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

Study of the incidence of acute lung injury and acute respiratory distress syndrome in the intensive care units in the region of Vitória in Espírito Santo

INTRODUÇÃO: Existem muitas controvérsias, nos estudos epidemiológicos existentes, a respeito da incidência e desfechos da síndrome de lesão pulmonar aguda. A incidência e as características clínicas da síndrome dependem principalmente da definição utilizada e da metodologia empregada no estudo, bem como da disponibilização e utilização dos leitos nas unidades de terapia intensiva da região estudada. Pela ausência de dados epidemiológicos existentes de lesão pulmonar aguda na Grande Vitória, no Espírito Santo, realizamos este estudo para analisar a incidência, características, sobrevida aos 28 dias e mortalidade hospitalar. MÉTODOS: Os pacientes internados nas 14 unidades de terapia intensiva da Grande Vitória, durante o período de 15 meses, submetidos à ventilação mecânica e que preencheram os critérios de lesão pulmonar aguda da Conferência de Consenso Européia-Americana de 1994 foram selecionados prospectivamente para o estudo. Os pacientes também foram classificados de acordo com a nova definição de Berlim. Avaliamos as características clínicas e funcionais no primeiro dia de internação, durante a primeira semana, no 14º dia e no 28º dia de evolução. Foram calculadas a incidência da síndrome acumulada/ano, a sobrevida aos 28 dias e a mortalidade hospitalar. RESULTADOS: Foram avaliados 7.133 pacientes admitidos nas unidades de terapia intensiva, dos quais 130 (1,8%) foram selecionados. A mediana de tempo para o diagnóstico de lesão pulmonar aguda foi de 2 dias (IQ: 0-3 dias), sendo 25,4% dos diagnósticos realizados no momento da internação na unidade de terapia intensiva. Os fatores de risco foram principalmente pneumonia (35,3%), sepse não pulmonar (31,5%) e trauma (16,9%). A média de idade dos pacientes foi de 44,2 ± 15,9 anos, sendo 61,5% do sexo masculino. A média do APACHE II foi de 20,7 ± 7,9 e a média da PaO2/FiO2, de 206,7 ± 61,6. O tempo médio em ventilação mecânica foi de 21 ± 15 dias e o tempo médio de permanência na unidade de terapia intensiva foi de 26,4 ± 18,7 dias. De acordo com a nova definição de Berlim, os pacientes com a síndrome de desconforto respiratório agudo foram classificados em: leve, com 49 casos (37,7%); moderada, com 68(52,3%); e grave, com 13(10%). A incidência acumulada de LPA foi de 10,1 casos/100.000 habitantes/ano, sendo 3,8 casos/100.000 habitantes/ano para LPA sem SDRA e 6,3 casos/100.000 habitantes/ano para SDRA, representando 1,7% das admissões no ano. A relação PaO2/FiO2 nos dias 6 e 7 de evolução após o diagnóstico da síndrome foi um fator preditor independente para a mortalidade aos 28 dias, que foi de 38,5% (95% IC, 30,1-46,8). A mortalidade intrahospitalar foi de 49,2% (95% IC, 40,6-57,8), não diferindo entre os pacientes com LPA sem SDRA e SDRA. CONCLUSÕES: A incidência de LPA nos pacientes submetidos à ventilação mecânica invasiva na região da Grande Vitória, Espírito Santo, foi baixa, sendo a maioria dos casos diagnosticada 2 dias após a admissão nas unidades de terapia intensiva. A mortalidade aos 28 dias e a hospitalar dos pacientes com LPA sem SDRA e com SDRA não foram estatisticamente diferentes neste estudo. As mudanças nas práticas assistenciais nas unidades de terapia intensiva poderão contribuir para a redução da incidência da SDRA intrahospitalarINTRODUCTION: There are many controversies in the existing epidemiological studies regarding the incidence and outcomes in acute lung injury. The incidence and clinical features of the syndrome mainly depend on the definition adopted and on the methodology employed in the study, as well as on the availability and use of beds in intensive therapy units in the regions studied. Due to the absence of existing epidemiological data concerning acute lung injury in Vitória, Espírito Santo, we conducted this study to analyze the incidence, clinical characteristics, survival rate at 28 days, and mortality rate. METHODS: The patients hospitalized in the 14 units of intensive therapy in the region of Grande Vitória for the period of 15 months submitted to mechanical ventilation, who fulfilled the criteria of acute lung injury as defined by the Conference of European-American Consensus of 1994, were prospectively selected for the study. These patients were also classified according to the new Berlin definition. We evaluated the clinical and functional characteristics on the first day of hospitalization, during the first week, on day 14 and on day 28 of clinical evolution. We calculated the cumulative incidence/year for the syndrome, the survival rate at 28 days, and hospital mortality. RESULTS: A total of 7,133 patients admitted to the intensive care units was evaluated, of whom 130 (1.8%) were selected. The median time to diagnosis of acute lung injury was 2 days (IQR: 0-3 days), 25.4% of diagnoses being made at admission to the intensive care unit. The risk factors were mainly pneumonia (35.3%), nonpulmonary sepsis (31.5%) and trauma (16.9%). The patients\' mean age was 44.2 ± 15.9 years, 61.5% being male. The APACHE II prognostic score averaged 20.7 ± 7.9, mean arterial oxygenation variable PaO2/FiO2 206 ± 61.6 and time on mechanical ventilation with a mean of 21 ± 15 days. The average length of stay in intensive care unit was 26.4 ± 18.7 days. Based on the new Berlin definition, patients with acute respiratory distress syndrome were classified as mild: 49 (37.7%); moderate: 68 (52.3%); and severe: 13 (10%). The cumulative incidence was 10.1 cases per 100,000 inhabitants /year for ALI, of which 3.8 cases per 100,000 inhabitants / year were for non-ARDS ALI and 6.3 cases per 100,000 inhabitants / year were for ARDS, representing 1.7% of admissions in the year. The variable arterial oxygenation on days 6 and 7 of evolution after the diagnosis of the syndrome was an independent factor for mortality at 28 days, which was 38.5% (95% CI, 30.1 to 46.8). In-hospital mortality was 49.2% (95% CI, 40.6 to 57.8), and did not differ between patients with ALI non-ARDS and acute respiratory distress syndrome Summary (ARDS). CONCLUSIONS: The incidence of acute lung injury in patients undergoing invasive mechanical ventilation in the region of Grande Vitória, Espírito Santo was low, most of them being diagnosed 2 days after admission to intensive care units. Mortality at 28 days and hospital mortality of patients with ALI non-ARDS were not statistically different in this study. Changes in care practices in intensive therapy units can contribute to reduce the incidence of in-hospital ARD

Respiratory evaluation of patients requiring vantilator support due to acute respiratory failure

This review, based on relevant published evidence and the authors’ clinical experience, presents how to evaluate a patient with acute respiratory failure re- quiring ventilatory support. This patient must be care- fully evaluated by nurses, physiotherapists, respira- tory care practitioners and physicians regarding the elucidation of the cause of the acute episode of respi- ratory failure by means of physical examination with the measurement of respiratory parameters and as- sessment of arterial blood gases analysis to make a correct respiratory diagnosis. After the initial evalua- tion, the patient must quickly receive adequate oxy- gen and ventilatory support that has to be carefully monitored until its discontinuation. When available, a noninvasive ventilation trial must be done in patients presenting desaturation during oxygen mask and or PaCO2 retention, especially in cases of cardiogenic pulmonary edema and severe exacerbation of chronic obstructive pulmonary disease. In cases of noninva- sive ventilation trial-failure, endotracheal intubation and invasive protective mechanical ventilation must be promptly initiated. In severe ARDS patients, low tidal ventilation, higher PEEP levels, prone position-ing and recruitment maneuvers with adequate PEEP titration should be used. Recently, new modes of ven- tilation should allow a better patient-ventilator inter- action or synchrony permitting a sufficient unloading of respiratory muscles and increase patient comfort. Patients with chronic obstructive pulmonary disease may be considered for a trial for early extubation to noninvasive positive pressure ventilation in centers with extensive experience in noninvasive positive pres- sure ventilation

Respiratory evaluation of patients requiring vantilator support due to acute respiratory failure

This review, based on relevant published evidence and the authors’ clinical experience, presents how to evaluate a patient with acute respiratory failure re- quiring ventilatory support. This patient must be care- fully evaluated by nurses, physiotherapists, respira- tory care practitioners and physicians regarding the elucidation of the cause of the acute episode of respi- ratory failure by means of physical examination with the measurement of respiratory parameters and as- sessment of arterial blood gases analysis to make a correct respiratory diagnosis. After the initial evalua- tion, the patient must quickly receive adequate oxy- gen and ventilatory support that has to be carefully monitored until its discontinuation. When available, a noninvasive ventilation trial must be done in patients presenting desaturation during oxygen mask and or PaCO2 retention, especially in cases of cardiogenic pulmonary edema and severe exacerbation of chronic obstructive pulmonary disease. In cases of noninva- sive ventilation trial-failure, endotracheal intubation and invasive protective mechanical ventilation must be promptly initiated. In severe ARDS patients, low tidal ventilation, higher PEEP levels, prone position-ing and recruitment maneuvers with adequate PEEP titration should be used. Recently, new modes of ven- tilation should allow a better patient-ventilator inter- action or synchrony permitting a sufficient unloading of respiratory muscles and increase patient comfort. Patients with chronic obstructive pulmonary disease may be considered for a trial for early extubation to noninvasive positive pressure ventilation in centers with extensive experience in noninvasive positive pres- sure ventilation

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 = 501experimental 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 outcomewas all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stayventilator-free days through day 28pneumothorax requiring drainage within 7 daysbarotrauma within 7 daysand ICU, in-hospital, and 6-month mortality. RESULTS A total of 1010 patients (37.5% femalemean [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], 1.2095% CI, 1.01 to 1.42P =.041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%HR, 1.1895% CI, 1.01 to 1.38P =.04), decreased the number of mean ventilator-free days (5.3 vs 6.4difference, -1.195% CI, -2.1 to -0.1P =.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. (C) 2017 American Medical Association. All rights reserved.Brazilian Ministry of HealthBrazilian Ministry of HealthHCor Res Inst, Sao Paulo, BrazilUniv Sao Paulo, Cardiopulmonary Dept, Div Pulm, Heart Inst Incor, Sao Paulo, BrazilHosp Moinhos de Vento, Porto Alegre, RS, BrazilIrmandade Santa Casa Misericordia Porto Alegre, Porto Alegre, RS, BrazilFed Univ Sao Paulo UNIFESP, Anesthesiol Pain & Intens Care Dept, Sao Paulo, BrazilUniv Sao Paulo, Dept Epidemiol, Sch Publ Hlth, Sao Paulo, BrazilHosp Maternidade Sao Vicente Paulo, Barbalha, BrazilHosp Nereu Ramos, Florianopolis, SC, BrazilHosp Unimed Vitoria, Vitoria, BrazilHosp & Prontosocorro 28 Agosto, Manaus, Amazonas, BrazilUniv Sao Paulo, Unidade Emergencia Hosp Clin FMRP, Ribeirao Preto, BrazilHosp Estadual Dr Jayme Santos Neves, Serra, BrazilFundacao Univ Fed Grande Dourados, Univ Hosp, Dourados, BrazilUniv ICESI, Fdn Valle Lili, Dept Intens Care Med, Cali, ColombiaHosp Univ Oeste Parana, Cascavel, BrazilHosp Pablo Tobon Uribe, Medellin, ColombiaHosp Clin Porto Alegre, Porto Alegre, RS, BrazilHosp Reg Hans Dieter Schmidt, Joinville, BrazilUniv Malaya, Med Ctr, Kuala Lumpur, MalaysiaJagiellonian Univ, Med Coll, Dept Intens Care & Perioperat Med, Krakow, PolandHosp Nacl Alejandro Posadas, Moron, ArgentinaFed Univ Sao Paulo UNIFESP, Anesthesiol Pain & Intens Care Dept, Sao Paulo, BrazilWeb of Scienc