Showing papers by "Marcelo B. P. Amato published in 2017"

An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline: Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome

Abstract: Background: This document provides evidence-based clinical practice guidelines on the use of mechanical ventilation in adult patients with acute respiratory distress syndrome (ARDS).Methods: A multidisciplinary panel conducted systematic reviews and metaanalyses of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.Results: For all patients with ARDS, the recommendation is strong for mechanical ventilation using lower tidal volumes (4–8 ml/kg predicted body weight) and lower inspiratory pressures (plateau pressure < 30 cm H2O) (moderate confidence in effect estimates). For patients with severe ARDS, the recommendation is strong for prone positioning for more than 12 h/d (moderate confidence in effect estimates). For patients with moderate or severe ARDS, the recommendation is strong against routine use of high-frequency oscillatory ventilation (high confidence in effect estimates) and conditional for higher positiv...

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

Abstract: 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

Chest electrical impedance tomography examination, data analysis, terminology, clinical use and recommendations: consensus statement of the TRanslational EIT developmeNt stuDy group

Abstract: Electrical impedance tomography (EIT) has undergone 30 years of development. Functional chest examinations with this technology are considered clinically relevant, especially for monitoring regional lung ventilation in mechanically ventilated patients and for regional pulmonary function testing in patients with chronic lung diseases. As EIT becomes an established medical technology, it requires consensus examination, nomenclature, data analysis and interpretation schemes. Such consensus is needed to compare, understand and reproduce study findings from and among different research groups, to enable large clinical trials and, ultimately, routine clinical use. Recommendations of how EIT findings can be applied to generate diagnoses and impact clinical decision-making and therapy planning are required. This consensus paper was prepared by an international working group, collaborating on the clinical promotion of EIT called TRanslational EIT developmeNt stuDy group. It addresses the stated needs by providing (1) a new classification of core processes involved in chest EIT examinations and data analysis, (2) focus on clinical applications with structured reviews and outlooks (separately for adult and neonatal/paediatric patients), (3) a structured framework to categorise and understand the relationships among analysis approaches and their clinical roles, (4) consensus, unified terminology with clinical user-friendly definitions and explanations, (5) a review of all major work in thoracic EIT and (6) recommendations for future development (193 pages of online supplements systematically linked with the chief sections of the main document). We expect this information to be useful for clinicians and researchers working with EIT, as well as for industry producers of this technology.

Fifty Years of Research in ARDS. Spontaneous Breathing during Mechanical Ventilation. Risks, Mechanisms, and Management.

Abstract: Spontaneous respiratory effort during mechanical ventilation has long been recognized to improve oxygenation, and because oxygenation is a key management target, such effort may seem beneficial Also, disuse and loss of peripheral muscle and diaphragm function is increasingly recognized, and thus spontaneous breathing may confer additional advantage Reflecting this, epidemiologic data suggest that the use of partial (vs full) support modes of ventilation is increasing Notwithstanding the central place of spontaneous breathing in mechanical ventilation, accumulating evidence indicates that it may cause-or worsen-acute lung injury, especially if acute respiratory distress syndrome is severe and spontaneous effort is vigorous This Perspective reviews the evidence for this phenomenon, explores mechanisms of injury, and provides suggestions for clinical management and future research

Fifty Years of Research in ARDS. Respiratory Mechanics in Acute Respiratory Distress Syndrome.

Abstract: Acute respiratory distress syndrome is a multifactorial lung injury that continues to be associated with high levels of morbidity and mortality. Mechanical ventilation, although lifesaving, is associated with new iatrogenic injury. Current best practice involves the use of small Vt, low plateau and driving pressures, and high levels of positive end-expiratory pressure. Collectively, these interventions are termed “lung-protective ventilation.” Recent investigations suggest that individualized measurements of pulmonary mechanical variables rather than population-based ventilation prescriptions may be used to set the ventilator with the potential to improve outcomes beyond those achieved with standard lung protective ventilation. This review outlines the measurement and application of clinically applicable pulmonary mechanical concepts, such as plateau pressures, driving pressure, transpulmonary pressures, stress index, and measurement of strain. In addition, the concept of the “baby lung” and the utility o...

Volume-controlled Ventilation Does Not Prevent Injurious Inflation during Spontaneous Effort

Abstract: Rationale: Spontaneous breathing during mechanical ventilation increases transpulmonary pressure and Vt, and worsens lung injury. Intuitively, controlling Vt and transpulmonary pressure might limit injury caused by added spontaneous effort.Objectives: To test the hypothesis that, during spontaneous effort in injured lungs, limitation of Vt and transpulmonary pressure by volume-controlled ventilation results in less injurious patterns of inflation.Methods: Dynamic computed tomography was used to determine patterns of regional inflation in rabbits with injured lungs during volume-controlled or pressure-controlled ventilation. Transpulmonary pressure was estimated by using esophageal balloon manometry [Pl(es)] with and without spontaneous effort. Local dependent lung stress was estimated as the swing (inspiratory change) in transpulmonary pressure measured by intrapleural manometry in dependent lung and was compared with the swing in Pl(es). Electrical impedance tomography was performed to evaluate the infla...

Effect of Intensive vs Moderate Alveolar Recruitment Strategies Added to Lung-Protective Ventilation on Postoperative Pulmonary Complications: A Randomized Clinical Trial.

Abstract: Importance Perioperative lung-protective ventilation has been recommended to reduce pulmonary complications after cardiac surgery. The protective role of a small tidal volume (V T ) has been established, whereas the added protection afforded by alveolar recruiting strategies remains controversial. Objective To determine whether an intensive alveolar recruitment strategy could reduce postoperative pulmonary complications, when added to a protective ventilation with small V T . Design, Setting, and Participants Randomized clinical trial of patients with hypoxemia after cardiac surgery at a single ICU in Brazil (December 2011-2014). Interventions Intensive recruitment strategy (n=157) or moderate recruitment strategy (n=163) plus protective ventilation with small V T . Main Outcomes and Measures Severity of postoperative pulmonary complications computed until hospital discharge, analyzed with a common odds ratio (OR) to detect ordinal shift in distribution of pulmonary complication severity score (0-to-5 scale, 0, no complications; 5, death). Prespecified secondary outcomes were length of stay in the ICU and hospital, incidence of barotrauma, and hospital mortality. Results All 320 patients (median age, 62 years; IQR, 56-69 years; 125 women [39%]) completed the trial. The intensive recruitment strategy group had a mean 1.8 (95% CI, 1.7 to 2.0) and a median 1.7 (IQR, 1.0-2.0) pulmonary complications score vs 2.1 (95% CI, 2.0-2.3) and 2.0 (IQR, 1.5-3.0) for the moderate strategy group. Overall, the distribution of primary outcome scores shifted consistently in favor of the intensive strategy, with a common OR for lower scores of 1.86 (95% CI, 1.22 to 2.83; P = .003). The mean hospital stay for the moderate group was 12.4 days vs 10.9 days in the intensive group (absolute difference, −1.5 days; 95% CI, −3.1 to −0.3; P = .04). The mean ICU stay for the moderate group was 4.8 days vs 3.8 days for the intensive group (absolute difference, −1.0 days; 95% CI, −1.6 to −0.2; P = .01). Hospital mortality (2.5% in the intensive group vs 4.9% in the moderate group; absolute difference, −2.4%, 95% CI, −7.1% to 2.2%) and barotrauma incidence (0% in the intensive group vs 0.6% in the moderate group; absolute difference, −0.6%; 95% CI, −1.8% to 0.6%; P = .51) did not differ significantly between groups. Conclusions and Relevance Among patients with hypoxemia after cardiac surgery, the use of an intensive vs a moderate alveolar recruitment strategy resulted in less severe pulmonary complications while in the hospital. Trial Registration clinicaltrials.gov Identifier:NCT01502332

Respiratory support in patients with acute respiratory distress syndrome: an expert opinion.

Abstract: Acute respiratory distress syndrome (ARDS) is a common condition in intensive care unit patients and remains a major concern, with mortality rates of around 30–45% and considerable long-term morbidity. Respiratory support in these patients must be optimized to ensure adequate gas exchange while minimizing the risks of ventilator-induced lung injury. The aim of this expert opinion document is to review the available clinical evidence related to ventilator support and adjuvant therapies in order to provide evidence-based and experience-based clinical recommendations for the management of patients with ARDS.

Transpulmonary Pressure Describes Lung Morphology During Decremental Positive End-Expiratory Pressure Trials in Obesity.

Abstract: Objectives Atelectasis develops in critically ill obese patients when undergoing mechanical ventilation due to increased pleural pressure. The current study aimed to determine the relationship between transpulmonary pressure, lung mechanics, and lung morphology and to quantify the benefits of a decremental positive end-expiratory pressure trial preceded by a recruitment maneuver. Design Prospective, crossover, nonrandomized interventional study. Setting Medical and Surgical Intensive Care Units at Massachusetts General Hospital (Boston, MA) and University Animal Research Laboratory (Sao Paulo, Brazil). Patients/subjects Critically ill obese patients with acute respiratory failure and anesthetized swine. Interventions Clinical data from 16 mechanically ventilated critically ill obese patients were analyzed. An animal model of obesity with reversible atelectasis was developed by placing fluid filled bags on the abdomen to describe changes of lung mechanics, lung morphology, and pulmonary hemodynamics in 10 swine. Measurements and main results In obese patients (body mass index, 48 ± 11 kg/m), 21.7 ± 3.7 cm H2O of positive end-expiratory pressure resulted in the lowest elastance of the respiratory system (18.6 ± 6.1 cm H2O/L) after a recruitment maneuver and decremental positive end-expiratory pressure and corresponded to a positive (2.1 ± 2.2 cm H2O) end-expiratory transpulmonary pressure. Ventilation at lowest elastance positive end-expiratory pressure preceded by a recruitment maneuver restored end-expiratory lung volume (30.4 ± 9.1 mL/kg ideal body weight) and oxygenation (273.4 ± 72.1 mm Hg). In the swine model, lung collapse and intratidal recruitment/derecruitment occurred when the positive end-expiratory transpulmonary pressure decreased below 2-4 cm H2O. After the development of atelectasis, a decremental positive end-expiratory pressure trial preceded by lung recruitment identified the positive end-expiratory pressure level (17.4 ± 2.1 cm H2O) needed to restore poorly and nonaerated lung tissue, reestablishing lung elastance and oxygenation while avoiding increased pulmonary vascular resistance. Conclusions In obesity, low-to-negative values of transpulmonary pressure predict lung collapse and intratidal recruitment/derecruitment. A decremental positive end-expiratory pressure trial preceded by a recruitment maneuver reverses atelectasis, improves lung mechanics, distribution of ventilation and oxygenation, and does not increase pulmonary vascular resistance.

Applying Precision Medicine to Trial Design Using Physiology. Extracorporeal CO2 Removal for Acute Respiratory Distress Syndrome

Abstract: In clinical trials of therapies for acute respiratory distress syndrome (ARDS), the average treatment effect in the study population may be attenuated because individual patient responses vary widely. This inflates sample size requirements and increases the cost and difficulty of conducting successful clinical trials. One solution is to enrich the study population with patients most likely to benefit, based on predicted patient response to treatment (predictive enrichment). In this perspective, we apply the precision medicine paradigm to the emerging use of extracorporeal CO2 removal (ECCO2R) for ultraprotective ventilation in ARDS. ECCO2R enables reductions in tidal volume and driving pressure, key determinants of ventilator-induced lung injury. Using basic physiological concepts, we demonstrate that dead space and static compliance determine the effect of ECCO2R on driving pressure and mechanical power. This framework might enable prediction of individual treatment responses to ECCO2R. Enriching clinical trials by selectively enrolling patients with a significant predicted treatment response can increase treatment effect size and statistical power more efficiently than conventional enrichment strategies that restrict enrollment according to the baseline risk of death. To support this claim, we simulated the predicted effect of ECCO2R on driving pressure and mortality in a preexisting cohort of patients with ARDS. Our computations suggest that restricting enrollment to patients in whom ECCO2R allows driving pressure to be decreased by 5 cm H2O or more can reduce sample size requirement by more than 50% without increasing the total number of patients to be screened. We discuss potential implications for trial design based on this framework.

Neurally Adjusted Ventilatory Assist (NAVA) or Pressure Support Ventilation (PSV) during spontaneous breathing trials in critically ill patients: a crossover trial

Abstract: Neurally Adjusted Ventilatory Assist (NAVA) is a proportional ventilatory mode that uses the electrical activity of the diaphragm (EAdi) to offer ventilatory assistance in proportion to patient effort. NAVA has been increasingly used for critically ill patients, but it has not been evaluated during spontaneous breathing trials (SBT). We designed a pilot trial to assess the feasibility of using NAVA during SBTs, and to compare the breathing pattern and patient-ventilator asynchrony of NAVA with Pressure Support (PSV) during SBTs. We conducted a crossover trial in the ICU of a university hospital in Brazil and included mechanically ventilated patients considered ready to undergo an SBT on the day of the study. Patients underwent two SBTs in randomized order: 30 min in PSV of 5 cmH2O or NAVA titrated to generate equivalent peak airway pressure (Paw), with a positive end-expiratory pressure of 5 cmH2O. The ICU team, blinded to ventilatory mode, evaluated whether patients passed each SBT. We captured flow, Paw and electrical activity of the diaphragm (EAdi) from the ventilator and used it to calculate respiratory rate (RR), tidal volume (VT), and EAdi. Detection of asynchrony events used waveform analysis and we calculated the asynchrony index as the number of asynchrony events divided by the number of neural cycles. We included 20 patients in the study. All patients passed the SBT in PSV, and three failed the SBT in NAVA. Five patients were reintubated and the extubation failure rate was 25% (95% CI 9–49%). Respiratory parameters were similar in the two modes: VT = 6.1 (5.5–6.5) mL/Kg in NAVA vs. 5.5 (4.8–6.1) mL/Kg in PSV (p = 0.076) and RR = 27 (17–30) rpm in NAVA vs. 26 (20–30) rpm in PSV, p = 0.55. NAVA reduced AI, with a median of 11.5% (4.2–19.7) compared to 24.3% (6.3–34.3) in PSV (p = 0.033). NAVA reduces patient-ventilator asynchrony index and generates a respiratory pattern similar to PSV during SBTs. Patients considered ready for mechanical ventilation liberation may be submitted to an SBT in NAVA using the same objective criteria used for SBTs in PSV. ClinicalTrials.gov ( NCT01337271 ), registered April 12, 2011.

Randomized, multicenter trial of lateral Trendelenburg versus semirecumbent body position for the prevention of ventilator-associated pneumonia

Abstract: The lateral Trendelenburg position (LTP) may hinder the primary pathophysiologic mechanism of ventilator-associated pneumonia (VAP). We investigated whether placing patients in the LTP would reduce the incidence of VAP in comparison with the semirecumbent position (SRP). This was a randomized, multicenter, controlled study in invasively ventilated critically ill patients. Two preplanned interim analyses were performed. Patients were randomized to be placed in the LTP or the SRP. The primary outcome, assessed by intention-to-treat analysis, was incidence of microbiologically confirmed VAP. Major secondary outcomes included mortality, duration of mechanical ventilation, and intensive care unit length of stay. At the second interim analysis, the trial was stopped because of low incidence of VAP, lack of benefit in secondary outcomes, and occurrence of adverse events. A total of 194 patients in the LTP group and 201 in the SRP group were included in the final intention-to-treat analysis. The incidence of microbiologically confirmed VAP was 0.5% (1/194) and 4.0% (8/201) in LTP and SRP patients, respectively (relative risk 0.13, 95% CI 0.02–1.03, p = 0.04). The 28-day mortality was 30.9% (60/194) and 26.4% (53/201) in LTP and SRP patients, respectively (relative risk 1.17, 95% CI 0.86–1.60, p = 0.32). Likewise, no differences were found in other secondary outcomes. Six serious adverse events were described in LTP patients (p = 0.01 vs. SRP). The LTP slightly decreased the incidence of microbiologically confirmed VAP. Nevertheless, given the early termination of the trial, the low incidence of VAP, and the adverse events associated with the LTP, the study failed to prove any significant benefit. Further clinical investigation is strongly warranted; however, at this time, the LTP cannot be recommended as a VAP preventive measure. NCT01138540.

Mapping Regional Differences of Local Pressure-Volume Curves With Electrical Impedance Tomography.

Abstract: Objectives:Lung-protective mechanical ventilation aims to prevent alveolar collapse and overdistension, but reliable bedside methods to quantify them are lacking. We propose a quantitative descriptor of the shape of local pressure-volume curves derived from electrical impedance tomography, for compu

Monitoring of Pneumothorax Appearance with Electrical Impedance Tomography during Recruitment Maneuvers

Abstract: 1. Petrache I, Berdyshev EV. Ceramide signaling and metabolism in pathophysiological states of the lung. Annu Rev Physiol 2016;78: 463–480. 2. Moffatt MF, Gut IG, Demenais F, Strachan DP, Bouzigon E, Heath S, von Mutius E, Farrall M, Lathrop M, Cookson WO; GABRIEL Consortium. A large-scale, consortium-based genomewide association study of asthma. N Engl J Med 2010;363:1211–1221. 3. Worgall TS, Veerappan A, Sung B, Kim BI, Weiner E, Bholah R, Silver RB, Jiang XC, Worgall S. Impaired sphingolipid synthesis in the respiratory tract induces airway hyperreactivity. Sci Transl Med 2013;5:186ra67. 4. Mainardi TR, Mellins RB, Miller RL, Acosta LM, Cornell A, Hoepner L, Quinn JW, Yan B, Chillrud SN, Olmedo OE, et al. Exercise-induced wheeze, urgent medical visits, and neighborhood asthma prevalence. Pediatrics 2013;131:e127–e135. 5. Bui HH, Leohr JK, Kuo MS. Analysis of sphingolipids in extracted human plasma using liquid chromatography electrospray ionization tandem mass spectrometry. Anal Biochem 2012;423: 187–194. 6. Moffatt MF, Kabesch M, Liang L, Dixon AL, Strachan D, Heath S, Depner M, von Berg A, Bufe A, Rietschel E, et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 2007; 448:470–473. 7. Oyeniran C, Sturgill JL, Hait NC, Huang WC, Avni D, Maceyka M, Newton J, Allegood JC, Montpetit A, Conrad DH, et al. Aberrant ORM (yeast)-like protein isoform 3 (ORMDL3) expression dysregulates ceramide homeostasis in cells and ceramide exacerbates allergic asthma in mice. J Allergy Clin Immunol 2015; 136:1035–1046.e6.

Continuous Negative Abdominal Pressure Recruits Lungs at Lower Distending Pressures.

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The Increasing Call for Protective Ventilation During Anesthesia.

Abstract: The Increasing Call for Protective Ventilation During Anesthesia To the Editor Fernandez-Bustamante et al1 show that postoperative pulmonary complications occur in one-third of noncardiothoracic surgical patients with severe systemic disease despite current intraoperative ventilation practices considered to be protective. During general anesthesia, the combination of reduced functional residual capacity, airway closure, and a high inspiratory oxygen fraction are the main factors implicated in the development of atelectasis. The study by Fernandez-Bustamante et al1 raises attention once more to the occurrence of atelectasis as well as the prolonged oxygen therapy requirement. Notwithstanding that both have been considered mild postoperative pulmonary complications, they might also play a role as triggering factors in a potentially hazardous chain of events. An emerging concept is that ventilator-induced lung injury should be prevented whenever possible. There is growing recognition that most postoperative pulmonary complications occur as a 2-hit phenomenon, mechanical ventilation being the second hit. Positron emission tomography studies using 18F fluorodeoxyglucose (18F-FDG), an inflammatory marker, revealed that 18F-FDG uptake in normal lungs was associated with high tidal regional strain, even when global strain remained at presumably safe ranges. A surprisingly high pulmonary uptake of 18F-FDG was observed in patients with head injury under conventional mechanical ventilation and normal lungs, suggesting an occult but ongoing pulmonary inflammation.2 This suggests the vulnerability of normal lungs on ventilatory support in the presence of any additional stimulus that can precipitate tissue damage. The surgical trauma may also induce an inflammatory response that makes the lung more vulnerable to mechanical ventilation. A ventilation strategy using low tidal volume, lung recruitment, and positive end-expiratory pressure (PEEP) of 6 to 8 cm of water to avoid a second hit in at-risk patients during major abdominal surgery improved clinical outcomes.3 In contrast, in patients undergoing open abdominal surgery,4 PEEP of 12 cm of water with recruitment maneuvers presented no benefits in terms of protection against postoperative pulmonary complications. To understand these contradictory data, one needs to consider local mechanisms of ventilator-induced lung injury. Using synchrotron-based radiography, it was estimated that local strain in the alveolar wall of heterogeneous lungs is amplified up to 4-fold the value of the global strain.5 Noticeably, none of the recent clinical studies on protective ventilation during anesthesia3,4 attempted to individualize the level of PEEP. Excessive or suboptimal PEEP may fail to prevent the second hit in at-risk patients. We thus suggest that a PEEP titration procedure should be part of a protective ventilation concept. The challenge is to make the PEEP titration simple enough to make it feasible in routine anesthesia.

Statistical analysis plan for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART). A randomized controlled trial

Abstract: RESUMO Fundamentacao: O estudo Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) e um ensaio clinico internacional, multicentrico, randomizado, pragmatico e controlado com ocultacao da alocacao que envolve 120 unidades de terapia intensiva no Brasil, Argentina, Colombia, Espanha, Italia, Polonia, Portugal, Malasia e Uruguai, com o objetivo primario de determinar se o recrutamento alveolar gradual maximo associado com titulacao da pressao positiva expiratoria final, ajustada segundo a complacencia estatica do sistema respiratorio (estrategia ART), e capaz de aumentar, quando comparada aos resultados do tratamento convencional (estrategia ARDSNet), a sobrevivencia em 28 dias de pacientes com sindrome do desconforto respiratorio agudo. Objetivo: Descrever o processo de gerenciamento dos dados e o plano de analise estatistica em um ensaio clinico internacional. Metodos: O plano de analise estatistica foi delineado pelo comite executivo e revisado pelo comite diretivo do ART. Foi oferecida uma visao geral do delineamento do estudo, com foco especial na descricao de desfechos primario (sobrevivencia aos 28 dias) e secundarios. Foram descritos o processo de gerenciamento dos dados, o comite de monitoramento de dados, a analise interina e o calculo do tamanho da amostra. Tambem foram registrados o plano de analise estatistica para os desfechos primario e secundarios, e os subgrupos de analise pre-especificados. Detalhes para apresentacao dos resultados, inclusive modelos de tabelas para as caracteristicas basais, adesao ao protocolo e efeito nos desfechos clinicos, foram fornecidos. Conclusao: Em acordo com as melhores praticas em ensaios clinicos, submetemos nossos planos de analise estatistica e de gerenciamento de dados para publicacao antes do fechamento da base de dados e inicio das analises. Antecipamos que este documento deve prevenir vies em analises e incrementar a utilidade dos resultados a serem relatados. Registro do estudo: Numero no registro ClinicalTrials.gov NCT01374022.

Physiologic effects of alveolar recruitment and inspiratory pauses during moderately-high-frequency ventilation delivered by a conventional ventilator in a severe lung injury model.

Abstract: Background and aims To investigate whether performing alveolar recruitment or adding inspiratory pauses could promote physiologic benefits (VT) during moderately-high-frequency positive pressure ventilation (MHFPPV) delivered by a conventional ventilator in a porcine model of severe acute respiratory distress syndrome (ARDS). Methods Prospective experimental laboratory study with eight pigs. Induction of acute lung injury with sequential pulmonary lavages and injurious ventilation was initially performed. Then, animals were ventilated on a conventional mechanical ventilator with a respiratory rate (RR) = 60 breaths/minute and PEEP titrated according to ARDS Network table. The first two steps consisted of a randomized order of inspiratory pauses of 10 and 30% of inspiratory time. In final step, we removed the inspiratory pause and titrated PEEP, after lung recruitment, with the aid of electrical impedance tomography. At each step, PaCO2 was allowed to stabilize between 57–63 mmHg for 30 minutes. Results The step with RR of 60 after lung recruitment had the highest PEEP when compared with all other steps (17 [16,19] vs 14 [10, 17]cmH2O), but had lower driving pressures (13 [13,11] vs 16 [14, 17]cmH2O), higher P/F ratios (212 [191,243] vs 141 [105, 184] mmHg), lower shunt (23 [20, 23] vs 32 [27, 49]%), lower dead space ventilation (10 [0, 15] vs 30 [20, 37]%), and a more homogeneous alveolar ventilation distribution. There were no detrimental effects in terms of lung mechanics, hemodynamics, or gas exchange. Neither the addition of inspiratory pauses or the alveolar recruitment maneuver followed by decremental PEEP titration resulted in further reductions in VT. Conclusions During MHFPPV set with RR of 60 bpm delivered by a conventional ventilator in severe ARDS swine model, neither the inspiratory pauses or PEEP titration after recruitment maneuver allowed reduction of VT significantly, however the last strategy decreased driving pressures and improved both shunt and dead space.

Alveolar Recruitment Strategies After Cardiac Surgery-Reply.

Abstract: to confounding factors, not a causal influence.2,3 To draw causal inference regarding any risk factor, we concur with major medical groups4 that researchers will need to find commensurate results from multiple methods. For instance, our findings regarding antidepressant use during pregnancy and preterm birth using multiple designs with the large Swedish registers are consistent with the findings by Yonkers and colleagues using a smaller but wellcharacterized sample of pregnant women.5 Ultimately, understanding the causal risk factors for birth and neurodevelopmental problems will require researchers to consider risk factors across numerous domains, while leveraging the advantages and limitations of multiple research designs.