dysfunction at hospital admission may be an important prognostic factor for respiratory failure in patients with COVID-19. We must administer intensive care to these patients earlier to inhibit severe disease progression.Copyright ©2021 The Japan Society of Hepatology.

Managing Severe Acute Asthma Exacerbation in Pregnancy during the COVID-19 Pandemic: A Case Report from a Resource-limited Setting

BACKGROUND: One-third of pregnant women will experience worsening asthma requiring emergency hospitalization. However, no report comprehensively discussed the management of asthma attacks in pregnant women in impoverished settings. We attempt to illuminate what general practitioners can do to stabilize and improve the outcome of severe acute asthma exacerbations in primary care with resource limitations. CASE REPORT: A nulliparous 29-year-old woman in her 21st week of pregnancy presented severe acute asthma exacerbation in moderate persistent asthma with uncontrolled asthma status along with gestational hypertension, uncompensated metabolic acidosis with a high anion gap, anemia, respiratory infection, and asymptomatic bacteriuria, all of which influenced her exacerbations. This patient was admitted to our resource-limited subdistrict hospital in Indonesia during the COVID-19 pandemic for optimal stabilization. Crystalloid infusions, oxygen supplementation, nebulized beta-agonist with anticholinergic agents, inhaled corticosteroids, intravenous methylprednisolone, broad-spectrum antibiotics, subcutaneous terbutaline, mucolytics, magnesium sulphate, oral antihypertensives, and continuous positive airway pressure were used to treat her life-threatening asthma. After she was stabilized, we referred the patient to a higher-level hospital with more advanced pulmonary management under the supervision of a multidisciplinary team to anticipate the worst scenario of pregnancy termination. CONCLUSION(S): Limitations in primary care, including the lack of sophisticated intensive care units and laboratory panels, may complicate challenges in managing severe acute asthma exacerbation during pregnancy. To enhance maternal-fetal outcomes, all multidisciplinary team members should be well-informed about key asthma management strategies during pregnancy using evidence-based guidelines regarding the drug, rationale, and safety profile.Copyright © 2023 Muhammad Habiburrahman, Triya Damayanti, Mohammad Adya Firmansha Dilmy, Hariyono Winarto.

Analysis of Quality Metrics Relating to the Intubation of Covid-19 patients on a General ICU

Introduction: Most modern healthcare systems are striving to improve patient outcomes in an evidence-based manner. Increasingly, performance metrics are seen as key tools for accurately measuring and improving patient outcomes and healthcare value.1 However, in order to achieve better outcomes, process measures need to be identified. Process measures are evidence-based, best practices metrics that can be measured and thus, used to identify if outcomes are being met. Good process measures can improve patient outcomes by reducing the amount of variation in care delivery. During the Covid-19 pandemic, vast quantities of data were generated while managing ARDS (Acute Respiratory Distress Syndrome) on the ICU. Furthermore, there was as a concomitant evolution of treatment strategies, which made it exceedingly difficult to identify processes that were actually improving patient outcomes. Objective(s): The aim of our quality improvement project was to promote standardised high quality care for intubated Covid-19 patients by identifying potential quality indicators and trends in their management. It is our intention to expand on this work to report metrics on all severe acute respiratory failure patients. Method(s): 15 process metrics surrounding the early care of intubated of Covid-19 patients were selected via a consultant led review process and a literature review in an effort to identify markers of quality surrounding intubation on our ITU. The variables selected included: - P/F ratio 24 hours pre-intubation, CPAP (continuous positive airway pressure) duration prior to intubation, Recording intubation location, Enhanced thromboprophylaxis prescribed, Permissive hypercapnia, Driving pressure documented, prone position and paralysis initiated if P/F ratio was less than 20 kPa, Echo post intubation. Result(s): Data surrounding the intubation of Covid-19 patients was collected over an 11 week period between September and November 2021. The data was collected in a standardised fashion from patient notes and nursing notes, then stored in an excel file. Our data showed more than half the patients admitted were either intubated on the ward or immediately following arrival onto our ICU, possible indicating a delay in admitting Covid-19 patients. Our data also demonstrated heterogeneity of duration in CPAP prior to intubation which may also indicate delayed intubation for these patients.2 Conclusion(s): Our data demonstrated a reasonable degree of heterogeneity in our approach to the early care of intubated Covid-19 Patients. Areas of concern highlighted were the number of patients intubated on the ward or immediately upon arrival to ITU, rather than admitting prior to deterioration (most likely due to bed pressure) and variation in post intubation respiratory sampling between invasive and non-invasive broncheoalveolar lavage. Ongoing PDSA (plan-do-study-act) cycling are in progress to refine the data collection processes and reporting for all severe acute respiratory failure patients.

Blood purification treatment and cytokine removal using Cytosorb device in critically ill patients with COVID-19 infection

Introduction: Acute kidney injury (AKI) is a complication of SARS-CoV-2 disease, associated with worse clinical outcomes. Renal replacement therapy (RRT) in combination with sequential extracorporeal blood purification therapies (EBPT) might support renal function, attenuate systemic inflammation, and prevent or mitigate multiple organ dysfunctions. Method(s): We retrospectively analyzed 20 patients admitted in ICU for ARDS and who developed moderate-to-severe AKI requiring RRT. Cytokine hemadsorption with Cytosorb was performed in association with CRRT. The main indication for this treatment was the worsening of hemodynamic and respiratory conditions and suspicion of cytokine storm. The protocol consisted in the use of 3-4 cartridges in total;among these, the first 2 were changed after 12 hours of treatment to maximize cytokine removal, while the others after 24 hours. We examined comorbidities, clinical and laboratory characteristics and the impact of treatment in terms of mortality rate and changes in data before and after treatment. Result(s): Nineteen patients (95%) had an AKI at any time during their ICU stay. Of these, 5 patients (25%) had AKI stage II and 14 patients (70%) had AKI stage III. All patients included in this subgroup were mechanical ventilated and required vasopressor's use. Mean prescribed CRRT dose was 31.2 +/- 11.7 ml/kg/h. The median time to strating RRT after ICU admission was 7 days (IQR 3.5-15 days) and the median duration was 7 days (IQR 2.5-12.5 days). Mean SOFA score at the time of RRT start was extremely high (14.5 +/- 2.8). Mortality rate was important (18 patients, 90%) in our cohort. Comparing clinical and laboratory data before and after treatment, a significant improvement of inflammatory markers was reported, with the reduction of C-reactive protein (CRP, 143 [62.1- 328.5] vs 83.5 [66.7-153.5] mg/L);however, no significant changes in IL-6, WBC and PCT values were observed. A slight increase of PaO2/FiO2 were described, although not statistically significant (PaO2/FiO2 ratio 144 [82.7-174.2] vs 183 [132-355.5] mmHg). Conclusion(s): Our experience supports the need of an adequate timing for the use of Cytosorb in critically ill patients with Covid-19. Although a discrete efficacy in improving inflammatory cascade, the late use of EBPT, when organ dysfunction was already ongoing, didn't impact survival.

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.

Comparing effects of invasive versus non-invasive ventilation on P/F ratio, CRP and respiratory rate of COVID patients, a retrospective observational study

Introduction: Some of the COVID pneumonitis patients are happily hypoxic and not showing signs of severe respiratory distress despite being significantly hypoxic,1 leading to a delay to start a timely treatment and may worsen the prognosis.2 Studies have shown that non-invasive ventilation could be used in severe COVID pneumonitis and could avoid intubation in some of those patients.3 Effects of different modalities of ventilation on the oxygenation of COVID-19 patients and on the inflammatory process accompanying COVID-19 pneumonitis need thorough investigation in a trial to reach to an understanding of the pathophysiological process and may be a guide to formulate the optimum protocol to ventilate COVID-19 patients. Objective(s): Comparing the effects of invasive versus non-invasive ventilation on P/F ratio, CRP and respiratory rate of COVID-19 patients. Method(s): In this retrospective observational study, we compared the effect of NIV on the P/F ratio, CRP trends and Respiratory rates of COVID patients during their ITU admission in comparison with intubated ventilated patients. The study was carried out in a single center in England before introduction of the Tocilizumab in the guidelines of COVID treatment and included 74 COVID patients divided in to two groups, group A which included 15 patients who were non-invasively ventilated and avoided intubation during their ITU admission while group B included 59 patients who were intubated at certain point of their course of admission. Patients Respiratory rate, modality of ventilation, time of intubation (if any), modes of ventilation, FIO2, P/F ratio and CRP trends were followed during their admission. The collected data of 3 variable (CRP, RR and P/F ratio) has been blotted and a summative means were calculated. The least square means of the linear models of the ventilated and non-ventilated patients were used to compare both groups. Result(s): 36.4 % of intubations was done before or during the first 20 hours of the ITU admissions and 50% during the first 40 hours. The study also has shown the probabilities in the difference between slopes as following. Firstly, regarding P/F ratio the probability was 0.058 in favor of non-invasive ventilation. Secondly, RR probability was <0.0001 significantly in favor of non-invasive ventilation. Lastly, CRP probability was 0.024 significantly in favor of non-invasively ventilated patients. Conclusion(s): CRP and respiratory rate were significantly less in non-invasively ventilated COVID pneumonitis patients in comparison with ventilated patients while there was no significant difference in P/F ratio trends between both groups.

A systematic review of the use of CytoSorb© Hemoadsorption in patients undergoing veno-venous ECMO support for severe acute respiratory distress syndrome

Objectives: Acute respiratory distress syndrome (ARDS) often results in high mortality and morbidity. Hemoadsorption therapy, such as CytoSorb©, is being increasingly used to target the underlying hyperinflammation that occurs with ARDS. This review aims to evaluate the available data on the use of CytoSorb in combination with veno-venous extracorporeal membrane oxygenation (V-V ECMO) in severe ARDS cases, and to assess its effects on inflammatory, laboratory, and clinical parameters, as well as on patient outcomes. Method(s): A systematic literature review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) statement. Whenever possible, an analysis of changes in relevant biomarkers and clinical parameters was performed. Result(s): CytoSorb© therapy was associated with significant reductions in circulating levels of C-reactive protein and interleukin-6 (p = 0.039 and p = 0.049, respectively), as well as an increase in PaO2/FiO2 levels (p = 0.028). There was also a trend towards reduced norepinephrine dosage (p = 0.067). Mortality rates in patients treated with CytoSorb©tended to be lower than in the control groups, but these studies had high heterogeneity and low power. In an exploratory analysis of 90-day mortality in COVID19 patients receiving V-V ECMO, the therapy was associated with a reduced risk of death. Conclusion(s): Overall, the reviewed data suggests that CytoSorb© therapy can effectively reduce inflammation and potentially improve survival in ARDS patients treated with V-V ECMO. Therefore, early initiation of CytoSorb ©in conjunction with ECMO may offer a promising approach to enhance lung rest and promote recovery in patients with severe ARDS. A randomised trial is warranted to confirm our findings.

Lung inhomogeneities in COVID-19 related acute respiratory distress syndrome

Introduction: In acute respiratory distress syndrome (ARDS) inhomogeneities in lung aeration can act as local multipliers of pressure during inspiration (stress risers), increasing the risk of lung damage even in presence of airway pressures considered safe [1]. In this study we aimed to describe lung inhomogeneities in COVID-19 related ARDS (C-ARDS) and to relate these to disease severity and lung morphology. Method(s): We enrolled patients with C-ARDS within 3 days from mechanical ventilation start, deeply sedated and paralyzed. Lung CT scan was obtained at PEEP of 5 cmH2O to measure lung weight compartments (non-, poorly-, well- and over-aerated). Lung inhomogeneities were computed as the gas/tissue ratio of each voxel compared to the neighboring voxels. We considered values > 1.61 as pathologic lung inhomogeneities, as previously described [1]. The fraction of total lung volume with pathologic inhomogeneities (extent) and the average severity of inhomogeneities contained in that fraction (intensity) was calculated. Respiratory system compliance and blood gas analysis were obtained at the same PEEP level of the CT scan. Some results have been presented in another publication [2]. Result(s): Forty patients were studied in the supine position 1 (0-1) days after ICU admission. The extent of pathologic lung inhomogeneities represented 18 +/- 4% of total lung volume. The intensity of pathologic lung inhomogeneities was on average 2.53 +/- 0.12. Extent was positively correlated with the amount of poorly aerated lung weight ( r2 = 0.51, p < 0.001) (Fig. 1) and negatively correlated with the amount of non-aerated lung weight ( r2 = 0.22, p = 0.002). No correlation was found between extent and intensity and PaO2/ FiO2, dead space fraction or respiratory system compliance. Conclusion(s): In C-ARDS lung inhomogeneities represent roughly 20% of total lung volume. In these regions local stress is increased with risk of secondary lung damage.

Non-invasive ventilation in >= 70 year old COVID-19 patients in a level two unit: retrospective cohort analysis, comparison with COVIP substudy and defense of a multifaceted work of breathing control driven strategy

Introduction: The debate about optimal management of patients with COVID-19 ARDS remains, including medical treatment, ventilatory strategies, awake proning and others. COVIP is a multicentric observational study with over 3000 patients under NIV. A substudy by Polok and al. evaluated patients (PTS) >= 70 years old. At our intermediate care unit (IU) we used a strategy of high dose corticosteroid started when the work of breathing (WOB) increased, prolonged awake prone positioning (> 12 h) and high CPAP ventilatory strategy. We describe our cohort of >= 70 years old NIV PTS and compare it to COVIP substudy results. Method(s): Descriptive retrospective study. Data were collected from electronic medical records of 95 COVID-19 PTS aged 70 years old or above under NIV at the IU between September/20 and March/21. Categorical data are presented as frequency (percentage) and were compared using chi2-test. Continuous variables were compared using Mann-Whitney U test. Cohort results were compared with those from Polok et al. COVIP substudy (COVIPss). Result(s): 95 of PTS were submitted to NIV. Median age was 76 years and 49.5% were male, versus 75.7 and 71.4% in COVIPss. Median admission SOFA score was 4 and CFS was 3 with 14% considered frail (CFS > 5). In COVIPss median SOFA was 5 and 17% of PTS were frail. The preferred mode was CPAP with median maximum pressure of 13. Mean PaO2/fiO2 ratio after start of NIV was 125, 30% < 100. NIV failure occurred in 46.3% versus 74,7% in COVIPss. Our intra-unit mortality was 31.6%. 14 PTS (14.7%) were submitted to invasive mechanical ventilation and 57% of those died. In COVIPss mortality at 30d was 52.9% in NIV and 47.7 in IMV groups. Conclusion(s): We argue that NIV is a valid option for COVID ARDS management if supported by a multifaceted strategy such as ours, using prone and CPAP for WOB control. We agree with COVIPss authors as NIV trial should be short and intubation promptly if WOB not controlled. Comparison with COVIP substudy NIV failure and mortality results, support our belief.

Hypoxemia as a risk factor for acute kidney injury in COVID-19.

OBJECTIVE: To demonstrate if in patients with COVID-19 hypoxemia is a risk factor of acute kidney injury. MATERIALS AND METHODS: Cross-sectional, retrospective, descriptive, analytical study was done from May 1st to September 30th, 2020, including patients over 18 years of age admitted to the emergency service of a COVID-19 care medical center with the criteria of a suspected case of COVID-19 plus chest tomography with suggestive images. They were classified by the serum creatinine (SCr) value: Group 1 (G1) without acute kidney injury and group 2 (G2) with acute kidney injury. RESULT(S): One hundred and five patients were recruited. G1 included 32 patients (30.5%) and G2 73 (69.5%). Median SCr at admission was 0.7 and 1.0 mg/dL for G1 and G2, respectively (p = 0.05). The median PaO2/FiO2 at admission for G1 was 90 mmHg and for G2 105 mmHg (p = 0.76) without finding association with admission acute kidney injury;arterial oxygen saturation (SatO2) equal or higher than 92% to the moment of admission to the emergency department presented a negative correlation for the development of acute kidney injury (Pearson: -0.537, p = 0.04). CONCLUSION(S): In the initial phase of COVID-19, hypoxemia is not a triggering factor for acute kidney injury;however, SatO2 can be a distracting marker of respiratory stability since persistent hypoxemia would be one more conditioning of acute kidney injury.Copyright © 2022 Comunicaciones Cientificas Mexicanas S.A. de C.V.. All rights reserved.

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.

Latent class analysis of imaging and clinical respiratory parameters from patients with COVID-19-related ARDS identifies recruitment subphenotypes

Introduction: Patients with COVID-19-related acute respiratory distress syndrome (ARDS) require respiratory support with invasive mechanical ventilation and show varying responses to recruitment manoeuvres. In patients with ARDS not related to COVID-19, two pulmonary subphenotypes that differed in recruitability were identified using latent class analysis (LCA) of imaging and clinical respiratory parameters [1]. We aimed to validate these phenotypes and evaluate if similar subphenotypes are present in patients with COVID-19-related ARDS. Method(s): This is the retrospective analysis of mechanically ventilated patients with COVID-19-related ARDS who underwent CT scans at positive end-expiratory pressure of 10 cmH2O and after a recruitment manoeuvre at 20 cmH2O. LCA was applied to quantitative CT-derived parameters, clinical respiratory parameters, blood gas analysis and routine laboratory values before recruitment to identify subphenotypes. Result(s): 99 patients were included. Using 12 variables, a two-class LCA model was identified as best fitting. Subphenotype 2 (recruitable) was characterized by a lower PaO2/ FiO2, lower normally aerated lung volume and lower compliance as opposed to a higher nonaerated lung mass and higher mechanical power when compared to subphenotype 1 (non-recruitable) (Fig. 1). Patients with subphenotype 2 had more decrease in non-aerated lung mass in response to a standardized recruitment manoeuvre (p = 0.024) and were mechanically ventilated longer until successful extubation (adjusted SHR 0.46, 95% CI 0.23-0.91, p = 0.026), while no difference in survival was found (p = 0.814). Conclusion(s): A recruitable and non-recruitable subphenotype were identified in patients with COVID-19-related ARDS. The subphenotypes are similar to non-COVID-19-related ARDS and are promising for identification of recruitable patients in future practice as they can be classified with only few clinically available parameters before the recruitment manoeuvre.

A nationwide cohort study of pregnant and postpartum patients with severe COVID-19 pneumonitis in ICU in Israel

Introduction: This study included pregnant patients with severe COVID to test the hypothesis that the impact of delivery on maternal outcome depends upon illness severity at the time of delivery;we hypothesized that patients not yet requiring IPPV would improve following delivery (due to improvement in respiratory mechanics), while patients already on IPPV, or close to requiring ventilation, would deteriorate (due to maternal cardiovascular intolerance to autotransfusion). Method(s): This multicenter, prospective/retrospective cohort study evaluated Israeli ICU admissions of pregnant women with COVID-19 pneumonitis from 1-Feb-2020 to 31-Jan-2022. We assessed maternal, neonatal outcomes and longitudinal maternal clinical data. The primary outcome was maternal outcome (no-IPPV, IPPV, ECMO, death). The primary longitudinal outcome was SOFA score, the secondary longitudinal outcome was the novel PORCH score (PEEP, Oxygenation, Respiratory-support, Chest-X-ray, Haemodynamic-support). Patients were classified into: no-delivery, postpartum admission, deliverycritical and delivery-not-critical groups. Result(s): 84 patients in 13 ICUs were analysed;there were 34 nodelivery, 4 postpartum, 32 delivery-critical, 14 delivery-not-critical patients. Delivery-critical and postpartum had worse outcomes with, 26/32(81%) and 4/4(100%) requiring IPPV;12/32(38%) and 3/4(75%) requiring ECMO;1/32(3%) and 2/4(50%) dying. Deliverynot- critical and no-delivery had far better outcomes with, respectively, 6/34(18%) and 2/14(14%) requiring mechanical ventilation;no patients required ECMO or died. SpO2, S/F ratio, P/F ratio in Deliverycritical deteriorated on the day of delivery, continued to deteriorate, and took longer to recover;delivery-not-critical improved rapidly following delivery. The day of delivery was a highly significant covariate for PORCH (p < 0.0001), not SOFA (p = 0.09). Conclusion(s): Interventional delivery should be considered for maternal indications before patients deteriorate and require IPPV.

A Joint Analysis of Two Randomized Controlled Trials on Enoxaparin for Covid-19

Background: COVID-19 carries a high risk of vascular thrombosis. This joint analysis of two randomized-controlled trials (RCTs) aims to assess the safety and efficacy of enoxaparin at therapeutic dose compared to prophylactic dose in people hospitalized with COVID-19. Method(s): A joint analysis of two RCTs, COVID-19 HD (NCT044082359) and EMOS-COVID (NCT04646655), was performed. Both studies enrolled inpatients with COVID-19- associated respiratory compromise (as identified by respiratory rate >=25 breaths/min or arterial oxygen saturation <=93% at rest or PaO2/FiO2 <=300 mmHg for COVID-19 HD and by PaO2/FiO2 <=250 mmHg for EMOS-COVID) and/or coagulopathy (D-dimer > 2000 ng/ml for both RCTs or sepsis-Induced coagulopathy score >4 for COVIDHD). In both RCTs patients were randomly assigned to two arms: enoxaparin at prophylactic dose (standard 4.000 IU;in the EMOS-COVID 6000 IU if body weight >100 kg) and at therapeutic dose (70 U/Kg every 12 h). The primary efficacy endpoint of the joint analysis was clinical worsening, defined as the occurrence of at least one among: in-hospital death;acute myocardial infarction;symptomatic arterial or venous thromboembolism;need of either Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) in patients who were in standard oxygen therapy at randomization;need for IMV in any patient. The primary outcome was assessed as time-to-event, described with hazard ratio (HR) and with Kaplan-Meier survival estimate. The primary safety endpoint was major bleeding for both trials and for the joint analysis. Result(s): COVID-19 HD enrolled 142 people between July 2, 2020 and February 15, 2022, while EMOS-COVID enrolled 141 people from July 27, 2020 to June 5, 2021, resulting in 283 patients included in this joint analysis. Two-hundredseven (73.1%) were males, with a mean age of 61.1 years (SD +/-10.7), a mean BMI of 29.7 kg/m2 (SD +/-5.0), and 115 (40.6%) were on NIV or Cpap at randomization, with no significant difference between the study groups. 21/139 people in the high dose group reached the primary endpoint compared to 32/144 in the prophylactic group (HR 0.63, 95%CI 0.36 to 1.10). Figure 1 shows the Kaplan- Meier survival estimates of clinical worsening. No major bleeding was observed during the study time. Conclusion(s): The results of this joint analysis did not highlight significant differences in clinical worsening between COVID-19 patients that received enoxaparin at therapeutic compared to prophylactic dose. (Figure Presented).

Sedation in the ICU: association between dexmedetomidine and 28-day mortality in patients with COVID-19

Introduction: The aim of our study is to evaluate the relationship between dexmedetomidine (DEX) use as a sedative agent in mechanical ventilated ICU patients and 28-day mortality. DEX, a selective alfa-2 adrenergic receptor agonist, widely used for its sedative and analgesic properties, has been linked to increasing parasympathetic tone, reducing the inflammatory response and oxidative stress [1]. Since severe COVID-19 is associated with an hyperinflammatory state, it is hypothesized that DEX might improve outcomes in these patients. Method(s): This is a retrospective observational study of mechanically ventilated patients admitted with COVID-19 pneumonia in the ICU of a tertiary center in Portugal, between March 2020 and December 2021. Logistic regression analysis was performed to evaluate the association of DEX use and 28-day mortality from time of intubation. Result(s): A total of 277 patients were analyzed, 151 in the DEX group and 126 in the no DEX group. Patients in the DEX group were younger (53.3 vs. 63.3 years, p < 0.001), had less comorbidities (2.8 vs. 3.5, p = 0.01), lower SOFA at admission (6.2 vs. 7.1, p = 0.01) but had a prolonged ICU stay (21.4 vs. 15.9, p < 0.001). Male gender (65.6 vs. 69.0, p = 0.54), incidence of obesity (56.3 vs. 46.8, p = 0.12), coronary artery disease (4.0 vs. 7.9, p = 0.16) and atrial fibrillation (4.0 vs. 7.1, p = 0.25) were similar between groups. PaO2/ FiO2 ratio at admission (111.1 vs. 108.1, p = 0.61), days spent in RASS < 3 (13.7 vs. 12.4, p = 0.31) and opioid use (14.8 vs. 13.1, p = 0.16) were also similar. From time of intubation, 28-day mortality in the cohort receiving DEX was 14.7% compared to 59.5% in the no DEX group (OR 0.12;95% CI 0.07-0.21;p = 0.01). Conclusion(s): Use of DEX was associated with lower 28-day mortality in COVID-19 critically ill patients requiring invasive mechanical ventilation in our study analysis. Considering the limitations of a retrospective observational study, RCTs are needed to confirm the results.

Risk factors for nosocomial infections in COVID-19 ICU population

Introduction: The aim of this study is to identify the factors associated with an increased risk of developing nosocomial infections (NI) in COVID-19 patients admitted with pulmonary involvement in the ICU. NI in COVID-19 ICU population are an important cause of morbidity and mortality worldwide and its prompt identification might lead to its prevention and better outcomes. Method(s): This is a retrospective observational study of patients admitted with COVID-19 pneumonia in the ICU of a tertiary center in Portugal, between March 2020 and December 2021. We considered NI as any infection acquired > 48 h post ICU admission. Clinical, analytical and baseline patient data were evaluated. Logistic regression analysis was performed to correlate patient related variables with the development of NI. Result(s): A total of 338 patients were enrolled, from which 167 (47.9%) presented with NI. Baseline characteristics are described in Table 1. In the logistic regression analysis, older age (OR 1.13;95% CI 1.03-1.25;p = 0.013), coronary artery disease (CAD) (OR 28.7;95% CI 1.92-429;p = 0.02), obesity (OR 3.14;95% CI 0.86-11.42;p = 0.008), chronic liver disease (CLD) (OR 104.33;95% CI 1,.04-1008.49;p = 0.04), use of dexamethasone (OR 21.89;95% CI 3.04-157.85;p = 0.002) and days in RASS < 3 (OR 1.4;95% CI 1.05-1.86;p = 0.02) were associated with an increased risk of developing NI in the ICU. Surprisingly, SOFA at admission, days of invasive mechanical ventilation, days of sedation and PaO2/ FiO2 ratio at admission, although statistically significantly different between groups, did not correlate with the risk of infection. Conclusion(s): We identified prolonged deep sedation, corticosteroid use, and patient characteristics (CAD, obesity, CLD, older age) as independent risk factors for NI development in COVID-19 critically ill patients. It is also noteworthy to point out for the presence of confounding variables, including the excessive workload in the ICU during this period, leading to an increase in NI numbers.