João Batista Borges

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 H2O, 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 H2O/L per sec) and the presence of intrinsic-PEEP (≥5 cm H2O) 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.

Regional lung perfusion estimated by electrical impedance tomography in a piglet model of lung collapse

The assessment of the regional match between alveolar ventilation and perfusion in critically ill patients requires simultaneous measurements of both parameters. Ideally, assessment of lung perfusion should be performed in real-time with an imaging technology that provides, through fast acquisition of sequential images, information about the regional dynamics or regional kinetics of an appropriate tracer. We present a novel electrical impedance tomography (EIT)-based method that quantitatively estimates regional lung perfusion based on first-pass kinetics of a bolus of hypertonic saline contrast. Pulmonary blood flow was measured in six piglets during control and unilateral or bilateral lung collapse conditions. The first-pass kinetics method showed good agreement with the estimates obtained by single-photon-emission computerized tomography (SPECT). The mean difference (SPECT minus EIT) between fractional blood flow to lung areas suffering atelectasis was -0.6%, with a SD of 2.9%. This method outperformed the estimates of lung perfusion based on impedance pulsatility. In conclusion, we describe a novel method based on EIT for estimating regional lung perfusion at the bedside. In both healthy and injured lung conditions, the distribution of pulmonary blood flow as assessed by EIT agreed well with the one obtained by SPECT. The method proposed in this study has the potential to contribute to a better understanding of the behavior of regional perfusion under different lung and therapeutic conditions.

Open Lung Approach for the Acute Respiratory Distress Syndrome: A Pilot, Randomized Controlled Trial*

Objective:The open lung approach is a mechanical ventilation strategy involving lung recruitment and a decremental positive end-expiratory pressure trial. We compared the Acute Respiratory Distress Syndrome network protocol using low levels of positive end-expiratory pressure with open lung approach resulting in moderate to high levels of positive end-expiratory pressure for the management of established moderate/severe acute respiratory distress syndrome. Design:A prospective, multicenter, pilot, randomized controlled trial. Setting:A network of 20 multidisciplinary ICUs. Patients:Patients meeting the American-European Consensus Conference definition for acute respiratory distress syndrome were considered for the study. Interventions:At 12-36 hours after acute respiratory distress syndrome onset, patients were assessed under standardized ventilator settings (FIO2≥0.5, positive end-expiratory pressure ≥10 cm H2O). If Pao2/FIO2 ratio remained less than or equal to 200 mm Hg, patients were randomized to open lung approach or Acute Respiratory Distress Syndrome network protocol. All patients were ventilated with a tidal volume of 4 to 8 ml/kg predicted body weight. Measurements and Main Results:From 1,874 screened patients with acute respiratory distress syndrome, 200 were randomized: 99 to open lung approach and 101 to Acute Respiratory Distress Syndrome network protocol. Main outcome measures were 60-day and ICU mortalities, and ventilator-free days. Mortality at day-60 (29% open lung approach vs. 33% Acute Respiratory Distress Syndrome Network protocol, p = 0.18, log rank test), ICU mortality (25% open lung approach vs. 30% Acute Respiratory Distress Syndrome network protocol, p = 0.53 Fisher’s exact test), and ventilator-free days (8 [0-20] open lung approach vs. 7 [0-20] d Acute Respiratory Distress Syndrome network protocol, p = 0.53 Wilcoxon rank test) were not significantly different. Airway driving pressure (plateau pressure - positive end-expiratory pressure) and PaO2/FIO2 improved significantly at 24, 48 and 72 hours in patients in open lung approach compared with patients in Acute Respiratory Distress Syndrome network protocol. Barotrauma rate was similar in both groups. Conclusions:In patients with established acute respiratory distress syndrome, open lung approach improved oxygenation and driving pressure, without detrimental effects on mortality, ventilator-free days, or barotrauma. This pilot study supports the need for a large, multicenter trial using recruitment maneuvers and a decremental positive end-expiratory pressure trial in persistent acute respiratory distress syndrome.

Early inflammation mainly affects normally and poorly aerated lung in experimental ventilator-induced lung injury*.

Objective:The common denominator in most forms of ventilator-induced lung injury is an intense inflammatory response mediated by neutrophils. PET with [18F]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which, during lung inflammatory processes, mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. The aim of this study was to assess the location and magnitude of lung inflammation using PET imaging of [18F]fluoro-2-deoxy-D-glucose in a porcine experimental model of early acute respiratory distress syndrome. Design:Prospective laboratory investigation. Setting:A university animal research laboratory. Subjects:Seven piglets submitted to experimental ventilator-induced lung injury and five healthy controls. Interventions:Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. All animals were subsequently studied with dynamic PET imaging of [18F]fluoro-2-deoxy-D-glucose. CT scans were acquired at end expiration and end inspiration. Measurements and Main Results:[18F]fluoro-2-deoxy-D-glucose uptake rate was computed for the whole lung, four isogravitational regions, and regions grouping voxels with similar density. Global and intermediate gravitational zones [18F]fluoro-2-deoxy-D-glucose uptakes were higher in ventilator-induced lung injury piglets compared with controls animals. Uptake of normally and poorly aerated regions was also higher in ventilator-induced lung injury piglets compared with control piglets, whereas regions suffering tidal recruitment or tidal hyperinflation had [18F]fluoro-2-deoxy-D-glucose uptakes similar to controls. Conclusions:The present findings suggest that normally and poorly aerated regions—corresponding to intermediate gravitational zones—are the primary targets of the inflammatory process accompanying early experimental ventilator-induced lung injury. This may be attributed to the small volume of the aerated lung, which receives most of ventilation.

Capnography reflects ventilation/perfusion distribution in a model of acute lung injury

Background: Changes in the shape of the capnogram may reflect changes in lung physiology. We studied the effect of different ventilation/perfusion ratios (V/Q) induced by positive end‐expiratory pressures (PEEP) and lung recruitment on phase III slope (SIII) of volumetric capnograms.

Non-lobar atelectasis generates inflammation and structural alveolar injury in the surrounding healthy tissue during mechanical ventilation

IntroductionWhen alveoli collapse the traction forces exerted on their walls by adjacent expanded units may increase and concentrate. These forces may promote its re-expansion at the expense of potentially injurious stresses at the interface between the collapsed and the expanded units. We developed an experimental model to test the hypothesis that a local non-lobar atelectasis can act as a stress concentrator, contributing to inflammation and structural alveolar injury in the surrounding healthy lung tissue during mechanical ventilation.MethodsA total of 35 rats were anesthetized, paralyzed and mechanically ventilated. Atelectasis was induced by bronchial blocking: after five minutes of stabilization and pre-oxygenation with FIO2 = 1.0, a silicon cylinder blocker was wedged in the terminal bronchial tree. Afterwards, the animals were randomized between two groups: 1) Tidal volume (VT) = 10 ml/kg and positive end-expiratory pressure (PEEP) = 3 cmH2O (VT10/PEEP3); and 2) VT = 20 ml/kg and PEEP = 0 cmH2O (VT20/zero end-expiratory pressure (ZEEP)). The animals were then ventilated during 180 minutes. Three series of experiments were performed: histological (n = 12); tissue cytokines (n = 12); and micro-computed tomography (microCT; n = 2). An additional six, non-ventilated, healthy animals were used as controls.ResultsAtelectasis was successfully induced in the basal region of the lung of 26 out of 29 animals. The microCT of two animals revealed that the volume of the atelectasis was 0.12 and 0.21 cm3. There were more alveolar disruption and neutrophilic infiltration in the peri-atelectasis region than the corresponding contralateral lung (control) in both groups. Edema was higher in the peri-atelectasis region than the corresponding contralateral lung (control) in the VT20/ZEEP than VT10/PEEP3 group. The volume-to-surface ratio was higher in the peri-atelectasis region than the corresponding contralateral lung (control) in both groups. We did not find statistical difference in tissue interleukin-1β and cytokine-induced neutrophil chemoattractant-1 between regions.ConclusionsThe present findings suggest that a local non-lobar atelectasis acts as a stress concentrator, generating structural alveolar injury and inflammation in the surrounding lung tissue.

Real‐time ventilation and perfusion distributions by electrical impedance tomography during one‐lung ventilation with capnothorax

Carbon dioxide insufflation into the pleural cavity, capnothorax, with one‐lung ventilation (OLV) may entail respiratory and hemodynamic impairments. We investigated the online physiological effects of OLV/capnothorax by electrical impedance tomography (EIT) in a porcine model mimicking the clinical setting.

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 (R2 = 0.84) and between logarithmically transformed PaO2/Fio2 and CT shunt (R2 = 0.86), allowing us to construct a look-up table with prediction intervals. Strong linear correlations were also demonstrated within-patients (R2 = 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.

Lung inflammation persists after 27 hours of protective Acute Respiratory Distress Syndrome Network Strategy and is concentrated in the nondependent lung.

Objective: PET with [18F]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which during lung inflammation mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. We aimed at studying the location and evolution of inflammation by PET imaging, relating it to morphology (CT), during the first 27 hours of application of protective-ventilation strategy as suggested by the Acute Respiratory Distress Syndrome Network, in a porcine experimental model of acute respiratory distress syndrome. Design: Prospective laboratory investigation. Setting: University animal research laboratory. Subjects: Ten piglets submitted to an experimental model of acute respiratory distress syndrome. Interventions: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. During 27 hours of controlled mechanical ventilation according to Acute Respiratory Distress Syndrome Network strategy, the animals were studied with dynamic PET imaging of [18F]fluoro-2-deoxy-D-glucose at two occasions with 24-hour interval between them. Measurements and Main Results: [18F]fluoro-2-deoxy-D-glucose uptake rate was computed for the total lung, four horizontal regions from top to bottom (nondependent to dependent regions) and for voxels grouped by similar density using standard Hounsfield units classification. The global lung uptake was elevated at 3 and 27 hours, suggesting persisting inflammation. In both PET acquisitions, nondependent regions presented the highest uptake (p = 0.002 and p = 0.006). Furthermore, from 3 to 27 hours, there was a change in the distribution of regional uptake (p = 0.003), with more pronounced concentration of inflammation in nondependent regions. Additionally, the poorly aerated tissue presented the largest uptake concentration after 27 hours. Conclusions: Protective Acute Respiratory Distress Syndrome Network strategy did not attenuate global pulmonary inflammation during the first 27 hours after severe lung insult. The strategy led to a concentration of inflammatory activity in the upper lung regions and in the poorly aerated lung regions. The present findings suggest that the poorly aerated lung tissue is an important target of the perpetuation of the inflammatory process occurring during ventilation according to the Acute Respiratory Distress Syndrome Network strategy.

Corrections of Enghoff's dead space formula for shunt effects still overestimate Bohr's dead space

Dead space ratio is determined using Enghoffs modification (VD(B-E)/VT) of Bohrs formula (VD(Bohr)/VT) in which arterial is used as a surrogate of alveolar PCO₂. In presence of intrapulmonary shunt Enghoffs approach overestimates dead space. In 40 lung-lavaged pigs we evaluated the Kuwabaras and Niklasons algorithms to correct for shunt effects and hypothesized that corrected VD(B-E)/VT should provide similar values as VD(Bohr)/VT. We analyzed 396 volumetric capnograms and arterial and mixed-venous blood samples to calculate VD(Bohr)/VT and VD(B-E)/VT. Thereafter, we corrected the latter for shunt effects using Kuwabaras (K) VD(B-E)/VT and Niklasons (N) VD(B-E)/VT algorithms. Uncorrected VD(B-E)/VT (mean ± SD of 0.70 ± 0.10) overestimated VD(Bohr)/VT (0.59 ± 0.12) (p < 0.05), over the entire range of shunts. Mean (K) VD(B-E)/VT was significantly higher than VD(Bohr)/VT (0.67 ± 0.08, bias -0.085, limits of agreement -0.232 to 0.085; p < 0.05) whereas (N)VD(B-E)/VT showed a better correction for shunt effects (0.64 ± 0.09, bias 0.048, limits of agreement -0.168 to 0.072; p < 0.05). Neither Kuwabaras nor Niklasons algorithms were able to correct Enghoffs dead space formula for shunt effects.