Effect of esketamine combined with dexmedetomidine on delirium in sedation for mechanically ventilated ICU patients: protocol for a nested substudy within a randomized controlled trial.

BACKGROUND: Use of sedatives and analgesics is associated with the occurrence of delirium in critically ill patients receiving mechanical ventilation. Dexmedetomidine reduces the occurrence of delirium but may cause hypotension, bradycardia, and insufficient sedation. This substudy aims to determine whether the combination of esketamine with dexmedetomidine can reduce the side effects and risk of delirium than dexmedetomidine alone in mechanically ventilated patients. METHODS: This single-center, randomized, active-controlled, superiority trial will be conducted at The First Affiliated Hospital of Nanjing Medical University. A total of 134 mechanically ventilated patients will be recruited and randomized to receive either dexmedetomidine alone or esketamine combined with dexmedetomidine, until extubation or for a maximum of 14 days. The primary outcome is the occurrence of delirium, while the second outcomes include the number of delirium-free days; subtype, severity, and duration of delirium; time to first onset of delirium; total dose of vasopressors and antipsychotics; duration of mechanical ventilation; ICU and hospital length of stay (LOS); accidental extubation, re-intubation, re-admission; and mortality in the ICU at 14 and 28 days. DISCUSSION: There is an urgent need for a new combination regimen of dexmedetomidine due to its evident side effects. The combination of esketamine and dexmedetomidine has been applied throughout the perioperative period. However, there is still a lack of evidence on the effects of this regimen on delirium in mechanically ventilated ICU patients. This substudy will evaluate the effects of the combination of esketamine and dexmedetomidine in reducing the risk of delirium for mechanically ventilated patients in ICU, thus providing evidence of this combination to improve the short-term prognosis. The study protocol has obtained approval from the Medical Ethics Committee (ID: 2022-SR-450). TRIAL REGISTRATION: ClinicalTrials.gov: NCT05466708, registered on 20 July 2022.

Chest Physiotherapy for Mechanically Ventilated Children: A Systematic Review.

The aim of this study was to appraise and summarize the effects of chest physiotherapy in mechanically ventilated children. A systematic review was completed by searching Medline, Embase, Cinahl Plus, PEDro, and Web of Science from inception to February 9, 2021. Studies investigating chest physiotherapy for mechanically ventilated children (0-18 years), in a pediatric intensive care unit were included. Chest physiotherapy was defined as any intervention performed by a qualified physiotherapist. Measurements of effectiveness and safety were included. Exclusion criteria included preterm infants, children requiring noninvasive ventilation, and those in a nonacute setting. Thirteen studies met the inclusion criteria: two randomized controlled trials, three randomized crossover trials, and eight observational studies. The Cochrane risk of bias and the Critical Appraisal Skills Program tools were used for quality assessment. Oxygen saturations decreased after physiotherapy involving manual hyperinflations (MHI) and chest wall vibrations (CWV). Although statistically significant, these results were not of clinical importance. In contrast, oxygen saturations improved after the expiratory flow increase technique; however, this was not clinically significant. An increase in expiratory tidal volume was demonstrated 30 minutes after MHI and CWV. There was no sustained change in tidal volume following a physiotherapy-led recruitment maneuver. Respiratory compliance and dead-space increased immediately after MHI and CWV. Atelectasis scores improved following intrapulmonary percussive ventilation, and MHI and CWV. Evidence to support chest physiotherapy in ventilated children remains inconclusive. There are few high-quality studies, with heterogeneity in interventions and populations. Future studies are required to investigate multiple physiotherapy interventions and the impact on long-term outcomes.

Mechanical ventilation in patients with idiopathic pulmonary fibrosis in Korea: a nationwide cohort study.

BACKGROUND/AIMS: The prognosis of patients with idiopathic pulmonary fibrosis (IPF) and respiratory failure requiring mechanical ventilation is poor. Therefore, mechanical ventilation is not recommended. Recently, outcomes of mechanical ventilation, including those for patients with IPF, have improved. The aim of this study was to investigate changes in the use of mechanical ventilation in patients with IPF and their outcomes over time. METHODS: This retrospective, observational cohort study used data from the National Health Insurance Service database. Patients diagnosed with IPF between January 2011 and December 2019 who were placed on mechanical ventilation were included. We analyzed changes in the use of mechanical ventilation in patients with IPF and their mortality using the Cochran- Armitage trend test. RESULTS: Between 2011 and 2019, 1,227 patients with IPF were placed on mechanical ventilation. The annual number of patients with IPF with and without mechanical ventilation increased over time. However, the ratio was relatively stable at approximately 3.5%. The overall hospital mortality rate was 69.4%. There was no improvement in annual hospital mortality rate. The overall 30-day mortality rate was 68.7%, which did not change significantly. The overall 90-day mortality rate was 85.3%. The annual 90-day mortality rate was decreased from 90.9% in 2011 to 83.1% in 2019 (p = 0.028). CONCLUSION: Despite improvements in intensive care and ventilator management, the prognosis of patients with IPF receiving mechanical ventilation has not improved significantly.

Adjustments of Ventilator Parameters during Operating Room-to-ICU Transition and 28-Day Mortality.

Rationale: Lung-protective mechanical ventilation strategies have been proven beneficial in the operating room (OR) and the ICU. However, differential practices in ventilator management persist, often resulting in adjustments of ventilator parameters when transitioning patients from the OR to the ICU. Objectives: To characterize patterns of ventilator adjustments during the transition of mechanically ventilated surgical patients from the OR to the ICU and assess their impact on 28-day mortality. Methods: Hospital registry study including patients undergoing general anesthesia with continued, controlled mechanical ventilation in the ICU between 2008 and 2022. Ventilator parameters were assessed 1 hour before and 6 hours after the transition. Measurements and Main Results: Of 2,103 patients, 212 (10.1%) died within 28 days. Upon OR-to-ICU transition, VT and driving pressure decreased (-1.1 ml/kg predicted body weight [IQR, -2.0 to -0.2]; P < 0.001; and -4.3 cm H2O [-8.2 to -1.2]; P < 0.001). Concomitantly, respiratory rates increased (+5.0 breaths/min [2.0 to 7.5]; P < 0.001), resulting overall in slightly higher mechanical power (MP) in the ICU (+0.7 J/min [-1.9 to 3.0]; P < 0.001). In adjusted analysis, increases in MP were associated with a higher 28-day mortality rate (adjusted odds ratio, 1.10; 95% confidence interval, 1.06-1.14; P < 0.001; adjusted risk difference, 0.7%; 95% confidence interval, 0.4-1.0, both per 1 J/min). Conclusion: During transition of mechanically ventilated patients from the OR to the ICU, ventilator adjustments resulting in higher MP were associated with a greater risk of 28-day mortality.

Interhospital Variation in Admissions Managed With Critical Care Therapies or Invasive Hemodynamic Monitoring in Tertiary Cardiac Intensive Care Units: An Analysis From the Critical Care Cardiology Trials Network Registry.

BACKGROUND: Wide interhospital variations exist in cardiovascular intensive care unit (CICU) admission practices and the use of critical care restricted therapies (CCRx), but little is known about the differences in patient acuity, CCRx utilization, and the associated outcomes within tertiary centers. METHODS: The Critical Care Cardiology Trials Network is a multicenter registry of tertiary and academic CICUs in the United States and Canada that captured consecutive admissions in 2-month periods between 2017 and 2022. This analysis included 17 843 admissions across 34 sites and compared interhospital tertiles of CCRx (eg, mechanical ventilation, mechanical circulatory support, continuous renal replacement therapy) utilization and its adjusted association with in-hospital survival using logistic regression. The Pratt index was used to quantify patient-related and institutional factors associated with CCRx variability. RESULTS: The median age of the study population was 66 (56-77) years and 37% were female. CCRx was provided to 62.2% (interhospital range of 21.3%-87.1%) of CICU patients. Admissions to CICUs with the highest tertile of CCRx utilization had a greater burden of comorbidities, had more diagnoses of ST-elevation myocardial infarction, cardiac arrest, or cardiogenic shock, and had higher Sequential Organ Failure Assessment scores. The unadjusted in-hospital mortality (median, 12.7%) was 9.6%, 11.1%, and 18.7% in low, intermediate, and high CCRx tertiles, respectively. No clinically meaningful differences in adjusted mortality were observed across tertiles when admissions were stratified by the provision of CCRx. Baseline patient-level variables and institutional differences accounted for 80% and 5.3% of the observed CCRx variability, respectively. CONCLUSIONS: In a large registry of tertiary and academic CICUs, there was a >4-fold interhospital variation in the provision of CCRx that was primarily driven by differences in patient acuity compared with institutional differences. No differences were observed in adjusted mortality between low, intermediate, and high CCRx utilization sites.

Factores asociados a ventilación mecánica prolongada en niños con fallo respiratorio de causa pulmonar: Estudio de cohortes del registro de LARed Network / Factors associated with prolonged mechanical ventilation in children with pulmonary failure: Cohort study from the LARed Network registry

Objetivos Identificar los factores asociados con la ventilación mecánica prolongada (pVMI) en pacientes pediátricos en la unidad de cuidados intensivos pediátricos (UCIP). Diseño Análisis secundario de una cohorte prospectiva. Ámbito UCIP en los centros que integran LARed Network entre abril del 2017 y enero del 2022. Participantes Pacientes pediátricos en ventilación mecánica (VMI) debido a causas respiratorias. Definimos pVMI como eventos con tiempo VMI mayor al percentil 75 global. Intervenciones Ninguna.Variables de interés principales Datos demográficos, diagnósticos, puntajes de gravedad, terapias, complicaciones, estancias y morbimortalidad. Resultados Se incluyó a 1.698 niños con VMI de 8 ± 7 días y se definió pVMI en 9 días. Los factores relacionados al ingreso fueron la edad menor de 6 meses (OR 1,61, IC del 95%, 1,17-2,22), la displasia broncopulmonar (OR 3,71, IC del 95%, 1,87-7,36) y las infecciones fúngicas (OR 6,66, IC del 95%, 1,87-23,74), mientras que los pacientes con asma tuvieron menor riesgo de pVMI (OR 0,30, IC del 95%, 0,12-0,78). En cuanto a la evolución y la estancia en UCIP, se relacionó a neumonía asociada a la ventilación mecánica (OR 4,27, IC del 95%, 1,79-10,20), necesidad de traqueostomía (OR 2,91, IC del 95%, 1,89-4,48), transfusiones (OR 2,94, IC del 95%, 2,18-3,96), bloqueo neuromuscular (OR 2,08, IC del 95%, 1,48-2,93) y ventilación de alta frecuencia (OR 2,91, IC del 95%, 1,89-4,48) y una mayor estadía en UCIP (OR 1,13, IC del 95%, 1,10-1,16). Además, la presión media aérea mayor a 13cmH2O se asoció a pVMI (OR 1,57, IC del 95%, 1,12-2,21). Conclusiones Se identificaron factores relacionados con VMI de duración mayor a 9 días en pacientes pediátricos en UCIP en cuanto a ingreso, evolución y estancia. (AU)

Objectives To identify factors associated with prolonged mechanical ventilation (pMV) in pediatric patients in pediatric intensive care units (PICUs). Design Secondary analysis of a prospective cohort.SettingPICUs in centers that are part of the LARed Network between April 2017 and January 2022. Participants Pediatric patients on mechanical ventilation (IMV) due to respiratory causes. We defined IMV time greater than the 75th percentile of the global cohort. Interventions None.Main variables of interestDemographic data, diagnoses, severity scores, therapies, complications, length of stay, morbidity, and mortality. Results One thousand 6hundred and ninety 8children with MV of 8±7 days were included, and pIMV was defined as 9 days. Factors related to admission were age under 6 months (OR 1.61, 95% CI 1.17–2.22), bronchopulmonary dysplasia (OR 3.71, 95% CI 1.87–7.36), and fungal infections (OR 6.66, 95% CI 1.87–23.74), while patients with asthma had a lower risk of pIMV (OR 0.30, 95% CI 0.12–0.78). Regarding evolution and length of stay in the PICU, it was related to ventilation-associated pneumonia (OR 4.27, 95% CI 1.79–10.20), need for tracheostomy (OR 2.91, 95% CI 1.89–4.48), transfusions (OR 2.94, 95% CI 2.18–3.96), neuromuscular blockade (OR 2.08, 95% CI 1.48–2.93), high-frequency ventilation (OR 2.91, 95% CI 1.89–4.48), and longer PICU stay (OR 1.13, 95% CI 1.10–1.16). In addition, mean airway pressure greater than 13cmH2O was associated with pIMV (OR 1.57, 95% CI 1.12–2.21). Conclusions Factors related to IMV duration greater than 9 days in pediatric patients in PICUs were identified in terms of admission, evolution, and length of stay. (AU)

Factors associated with prolonged mechanical ventilation in children with pulmonary failure: Cohort study from the LARed Network registry.

OBJECTIVES: To identify factors associated with prolonged mechanical ventilation (pMV) in pediatric patients in pediatric intensive care units (PICUs). DESIGN: Secondary analysis of a prospective cohort. SETTING: PICUs in centers that are part of the LARed Network between April 2017 and January 2022. PARTICIPANTS: Pediatric patients on mechanical ventilation (IMV) due to respiratory causes. We defined IMV time greater than the 75th percentile of the global cohort. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Demographic data, diagnoses, severity scores, therapies, complications, length of stay, morbidity, and mortality. RESULTS: 1698 children with MV of 8±7 days were included, and pIMV was defined as 9 days. Factors related to admission were age under 6 months (OR 1.61, 95% CI 1.17-2.22), bronchopulmonary dysplasia (OR 3.71, 95% CI 1.87-7.36), and fungal infections (OR 6.66, 95% CI 1.87-23.74), while patients with asthma had a lower risk of pIMV (OR 0.30, 95% CI 0.12-0.78). Regarding evolution and length of stay in the PICU, it was related to ventilation-associated pneumonia (OR 4.27, 95% CI 1.79-10.20), need for tracheostomy (OR 2.91, 95% CI 1.89-4.48), transfusions (OR 2.94, 95% CI 2.18-3.96), neuromuscular blockade (OR 2.08, 95% CI 1.48-2.93), high-frequency ventilation (OR 2.91, 95% CI 1.89-4.48), and longer PICU stay (OR 1.13, 95% CI 1.10-1.16). In addition, mean airway pressure greater than 13cmH2O was associated with pIMV (OR 1.57, 95% CI 1.12-2.21). CONCLUSIONS: Factors related to IMV duration greater than 9 days in pediatric patients in PICUs were identified in terms of admission, evolution, and length of stay.

Factors associated with intubation in patients with acute hypoxaemic respiratory failure treated with high-flow nasal cannula oxygen therapy: A prospective, observational study.

BACKGROUND: High-flow nasal cannula (HFNC) oxygen is an alternative to conventional oxygen in acute hypoxaemic respiratory failure. Some patients require intubation, with a risk of delay; thus, early predictors may identify those requiring earlier intubation. The "ROX" index (ratio of pulse oximetry/fraction of inspired oxygen to respiratory rate) predicts intubation in patients with pneumonia treated with HFNC therapy, but this index has not been validated in non-pneumonia causes of acute hypoxaemic respiratory failure. AIM/OBJECTIVE: The aim of this study was to identify factors associated with intubation in a heterogeneous group of patients with acute hypoxaemic respiratory failure treated with HFNC oxygen. METHODS: This prospective observational study was undertaken in an Australian tertiary intensive care unit and included patients over 18 y of age with acute hypoxaemic respiratory failure who were treated with oxygen via HFNC. Vital signs and arterial blood gases were recorded prospectively at baseline and regular prespecified intervals for 48 h after HFNC initiation. Multivariate logistic regression was used to identify the factors associated with intubation. RESULTS: Forty-three patients were included (N = 43). The multivariate factors associated with intubation were admission Sequential Organ Failure Assessment score (odds ratio [OR]: 1.94 [95% confidence interval {CI}: 1.06-3.57]; p = 0.032) and Pneumonia Severity Index (OR: 0.95 [95% CI: 0.90-0.99]; p = 0.034). The ROX index was not independently associated with intubation when adjusted for Sequential Organ Failure Assessment score (OR: 0.71 [95% CI: 0.47-1.06]; p = 0.09). There was no difference in mortality between patients intubated early (<24 h) compared to those intubated late. CONCLUSIONS: Intubation was associated with admission Sequential Organ Failure Assessment score and Pneumonia Severity Index. The ROX index was not associated with intubation when adjusted for admission Sequential Organ Failure Assessment score. Outcomes were similar irrespective of whether patients were intubated late rather than early.

2023 American Heart Association and American Academy of Pediatrics Focused Update on Neonatal Resuscitation: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

This 2023 focused update to the neonatal resuscitation guidelines is based on 4 systematic reviews recently completed under the direction of the International Liaison Committee on Resuscitation Neonatal Life Support Task Force. Systematic reviewers and content experts from this task force performed comprehensive reviews of the scientific literature on umbilical cord management in preterm, late preterm, and term newborn infants, and the optimal devices and interfaces used for administering positive-pressure ventilation during resuscitation of newborn infants. These recommendations provide new guidance on the use of intact umbilical cord milking, device selection for administering positive-pressure ventilation, and an additional primary interface for administering positive-pressure ventilation.

Ultrasound assessment of diaphragm thickness, contractility, and strain in healthy pediatric patients.

BACKGROUND: Ultrasound-based diaphragmatic assessments are becoming more common in pediatric acute care, but baseline pediatric diaphragm thickness and contractility values remain unknown. METHODS: We conducted a prospective, observational study of healthy children aged <18 years undergoing elective surgery. Diaphragm thickness at end-expiration (Tdi-exp), thickening fraction (DTF) and excursion were measured by ultrasound during spontaneous breathing and during mechanical ventilation. Diaphragm strain and peak strain rate were ascertained post hoc. Measurements were compared across a priori specified age groups (<1 year, 1 to <3, 3 to <6, 6 to <12, and 12 to <18 years) and with versus without mechanical ventilation. RESULTS: Fifty subjects were evaluated (n = 10 per age group). Baseline mean Tdi-exp was 0.19 ± 0.04 cm, DTF 0.19 ± 0.09, excursion 1.69 ± 0.97 cm, strain -10.3 ± 4.9, peak strain rate -0.48 ± 0.21 s-1 . No significant difference in Tdi-exp or DTF was observed across age groups (p > .05). Diaphragm excursion increased with age (p < .0001). Diaphragm strain was significantly greater in the 12-17-year age group (-14.3 ± 6.4), p = .048, but there were no age-related differences in peak strain rate (p = .08). During mechanical ventilation, there were significant decreases in DTF 0.12 ± 0.04 (p < .0001), excursion 1.08 ± 0.31 cm (p < .0001), strain -4.60 ± 1.93 (p < .0001), and peak strain rate -0.20 ± 0.10 s-1 (p < .0001) while there was no change in Tdi-exp 0.18 ± 0.03 cm (p = .25) when compared to baseline values. CONCLUSION: Pediatric Tdi-exp, DTF, and diaphragm peak strain rate were similar across age groups. Diaphragm excursion and strain varied across age groups. All measures of diaphragm contractility were diminished during mechanical ventilation.

Lesão renal aguda e COVID-19 em adultos jovens na terapia intensiva / Lesión renal aguda y COVID-19 en adultos jóvenes en cuidados intensivos / Acute kidney injury and COVID-19 in young adults in intensive care

Resumo Objetivo Descrever a prevalência de lesão renal aguda em adultos jovens com diagnóstico da COVID-19 admitidos em unidade terapia intensiva. Métodos Estudo retrospectivo, quantitativo e analítico. A amostra foi de adultos jovens (20 a 40 anos) admitidos em unidades de terapia intensiva, com diagnóstico de infecção por SARS-CoV-2 entre março e dezembro de 2020. Os dados foram obtidos por meio do prontuário eletrônico, e a lesão renal aguda foi definida pelo valor da creatinina, segundo critérios das diretrizes da Kidney Disease Improving Global Outcomes. A significância estatística foi de p≤0,05. Resultados Foram internados 58 adultos jovens, sendo 63,8% do sexo masculino. A hipertensão arterial sistêmica esteve presente em 39,6%, a obesidade em 18,9% e o diabetes mellitus em 8,6%. A lesão renal aguda foi identificada em 55,1%, sendo o estágio 3 predominante em 43,1% deles. Nesses pacientes, o uso de ventilação mecânica e de drogas vasoativas foi significativo em 92%, assim como a disfunção orgânica respiratória (80%), seguida da renal (76%). Fatores de risco, como transplante renal ou doença renal crônica e obesidade, aumentaram em 12,3 e 9,0 vezes, respectivamente, a chance de desenvolver lesão renal aguda. Conclusão Este estudo demonstrou alta prevalência de lesão renal em adultos jovens e sua associação com comorbidades prévias. Obesidade, transplante renal e doença renal crônica elevaram a chance de o adulto jovem desenvolver lesão renal aguda, resultando em desfechos a favor da morbimortalidade.

Resumen Objetivo Describir la prevalencia de lesión renal aguda en adultos jóvenes con diagnóstico de COVID-19 admitidos en unidad de cuidados intensivos. Métodos Estudio retrospectivo, cuantitativo y analítico. La muestra fue de adultos jóvenes (20 a 40 años) admitidos en unidades de cuidados intensivos, con diagnóstico de infección por SARS-CoV-2 entre marzo y diciembre de 2020. Los datos se obtuvieron por medio de historias clínicas electrónicas, y la lesión renal aguda fue definida por el valor de la creatinina, de acuerdo con criterios de las directrices de la Kidney Disease Improving Global Outcomes. La significación estadística fue de p≤0,05. Resultados Hubo 58 adultos jóvenes internados, el 63,8 % de sexo masculino. La hipertensión arterial sistémica estuvo presente en el 39,6 %, la obesidad en el 18,9 % y la diabetes mellitus en el 8,6 %. Se identificó lesión renal aguda en el 55,1 %, de nivel 3 como predominante en el 43,1 % de los casos. En esos pacientes, el uso de ventilación mecánica y de drogas vasoactivas fue significativo en el 92 %, así como también la disfunción orgánica respiratoria (80 %), seguida de la renal (76 %). Los factores de riesgo, como trasplante renal o enfermedad renal crónica y obesidad, aumentaron 12,3 y 9,0 veces respectivamente la probabilidad de presentar lesión renal aguda. Conclusión Este estudio demostró alta prevalencia de lesión renal en adultos jóvenes y su asociación con comorbilidades previas. La obesidad, el trasplante renal y la enfermedad renal crónica aumentaron la probabilidad de que los adultos jóvenes presenten lesión renal aguda, lo que da como resultado desenlaces a favor de la morbimortalidad.

Abstract Objective To describe acute kidney injury prevalence in young adults diagnosed with COVID-19 admitted to the Intensive Care Unit. Methods This is a retrospective, quantitative and analytical study. The sample consisted of young adults (20 to 40 years old) admitted to Intensive Care Units, diagnosed with SARS-CoV-2 infection between March and December 2020. Data were obtained through electronic medical records, and kidney injury acute was defined by the creatinine value, according to the Kidney Disease Improving Global Outcomes guidelines criteria. Statistical significance was p≤0.05. Results A total of 58 young adults were hospitalized, 63.8% of whom were male. Hypertension was present in 39.6%, obesity in 18.9%, and diabetes mellitus in 8.6%. Acute kidney injury was identified in 55.1%, with stage 3 predominating in 43.1% of them. In these patients, the use of mechanical ventilation and vasoactive drugs was significant in 92% as well as respiratory organ dysfunction (80%), followed by renal organ dysfunction (76%). Risk factors such as kidney transplantation or chronic kidney disease and obesity increased by 12.3 and 9.0 times, respectively, the chances of developing acute kidney injury. Conclusion This study demonstrated a high kidney injury prevalence in young adults and its association with previous comorbidities. Obesity, kidney transplantation and chronic kidney disease increased the chance of young adults to develop acute kidney injury, resulting in outcomes in favor of morbidity and mortality.

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 / Driving pressure, em oposição ao volume corrente ajustado para o peso corporal predito, associa-se com a mortalidade: resultados de uma coorte prospectiva de pacientes com síndrome do desconforto respiratório agudo por COVID-19

ABSTRACT 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.

RESUMO Objetivo: Avaliar a associação entre driving pressure e volume corrente ajustado pelo peso predito com a mortalidade em uma coorte de pacientes com síndrome do desconforto respiratório agudo por COVID-19. Métodos: Estudo prospectivo e observacional que incluiu pacientes com síndrome do desconforto respiratório agudo por COVID-19 admitidos em duas unidades de terapia intensiva. Foi realizada análise multivariada para determinar se a driving pressure e o volume corrente/kg de peso predito, aferidos no primeiro dia de ventilação mecânica, associavam-se de forma independente com a mortalidade hospitalar. Resultados: Foram incluídos 231 pacientes. A mediana de idade foi de 64 (53 - 74) anos, e a mediana do Simplified Acute and Physiology Score 3 foi de 45 (39 - 54). A mortalidade hospitalar foi de 51,9%. A driving pressure se associou de forma independente com a mortalidade hospitalar (razão de chance de 1,21; IC95% de 1,04 - 1,41 para cada cm H2O de aumento da driving pressure, p = 0,01). Com base na análise de dupla estratificação, encontrou-se que, para o mesmo nível de volume corrente/kg de peso predito, o risco de mortalidade hospitalar aumentava com o incremento da driving pressure. No entanto, mudanças no volume corrente/kg de peso predito não se associaram com a mortalidade quando não resultavam em aumento da driving pressure. Conclusão: Em pacientes com síndrome do desconforto respiratório agudo por COVID-19, exposição a maior driving pressure, ao contrário da exposição a maior volume corrente/kg de peso predito, associou-se com maior mortalidade hospitalar. Os resultados sugerem que a driving pressure poderia ser o alvo primário para a condução da ventilação mecânica protetora nesses pacientes.

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 / Estudo randomizado prospectivo e controlado de avaliação dos efeitos de uma estratégia de limitação da driving pressure em pacientes com síndrome do desconforto respiratório agudo devido à pneumonia adquirida na comunidade (estudo STAMINA): protocolo e plano de análise estatística

ABSTRACT 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.

RESUMO Contexto: Em estudos observacionais sobre a síndrome do desconforto respiratório agudo, sugeriu-se que a driving pressure é o principal fator de lesão pulmonar induzida por ventilador e de mortalidade. Não está claro se uma estratégia de limitação da driving pressure pode melhorar os desfechos clínicos. Objetivo: Descrever o protocolo e o plano de análise estatística que serão usados para testar se uma estratégia de limitação da driving pressure envolvendo a titulação da pressão positiva expiratória final de acordo com a melhor complacência respiratória e a redução do volume corrente é superior a uma estratégia padrão envolvendo o uso da tabela de pressão positiva expiratória final baixa do protocolo ARDSNet, em termos de aumento do número de dias sem ventilador em pacientes com síndrome do desconforto respiratório agudo devido à pneumonia adquirida na comunidade. Métodos: O estudo STAMINA (ventilator STrAtegy for coMmunIty acquired pNeumoniA) é randomizado, multicêntrico e aberto e compara uma estratégia de limitação da driving pressure com a tabela de pressão positiva expiratória final baixa do protocolo ARDSnet em pacientes com síndrome do desconforto respiratório agudo moderada a grave devido à pneumonia adquirida na comunidade internados em unidades de terapia intensiva. Esperamos recrutar 500 pacientes de 20 unidades de terapia intensiva brasileiras e duas colombianas. Eles serão randomizados para um grupo da estratégia de limitação da driving pressure ou para um grupo de estratégia padrão usando a tabela de pressão positiva expiratória final baixa do protocolo ARDSnet. No grupo da estratégia de limitação da driving pressure, a pressão positiva expiratória final será titulada de acordo com a melhor complacência do sistema respiratório. Desfechos: O desfecho primário é o número de dias sem ventilador em 28 dias. Os desfechos secundários são a mortalidade hospitalar e na unidade de terapia intensiva e a necessidade de terapias de resgate, como suporte de vida extracorpóreo, manobras de recrutamento e óxido nítrico inalado. Conclusão: O STAMINA foi projetado para fornecer evidências sobre se uma estratégia de limitação da driving pressure é superior à estratégia da tabela de pressão positiva expiratória final baixa do protocolo ARDSnet para aumentar o número de dias sem ventilador em 28 dias em pacientes com síndrome do desconforto respiratório agudo moderada a grave. Aqui, descrevemos a justificativa, o desenho e o status do estudo.

Association of biomarkers with successful ventilatory weaning in COVID-19 patients: an observational study / Associação entre biomarcadores e sucesso do desmame ventilatório em pacientes com COVID-19: um estudo observacional

ABSTRACT Objective: To evaluate the association of biomarkers with successful ventilatory weaning in COVID-19 patients. Methods: An observational, retrospective, and single-center study was conducted between March 2020 and April 2021. C-reactive protein, total lymphocytes, and the neutrophil/lymphocyte ratio were evaluated during attrition and extubation, and the variation in these biomarker values was measured. The primary outcome was successful extubation. ROC curves were drawn to find the best cutoff points for the biomarkers based on sensitivity and specificity. Statistical analysis was performed using logistic regression. Results: Of the 2,377 patients admitted to the intensive care unit, 458 were included in the analysis, 356 in the Successful Weaning Group and 102 in the Failure Group. The cutoff points found from the ROC curves were −62.4% for C-reactive protein, +45.7% for total lymphocytes, and −32.9% for neutrophil/lymphocyte ratio. These points were significantly associated with greater extubation success. In the multivariate analysis, only C-reactive protein variation remained statistically significant (OR 2.6; 95%CI 1.51 - 4.5; p < 0.001). Conclusion: In this study, a decrease in C-reactive protein levels was associated with successful extubation in COVID-19 patients. Total lymphocytes and the neutrophil/lymphocyte ratio did not maintain the association after multivariate analysis. However, a decrease in C-reactive protein levels should not be used as a sole variable to identify COVID-19 patients suitable for weaning; as in our study, the area under the ROC curve demonstrated poor accuracy in discriminating extubation outcomes, with low sensitivity and specificity.

RESUMO Objetivo: Avaliar a associação de biomarcadores com o sucesso do desmame ventilatório em pacientes com COVID-19. Métodos: Trata-se de estudo observacional, retrospectivo e de centro único realizado entre março de 2020 e abril de 2021. Foram avaliados a proteína C-reativa, os linfócitos totais e a relação neutrófilos/linfócitos durante o atrito e a extubação; mediu-se a variação desses valores de biomarcadores. O desfecho primário foi o sucesso da extubação. As curvas ROC foram desenhadas para encontrar os melhores pontos de corte dos biomarcadores segundo a sensibilidade e a especificidade. A análise estatística foi realizada por meio de regressão logística. Resultados: Dos 2.377 pacientes admitidos na unidade de terapia intensiva, 458 foram incluídos na análise, 356 no Grupo Sucesso do desmame e 102 no Grupo Fracasso do desmame. Os pontos de corte encontrados nas curvas ROC foram −62,4% para proteína C-reativa, +45,7% para linfócitos totais e −32,9% para relação neutrófilo/linfócito. Esses pontos foram significativamente associados ao maior sucesso da extubação. Na análise multivariada, apenas a variação da proteína C-reativa permaneceu estatisticamente significativa (RC 2,6; IC95% 1,51 - 4,5; p < 0,001). Conclusão: Neste estudo, uma diminuição nos níveis de proteína C-reativa foi associada ao sucesso da extubação em pacientes com COVID-19. Os linfócitos totais e a relação neutrófilos/linfócitos não mantiveram a associação após a análise multivariada. No entanto, uma diminuição nos níveis de proteína C-reativa não deve ser usada como única variável para identificar pacientes com COVID-19 adequados para o desmame; como em nosso estudo, a área sob a curva ROC demonstrou baixa precisão na discriminação dos resultados de extubação, com baixas sensibilidade e especificidade.

Incidence, risk factors, progression, and involution in retinopathy of prematurity at a tertiary care center in South India.

BACKGROUND: Retinopathy of prematurity (ROP) is a vasculoproliferative disorder of immature retina, seen in preterm babies. Multiple risk factors attribute to this condition. Our aim was to correlate the role of any early neonatal surgeries with low gestational age (GA) and birth weight (BW) on preterm babies as a risk factor on the progression of ROP. METHODS: A prospective, cohort study conducted in a hospital in South India over 3 years, including 600 babies with GA <35 weeks and BW <2500 g. Babies were divided into Group A (ROP) and Group B (no ROP). Group A included A1 (severe ROP) and A2 (nonsevere ROP) based on early treatment of ROP classification. We compared various risk factors of ROP, specifically the association of any early neonatal surgery undergone by these babies, on progression of ROP. The Chi-square test, unpaired t-test, and one-way analysis of variance tests were used for the comparisons and considered statistically significant if P < 0.05. RESULTS: 28.7% babies developed ROP, with 37.6% requiring treatment (Aggressive ROP in 2.1% of babies). Low GA and BW, longer duration on ventilator, respiratory distress syndrome, apnea of prematurity, Patent Ductus Arteriosus, sepsis, anemia, thrombocytopenia, history of blood transfusion, and history of early neonatal surgery under GA were associated with babies with ROP (P < 0.005), strongly with severe ROP. The most common surgeries undergone by the babies developing ROP were inguinal herniotomy under general anesthesia. CONCLUSION: The study predicts preterm babies undergoing early surgical interventions are at risk of progressing to severe ROP, hence warranting frequent follow-ups.

Relationship between handgrip strength and inspiratory muscles with the success of the spontaneous breathing trial

Introduction: In critically ill patients on mechanical ventilation, the loss of inspiratory and peripheral muscle strength is associated with prolonged mechanical ventilation and failed weaning. Objective: To determine the relationship between handgrip strength and inspiratory muscle strength with the success of the Spontaneous Breathing Trial in adults with ventilatory support greater than 48 hours. Methodology: Prospective observational cross-sectional study performed at a tertiary hospital in Colombia. Handgrip strength and Maximal Inspiratory Pressure were measured once a day before Spontaneous Breathing Trial testing. Pearson's test and Cohen's D test were used to analyze correlations. Results: A total of 51 patients were included, 57% male, with a mean age of 51.9±20 years. A positive correlation was identified between Maximal Inspiratory Pressure and grip strength; and a negative correlation between grip strength and Maximal Inspiratory Pressure with the days of stay in the intensive care unit, (r -0.40; p<0.05) and (r -0.45; p<0.05). Conclusions: Handgrip strength and Maximal Inspiratory Pressure were positively correlated with Spontaneous Breathing Trial success. The importance of these measures to guide ventilator disconnection processes is highlighted.

Introducción: En el paciente críticamente enfermo con ventilación mecánica, la pérdida de la fuerza de los músculos inspiratorios y periféricos se asocia con ventilación mecánica prolongada y destete fallido. Objetivo: Determinar la relación entre la fuerza de prensión manual y la fuerza de músculos inspiratorios con el éxito de la prueba de respiración espontánea en adultos con soporte ventilatorio mayor a 48 horas. Metodología: Estudio prospectivo observacional de corte transversal realizado en un hospital de tercer nivel en Colombia. La fuerza de prensión manual y la presión inspiratoria máxima se midieron una vez al día antes de la prueba de prueba de respiración espontánea. Se utilizaron la prueba de Pearson y la prueba D de Cohen para analizar las correlaciones. Resultados: Se incluyeron 51 pacientes, 57 % de sexo masculino, con una edad promedio de 51,9 ± 20 años. Se identificó una correlación positiva entre Presión Inspiratoria Máxima y fuerza de la mano; y una correlación negativa entre la fuerza de la mano y la Presión Inspiratoria Máxima con los días de estancia en la Unidad de Cuidados Intensivos, (r -0,40; p < 0,05) y (r -0,45;p < 0,05). Conclusiones: La fuerza de prensión manual y la Presión Inspiratoria Máxima se correlacionaron positivamente con el éxito de la Prueba de Respiración Espontánea. Se destaca la importancia de estas mediciones para guiar procesos de desconexión del ventilador.

Effects of atelectatic areas on the surrounding lung tissue during mechanical ventilation in an experimental model of acute lung injury induced by lipopolysaccharide / Efeitos das áreas atelectásicas no tecido pulmonar circundante durante a ventilação mecânica em um modelo experimental de lesão pulmonar aguda induzida por lipopolissacarídeo

ABSTRACT Objective: To assess the effect of atelectasis during mechanical ventilation on the periatelectatic and normal lung regions in a model of atelectasis in rats with acute lung injury induced by lipopolysaccharide. Methods: Twenty-four rats were randomized into the following four groups, each with 6 animals: the Saline-Control Group, Lipopolysaccharide Control Group, Saline-Atelectasis Group, and Lipopolysaccharide Atelectasis Group. Acute lung injury was induced by intraperitoneal injection of lipopolysaccharide. After 24 hours, atelectasis was induced by bronchial blocking. The animals underwent mechanical ventilation for two hours with protective parameters, and respiratory mechanics were monitored during this period. Thereafter, histologic analyses of two regions of interest, periatelectatic areas and the normally-aerated lung contralateral to the atelectatic areas, were performed. Results: The lung injury score was significantly higher in the Lipopolysaccharide Control Group (0.41 ± 0.13) than in the Saline Control Group (0.15 ± 0.51), p < 0.05. Periatelectatic regions showed higher lung injury scores than normally-aerated regions in both the Saline-Atelectasis (0.44 ± 0.06 x 0.27 ± 0.74 p < 0.05) and Lipopolysaccharide Atelectasis (0.56 ± 0.09 x 0.35 ± 0.04 p < 0.05) Groups. The lung injury score in the periatelectatic regions was higher in the Lipopolysaccharide Atelectasis Group (0.56 ± 0.09) than in the periatelectatic region of the Saline-Atelectasis Group (0.44 ± 0.06), p < 0.05. Conclusion: Atelectasis may cause injury to the surrounding tissue after a period of mechanical ventilation with protective parameters. Its effect was more significant in previously injured lungs.

RESUMO Objetivo: Avaliar o efeito da atelectasia durante a ventilação mecânica nas regiões periatelectáticas e pulmonares normais em um modelo de atelectasia em ratos com lesão pulmonar aguda induzida por lipopolissacarídeo. Métodos: Foram distribuídos aleatoriamente 24 ratos em quatro grupos, cada um com 6 animais: Grupo Salina-Controle, Grupo Lipopolissacarídeo-Controle, Grupo Salina-Atelectasia e Grupo Lipopolissacarídeo-Atelectasia. A lesão pulmonar aguda foi induzida por injeção intraperitoneal de lipopolissacarídeo. Após 24 horas, a atelectasia foi induzida por bloqueio brônquico. Os animais foram submetidos à ventilação mecânica por 2 horas com parâmetros ventilatórios protetores, e a mecânica respiratória foi monitorada durante esse período. Em seguida, foram realizadas análises histológicas de duas regiões de interesse: as áreas periatelectásicas e o pulmão normalmente aerado contralateral às áreas atelectásicas. Resultados: O escore de lesão pulmonar foi significativamente maior no Grupo Controle-Lipopolissacarídeo (0,41 ± 0,13) do que no Grupo Controle-Solução Salina (0,15 ± 0,51), com p < 0,05. As regiões periatelectásicas apresentaram escores maiores de lesão pulmonar do que as regiões normalmente aeradas nos Grupos Atelectasia-Solução Salina (0,44 ± 0,06 versus 0,27 ± 0,74, p < 0,05) e Atelectasia-Lipopolissacarídeo (0,56 ± 0,09 versus 0,35 ± 0,04, p < 0,05). O escore de lesão pulmonar nas regiões periatelectásicas foi maior no Grupo Atelectasia-Lipopolissacarídeo (0,56 ± 0,09) do que na região periatelectásica do Grupo Atelectasia-Solução Salina (0,44 ± 0,06), p < 0,05. Conclusão: A atelectasia pode causar lesão no tecido circundante após um período de ventilação mecânica com parâmetros ventilatórios protetores. Seu efeito foi mais significativo em pulmões previamente lesionados.

Impact of vertical positioning on lung aeration among mechanically ventilated intensive care unit patients: a randomized crossover clinical trial / Impacto do posicionamento vertical na aeração pulmonar em pacientes de unidades de terapia intensiva ventilados mecanicamente: um estudo clínico transversal randomizado

ABSTRACT Objective: To assess the impact of different vertical positions on lung aeration in patients receiving invasive mechanical ventilation. Methods: An open-label randomized crossover clinical trial was conducted between January and July 2020. Adults receiving invasive mechanical ventilation for > 24 hours and < 7 days with hemodynamic, respiratory and neurological stability were randomly assigned at a 1:1 ratio to the sitting position followed by passive orthostasis condition or the passive orthostasis followed by the sitting position condition. The primary outcome was lung aeration assessed using the lung ultrasound score (score ranges from 0 [better] to 36 [worse]). Results: A total of 186 subjects were screened; of these subjects, 19 were enrolled (57.8% male; mean age, 73.2 years). All participants were assigned to receive at least one verticalization protocol. Passive orthostasis resulted in mean lung ultrasound scores that did not differ significantly from the sitting position (11.0 versus 13.7; mean difference, -2.7; [95%CI -6.1 to 0.71; p = 0.11). Adverse events occurred in three subjects in the passive orthostasis group and in one in the sitting position group (p = 0.99). Conclusion: This analysis did not find significant differences in lung aeration between the sitting and passive orthostasis groups. A randomized crossover clinical trial assessing the impact of vertical positioning on lung aeration in patients receiving invasive mechanical ventilation is feasible. Unfortunately, the study was interrupted due to the need to treat COVID-19 patients. ClinicalTrials.gov registry: NCT04176445

RESUMO Objetivo: Avaliar o impacto de diferentes posicionamentos verticais na aeração pulmonar em pacientes em ventilação mecânica invasiva. Métodos: Trata-se de ensaio clínico aberto, randomizado e transversal, realizado entre janeiro e julho de 2020. Adultos em ventilação mecânica invasiva por mais de 24 horas e menos de 7 dias com estabilidade hemodinâmica, respiratória e neurológica foram distribuídos aleatoriamente em uma proporção de 1:1 à postura sentada seguida da condição de ortostatismo passivo ou o ortostatismo passivo seguido de postura sentada. O desfecho primário foi a aeração pulmonar avaliada pelo lung ultrasound score. O escore varia de zero (melhor) a 36 (pior). Resultados: Foram selecionados 186 indivíduos; destes, 19 foram incluídos (57,8% do sexo masculino; média idade de 73,2 anos). Todos os participantes foram selecionados para receber pelo menos um protocolo de verticalização. O ortostatismo passivo resultou em escores médios de aeração pulmonar por ultrassonografia que não diferiram significativamente da postura sentada (11,0 versus 13,7; diferença média, -2,7; IC95% -6,1 a 0,71; p = 0,11). Ocorreram eventos adversos em três indivíduos no grupo ortostatismo passivo e em um no grupo postura sentada (p = 0,99). Conclusão: Esta análise não encontrou diferenças significativas na aeração pulmonar entre os grupos ortostatismo passivo e postura sentada. É factível conduzir um estudo clínico transversal randomizado para avaliar o impacto do posicionamento vertical na aeração pulmonar em pacientes em ventilação mecânica invasiva. Infelizmente, o estudo foi interrompido devido à necessidade de tratar pacientes com COVID-19. Registro ClinicalTrials.gov: NCT04176445

[Comment on article "Risk factors at admission associated with intubation in patients with COVID-19"]. / Comentario al artículo "Factores de riesgo al ingreso asociados a intubación en pacientes con COVID-19".

Risk factors associated with intubation in patients with COVID-19, should not be confused with criteria for intubation in patients with respiratory problems. In the treatment of patients with COVID-19, it is important to consider the time from the onset of symptoms and the delay of patients to seek hospital care. This could be another factor influencing patient's evolution. Taking account steroids as a predictor of intubation requires a more in-depth analysis of the steroid used, its dose and the timing in which they are used. There are many factors that can explain the uncertain evolution of patients with COVID-19. Identifying them can help to develop strategies to reduce the delay in mechanical ventilation, and therefore improve the prognosis.

Los factores de riesgo asociados a intubación en pacientes con COVID-19, no se debe confundir con los criterios para intubación en pacientes con problemas respiratorios. En el tratamiento de pacientes con COVID -19 es importante considerar el tiempo desde el inicio de los síntomas y el retraso en la atención hospitalaria. Esto puede ser otro factor que influya en la evolución de los pacientes. Considerar a los esteroides como un factor predictor de intubación, requiere un análisis más profundo sobre el tipo, la dosis y el momento en el que se utilizan. Hay muchos factores que pueden explicar la mala evolución de los pacientes con COVID-19. Identificarlos puede ayudar a que surjan estrategias para disminuir el retraso en la ventilación mecánica, y por lo tanto mejorar el pronóstico.