Vaporized perfluorocarbon improves oxygenation and pulmonary function in an ovine model of acute respiratory distress syndrome.

BACKGROUND: Perfluorocarbon liquids are being used experimentally and in clinical trials for the treatment of acute lung injury. Their resemblance to inhaled anesthetic agents suggests the possibility of application by vaporization. The authors' aim was to develop the technical means for perfluorocarbon vaporization and to investigate its effects on gas exchange and lung function in an ovine model of oleic acid-induced lung injury. METHODS: Two vaporizers were calibrated for perfluorohexane and connected sequentially in the inspiratory limb of a conventional anesthetic machine. Twenty sheep were ventilated in a volume controlled mode at an inspired oxygen fraction of 1.0. Lung injury was induced by intravenous injection of 0.1 ml oleic acid per kilogram body weight. Ten sheep were treated with vaporized perfluorohexane for 30 min and followed for 2 h; 10 sheep served as controls. Measurements of blood gases and respiratory and hemodynamic parameters were obtained at regular intervals. RESULTS: Vaporization of perfluorohexane significantly increased arterial oxygen tension 30 min after the end of treatment (P < 0.01). At 2 h after treatment the oxygen tension was 376+/-182 mmHg (mean +/- SD). Peak inspiratory pressures (P < 0.01) and compliance (P < 0.01) were significantly reduced from the end of the treatment interval onward. CONCLUSION: Vaporization is a new application technique for perfluorocarbon that significantly improved oxygenation and pulmonary function in oleic acid-induced lung injury.     

Effects of Vaporized Perfluorocarbon on Pulmonary Blood Flow and Ventilation/Perfusion Distribution in a Model of Acute Respiratory Distress Syndrome

Background : Perfluorocarbon (PFC) liquids are known to improve gas exchange and pulmonary function in various models of acute respiratory failure . Vaporization has been recently reported as a new method of delivering PFC to the lung. Our aim was to study the effect of PFC vapor on the ventilation/perfusion ( A/ ) matching and relative pulmonary blood flow ( rel) distribution.

Methods : In nine sheep, lung injury was induced using oleic acid. Four sheep were treated with vaporized perfluorohexane (PFX) for 30 min, whereas the remaining sheep served as control animals. Vaporization was achieved using a modified isoflurane vaporizer. The animals were studied for 90 min after vaporization. A/ distributions were estimated using the multiple inert gas elimination technique. Change in rel distribution was assessed using fluorescent-labeled microspheres.

Results : Treatment with PFX vapor improved oxygenation significantly and led to significantly lower shunt values (P < 0.05, repeated-measures analysis of covariance). Analysis of the multiple inert gas elimination technique data showed that animals treated with PFX vapor demonstrated a higher A/ he-terogeneity than the control animals (P < 0.05, repeated-measures analysis of covariance). Microsphere data showed a redistribution of rel attributable to oleic acid injury. rel shifted from areas that were initially high-flow to areas that were initially low-flow, with no difference in redistribution between the groups. After established injury, rel was redistributed to the nondependent lung areas in control animals, whereas rel distribution did not change in treatment animals.     

Effects of vaporized perfluorocarbon on pulmonary blood flow and ventilation/perfusion distribution in a model of acute respiratory distress syndrome.

BACKGROUND: Perfluorocarbon (PFC) liquids are known to improve gas exchange and pulmonary function in various models of acute respiratory failure. Vaporization has been recently reported as a new method of delivering PFC to the lung. Our aim was to study the effect of PFC vapor on the ventilation/perfusion (VA/Q) matching and relative pulmonary blood flow (Qrel) distribution. METHODS: In nine sheep, lung injury was induced using oleic acid. Four sheep were treated with vaporized perfluorohexane (PFX) for 30 min, whereas the remaining sheep served as control animals. Vaporization was achieved using a modified isoflurane vaporizer. The animals were studied for 90 min after vaporization. VA/Q distributions were estimated using the multiple inert gas elimination technique. Change in Qrel distribution was assessed using fluorescent-labeled microspheres. RESULTS: Treatment with PFX vapor improved oxygenation significantly and led to significantly lower shunt values (P < 0.05, repeated-measures analysis of covariance). Analysis of the multiple inert gas elimination technique data showed that animals treated with PFX vapor demonstrated a higher VA/Q heterogeneity than the control animals (P < 0.05, repeated-measures analysis of covariance). Microsphere data showed a redistribution of Qrel attributable to oleic acid injury. Qrel shifted from areas that were initially high-flow to areas that were initially low-flow, with no difference in redistribution between the groups. After established injury, Qrel was redistributed to the nondependent lung areas in control animals, whereas Qrel distribution did not change in treatment animals. CONCLUSION: In oleic acid lung injury, treatment with PFX vapor improves gas exchange by increasing VA/Q heterogeneity in the whole lung without a significant change in gravitational gradient.     

Comparative Effects of Vaporized Perfluorohexane and Partial Liquid Ventilation in Oleic Acid- induced Lung Injury

Background: It is currently not known whether vaporized perfluorohexane is superior to partial liquid ventilation (PLV) for therapy of acute lung injury. In this study, the authors compared the effects of both therapies in oleic acid-induced lung injury.

Methods: Lung injury was induced in 30 anesthetized and mechanically ventilated pigs by means of central venous infusion of oleic acid. Animals were assigned to one of the following groups: (1) control or gas ventilation (GV), (2) 2.5% perfluorohexane vapor, (3) 5% perfluorohexane vapor, (4) 10% perfluorohexane vapor, or (5) PLV with perfluorooctane (30 ml/kg). Two hours after randomization, lungs were recruited and positive end-expiratory pressure was adjusted to obtain minimal elastance. Ventilation was continued during 4 additional hours, when animals were killed for lung histologic examination.

Results: Gas exchange and elastance were comparable among vaporized perfluorohexane, PLV, and GV before the open lung approach was used and improved in a similar fashion in all groups after positive end-expiratory pressure was adjusted to optimal elastance (P < 0.05). A similar behavior was observed in functional residual capacity (FRC) in animals treated with vaporized perfluorohexane and GV. Lung resistance improved after recruitment (P < 0.05), but values were higher in the 10% perfluorohexane and PLV groups as compared with GV (P < 0.05). Interestingly, positive end-expiratory pressure values required to obtain minimal elastance were lower with 5% perfluorohexane than with PLV and GV (P < 0.05). In addition, diffuse alveolar damage was significantly lower in the 5% and 10% perfluorohexane vapor groups as compared with PLV and GV (P < 0.05).     

Reduktion der Aggressivität der Beatmung nach Therapie eines Ölsäure-induzierten Lungenversagens durch Inhalation von Perfluorhexan

INTRODUCTION: The application of perfluorohexane (PFH) vapor led to an improvement of oxygenation and mechanical lung function in a model of oleic acid-induced ARDS in sheep. The aim of this study was to investigate the effects of PFH on gas exchange over an extended time period and to reduce the invasiveness of ventilation. METHOD: ARDS was induced in sheep ( n=12) by injecting 0.1 ml/kg body weight oleic acid intravenously. Six sheep were treated for 30 min with 18 vol.% PFH (PFH-Tx) and followed up over a time period of 240 min while untreated sheep ( n=6) served as controls. Subsequently the F(I)O(2) was reduced to generate a p(a)O(2) between 100-140 mmHg. Gas exchange, respiratory and hemodynamic data were collected at regular intervals. Data were analysed using covariance analysis. RESULTS: PFH treatment led to an improvement in oxygenation ( p<0.01) and in mechanical lung function ( p<0.01). Furthermore, mean pulmonary artery pressure ( p<0.01) and shunt ( p<0.01) were lower in PFH-Tx. F(I)O(2) could be reduced in all PFH-treated animals ( p<0.01). CONCLUSION: Treatment of oleic acid-induced lung injury with PFH vapor improved oxygenation and mechanical lung function over a extended time period allowing a reduction in the invasiveness of 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 x 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).     

Continuous Arterial PO(2) and PCO(2) Measurements in Swine during Nitrous Oxide and Xenon Elimination: Prevention of Diffusion Hypoxia

Background: During nitrous oxide (N2 O) elimination, arterial oxygen tension (PaO(2)) decreases because of the phenomenon commonly called diffusive hypoxia. The authors questioned whether similar effects occur during xenon elimination.

Methods: Nineteen anesthetized paralyzed pigs were mechanically ventilated randomly for 30 min using inspiratory gas mixtures of 30% oxygen and either 70% N2 O or xenon. The inspiratory gas was replaced by a mixture of 70% nitrogen and 30% oxygen. PaO(2) and carbon dioxide tensions were recorded continuously using an indwelling arterial sensor.

Results: The PaO(2) decreased from 119 +/- 10 mmHg to 102 +/- 12 mmHg (mean +/- SD) during N2 O washout (P < 0.01) and from 116 +/- 9 mmHg to 110 +/- 8 mmHg during xenon elimination (P < 0.01), with a significant difference (P < 0.01) between baseline and minimum PaO(2) values (Delta PaO(2), 17 +/- 6 mmHg during N2 O washout and 6 +/- 3 mmHg during xenon washout). The PaCO(2) value also decreased (from 39.3 +/- 6.3 mmHg to 37.6 +/- 5.8 mmHg) during N2 O washout (P < 0.01) and during xenon elimination (from 35.4 +/- 1.6 mmHg to 34.9 +/- 1.6 mmHg; P < 0.01). The Delta PaCO(2) was 1.7 +/- 0.9 mmHg in the N2 O group and 0.5 +/- 0.3 mmHg in the xenon group (P < 0.01).     

Vaporized Perfluorohexane Attenuates Ventilator-induced Lung Injury in Isolated, Perfused Rabbit Lungs

Background: The authors tested the hypothesis that administration of vaporized perfluorohexane may attenuate ventilator-induced lung injury.

Methods: In isolated, perfused rabbit lungs, airway pressure-versus-time curves were recorded. At baseline, peak inspiratory pressure and positive end-expiratory pressure of mechanically ventilated lungs were set to obtain straight pressure-versus-time curves in both the lower and upper ranges, which are associated with less collapse and overdistension, respectively. After that, peak inspiratory pressure and positive end-expiratory pressure were set at 30 cm H2O and 0, respectively, and animals were randomly assigned to one of two groups: (1) simultaneous administration of 14% perfluorohexane vapor in room air (n = 7) and (2) control group-ventilation with room air (n = 7). After 20 min of cycling collapse and overdistension, tidal volume and positive end-expiratory pressure were set back to baseline levels, administration of perfluorohexane in the therapy group was stopped, and mechanical ventilation was continued for up to 60 min. Lung weight, mean pulmonary artery pressure, and concentration of thromboxane B2 in the perfusate were measured. In addition, the distribution of pulmonary perfusate flow was assessed by using fluorescent-labeled microspheres.

Results: Significantly higher peak inspiratory values developed in control lungs than in lungs treated with perfluorohexane. In addition, upper ranges of pressure-versus-time curves were closer to straight lines in the perfluorohexane group. Lung weight, mean pulmonary arterial pressure, and release of thromboxane B2 were significantly higher in controls than in perfluorohexane-treated lungs. Also, redistribution of pulmonary perfusate flow from caudal to cranial zones was less important in the treatment group.     

Comparative effects of vaporized perfluorohexane and partial liquid ventilation in oleic acid-induced lung injury

BACKGROUND: It is currently not known whether vaporized perfluorohexane is superior to partial liquid ventilation (PLV) for therapy of acute lung injury. In this study, the authors compared the effects of both therapies in oleic acid-induced lung injury. METHODS: Lung injury was induced in 30 anesthetized and mechanically ventilated pigs by means of central venous infusion of oleic acid. Animals were assigned to one of the following groups: (1) control or gas ventilation (GV), (2) 2.5% perfluorohexane vapor, (3) 5% perfluorohexane vapor, (4) 10% perfluorohexane vapor, or (5) PLV with perfluorooctane (30 ml/kg). Two hours after randomization, lungs were recruited and positive end-expiratory pressure was adjusted to obtain minimal elastance. Ventilation was continued during 4 additional hours, when animals were killed for lung histologic examination. RESULTS: Gas exchange and elastance were comparable among vaporized perfluorohexane, PLV, and GV before the open lung approach was used and improved in a similar fashion in all groups after positive end-expiratory pressure was adjusted to optimal elastance (P < 0.05). A similar behavior was observed in functional residual capacity (FRC) in animals treated with vaporized perfluorohexane and GV. Lung resistance improved after recruitment (P < 0.05), but values were higher in the 10% perfluorohexane and PLV groups as compared with GV (P < 0.05). Interestingly, positive end-expiratory pressure values required to obtain minimal elastance were lower with 5% perfluorohexane than with PLV and GV (P < 0.05). In addition, diffuse alveolar damage was significantly lower in the 5% and 10% perfluorohexane vapor groups as compared with PLV and GV (P < 0.05). CONCLUSIONS: Although the use of 5% vaporized perfluorohexane permitted the authors to reduce pressures needed to stabilize the lungs and was associated with better histologic findings than were PLV and GV, none of these perfluorocarbon therapies improved gas exchange or lung mechanics as compared with GV.     

Effects of Peak Inspiratory Flow on Development of Ventilator-induced Lung Injury in Rabbits

Background: A lung-protecting strategy is essential when ventilating acute lung injury/acute respiratory distress syndrome patients. Current emphasis is on limiting inspiratory pressure and volume. This study was designed to investigate the effect of peak inspiratory flow on lung injury.

Methods: Twenty-four rabbits were anesthetized, tracheostomized, ventilated with a Siemens Servo 300, and randomly assigned to three groups as follows: 1) the pressure regulated volume control group received pressure-regulated volume control mode with inspiratory time set at 20% of total cycle time, 2) the volume control with 20% inspiratory time group received volume-control mode with inspiratory time of 20% of total cycle time, and 3) the volume control with 50% inspiratory time group received volume-control mode with inspiratory time of 50% of total cycle time. Tidal volume was 30 ml/kg, respiratory rate was 20 breaths/min, and positive end-expiratory pressure was 0 cm H2O. After 6 h mechanical ventilation, the lungs were removed for histologic examination.

Results: When mechanical ventilation started, peak inspiratory flow was 28.8 +/- 1.4 l/min in the pressure regulated volume control group, 7.5 +/- 0.5 l/min in the volume control with 20% inspiratory time group, and 2.6 +/- 0.3 l/min in the volume control with 50% inspiratory time group. Plateau pressure did not differ significantly among the groups. Gradually during 6 h, Pao2 in the pressure regulated volume control group decreased from 688 +/- 39 to a significantly lower 304 +/- 199 mm Hg (P < 0.05) (mean +/- SD). The static compliance of the respiratory system for the pressure regulated volume control group also ended significantly lower after 6 h (P < 0.05). Wet to dry ratio for the pressure regulated volume control group was larger than for other groups (P < 0.05). Macroscopically and histologically, the lungs of the pressure regulated volume control group showed more injury than the other groups.     

Continuous Venovenous Hemofiltration Improves Arterial Oxygenation in Endotoxin-induced Lung Injury in Pigs

Background: Hypoxemia is common in septic acute lung failure. Therapy is mainly supportive, and most trials using specific inhibitors of key inflammatory mediators (i.e., tumor necrosis factor [alpha], interleukin 1) have failed to prove beneficial. The authors investigated if a nonspecific blood purification technique, using zero-balanced high-volume continuous venovenous hemofiltration (CVVH), might improve arterial oxygenation in a fluid-resuscitated porcine model of endotoxin-induced acute lung injury.

Methods: Piglets of both sexes weighing 25-30 kg were anesthetized and mechanically ventilated. After baseline measurements, animals received an intravenous infusion of 0.5 mg/kg endotoxin (Escherichia coli lipopolysaccharide). One hour after endotoxin, animals were randomly assigned to either treatment with CVVH (endotoxin + hemofiltration, n = 6) or spontaneous course (endotoxin, n = 6). At 4 h after randomization, animals were killed. Hemofiltration was performed from femoral vein to femoral vein using a standard circuit with an EF60 polysulphone hemofilter.

Results: Endotoxin challenge induced arterial hypoxemia, an increase in peak inspiratory pressure, pulmonary hypertension, and systemic hypotension. Treatment with CVVH did not improve systemic or pulmonary hemodynamics. However, arterial oxygenation was increased in endotoxin-challenged animals at 5 h after completion of endotoxin infusion, as compared with animals not receiving CVVH (arterial oxygen tension, 268 +/- 33 vs. 176 +/- 67 mmHg, respectively, P < 0.01). In addition, treatment with CVVH attenuated the endotoxin-induced increase in peak inspiratory pressure and increased lung compliance.     

Optimal Mean Airway Pressure during High-frequency Oscillation: Predicted by the Pressure-Volume Curve

Background: A number of groups have recommended setting positive end-expiratory pressure during conventional mechanical ventilation in adults at 2 cm H2O above the lower corner pressure (PCL) of the inspiratory pressure-volume (P-V) curve of the respiratory system. No equivalent recommendations for the setting of the mean airway pressure (Paw) during high-frequency oscillation (HFO) exist. The authors questioned if the Paw resulting in the best oxygenation without hemodynamic compromise during HFO is related to the static P-V curve in a large animal model of acute respiratory distress syndrome.

Methods: Saline lung lavage was performed in seven sheep (28 +/- 5 kg, mean +/- SD) until the arterial oxygen partial pressure/fraction of inspired oxygen ratio decreased to 85 +/- 27 mmHg at a positive end-expiratory pressure of 5 cm H2O (initial injury). The PCL (20 +/- 1 cm H2O) on the inflation limb and the point of maximum curvature change (PMC; 26 +/- 1 cm H2O) on the deflation limb of the static P-V curve were determined. The sheep were subjected to four 1-h cycles of HFO at different levels of Paw (PCL + 2, + 6, + 10, + 14 cm H2O), applied in random order. Each cycle was preceded by a recruitment maneuver at a sustained Paw of 50 cm H2O for 60 s.

Results: High-frequency oscillation with a Paw of 6 cm H2O above PCL (PCL + 6) resulted in a significant improvement in oxygenation (P < 0.01 vs. initial injury). No further improvement in oxygenation was observed with higher Paw, but cardiac output decreased, pulmonary vascular resistance increased, and oxygen delivery decreased at Paw greater than PCL + 6. The PMC on the deflation limb of the P-V curve was equal to the PCL + 6 (r = 0.77, P < 0.05).     

Influence of fructose-1,6-diphosphate on endotoxin-induced lung injuries in sheep

BACKGROUND: Fructose-1,6-diphosphate (FDP) is reported to have a salutary effect in endotoxin shock and sepsis. This investigation describes the effect of FDP on pulmonary and systemic hemodynamics, lung lymph protein clearance, and leukocyte count in sheep infused with Escherichia coli endotoxin. MATERIALS AND METHODS: Anesthetized sheep (n = 18), some of which underwent thoracotomy to cannulate lymphatic nodes, were used in this study. After stabilization, all sheep received E. coli endotoxin, 5 microg/kg i.v. infusion over 30 min. Concomitant with the endotoxin infusion, half of the animals were randomly selected to receive an i.v. bolus of FDP (10%), 50 mg/kg, followed by a continuous infusion of 5 mg.kg(-1).min(-1) for 4 h; the rest were treated in the same manner with glucose (10%) in 0.9% NaCl. RESULTS: Pulmonary artery pressure (PAP) and resistance in the glucose group increased from 20.8 +/- 1.6 to 36.7 +/- 3.2 mmHg (P < 0.007) and from 531 +/- 114 to 1137 +/- 80 dyn.s(-1).cm(-5), respectively (P < 0.005). Despite an increase during endotoxin infusion, these parameters in the FDP group returned to control values. There were no differences in left ventricular pressures, cardiac output, heart rate, and arterial oxygen tension between the groups. In the glucose group, lymph protein clearance was higher (P < 0.01) and blood leukocyte count was lower (P < 0.02). The wet/dry lung weight ratio (g/g) for the glucose group was 5.57 +/- 0.04 and for the FDP-treated group 4.76 +/- 0.06 (P < 0.0005). CONCLUSION: FDP treatment attenuated significantly the characteristic pulmonary hypertension, lung lymph protein clearance, and pulmonary vascular leakage seen in sheep infused with endotoxin.     

Cardiorespiratory Effects of Automatic Tube Compensation during Airway Pressure Release Ventilation in Patients with Acute Lung Injury

Background: Spontaneous breaths during airway pressure release ventilation (APRV) have to overcome the resistance of the artificial airway. Automatic tube compensation provides ventilatory assistance by increasing airway pressure during inspiration and lowering airway pressure during expiration, thereby compensating for resistance of the artificial airway. The authors studied if APRV with automatic tube compensation reduces the inspiratory effort without compromising cardiovascular function, end-expiratory lung volume, and gas exchange in patients with acute lung injury.

Methods: Fourteen patients with acute lung injury were breathing spontaneously during APRV with or without automatic tube compensation in random order. Airway pressure, esophageal and abdominal pressure, and gas flow were continuously measured, and tracheal pressure was estimated. Trans-diaphragmatic pressure time product was calculated. End-expiratory lung volume was determined by nitrogen washout. The validity of the tracheal pressure calculation was investigated in seven healthy ventilated pigs.

Results: Automatic tube compensation during APRV increased airway pressure amplitude from 7.7 +/- 1.9 to 11.3 +/- 3.1 cm H2O (mean +/- SD;P < 0.05) while decreasing trans-diaphragmatic pressure time product from 45 +/- 27 to 27 +/- 15 cm H2O [middle dot] s-1 [middle dot] min-1 (P < 0.05), whereas tracheal pressure am-plitude remained essentially unchanged (10.3 +/- 3.5 vs. 10.1 +/- 3.5 cm H2O). Minute ventilation increased from 10.4 +/- 1.6 to 11.4 +/- 1.5 l/min (P < 0.001), decreasing arterial carbon dioxide tension from 52 +/- 9 to 47 +/- 6 mmHg (P < 0.05) without affecting arterial blood oxygenation or cardiovascular function. End-expiratory lung volume increased from 2,806 +/- 991 to 3,009 +/- 994 ml (P < 0.05). Analysis of tracheal pressure-time curves indicated nonideal regulation of the dynamic pressure support during automatic tube compensation as provided by a standard ventilator.     

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 H(2)O. 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 x 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 (r(2) = 0.62 and r(2) = 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.     

Effect of rate and inspiratory flow on ventilator-induced lung injury

BACKGROUND: We examined the effects of decreasing respiratory rate (RR) at variable inspiratory times (It) and reducing inspiratory flow on the development of ventilator-induced lung injury. METHODS: Forty sheep weighing 24.6+/-3.2 kg were ventilated for 6 hours with one of five strategies (FIO2 = 1.0, positive end-expiratory pressure = 5 cm H2O): (1) pressure-controlled ventilation (PCV), RR = 15 breaths/min, peak inspiratory pressure (PIP) = 25 cm H2O, n = 8; (2) PCV, RR = 15 breaths/min, PIP = 50 cm H2O, n = 8; (3) PCV, RR = 5 breaths/min, PIP = 50 cm H2O, It = 6 seconds, n = 8; (4) PCV, RR = 5 breaths/min, PIP = 50 cm H2O, It = 2 seconds, n = 8; and (5) limited inspiratory flow volume-controlled ventilation, RR = 5 breaths/min, pressure-limit = 50 cm H2O, flow = 15 L/min, n = 8. RESULTS: Decreasing RR at conventional flows did not reduce injury. However, limiting inspiratory flow rate (LIFR) maintained compliance and resulted in lower Qs/Qt (HiPIP = 38+/-18%, LIFR = 19+/-6%, p < 0.001), reduced histologic injury (HiPIP = 14+/-0.9, LIFR = 2.2+/-0.9, p < 0.05), decreased intra-alveolar neutrophils (HiPIP = 90+/-49, LIFR = 7.6+/-3.8,p = 0.001), and reduced wet-dry lung weight (HiPIP = 87.3+/-8.5%, LIFR = 40.8+/-17.4%,p < 0.001). CONCLUSIONS: High-pressure ventilation for 6 hours using conventional flow patterns produces severe lung injury, irrespective of RR or It. Reduction of inspiratory flow at similar PIP provides pulmonary protection.     

Vaporized perfluorohexane attenuates ventilator-induced lung injury in isolated, perfused rabbit lungs

BACKGROUND: The authors tested the hypothesis that administration of vaporized perfluorohexane may attenuate ventilator-induced lung injury. METHODS: In isolated, perfused rabbit lungs, airway pressure-versus-time curves were recorded. At baseline, peak inspiratory pressure and positive end-expiratory pressure of mechanically ventilated lungs were set to obtain straight pressure-versus-time curves in both the lower and upper ranges, which are associated with less collapse and overdistension, respectively. After that, peak inspiratory pressure and positive end-expiratory pressure were set at 30 cm H2O and 0, respectively, and animals were randomly assigned to one of two groups: (1) simultaneous administration of 14% perfluorohexane vapor in room air (n = 7) and (2) control group-ventilation with room air (n = 7). After 20 min of cycling collapse and overdistension, tidal volume and positive end-expiratory pressure were set back to baseline levels, administration of perfluorohexane in the therapy group was stopped, and mechanical ventilation was continued for up to 60 min. Lung weight, mean pulmonary artery pressure, and concentration of thromboxane B2 in the perfusate were measured. In addition, the distribution of pulmonary perfusate flow was assessed by using fluorescent-labeled microspheres. RESULTS: Significantly higher peak inspiratory values developed in control lungs than in lungs treated with perfluorohexane. In addition, upper ranges of pressure-versus-time curves were closer to straight lines in the perfluorohexane group. Lung weight, mean pulmonary arterial pressure, and release of thromboxane B2 were significantly higher in controls than in perfluorohexane-treated lungs. Also, redistribution of pulmonary perfusate flow from caudal to cranial zones was less important in the treatment group. CONCLUSION: The authors conclude that the administration of perfluorohexane vapor attenuates the development of ventilator-induced lung injury in isolated, perfused rabbit lungs.     

Cardiorespiratory effects of automatic tube compensation during airway pressure release ventilation in patients with acute lung injury

BACKGROUND: Spontaneous breaths during airway pressure release ventilation (APRV) have to overcome the resistance of the artificial airway. Automatic tube compensation provides ventilatory assistance by increasing airway pressure during inspiration and lowering airway pressure during expiration, thereby compensating for resistance of the artificial airway. The authors studied if APRV with automatic tube compensation reduces the inspiratory effort without compromising cardiovascular function, end-expiratory lung volume, and gas exchange in patients with acute lung injury. METHODS: Fourteen patients with acute lung injury were breathing spontaneously during APRV with or without automatic tube compensation in random order. Airway pressure, esophageal and abdominal pressure, and gas flow were continuously measured, and tracheal pressure was estimated. Transdiaphragmatic pressure time product was calculated. End-expiratory lung volume was determined by nitrogen washout. The validity of the tracheal pressure calculation was investigated in seven healthy ventilated pigs. RESULTS: Automatic tube compensation during APRV increased airway pressure amplitude from 7.7+/-1.9 to 11.3+/-3.1 cm H2O (mean +/- SD; P < 0.05) while decreasing trans-diaphragmatic pressure time product from 45+/-27 to 27+/-15 cm H2O x s(-1) x min(-1) (P < 0.05), whereas tracheal pressure amplitude remained essentially unchanged (10.3+/-3.5 vs. 10.1+/-3.5 cm H2O). Minute ventilation increased from 10.4+/-1.6 to 11.4+/-1.5 l/min (P < 0.001), decreasing arterial carbon dioxide tension from 52+/-9 to 47+/-6 mmHg (P < 0.05) without affecting arterial blood oxygenation or cardiovascular function. End-expiratory lung volume increased from 2,806+/-991 to 3,009+/-994 ml (P < 0.05). Analysis of tracheal pressure-time curves indicated nonideal regulation of the dynamic pressure support during automatic tube compensation as provided by a standard ventilator. CONCLUSION: In the studied patients with acute lung injury, automatic tube compensation markedly unloaded the inspiratory muscles and increased alveolar ventilation without compromising cardiorespiratory function and end-expiratory lung volume.     

肺牵张指数指导不同原因急性呼吸窘迫综合征复张后呼气末正压选择的实验研究

目的研究以肺牵张指数指导不同原因急性呼吸窘迫综合征(ARDS)肺复张后呼气末正压(PEEP)的选择。方法通过静脉注射油酸、生理盐水肺灌洗和盐酸吸入建立三种犬ARDS模型。容量控制通气,回归法计算肺牵张指数(b)。调整PEEP使b=1,肺复张后再次调整PEEP,分别使b=1、<1与>1。稳定通气30 min后测定肺复张容积,同时观察呼吸力学和肺气体交换。结果盐水灌洗组复张后b=1时的PEEP为(12．8±1．8)cm H2O,显著高于盐酸吸入组[(9．2±1．8)cm H2O,P<0．05],但与油酸组比较无显著差异。与复张前b=1相比,三组复张后b=1时的氧合指数均显著升高。复张后b=1时,油酸组氧合指数为(399±61)mm Hg,较b<1[(307±71)mm Hg]时显著增加(P<0．05),与b>1时比较无显著差异。复张后b=1时,盐水灌洗组氧合指数显著高于盐酸吸入组(P<0．05),但与油酸组比较无显著差异(P>0．05)。三组动物复张后b=1时肺复张容积无明显差异,但均显著高于复张前b=1时的复张容积(P<0．05)。与复张后b>1比较,三组动物复张后b=1时均具有较高的肺顺应性和明显较低的气道平台压。结论肺牵张指数可指导不同原因ARDS复张后的PEEP选择。     

Ventilation with Constant Versus Decelerating Inspiratory Flow in Experimentally Induced Acute Respiratory Failure

Background: Recognition of the potential for ventilator-associated lung injury has renewed the debate on the importance of the inspiratory flow pattern. The aim of this study was to determine whether a ventilatory pattern with decelerating inspiratory flow, with the major part of the tidal volume delivered early, would increase functional residual capacity at unchanged (or even reduced) inspiratory airway pressures and improve gas exchange at different positive end-expiratory pressure levels.

Methods: Surfactant depletion was induced by repeated bronchoalveolar lavage in 13 anesthetized piglets. Decelerating and constant inspiratory flow ventilation was applied at positive end-expiratory pressure levels of 22, 17, 13, 9, and 4 cm H2 O. Tidal volume, inspiration-to-expiration ratio, and ventilatory frequency were kept constant. Airway pressures, gas exchange, functional residual capacity (using a wash-in/washout method with sulfurhexafluoride), central hemodynamics, and extravascular lung water (using the thermo-dye-indicator dilution technique) were measured.

Results: Decelerating inspiratory flow yielded a lower arterial carbon dioxide tension compared to constant flow, that is, it improved alveolar ventilation. There were no differences between the flow patterns regarding end-inspiratory occlusion airway pressure, end-inspiratory lung volume, static compliance, or arterial oxygen tension. No differences were seen in hemodynamics and oxygen delivery.