Pulmonar recruitment in acute respiratory distress syndrome. What is the best strategy?

Supporting patients with acute respiratory distress syndrome (ARDS), using a protective mechanical ventilation strategy characterized by low tidal volume and limitation of positive end-expiratory pressure (PEEP) is a standard practice in the intensive care unit. However, these strategies can promote lung de-recruitment, leading to the cyclic closing and reopening of collapsed alveoli and small airways. Recruitment maneuvers (RM) can be used to augment other methods, like positive end-expiratory pressure and positioning, to improve aerated lung volume. Clinical practice varies widely, and the optimal method and patient selection for recruitment maneuvers have not been determined, considerable uncertainty remaining regarding the appropriateness of RM. This review aims to discuss recent findings about the available types of RM, and compare the effectiveness, indications and adverse effects among them, as well as their impact on morbidity and mortality in ARDS patients. Recent developments include experimental and clinical evidence that a stepwise extended recruitment maneuver may cause an improvement in aerated lung volume and decrease the biological impact seen with the traditionally used sustained inflation, with less adverse effects. Prone positioning can reduce mortality in severe ARDS patients and may be an useful adjunct to recruitment maneuvers and advanced ventilatory strategies, such noisy ventilation and BIVENT, which have been useful in providing lung recruitment.

Pulmonar recruitment in acute respiratory distress syndrome. what is the best strategy? / Recrutamento pulmonar na síndrome do desconforto respiratório agudo. qual a melhor estratégia?

Supporting patients with acute respiratory distress syndrome (ARDS), using a protective mechanical ventilation strategy characterized by low tidal volume and limitation of positive end-expiratory pressure (PEEP) is a standard practice in the intensive care unit. However, these strategies can promote lung de-recruitment, leading to the cyclic closing and reopening of collapsed alveoli and small airways. Recruitment maneuvers (RM) can be used to augment other methods, like positive end-expiratory pressure and positioning, to improve aerated lung volume. Clinical practice varies widely, and the optimal method and patient selection for recruitment maneuvers have not been determined, considerable uncertainty remaining regarding the appropriateness of RM. This review aims to discuss recent findings about the available types of RM, and compare the effectiveness, indications and adverse effects among them, as well as their impact on morbidity and mortality in ARDS patients. Recent developments include experimental and clinical evidence that a stepwise extended recruitment maneuver may cause an improvement in aerated lung volume and decrease the biological impact seen with the traditionally used sustained inflation, with less adverse effects. Prone positioning can reduce mortality in severe ARDS patients and may be an useful adjunct to recruitment maneuvers and advanced ventilatory strategies, such noisy ventilation and BIVENT, which have been useful in providing lung recruitment.

O suporte a pacientes com a Síndrome do Desconforto Respiratório Agudo (SDRA), realizado com baixos volumes correntes e limite da pressão positiva ao final da expiração (PEEP), é o padrão ouro no tratamento de pacientes internados em Unidades de Terapia Intensiva. No entanto, essas estratégias podem promover o desrecrutamento pulmonar levando ao fechamento e reabertura cíclicos de alvéolos colapsados e de pequenas vias aéreas. As manobras de recrutamento (MR) podem ser usadas em conjunto a outros métodos, como a PEEP e posicionamento dos pacientes, para promover melhora no volume pulmonar aerado. Diversos métodos são utilizados na prática clínica, mas o mais adequado e a seleção de qual paciente se beneficiaria de MR ainda não estão estabelecidos. Além disso, ainda permanecem consideráveis incertezas em relação a adequação da MR. Esta revisão objetiva discutir as últimas descobertas acerca das MR existentes e compará-las no que tange a suas eficácias, indicações e complicações. Descobertas recentes incluem evidencias clínicas e experimentais que a manobra de recrutamento em "STEP" pode promover uma melhora do volume pulmonar aerado e reduzir o impacto biológico observado na insulflação sustentada tradicionalmente usada. O posicionamento em prona pode reduzir a mortalidade em pacientes com SDRA grave e ser um coadjuvante nas manobras de recrutamento e estratégias ventilatórias avançadas como a ventilação variável e o BIVENT tem se mostrado úteis em proporcionar recrutamento pulmonar.

Effects of short-term propofol and dexmedetomidine on pulmonary morphofunction and biological markers in experimental mild acute lung injury.

We evaluated whether the short-term use of dexmedetomidine and propofol may attenuate inflammatory response and improve lung morphofunction in experimental acute lung injury (ALI). Thirty-six Wistar rats were randomly divided into five groups. Control (C) and ALI animals received sterile saline solution and Escherichia coli lipopolysaccharide by intraperitoneal injection respectively. After 24h, ALI animals were randomly treated with dexmedetomidine, propofol, or thiopental sodium for 1h. Propofol reduced static lung elastance and resistive pressure and was associated with less alveolar collapse compared to thiopental sodium and dexmedetomidine. Dexmedetomidine improved oxygenation, but did not modify lung mechanics or histology. Propofol was associated with lower IL (interleukin)-6 and IL-1ß expression, whereas dexmedetomidine led to reduced inducible nitric oxide (iNOS) and increased nuclear factor erythroid 2-related factor 2 (Nrf2) expression in lung tissue compared to thiopental sodium. In conclusion, in this model of mild ALI, short-term use of dexmedetomidine and propofol led to different functional effects and activation of biological markers associated with pulmonary inflammation.

Effects of sigh during pressure control and pressure support ventilation in pulmonary and extrapulmonary mild acute lung injury.

INTRODUCTION: Sigh improves oxygenation and lung mechanics during pressure control ventilation (PCV) and pressure support ventilation (PSV) in patients with acute respiratory distress syndrome. However, so far, no study has evaluated the biological impact of sigh during PCV or PSV on the lung and distal organs in experimental pulmonary (p) and extrapulmonary (exp) mild acute lung injury (ALI). METHODS: In 48 Wistar rats, ALI was induced by Escherichia coli lipopolysaccharide either intratracheally (ALIp) or intraperitoneally (ALIexp). After 24 hours, animals were anesthetized and mechanically ventilated with PCV or PSV with a tidal volume of 6 mL/kg, FiO2 = 0.4, and PEEP = 5 cmH2O for 1 hour. Both ventilator strategies were then randomly assigned to receive periodic sighs (10 sighs/hour, Sigh) or not (non-Sigh, NS). Ventilatory and mechanical parameters, arterial blood gases, lung histology, interleukin (IL)-1ß, IL-6, caspase-3, and type III procollagen (PCIII) mRNA expression in lung tissue, and number of apoptotic cells in lung, liver, and kidney specimens were analyzed. RESULTS: In both ALI etiologies: (1) PCV-Sigh and PSV-Sigh reduced transpulmonary pressure, and (2) PSV-Sigh reduced the respiratory drive compared to PSV-NS. In ALIp: (1) PCV-Sigh and PSV-Sigh decreased alveolar collapse as well as IL-1ß, IL-6, caspase-3, and PCIII expressions in lung tissue, (2) PCV-Sigh increased alveolar-capillary membrane and endothelial cell damage, and (3) abnormal myofibril with Z-disk edema was greater in PCV-NS than PSV-NS. In ALIexp: (1) PSV-Sigh reduced alveolar collapse, but led to damage to alveolar-capillary membrane, as well as type II epithelial and endothelial cells, (2) PCV-Sigh and PSV-Sigh increased IL-1ß, IL-6, caspase-3, and PCIII expressions, and (3) PCV-Sigh increased the number of apoptotic cells in the lung compared to PCV-NS. CONCLUSIONS: In these models of mild ALIp and ALIexp, sigh reduced alveolar collapse and transpulmonary pressures during both PCV and PSV; however, improved lung protection only during PSV in ALIp.

The biological effects of higher and lower positive end-expiratory pressure in pulmonary and extrapulmonary acute lung injury with intra-abdominal hypertension.

INTRODUCTION: Mechanical ventilation with high positive end-expiratory pressure (PEEP) has been used in patients with acute respiratory distress syndrome (ARDS) and intra-abdominal hypertension (IAH), but the role of PEEP in minimizing lung injury remains controversial. We hypothesized that in the presence of acute lung injury (ALI) with IAH: 1) higher PEEP levels improve pulmonary morphofunction and minimize lung injury; and 2) the biological effects of higher PEEP are more effective in extrapulmonary (exp) than pulmonary (p) ALI. METHODS: In 48 adult male Wistar rats, ALIp and ALIexp were induced by Escherichia coli lipopolysaccharide intratracheally and intraperitoneally, respectively. After 24 hours, animals were anesthetized and mechanically ventilated (tidal volume of 6 mL/kg). IAH (15 mmHg) was induced and rats randomly assigned to PEEP of 5 (PEEP5), 7 (PEEP7) or 10 (PEEP10) cmH2O for 1 hour. RESULTS: In both ALIp and ALIexp, higher PEEP levels improved oxygenation. PEEP10 increased alveolar hyperinflation and epithelial cell damage compared to PEEP5, independent of ALI etiology. In ALIp, PEEP7 and PEEP10 increased lung elastance compared to PEEP5 (4.3 ± 0.7 and 4.3 ± 0.9 versus 3.1 ± 0.3 cmH2O/mL, respectively, P <0.01), without changes in alveolar collapse, interleukin-6, caspase-3, type III procollagen, receptor for advanced glycation end-products, and vascular cell adhesion molecule-1 expressions. Moreover, PEEP10 increased diaphragmatic injury compared to PEEP5. In ALIexp, PEEP7 decreased lung elastance and alveolar collapse compared to PEEP5 (2.3 ± 0.5 versus 3.6 ± 0.7 cmH2O/mL, P <0.02, and 27.2 (24.7 to 36.8) versus 44.2 (39.7 to 56.9)%, P <0.05, respectively), while PEEP7 and PEEP10 increased interleukin-6 and type III procollagen expressions, as well as type II epithelial cell damage compared to PEEP5. CONCLUSIONS: In the current models of ALI with IAH, in contrast to our primary hypothesis, higher PEEP is more effective in ALIp than ALIexp as demonstrated by the activation of biological markers. Therefore, higher PEEP should be used cautiously in the presence of IAH and ALI, mainly in ALIexp.

Oxigenação extracorpórea por membrana em cães sem auxílio circulatório / Pumpless extracorporeal membrane oxygenation in dogs

A oxigenação extracorpórea por membrana com desvio arterio-venoso (AV-ECMO), em seres humanos, é uma técnica de suporte à vida capaz de assumir em parte ou totalmente as funções dos pulmões, quando estes já não são capazes de promover uma adequada hematose. Para conhecer a viabilidade deste método em cães (Canis familiaris), o presente estudo aplicou a AV-ECMO em dez indivíduos adultos, sem raça definida, com uma expectativa de três horas de duração para cada experimento. No grupo 1 (n=4), ventilação mecânica e infusão contínua de dopamina foram associadas ao suporte extracorpóreo. No grupo 2 (n=6), nenhuma medida de terapia intensiva foi instituída concomitantemente à AV-ECMO. O comportamento dos parâmetros de gasometria e os níveis de lactato foram avaliados a cada 10 minutos e 1 hora, respectivamente, por meio de da avaliação de amostras sanguíneas arteriais. O suporte inotrópico foi capaz de promover uma melhor perfusão tecidual com sangue oxigenado, sugerida pelos níveis de lactato e pressão arterial média mensurados, assim como a hemogasometria revelou melhores resultados quando a ventilação mecânica foi utilizada simultaneamente à AV-ECMO. Portanto, aplicada conjuntamente com suporte da terapia intensiva, a AV-ECMO é uma técnica viável para o uso em cães com falência respiratória, refratária aos tratamentos convencionais.

In humans, arteriovenous extracorporeal membrane oxygenation (AV-ECMO) is a life support technique capable to assume in part or totally lungs functions, when these are not able to promote appropriated hematosis. To know the viability of this method in dogs (Canis familiaris), the present study applied AV-ECMO in ten adult mixed-breed dogs, with expected three hours of duration to each experiment. In Group 1 (n=4), mechanical ventilation and dopamine continuous infusion were associated with the extracorporeal support. In Group 2 (n=6), any other measure of intensive care was used concomitantly AV-ECMO. Blood gas analysis and lactate levels were evaluated every 10 minutes and one hour, respectively, from arterial blood samples. Inotropic support improved the blood flow through the circuit promoting a better tissue perfusion with oxygenated blood, suggested by the lactate and mean arterial pressure levels measured. Mechanical ventilation used simultaneously with AV-ECMO was able to further improve levels of blood gases. Therefore, if applied along intensive care support, AV-ECMO is a viable technique for use in dogs with respiratory failure refractory to conventional treatments.

Biphasic positive airway pressure minimizes biological impact on lung tissue in mild acute lung injury independent of etiology.

INTRODUCTION: Biphasic positive airway pressure (BIVENT) is a partial support mode that employs pressure-controlled, time-cycled ventilation set at two levels of continuous positive airway pressure with unrestricted spontaneous breathing. BIVENT can modulate inspiratory effort by modifying the frequency of controlled breaths. Nevertheless, the optimal amount of inspiratory effort to improve respiratory function while minimizing ventilator-associated lung injury during partial ventilatory assistance has not been determined. Furthermore, it is unclear whether the effects of partial ventilatory support depend on acute lung injury (ALI) etiology. This study aimed to investigate the impact of spontaneous and time-cycled control breaths during BIVENT on the lung and diaphragm in experimental pulmonary (p) and extrapulmonary (exp) ALI. METHODS: This was a prospective, randomized, controlled experimental study of 60 adult male Wistar rats. Mild ALI was induced by Escherichia coli lipopolysaccharide either intratracheally (ALI(p)) or intraperitoneally (ALI(exp)). After 24 hours, animals were anesthetized and further randomized as follows: (1) pressure-controlled ventilation (PCV) with tidal volume (V(t)) = 6 ml/kg, respiratory rate = 100 breaths/min, PEEP = 5 cmH2O, and inspiratory-to-expiratory ratio (I:E) = 1:2; or (2) BIVENT with three spontaneous and time-cycled control breath modes (100, 75, and 50 breaths/min). BIVENT was set with two levels of CPAP (P(high) = 10 cmH2O and P(low) = 5 cmH2O). Inspiratory time was kept constant (T(high) = 0.3 s). RESULTS: BIVENT was associated with reduced markers of inflammation, apoptosis, fibrogenesis, and epithelial and endothelial cell damage in lung tissue in both ALI models when compared to PCV. The inspiratory effort during spontaneous breaths increased during BIVENT-50 in both ALI models. In ALI(p), alveolar collapse was higher in BIVENT-100 than PCV, but decreased during BIVENT-50, and diaphragmatic injury was lower during BIVENT-50 compared to PCV and BIVENT-100. In ALI(exp), alveolar collapse during BIVENT-100 and BIVENT-75 was comparable to PCV, while decreasing with BIVENT-50, and diaphragmatic injury increased during BIVENT-50. CONCLUSIONS: In mild ALI, BIVENT had a lower biological impact on lung tissue compared to PCV. In contrast, the response of atelectasis and diaphragmatic injury to BIVENT differed according to the rate of spontaneous/controlled breaths and ALI etiology.

Oleanolic acid improves pulmonary morphofunctional parameters in experimental sepsis by modulating oxidative and apoptotic processes.

We compared the effects of oleanolic acid (OA) vs. dexamethasone on lung mechanics and histology, inflammation, and apoptosis in lung and distal organs in experimental sepsis. Seventy-eight BALB/c mice were randomly divided into two groups. Sepsis was induced by cecal ligation and puncture, while the control group underwent sham surgery. 1h after surgery, all animals were further randomized to receive saline (SAL), OA and dexamethasone (DEXA) intraperitoneally. Both OA and DEXA improved lung mechanics and histology, which were associated with fewer lung neutrophils and less cell apoptosis in lung, liver, and kidney than SAL. However, only animals in the DEXA group had lower levels of interleukin (IL)-6 and KC (murine analog of IL-8) in bronchoalveolar lavage fluid than SAL animals. Conversely, OA was associated with lower inducible nitric oxide synthase expression and higher superoxide dismutase than DEXA. In the experimental sepsis model employed herein, OA and DEXA reduced lung damage and distal organ apoptosis through distinct anti-inflammatory mechanisms.

Estudo comparativo entre as técnicas de sutura total e serosubmucosa em anastomoses colônicas na presença de um protetor intraluminar em cães / Comparative study of all-layers suture and extramucosal single layer suture with an intraluminal protector in dogs

OBJETIVO: Avaliar a cicatrização comparando as técnicas de sutura total e parcial em anastomoses colônicas término-terminais na presença de um protetor intraluminar confeccionado a partir de um dreno de Penrose. MÉTODOS: Foram realizadas anastomoses colônicas em 10 cães nos quais foi suturado a mucosa / submucosa um protetor intraluminar por meio da eversão do segmento intestinal proximal em 10 cm. Os animais foram distribuidos em dois grupos experimentais: Grupo 1 - sutura total e Grupo 2 - sutura serosubmucosa. Os animais foram reoperados com sete dias de pós-operatório para coleta de material e subseqüente análise histopatológica. RESULTADOS: Observamos no exame histopatológico das anastomoses realizadas com sutura serosubmucosa (Grupo 2) uma melhor cicatrização caracterizada por um menor infiltrado inflamatório e por uma maior integridade das camadas intestinais quando comparadas com o Grupo 1. CONCLUSÃO: O uso da técnica de sutura parcial mostrou-se superior a de sutura total nas anastomoses colônicas na presença de protetor intraluminar.

BACKGROUND: This study aims to evaluate the colonic anastomotic healing testing of all layers suture and single layer suture using an intraluminal protector. The intraluminal protector was shaped from a Penrose drain and then fixed 10 cm from the superior end of the anastomotic site. METHODS: Colonic anastomoses were done in 10 dogs, which were sutured, in the proximal segment with an intraluminal protector made of Penrose n.3 drain, using interrupted mucosal / submucosal suture. In the subsequent anastomoses, the animals were subdivided in two experimental groups: 1 - in all layers and 2 - extramucosal. In the seventh postoperative day, a tissue fragment was collected for histopathological analysis. RESULTS: Group 2 histopathological examinations had a better scar (extramucosal suture), characterized by a lesser inflammatory process than in animals in which all layers suture was used (group 1). CONCLUSION: The use of extramucosal suture was better than total suture in colonic anastomoses with the presence of an intraluminal protector.