Role of Pv-aCO2 gradient and Pv-aCO2/Ca-vO2 ratio during cardiac surgery: a retrospective observational study.

INTRODUCTION: Arterial lactate, mixed venous O2 saturation, venous minus arterial CO2 partial pressure (Pv-aCO2) and the ratio between this gradient and the arterial minus venous oxygen content (Pv-aCO2/Ca-vO2) were proposed as markers of tissue hypoperfusion and oxygenation. The main goals were to characterize the determinants of Pv-aCO2 and Pv-aCO2/Ca-vO2, and the interchangeability of the variables calculated from mixed and central venous samples. METHODS: 35 cardiac surgery patients were included. Variables were measured or calculated: after anesthesia induction (T1), end of surgery (T2), and at 6...8.ßhours intervals after ICU admission (T3 and T4). RESULTS: Macrohemodynamics was characterized by increased cardiac index and low systemic vascular resistances after surgery (p.ß<.ß0.05). Hemoglobin, arterial-pH, lactate, and systemic O2 metabolism showed significant changes during the study (p.ß<.ß0.05). Pv-aCO2 remained high and without changes, Pv-aCO2/Ca-vO2 was also high and decreased at T4 (p.ß<.ß0.05). A significant correlation was observed globally and at each time interval, between Pv-aCO2 or Pv-aCO2/Ca-vO2 with factors that may affect the CO2 hemoglobin dissociation. A multilevel linear regression model with Pv-aCO2 and Pv-aCO2/Ca-vO2 as outcome variables showed a significant association for Pv-aCO2 with SvO2, and BE (p.ß<.ß0.05), while Pv-aCO2/Ca-vO2 was significantly associated with Hb, SvO2, and BE (p.ß<.ß0.05) but not with cardiac output. Measurements and calculations from mixed and central venous blood were not interchangeable. CONCLUSIONS: Pv-aCO2 and Pv-aCO2/Ca-vO2 could be influenced by different factors that affect the CO2 dissociation curve, these variables should be considered with caution in cardiac surgery patients. Finally, central venous and mixed values were not interchangeable.

Role of Pv-aCO2 gradient and Pv-aCO2/Ca-vO2 ratio during cardiac surgery: a retrospective observational study

Abstract Introduction: Arterial lactate, mixed venous O2 saturation, venous minus arterial CO2 partial pressure (Pv-aCO2) and the ratio between this gradient and the arterial minus venous oxygen content (Pv-aCO2/Ca-vO2) were proposed as markers of tissue hypoperfusion and oxygenation. The main goals were to characterize the determinants of Pv-aCO2 and Pv-aCO2/Ca-vO2, and the interchangeability of the variables calculated from mixed and central venous samples. Methods: 35 cardiac surgery patients were included. Variables were measured or calculated: after anesthesia induction (T1), end of surgery (T2), and at 6-8 hours intervals after ICU admission (T3 and T4). Results: Macrohemodynamics was characterized by increased cardiac index and low systemic vascular resistances after surgery (p < 0.05). Hemoglobin, arterial-pH, lactate, and systemic O2 metabolism showed significant changes during the study (p < 0.05). Pv-aCO2 remained high and without changes, Pv-aCO2/Ca-vO2 was also high and decreased at T4 (p < 0.05). A significant correlation was observed globally and at each time interval, between Pv-aCO2 or Pv-aCO2/Ca-vO2 with factors that may affect the CO2 hemoglobin dissociation. A multilevel linear regression model with Pv-aCO2 and Pv-aCO2/Ca-vO2 as outcome variables showed a significant association for Pv-aCO2 with SvO2, and BE (p < 0.05), while Pv-aCO2/Ca-vO2 was significantly associated with Hb, SvO2, and BE (p < 0.05) but not with cardiac output. Measurements and calculations from mixed and central venous blood were not interchangeable. Conclusions: Pv-aCO2 and Pv-aCO2/Ca-vO2 could be influenced by different factors that affect the CO2 dissociation curve, these variables should be considered with caution in cardiac surgery patients. Finally, central venous and mixed values were not interchangeable.

Early goal-directed therapy using a physiological holistic view: the ANDROMEDA-SHOCK-a randomized controlled trial.

BACKGROUND: Septic shock is a highly lethal condition. Early recognition of tissue hypoperfusion and its reversion are key factors for limiting progression to multiple organ dysfunction and death. Lactate-targeted resuscitation is the gold-standard under current guidelines, although it has several pitfalls including that non-hypoxic sources of lactate might predominate in an unknown proportion of patients. Peripheral perfusion-targeted resuscitation might provide a real-time response to increases in flow that could lead to a more timely decision to stop resuscitation, thus avoiding fluid overload and the risks of over-resuscitation. This article reports the rationale, study design and analysis plan of the ANDROMEDA-SHOCK Study. METHODS: ANDROMEDA-SHOCK is a randomized controlled trial which aims to determine if a peripheral perfusion-targeted resuscitation is associated with lower 28-day mortality compared to a lactate-targeted resuscitation in patients with septic shock with less than 4 h of diagnosis. Both groups will be treated with the same sequential approach during the 8-hour study period pursuing normalization of capillary refill time versus normalization or a decrease of more than 20% of lactate every 2 h. The common protocol starts with fluid responsiveness assessment and fluid loading in responders, followed by a vasopressor and an inodilator test if necessary. The primary outcome is 28-day mortality, and the secondary outcomes are: free days of mechanical ventilation, renal replacement therapy and vasopressor support during the first 28 days after randomization; multiple organ dysfunction during the first 72 h after randomization; intensive care unit and hospital lengths of stay; and all-cause mortality at 90-day. A sample size of 422 patients was calculated to detect a 15% absolute reduction in mortality in the peripheral perfusion group with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. CONCLUSIONS: If peripheral perfusion-targeted resuscitation improves 28-day mortality, this could lead to simplified algorithms, assessing almost in real-time the reperfusion process, and pursuing more physiologically sound objectives. At the end, it might prevent the risk of over-resuscitation and lead to a better utilization of intensive care unit resources. Trial registration ClinicalTrials.gov Identifier: NCT03078712 (registered retrospectively March 13th, 2017).

Mildly elevated lactate levels are associated with microcirculatory flow abnormalities and increased mortality: a microSOAP post hoc analysis.

BACKGROUND: Mildly elevated lactate levels (i.e., 1-2 mmol/L) are increasingly recognized as a prognostic finding in critically ill patients. One of several possible underlying mechanisms, microcirculatory dysfunction, can be assessed at the bedside using sublingual direct in vivo microscopy. We aimed to evaluate the association between relative hyperlactatemia, microcirculatory flow, and outcome. METHODS: This study was a predefined subanalysis of a multicenter international point prevalence study on microcirculatory flow abnormalities, the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Microcirculatory flow abnormalities were assessed with sidestream dark-field imaging. Abnormal microcirculatory flow was defined as a microvascular flow index (MFI) < 2.6. MFI is a semiquantitative score ranging from 0 (no flow) to 3 (continuous flow). Associations between microcirculatory flow abnormalities, single-spot lactate measurements, and outcome were analyzed. RESULTS: In 338 of 501 patients, lactate levels were available. For this substudy, all 257 patients with lactate levels ≤ 2 mmol/L (median [IQR] 1.04 [0.80-1.40] mmol/L) were included. Crude ICU mortality increased with each lactate quartile. In a multivariable analysis, a lactate level > 1.5 mmol/L was independently associated with a MFI < 2.6 (OR 2.5, 95% CI 1.1-5.7, P = 0.027). CONCLUSIONS: In a heterogeneous ICU population, a single-spot mildly elevated lactate level (even within the reference range) was independently associated with increased mortality and microvascular flow abnormalities. In vivo microscopy of the microcirculation may be helpful in discriminating between flow- and non-flow-related causes of mildly elevated lactate levels. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01179243 . Registered on August 3, 2010.

Organizational Issues, Structure, and Processes of Care in 257 ICUs in Latin America: A Study From the Latin America Intensive Care Network.

OBJECTIVE: Latin America bears an important burden of critical care disease, yet the information about it is scarce. Our objective was to describe structure, organization, processes of care, and research activities in Latin-American ICUs. DESIGN: Web-based survey submitted to ICU directors. SETTINGS: ICUs located in nine Latin-American countries. SUBJECTS: Individual ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred fifty-seven of 498 (52%) of submitted surveys responded: 51% from Brazil, 17% Chile, 13% Argentina, 6% Ecuador, 5% Uruguay, 3% Colombia, and 5% between Mexico, Peru, and Paraguay. Seventy-nine percent of participating hospitals had less than 500 beds; most were public (59%) and academic (66%). ICUs were mainly medical-surgical (75%); number of beds was evenly distributed in the entire cohort; 77% had 24/7 intensivists; 46% had a physician-to-patient ratio between 1:4 and 7; and 69% had a nurse-to-patient ratio of 1 ≥ 2.1. The 24/7 presence of other specialists was deficient. Protocols in use averaged 9 ± 3. Brazil (vs the rest) had larger hospitals and ICUs and more quality, surveillance, and prevention committees, but fewer 24/7 intensivists and poorer nurse-to-patient ratio. Although standard monitoring, laboratory, and imaging practices were almost universal, more complex measurements and treatments and portable equipment were scarce after standard working hours, and in public hospitals. Mortality was 17.8%, without differences between countries. CONCLUSIONS: This multinational study shows major concerns in the delivery of critical care across Latin America, particularly in human resources. Technology was suboptimal, especially in public hospitals. A 24/7 availability of supporting specialists and of key procedures was inadequate. Mortality was high in comparison to high-income countries.

International study on microcirculatory shock occurrence in acutely ill patients.

OBJECTIVES: Microcirculatory alterations are associated with adverse outcome in subsets of critically ill patients. The prevalence and significance of microcirculatory alterations in the general ICU population are unknown. We studied the prevalence of microcirculatory alterations in a heterogeneous ICU population and its predictive value in an integrative model of macro- and microcirculatory variables. DESIGN: Multicenter observational point prevalence study. SETTING: The Microcirculatory Shock Occurrence in Acutely ill Patients study was conducted in 36 ICUs worldwide. PATIENTS: A heterogeneous ICU population consisting of 501 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic, hemodynamic, and laboratory data were collected in all ICU patients who were 18 years old or older. Sublingual Sidestream Dark Field imaging was performed to determine the prevalence of an abnormal capillary microvascular flow index (< 2.6) and its additional value in predicting hospital mortality. In 501 patients with a median Acute Physiology and Chronic Health Evaluation II score of 15 (10-21), a Sequential Organ Failure Assessment score of 5 (2-8), and a hospital mortality of 28.4%, 17% exhibited an abnormal capillary microvascular flow index. Tachycardia (heart rate > 90 beats/min) (odds ratio, 2.71; 95% CI, 1.67-4.39; p < 0.001), mean arterial pressure (odds ratio, 0.979; 95% CI, 0.963-0.996; p = 0.013), vasopressor use (odds ratio, 1.84; 95% CI, 1.11-3.07; p = 0.019), and lactate level more than 1.5 mEq/L (odds ratio, 2.15; 95% CI, 1.28-3.62; p = 0.004) were independent risk factors for hospital mortality, but not abnormal microvascular flow index. In reference to microvascular flow index, a significant interaction was observed with tachycardia. In patients with tachycardia, the presence of an abnormal microvascular flow index was an independent, additive predictor for in-hospital mortality (odds ratio, 3.24; 95% CI, 1.30-8.06; p = 0.011). This was not true for nontachycardic patients nor for the total group of patients. CONCLUSIONS: In a heterogeneous ICU population, an abnormal microvascular flow index was present in 17% of patients. This was not associated with mortality. However, in patients with tachycardia, an abnormal microvascular flow index was independently associated with an increased risk of hospital death.

El salbutamol mejora la contractilidad diafragmática en la obstrucción crónica de la vía aérea / Salbutamol Improves Diaphragmatic Contractility in Chronic Airway Obstruction

Introducción: Las enfermedades con obstrucción crónica de la vía aérea, como la enfermedad pulmonar obstructiva crónica, asocian alteraciones funcionales de los músculos respiratorios. Los agonistas adrenérgicos ¦Â2 mejoran la fuerza muscular en condiciones fisiológicas y patológicas. Nuestro objetivo ha sido estudiar los efectos del salbutamol sobre la contractilidad diafragmática en un modelo animal de obstrucción crónica de la vía aérea lograda por obstrucción traqueal (OT) extrínseca. Materiales y métodos: Se aleatorizaron 24 ratas Sprague-Dawley en 4 grupos: a) control; b) OT; c) OT+salbutamol agudo, y d) OT+salbutamol crónico. Se estudiaron los gases sanguíneos, el equilibrio ácido-base y la fuerza diafragmática in vitro, a través de las siguientes medidas: tensión máxima (Tmáx), tiempo de contracción (TC), velocidad de contracción (dT/dtmáx), tiempo de relajación media (TR1/2), velocidad de relajación (−dT/dtmáx) y curvas fuerza-frecuencia. Resultados: Los 3 grupos sometidos a OT presentaron una disminución significativa del pH y un incremento de la presión arterial de anhídrido carbónico y del bicarbonato en sangre arterial (p<0,05). El grupo OT experimentó una disminución significativa de Tmáx, de dT/dtmáx y de la curva fuerza-frecuencia en comparación con los otros grupos (p<0,05). La −dT/dtmáx fue mayor en el grupo OT+salbutamol crónico comparado con el grupo OT (p<0,05). Los valores medios (¡À error estándar) de Tmáx fueron: control, 6,46¡À0,90N/cm2; OT, 3,28¡À0,55N/cm2; OT+salbutamol agudo, 6,18¡À0,71N/cm2; OT+salbutamol crónico, 7,09¡À0,59N/cm2. Conclusiones: La disfunción diafragmática asociada a obstrucción crónica de la vía aérea mejora con salbutamol administrado tanto en forma aguda como crónica. Los mecanismos involucrados en la disfunción muscular deben analizarse más profundamente(AU)

Introduction: Chronic airflow obstruction in conditions such as chronic obstructive pulmonary disease is associated with respiratory muscle dysfunction. Our aim was to study the effects of salbutamol¡ªa ¦Â-adrenergic agonist known to improve muscle strength in physiologic and pathologic conditions¡ªon diaphragm contractility in an animal model of chronic airway obstruction achieved by tracheal banding.Materials and Methods: Twenty-four Sprague-Dawley rats were randomized into a control group and 3 tracheal banding groups, 1 that received acute salbutamol treatment, 1 that received chronic salbutamol treatment, and 1 that received nothing. Arterial blood gases, acid-base balance, and in vitro diaphragmatic contractility were evaluated by measuring peak twitch tension, contraction time, contraction velocity, half-relaxation time, relaxation velocity, and force-frequency curves.Results: The 3 study groups had significantly reduced arterial pH and increased PaCO2 and bicarbonate levels compared to the control group (P<.05). The untreated tracheal banding group had significantly reduced peak twitch tension and contraction velocity, and a significantly lower force-frequency curve in comparison with the other groups (P<.05). The chronic treatment group had a higher relaxation velocity than the untreated study group (P<.05). The mean (SE) peak twitch tension values were 6.46 (0.90)N/cm2 for the control group, 3.28 (0.55)N/cm2 for the untreated tracheal banding group, 6.18 (0.71)N/cm2 for the acute treatment group, and 7.09 (0.59)N/cm2 for the chronic treatment group.Conclusions: Diaphragmatic dysfunction associated with chronic airflow obstruction improves with both the acute and chronic administration of salbutamol. The mechanisms involved in respiratory muscle dysfunction warrant further study(AU)

[Salbutamol improves diaphragmatic contractility in chronic airway obstruction]. / El salbutamol mejora la contractilidad diafragmática en la obstrucción crónica de la vía aérea.

INTRODUCTION: Chronic airflow obstruction in conditions such as chronic obstructive pulmonary disease is associated with respiratory muscle dysfunction. Our aim was to study the effects of salbutamol-a beta-adrenergic agonist known to improve muscle strength in physiologic and pathologic conditions-on diaphragm contractility in an animal model of chronic airway obstruction achieved by tracheal banding. MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were randomized into a control group and 3 tracheal banding groups, 1 that received acute salbutamol treatment, 1 that received chronic salbutamol treatment, and 1 that received nothing. Arterial blood gases, acid-base balance, and in vitro diaphragmatic contractility were evaluated by measuring peak twitch tension, contraction time, contraction velocity, half-relaxation time, relaxation velocity, and force-frequency curves. RESULTS: The 3 study groups had significantly reduced arterial pH and increased PaCO2 and bicarbonate levels compared to the control group (P<.05). The untreated tracheal banding group had significantly reduced peak twitch tension and contraction velocity, and a significantly lower force-frequency curve in comparison with the other groups (P<.05). The chronic treatment group had a higher relaxation velocity than the untreated study group (P<.05). The mean (SE) peak twitch tension values were 6.46 (0.90)N/cm(2) for the control group, 3.28 (0.55)N/cm(2) for the untreated tracheal banding group, 6.18 (0.71)N/cm(2) for the acute treatment group, and 7.09 (0.59)N/cm(2) for the chronic treatment group. CONCLUSIONS: Diaphragmatic dysfunction associated with chronic airflow obstruction improves with both the acute and chronic administration of salbutamol. The mechanisms involved in respiratory muscle dysfunction warrant further study.

Central venous to mixed venous blood oxygen and lactate gradients are associated with outcome in critically ill patients.

OBJECTIVE: Blood O(2) saturation and lactate concentration gradients from superior vena cava (SVC) to pulmonary artery (PA) occur in critically ill patients. These gradients (DeltaSO(2) and Delta[Lac]) may be positive or negative. We tested the hypothesis that positive DeltaSO(2) and Delta[Lac] are associated with improved survival in critically ill patients. DESIGN AND SETTING: Multinational, prospective observational study conducted in six medical and surgical ICUs. PATIENTS: Consecutive sample of 106 adults requiring insertion of a pulmonary artery catheter (PAC). Average age was 59.5 +/- 15.5 years, APACHE II score was 15.5 +/- 6.7 (mean +/- SD). Main outcome measure was 28-day mortality. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We drew blood samples from the proximal and distal ports of PACs every 6 h from the time of PAC insertion (Initial measurement) until its removal (Final measurement). Samples were analyzed for SO(2), [Lac], glucose concentration and blood gases. Hemodynamic measurements were obtained after blood samples. We monitored patients for 30.9 +/- 11.0 h. Overall mortality rate was 25.5%. More survivors had mean and final DeltaSO(2) > or = 0 and Delta[Lac] > or = 0 than decedents (p < 0.01; p < 0.05 respectively). On the average, DeltaSO(2) and Delta[Lac] were positive in survivors and negative in decedents. Survival odds ratios for final measurements of DeltaSO(2) > or = 0 and Delta[Lac] > or = 0 were 19.22 and 7.70, respectively (p < 0.05). CONCLUSIONS: A strong association exists between positive DeltaSO(2) and Delta[Lac] and survival in critically ill patients. Whether therapy aimed at increasing DeltaSO(2) and Delta[Lac] results in improved ICU survival remains to be determined.

[Physiologic effects of noninvasive ventilation in patients with chronic obstructive pulmonary disease]. / Efectos fisiológicos de la ventilación no invasiva en pacientes con EPOC.

OBJECTIVE: Noninvasive mechanical ventilation has been of use in the treatment of some forms of chronic and acute respiratory failure. However, the benefits of its use in patients in the stable phase of severe chronic obstructive pulmonary disease (COPD) remain unclear. A combination of continuous positive airway pressure (CPAP) and pressure support ventilation (PSV) may improve respiratory mechanics and alveolar ventilation, and reduce inspiratory muscle effort. In this study, we analyzed the physiologic effects of differing levels of CPAP and CPAP plus PSV in patients with stable severe COPD. PATIENTS AND METHODS: Work of breathing, breathing pattern, oxygen saturation measured by pulse oximetry, PaO2, and PaCO2 were analyzed in a group of 18 patients under the following conditions: a) baseline; b) CPAP, 3 cm H20; c) CPAP, 6 cm H20; d) CPAP 3 cm H20 plus PSV 8 cm H20; and e) CPAP 3 cm H20 plus PSV 12 cm H20. RESULTS: CPAP at pressures of 3 and 6 cm H20 was associated with an increase in tidal volume (VT) from a mean (SD) baseline value of 0.52 (0.04) L to 0.62 (0.04) and 0.61 (0.03) L, respectively. Minute ventilation increased from 8.6 (0.5) L/min to 10.8 (0.6) and 10.9 (0.5) L/min, respectively. Mean inspiratory flow (VT/Ti) increased from 0.35 (0.02) L/s to 0.44 (0.02) and 0.41 (0.02) L/s, respectively, and dynamic intrinsic positive end-expiratory pressure (PEEPi,dyn) was reduced from 1.63 (0.7) cm H20 to 1.1 (0.06) and 0.37 (0.4) cm H20, respectively. CPAP did not reduce the work of breathing. Association of CPAP at 3 cm H20 with PSV of 8 or 12 cm H20 increased VT to 0.72 (0.07) and 0.87 (0.08) L, respectively, while minute ventilation increased to 12.9 (0.8) and 14.9 (1.1) L/s, respectively. Mean inspiratory flow also increased to 0.50 (0.03) and 0.57 (0.03) L/s, respectively. Work of breathing was reduced from 0.90 (0.01) J/L to 0.48 (0.06) and 0.30 (0.06) J/L, respectively, while PEEPi,dyn increased to 1.30 (0.02) and 2.42 (0.08) cm H20, respectively. With combined CPAP of 3 cm H20 and PSV of 12 cm H20, PaCO2 was reduced from a baseline value of 41.2 (1.5) mm Hg to 38.7 (1.9) mm Hg. All of the changes were statistically significant (P< .05). CONCLUSIONS: CPAP of 3 cm H20 in combination with PSV improved breathing pattern, increased alveolar ventilation, and reduced work of breathing. These results offer a rational basis for the use of noninvasive mechanical ventilation in the treatment of patients with stable severe COPD.

Efectos fisiológicos de la ventilación no invasiva en pacientes con EPOC / Physiologic effects of noninvasive ventilation in patients with chronic obstructive pulmonary disease

Objetivo: La ventilación mecánica no invasiva ha sido útil en el tratamiento de algunas formas de insuficiencia respiratoria aguda y crónica. Sin embargo, sus posibles beneficios para pacientes con enfermedad pulmonar obstructiva crónica (EPOC) grave en fase estable continúan siendo objeto de controversia. La combinación de presión positiva continua de la vía aérea (CPAP) y presión de soporte (PS) puede mejorar la mecánica respiratoria, el trabajo muscular y la ventilación alveolar. Estudiamos los efectos fisiológicos de diferentes cifras de CPAP y CPAP + PS en pacientes con EPOC grave en fase estable. Pacientes y métodos: En 18 pacientes se determinaron el trabajo respiratorio, el patrón respiratorio, la oximetría de pulso y los gases sanguíneos en las siguientes condiciones: a) basal; b) CPAP: 3 cmH2O; c) CPAP: 6 cmH2O; d) CPAP + PS: 3 y 8 cmH2O, respectivamente, y e) CPAP + PS: 3 y 12 cmH2O, respectivamente. Resultados: La CPAP de 3 y 6 cmH2O se asoció con aumento del volumen corriente (Vc), que de un valor basal medio (± desviación estándar) de 0,52 ± 0,04 pasó a 0,62 ± 0,04 y 0,61 ± 0,03 l, respectivamente. La ventilación minuto aumentó de 8,6 ± 0,5 a 10,8 ± 0,6 y 10,9 ± 0,5 l/min, respectivamente. El flujo medio inspiratorio (Vc/Ti) pasó de 0,35 ± 0,02 a 0,44 ± 0,02 y 0,41 ± 0,02 ml/min, y la presión positiva al final de la inspiración intrínseca (PEEPi dinámica) disminuyó de 1,63 ± 0,7 a 1,1 ± 0,06 y 0,37 ± 0,4 cmH2O, respectivamente. La CPAP no disminuyó el trabajo respiratorio. La asociación de CPAP de 3 cmH2O con PS de 8 y 12 cmH2O aumentó el Vc a 0,72 ± 0,07 y 0,87 ± 0,08 l, mientras la ventilación minuto aumentó a 12,9 ± 0,8 y 14,9 ± 1,1 l/min, respectivamente. El Vc/Ti también aumentó a 0,50 ± 0,03 y 0,57 ± 0,03 l/s, respectivamente. El trabajo respiratorio disminuyó desde 0,90 ± 0,01 a 0,48 ± 0,06 y 0,30 ± 0,06 J/l, mientras que la PEEPi dinámica aumentó a 1,30 ± 0,02 y 2,42 ± 0,08 cmH2O, respectivamente. Con CPAP de 3 cmH2O y PS de 12 cmH2O la presión arterial de anhídrido carbónico disminuyó de un valor basal de 41,2 ± 1,5 a 38,7 ± 1,9 Torr. Todos estos cambios fueron estadísticamente significativos (p < 0,05). Conclusiones: El uso de CPAP de 3 cmH2O con PS mejoró el patrón ventilatorio, aumentó la ventilación alveolar y disminuyó el trabajo respiratorio. Estos resultados ofrecen fundamentos para un uso racional de la ventilación mecánica no invasiva para el tratamiento de los pacientes con EPOC grave en fase estable

Objective: Noninvasive mechanical ventilation has been of use in the treatment of some forms of chronic and acute respiratory failure. However, the benefits of its use in patients in the stable phase of severe chronic obstructive pulmonary disease (COPD) remain unclear. A combination of continuous positive airway pressure (CPAP) and pressure support ventilation (PSV) may improve respiratory mechanics and alveolar ventilation, and reduce inspiratory muscle effort. In this study, we analyzed the physiologic effects of differing levels of CPAP and CPAP plus PSV in patients with stable severe COPD. Patients and methods: Work of breathing, breathing pattern, oxygen saturation measured by pulse oximetry, PaO2, and PaCO2 were analyzed in a group of 18 patients under the following conditions: a) baseline; b) CPAP, 3 cm H20; c) CPAP, 6 cm H20; d) CPAP 3 cm H20 plus PSV 8 cm H20; and e) CPAP 3 cm H20 plus PSV 12 cm H20. Results: CPAP at pressures of 3 and 6 cm H20 was associated with an increase in tidal volume (VT) from a mean (SD) baseline value of 0.52 (0.04) L to 0.62 (0.04) and 0.61 (0.03) L, respectively. Minute ventilation increased from 8.6 (0.5) L/min to 10.8 (0.6) and 10.9 (0.5) L/min, respectively. Mean inspiratory flow (VT/Ti) increased from 0.35 (0.02) L/s to 0.44 (0.02) and 0.41 (0.02) L/s, respectively, and dynamic intrinsic positive end-expiratory pressure (PEEPi,dyn) was reduced from 1.63 (0.7) cm H20 to 1.1 (0.06) and 0.37 (0.4) cm H20, respectively. CPAP did not reduce the work of breathing. Association of CPAP at 3 cm H20 with PSV of 8 or 12 cm H20 increased VT to 0.72 (0.07) and 0.87 (0.08) L, respectively, while minute ventilation increased to 12.9 (0.8) and 14.9 (1.1) L/s, respectively. Mean inspiratory flow also increased to 0.50 (0.03) and 0.57 (0.03) L/s, respectively. Work of breathing was reduced from 0.90 (0.01) J/L to 0.48 (0.06) and 0.30 (0.06) J/L, respectively, while PEEPi,dyn increased to 1.30 (0.02) and 2.42 (0.08) cm H20, respectively. With combined CPAP of 3 cm H20 and PSV of 12 cm H20, PaCO2 was reduced from a baseline value of 41.2 (1.5) mm Hg to 38.7 (1.9) mm Hg. All of the changes were statistically significant (P<.05). Conclusions: CPAP of 3 cm H20 in combination with PSV improved breathing pattern, increased alveolar ventilation, and reduced work of breathing. These results offer a rational basis for the use of noninvasive mechanical ventilation in the treatment of patients with stable severe COPD

Septic diaphragmatic dysfunction is prevented by Mn(III)porphyrin therapy and inducible nitric oxide synthase inhibition.

OBJECTIVE: Decreased diaphragmatic contractility and organ failure observed during sepsis is mediated by an overproduction of nitric oxide ((.)NO)-derived species, mitochondria being a major target of oxidative and nitrative stress. We tested the potential protective effects of (a) a novel synthetic antioxidant, the manganese(III) 5,10,15,20-tetrakis(N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP(5+)) and (b) the inducible (.)NO synthase inhibitor aminoguanidine (AG) on a rat model of sepsis. SETTING: University research laboratories. SUBJECTS AND INTERVENTIONS: Sepsis was induced by cecal ligation and perforation in rats. MEASUREMENTS AND RESULTS: Systemic hemodynamics, pulmonary gas exchange, in vitro diaphragmatic function and mitochondrial respiration were evaluated. Moreover, plasma and mitochondrial oxidative and nitrative stress parameters were investigated. Sepsis determined diaphragmatic dysfunction and a significant decrease in mitochondrial coupling and respiration. Oxidative stress was evidenced by decreased plasma antioxidants and increased lipid oxidation. Tyrosine nitration was increased in the plasma and mitochondria of the septic animals. These alterations were ameliorated or prevented by either MnTE-2-PyP(5+) or AG. CONCLUSIONS: Our results demonstrate that overproduction of (.)NO and (.)NO-derived reactive species play a critical role in mitochondrial impairment and diaphragmatic function during sepsis. More importantly, AG but mainly the novel metalloporphyrin MnTE-2-PyP(5+) were able to ameliorate diaphragmatic and mitochondrial dysfunction and could contribute to preventing organ failure during severe sepsis.