Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): study protocol for a randomized controlled trial

BACKGROUND: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). METHODS/DESIGN: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH2O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure 6430 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. DISCUSSION: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration metho

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

O efeito de um programa de exercício físico aeróbio combinado com exercícios de resistência muscular localizada na melhora da circulação sistêmica e local: um estudo de caso El efecto de un programa de ejercício físico aeróbico combinado con los ejercicios de resistencia muscular localizada en la mejora de la circulacion sistemica y local. Estudio de un caso The effect of a program of combined aerobic physical exercise with exercises of localized muscular resistance in the improvement of systemic and local circulation: a case study

INTRODUÇÃO: A trombofilia, estado que predispõe à ocorrência de trombose, decorre da existência de alterações da hemostasia, podendo ser congênita ou adquirida. A deficiência de proteína S, que ocorre pela falta do co-fator para a proteína C, é uma alteração congênita que pode resultar em trombofilia. A reabilitação física, considerada uma terapêutica eficaz, tem seu papel definido na prevenção e tratamento de doenças cardiovasculares. OBJETIVO: Este estudo se propôs a verificar a influência do exercício físico aeróbio associado aos exercícios de resistência muscular localizada na circulação sistêmica e colateral do membro superior e inferior direito e na redução das conseqüências causadas pelas retrações decorrentes das cirurgias. MATERIAL E MÉTODO: A amostra foi composta por uma paciente do sexo feminino, 19 anos, portadora da síndrome de hipercoagulabilidade (trombofilia) congênita por deficiência da proteína S, com obstrução total na artéria axilar direita e parcial na artéria femoral superficial direita. O programa de exercícios foi dividido em duas fases. Fase I: Atividades para aumento da amplitude de movimentos, em que se realizavam aplicação de calor, alongamentos passivos manuais mantidos, drenagem linfática e manipulações Effleurage. Fase II: Constituída de exercício aeróbio (45 minutos de caminhada, três vezes por semana, intensidade de 60% a 85% da freqüência cardíaca máxima) e exercícios de resistência muscular localizada (contrações dinâmicas, três séries com o máximo de repetições possíveis, baixa intensidade, favorecendo fatores aeróbios). RESULTADOS: 1. Melhora da circulação colateral à artéria axilar, constatada pelo aumento na velocidade de pulso sistólico (verificado através do exame doppler pulsado) - na artéria radial, passou de 3,4cm/s para 16,8cm/s; na artéria braquial, de 8,7cm/s para 45,9cm/s. 2. Melhor tolerância ao exercício aeróbio. 3. Recuperação da capacidade funcional e amplitude de movimento do ombro. 4. Recuperação plena da autonomia para as atividades diárias. CONCLUSÕES: Os resultados obtidos demonstraram que a terapêutica adotada foi eficaz no tratamento dos transtornos provocados pela trombofilia.<br>INTRODUCIÓN: La trombofilia resulta de la existencia de alteraciones de la hemóstasis, pudiendo ser congénita o adquirida. La deficiencia de proteína S ocurre por la falta del cofactor para la proteína C, y una alteración congénita que puede resultar en trombofilia. La reabilitación física, considerada una terapéutica eficaz, tiene su papel definido en la prevención y el tratamiento de enfermedades cardiovasculares. OBJETIVO: En este estudio se propuso verificar la influencia del ejercicio físico aeróbico asociado a los ejercicios de resistencia muscular localizada en la circulación sistémica y colateral del miembro superior e inferior derecho y en la redución de las consecuencias causadas por las retraciones resultantes de las cirugias. MATERIAL Y MÉTODO: La muestra fué compuesta por una paciente de sexo femenino, de 19 años, portadora del síndrome de hipercoagulabilidad (trombofilia) congénita por deficiencia de proteína S, con obstrucción total de la arteria axilar derecha y parcial de la arteria femoral superficial derecha. El programa de ejercicios fué dividido en dos fases. Fase I: Actividades para el aumento de la amplitud de movimientos, realizada mediante la aplicación de calor, elongamientos pasivos manuales mantenidos, drenage linfático y manipulaciones Effleurage. Fase II: Constituída de ejercicio aeróbico (45 minutos de caminata, 3 veces por semana, intensidad de 60% a 85% de la frecuencia cardíaca máxima), y ejercicios de resistencia muscular localizada (contraciones dinámicas, tres series con el máximo de repeticiones posibles, baja intensidad, favoreciendo factores aeróbicos). RESULTADOS: 1. Mejora de la circulación colateral de la arteria axilar, constatada por el aumento de la velocidad de pulso sistólico (verificado a través del examen doppler pulsado) - en la arteria radial paso de 3,4 cm/s a 16,8 cm/s; en la arteria braquial, de 8,7cm/s a 45,9 cm/s. 2. Mejor tolerancia al ejercicio aeróbico. 3. Recuperación de la capacidad funcional y amplitud del movimiento del hombro. 4. Recuperación plena de la autonomía para las actividades diárias. CONCLUSIONES: Los resultados obtenidos demostraron que la terapéutica adoptada fué eficaz en el tratamiento de los transtornos provocados por la trombofilia.<br>INTRODUCTION: Thrombophilia, elapses the existence of alterations of the hemostasis, being congenital or to be acquired. The protein S deficiency, occurs for the lack of the cofactor for protein C, is a congenital alteration that can result in thrombophilia. Physical rehabilitation, an efficient therapeutic option, has its paper defined in the prevention and treatment of cardiovascular illnesses. OBJECTIVE: This study aimed to verify the influence of the associated aerobic physical exercise to the exercises of muscular resistance in the systemic and collateral circulation of the right upper/lower member and in the reduction of the consequences caused for the decurrent retractions of the surgeries. MATERIAL AND METHOD: The sample, composed by a patient of the feminine sex, 19 years, carrier of the syndrome of congenital thrombophilia because of protein S deficiency, with total obstruction of the right axillary artery and partial obstruction of the right superficial femoral artery. The program of exercises were divided in two phases. Phase I: Activities for increase of the amplitude of movements, became fulfilled kept application of heat, manual passive stretching, lymphatic draining and Effleurage manipulations. Phase II: Constituted of aerobic exercise (45 minutes of walked, 3 times per week, intensity of 60% 85% of the maximum cardiac frequency), and exercises of located muscular resistance (dynamic contractions, three series with the maximum of possible repetitions, low intensity, favoring aerobic factors). RESULT: 1. Improvement of the collateral circulation to the axillary artery, evidenced for the increase in the speed of systolic pulse (verified by pulsed Doppler examination) - in the radial artery passed of 3.4 cm/s for 16.8 cm/s; in the brachial artery, of 8.7 cm/s for 45.9 cm/s. 2. Better tolerance to the aerobic exercise. 3. Recovery of the functional capacity and amplitude of movement of shoulder. 4. Full recovery of the autonomy for the daily activities. CONCLUSIONS: The gotten results had demonstrated that the adopted therapy was efficient in the treatment of thrombophilia consequences

Effect of lung recruitment and titrated Positive End-Expiratory Pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome - A randomized clinical trial

IMPORTANCE: The effects of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remain uncertain. OBJECTIVE: To determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017, enrolling adults with moderate to severe ARDS. INTERVENTIONS: An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory-system compliance (n = 501; experimental group) or a control strategy of low PEEP (n = 509). All patients received volume-assist control mode until weaning. MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stay; ventilator-free days through day 28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU, in-hospital, and 6-month mortality. RESULTS: A total of 1010 patients (37.5% female; mean [SD] age, 50.9 [17.4] years) were enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group and 251 of 509 patients (49.3%) in the control group had died (hazard ratio [HR], 1.20; 95% CI, 1.01 to 1.42; P = .041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%; HR, 1.18; 95% CI, 1.01 to 1.38; P = .04), decreased the number of mean ventilator-free days (5.3 vs 6.4; difference, −1.1; 95% CI, −2.1 to −0.1; P = .03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%; difference, 2.0%; 95% CI, 0.0% to 4.0%; P = .03), and the risk of barotrauma (5.6% vs 1.6%; difference, 4.0%; 95% CI, 1.5% to 6.5%; P = .001). There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality. CONCLUSIONS AND RELEVANCE: In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01374022

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.13Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt