Jörg Zinserling

The Effects of Different Ventilatory Settings on Pulmonary and Systemic Inflammatory Responses During Major Surgery

Mechanical ventilation with high tidal volumes (VT) and zero or low positive end-expiratory pressure increased mediator release to inflammatory stimuli or acute lung injury. We studied whether mechanical ventilation modifies the inflammatory responses during major thoracic or abdominal surgery. Sixty-four patients undergoing elective thoracotomy (n = 34) or laparotomy (n = 30) were randomized to receive either mechanical ventilation with VT = 12 or 15 mL/kg ideal body weight, respectively, and zero end-expiratory pressure, or VT = 6 mL/kg ideal body weight with positive end-expiratory pressure of 10 cm H2O. In 62 patients who completed the study, arterial oxygena- tion was not different between groups. Tumor necrosis factor, interleukin (IL)-1, IL-6, IL-8, IL-10, and IL-12 were determined by cytometric bead array in plasma after 0, 1, 2, and 3 h and in tracheal aspirates after 3 h of mechanical ventilation. Data were log-transformed and analyzed using parametric or nonparametric tests, as indicated. All plasma mediators increased more during abdominal than during thoracic surgery, although the differences were small. However, neither time course nor concentrations of pulmonary or systemic mediators differed between the two ventilatory settings. Our data suggest that the ventilatory settings we studied do not affect inflammatory reactions during major surgery within 3 h.

Effects of mechanical ventilation on release of cytokines into systemic circulation in patients with normal pulmonary function.

BackgroundMechanical ventilation with high tidal volumes (VT) in contrast to mechanical ventilation with low VT has been shown to increase plasma levels of proinflammatory and antiinflammatory mediators in patients with acute lung injury. The authors hypothesized that, in patients without previous lung injury, a conventional potentially injurious ventilatory strategy with high VT and zero end-expiratory pressure (ZEEP) will not cause a cytokine release into systemic circulation. MethodsA total of 39 patients with American Society of Anesthesiologists physical status I–II and without signs of systemic infection scheduled for elective surgery with general anesthesia were randomized to receive mechanical ventilation with either (1) VT = 15 ml/kg ideal body weight on ZEEP, (2) VT = 6 ml/kg ideal body weight on ZEEP, or (3) VT = 6 ml/kg ideal body weight on positive end-expiratory pressure of 10 cm H2O. Plasma levels of proinflammatory and antiinflammatory mediators tumor necrosis factor, interleukin (IL)-6, IL-10, and IL-1 receptor antagonist were determined before and 1 h after the initiation of mechanical ventilation. ResultsPlasma levels of all cytokines remained low in all settings. IL-6, tumor necrosis factor, and IL-1 receptor antagonist did not change significantly after 1 h of mechanical ventilation. IL-10 was below the detection limit (10 pg/ml) in 35 of 39 patients. There were no differences between groups. ConclusionsInitiation of mechanical ventilation for 1 h in patients without previous lung injury caused no consistent changes in plasma levels of studied mediators. Mechanical ventilation with high VT on ZEEP did not result in higher cytokine levels compared with lung-protective ventilatory strategies. Previous lunge damage seems to be mandatory to cause an increase in plasma cytokines after 1 h of high VT mechanical ventilation.

Spontaneous breathing improves lung aeration in oleic acid-induced lung injury.

Background Experimental and clinical studies have shown reduction in intrapulmonary shunt with improved oxygenation by spontaneous breathing with airway pressure release ventilation (APRV) in acute lung injury. The mechanisms of these findings are not clear. The authors hypothesized that spontaneous breathing results in better aeration of lung tissue and that improvement in oxygenation can be explained by these changes. This hypothesis was studied in a porcine model of oleic acid–induced lung injury. Methods Two hours after induction of lung injury, 24 pigs were randomly assigned to APRV with or without spontaneous breathing at a positive end-expiratory pressure of 5 cm H2O. Hemodynamics, spirometry, and end-expiratory lung volume by nitrogen washout were measured at baseline, after 2 h of lung injury, and after 2 and 4 h of mechanical ventilation in the specific mode. Finally, spiral computed tomography of the chest was performed at end-expiratory lung volume in 22 pigs. Results Arterial carbon dioxide tension and mean and end-inspiratory airway pressures were comparable between settings. Four hours of APRV with spontaneous breathing resulted in improved oxygenation compared with APRV without spontaneous breathing (arterial oxygen tension, 144 ± 65 vs. 91 ± 50 mmHg, P < 0.01 for interaction time × mode), higher end-expiratory lung volume (786 ± 320 vs. 384 ± 148 ml, P < 0.001), and better aeration. End-expiratory lung volume and venous admixture were both correlated with the amount of lung reaeration (r2 = 0.62 and r2 = 0.61, respectively). Conclusions The results support the hypothesis that spontaneous breathing during APRV improves oxygenation mainly by recruitment of nonaerated lung and improved aeration of the lungs.

The effects of prone positioning on intraabdominal pressure and cardiovascular and renal function in patients with acute lung injury.

To detect any harmful effects of prone positioning on intraabdominal pressure (IAP) and cardiovascular and renal function, we studied 16 mechanically ventilated patients with acute lung injury randomly in prone and supine positions, without minimizing the restriction of the abdomen. Effective renal blood flow index and glomerular filtration rate index were determined by the paraaminohippurate and inulin clearance techniques. Prone positioning resulted in an increase in IAP from 12 ± 4 to 14 ± 5 mm Hg (P < 0.05), Pao2/fraction of inspired oxygen from 220 ± 91 to 267 ± 82 mm Hg (P < 0.05), cardiac index from 4.1 ± 1.1 to 4.4 ± 0.7 L/min (P < 0.05), mean arterial pressure from 77 ± 10 to 82 ± 11 mm Hg (P < 0.01), and oxygen delivery index from 600 ± 156 to 648 ± 95 mL · min−1 · m−2 (P < 0.05). Renal fraction of cardiac output decreased from 19.1% ± 12.5% to 15.5% ± 8.8% (P < 0.05), and renal vascular resistance index increased from 11762 ± 6554 dynes · s · cm−5 · m2 to 15078 ± 10594 dynes · s · cm−5 · m2 (P < 0.05), whereas effective renal blood flow index, glomerular filtration rate index, filtration fraction, urine volume, fractional sodium excretion, and osmolar and free water clearances remained constant during prone positioning. Prone positioning, when used in patients with acute lung injury, although it is associated with a small increase in IAP, contributes to improved arterial oxygenation and systemic blood flow without affecting renal perfusion and function. Apparently, special support to allow free chest and abdominal movement seems unnecessary when mechanically ventilated, hemodynamically stable patients without abdominal hypertension are proned to improve gas exchange.

Electrical impedance tomography compared with thoracic computed tomography during a slow inflation maneuver in experimental models of lung injury

Objective:To determine the validity of functional electric impedance tomography to monitor regional ventilation distribution in experimental acute lung injury, and to develop a simple electric impedance tomography index detecting alveolar recruitment. Design:Randomized prospective experimental study. Setting:Academic research laboratory. Subjects:Sixteen anesthetized, tracheotomized, and mechanically ventilated pigs. Interventions:Acute lung injury was induced either by acid aspiration (direct acute lung injury) or by abdominal hypertension plus oleic acid injection (indirect acute lung injury) in ten pigs. Six pigs with normal lungs were studied as a control group and with endotracheal suction-related atelectasis. After 4 hrs of mechanical ventilation, a slow inflation was performed. Measurements and Main Results:During slow inflation, simultaneous measurements of regional ventilation by electric impedance tomography and dynamic computed tomography were highly correlated in quadrants of a transversal thoracic plane (r2 = .63–.88, p < .0001, bias <5%) in both direct and indirect acute lung injury. Variability between methods was lower in direct than indirect acute lung injury (11 ± 2% vs. 18 ± 3%, respectively, p < .05). Electric impedance tomography indexes to detect alveolar recruitment were determined by mathematical curve analysis of regional impedance time curves. Empirical tests of different methods revealed that regional ventilation delay, that is, time delay of regional impedance time curve to reach a threshold, correlated well with recruited volume as measured by CT (r2 = .63). Correlation coefficients in subgroups were r2 = .71 and r2 = .48 in pigs with normal lungs with and without closed suction related atelectasis and r2 = .79 in pigs subject to indirect acute lung injury, respectively, whereas no significant correlation was found in pigs undergoing direct acute lung injury. Conclusions:Electric impedance tomography allows assessment of regional ventilation distribution and recruitment in experimental models of direct and indirect acute lung injury as well as normal lungs. Except for pigs with direct acute lung injury, regional ventilation delay determined during a slow inflation from impedance time curves appears to be a simple index for clinical monitoring of alveolar recruitment.

Spontaneous breathing with airway pressure release ventilation favors ventilation in dependent lung regions and counters cyclic alveolar collapse in oleic-acid-induced lung injury: a randomized controlled computed tomography trial

IntroductionExperimental and clinical studies have shown a reduction in intrapulmonary shunt with spontaneous breathing during airway pressure release ventilation (APRV) in acute lung injury. This reduction was related to reduced atelectasis and increased aeration. We hypothesized that spontaneous breathing will result in better ventilation and aeration of dependent lung areas and in less cyclic collapse during the tidal breath.MethodsIn this randomized controlled experimental trial, 22 pigs with oleic-acid-induced lung injury were randomly assigned to receive APRV with or without spontaneous breathing at comparable airway pressures. Four hours after randomization, dynamic computed tomography scans of the lung were obtained in an apical slice and in a juxtadiaphragmatic transverse slice. Analyses of regional attenuation were performed separately in nondependent and dependent halves of the lungs on end-expiratory scans and end-inspiratory scans. Tidal changes were assessed as differences between inspiration and expiration of the mechanical breaths.ResultsWhereas no differences were observed in the apical slices, spontaneous breathing resulted in improved tidal ventilation of dependent lung regions (P < 0.05) and less cyclic collapse (P < 0.05) in the juxtadiaphragmatic slices. In addition, with spontaneous breathing, the end-expiratory aeration increased and nonaerated tissue decreased in dependent lung regions close to the diaphragm (P < 0.05 for the interaction ventilator mode and lung region).ConclusionSpontaneous breathing during APRV redistributes ventilation and aeration to dependent, usually well-perfused, lung regions close to the diaphragm, and may thereby contribute to improved arterial oxygenation. Spontaneous breathing also counters cyclic collapse, which is a risk factor for ventilation-associated lung injury.

Comparative Pharmacodynamic Modeling of the Electroencephalography-slowing Effect of Isoflurane, Sevoflurane, and Desflurane

BACKGROUND The most common measure to compare potencies of volatile anesthetics is minimum alveolar concentration (MAC), although this value describes only a single point on a quantal concentration-response curve and most likely reflects more the effects on the spinal cord rather than on the brain. To obtain more complete concentration-response curves for the cerebral effects of isoflurane, sevoflurane, and desflurane, the authors used the spectral edge frequency at the 95th percentile of the power spectrum (SEF95) as a measure of cerebral effect. METHODS Thirty-nine patients were randomized to isoflurane, sevoflurane, or desflurane groups. After induction with propofol, intubation, and a waiting period, end-tidal anesthetic concentrations were randomly varied between 0.6 and 1.3 MAC, and the EEG was recorded continuously. Population pharmacodynamic modeling was performed using the software package NONMEM. RESULTS The population mean EC50 values of the final model for SEF95 suppression were 0.66+/-0.08 (+/- SE of estimate) vol% for isoflurane, 1.18+/-0.10 vol% for sevoflurane, and 3.48+/-0.66 vol% for desflurane. The slopes of the concentration-response curves were not significantly different; the common value was lambda = 0.86+/-0.06. The Ke0 value was significantly higher for desflurane (0.61+/-0.11 min(-1)), whereas separate values for isoflurane and sevoflurane yielded no better fit than the common value of 0.29+/-0.04 min(-1). When concentration data were converted into fractions of the respective MAC values, no significant difference of the C50 values for the three anesthetic agents was found. CONCLUSIONS This study demonstrated that (1) the concentration-response curves for spectral edge frequency slowing have the same slope, and (2) the ratio C50(SEF95)/MAC is the same for all three anesthetic agents. The authors conclude that MAC and MAC multiples, for the three volatile anesthetics studied, are valid representations of the concentration-response curve for anesthetic suppression of SEF95.

Electrical impedance tomography guided ventilation therapy.

Purpose of reviewComputed tomography (CT) in patients with acute respiratory distress syndrome has shown that intrapulmonary gas is not homogeneously distributed. Although regional ventilation can be studied by isotope and magnetic resonance techniques while aeration of the lungs can be imaged using CT, these techniques are not available at the bedside. Recently, electrical impedance tomography has been introduced as a true bedside technique which provides information on regional ventilation distribution. Recent findingsElectrical impedance tomography can reliably determine regional ventilation in healthy lungs and various models of induced lung injury when compared with CT, electron beam CT, and single photon emission CT. In healthy volunteers and patients with acute lung injury, relative impedance changes on the electrical impedance tomography image demonstrate an excellent correlation with regional changes in lung air content detected by CT. In a limited number of patients with respiratory dysfunction, gas exchange was found to improve when electrical impedance tomography was used to adjust ventilator settings, improving regional ventilation and avoiding tidal alveolar collapse. SummaryIn view of recently published data, it can be concluded that, in critically ill patients, electrical impedance tomography determines reliable regional ventilation. Therefore, this technique has the potential to become a valuable bedside tool.

Tidal recruitment assessed by electrical impedance tomography and computed tomography in a porcine model of lung injury

Objectives:To determine the validity of electrical impedance tomography to detect and quantify the amount of tidal recruitment caused by different positive end-expiratory pressure levels in a porcine acute lung injury model. Design:Randomized, controlled, prospective experimental study. Setting:Academic research laboratory. Subjects:Twelve anesthetized and mechanically ventilated pigs. Interventions:Acute lung injury was induced by central venous oleic acid injection and abdominal hypertension in seven animals. Five healthy pigs served as control group. Animals were ventilated with positive end-expiratory pressure of 0, 5, 10, 15, 20, and 25 cm H2O, respectively, in a randomized order. Measurements and Main Results:At any positive end-expiratory pressure level, electrical impedance tomography was obtained during a slow inflation of 12 mL/kg of body weight. Regional-ventilation-delay indices quantifying the time until a lung region reaches a certain amount of impedance change were calculated for lung quadrants and for every single electrical impedance tomography pixel, respectively. Pixel-wise calculated regional-ventilation-delay indices were plotted in a color-coded regional-ventilation-delay map. Regional-ventilation-delay inhomogeneity that quantifies heterogeneity of ventilation time courses was evaluated by calculating the scatter of all pixel-wise calculated regional-ventilation-delay indices. End-expiratory and end-inspiratory computed tomography scans were performed at each positive end-expiratory pressure level to quantify tidal recruitment of the lung. Tidal recruitment showed a moderate inter-individual (r = .54; p < .05) and intra-individual linear correlation (r = .46 up to r = .73 and p < .05, respectively) with regional-ventilation-delay obtained from lung quadrants. Regional-ventilation-delay inhomogeneity was excellently correlated with tidal recruitment intra- (r = .90 up to r = .99 and p < .05, respectively) and inter-individually (r = .90; p < .001). Conclusions:Regional-ventilation-delay can be noninvasively measured by electrical impedance tomography during a slow inflation of 12 mL/kg of body weight and visualized using ventilation delay maps. Our experimental data suggest that the impedance tomography-based analysis of regional-ventilation-delay inhomogeneity provides a good estimate of the amount of tidal recruitment and may be useful to individualize ventilatory settings.

Effects of spontaneous breathing during airway pressure release ventilation on intestinal blood flow in experimental lung injury.

Background In critical illness, the gut is susceptible to hypoperfusion and hypoxia. Positive-pressure ventilation can affect systemic hemodynamics and regional blood flow distribution, with potentially deleterious effects on the intestinal circulation. The authors hypothesized that spontaneous breathing (SB) with airway pressure release ventilation (APRV) provides better systemic and intestinal blood flow than APRV without SB. Methods Twelve pigs with oleic acid–induced lung injury received APRV with and without SB. When SB was abolished, either the tidal volume or the ventilator rate was increased to maintain pH and arterial carbon dioxide tension constant as compared to APRV with SB. Systemic hemodynamics were determined by double indicator dilution. Blood flow to the intestinal mucosa–submucosa and muscularis–serosa was measured using colored microspheres. Results Systemic blood flow increased during APRV with SB. During APRV with SB, mucosal–submucosal blood flow (ml · g−1 · min−1) was 0.39 ± 0.21 in the stomach, 0.76 ± 0.35 in the duodenum, 0.71 ± 0.35 in the jejunum, 0.71 ± 0.59 in the ileum, and 0.63 ± 0.21 in the colon. During APRV without SB and high tidal volumes, it decreased to 0.19 ± 0.03 in the stomach, 0.42 ± 0.21 in the duodenum, 0.37 ± 0.10 in the jejunum, 0.3 ± 0.14 in the ileum, and 0.41 ± 0.14 in the colon (P < 0.001, respectively). During APRV without SB and low tidal volumes, the respective mucosal–submucosal blood flows decreased to 0.24 ± 0.10 (P < 0.01), 0.54 ± 0.21 (P < 0.05), 0.48 ± 0.17 (P < 0.01), 0.43 ± 0.21 (P < 0.01), and 0.50 ± 0.17 (P < 0.001) as compared to APRV with SB. Muscularis–serosal perfusion decreased during full ventilatory support with high tidal volumes in comparison with APRV with SB. Conclusion Maintaining SB during APRV was associated with better systemic and intestinal blood flows. Improvements were more pronounced in the mucosal–submucosal layer.