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

Colistina parenteral no tratamento de infeccoes graves: experiencia em centro unico

Objetivo: Descrever a experiência de um único centro com o uso de colistina para tratar infecções hospitalares causadas por bactérias Gram-negativas resistentes a múltiplos fármacos e identificar fatores associados com lesão renal aguda e mortalidade. Métodos: Estudo longitudinal retrospectivo que avaliou pacientes gravemente enfermos, com infecções causadas por bactérias Gram-negativas resistentes a múltiplos fármacos. Foram considerados elegíveis para este estudo, durante o período compreendido entre janeiro e dezembro de 2008, todos os pacientes adultos com necessidade de tratamento com colistina endovenosa (colistimetato de sódio). As informações coletadas incluem dados demográficos, diagnóstico, duração do tratamento, presença de lesão renal aguda e mortalidade em 30 dias. Resultados: A colistina foi utilizada para tratar uma infecção em 109 de 789 pacientes (13,8%) admitidos à unidade de terapia intensiva. A mortalidade em 30 dias observada nestes pacientes foi de 71,6%. Vinte e nove pacientes (26,6%) tinham lesão renal prévia ao tratamento com colistina, sendo que seis deles conseguiram recuperar a função renal, mesmo durante o tratamento com colistina. Vinte e um pacientes (19,2%) desenvolveram lesão renal aguda durante o tratamento com colistina, sendo que 11 destes pacientes necessitaram ser submetidos à diálise. A variável independentemente associada com a presença de lesão renal aguda foi a pontuação segundo o sistema Sequential Organ Failure Assessment no início do tratamento com colistina (OR=1,46; IC95%=1,20-1,79; p<0,001). Idade (OR=1,03; IC95%=1,00-1,05; p=0,02) e uso de vasopressores (OR=12,48; IC95%=4,49-34,70; p<0,001) foram fatores associados a óbito, segundo um modelo de regressão logística. Conclusões: Disfunção de órgão quando do início do tratamento com colistina associou-se com lesão renal aguda. Em um pequeno grupo de pacientes, pudemos observar uma melhora da função renal durante o tratamento com colistina. Idade e uso de vasopressores associaram-se a óbito

Study flowchart.

<p>Study flowchart.</p

Main characteristics according to the type of hospital.

<p>APACHE–Acute Physiological and Chronic Health Evaluation, SOFA–Sequential Organ Failure Assessment, ICU–intensive care unit, CVP–central venous pressure, ScvO–central venous oxygen saturation, OR–odds ratio, CI–confidence interval, NS–non-significant, NA–not applicable, significant variable in the univariate analysis but not included in the multivariate analysis due to missing data. The results are expressed as a number (%) or median (25%–75%). *Total number of patient variables according to the bundle evaluated [(fluid resuscitation (n = 243), vasopressors (n = 198), CVP and Scv0? (n = 197)]. ** only those not in previous antibiotics use or in whom the previous antibiotics was changed. (public: n = 115, public: n = 187).*** Approximately currency: 1R = 1.8 US. Chi-squared and Mann Whitney tests (univariate). Diagnosis within one hour was included in the multivariate analysis. Multivariate analysis with stepwise forward regression, reference: private hospitals. Hosmer-Lemeshow test p = 0.41.</p

Risk factors for hospital mortality (global analysis).

<p>APACHE–Acute Physiological and Chronic Health Evaluation, SOFA–Sequential Organ Failure Assessment, ICU–intensive care unit, CVP–central venous pressure, ScvO–central venous oxygen saturation, OR–odds ratio, CI–confidence interval, NS–non-significant, NA–not applicable, significant variable in the univariate analysis but not included in the multivariate analysis due to missing data. The results are expressed as a number (%) or median (25%–75%). *Total number of patient variables according to the bundle evaluated [(fluid resuscitation (n = 243), vasopressors (n = 198), CVP and Scv0? (n = 197)]. ** only those not in previous antibiotics use or in whom the previous antibiotics was changed. (public: n = 115, public: n = 187).*** Approximately currency: 1R = 1.8 US. Chi-squared and Mann Whitney tests (univariate). Multivariate analysis with stepwise forward regression, reference: non-survivors. Hosmer-Lemeshow test p = 0.19.</p

Risk factors for hospital mortality according to the type of institution.

<p>APACHE–Acute Physiological and Chronic Health Evaluation, SOFA–Sequential Organ Failure Assessment, ICU–intensive care unit, CVP–central venous pressure, ScvO–central venous oxygen saturation, OR–odds ratio, CI–confidence interval, NS–non-significant, NA–not applicable, significant variable in the univariate analysis but not included in the multivariate analysis due to missing data. The results are expressed as a number (%) or median (25%–75%).* Total number of patients variable according to the bundle. **Multivariate analysis with stepwise forward regression, reference: non-survivors. ** only those not in previous antibiotics use or in whom the previous antibiotics was changed. (public: n = 115, public: n = 187).*** Approximately currency: 1R = 1.8 US. Hosmer-Lemeshow for public hospitals p = 0.93, private hospitals p = 0.26.</p

Comparison of propensity scores for patients from public and private hospitals within each propensity score quintile.

<p>The groups are comparable because there is sufficient overlap in the propensity score within each block.</p

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