Dexamethasone doses in patients with COVID-19 and hypoxia: A systematic review and meta-analysis.

BACKGROUND: The optimal dose of dexamethasone for severe/critical COVID-19 is uncertain. We compared higher versus standard doses of dexamethasone in adults with COVID-19 and hypoxia. METHODS: We searched PubMed and trial registers until 23 June 2023 for randomised clinical trials comparing higher (>6 mg) versus standard doses (6 mg) of dexamethasone in adults with COVID-19 and hypoxia. The primary outcome was mortality at 1 month. Secondary outcomes were mortality closest to 90 days; days alive without life support; and the occurrence of serious adverse events/reactions (SAEs/SARs) closest to 1 month. We assessed the risk of bias using the Cochrane RoB2 tool, risk of random errors using trial sequential analysis, and certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We included eight trials (2478 participants), of which four (1293 participants) had low risk of bias. Higher doses of dexamethasone probably resulted in little to no difference in mortality at 1 month (relative risk [RR] 0.97, 95% CI: 0.79-1.19), mortality closest to Day 90 (RR 1.01, 95% CI: 0.86-1.20), and SAEs/SARs (RR 1.00, 95% CI: 0.97-1.02). Higher doses of dexamethasone probably increased the number of days alive without invasive mechanical ventilation and circulatory support but had no effect on days alive without renal replacement therapy. CONCLUSIONS: Based on low to moderate certainty evidence, higher versus standard doses of dexamethasone probably result in little to no difference in mortality, SAEs/SARs, and days alive without renal replacement therapy, but probably increase the number of days alive without invasive mechanical ventilation and circulatory support.

Trigger reverso durante ventilación mecánica: diagnóstico e implicaciones clínicas / Reverse triggering during mechanical ventilation: Diagnosis and clinical implications

Esta revisión aborda el fenómeno «trigger reverso», una asincronía que se presenta en pacientes sedados o en transición de despertar, con una prevalencia en estos grupos del 30% al 90%. Los mecanismos fisiopatológicos aún no están claros, pero se propone el «entrainment» como uno de ellos. Detectar esta asincronía es complejo y se han usado métodos como inspección visual, presión esofágica, ecografía diafragmática y métodos automáticos. El trigger reverso puede tener efectos en la función pulmonar y diafragmática, mediados porbablemente por el nivel de esfuerzo respiratorio y la activación excéntrica del diafragma. El manejo óptimo no está establecido y puede incluir ajuste de parámetros ventilatorios, frecuencia respiratoria, nivel de sedación y en casos extremos, bloqueo neuromuscular. Es importante comprender su significación, su detección e incrementar la investigación para mejorar su manejo clínico y sus potenciales efectos en los pacientes críticamente enfermos. (AU)

This review addresses the phenomenon of “reverse triggering”, an asynchrony that occurs in deeply sedated or patients in transition from deep to light sedation. Reverse triggering has been reported to occur between 30% and 90% of ventilated patients. The pathophysiological mechanisms are still unclear, but “entrainment” is proposed as one of them. Detecting this asynchrony is crucial, and methods such as visual inspection, esophageal pressure, diaphragmatic ultrasound, and automatic methods have been used. Reverse triggering may have effects on lung and diaphragm function, probably mediated by the level of breathing effort and eccentric activation of the diaphragm. The optimal management of reverse triggering is not established and may include adjustment of ventilatory parameters as well as sedation level, and in extreme cases, neuromuscular blockade. It is important to understand the significance of this condition, its detection, but also to conduct dedicated research to improve its clinical management and its potential effects in critically ill patients. (AU)

Reverse triggering during mechanical ventilation: Diagnosis and clinical implications.

This review addresses the phenomenon of "reverse triggering", an asynchrony that occurs in deeply sedated patients or patients in transition from deep to light sedation. Reverse triggering has been reported to occur in 30-90% of all ventilated patients. The underlying pathophysiological mechanisms remain unclear, but "entrainment" is proposed as one of them. Detecting this asynchrony is crucial, and methods such as visual inspection, esophageal pressure, diaphragmatic ultrasound and automated methods have been used. Reverse triggering may have effects on lung and diaphragm function, probably mediated by the level of breathing effort and eccentric activation of the diaphragm. The optimal management of reverse triggering has not been established, but may include the adjustment of ventilatory parameters as well as of sedation level, and in extreme cases, neuromuscular block. It is important to understand the significance of this condition and its detection, but also to conduct dedicated research to improve its clinical management and potential effects in critically ill patients.

Failure of First Transition to Pressure Support Ventilation After Spontaneous Awakening Trials in Hypoxemic Respiratory Failure: Influence of COVID-19.

OBJECTIVES: To describe the rate of failure of the first transition to pressure support ventilation (PSV) after systematic spontaneous awakening trials (SATs) in patients with acute hypoxemic respiratory failure (AHRF) and to assess whether the failure is higher in COVID-19 compared with AHRF of other etiologies. To determine predictors and potential association of failure with outcomes. DESIGN: Retrospective cohort study. SETTING: Twenty-eight-bedded medical-surgical ICU in a private hospital (Argentina). PATIENTS: Subjects with arterial pressure of oxygen (AHRF to Fio2 [Pao2/Fio2] < 300 mm Hg) of different etiologies under controlled mechanical ventilation (MV). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We collected data during controlled ventilation within 24 hours before SAT followed by the first PSV transition. Failure was defined as the need to return to fully controlled MV within 3 calendar days of PSV start. A total of 274 patients with AHRF (189 COVID-19 and 85 non-COVID-19) were included. The failure occurred in 120 of 274 subjects (43.7%) and was higher in COVID-19 versus non-COVID-19 (49.7% and 30.5%; p = 0.003). COVID-19 diagnosis (odds ratio [OR]: 2.22; 95% CI [1.15-4.43]; p = 0.020), previous neuromuscular blockers (OR: 2.16; 95% CI [1.15-4.11]; p = 0.017) and higher fentanyl dose (OR: 1.29; 95% CI [1.05-1.60]; p = 0.018) increased the failure chances. Higher BMI (OR: 0.95; 95% CI [0.91-0.99]; p = 0.029), Pao2/Fio2 (OR: 0.87; 95% CI [0.78-0.97]; p = 0.017), and pH (OR: 0.61; 95% CI [0.38-0.96]; p = 0.035) were protective. Failure groups had higher 60-day ventilator dependence (p < 0.001), MV duration (p < 0.0001), and ICU stay (p = 0.001). Patients who failed had higher mortality in COVID-19 group (p < 0.001) but not in the non-COVID-19 (p = 0.083). CONCLUSIONS: In patients with AHRF of different etiologies, the failure of the first PSV attempt was 43.7%, and at a higher rate in COVID-19. Independent risk factors included COVID-19 diagnosis, fentanyl dose, previous neuromuscular blockers, acidosis and hypoxemia preceding SAT, whereas higher BMI was protective. Failure was associated with worse outcomes.

Study protocol for a randomized controlled trial of Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation: the PROMIZING study.

BACKGROUND: Proportional assist ventilation with load-adjustable gain factors (PAV+) is a mechanical ventilation mode that delivers assistance to breathe in proportion to the patient's effort. The proportional assistance, called the gain, can be adjusted by the clinician to maintain the patient's respiratory effort or workload within a normal range. Short-term and physiological benefits of this mode compared to pressure support ventilation (PSV) include better patient-ventilator synchrony and a more physiological response to changes in ventilatory demand. METHODS: The objective of this multi-centre randomized controlled trial (RCT) is to determine if, for patients with acute respiratory failure, ventilation with PAV+ will result in a shorter time to successful extubation than with PSV. This multi-centre open-label clinical trial plans to involve approximately 20 sites in several continents. Once eligibility is determined, patients must tolerate a short-term PSV trial and either (1) not meet general weaning criteria or (2) fail a 2-min Zero Continuous Positive Airway Pressure (CPAP) Trial using the rapid shallow breathing index, or (3) fail a spontaneous breathing trial (SBT), in this sequence. Then, participants in this study will be randomized to either PSV or PAV+ in a 1:1 ratio. PAV+ will be set according to a target of muscular pressure. The weaning process will be identical in the two arms. Time to liberation will be the primary outcome; ventilator-free days and other outcomes will be measured. DISCUSSION: Meta-analyses comparing PAV+ to PSV suggest PAV+ may benefit patients and decrease healthcare costs but no powered study to date has targeted the difficult to wean patient population most likely to benefit from the intervention, or used consistent timing for the implementation of PAV+. Our enrolment strategy, primary outcome measure, and liberation approaches may be useful for studying mechanical ventilation and weaning and can offer important results for patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02447692 . Prospectively registered on May 19, 2015.

Dynamic Relative Regional Lung Strain Estimated by Electrical Impedance Tomography in an Experimental Model of ARDS.

BACKGROUND: To analyze the role of PEEP on dynamic relative regional strain (DRRS) in a model of ARDS, respective maps were generated by electrical impedance tomography (EIT). METHODS: Eight ARDS pigs submitted to PEEP steps of 0, 5, 10, and 15 cm H2O at fixed ventilation were evaluated by EIT images. DRRS was calculated as (VT-EIT/EELI)/(VT-EIT[15PEEP]/EELI[15PEEP]), where the tidal volume (VT)-EIT and end-expiratory lung impedance (EELI) are the tidal and end-expiratory change in lung impedance, respectively. The measurement at 15 PEEP was taken as reference (end-expiratory transpulmonary pressure > 0 cm H2O). The relationship between EIT variables (center of ventilation, EELI, and DRRS) and airway pressures was assessed with mixed-effects models using EIT measurements as dependent variables and PEEP as fixed-effect variable. RESULTS: At constant ventilation, respiratory compliance increased progressively with PEEP (lowest value at zero PEEP 10 ± 3 mL/cm H2O and highest value at 15 PEEP 16 ± 6 mL/cm H2O; P < .001), whereas driving pressure decreased with PEEP (highest value at zero PEEP 34 ± 6 cm H2O and lowest value at 15 PEEP 21 ± 4 cm H2O; P < .001). The mixed-effect regression models showed that the center of ventilation moved to dorsal lung areas with a slope of 1.81 (1.44-2.18) % points by each cm H2O of PEEP; P < .001. EELI increased with a slope of 0.05 (0.02-0.07) (arbitrary units) for each cm H2O of PEEP; P < .001. DRRS maps showed that local strain in ventral lung areas decreased with a slope of -0.02 (-0.24 to 0.15) with each cm H2O increase of PEEP; P < .001. CONCLUSIONS: EIT-derived DRRS maps showed high strain in ventral lung zones at low levels of PEEP. The findings suggest overdistention of the baby lung.

Incidencia de trombosis venosa profunda en pacientes con síndrome de distrés respiratorio agudo secundario a COVID-19, bajo tromboprofilaxis con dosis intermedia de heparina de bajo peso molecular / Deep venous thrombosis incidence in patients with COVID-19 acute respiratory distress syndrome, under intermediate dose of chemical thromboprophylaxis

Resumen A pesar de la tromboprofilaxis estándar, el diagnóstico de trombosis es común en pacientes críticos con COVID-19. El objetivo del presente estudio fue evaluar la incidencia de trombosis venosa profunda (TVP) en pacientes con neumonía grave por COVID-19 con requerimientos de asistencia respiratoria mecánica, bajo tromboprofilaxis química con dosis intermedia (1 mg/kg/día) de heparina de bajo peso molecular (enoxaparina). Se trató de un estudio unicéntrico, descriptivo y de corte transversal de datos recopilados en forma prospectiva. Se realizó búsqueda activa y sistemática de TVP en miembros inferiores (o en confluente yúgulosubclavio en su defecto) mediante doppler venoso cada 7 días. Se continuó con la evaluación por doppler semanal hasta la finalización de la ventilación mecánica, el cum plimiento de los 28 días de internación en unidad de cuidados intensivos, el fallecimiento o la suspensión de la tromboprofilaxis con enoxaparina por cualquier causa. Se incluyeron 46 pacientes. Se realizó diagnóstico de TVP en 5 (3 en miembros inferiores y 2 en con fluente yúgulosubclavio). Tres diagnósticos de TVP fueron asociados a la presencia de catéter venoso central (2 en miembros inferiores y 1 en el confluente yúgulosubclavio), dos fallecieron durante el seguimiento por causas vinculadas al síndrome de distrés respiratorio agudo (SDRA) pero no por eventos trombóticos o de sangrado mayor. En todos los casos, los eventos trombóticos fueron asintomáticos. En nuestra serie de pacientes con SDRA moderado/grave secundario a neumonía por COVID-19, la incidencia de TVP fue del 10.9% en aquellos bajo tromboprofilaxis con dosis intermedia (1 mg/kg/día) de enoxaparina.

Abstract Despite standard thrombo prophylaxis, venous thrombosis is common in critically ill patients with COVID-19. The objective of this study was to evaluate deep venous thrombosis (DVT) incidence in patients with severe COVID-19 pneumonia with mechanical ventilation requirements under intermediate dose of chemical thromboprophylaxis (1 mg/kg/day of enoxaparin). This was a single-center, descriptive, cross-sectional study of prospectively collected data. An active and systematic protocol with venous doppler was carried out for DVT diagnosis in lower limbs (or in jugulo-subclavian venous confluence) every 7 days. Weekly doppler evaluation was continued until the end of mechanical ventilation, up to 28 days of intensive care unit admission, until death or until the thromboprophylaxis suspension for any cause. Forty-six patients were included. DVT was diagnosed in 5 (3 in lower limbs and 2 in jugulo-subclavian conflu ent). In 3 cases, DVT was catheter-related (2 in lower limbs and 1 in jugulo-subclavian confluent), 2 died during follow-up due to acute respiratory distress syndrome (ARDS) complications without thrombotic events or major bleeding. All thrombotic events were asymptomatic. In our series of patients with moderate/severe COVID-19 ARDS, DVT incidence was 10.9% under thromboprophylaxis with intermediate dose (1 mg/kg/ day) of enoxaparin.

[Deep venous thrombosis incidence in patients with COVID-19 acute respiratory distress syndrome, under intermediate dose of chemical thromboprophylaxis]. / Incidencia de trombosis venosa profunda en pacientes con síndrome de distrés respiratorio agudo secundario a COVID-19, bajo tromboprofilaxis con dosis intermedia de heparina de bajo peso molecular.

Despite standard thromboprophylaxis, venous thrombosis is common in critically ill patients with COVID-19. The objective of this study was to evaluate deep venous thrombosis (DVT) incidence in patients with severe COVID-19 pneumonia with mechanical ventilation requirements under intermediate dose of chemical thromboprophylaxis (1 mg/kg/day of enoxaparin). This was a single-center, descriptive, cross-sectional study of prospectively collected data. An active and systematic protocol with venous doppler was carried out for DVT diagnosis in lower limbs (or in jugulo-subclavian venous confluence) every 7 days. Weekly doppler evaluation was continued until the end of mechanical ventilation, up to 28 days of intensive care unit admission, until death or until the thromboprophylaxis suspension for any cause. Forty-six patients were included. DVT was diagnosed in 5 (3 in lower limbs and 2 in jugulo-subclavian confluent). In 3 cases, DVT was catheter-related (2 in lower limbs and 1 in jugulo-subclavian confluent), 2 died during follow-up due to acute respiratory distress syndrome (ARDS) complications without thrombotic events or major bleeding. All thrombotic events were asymptomatic. In our series of patients with moderate/severe COVID-19 ARDS, DVT incidence was 10.9% under thromboprophylaxis with intermediate dose (1 mg/kg/ day) of enoxaparin.

A pesar de la tromboprofilaxis estándar, el diagnóstico de tromb osis es común en pacientes críticos con COVID-19. El objetivo del presente estudio fue evaluar la incidencia de trombosis venosa profunda (TVP) en pacientes con neumonía grave por COVID-19 con requerimientos de asistencia respiratoria mecánica, bajo tromboprofilaxis química con dosis intermedia (1 mg/kg/día) de heparina de bajo peso molecular (enoxaparina). Se trató de un estudio unicéntrico, descriptivo y de corte transversal de datos recopilados en forma prospectiva. Se realizó búsqueda activa y sistemática de TVP en miembros inferiores (o en confluente yúgulosubclavio en su defecto) mediante doppler venoso cada 7 días. Se continuó con la evaluación por doppler semanal hasta la finalización de la ventilación mecánica, el cum plimiento de los 28 días de internación en unidad de cuidados intensivos, el fallecimiento o la suspensión de la tromboprofilaxis con enoxaparina por cualquier causa. Se incluyeron 46 pacientes. Se realizó diagnóstico de TVP en 5 (3 en miembros inferiores y 2 en confluente yúgulosubclavio). Tres diagnósticos de TVP fueron asociados a la presencia de catéter venoso central (2 en miembros inferiores y 1 en el confluente yúgulosubclavio), dos fallecieron durante el seguimiento por causas vinculadas al síndrome de distrés respiratorio agudo (SDRA) pero no por eventos trombóticos o de sangrado mayor. En todos los casos, los eventos trombóticos fueron asintomáticos. En nuestra serie de pacientes con SDRA moderado/grave secundario a neumonía por COVID-19, la incidencia de TVP fue del 10.9% en aquellos bajo tromboprofilaxis con dosis intermedia (1 mg/kg/día) de enoxaparina.

Echocardiographic findings in patients under mechanical ventilation with COVID-19 acute respiratory distress syndrome / Hallazgos ecocardiográficos en pacientes bajo ventilación mecánica con síndrome de dificultad respiratoria aguda por COVID-19

Abstract Coronavirus disease 2019 (COVID-19) produces a significant burden to severely ill patients affected by acute respiratory failure. The aim of this study was to describe echocardiographic findings in a series of mechanically ventilated patients with moderate and severe acute respiratory distress syndrome (ARDS) due to COVID-19. This was a single center, descriptive and cros s-sectional study of prospectively collected data. Patients had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate or severe ARDS. Initial echocardiogram was performed within 7 days of intensive care unit admission and every 15 days until mechanical ventilation ended, 28 days or death. Time spent by the physician for each study was measured. Multiple echographic measurements were acquired; 33 patients were analyzed. Total number of echocardiograms performed was 76. The median imaging time required to complete a standard study was 13 [10-15] minutes. Chronic structural abnormalities were present in 16 patients (48%), being LV hypertrophy the main finding in 11 patients (33%). The most frequent acute or dynamic finding was RV enlargement (43%) when considering all echocardiograms performed from admission to day 28 of follow-up. Other findings were: pulmonary hypertension (15%), new or dynamic left ventricle (LV) regional wall motion abnormalities (15%), new or dynamic LV global contractility deterioration (6%) and hypercontractility (12%).

Resumen La enfermedad por coronavirus 2019 (COVID-19) produce una carga significativa para los pacientes gravemente enfermos afectados por insuficiencia respiratoria aguda. El objetivo de este estudio fue describir los hallazgos ecocardiográficos en una serie de pacientes ventilados mecánicamente con síndrome de dificultad respiratoria aguda (SDRA) moderado y grave debido a COVID-19. Se trata de un estudio unicéntrico, descriptivo y de corte transversal de datos recopilados en forma prospectiva. Los pacientes tenían una infección por el coronavirus SARS-Cov-2 y SDRA moderado o grave. El ecocardiogra ma inicial se realizó dentro de los 7 días del ingreso en la unidad de cuidados intensivos y luego cada 15 días hasta finalizar la ventilación mecánica, 28 días o fallecimiento. Se midió el tiempo empleado por el operador en cada estudio. Se adquirieron múltiples medidas ecográficas. Se analizaron 33 pacientes. El número total de ecocardiogramas realizados fue de 76. El tiempo necesario (mediana [RIQ]) para la obtención de las imágenes de un estudio estándar fue de 13 [10-15] minutos. Las anomalías estructurales crónicas estuvieron presentes en 16 pacientes (48%), siendo la hipertrofia ventricular izquierda la principal (11 pacientes, 33%). El hallazgo agudo o dinámico más frecuente fue el agrandamiento del ventrículo derecho (VD) (43%) al considerar todos los ecocardiogramas realizados desde el ingreso hasta el día 28 de seguimiento. Otros hallazgos fueron: hipertensión pulmonar (15%), anomalías del movimiento de la pared regional del VI nuevas o dinámicas (15%), deterioro de la contractilidad global del ventrículo izquierdo, nuevo o dinámico (6%), e hipercontractilidad (12%).

Echocardiographic findings in patients under mechanical ventilation with COVID-19 acute respiratory distress syndrome.

Coronavirus disease 2019 (COVID-19) produces a significant burden to severely ill patients affected by acute respiratory failure. The aim of this study was to describe echocardiographic findings in a series of mechanically ventilated patients with moderate and severe acute respiratory distress syndrome (ARDS) due to COVID-19. This was a single center, descriptive and cros s-sectional study of prospectively collected data. Patients had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate or severe ARDS. Initial echocardiogram was performed within 7 days of intensive care unit admission and every 15 days until mechanical ventilation ended, 28 days or death. Time spent by the physician for each study was measured. Multiple echographic measurements were acquired; 33 patients were analyzed. Total number of echocardiograms performed was 76. The median imaging time required to complete a standard study was 13 [10-15] minutes. Chronic structural abnormalities were present in 16 patients (48%), being LV hypertrophy the main finding in 11 patients (33%). The most frequent acute or dynamic finding was RV enlargement (43%) when considering all echocardiograms performed from admission to day 28 of follow-up. Other findings were: pulmonary hypertension (15%), new or dynamic left ventricle (LV) regional wall motion abnormalities (15%), new or dynamic LV global contractility deterioration (6%) and hypercontractility (12%).

La enfermedad por coronavirus 2019 (COVID-19) produce una carga significativa para los pacientes gravemente enfermos afectados por insuficiencia respiratoria aguda. El objetivo de este estudio fue describir los hallazgos ecocardiográficos en una serie de pacientes ventilados mecánicamente con síndrome de dificultad respiratoria aguda (SDRA) moderado y grave debido a COVID-19. Se trata de un estudio unicéntrico, descriptivo y de corte transversal de datos recopilados en forma prospectiva. Los pacientes tenían una infección por el coronavirus SARS-Cov-2 y SDRA moderado o grave. El ecocardiograma inicial se realizó dentro de los 7 días del ingreso en la unidad de cuidados intensivos y luego cada 15 días hasta finalizar la ventilación mecánica, 28 días o fallecimiento. Se midió el tiempo empleado por el operador en cada estudio. Se adquirieron múltiples medidas ecográficas. Se analizaron 33 pacientes. El número total de ecocardiogramas realizados fue de 76. El tiempo necesario (mediana [RIQ]) para la obtención de las imágenes de un estudio estándar fue de 13 [10-15] minutos. Las anomalías estructurales crónicas estuvieron presentes en 16 pacientes (48%), siendo la hipertrofia ventricular izquierda la principal (11 pacientes, 33%). El hallazgo agudo o dinámico más frecuente fue el agrandamiento del ventríc ulo derecho (VD) (43%) al considerar todos los ecocardiogramas realizados desde el ingreso hasta el día 28 de seguimiento. Otros hallazgos fueron: hipertensión pulmonar (15%), anomalías del movimiento de la pared regional del VI nuevas o dinámicas (15%), deterioro de la contractilidad global del ventrículo izquierdo, nuevo o dinámico (6%), e hipercontractilidad (12%).

High-Flow Oxygen Therapy Application in Chronic Obstructive Pulmonary Disease Patients With Acute Hypercapnic Respiratory Failure: A Multicenter Study.

OBJECTIVES: To evaluate the effect of high-flow oxygen implementation on the respiratory rate as a first-line ventilation support in chronic obstructive pulmonary disease patients with acute hypercapnic respiratory failure. DESIGN: Multicenter, prospective, analytic observational case series study. SETTING: Five ICUs in Argentina, between August 2018 and September 2019. PATIENTS: Patients greater than or equal to 18 years old with moderate to very severe chronic obstructive pulmonary disease, who had been admitted to the ICU with a diagnosis of hypercapnic acute respiratory failure, were entered in the study. INTERVENTIONS: High-flow oxygen therapy through nasal cannula delivered using high-velocity nasal insufflation. MEASUREMENTS AND MAIN RESULTS: Forty patients were studied, 62.5% severe chronic obstructive pulmonary disease. After the first hour of high-flow nasal cannula implementation, there was a significant decrease of respiratory rate compared with baseline values, with a 27% decline (29 vs 21 breaths/min; p < 0.001). Furthermore, a significant reduction of Paco2 (57 vs 52 mm Hg [7.6 vs 6.9 kPa]; p < 0.001) was observed. The high-flow nasal cannula application failed in 18% patients. In this group, the respiratory rate, pH, and Paco2 showed no significant change during the first hour in these patients. CONCLUSIONS: High-flow oxygen therapy through nasal cannula delivered using high-velocity nasal insufflation was an effective tool for reducing respiratory rate in these chronic obstructive pulmonary disease patients with acute hypercapnic respiratory failure. Early determination and subsequent monitoring of clinical and blood gas parameters may help predict the outcome.

Prevalence of Reverse Triggering in Early ARDS: Results From a Multicenter Observational Study.

BACKGROUND: The prevalence of reverse triggering (RT) in the early phase of ARDS is unknown. RESEARCH QUESTION: During early ARDS, what is the proportion of patients affected by RT, what are its potential predictors, and what is its association with clinical outcomes? STUDY DESIGN AND METHODS: This was prospective, multicenter, and observational study. Patients who met the Berlin definition of ARDS with less than 72 h of mechanical ventilation and had not been paralyzed with neuromuscular blockers were screened. A 30-min recording of respiratory signals was obtained from the patients as soon as they were enrolled, and the number of breaths with RT were counted. RESULTS: One hundred patients were included. ARDS was mild to moderate in 92% of them. The recordings were obtained after a median of 1 day (interquartile range, 1-2 days) of ventilation. Fifty patients had RT, and most of these events (97%) were not associated with breath stacking. Detecting RT was associated with lower tidal volume (Vt) and less opiate infusion. The presence of RT was not associated with time to discontinuation of mechanical ventilation (subdistribution hazard ratio, 1.03; 95% CI, 0.6-1.77), but it possibly was associated with a reduced hospital mortality (hazard ratio, 0.65; 95% CI, 0.57-0.73). INTERPRETATION: Fifty percent of patients receiving assist-control ventilation for mild or moderate ARDS, sedated and nonparalyzed, demonstrate RT without breath stacking on the first day of mechanical ventilation. RT may be associated with low VTS and opiate doses. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02732041; URL: www.clinicaltrials.gov.

Renal length and volume prediction in healthy children.

INTRODUCTION: Little information is available regarding the evaluation of renal volume in healthy Latin-American children of different ages. The objective of this work was to establish a predictive model of renal size (volume and length) and develop a web-based calculator. MATERIALS AND METHODS: A selective and representative sample was obtained randomly from the database of healthy children living in Resistencia city, Chaco, Argentina: a) the National Health Program for children under 6 years old; b) school children until 18 years old (primary and middle education). Renal dimensions were obtained by ultrasonography via a single experienced operator at the indicated site (schools or primary health care centers). Renal volume was calculated using Dinkel's formula. A multiple linear regression model was applied using potential predictors. The final model was implemented in a free web-based application. RESULTS: Random selection was made from the database to include 882 subjects with ages between 0.03 and 230.63 months. The data was divided into two sets (one for training and the other for model testing). The training set (423) included 212 (50%) females. Significant predictors included age, height, current weight and birth weight, and the interaction between age and present weight. Using the test dataset, both renal volume and length root mean square errors were 5.06 cm3 and 0.59 cm. CONCLUSION: The prediction model was accurate and allowed for the development a freely-available web app: Renal size prediction (https://porbm28.shinyapps.io/RenalVolume/). Once the models are validated by additional studies, the app could be a useful tool to predict renal volume and length in pediatric clinical practice.

Automatic detection of reverse-triggering related asynchronies during mechanical ventilation in ARDS patients using flow and pressure signals.

Asynchrony due to reverse-triggering (RT) may appear in ARDS patients. The objective of this study is to validate an algorithm developed to detect these alterations in patient-ventilator interaction. We developed an algorithm that uses flow and airway pressure signals to classify breaths as normal, RT with or without breath stacking (BS) and patient initiated double-triggering (DT). The diagnostic performance of the algorithm was validated using two datasets of breaths, that are classified as stated above. The first dataset classification was based on visual inspection of esophageal pressure (Pes) signal from 699 breaths recorded from 11 ARDS patients. The other classification was obtained by vote of a group of 7 experts (2 physicians and 5 respiratory therapists, who were trained in ICU), who evaluated 1881 breaths gathered from recordings from 99 subjects. Experts used airway pressure and flow signals for breaths classification. The RT with or without BS represented 19% and 37% of breaths in Pes dataset while their frequency in the expert's dataset were 3% and 12%, respectively. The DT was very infrequent in both datasets. Algorithm classification accuracy was 0.92 (95% CI 0.89-0.94, P < 0.001) and 0.96 (95% CI 0.95-0.97, P < 0.001), in comparison with Pes and experts' opinion. Kappa statistics were 0.86 and 0.84, respectively. The algorithm precision, sensitivity and specificity for individual asynchronies were excellent. The algorithm yields an excellent accuracy for detecting clinically relevant asynchronies related to RT.

Effect of PEEP on Dead Space in an Experimental Model of ARDS.

BACKGROUND: The difference between Bohr and Enghoff dead space are not well described in ARDS patients. We aimed to analyze the effect of PEEP on the Bohr and Enghoff dead spaces in a model of ARDS. METHODS: 10 pigs submitted to randomized PEEP steps of 0, 5, 10, 15, 20, 25 and 30 cm H2O were evaluated with the use of lung ultrasound images, alveolar-arterial oxygen difference (P(A-a)O2 ), transpulmonary mechanics, and volumetric capnography at each PEEP step. RESULTS: At PEEP ≥ 15 cm H2O, atelectasis and P(A-a)O2 progressively decreased while end-inspiratory transpulmonary pressure (PL), end-expiratory PL, and driving PL increased (all P < .001). Bohr dead space (VDBohr /VT), airway dead space (VDaw /VT), and alveolar dead space (VDalv /VTalv ) reached their highest values at PEEP 30 cm H2O (0.69 ± 0.10, 0.53 ± 0.13 and 0.35 ± 0.06, respectively). At PEEP <15 cm H2O, the increases in atelectasis and P(A-a)O2 were associated with negative end-expiratory PL and highest driving PL. VDBohr /VT and VDaw /VT showed the lowest values at PEEP 0 cm H2O (0.51 ± 0.08 and 0.32 ± 0.08, respectively), whereas VDalv /VTalv increased to 0.27 ± 0.05. Enghoff dead space and its derived VDalv /VTalv showed high values at low PEEPs (0.86 ± 0.02 and 0.79 ± 0.04, respectively) and at high PEEPs (0.84 ± 0.04 and 0.65 ± 0.12), with the lowest values at 15 cm H2O (0.77 ± 0.05 and 0.61 ± 0.11, respectively; all P < .001). CONCLUSIONS: Bohr dead space was associated with lung stress, whereas Enghoff dead space was partially affected by the shunt effect.

Gas exchange and lung mechanics in patients with acute respiratory distress syndrome: comparison of three different strategies of positive end expiratory pressure selection.

PURPOSE: The purpose of the study was to compare gas exchange and lung mechanics between different strategies to select positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS). METHODS: In 20 consecutive ARDS patients, 3 PEEP selection strategies were evaluated. One strategy was based on oxygenation using the ARDS network PEEP/fraction of inspired oxygen (Fio2) table; and two were based on lung mechanics, either PEEP titrated to reach a plateau pressure of 28 to 30 cm H2O as in the ExPress trial or best respiratory compliance method during a derecruitment maneuver. Gas exchange, airway pressures, stress index (SI), and end-expiratory transpulmonary pressure (P(tpe)) and end-inspiratory transpulmonary pressure (P(tpi)) values were assessed. Data are expressed as median (interquartile range [IQR]). RESULTS: Lower total PEEP levels were observed with the use of the PEEP/Fio2 table (8.7 [6-10] cm H2O); intermediate PEEP levels, with the Best Compliance approach (13.0 [10.2-13.8] cm H2O); and higher PEEP levels, with the ExPress strategy (16.5 [15.0-18.5] cm H2O) (P < .01). Pao2/Fio2 ratio was lower with the PEEP/Fio2 table. Oxygenation with Best Compliance approach and ExPress strategy was not different with lower plateau pressure in the former (23 [20-25] vs 30 [29-30] cm H2O; P < .01). Paco2 was slightly higher with the ExPress method than the others 2 strategies. Negative P(tpe) was observed in 35% of the patients with the PEEP/Fio2 table, in 15% applying the Best Compliance, and in only 1 case with the ExPress method. Higher SI and P(tpi), with lower lung compliance, were obtained with ExPress strategy. CONCLUSIONS: Using a best respiratory compliance approach resulted in better oxygenation levels without risk of overdistension according to SI and P(tpi), achieving a mild risk of lung collapse according to P(tpe).

Transpulmonary pressure and gas exchange during decremental PEEP titration in pulmonary ARDS patients.

BACKGROUND: Selection of the PEEP associated with the best compliance of the respiratory system during decremental PEEP titration can be used for the treatment of patients suffering from ARDS. We describe changes in transpulmonary pressure (Ptp) and gas exchange during a decremental PEEP titration maneuver in subjects with pulmonary ARDS. METHODS: Eleven subjects with early ARDS were included. After a recruitment maneuver they were ventilated in volume-controlled ventilation and PEEP was decreased from 30 to 0 cm H2O by steps of 3 cm H2O. Static airway pressure (Paw), esophageal pressure (Pes), Ptp (Paw - Pes), the ratio of dead space to tidal volume (VD/VT), and PaO2 were recorded at each step. RESULTS: A linear correlation was found between Paw and Ptp. Expiratory Ptp became negative in all subjects when PEEP decreased below 8.9 ± 5.2 cm H2O. VD/VT was 0.67 ± 0.06 with 30 cm H2O of PEEP, and decreased 15.4 ± 8.5% during the maneuver, when PEEP and expiratory Ptp were 10.6 ± 4.1 cm H2O and 1.2 ± 2.8 cm H2O, respectively. VD/VT was significantly higher during ventilation at high (> 18 cm H2O), compared to low, inspiratory Ptp values (P < .001). PaO2 decreased when expiratory Ptp became negative (P < .001). CONCLUSIONS: During decremental PEEP titration we sequentially observed high inspiratory Ptp that stressed lung tissue and increased VD/VT, and negative Ptp, indicating high risk of alveolar collapse, explaining worse oxygenation. PEEP selection based on Ptp and VD/VT in ARDS may help to avoid these situations.

Muscle weakness in septic patients requiring mechanical ventilation: protective effect of transcutaneous neuromuscular electrical stimulation.

PURPOSE: The aim of this study was to evaluate the effect of transcutaneous neuromuscular electrical stimulation (NMES) on muscle strength in septic patients requiring mechanical ventilation (MV). METHODS: Sixteen septic patients requiring MV and having 1 or more organ failure other than respiratory dysfunction were enrolled within 48 hours from admission to the intensive care unit. Neuromuscular electrical stimulation was administered twice a day on brachial biceps and vastus medialis (quadriceps) of 1 side of the body until MV withdrawal. Blinded investigators measured arm and thigh circumferences, biceps thickness by ultrasonography, and muscle strength after awakening with Medical Research Council scale. RESULTS: Two patients died before strength evaluation and were excluded from the analysis. Neuromuscular electrical stimulation was applied for 13 days (interquartile range, 7-30 days). Biceps (P = .005) and quadriceps (P = .034) strengths were significantly higher on the stimulated side at the last day of NMES. Improvement was mainly observed in more severe and weaker patients. Circumference of the nonstimulated arm decreased at the last day of NMES (P = .015), whereas no other significant differences in limb circumferences or biceps thickness were observed. CONCLUSION: Neuromuscular electrical stimulation was associated with an increase in strength of the stimulated muscle in septic patients requiring MV. Neuromuscular electrical stimulation may be useful to prevent muscle weakness in this population.