A Prototype Implantable Artificial Bronchus Reduces Lung Hyperinflation in Recently Deceased Patients with Emphysema.

BACKGROUND: Several minimally invasive treatments have been offered to patients with severe emphysema over the last two decades. Currently, endobronchial valves (EBVs) are the only approved therapeutic option, but this method has drawbacks: only a few can undergo this therapy and the incidence of pneumothorax remains high. A minimally invasive technique, appropriate for a broader patient population and posing fewer risks, would represent a desirable alternative to improve lung function in these patients. OBJECTIVE: The objective of this study was to demonstrate whether a new prototype implantable artificial bronchus (IAB) releases trapped air from the lungs of recently deceased patients with emphysema. METHOD: Seven recently deceased patients with emphysema were mechanically ventilated and the respiratory rate increased from 12 bpm (resting) to 30 bpm (exercise), inducing air trapping and dynamic hyperinflation. This protocol was performed twice, before and after IAB placement. Ventilation parameters and the fraction of inspired oxygen were similar in all patients. Respiratory system plateau pressure (Pplat,rs) and intrinsic positive end-expiratory pressure (iPEEP) were measured. RESULTS: IAB implantation significantly reduced Pplat,rs (p = 0.017) in 6 of 7 deceased patients with emphysema and iPEEP (p = 0.03) in 5 of 7 patients. CONCLUSIONS: Placement of one or two IABs in segmental bronchi (up to 15th generation) proved to be feasible and improved lung function. These findings should provide a basis for subsequent clinical studies to assess the safety and efficacy of IAB in patients with emphysema, as well as identify short- and long-term effects of this innovative procedure.

Mechanical ventilation in patients in the intensive care unit of a general university hospital in southern Brazil: an epidemiological study.

OBJECTIVES: To determine the characteristics, the frequency and the mortality rates of patients needing mechanical ventilation and to identify the risk factors associated with mortality in the intensive care unit (ICU) of a general university hospital in southern Brazil. METHOD: Prospective cohort study in patients admitted to the ICU who needed mechanical ventilation for at least 24 hours between March 2004 and April 2007. RESULTS: A total of 1,115 patients admitted to the ICU needed mechanical ventilation. The mortality rate was 51%. The mean age (± standard deviation) was 57±18 years, and the mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 22.6±8.3. The variables independently associated with mortality were (i) conditions present at the beginning of mechanical ventilation, age (hazard ratio: 1.01; p<0.001); the APACHE II score (hazard ratio: 1.01; p<0.005); acute lung injury/acute respiratory distress syndrome (hazard ratio: 1.38; p=0.009), sepsis (hazard ratio: 1.33; p=0.003), chronic obstructive pulmonary disease (hazard ratio: 0.58; p=0.042), and pneumonia (hazard ratio: 0.78; p=0.013) as causes of mechanical ventilation; and renal (hazard ratio: 1.29; p=0.011) and neurological (hazard ratio: 1.25; p=0.024) failure, and (ii) conditions occurring during the course of mechanical ventilation, acute lung injuri/acute respiratory distress syndrome (hazard ratio: 1.31; p<0.010); sepsis (hazard ratio: 1.53; p<0.001); and renal (hazard ratio: 1.75; p<0.001), cardiovascular (hazard ratio: 1.32; p≤0.009), and hepatic (hazard ratio: 1.67; p≤0.001) failure. CONCLUSIONS: This large cohort study provides a comprehensive profile of mechanical ventilation patients in South America. The mortality rate of patients who required mechanical ventilation was higher, which may have been related to the severity of illness of the patients admitted to our ICU. Risk factors for hospital mortality included conditions present at the start of mechanical ventilation conditions that occurred during mechanical support.

Mechanical ventilation in patients in the intensive care unit of a general university hospital in southern Brazil: an epidemiological study

OBJECTIVES: To determine the characteristics, the frequency and the mortality rates of patients needing mechanical ventilation and to identify the risk factors associated with mortality in the intensive care unit (ICU) of a general university hospital in southern Brazil. METHOD: Prospective cohort study in patients admitted to the ICU who needed mechanical ventilation for at least 24 hours between March 2004 and April 2007. RESULTS: A total of 1,115 patients admitted to the ICU needed mechanical ventilation. The mortality rate was 51%. The mean age (± standard deviation) was 57±18 years, and the mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 22.6±8.3. The variables independently associated with mortality were (i) conditions present at the beginning of mechanical ventilation, age (hazard ratio: 1.01; p<0.001); the APACHE II score (hazard ratio: 1.01; p<0.005); acute lung injury/acute respiratory distress syndrome (hazard ratio: 1.38; p=0.009), sepsis (hazard ratio: 1.33; p=0.003), chronic obstructive pulmonary disease (hazard ratio: 0.58; p=0.042), and pneumonia (hazard ratio: 0.78; p=0.013) as causes of mechanical ventilation; and renal (hazard ratio: 1.29; p=0.011) and neurological (hazard ratio: 1.25; p=0.024) failure, and (ii) conditions occurring during the course of mechanical ventilation, acute lung injuri/acute respiratory distress syndrome (hazard ratio: 1.31; p<0.010); sepsis (hazard ratio: 1.53; p<0.001); and renal (hazard ratio: 1.75; p<0.001), cardiovascular (hazard ratio: 1.32; p≤0.009), and hepatic (hazard ratio: 1.67; p≤0.001) failure. CONCLUSIONS: This large cohort study provides a comprehensive profile of mechanical ventilation patients in South America. The mortality rate of patients who required mechanical ventilation was higher, which may have been related to the severity of illness of the patients admitted to our ICU. Risk factors for hospital mortality included conditions present at the start of mechanical ventilation conditions that occurred during mechanical support.

Pulse pressure variation and prediction of fluid responsiveness in patients ventilated with low tidal volumes.

OBJECTIVE: To determine the utility of pulse pressure variation (ΔRESP PP) in predicting fluid responsiveness in patients ventilated with low tidal volumes (V T) and to investigate whether a lower ΔRESP PP cut-off value should be used when patients are ventilated with low tidal volumes. METHOD: This cross-sectional observational study included 37 critically ill patients with acute circulatory failure who required fluid challenge. The patients were sedated and mechanically ventilated with a V T of 6-7 ml/kg ideal body weight, which was monitored with a pulmonary artery catheter and an arterial line. The mechanical ventilation and hemodynamic parameters, including ΔRESP PP, were measured before and after fluid challenge with 1,000 ml crystalloids or 500 ml colloids. Fluid responsiveness was defined as an increase in the cardiac index of at least 15%. ClinicalTrial.gov: NCT01569308. RESULTS: A total of 17 patients were classified as responders. Analysis of the area under the ROC curve (AUC) showed that the optimal cut-off point for ΔRESP PP to predict fluid responsiveness was 10% (AUC = 0.74). Adjustment of the ΔRESP PP to account for driving pressure did not improve the accuracy (AUC = 0.76). A ΔRESP PP ≥ 10% was a better predictor of fluid responsiveness than central venous pressure (AUC = 0.57) or pulmonary wedge pressure (AUC = 051). Of the 37 patients, 25 were in septic shock. The AUC for ΔRESP PP ≥ 10% to predict responsiveness in patients with septic shock was 0.484 (sensitivity, 78%; specificity, 93%). CONCLUSION: The parameter D RESP PP has limited value in predicting fluid responsiveness in patients who are ventilated with low tidal volumes, but a ΔRESP PP>10% is a significant improvement over static parameters. A ΔRESP PP ≥ 10% may be particularly useful for identifying responders in patients with septic shock.

Pulse pressure variation and prediction of fluid responsiveness in patients ventilated with low tidal volumes

OBJECTIVE: To determine the utility of pulse pressure variation (ΔRESP PP) in predicting fluid responsiveness in patients ventilated with low tidal volumes (V T) and to investigate whether a lower ΔRESP PP cut-off value should be used when patients are ventilated with low tidal volumes. METHOD: This cross-sectional observational study included 37 critically ill patients with acute circulatory failure who required fluid challenge. The patients were sedated and mechanically ventilated with a V T of 6-7 ml/kg ideal body weight, which was monitored with a pulmonary artery catheter and an arterial line. The mechanical ventilation and hemodynamic parameters, including ΔRESP PP, were measured before and after fluid challenge with 1,000 ml crystalloids or 500 ml colloids. Fluid responsiveness was defined as an increase in the cardiac index of at least 15%. ClinicalTrial.gov: NCT01569308. RESULTS: A total of 17 patients were classified as responders. Analysis of the area under the ROC curve (AUC) showed that the optimal cut-off point for ΔRESP PP to predict fluid responsiveness was 10% (AUC = 0.74). Adjustment of the ΔRESP PP to account for driving pressure did not improve the accuracy (AUC = 0.76). A ΔRESP PP>10% was a better predictor of fluid responsiveness than central venous pressure (AUC = 0.57) or pulmonary wedge pressure (AUC = 051). Of the 37 patients, 25 were in septic shock. The AUC for ΔRESP PP>10% to predict responsiveness in patients with septic shock was 0.484 (sensitivity, 78%; specificity, 93%). CONCLUSION: The parameter D RESP PP has limited value in predicting fluid responsiveness in patients who are ventilated with low tidal volumes, but a ΔRESP PP>10% is a significant improvement over static parameters. A ΔRESP PP > 10% may be particularly useful for identifying responders in patients with septic shock.

Mobilização do paciente crítico em ventilação mecânica: relato de caso / Mobilization of the critically ill patient in mechanical ventilation

A polineuropatia do paciente crítico (PNPC) é uma patologia relativamente comum no ambiente de terapia intensiva e ocasiona aumento do tempo de internação e de ventilação mecânica. Uma das causas relacionadas a essa patologia é a imobilização do paciente. O caso relatado é de um paciente de 18 anos, desnutrido, usuário de crack e com vírus da imunodeficiência humana e tuberculose pulmonar e intestinal. O paciente apresentou insuficiência respiratória necessitando de ventilação mecânica (VM) prolongada e PNPC associada. A fisioterapia com mobilização do paciente mesmo em uso de VM parece ter sido fundamental para a melhora da recuperação funcional associada à adequada nutrição e o tratamento das patologias apresentadas pelo paciente.

Polyneuropathy of critically ill patients, a relatively common condition in intensive care settings, increases length of hospitalization and mechanical ventilation. This disease is associated with patient immobilization. This report describes the case of an 18-year-old malnourished crack user and HIV-positive patient that had intestinal and pulmonary tuberculosis. The patient developed respiratory failure, which required prolonged mechanical ventilation, and polyneuropathy. Physical therapy with mobilization of the patient even while receiving mechanical ventilation, together with appropriate nutrition and treatment of the diseases, was instrumental in improving functional recovery.

Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function.

As a cornerstone of the innate immune response, neutrophils are the archetypical phagocytic cell; they actively seek out, ingest, and destroy pathogenic microorganisms. To achieve this essential role in host defense, neutrophils deploy a potent antimicrobial arsenal that includes oxidants, proteinases, and antimicrobial peptides. Importantly, oxidants produced by neutrophils, referred to in this article as reactive oxygen (ROS) and reactive nitrogen (RNS) species, have a dual function. On one hand they function as potent antimicrobial agents by virtue of their ability to kill microbial pathogens directly. On the other hand, they participate as signaling molecules that regulate diverse physiological signaling pathways in neutrophils. In the latter role, ROS and RNS serve as modulators of protein and lipid kinases and phosphatases, membrane receptors, ion channels, and transcription factors, including NF-kappaB. The latter regulates expression of key cytokines and chemokines that further modulate the inflammatory response. During the inflammatory response, ROS and RNS modulate phagocytosis, secretion, gene expression, and apoptosis. Under pathological circumstances such as acute lung injury and sepsis, excess production of ROS may influence vicinal cells such as endothelium or epithelium, contributing to inflammatory tissue injury. A better understanding of these pathways will help identify novel targets for amelioration of the untoward effects of inflammation.

Neutrophil apoptosis: a marker of disease severity in sepsis and sepsis-induced acute respiratory distress syndrome.

INTRODUCTION: Apoptosis of neutrophils (polymorphonuclear neutrophils [PMNs]) may limit inflammatory injury in sepsis and acute respiratory distress syndrome (ARDS), but the relationship between the severity of sepsis and extent of PMN apoptosis and the effect of superimposed ARDS is unknown. The objective of this study was to correlate neutrophil apoptosis with the severity of sepsis and sepsis-induced ARDS. METHODS: A prospective cohort study was conducted in intensive care units of three tertiary hospitals in Porto Alegre, southern Brazil. Fifty-seven patients with sepsis (uncomplicated sepsis, septic shock, and sepsis-induced ARDS) and 64 controls were enrolled. Venous peripheral blood was collected from patients with sepsis within 24 hours of diagnosis. All surgical groups, including controls, had their blood drawn 24 hours after surgery. Control patients on mechanical ventilation had blood collected within 24 hours of initiation of mechanical ventilation. Healthy controls were blood donors. Neutrophils were isolated, and incubated ex vivo, and apoptosis was determined by light microscopy on cytospun preparations. The differences among groups were assessed by analysis of variance with Tukeys. RESULTS: In medical patients, the mean percentage of neutrophil apoptosis (+/- standard error of the mean [SEM]) was lower in sepsis-induced ARDS (28% +/- 3.3%; n = 9) when compared with uncomplicated sepsis (57% +/- 3.2%; n = 8; p < 0.001), mechanical ventilation without infection, sepsis, or ARDS (53% +/- 3.0%; n = 11; p < 0.001) and healthy controls (69% +/- 1.1%; n = 33; p < 0.001) but did not differ from septic shock (38% +/- 3.7%; n = 12; p = 0.13). In surgical patients with sepsis, the percentage of neutrophil apoptosis was lower for all groups when compared with surgical controls (52% +/- 3.6%; n = 11; p < 0.001). CONCLUSION: In medical patients with sepsis, neutrophil apoptosis is inversely proportional to the severity of sepsis and thus may be a marker of the severity of sepsis in this population.

Acute lung injury and acute respiratory distress syndrome at the intensive care unit of a general university hospital in Brazil. An epidemiological study using the American-European Consensus Criteria.

OBJECTIVES: To determine: (1) the frequency of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); (2) the mortality associated with these syndromes and (3) the influence of risk factors, comorbidities and organ system dysfunction in the mortality of ALI patients. DESIGN: Prospective cohort study. SETTING: Intensive care unit (ICU) of a general university hospital in Brazil. PATIENTS AND PARTICIPANTS: All patients that remained in the ICU for more than 24 h were evaluated regarding the presence/development of ALI/ARDS according to the 1994 American-European Consensus Conference. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: One thousand three hundred and one patients were studied and analyzed regarding mortality, risk factors, comorbidities and organ system dysfunction(s). The frequency of ALI was 3.8% (50), of which ARDS was 2.3% (30) and ALI/non-ARDS 1.5% (20) (p=0.15). The ICU mortality of patients with ALI was 44.0%; in ALI/non-ARDS and ARDS patients it was 40.0% and 46.7%, respectively (p=0.43). The hospital mortality of ALI patients was 48.0%; in ALI/non-ARDS and ARDS patients it was 50.0% and 46.7%, respectively (p=0.21). A multivariate analysis demonstrated that renal (ICU and hospital: p=0.002) and hematological dysfunction (ICU: p=0.008; hospital: p=0.02) were independently associated with ICU and hospital mortality in ALI patients. CONCLUSIONS: (1) The frequency of ALI was 3.8%, of which the frequency of ARDS was 2.3% and of ALI/non-ARDS 1.5%; (2) The ICU and hospital mortality of ALI patients was 44.0% and 48.0%, respectively; mortality rates of ARDS and ALI/non-ARDS did not differ significantly; (3) Renal and hematological dysfunction were associated with mortality in ALI patients.