Epidemiology of acute hypoxaemic respiratory failure in Australian and New Zealand intensive care units during 2005-2022. A binational, registry-based study.

PURPOSE: Acute hypoxaemic respiratory failure (AHRF) is a common reason for intensive care unit (ICU) admission. However, patient characteristics, outcomes, and trends over time are unclear. We describe the epidemiology and outcomes of patients with AHRF over time. METHODS: In this binational, registry-based study from 2005 to 2022, we included all adults admitted to an Australian or New Zealand ICU with an arterial blood gas within the first 24 h of ICU stay. AHRF was defined as a partial pressure of oxygen/inspired oxygen ratio (PaO2/FiO2) ≤ 300. The primary outcome was adjusted in-hospital mortality, categorised based on PaO2/FiO2 (mild: 200-300, moderate: 100-200, and severe < 100, and non-linearly). We investigated how adjusted mortality evolved based on temporal trends (by year of admission), sex, age, admission diagnosis and the receipt of mechanical ventilation. RESULTS: Of 1,560,221 patients, 826,106 (52.9%) were admitted with or developed AHRF within the first 24 h of ICU stay. Of these 826,106 patients, 51.4% had mild, 39.3% had moderate, and 9.3% had severe AHRF. Compared to patients without AHRF (5.3%), patients with mild (8%), moderate (14.2%) and severe (29.9%) AHRF had higher in-hospital mortality rates. As PaO2/FiO2 ratio decreased, adjusted in-hospital mortality progressively increased, particularly below an inflection point at a PaO2/FiO2 ratio of 200. The adjusted in-hospital mortality for all patients decreased over time (13.3% in 2005 to 8.2% in 2022), and this trend was similar in patients with and without AHRF. CONCLUSION: The healthcare burden due to AHRF may be larger than expected, and mortality rates remain high in severe AHRF. Although mortality has decreased over time, this may reflect improvements in ICU care in general, rather than specifically in AHRF. More research is required to earlier identify AHRF and stratify these patients at risk of deterioration early, and to validate our findings.

Effect of Extended Prone Positioning in Intubated COVID-19 Patients with Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

INPLASY REGISTRATION NUMBER: INPLASY202390072.

Post-pandemic acute respiratory distress syndrome: A New Global Definition with extension to lower-resource regions.

Acute respiratory distress syndrome (ARDS), first described in 1967, is characterized by acute respiratory failure causing profound hypoxemia, decreased pulmonary compliance, and bilateral CXR infiltrates. After several descriptions, the Berlin definition was adopted in 2012, which established three categories of severity according to hypoxemia (mild, moderate and severe), specified temporal aspects for diagnosis, and incorporated the use of non-invasive ventilation. The COVID-19 pandemic led to changes in ARDS management, focusing on continuous monitoring of oxygenation and on utilization of high-flow oxygen therapy and lung ultrasound. In 2021, a New Global Definition based on the Berlin definition of ARDS was proposed, which included a category for non-intubated patients, considered the use of SpO2, and established no particular requirement for oxygenation support in regions with limited resources. Although debates persist, the continuous evolution seeks to adapt to clinical and epidemiological needs, and to the search of personalized treatments.

Ketamine-based Sedation Use in Mechanically Ventilated Critically Ill Patients with COVID-19: A Multicenter Cohort Study.

Backgrounds: Ketamine possesses analgesia, anti-inflammation, anticonvulsant, and neuroprotection properties. However, the evidence that supports its use in mechanically ventilated critically ill patients with COVID-19 is insufficient. The study's goal was to assess ketamine's effectiveness and safety in critically ill, mechanically ventilated (MV) patients with COVID-19. Methods: Adult critically ill patients with COVID-19 were included in a multicenter retrospective-prospective cohort study. Patients admitted between March 1, 2020, and July 31, 2021, to five ICUs in Saudi Arabia were included. Eligible patients who required MV within 24 hours of ICU admission were divided into two sub-cohort groups based on their use of ketamine (Control vs. Ketamine). The primary outcome was the length of stay (LOS) in the hospital. P/F ratio differences, lactic acid normalization, MV duration, and mortality were considered secondary outcomes. Propensity score (PS) matching was used (1:2 ratio) based on the selected criteria. Results: In total, 1,130 patients met the eligibility criteria. Among these, 1036 patients (91.7 %) were in the control group, whereas 94 patients (8.3 %) received ketamine. The total number of patients after PS matching, was 264 patients, including 88 patients (33.3 %) who received ketamine. The ketamine group's LOS was significantly lower (beta coefficient (95 % CI): -0.26 (-0.45, -0.07), P = 0.008). Furthermore, the PaO2/FiO2 ratio significantly improved 24 hours after the start of ketamine treatment compared to the pre-treatment period (6 hours) (124.9 (92.1, 184.5) vs. 106 (73.1, 129.3; P = 0.002). Additionally, the ketamine group had a substantially shorter mean time for lactic acid normalization (beta coefficient (95 % CI): -1.55 (-2.42, -0.69), P 0.01). However, there were no significant differences in the duration of MV or mortality. Conclusions: Ketamine-based sedation was associated with lower hospital LOS and faster lactic acid normalization but no mortality benefits in critically ill patients with COVID-19. Thus, larger prospective studies are recommended to assess the safety and effectiveness of ketamine as a sedative in critically ill adult patients.

Correlation and Prognostic Significance of Oxygenation Indices in Invasively Ventilated Adults (OXIVA-CARDS) with COVID-19-associated ARDS: A Retrospective Study.

Background: Oxygenation index [OI = (MAP × FiO2 × 100)/PaO2] assesses the severity of hypoxic respiratory failure. Oxygen saturation index [OSI = (MAP × FiO2 × 100)/SpO2] is a noninvasive method to assesses the severity of hypoxic respiratory failure. Conventionally used PaO2/FiO2 (P/F) ratio to measure the severity of ARDS requires arterial blood gas (ABG) sampling. It tenders limited prognostic information mandating the need for better markers. Oxygenation index (needs arterial sampling) and OSI (a noninvasive method) are substitutes to provide mortality information in ARDS patients. We evaluated the correlation between P/F, OI, and OSI in invasively ventilated COVID-19 ARDS patients (C-ARDS) and looked at its relationship with mortality. Patients and methods: A retrospective study of invasively ventilated C-ARDS >18 years of age managed in COVID ICU. Ventilator settings (FiO2, mean airway pressure), pulse oximetry (SpO2), and ABG values (PaO2) were simultaneously noted at the time of sample collection. Patient outcomes (alive and deceased) were documented. Differences in parameters between survivors and nonsurvivors were assessed using independent sample t-test. Receiver operating characteristic (ROC) analysis with Youden's index was used to identify cutoff values to determine survival. Results: A total of 1557 measurements for 203 patients were collected over the maximum duration of 21 days after ventilation. About 147 (72.4%) were males and 56 (27.6%) were females. On day one of ventilation, 161 (79.3%) had P/F ratio <200, 28 (13.8%) had P/F ratio between 200 and 300, and 14 (6.9%) had P/F ratio >300. There was a linear relationship between P/F ratio and OSI (r = -0.671), P/F and OI (r = -0.753), and OSI and OI (r = 0.893) (p < 0.001). After natural log transform, the correlation between these factors became stronger [P/F ratio and OSI (r = -0.797), PF and OI (r = -0.949), and OSI and OI (r = 0.902) (p < 0.001)]. About 74 (36.5%) patients survived. Survivors had significantly higher P/F ratio as compared with nonsurvivors (p < 0.05). Oxygen saturation index and OI were significantly lower in survivors as compared with nonsurvivors. Based on day-1 reading, a higher OSI (AUC = 0.719, 95% CI = 0.648-0.790) and OI (AUC = 0.752. 95% CI = 0.684-0.819) significantly can predict mortality. On the other hand, a higher P/F ratio can predict survival (AUC = 0.734, 95% CI = 0.664-0.805). P/F ratio of 160 on day 1 can predict survival. Oxygen saturation index values above 10.4% and OI above 13.5% were the cutoff derived for day 1 values to predict mortality. Conclusion: Noninvasive OSI can be used to assess the severity of hypoxic respiratory failure in C-ARDS without arterial access in resource-limited settings. Oxygen saturation index can noninvasively provide prognostic information in invasively ventilated C-ARDS patients. How to cite this article: Vadi S, Suthar D, Sanwalka N. Correlation and Prognostic Significance of Oxygenation Indices in Invasively Ventilated Adults (OXIVA-CARDS) with COVID-19-associated ARDS: A Retrospective Study. Indian J Crit Care Med 2023;27(11):801-805.

Individualized PEEP without Recruitment Maneuvers Improves Intraoperative Oxygenation: A Randomized Controlled Study.

Individualized positive end-expiratory pressure (PEEP) combined with recruitment maneuvers improves intraoperative oxygenation in individuals undergoing robot-assisted prostatectomy. However, whether electrical impedance tomography (EIT)-guided individualized PEEP without recruitment maneuvers can also improve intraoperative oxygenation is unknown. To test this, fifty-six male patients undergoing elective robot-assisted laparoscopic prostatectomy were randomly assigned to either individualized PEEP (Group PEEPIND, n = 28) or a control with a fixed PEEP of 5 cm H2O (Group PEEP5, n = 28). Individualized PEEP was guided by EIT after placing the patients in the Trendelenburg position and performing intraperitoneal insufflation. Patients in Group PEEPIND maintained individualized PEEP without intermittent recruitment maneuvers, and those in Group PEEP5 maintained a PEEP of 5 cm H2O intraoperatively. Both groups were extubated in a semi-sitting position once the extubation criteria were met. The primary outcome was arterial oxygen partial pressure (PaO2)/inspiratory oxygen fraction (FiO2) prior to extubation. Other outcomes included intraoperative driving pressure, plateau pressure and dynamic, respiratory system compliance, and the incidence of postoperative hypoxemia in the post-operative care unit (PACU). Our results showed that the intraoperative median for PEEPIND was 16 cm H2O (ranging from 12 to 18 cm H2O). EIT-guided PEEPIND was associated with higher PaO2/FiO2 before extubation compared to PEEP5 (71.6 ± 10.7 vs. 56.8 ± 14.1 kPa, p = 0.003). Improved oxygenation extended into the PACU with a lower incidence of postoperative hypoxemia (3.8% vs. 26.9%, p = 0.021). Additionally, PEEPIND was associated with lower driving pressures (12.0 ± 3.0 vs. 15.0 ± 4.4 cm H2O, p = 0.044) and better compliance (44.5 ± 12.8 vs. 33.6 ± 9.1 mL/cm H2O, p = 0.017). Our data indicated that individualized PEEP guided by EIT without intraoperative recruitment maneuvers also improved perioperative oxygenation in patients undergoing robot-assisted laparoscopic radical prostatectomy, which could benefit patients with the risk of intraoperative hemodynamic instability caused by recruitment maneuvers. Trial registration: China Clinical Trial Registration Center Identifier: ChiCTR2100053839. This study was registered on 1 December 2021. The first patient was recruited on 15 December 2021.

Development and Validation of a Rapid and Efficient Prognostic Scoring System for Sepsis Based on Oxygenation Index, Lactate and Glasgow Coma Scale.

Objective: To develop a concise scoring system for efficient and rapid assessment of sepsis prognosis applicable to emergency departments. Methods: This was a single-center retrospective cohort study of patients with sepsis. In this study, a new scoring system (oxygenation index, lactate, and Glasgow coma scale: GOL) was developed through a derivation group, and then the GOL was validated using a validation group. Multivariate logistic regression analysis was performed to investigate the relationship between GOL and 28-day adverse outcomes. The GOL was compared with the previous scoring system using receiver operating characteristic curves (ROC) and decision analysis curves. The endpoints of this study were mortality, mechanical ventilation (MV), and admission to the intensive care unit (AICU). Results: 608 patients were included in the derivation group and 213 patients in the validation group, with 131 and 42 deaths, respectively. In the validation group, lactate (Lac), oxygenation index (PaO2/FiO2), and Glasgow coma scale score (GCS), the three best performers in predicting 28-day mortality from receiver operating characteristic curves, were used to construct the GOL. The higher the GOL score, the higher the incidence of death, MV and AICU within 28 days. Multifactorial logistic regression analysis showed that when the GOL was greater than 1, it was an independent risk factor for 28-day mortality, MV, and AICU. In predicting 28-day mortality, GOL was superior to the quick Sequential Organ Failure Assessment (qSOFA), Mortality in Emergency Department Sepsis Score (MEDS), Systemic Inflammatory Response Syndrome Score (SIRS), and Modified Early Warning Score (MEWS), and was comparable to the Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA). Conclusion: The GOL is a simple, rapid, and accurate method for early identification of patients at increased risk of in-hospital death from sepsis.

The PaO2/FiO2 is independently associated with 28-day mortality in patients with sepsis: a retrospective analysis from MIMIC-IV database.

BACKGROUND: To clarify the relationship between the PaO2/FiO2 and 28-day mortality in patients with sepsis. METHODS: This was a retrospective cohort study regarding MIMIC-IV database. Nineteen thousand two hundred thirty-three patients with sepsis were included in the final analysis. PaO2/FiO2 was exposure variable, 28-day mortality was outcome variable. PaO2/FiO2 was log-transformed as LnPaO2/FiO2. Binary logistic regression was used to explore the independent effects of LnPaO2/FiO2 on 28-day mortality using non-adjusted and multivariate-adjusted models. A generalized additive model (GAM) and smoothed curve fitting was used to investigate the non-linear relationship between LnPaO2/FiO2 and 28-day mortality. A two-piecewise linear model was used to calculate the OR and 95% CI on either side of the inflection point. RESULTS: The relationship between LnPaO2/FiO2 and risk of 28-day death in sepsis patients was U-shape. The inflection point of LnPaO2/FiO2 was 5.30 (95%CI: 5.21-5.39), which indicated the inflection point of PaO2/FiO2 was 200.33 mmHg (95%CI: 183.09 mmHg-219.20 mmHg). On the left of inflection point, LnPaO2/FiO2 was negatively correlated with 28-day mortality (OR: 0.37, 95%CI: 0.32-0.43, p < 0.0001). On the right of inflection point, LnPaO2/FiO2 was positively correlated with 28-day mortality in patients with sepsis (OR: 1.53, 95%CI: 1.31-1.80, p < 0.0001). CONCLUSIONS: In patients with sepsis, either a high or low PaO2/FiO2 was associated with an increased risk of 28-day mortality. In the range of 183.09 mmHg to 219.20 mmHg, PaO2/FiO2 was associated with a lower risk of 28-day death in patients with sepsis.

Airways management in SARS-COV-2 acute respiratory failure: A prospective observational multi-center study.

Objective: Few studies have reported the implications and adverse events of performing endotracheal intubation for critically ill COVID-19 patients admitted to intensive care units. The aim of the present study was to determine the adverse events related to tracheal intubation in COVID-19 patients, defined as the onset of hemodynamic instability, severe hypoxemia, and cardiac arrest. Setting: Tertiary care medical hospitals, dual-centre study performed in Northern Italy from November 2020 to May 2021. Patients: Adult patients with positive SARS-CoV-2 PCR test, admitted for respiratory failure and need of advanced invasive airways management. Interventions: Endotracheal Intubation Adverse Events. Main variables of interests: The primary endpoint was to determine the occurrence of at least 1 of the following events within 30 minutes from the start of the intubation procedure and to describe the types of major adverse peri-intubation events: severe hypoxemia defined as an oxygen saturation as measured by pulse-oximetry <80%; hemodynamic instability defined as a SBP 65 mmHg recoded at least once or SBP < 90 mmHg for 30 minutes, a new requirement or increase of vasopressors, fluid bolus >15 mL/kg to maintain the target blood pressure; cardiac arrest. Results: Among 142 patients, 73.94% experienced at least one major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 65.49% of all patients undergoing emergency intubation, followed by severe hypoxemia (43.54%). 2.82% of the patients had a cardiac arrest. Conclusion: In this study of intubation practices in critically ill patients with COVID-19, major adverse peri-intubation events were frequent. Clinical Trial registration: www.clinicaltrials.gov identifier: NCT04909476.

Objetivo: Pocos estudios han informado las implicaciones y los eventos adversos de realizar una intubación endotraqueal para pacientes críticos con COVID-19 ingresados ​​en unidades de cuidados intensivos. El objetivo del presente estudio fue determinar los eventos adversos relacionados con la intubación traqueal en pacientes con COVID-19, definidos como la aparición de inestabilidad hemodinámica, hipoxemia severa y paro cardíaco. Ámbito: Hospitales médicos de atención terciaria, estudio de doble centro realizado en el norte de Italia desde noviembre de 2020 hasta mayo de 2021. Pacientes: Pacientes adultos con prueba PCR SARS-CoV-2 positiva, ingresados por insuficiencia respiratoria y necesidad de manejo avanzado de vías aéreas invasivas. Intervenciones: Eventos adversos de la intubación endotraqueal. Principales variables de interés: El punto final primario fue determinar la ocurrencia de al menos 1 de los siguientes eventos dentro de los 30 minutos posteriores al inicio del procedimiento de intubación y describir los tipos de eventos adversos periintubación mayores. : hipoxemia severa definida como una saturación de oxígeno medida por pulsioximetría <80%; inestabilidad hemodinámica definida como PAS 65 mmHg registrada al menos una vez o PAS < 90 mmHg durante 30 minutos, nuevo requerimiento o aumento de vasopresores, bolo de líquidos > 15 mL/kg para mantener la presión arterial objetivo; paro cardiaco. Resultados: Entre 142 pacientes, el 73,94% experimentó al menos un evento periintubación adverso importante. El evento predominante fue la inestabilidad cardiovascular, observada en el 65,49% de todos los pacientes sometidos a intubación de urgencia, seguido de la hipoxemia severa (43,54%). El 2,82% de los pacientes tuvo un paro cardíaco. Conclusión: En este estudio de prácticas de intubación en pacientes críticos con COVID-19, los eventos adversos periintubación mayores fueron frecuentes. Registro de ensayos clínicos: www.clinicaltrials.gov identificador: NCT04909476.

Characteristics and outcomes of patients with chronic obstructive pulmonary disease admitted to the intensive care unit due to acute hypercapnic respiratory failure.

BACKGROUND: The study aimed to describe the clinical course, outcomes, and prognostic factors of chronic obstructive pulmonary disease (COPD) patients with acute hypercapnic respiratory failure. METHODS: This retrospective study involved patients with acute hypercapnic respiratory failure due to COPD of any cause admitted to the intensive care unit (ICU) for non-invasive or invasive mechanical ventilation (IMV) support between December 2015 and February 2020. RESULTS: One hundred patients were evaluated. The main causes of acute hypercapnic respiratory failure were bronchitis, pneumonia, and heart failure. The patients' mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 23.0±7.2, and their IMV rate was 43%. ICU, in-hospital, and 90-day mortality rates were 21%, 29%, and 39%, respectively. Non-survivors had more pneumonia, shock within the first 24 hours of admission, IMV, vasopressor use, and renal replacement therapy, along with higher APACHE II scores, lower admission albumin levels and PaO2/ FiO2 ratios, and longer ICU and hospital stays than survivors. Logistic regression analysis identified APACHE II score (odds ratio [OR], 1.157; 95% confidence interval [CI], 1.017-1.317; P=0.026), admission PaO2/FiO2 ratio (OR, 0.989; 95% CI, 0.978-0.999; P=0.046), and vasopressor use (OR, 8.827; 95% CI, 1.650-47.215; P=0.011) as predictors of ICU mortality. APACHE II score (OR, 1.099; 95% CI, 1.021-1.182; P=0.011) and admission albumin level (OR, 0.169; 95% CI, 0.056-0.514; P=0.002) emerged as predictors of 90-day mortality. CONCLUSIONS: APACHE II scores, the PaO2/FiO2 ratio, vasopressor use, and albumin levels are significant short-term mortality predictors in severely ill COPD patients with acute hypercapnic respiratory failure.

Parasternal intercostal thickening at hospital admission: a promising indicator for mechanical ventilation risk in subjects with severe COVID-19.

We aimed to evaluate the ability of parasternal intercostal thickening fraction (PIC TF) to predict the need for mechanical ventilation, and survival in subjects with severe Coronavirus disease-2019 (COVID-19). This prospective observational study included adult subjects with severe COVID-19. The following data were collected within 12 h of admission: PIC TF, respiratory rate oxygenation index, [Formula: see text] ratio, chest CT, and acute physiology and chronic health evaluation II score. The ability of PIC TF to predict the need for ventilatory support (primary outcome) and a composite of invasive mechanical ventilation and/or 30-days mortality were performed using the area under the receiver operating characteristic (AUC) analysis. Multivariate analysis was done to identify the independent predictors for the outcomes. Fifty subjects were available for the final evaluation. The AUC (95% confidence interval [CI]) for the right and left PIC TF ability to predict the need for ventilator support was 0.94 (0.83-0.99), 0.94 (0.84-0.99), respectively, with a cut off value of > 8.3% and positive predictive value of 90-100%. The AUC for the right and left PIC TF to predict invasive mechanical ventilation and/or 30 days mortality was 0.95 (0.85-0.99) and 0.90 (0.78-0.97), respectively. In the multivariate analysis, only the PIC TF was found to independently predict invasive mechanical ventilation and/or 30-days mortality. In subjects with severe COVID-19, PIC TF of 8.3% can predict the need to ventilatory support with a positive predictive value of 90-100%. PIC TF is an independent risk factor for the need for invasive mechanical ventilation and/or 30-days mortality.

Natural Course of COVID-19 and Independent Predictors of Mortality.

BACKGROUND: During the SARS-CoV-2 pandemic, several biomarkers were shown to be helpful in determining the prognosis of COVID-19 patients. The aim of our study was to evaluate the prognostic value of N-terminal pro-Brain Natriuretic Peptide (NT-pro-BNP) in a cohort of patients with COVID-19. METHODS: One-hundred and seven patients admitted to the Covid Hospital of Messina University between June 2022 and January 2023 were enrolled in our study. The demographic, clinical, biochemical, instrumental, and therapeutic parameters were recorded. The primary outcome was in-hospital mortality. A comparison between patients who recovered and were discharged and those who died during the hospitalization was performed. The independent parameters associated with in-hospital death were assessed by multivariable analysis and a stepwise regression logistic model. RESULTS: A total of 27 events with an in-hospital mortality rate of 25.2% occurred during our study. Those who died during hospitalization were older, with lower GCS and PaO2/FiO2 ratio, elevated D-dimer values, INR, creatinine values and shorter PT (prothrombin time). They had an increased frequency of diagnosis of heart failure (p < 0.0001) and higher NT-pro-BNP values. A multivariate logistic regression analysis showed that higher NT-pro-BNP values and lower PT and PaO2/FiO2 at admission were independent predictors of mortality during hospitalization. CONCLUSIONS: This study shows that NT-pro-BNP levels, PT, and PaO2/FiO2 ratio are independently associated with in-hospital mortality in subjects with COVID-19 pneumonia. Further longitudinal studies are warranted to confirm the results of this study.

Use of the PaO2/FiO2 Ratio in Pulmonary Embolism: Evaluation of its Correlation with Pulmonary Arterial Computed Tomography Obstruction Index.

RATIONALE AND OBJECTIVES: The pulmonary arterial computed tomography obstruction index ratio (PACTOIR) is a parameter that provides an idea of the clinical severity of acute pulmonary embolism (APE). This study aimed to examine the correlation between the PaO2 /FiO2 ratio and PACTOIR in patients who presented to the emergency department and received a preliminary diagnosis of APE. MATERIALS AND METHODS: This study was conducted prospectively in the emergency department. The patients' sociodemographic characteristics, vital signs, PACTOIR, and PaO2 /FiO2 ratio were obtained. The correlation between PACTOIR and PaO2 /FiO2 ratio was then statistically evaluated. RESULTS: The study included 50 patients, of whom 31 (62%) were women, and 19(38%) were men. The female patients had a PaO2 /FiO2 ratio of 209 ± 67 and PACTOIR of 36.3 ± 15.5. The male patients had a PaO2 /FiO2 ratio of 169 ± 43 and PACTOIR of 39.7 ± 19. The PaO2 /FiO2 ratio of the patients with APE was negatively correlated with the PACTOIR value at a statistically significant level (r = -0.308, p = 0.031). The regression equation was as follows: PACTOIR = (-0.0869) x (PaO2 / FiO2) + (54.489). CONCLUSION: By calculating the PaO2 /FiO2 ratio in patients with APE, the degree of pulmonary artery obstruction and clinical severity can be predicted. Therefore, the ratio PaO2 /FiO2 can be used instead of PACTOIR.

Tocilizumab versus baricitinib in hospitalized patients with severe COVID-19: an open label, randomized controlled trial.

OBJECTIVE: Randomized controlled trials comparing tocilizumab and baricitinib in patients with coronavirus disease 2019 (COVID-19) are needed. This was an open-label, randomized controlled trial aiming to address this unmet need. METHODS: To determine whether baricitinib was non-inferior to tocilizumab, we assessed whether the upper boundary of the two-sided 95% CI of the hazard ratio (HR) did not exceed 1.50. The primary outcome was mechanical ventilation or death by day 28. Secondary outcomes included time to hospital discharge by day 28 and change in WHO progression scale at day 10. RESULTS: We assigned 251 patients with COVID-19 and a PaO2/FiO2 ratio of <200 to receive either tocilizumab (n = 126) or baricitinib (n = 125) plus standard of care. Baricitinib was non-inferior to tocilizumab for the primary composite outcome of mechanical ventilation or death by day 28 (mechanical ventilation or death for patients who received baricitinib, 39.2% [n = 49/125]; mechanical ventilation or death for patients who received tocilizumab, 44.4% [n = 56/126]; HR, 0.83; 95% CI, 0.56-1.21; p 0.001 for non-inferiority). Baricitinib was non-inferior to tocilizumab for the time to hospital discharge within 28 days (patients who received baricitinib- discharged alive: 58.4% [n = 73/125] vs. patients who received tocilizumab- discharged alive: 52.4% [n = 66/126]; HR, 0.85; 95% CI, 0.61-1.18; p < 0.001 for non-inferiority). There was no significant difference between the baricitinib and tocilizumab arms in the change in WHO scale at day 10 (0.0 [95% CI, 0.0-0.0] vs. 0.0 [95% CI, 0.0-1.0]; p 0.83). DISCUSSION: In the setting of this trial, baricitinib was non-inferior to tocilizumab with regards to the composite outcome of mechanical ventilation or death by day 28 and the time to discharge by day 28 in patients with severe COVID-19.

Índice de PaO2/FAO2: ¿un mejor indicador de oxigenación para valorar la hipoxemia? Resultados de un análisis de concordancia con el índice de PaO2/FiO2 / PaO2/FAO2 index: a better oxygenation indicator to assess hypoxemia? Results of an analysis of agreement with the PaO2/FiO2 index / Índice PaO2/FAO2: melhor indicador de oxigenação para avaliar hipoxemia? Resultados de uma análise de concordância com o índice de PaO2/FiO2

Resumen: Introducción: el cociente PaO2/FiO2 ajustado a la presión barométrica se utiliza para evaluar la oxigenación en la falla respiratoria; sin embargo, no toma en cuenta la PaCO2, a diferencia del índice PaO2/FAO2 (PaO2 dividida entre la fracción alveolar de oxígeno). Objetivo: evaluar la concordancia entre PaO2/FiO2 y PaO2/FAO2. Material y métodos: estudio observacional, ambispectivo, transversal y analítico en pacientes mayores de 18 años, bajo ventilación mecánica invasiva, con falla respiratoria hipoxémica y con diferentes valores de PaCO2. Resultados: se analizó la concordancia en 64 mediciones gasométricas tomadas al ingreso y cuando se documentó la mayor PaCO2 de 32 enfermos. El análisis de Bland y Altman mostró una media de las diferencias (bias) de 13 y un límite de concordancia de 95%, entre 54 y -24. La concordancia es mejor cuando la PaO2/FiO2 es menor de 150. Veintidós por ciento de las mediciones no concordaron en la asignación a grupos con hipoxemia leve, moderada o grave. Conclusiones: existe una moderada concordancia entre la PaO2/FAO2 y la PaO2/FiO2; sin embargo, en los enfermos con hipoxemia severa la concordancia es mejor. En los pacientes con PaO2/FiO2 ≥ 150, la hipercapnia explica en parte la baja concordancia. Posiblemente la PaO2/FAO2 es una mejor forma de evaluar el grado del trastorno en la oxigenación.

Abstract: Introduction: the PaO2/FiO2 ratio adjusted to barometric pressure is used to assess oxygenation in respiratory failure; however, it does not take PaCO2 into account, unlike the PaO2/FAO2 ratio (PaO2 divided by the alveolar fraction of oxygen). Objective: to evaluate the agreement between PaO2/FiO2 and PaO2/FAO2. Material and methods: observational, ambispective, cross-sectional and analytical study in patients older than 18 years, under invasive mechanical ventilation with respiratory failure and with different PaCO2 values. Results: agreement was analyzed in 64 gasometric measurements taken at admission and when the highest PaCO2 was documented, of 32 patients. The Bland and Altman analysis showed a mean of the differences (bias) of 13 and a 95% limit of agreement, between 54 and -24. Agreement is better when PaO2/FiO2 is greater than 150. Twenty two percent of the measurements did not agree in the assignment to groups with mild, moderate, or severe hypoxemia. Conclusions: there is moderate agreement between PaO2/FAO2 and PaO2/FiO2; however, in patients with severe hypoxemia, agreement is better. In patients with PaO2/FiO2 ≥ 150, hypercapnia partly explains the low agreement. PaO2/FAO2 is possibly a better way to assess the degree of oxygenation disturbance.

Resumo: Introdução: o cociente PaO2/FiO2 ajustado à pressão barométrica é utilizada para avaliar a oxigenação na insuficiência respiratória; entretanto, não considera a PaCO2, ao contrário da relação PaO2/FAO2 (PaO2 dividida pela fração alveolar de oxigênio). Objetivo: Avaliar a concordância entre PaO2/FiO2 e PaO2/FAO2. Material e métodos: estudo observacional, ambispectivo, transversal e analítico em pacientes maiores de 18 anos, sob ventilação mecânica invasiva com insuficiência respiratória hipoxêmica e com diferentes valores de PaCO2. Resultados: analisou-se a concordância em 64 gasometrias feitas na admissão e quando documentou-se a maior PaCO2, de 32 pacientes. A análise de Bland e Altman mostrou uma média das diferenças (bias) de 13 e limite de concordância de 95%, entre 54 e -24. A concordância é melhor quando a PaO2/FiO2 é maior que 150. 22% das medidas não concordaram na alocação dos grupos com hipoxemia leve, moderada ou grave. Conclusões: existe uma concordância moderada entre PaO2/FAO2 e a PaO2/FiO2; no entanto, em pacientes com hipoxemia grave a concordância é melhor. Em pacientes com PaO2/FiO2 ≥ 150, a hipercapnia explica em parte a baixa concordância. Possivelmente a PaO2/FAO2 seja a melhor forma de avaliar o grau de distúrbio da oxigenação.

Serum level of calpains product as a novel biomarker of acute lung injury following cardiopulmonary bypass.

Objective: The aim of this study was to test the hypothesis whether serum level of calpains could become a meaningful biomarker for diagnosis of acute lung injury (ALI) in clinical after cardiac surgery using cardiopulmonary bypass (CPB) technology. Methods and results: Seventy consecutive adults underwent cardiac surgery with CPB were included in this prospective study. Based on the American-European Consensus Criteria (AECC), these patients were divided into ALI (n = 20, 28.57%) and non-ALI (n = 50, 71.43%) groups. Serum level of calpains in terms of calpains' activity which was expressed as relative fluorescence unit (RFU) per microliter and measured at beginning of CPB (baseline), 1 h during CPB, end of CPB as well as 1, 12, and 24 h after CPB. Difference of serum level of calpains between two groups first appeared at the end of CPB and remained different at subsequent test points. Univariate and multivariate logistic regression analysis indicated that serum level of calpains 1 h after CPB was an independent predictor for postoperative ALI (OR 1.011, 95% CI 1.001, 1.021, p = 0.033) and correlated with a lower PaO2/FiO2 ratio in the first 2 days (The first day: r = -0.389, p < 0.001 and the second day: r = -0.320, p = 0.007) as well as longer mechanical ventilation time (r = 0.440, p < 0.001), intensive care unit (ICU) length of stay (LOS) (r = 0.419, p < 0.001) and hospital LOS (r = 0.297, p = 0.013). Conclusion: Elevated serum level of calpains correlate with impaired lung function and poor clinical outcomes, indicating serum level of calpains could act as a potential biomarker for postoperative ALI following CPB in adults. Clinical trial registration: [https://clinicaltrials.gov/show/NCT05610475], identifier [NCT05610475].

Ajuste de la relación o cociente PaO2 /Fio2 a la presión barométrica en la ciudad de La Paz 3600 msnm / Adjustment of the PaO2 /fio2 ratio or ratio to barometric pressure in the city of La Paz 3600 masl

La hipoxemia es común en los pacientes en estado crítico, la misma que puede ser causada por hipoventilación, trastornos en la ventilación/perfusión, los cortocircuitos de derecha-izquierda, o en la limitación de la difusión a través de la membrana alvéolo-capilar. Otra de las causas puede ser como resultado de las bajas presiones inspiradas de O2 como sucede en grandes alturas. La hipoxemia es uno de los parámetros importantes para la definición del síndrome de dificultad respiratoria aguda (SDRA). La relación PaO2/FiO2 se incluye en la definición de la conferencia del Consenso AmericanoEuropeo (lesión pulmonar aguda ≤ 300 y SIRA si es ≤ a 200). La hipoxia hipobárica es una manifestación que existe y que no se ha tomado en cuenta para la definición de LPA/SIRA. Cuando disminuye la presión barométrica (PB) como consecuencia de la disminución de la presión atmosférica (P atm), disminuye la presión parcial de oxígeno (PO2). Una de las formas para determinar la PaO2/FiO2 en relación a la presión barométrica es: PB ajustada: PAO2 x PaO2/FiO2/100, una fórmula similar a la publicada por West JB y utilizada en el estudio Alveoli: PaO2/FiO2 ajustada = PO2/FIO2 x (PB/760). La relación PO2/FIO2 debe ajustarse dependiendo de la presión barométrica.

Survey of Glasgow Coma Scale and PaO2/FIO2 ratio assessment methods for the Sequential Organ Failure Assessment score in Japanese intensive care units.

Aim: Accurately calculating the Sequential Organ Failure Assessment (SOFA) score is essential for medical resource allocation and decision-making. This study surveyed Japanese intensive care units regarding their assessment of the Glasgow Coma Scale (GCS) and PaO2/FIO2 ratio, components of the SOFA score. Methods: A cross-sectional, web-based survey was conducted among healthcare workers. The survey consisted of questions about the intensive care units where they work and questions for respondents. It was distributed to healthcare workers by e-mail through the Japanese Society of Intensive Care Medicine mailing list and social networking service. Results: Among 414 responses, we obtained 211 valid responses and 175 survey results from unique intensive care units. When assessing GCS in patients under the influence of sedatives, 45.1% (95% confidence interval, 37.6-52.8) of intensive care units assessed GCS assuming that the sedatives had no influence. For the PaO2/FIO2 ratio in the SOFA score, calculation based on the Japanese Intensive Care Patient Database definition document and mechanical ventilator settings were the most common methods in patients with oxygen masks and on extracorporeal membrane oxygenation, respectively. Approximately 60% of respondents indicated that it was difficult to assess GCS assuming that sedatives had no influence. Conclusion: In patients under the influence of sedatives, approximately half of the intensive care units assessed assumed GCS. There was variation in the methods used to assess the PaO2/FIO2 ratio. Standardized assessment methods for GCS and the PaO2/FIO2 ratio are needed to obtain valid SOFA score.

Correlation and validity of imputed PaO2/FiO2 and SpO2/FiO2 in patients with invasive mechanical ventilation at 2600m above sea level.

OBJECTIVE: To establish the correlation and validity between PaO2/FiO2 obtained on arterial gases versus noninvasive methods (linear, nonlinear, logarithmic imputation of PaO2/FiO2 and SpO2/FiO2) in patients under mechanical ventilation living at high altitude. DESIGN: Ambispective descriptive multicenter cohort study. SETTING: Two intensive care units (ICU) from Colombia at 2600m a.s.l. PATIENTS OR PARTICIPANTS: Consecutive critically ill patients older than 18 years with at least 24h of mechanical ventilation were included from June 2016 to June 2019. INTERVENTIONS: None. VARIABLES: Variables analyzed were demographic, physiological messures, laboratory findings, oxygenation index and clinical condition. Nonlinear, linear and logarithmic imputation formulas were used to calculate PaO2 from SpO2, and at the same time the SpO2/FiO2 by severe hypoxemia diagnosis. The intraclass correlation coefficient, area under the ROC curve, sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratio were calculated. RESULTS: The correlation between PaO2/FiO2 obtained from arterial gases, PaO2/FiO2 derived from one of the proposed methods (linear, non-linear, and logarithmic formula), and SpO2/FiO2 measured by the intraclass correlation coefficient was high (greater than 0.77, p<0.001). The different imputation methods and SpO2/FiO2 have a similar diagnostic performance in patients with severe hypoxemia (PaO2/FiO2 <150). PaO2/FiO2 linear imputation AUC ROC 0,84 (IC 0.81-0.87, p<0.001), PaO2/FiO2 logarithmic imputation AUC ROC 0.84 (IC 0.80-0.87, p<0.001), PaO2/FiO2 non-linear imputation AUC ROC 0.82 (IC 0.79-0.85, p<0.001), SpO2/FiO2 oximetry AUC ROC 0.84 (IC 0.81-0.87, p<0.001). CONCLUSIONS: At high altitude, the SaO2/FiO2 ratio and the imputed PaO2/FiO2 ratio have similar diagnostic performance in patients with severe hypoxemia ventilated by various pathological conditions.