Evaluation of d-dimer as outcome biomarker in COVID-19 acute respiratory distress patients.

Acute respiratory distress syndrome is a significant complication in critical care patients. COVID-19 (C19)-associated severe respiratory failure is related to it, and d-dimer rise predicts a worse outcome. To investigate the association between d-dimer and the severity of this respiratory syndrome, we conducted a study in C19 intubated patients. A retrospective, single-center observational study was conducted with 64 C19 adult intubated patients. Strata of d-dimer results between patients was evaluated using survival analysis. Survival was higher in mild respiratory distress patients. D-dimer showed poor sensitivity and specificity in predicting respiratory failure severity. Risk assessment for death showed a higher prevalence of admission d-dimer results (HR 1.335; 95% CI 0.695-2.564). Our sample confidently represented the medical profile of C19 severe patients. Sepsis development in C19 is associated with the inflammatory storm in respiratory distress syndrome. As the receiver operating curves show, the increase in d-dimer results is consistent with inflammation rather than a prognostic biomarker. As expected, severe respiratory distress patients presented higher mortality. In summary, d-dimer results are not associated with the prognosis of C19 respiratory distress syndrome patients.

Adherence to low tidal volume in the transition to spontaneous ventilation in patients with acute respiratory failure in intensive care units in Latin America (SPIRAL): a study protocol.

OBJECTIVE: Patients with acute respiratory failure often require mechanical ventilation to reduce the work of breathing and improve gas exchange; however, this may exacerbate lung injury. Protective ventilation strategies, characterized by low tidal volumes (≤ 8mL/kg of predicted body weight) and limited plateau pressure below 30cmH2O, have shown improved outcomes in patients with acute respiratory distress syndrome. However, in the transition to spontaneous ventilation, it can be challenging to maintain tidal volume within protective levels, and it is unclear whether low tidal volumes during spontaneous ventilation impact patient outcomes. We developed a study protocol to estimate the prevalence of low tidal volume ventilation in the first 24 hours of spontaneous ventilation in patients with hypoxemic acute respiratory failure and its association with ventilator-free days and survival. METHODS: We designed a multicenter, multinational, cohort study with a 28-day follow-up that will include patients with acute respiratory failure, defined as a partial oxygen pressure/fraction of inspired oxygen ratio < 300mmHg, in transition to spontaneous ventilation in intensive care units in Latin America. RESULTS: We plan to include 422 patients in ten countries. The primary outcomes are the prevalence of low tidal volume in the first 24 hours of spontaneous ventilation and ventilator-free days on day 28. The secondary outcomes are intensive care unit and hospital mortality, incidence of asynchrony and return to controlled ventilation and sedation. CONCLUSION: In this study, we will assess the prevalence of low tidal volume during spontaneous ventilation and its association with clinical outcomes, which can inform clinical practice and future clinical trials.

Pulmonary Contusion-An Unusual Clinical and Radiological Presentation: Case Report.

Pulmonary contusion (PC), defined as damage to the lung parenchyma with edema and hemorrhage, has classically been associated with acceleration-deceleration injuries. It is a frequent pathology in clinical practice. However, its clinical presentation and imaging findings are nonspecific. Patients with this entity can present with findings that can range from mild dyspnea to life-threatening respiratory failure and hemodynamic instability. We present the case of a 61-year-old man, a former smoker, who presented to the emergency department after suffering blunt chest trauma. On admission, he complained of only mild shortness of breath, and his vital signs were typical. Initial imaging identified asymmetric pulmonary infiltrates and mediastinal lymphadenopathy; this was suspicious for additional pathology in addition to PC. After an exhaustive evaluation, a neoplastic or infectious disease process was ruled out. Even though the patient presented with a clinical deterioration of respiratory function compatible with secondary acute respiratory distress syndrome, there was a complete recovery after supportive measures and supplemental oxygen. In conclusion, the nonspecific clinical and imaging findings in patients with pulmonary contusion warrant a complete evaluation of these cases. An early diagnosis is essential to establish adequate support and monitoring to prevent possible complications that could worsen the patient's prognosis.

Clinical outcomes in patients with diabetes and stress hyperglycemia that developed SARS-CoV-2 infection / Desenlaces clínicos de los pacientes con diabetes e hiperglucemia de estrés que presentaron infección por SARS-CoV-2

INTRODUCTION: Diabetes and stress hyperglycemia have been related with poorer clinical outcomes in patients infected by SARS-CoV-2 and at risk for severe disease. OBJECTIVE: To evaluate clinical outcomes in three groups of patients (with diabetes, without diabetes and with stress hyperglycemia) with SARS-CoV-2 infection. MATERIALS AND METHODS: A retrospective cohort study was conducted in Cali (Colombia). We included patients 18 years old or older with a diagnosis of SARS-CoV-2 infection, managed in the emergency room, hospitalization, or intensive care unit between March 2020 and December 2021. Immunocompromised patients and pregnant women were excluded. Patients were classified into three groups: without diabetes, with diabetes, and with stress hyperglycemia. A comparison between the groups was performed. RESULTS: A total of 945 patients were included (59.6% without diabetes, 27% with diabetes, and 13.4% with stress hyperglycemia). Fifty-five-point three percent required intensive care unit management, with a higher need in patients with stress hyperglycemia (89.8%) and diabetes (67.1%), with no difference between these groups (p = 0.249). We identified a higher probability of death in the group with stress hyperglycemia versus the one without diabetes (adjusted OR = 8.12; 95% CI: 5.12-12.88; p < 0.01). Frequency of acute respiratory distress syndrome, need for invasive mechanical ventilation, use of vasopressors and inotropes, need for de novo renal replacement therapy, and mortality was higher in patients with metabolic alterations (diabetes and stress hyperglycemia). CONCLUSIONS: Diabetes and stress hyperglycemia were associated with worse clinical outcomes and mortality in patients with COVID-19. These patients should be identified early and considered them high risk at the COVID-19 diagnosis to mitigate adverse outcomes.

Introducción. La diabetes y la hiperglucemia de estrés se han relacionado con peores desenlaces clínicos en pacientes infectados por SARS-CoV-2 y con riesgo de enfermedad grave. Objetivo. Evaluar los resultados clínicos en tres grupos de pacientes (con diabetes, sin diabetes o con hiperglucemia de estrés) con infección por SARS-CoV-2. Materiales y métodos. Se llevó a cabo un estudio retrospectivo de cohorte en Cali (Colombia). Se incluyeron pacientes de 18 años o más, con diagnóstico de infección por SARS-CoV-2 atendidos en urgencias, hospitalización o unidad de cuidados intensivos entre marzo de 2020 y diciembre de 2021. Se excluyeron los pacientes inmunocomprometidos y las mujeres embarazadas. Los pacientes fueron clasificados en tres grupos: sin diabetes, con diabetes y con hiperglucemia de estrés. Se realizó una comparación entre los grupos. Resultados. Se incluyeron 945 pacientes (59,6 % sin diabetes, 27 % con diabetes y 13,4 % con hiperglucemia de estrés). El 55,3 % requirió manejo en la unidad de cuidados intensivos, con mayor necesidad por parte de los pacientes con hiperglucemia de estrés (89,8 %) y diabetes (67,1%), sin diferencia entre estos grupos (p = 0,249). Se observó una mayor probabilidad de muerte en el grupo con hiperglucemia de estrés versus sin diabetes (OR ajustado = 8,12; IC95%: 5,12-12,88; p < 0,01). La frecuencia de síndrome de distrés respiratorio agudo, necesidad de ventilación mecánica invasiva, uso de vasopresores e inotrópicos, necesidad de terapia de reemplazo renal de novo y mortalidad fue mayor en pacientes con alteraciones metabólicas (diabetes e hiperglucemia de estrés). Conclusiones. La diabetes y la hiperglucemia de estrés se asociaron a peores resultados clínicos y mortalidad en pacientes con COVID-19. Estos pacientes deben ser identificados tempranamente y considerados de alto riesgo al momento del diagnóstico de COVID-19 para mitigar los desenlaces adversos.

LUS me up: elevating ARDS diagnosis.

Boumans et al. conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of lung ultrasound (LUS) in acute respiratory distress syndrome (ARDS). The study found that LUS has high specificity (0.942, 95% CI 0.856-0.978) but variable sensitivity (0.631, 95% CI 0.450-0.782) for identifying ARDS-related diffuse lung pathologies. LUS demonstrates comparable or superior performance to chest radiography and CT scans, facilitating rapid bedside diagnosis and management. However, variability in operator experience and interpretation criteria, as well as challenges in detecting mild or early-stage ARDS, remain. The study highlights the need for further research to refine LUS protocols and training, enhancing its application in clinical practice and improving patient outcomes.

Impact on pulmonary, cardiac, and renal function and long-term quality of life after hospitalization for acute respiratory distress syndrome due to COVID-19: Protocol of the Post-COVID Brazil 3 study.

RATIONALE: Evidence about long-term sequelae after hospitalization for acute respiratory distress syndrome due to COVID-19 is still scarce. PURPOSE: To evaluate changes in pulmonary, cardiac, and renal function and in quality of life after hospitalization for acute respiratory distress syndrome secondary to COVID-19. METHODS: This will be a multicenter case-control study of 220 participants. Eligible are patients who are hospitalized for acute respiratory distress syndrome due to COVID-19. In the control group, individuals with no history of hospitalization in the last 12 months or long-term symptoms of COVID-19 will be selected. All individuals will be subjected to pulmonary spirometry with a carbon monoxide diffusion test, chest tomography, cardiac and renal magnetic resonance imaging with gadolinium, ergospirometry, serum and urinary creatinine, total protein, and urinary microalbuminuria, in addition to quality-of-life questionnaires. Patients will be evaluated 12 months after hospital discharge, and controls will be evaluated within 90 days of inclusion in the study. For all the statistical analyses, p < 0.05 is the threshold for significance. RESULTS: The primary outcome of the study will be the pulmonary diffusing capacity for carbon monoxide measured after 12 months. The other parameters of pulmonary, cardiac, and renal function and quality of life are secondary outcomes. CONCLUSION: This study aims to determine the long-term sequelae of pulmonary, cardiac, and renal function and the quality of life of patients hospitalized for acute respiratory distress syndrome due to COVID-19 in the Brazilian population.

Predictive value of invasive mechanical ventilation parameters for mortality in COVID-19 related ARDS: a retrospective cohort study.

The 2019 coronavirus (COVID-19) can generate acute respiratory distress syndrome (ARDS), requiring advanced management within the Intensive Care Unit (ICU) using invasive mechanical ventilation (IMV However, managing this phenomenon has seen learning and improvements through direct experience. Therefore, this study aims were to describe the assessment of the different IMV variables in patients with post-COVID-19 hospitalized in the ICU and their relation with mortality. Observational and retrospective study. The sample was divided into two, the surviving group (SG) and the non-surviving group (NSG). Clinical data were extracted from the electronic clinical file and the respiratory therapist record sheet. The following information was obtained: Patient medical history: gender, age, co-morbidities, arterial gases, days on IMV, and IMV parameters. Out of a total of 101 patients, the total mortality was 32%. There was a significant decrease in respiratory rate (RR) (29.12 ± 4.24-26.78 ± 3.59, p = 0.006), Driving pressure (DP) (11.33 ± 2.39-9.67 ± 1.84, p = 0.002), Ventilatory rate (VR) (2.26 ± 0.66-1.89 ± 0.45, p = 0.001) and a significant rise in Static compliance (Cest) (35.49 ± 8.64-41.45 ± 9.62, p = 0.003) and relation between Arterial oxygen pressure/Inspirated oxygen fraction (PaO2/FiO2) (201.5 ± 53.98- 227.8 ± 52.11, p = 0.008) after 72 h of IMV, within the NSG compared to the SG. Apart from these points, multi-morbidity (HR = 3.208, p = 0.010) and DP (HR = 1.228, p = 0.030) and VR variables (HR = 2.267, p = 0.027) had more death probabilities. The results of this study indicate that there was a significant increase in RR, DP, VR, and CO2 and a significant drop in Cest and PaO2/FiO2 among the NSG compared with the SG. Apart from this, the DP and VR variables, multi-morbidity and being male. have more possibility of death.

Evaluation of the classifications of severity in acute respiratory distress syndrome in childhood by the Berlin Consensus and the Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVE: To compare two methods for defining and classifying the severity of pediatric acute respiratory distress syndrome: the Berlin classification, which uses the relationship between the partial pressure of oxygen and the fraction of inspired oxygen, and the classification of the Pediatric Acute Lung Injury Consensus Conference, which uses the oxygenation index. METHODS: This was a prospective study of patients aged 0 - 18 years with a diagnosis of acute respiratory distress syndrome who were invasively mechanically ventilated and provided one to three arterial blood gas samples, totaling 140 valid measurements. These measures were evaluated for correlation using the Spearman test and agreement using the kappa coefficient between the two classifications, initially using the general population of the study and then subdividing it into patients with and without bronchospasm and those with and without the use of neuromuscular blockers. The effect of these two factors (bronchospasm and neuromuscular blocking agent) separately and together on both classifications was also assessed using two-way analysis of variance. RESULTS: In the general population, who were 54 patients aged 0 - 18 years a strong negative correlation was found by Spearman's test (ρ -0.91; p < 0.001), and strong agreement was found by the kappa coefficient (0.62; p < 0.001) in the comparison between Berlin and Pediatric Acute Lung Injury Consensus Conference. In the populations with and without bronchospasm and who did and did not use neuromuscular blockers, the correlation coefficients were similar to those of the general population, though among patients not using neuromuscular blockers, there was greater agreement between the classifications than for patients using neuromuscular blockers (kappa 0.67 versus 0.56, p < 0.001 for both). Neuromuscular blockers had a significant effect on the relationship between the partial pressure of oxygen and the fraction of inspired oxygen (analysis of variance; F: 12.9; p < 0.001) and the oxygenation index (analysis of variance; F: 8.3; p = 0.004). CONCLUSION: There was a strong correlation and agreement between the two classifications in the general population and in the subgroups studied. Use of neuromuscular blockers had a significant effect on the severity of acute respiratory distress syndrome.

Prospective, randomized, controlled trial assessing the effects of a driving pressure-limiting strategy for patients with acute respiratory distress syndrome due to community-acquired pneumonia (STAMINA trial): protocol and statistical analysis plan.

BACKGROUND: Driving pressure has been suggested to be the main driver of ventilator-induced lung injury and mortality in observational studies of acute respiratory distress syndrome. Whether a driving pressure-limiting strategy can improve clinical outcomes is unclear. OBJECTIVE: To describe the protocol and statistical analysis plan that will be used to test whether a driving pressure-limiting strategy including positive end-expiratory pressure titration according to the best respiratory compliance and reduction in tidal volume is superior to a standard strategy involving the use of the ARDSNet low-positive end-expiratory pressure table in terms of increasing the number of ventilator-free days in patients with acute respiratory distress syndrome due to community-acquired pneumonia. METHODS: The ventilator STrAtegy for coMmunIty acquired pNeumoniA (STAMINA) study is a randomized, multicenter, open-label trial that compares a driving pressure-limiting strategy to the ARDSnet low-positive end-expiratory pressure table in patients with moderate-to-severe acute respiratory distress syndrome due to community-acquired pneumonia admitted to intensive care units. We expect to recruit 500 patients from 20 Brazilian and 2 Colombian intensive care units. They will be randomized to a driving pressure-limiting strategy group or to a standard strategy using the ARDSNet low-positive end-expiratory pressure table. In the driving pressure-limiting strategy group, positive end-expiratory pressure will be titrated according to the best respiratory system compliance. OUTCOMES: The primary outcome is the number of ventilator-free days within 28 days. The secondary outcomes are in-hospital and intensive care unit mortality and the need for rescue therapies such as extracorporeal life support, recruitment maneuvers and inhaled nitric oxide. CONCLUSION: STAMINA is designed to provide evidence on whether a driving pressure-limiting strategy is superior to the ARDSNet low-positive end-expiratory pressure table strategy for increasing the number of ventilator-free days within 28 days in patients with moderate-to-severe acute respiratory distress syndrome. Here, we describe the rationale, design and status of the trial.

GMP-compliant extracellular vesicles derived from umbilical cord mesenchymal stromal cells: manufacturing and pre-clinical evaluation in ARDS treatment.

BACKGROUND AIMS: Extracellular vesicles (EVs) represent a new axis of intercellular communication that can be harnessed for therapeutic purposes, as cell-free therapies. The clinical application of mesenchymal stromal cell (MSC)-derived EVs, however, is still in its infancy and faces many challenges. The heterogeneity inherent to MSCs, differences among donors, tissue sources, and variations in manufacturing conditions may influence the release of EVs and their cargo, thus potentially affecting the quality and consistency of the final product. We investigated the influence of cell culture and conditioned medium harvesting conditions on the physicochemical and proteomic profile of human umbilical cord MSC-derived EVs (hUCMSC-EVs) produced under current good manufacturing practice (cGMP) standards. We also evaluated the efficiency of the protocol in terms of yield, purity, productivity, and expression of surface markers, and assessed the biodistribution, toxicity and potential efficacy of hUCMSC-EVs in pre-clinical studies using the LPS-induced acute lung injury model. METHODS: hUCMSCs were isolated from a cord tissue, cultured, cryopreserved, and characterized at a cGMP facility. The conditioned medium was harvested at 24, 48, and 72 h after the addition of EV collection medium. Three conventional methods (nanoparticle tracking analysis, transmission electron microscopy, and nanoflow cytometry) and mass spectrometry were used to characterize hUCMSC-EVs. Safety (toxicity of single and repeated doses) and biodistribution were evaluated in naive mice after intravenous administration of the product. Efficacy was evaluated in an LPS-induced acute lung injury model. RESULTS: hUCMSC-EVs were successfully isolated using a cGMP-compliant protocol. Comparison of hUCMSC-EVs purified from multiple harvests revealed progressive EV productivity and slight changes in the proteomic profile, presenting higher homogeneity at later timepoints of conditioned medium harvesting. Pooled hUCMSC-EVs showed a non-toxic profile after single and repeated intravenous administration to naive mice. Biodistribution studies demonstrated a major concentration in liver, spleen and lungs. HUCMSC-EVs reduced lung damage and inflammation in a model of LPS-induced acute lung injury. CONCLUSIONS: hUCMSC-EVs were successfully obtained following a cGMP-compliant protocol, with consistent characteristics and pre-clinical safety profile, supporting their future clinical development as cell-free therapies.

Accuracy of the Verbal Autopsy questionnaire in the diagnosis of COVID-19 deaths in a Brazilian capital.

The Verbal Autopsy (VA) is a questionnaire about the circumstances surrounding a death. It was widely used in Brazil to assist in postmortem diagnoses and investigate excess mortality during the Coronavirus Disease 2019 (COVID-19) pandemic. This study aimed to determine the accuracy of investigating acute respiratory distress syndrome (ARDS) using VA. This is a cross-sectional study with prospective data collected from January 2020 to August 2021 at the Death Verification Service of Sao Luis city, Brazil. VA was performed for suspected COVID-19 deaths, and one day of the week was randomly chosen to collect samples from patients without suspected COVID-19. Two swabs were collected after death and subjected to reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 detection. Of the 250 cases included, the VA questionnaire identified COVID-19-related ARDS in 67.2% (52.98% were positive for COVID-19). The sensitivity of the VA questionnaire was 0.53 (0.45-0.61), the specificity was 0.75 (0.64-0.84), the positive predictive value was 0.81 (0.72-0.88), and the negative predictive value was 0.44 (0.36-0.53). The VA had a lower-than-expected accuracy for detecting COVID-19 deaths; however, because it is an easily accessible and cost-effective tool, it can be combined with more accurate methods to improve its performance.

Driving pressure, as opposed to tidal volume based on predicted body weight, is associated with mortality: results from a prospective cohort of COVID-19 acute respiratory distress syndrome patients.

OBJECTIVE: To evaluate the association between driving pressure and tidal volume based on predicted body weight and mortality in a cohort of patients with acute respiratory distress syndrome caused by COVID-19. METHODS: This was a prospective, observational study that included patients with acute respiratory distress syndrome due to COVID-19 admitted to two intensive care units. We performed multivariable analyses to determine whether driving pressure and tidal volume/kg predicted body weight on the first day of mechanical ventilation, as independent variables, are associated with hospital mortality. RESULTS: We included 231 patients. The mean age was 64 (53 - 74) years, and the mean Simplified Acute and Physiology Score 3 score was 45 (39 - 54). The hospital mortality rate was 51.9%. Driving pressure was independently associated with hospital mortality (odds ratio 1.21, 95%CI 1.04 - 1.41 for each cm H2O increase in driving pressure, p = 0.01). Based on a double stratification analysis, we found that for the same level of tidal volume/kg predicted body weight, the risk of hospital death increased with increasing driving pressure. However, changes in tidal volume/kg predicted body weight were not associated with mortality when they did not lead to an increase in driving pressure. CONCLUSION: In patients with acute respiratory distress syndrome caused by COVID-19, exposure to higher driving pressure, as opposed to higher tidal volume/kg predicted body weight, is associated with greater mortality. These results suggest that driving pressure might be a primary target for lung-protective mechanical ventilation in these patients.

Mortality Due to Acute Respiratory Distress Syndrome in Latin America.

OBJECTIVES: Mortality due to acute respiratory distress syndrome (ARDS) is a major global health problem. Knowledge of epidemiological data on ARDS is crucial to design management, treatment strategies, and optimize resources. There is ample data regarding mortality of ARDS from high-income countries; in this review, we evaluated mortality due to ARDS in Latin America. DATA SOURCES: We searched in PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Latin American and Caribbean Health Science Literature databases from 1967 to March 2023. STUDY SELECTION: We searched prospective or retrospective observational studies and randomized controlled trials conducted in Latin American countries reporting ARDS mortality. DATA EXTRACTION: Three pairs of independent reviewers checked all studies for eligibility based on their titles and abstracts. We performed meta-analysis of proportions using a random-effects model. We performed sensitivity analyses including studies with low risk of bias and with diagnosis using the Berlin definition. Subgroup analysis comparing different study designs, time of publication (up to 2000 and from 2001 to present), and studies in which the diagnosis of ARDS was made using Pa o2 /F io2 less than or equal to 200 and regional variations. Subsequently, we performed meta-regression analyses. Finally, we graded the certainty of the evidence (Grading of Recommendations Assessment, Development, and Evaluation). DATA SYNTHESIS: Of 3315 articles identified, 32 were included (3627 patients). Mortality was 52% in the pooled group (low certainty of evidence). In the sensitivity analysis (according to the Berlin definition), mortality was 46% (moderate certainty of evidence). In the subgroup analysis mortality was 53% (randomized controlled trials), 51% (observational studies), 66% (studies published up to 2000), 50% (studies after 2000), 44% (studies with Pa o2 /F io2 ≤ 200), 56% (studies from Argentina/Brazil), and 40% (others countries). No variables were associated with mortality in the meta-regression. CONCLUSIONS: ARDS mortality in Latin America remains high, as in other regions. These results should constitute the basis for action planning to improve the prognosis of patients with ARDS (PROSPERO [CRD42022354035]).

Time Course of Mechanical Ventilation Driving Pressure Levels in Pediatric Acute Respiratory Distress Syndrome: Outcomes in a Prospective, Multicenter Cohort Study From Colombia, 2018-2022.

OBJECTIVES: High driving pressure (DP, ratio of tidal volume (V t ) over respiratory system compliance) is a risk for poor outcomes in patients with pediatric acute respiratory distress syndrome (PARDS). We therefore assessed the time course in level of DP (i.e., 24, 48, and 72 hr) after starting mechanical ventilation (MV), and its association with 28-day mortality. DESIGN: Multicenter, prospective study conducted between February 2018 and December 2022. SETTING: Twelve tertiary care PICUs in Colombia. PATIENTS: One hundred eighty-four intubated children with moderate to severe PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The median (interquartile range [IQR]) age of the PARDS cohort was 11 (IQR 3-24) months. A total of 129 of 184 patients (70.2%) had a pulmonary etiology leading to PARDS, and 31 of 184 patients (16.8%) died. In the first 24 hours after admission, the plateau pressure in the nonsurvivor group, compared with the survivor group, differed (28.24 [IQR 24.14-32.11] vs. 23.18 [IQR 20.72-27.13] cm H 2 O, p < 0.01). Of note, children with a V t less than 8 mL/kg of ideal body weight had lower adjusted odds ratio (aOR [95% CI]) of 28-day mortality (aOR 0.69, [95% CI, 0.55-0.87]; p = 0.02). However, we failed to identify an association between DP level and the oxygenation index (aOR 0.58; 95% CI, 0.21-1.58) at each of time point. In a diagnostic exploratory analysis, we found that DP greater than 15 cm H 2 O at 72 hours was an explanatory variable for mortality, with area under the receiver operating characteristic curve of 0.83 (95% CI, 0.74-0.89); there was also increased hazard for death with hazard ratio 2.5 (95% CI, 1.07-5.92). DP greater than 15 cm H 2 O at 72 hours was also associated with longer duration of MV (10 [IQR 7-14] vs. 7 [IQR 5-10] d; p = 0.02). CONCLUSIONS: In children with moderate to severe PARDS, a DP greater than 15 cm H 2 O at 72 hours after the initiation of MV is associated with greater odds of 28-day mortality and a longer duration of MV. DP should be considered a variable worth monitoring during protective ventilation for PARDS.

Successful management of pulmonary edema secondary to accidental electrocution in a young dog.

BACKGROUND: Human records describe pulmonary edema as a life-threatening complication of electric shock. Successful management requires prompt recognition and intensive care. However, in companion animals, electrocutions are rarely reported, even though domestic environments are full of electrical devices and there is always the possibility of accidental injury. Therefore, it is important for veterinarians to know more about this condition in order to achieve successful patient outcomes. CASE PRESENTATION: A 3-month-old male Labrador Retriever was presented with a history of transient loss of consciousness after chewing on a household electrical cord. On admission, the puppy showed an orthopneic position with moderate respiratory distress. Supplemental oxygen via nasal catheter was provided, but the patient showed marked worsening of respiratory status. Point-of-care ultrasound exams suggested neurogenic pulmonary edema due to electrical shock close to the central nervous system and increased B-lines without evidence of cardiac abnormalities. Mechanical ventilation of the patient was initiated using volume-controlled mode with a tidal volume of 9 to 15 ml/kg until reaching an end-tidal carbon dioxide ≤ 40 mm Hg, followed by a stepwise lung-recruitment maneuver in pressure-controlled mode with increases of the peak inspiratory pressure (15 to 20 cm H2O) and positive end-expiratory pressure (3 to 10 cm H2O) for 30 min, and return to volume-controlled mode with a tidal volume of 15 ml/kg until reaching a peripheral oxygen saturation ≥ 96%. Weaning from the ventilator was achieved in six hours, and the patient was discharged two days after admission without neurological or respiratory deficits. CONCLUSIONS: We present a rather unusual case of a neurogenic pulmonary edema subsequent to accidental electrocution in a dog. Timely diagnosis by ultrasound and mechanical ventilation settings are described. Our case highlights that pulmonary edema should be considered a potentially life-threatening complication of electrical shock in small animal emergency and critical care medicine.

Conscious prone positioning in nonintubated COVID-19 patients with acute respiratory distress syndrome: systematic review and meta-analysis.

OBJECTIVE: To systematically review the effect of the prone position on endotracheal intubation and mortality in nonintubated COVID-19 patients with acute respiratory distress syndrome. METHODS: We registered the protocol (CRD42021286711) and searched for four databases and gray literature from inception to December 31, 2022. We included observational studies and clinical trials. There was no limit by date or the language of publication. We excluded case reports, case series, studies not available in full text, and those studies that included children < 18-years-old. RESULTS: We included ten observational studies, eight clinical trials, 3,969 patients, 1,120 endotracheal intubation events, and 843 deaths. All of the studies had a low risk of bias (Newcastle-Ottawa Scale and Risk of Bias 2 tools). We found that the conscious prone position decreased the odds of endotracheal intubation by 44% (OR 0.56; 95%CI 0.40 - 0.78) and mortality by 43% (OR 0.57; 95%CI 0.39 - 0.84) in nonintubated COVID-19 patients with acute respiratory distress syndrome. This protective effect on endotracheal intubation and mortality was more robust in those who spent > 8 hours/day in the conscious prone position (OR 0.43; 95%CI 0.26 - 0.72 and OR 0.38; 95%CI 0.24 - 0.60, respectively). The certainty of the evidence according to the GRADE criteria was moderate. CONCLUSION: The conscious prone position decreased the odds of endotracheal intubation and mortality, especially when patients spent over 8 hours/day in the conscious prone position and treatment in the intensive care unit. However, our results should be cautiously interpreted due to limitations in evaluating randomized clinical trials, nonrandomized clinical trials and observational studies. However, despite systematic reviews with meta-analyses of randomized clinical trials, we must keep in mind that these studies remain heterogeneous from a clinical and methodological point of view.

Lung tissue expression of epithelial injury markers is associated with acute lung injury severity but does not discriminate sepsis from ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients, and diffuse alveolar damage (DAD) is considered its histological hallmark. Sepsis is one of the most common aetiology of ARDS with the highest case-fatality rate. Identifying ARDS patients and differentiate them from other causes of acute respiratory failure remains a challenge. To address this, many studies have focused on identifying biomarkers that can help assess lung epithelial injury. However, there is scarce information available regarding the tissue expression of these markers. Evaluating the expression of elafin, RAGE, and SP-D in lung tissue offers a potential bridge between serological markers and the underlying histopathological changes. Therefore, we hypothesize that the expression of epithelial injury markers varies between sepsis and ARDS as well as according to its severity. METHODS: We compared the post-mortem lung tissue expression of the epithelial injury markers RAGE, SP-D, and elafin of patients that died of sepsis, ARDS, and controls that died from non-pulmonary causes. Lung tissue was collected during routine autopsy and protein expression was assessed by immunohistochemistry. We also assessed the lung injury by a semi-quantitative analysis. RESULTS: We observed that all features of DAD were milder in septic group compared to ARDS group. Elafin tissue expression was increased and SP-D was decreased in the sepsis and ARDS groups. Severe ARDS expressed higher levels of elafin and RAGE, and they were negatively correlated with PaO2/FiO2 ratio, and positively correlated with bronchopneumonia percentage and hyaline membrane score. RAGE tissue expression was negatively correlated with mechanical ventilation duration in both ARDS and septic groups. In septic patients, elafin was positively correlated with ICU admission length, SP-D was positively correlated with serum lactate and RAGE was correlated with C-reactive protein. CONCLUSIONS: Lung tissue expression of elafin and RAGE, but not SP-D, is associated with ARDS severity, but does not discriminate sepsis patients from ARDS patients.