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

Variação estacional dos hormônios tireoideanos e do cortisol em ovinos em ambiente tropical

Foram estudadas as variações nas concentrações de cortisol e dos hormônios da tireóide de ovinos da raça Corriedale criados em ambiente tropical. Vinte e um ovinos (14 machos e sete fêmeas) foram mantidos em uma câmara climática à 45ºC por nove dias, 8 horas por dia. Registraram-se a temperatura retal (TR) e a frequência respiratória (FR) dos animais, a temperatura ambiente (TA) e a pressão parcial de vapor (PV). Os animais foram posteriormente classificados de acordo com suas respostas quanto à TR e à FR, selecionando-se cinco animais mais aclimatados (grupo A) e cinco animais menos aclimatados (grupo NA) às altas temperaturas do ar. Esses dez animais foram transferidos para um cercado, onde foram registradas a TR e FR duas vezes ao dia e coletadas as amostras sanguíneas uma vez por semana, durante um ano. Foram observadas diferenças nas concentrações de cortisol, de tiroxina (T4) e de triiodotironina (T3), atribuídas às variações na TA e na PV. Ocorreram maiores concentrações de cortisol e menores de T4 e de T3 nos períodos de maior TA e/ou PV, sendo que as estimativas dos coeficientes de correlação (r) das variáveis TA e PV com o cortisol foram r = 0,224 e r = 0,395, respectivamente. As correlações entre os hormônios tireoideanos e a TA foram negativas (r = -0,156, para T4, e r = -0,151, para T3), evidenciando que um aumento na TA causou redução na taxa metabólica. As variáveis medidas não diferiram entre os grupos de animais classificados. Portanto, a utilização apenas das variáveis fisiológicas TR e FR como parâmetros para a seleção não é suficiente para se avaliar o grau de aclimatação dos animais ao ambiente tropical.The variation of cortisol and thyroid hormones in Corriedale sheep bred in a tropical environment was evaluated. Fourteen males and seven females were observed in a climatic chamber at 45ºC for nine days, eight hours per day. Rectal temperature (TR), respiratory rate (FR), air temperature (TA) and air humidity (PV) were recorded. The animals were ranked according to their responses for TR and FR and then the five highest (A group) and five lowest (NA group) ranked animals were selected. These ten animals were moved to a pen where they were observed along one year for TR and FR two times a day, and blood-sampled once a week. The results showed differences for T3, T4, and cortisol concentrations, which were attributed to variations in TA and PV. Cortisol concentrations were higher and T3 and T4 ones were lower under increased TA and PV. Correlations of TA and PV with cortisol values were r = .224 and r = .395 respectively. The negative correlations of TA with T3 (r = -.151) and T4 (r = -.156) showed that increase in TA may be followed by decrease in the metabolic rate. No significant difference for all variables investigated was found between the two groups, thus it is not recommended the use of TR and FR as the only criteria to evaluate sheep performance in tropical environments

Análise de algumas variáveis fisiológicas para avaliação do grau de adaptação de ovinos submetidos ao estresse por calor Analysis of some physiological variables for the evaluation of the degree of adaptation in sheep submitted to heat stress

Investigaram-se a temperatura retal, a freqüência respiratória e a taxa de evaporação total de ovinos Corriedale sob três temperaturas ambientes, visando uma melhor compreensão dos mecanismos de termorregulação desses animais. Inicialmente, 21 animais adultos foram alojados em câmara climática à temperatura de 45ºC, e pressão parcial de vapor (PV) variável, registrando-se a freqüência respiratória (FR) e a temperatura retal (TR). Baseando-se na FR e TR, foram selecionados 10 animais, cinco com os valores mais baixos, assumindo-os como mais adaptados ao calor (grupo 1) e cinco com valores mais altos, assumindo-os como menos adaptados (grupo 2). Os animais selecionados foram mantidos em câmara climática, onde mediram-se novamente TR, FR e taxa de evaporacão total (TET), sob 20, 30 e 40&ordm;C de temperatura do ar e PV variável. Não houve diferença estatística entre os grupos classificados, para todas as variáveis medidas. Concluiu-se que a utilização das variáveis fisiológicas TR e FR como parâmetros únicos para a seleção destes animais não é suficiente para avaliar o grau de adaptação a temperaturas elevadas.<br>It was investigated the rectal temperature, respiratory frequency and total evaporative heat loss rate in Corriedale sheep under three air temperatures, aiming a better comprehension of thermoregulation mechanisms of these animals. Initially, 21 adult animals were housed in climatic chamber under 45&ordm;C and variable air humidity (PV), recording the respiratory frequency (FR) and rectal temperature (TR). Basing on the FR and TR, it was selected 10 animals, five of the lowest values, assuming as being the best heat adapted (group 1) and five of the highest values, assuming as the worst heat adapted (group 2). The selected animals were maintained in climatic chamber, where it was measured again TR, FR and total evaporation rate (TET), under 20, 30 and 40&ordm;C of air temperature and variable PV. There was no statistical difference between the classified groups, for all the measured variables. In conclusion, the use of the physiological variables TR and FR as mainly parameters for these animals selection, is not enough for evaluate the level of adaptation under high temperatures

Avaliação das respostas fisiológicas de bezerros zebuínos puros e cruzados nascidos em clima subtropical Evaluation of physiological responses of straightbred and crossbred Zebu calves born in a subtropical environment

Estudou-se a influência de fatores climáticos sobre as respostas fisiológicas de bezerros, puros e cruzados, filhos de vacas da raça Nelore ou de alta mestiçagem de Nelore acasaladas com touros das raças Aberdeen Angus (AN), Simental (SN), Canchim (CN) e Nelore (NI e NR). Os bezerros AN, SN, CN e NI foram mantidos em sistema rotacionado intensivo, enquanto o grupo NR foi mantido em sistema extensivo. Os bezerros foram observados de forma direta desde o nascimento até a primeira mamada, medindo-se a latência para a primeira mamada (LM). Aproximadamente 24 horas após o parto, coletaram-se amostras de sangue do bezerro para as dosagens de proteína total (PT), glicose (Gli), triiodotironina (T3), tiroxina (T4), relação T4:T3, cortisol (Cort) e imunoglobulina G (IgGb), além das medidas de temperatura retal do bezerro (TR) e dos pesos de vacas e bezerros. Para análise dos efeitos de clima, foram tomadas no dia do nascimento as medidas de temperatura do ar (Temp), umidade do ar (UR) e precipitação (PRE). Os parâmetros fisiológicos foram estudados pelo método dos quadrados mínimos com modelos que incluíram os efeitos de ano e mês de nascimento, grupo e sexo do bezerro, categoria da vaca e hora do parto e das interações ano &times; grupo e ano &times; mês de nascimento, além das covariáveis peso do bezerro, PRE, Temp, UR e LM. Temp mostrou efeito significativo para as concentrações de T3, T4, T4:T3 e de Cort. Quanto maior Temp, menores as concentrações de T3 e de Cort e maiores as de T4 e de T4:T3. LM influenciou os níveis de Cort, PT e IgGb, de modo que, quanto maior LM, maior a concentração de Cort e menor as de IgGb e PT. Também houve efeito significativo de grupo do bezerro sobre PT, que foi maior nos bezerros NR que nos bezerros NI.<br>The influence of environmental parameters on the physiological responses of purebred and crossbred Nellore calves born in a subtropical region was studied. All calves were born from high grade Nellore cows sired by Aberdeen Angus (AN), Simmental (SN), Canchim (CN) and Nellore (NI) bulls. These calves were raised under intensive management and another group of Nellore calves (NR) was raised under extensive management, similar to the typical brazilian system for beef production. Calves were observed from birth until the end of the first suckling, and the variable first suckling latency (LM) was estimated. Aapproximately 24 hours after birth, blood samples were collected from each calf to measure the plasma concentrations of total protein (PT), glucose (Gli), triiodothyronin (T3), thyroxin (T4), T3:T4 ratio, cortisol (Cort) and immunoglobulin-G (IgGb). At the same time, the calves' rectal temperature was taken and the cows and the calves were weighed. Climatic data of temperature (Temp), relative humidity (UR) and rain precipitation (PRE) in the birth day were also recorded. Physiological parameters were analyzed by least squares method using a model that included the effects of year and month of calving, group of calf, sex of calf, cow category, calving time, year &times; group and year &times; month of birth interactions and the covariables calf's weight, PRE, Temp, UR and LM. The effect of Temp was significant for the concentrations of T3, T4, T4:T3 and Cort. The concentrations of T3 and Cort decreased and the levels of T4 and T4:T3 ratio increased as Temp increased. Similarly, the concentration of Cort increased and the concentrations of IgGb and PT decreased as LM increased. PT level was significantly higher in NR calves than in NI ones

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