High Positive End-Expiratory Pressure Renders Spontaneous Effort Noninjurious.

RATIONALE: In acute respiratory distress syndrome (ARDS), atelectatic solid-like lung tissue impairs transmission of negative swings in pleural pressure (Ppl) that result from diaphragmatic contraction. The localization of more negative Ppl proportionally increases dependent lung stretch by drawing gas either from other lung regions (e.g., nondependent lung [pendelluft]) or from the ventilator. Lowering the level of spontaneous effort and/or converting solid-like to fluid-like lung might render spontaneous effort noninjurious. OBJECTIVES: To determine whether spontaneous effort increases dependent lung injury, and whether such injury would be reduced by recruiting atelectatic solid-like lung with positive end-expiratory pressure (PEEP). METHODS: Established models of severe ARDS (rabbit, pig) were used. Regional histology (rabbit), inflammation (positron emission tomography; pig), regional inspiratory Ppl (intrabronchial balloon manometry), and stretch (electrical impedance tomography; pig) were measured. Respiratory drive was evaluated in 11 patients with ARDS. MEASUREMENTS AND MAIN RESULTS: Although injury during muscle paralysis was predominantly in nondependent and middle lung regions at low (vs. high) PEEP, strong inspiratory effort increased injury (indicated by positron emission tomography and histology) in dependent lung. Stronger effort (vs. muscle paralysis) caused local overstretch and greater tidal recruitment in dependent lung, where more negative Ppl was localized and greater stretch was generated. In contrast, high PEEP minimized lung injury by more uniformly distributing negative Ppl, and lowering the magnitude of spontaneous effort (i.e., deflection in esophageal pressure observed in rabbits, pigs, and patients). CONCLUSIONS: Strong effort increased dependent lung injury, where higher local lung stress and stretch was generated; effort-dependent lung injury was minimized by high PEEP in severe ARDS, which may offset need for paralysis.

Electrical impedance tomography in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a clinical entity that acutely affects the lung parenchyma, and is characterized by diffuse alveolar damage and increased pulmonary vascular permeability. Currently, computed tomography (CT) is commonly used for classifying and prognosticating ARDS. However, performing this examination in critically ill patients is complex, due to the need to transfer these patients to the CT room. Fortunately, new technologies have been developed that allow the monitoring of patients at the bedside. Electrical impedance tomography (EIT) is a monitoring tool that allows one to evaluate at the bedside the distribution of pulmonary ventilation continuously, in real time, and which has proven to be useful in optimizing mechanical ventilation parameters in critically ill patients. Several clinical applications of EIT have been developed during the last years and the technique has been generating increasing interest among researchers. However, among clinicians, there is still a lack of knowledge regarding the technical principles of EIT and potential applications in ARDS patients. The aim of this review is to present the characteristics, technical concepts, and clinical applications of EIT, which may allow better monitoring of lung function during ARDS.

Early induction of luteolysis in a timed AI protocol increases reproductive performance in beef cows.

The aim of this study was to produce a longer proestrus by early administration of prostaglandin F2α (PGF) in a timed artificial insemination (TAI) protocol in non-suckling Bos taurus (Angus crossbreed) beef cows. On day 0, cows (n = 489) were treated with an intravaginal 1 g progesterone (P4) device and 2 mg of estradiol benzoate. On day 7, cows were randomized into two groups: PGF7(n = 244; 500 µg of sodium cloprostenol 24 h before P4 device removal) or PFG8 (n = 245; 500 µg of sodium cloprostenol at P4 device removal). On day 8, P4 device was removed and cows received 0.5 mg of estradiol cypionate. All cows were submitted to TAI on day 10 (48-50 hours after P4 device removal). Cows treated with PGF on day 7 had greater expression of estrus (91.3 vs 79.1 %; P = 0.0011), regardless of CL presence at beginning of the protocol. Cows from PGF7 group had lower circulating P4 concentrations on day 8 in comparison with PGF8 treated cows (1.86 vs 2.99 ng/mL; P < 0.001). However, preovulatory follicle diameter did not differ among treatments at TAI (11.9 vs 11.8 mm; P = 0.7881). Pregnancy per TAI (P/TAI) was greater for PGF7 (63.9 vs 50.6 %; P = 0.0114) than PGF8 treated cows. In cows with follicles <8.5 mm at TAI, expression of estrus (33.3 vs 26.6 %; P = 0.6427) and P/TAI (40 vs 26.6 %; P = 0.3657) were low in both PGF7 and PGF8 treated cows, respectively. In cows with medium follicle size (8.5 to 11.9 mm) PGF7 treated cows had greater expression of estrus (90.5 vs 80 %; P = 0.033) and P/TAI (62.2 vs 49 %; P = 0.053). In cows with follicles >12 mm, expression of estrus was greater for PGF7 than PGF8 treated cows (99.1 vs 93.3 %; P = 0.045), however P/TAI did not differ (68.2 vs 59 %; P = 0.149). In cows with P4 < 1.99 ng/mL on day 8, expression of estrus was similar between PGF7 and PGF8 treated cows (92.6 vs 90.4 %; P = 0.53), and P/TAI tended to be greater for PGF7 than PGF8 treated cows (63 vs 52.1 % P = 0.076). However, in cows with P4 > 2 ng/mL PGF7 cows had higher expression of estrus (89 vs 67.5 %; P = 0.0005) and P/TAI (64.8 vs 48.7 %; P = 0.021) than PGF8. Thus, increasing the proestrous period by inducing luteolysis 24 hours earlier than removing the P4 intravaginal device enhanced fertility in non-suckling cyclic beef cows by increasing expression of estrus and P/TAI.

Bedside estimation of nonaerated lung tissue using blood gas analysis.

OBJECTIVES: Studies correlating the arterial partial pressure of oxygen to the fraction of nonaerated lung assessed by CT shunt yielded inconsistent results. We systematically analyzed this relationship and scrutinized key methodological factors that may compromise it. We hypothesized that both physiological shunt and the ratio between PaO2 and the fraction of inspired oxygen enable estimation of CT shunt at the bedside. DESIGN: : Prospective observational clinical and laboratory animal investigations. SETTING: ICUs (University Hospital Leipzig, Germany) and Experimental Pulmonology Laboratory (University of São Paulo, Brazil). PATIENTS, SUBJECTS AND INTERVENTIONS: Whole-lung CT and arterial blood gases were acquired simultaneously in 77 patients mechanically ventilated with pure oxygen. A subgroup of 28 patients was submitted to different Fio2. We also studied 19 patients who underwent repeat CT. Furthermore we studied ten pigs with acute lung injury at multiple airway pressures, as well as a theoretical model relating PaO2 and physiological shunt. We logarithmically transformed the PaO2/Fio2 to change this nonlinear relationship into a linear regression problem. MEASUREMENTS AND MAIN RESULTS: We observed strong linear correlations between Riley's approximation of physiological shunt and CT shunt (R = 0.84) and between logarithmically transformed PaO2/Fio2 and CT shunt (R = 0.86), allowing us to construct a look-up table with prediction intervals. Strong linear correlations were also demonstrated within-patients (R = 0.95). Correlations were significantly improved by the following methodological issues: measurement of PaO2/Fio2 during pure oxygen ventilation, use of logarithmically transformed PaO2/Fio2 instead of the "raw" PaO2/Fio2, quantification of nonaerated lung as percentage of total lung mass and definition of nonaerated lung by the [-200 to +100] Hounsfield Units interval, which includes shunting units within less opacified lung regions. CONCLUSION: During pure oxygen ventilation, logarithmically transformed PaO2/Fio2 allows estimation of CT shunt and its changes in patients during systemic inflammation. Relevant intrapulmonary shunting seems to occur in lung regions with CT numbers between [-200 and +100] Hounsfield Units.

Optimizing timed AI protocols for Angus beef heifers: Comparison of induction of synchronized ovulation with estradiol cypionate or GnRH.

This study compared estradiol cypionate (ECP) or GnRH as ovulation inducers at the end of a timed AI (TAI) protocol in Angus heifers. On day 0, heifers (n = 415), between 22 and 24 months of age, were treated with an intravaginal 1 g progesterone (P4) insert and 2 mg of estradiol benzoate. On day 8, heifers had P4 removed, received 500 µg cloprostenol, and were randomized into two groups: ECP [n = 214; 0.5 mg of ECP on day 8] or GnRH [n = 201; 25 µg of GnRH analog licerelin acetate on day 10]. All heifers received TAI on day 10; 48-50 h after P4 insert withdrawal. Estrus was determined by removal of tail paint. Ovaries of heifers were evaluated by ultrasound on day 0 to determine CL presence (with CL = 213, without CL = 202) and on day 10 to measure preovulatory follicle size. Heifers were divided into three categories based on preovulatory follicle diameter: <8.5 mm (smaller than deviation), 8.5-10.9 mm, or ≥11 mm. Pregnancy diagnosis was performed 32 days after TAI. Heifers treated with ECP had greater expression of estrus than GnRH-treated heifers (93.9% vs 67.7%; P < 0.0001), regardless of CL presence at beginning of protocol. Heifers with CL at beginning of protocol had larger preovulatory follicle diameter (10.4 mm vs 9.6 mm; P = 0.0058) and greater pregnancy per AI (P/AI; 61.0% vs 50.5%; P = 0.032) than heifers without CL at day 0. In heifers with CL at day 0, GnRH treatment increased P/AI compared to ECP treatment (68.0% vs 54.9%; P = 0.0498). Expression of estrus was greater in ECP-treated than GnRH-treated heifers that had small (<8.5 mm; 77.1% vs 5.6%; P < 0.001) or medium-sized (8.5-10.9 mm; 98.4% vs. 61.7%) follicles, but not in heifers with large follicles (≥11 mm; 97.9% vs 98.3%). The P/AI was very low in both treatments for heifers with follicles <8.5 mm (ECP-14.3% vs GnRH-16.7%). In heifers with medium-sized follicles (8.5-10.9 mm), ECP treatment tended to increase P/AI compared with GnRH-treated heifers (62.9 vs 46.7%; P = 0.074). In contrast, P/AI was greater for GnRH-treated than ECP-treated heifers with large preovulatory follicles (≥11 mm; 79.7% vs 60.4%; P = 0.032). Thus, the optimal inducer of ovulation in a TAI protocol for beef heifers appears to depend on the presence of a CL at beginning of protocol (GnRH > ECP if CL present) and size of the preovulatory follicle, with ECP increasing expression of estrus and tending to increase fertility in heifers with medium-sized follicles but GnRH increasing fertility in heifers having large preovulatory follicles.

Validation of Bohr dead space measured by volumetric capnography.

PURPOSE: Bohr's dead space (VD(Bohr)) is commonly calculated using end-tidal CO(2) instead of the true alveolar partial pressure of CO(2) (PACO(2)). The aim of this work was to validate VD(Bohr) using PACO(2) derived from volumetric capnography (VC) against VD(Bohr) with PACO(2) values obtained from the standard alveolar air formula. METHODS: Expired gases of seven lung-lavaged pigs were analyzed at different lung conditions using main-stream VC and multiple inert gas elimination technique (MIGET). PACO(2) was determined by VC as the midpoint of the slope of phase III of the capnogram, while mean expired partial pressure of CO(2) (PeCO(2)) was calculated as the mean expired fraction of CO(2) times the barometric minus the water vapor pressure. MIGET estimated expired CO(2) output (VCO(2)) and PeCO(2) by its V/Q algorithms. Then, PACO(2) was obtained applying the alveolar air formula (PACO(2) = VCO(2)/alveolar ventilation). RESULTS: We found close linear correlations between the two methods for calculating both PACO(2) (r = 0.99) and VD(Bohr) (r = 0.96), respectively (both p < 0.0001). Mean PACO(2) from VC was very similar to the one obtained by MIGET with a mean bias of -0.10 mmHg and limits of agreement between -2.18 and 1.98 mmHg. Mean VD(Bohr) from VC was close to the value obtained by MIGET with a mean bias of 0.010 ml and limits of agreement between -0.044 and 0.064 ml. CONCLUSIONS: VD(Bohr) can be calculated with accuracy using volumetric capnography.

Cell therapy for fibrotic interstitial pulmonary disease: experimental study.

Parte superior do formulário Digite um texto ou endereço de um site ou traduza um documento. The aim of this study is to evaluate the histological changes in lung parenchyma of pigs affected by interstitial lung disease induced after the infusion of bone marrow mononuclear cells (BMMCs). Ten female swines were submitted to pulmonary fibrosis induced by a single dose of intratracheal bleomicine sulfate. Animals were arranged into two groups: Group 1: induced-disease control and Group 2: cell therapy using BMMCs. Both groups were clinically evaluated for 180 days. High-resolution computed tomography (HRCT) was performed at 90 and 180 days. BMMC sampling was performed in cell therapy group at 90 days. Euthanasia was performed, and samples were collected for histology and immunohistochemistry. The 90-days HRCT demonstrated typical interstitial lesions in pulmonary parenchyma similarly to human disease. The 180-days HRCT in Group 1 demonstrated advanced stages of the disease when compared with Group 2. Immunohistochemistry analysis suggests the presence of pre-existent vessels and neoformed vessels as well as predominant young cells in the injured parenchyma of Group 2. Immunohistochemistry analysis suggests that cell therapy would promote a reconstructive response. Histology and HRCT analysis suggest a positive application of swine as a model for a bleomicine inducing of fibrotic interstitial pulmonary disease.

Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome.

RATIONALE: The hypothesis that lung collapse is detrimental during the acute respiratory distress syndrome is still debatable. One of the difficulties is the lack of an efficient maneuver to minimize it. OBJECTIVES: To test if a bedside recruitment strategy, capable of reversing hypoxemia and collapse in > 95% of lung units, is clinically applicable in early acute respiratory distress syndrome. METHODS: Prospective assessment of a stepwise maximum-recruitment strategy using multislice computed tomography and continuous blood-gas hemodynamic monitoring. MEASUREMENTS AND MAIN RESULTS: Twenty-six patients received sequential increments in inspiratory airway pressures, in 5 cm H(2)O steps, until the detection of Pa(O(2)) + Pa(CO(2)) >or= 400 mm Hg. Whenever this primary target was not met, despite inspiratory pressures reaching 60 cm H(2)O, the maneuver was considered incomplete. If there was hemodynamic deterioration or barotrauma, the maneuver was to be interrupted. Late assessment of recruitment efficacy was performed by computed tomography (9 patients) or by online continuous monitoring in the intensive care unit (15 patients) up to 6 h. It was possible to open the lung and to keep the lung open in the majority (24/26) of patients, at the expense of transient hemodynamic effects and hypercapnia but without major clinical consequences. No barotrauma directly associated with the maneuver was detected. There was a strong and inverse relationship between arterial oxygenation and percentage of collapsed lung mass (R = - 0.91; p < 0.0001). CONCLUSIONS: It is often possible to reverse hypoxemia and fully recruit the lung in early acute respiratory distress syndrome. Due to transient side effects, the required maneuver still awaits further evaluation before routine clinical application.

Paradoxical responses to positive end-expiratory pressure in patients with airway obstruction during controlled ventilation.

OBJECTIVE: To reevaluate the clinical impact of external positive end-expiratory pressure (external-PEEP) application in patients with severe airway obstruction during controlled mechanical ventilation. The controversial occurrence of a paradoxic lung deflation promoted by PEEP was scrutinized. DESIGN: External-PEEP was applied stepwise (2 cm H(2)O, 5-min steps) from zero-PEEP to 150% of intrinsic-PEEP in patients already submitted to ventilatory settings minimizing overinflation. Two commonly used frequencies during permissive hypercapnia (6 and 9/min), combined with two different tidal volumes (VT: 6 and 9 mL/kg), were tested. SETTING: A hospital intensive care unit. PATIENTS: Eight patients were enrolled after confirmation of an obstructive lung disease (inspiratory resistance, >20 cm H(2)O/L per sec) and the presence of intrinsic-PEEP (> or =5 cm H(2)O) despite the use of very low minute ventilation. INTERVENTIONS: All patients were continuously monitored for intra-arterial blood gas values, cardiac output, lung mechanics, and lung volume with plethysmography. MEASUREMENTS AND MAIN RESULTS: Three different responses to external-PEEP were observed, which were independent of ventilatory settings. In the biphasic response, isovolume-expiratory flows and lung volumes remained constant during progressive PEEP steps until a threshold, beyond which overinflation ensued. In the classic overinflation response, any increment of external-PEEP caused a decrease in isovolume-expiratory flows, with evident overinflation. In the paradoxic response, a drop in functional residual capacity during external-PEEP application (when compared to zero-external-PEEP) was commonly accompanied by decreased plateau pressures and total-PEEP, with increased isovolume-expiratory flows. The paradoxic response was observed in five of the eight patients (three with asthma and two with chronic obstructive pulmonary disease) during at least one ventilator pattern. CONCLUSIONS: External-PEEP application may relieve overinflation in selected patients with airway obstruction during controlled mechanical ventilation. No a priori information about disease, mechanics, or ventilatory settings was predictive of the response. An empirical PEEP trial investigating plateau pressure response in these patients appears to be a reasonable strategy with minimal side effects.

Imbalances in regional lung ventilation: a validation study on electrical impedance tomography.

Imbalances in regional lung ventilation, with gravity-dependent collapse and overdistention of nondependent zones, are likely associated to ventilator-induced lung injury. Electric impedance tomography is a new imaging technique that is potentially capable of monitoring those imbalances. The aim of this study was to validate electrical impedance tomography measurements of ventilation distribution, by comparison with dynamic computerized tomography in a heterogeneous population of critically ill patients under mechanical ventilation. Multiple scans with both devices were collected during slow-inflation breaths. Six repeated breaths were monitored by impedance tomography, showing acceptable reproducibility. We observed acceptable agreement between both technologies in detecting right-left ventilation imbalances (bias = 0% and limits of agreement = -10 to +10%). Relative distribution of ventilation into regions or layers representing one-fourth of the thoracic section could also be assessed with good precision. Depending on electrode positioning, impedance tomography slightly overestimated ventilation imbalances along gravitational axis. Ventilation was gravitationally dependent in all patients, with some transient blockages in dependent regions synchronously detected by both scanning techniques. Among variables derived from computerized tomography, changes in absolute air content best explained the integral of impedance changes inside regions of interest (r(2) > or = 0.92). Impedance tomography can reliably assess ventilation distribution during mechanical ventilation.