Does airway pressure release ventilation alter lung function after acute lung injury?

BACKGROUND: During airway pressure release ventilation (APRV), tidal ventilation occurs between the increased lung volume established by the application of continuous positive airway pressure (CPAP) and the relaxation volume of the respiratory system. Concern has been expressed that release of CPAP may cause unstable alveoli to collapse and not reinflate when airway pressure is restored. OBJECTIVE: To compare pulmonary mechanics and oxygenation in animals with acute lung injury during CPAP with and without APRV. DESIGN: Experimental, subject-controlled, randomized crossover investigation. SETTING: Anesthesiology research laboratory, University of South Florida College of Medicine Health Sciences Center. SUBJECTS: Ten pigs of either sex. INTERVENTIONS: Acute lung injury was induced with an intravenous infusion of oleic acid (72 micrograms/kg) followed by randomly alternated 60-min trials of CPAP with and without APRV. Continuous positive airway pressure was titrated to produce an arterial oxyhemoglobin saturation of at least 95% (FIO2 = 0.21). Airway pressure release ventilation was arbitrarily cycled to atmospheric pressure 10 times per minute with a release time titrated to coincide with attainment of respiratory system relaxation volume. MEASUREMENTS: Cardiac output, arterial and mixed venous pH, blood gas tensions, hemoglobin concentration and oxyhemoglobin saturation, central venous pressure, pulmonary and systemic artery pressures, pulmonary artery occlusion pressure, airway gas flow, airway pressure, and pleural pressure were measured. Tidal volume (VT), dynamic lung compliance, intrapulmonary venous admixture, pulmonary vascular resistance, systemic vascular resistance, oxygen delivery, oxygen consumption, and oxygen extraction ratio were calculated. MAIN RESULTS: Central venous infusion of oleic acid reduced PaO2 from 94 +/- 4 mm Hg to 52 +/- 9 mm Hg (mean +/- 1 SD) (p < 0.001) and dynamic lung compliance from 40 +/- 6 mL/cm H2O to 20 +/- 6 mL/cm H2O (p = 0.002) and increased venous admixture from 13 +/- 3% to 32 +/- 7% (p < 0.001) in ten swine weighing 33.3 +/- 4.1 kg while they were spontaneously breathing room air. After induction of lung injury, the swine received CPAP (14.7 +/- 3.3 cm H2O) with or without APRV at 10 breaths per minute with a release time of 1.1 +/- 0.2 s. Although mean transpulmonary pressure was significantly greater during CPAP (11.7 +/- 3.3 cm H2O) vs APRV (9.4 +/- 3.8 cm H2O) (p < 0.001), there were no differences in hemodynamic variables. PaCO2 was decreased and pHa was increased during APRV vs CPAP (p = 0.003 and p = 0.005). PaO2 declined from 83 +/- 4 mm Hg to 79 +/- 4 mm Hg (p = 0.004) during APRV, but arterial oxyhemoglobin saturation (96.6 +/- 1.4% vs 96.9 +/- 1.3%) did not. Intrapulmonary venous admixture (9 +/- 3% vs 11 +/- 5%) and oxygen delivery (469 +/- 67 mL/min vs 479 +/- 66 mL/min) were not altered. After treatment periods and removal of CPAP for 60 min, PaO2 and intrapulmonary venous admixture returned to baseline values. DISCUSSION: Intrapulmonary venous admixture, arterial oxyhemoglobin saturation, and oxygen delivery were maintained by APRV at levels induced by CPAP despite the presence of unstable alveoli. Decrease in PaO2 was caused by increase in pHa and decrease in PaCO2, not by deterioration of pulmonary function. We conclude that periodic decrease of airway pressure created by APRV does not cause significant deterioration in oxygenation or lung mechanics.     

Comparison of alveolar ventilation, oxygenation, pressure support, and respiratory system resistance in response to noninvasive versus conventional mechanical ventilation in foals

OBJECTIVE: To compare the efficacy of positive pressure ventilation applied through a mask versus an endotracheal tube, using anesthetized/paralyzed foals as a model for foals with hypoventilation. ANIMALS: Six 1-month-old foals. PROCEDURE: A crossover design was used to compare the physiologic response of foals to 2 ventilatory techniques, noninvasive mask mechanical ventilation (NIMV) versus endotracheal mechanical ventilation (ETMV), during a single period of anesthesia and paralysis. Arterial pH, PaO2, PaCO2, oxygen saturation, end-tidal CO2 tension, airway pressures, total respiratory system resistance, resistance across the upper airways (proximal to the midtracheal region), and positive end-expiratory pressures (PEEP) were measured. Only tidal volume (VT; 10, 12.5, and 15 ml/kg of body weight) or PEEP (7 cm of H2O) varied. RESULTS: Compared with ETMV, use of NIMV at equivalent VT resulted in PaCO2 and pH values that were significantly higher, but PaO2 was only slightly lower. Between the 2 methods, peak airway pressure was similar, but peak expiratory flow was significantly lower and total respiratory resistance higher at each VT for NIMV. Delivery of PEEP (7 cm of H2O) was slightly better for ETMV (7.1 +/- 1.3 cm of H2O) than for NIMV (5.6 +/- 0.6 cm of H2O). CONCLUSION: These data suggest that use of NIMV induces similar physiologic effects as ETMV, but the nasal cavities and mask contribute greater dead space, manifesting in hypercapnia. Increasing the VT used on a per kilogram of body weight basis, or the use of pressure-cycled ventilation might reduce hypercapnia during NIMV. CLINICAL RELEVANCE: Use of NIMV might be applicable in selected foals, such as those with hypoventilation and minimal changes in lung compliance, during weaning from endotracheal mechanical ventilation, or for short-term ventilation in weak foals.     

Pressure-controlled, inverse ratio ventilation that avoids air trapping in the adult respiratory distress syndrome

OBJECTIVES: To investigate physiologic and outcome data in patients switched from volume-cycled conventional ratio ventilation to pressure-controlled inverse ratio ventilation that did not produce air trapping and intrinsic positive end-expiratory pressure (PEEP). SETTING: Medical intensive care unit. DESIGN: Retrospective analysis of crossover data and outcome. PATIENTS: Fourteen patients with the adult respiratory distress syndrome who were receiving mechanical ventilation with volume-cycled, conventional ratio ventilation followed by pressure-controlled, inverse ratio ventilation. INTERVENTIONS: Our approach to pressure-controlled, inverse ratio ventilation was to use tidal volumes and applied PEEP values comparable to those volumes and values used on volume-cycled, conventional ratio ventilation, use inspiratory times to increase mean airway pressure instead of additional applied PEEP, and avoid air trapping (intrinsic PEEP). MEASUREMENTS AND MAIN RESULTS: With this approach, there was a reduction in peak airway pressure from 53 +/- 8.5 (SD) to 40 +/- 5.9 cm H2O (p < .01), and an increase in mean airway pressure from 20 +/- 3.9 to 30 +/- 5.2 cm H2O (p < .01). Tidal volume, mean inflation pressure, and compliance did not change. Oxygenation (PaO2) improved from 57 +/- 11.3 torr (7.6 +/- 1.5 kPa) to 94 +/- 40.2 torr (12.5 +/- 5.4 kPa) (p = .01) but the oxygenation index (mean airway pressure x FIO2 x 100/PaO2) did not change significantly (25.9 +/- 10.3 to 27.2 +/- 12.2). There was no significant change in PaCO2 or pH even though delivered minute ventilation decreased from 17.4 +/- 4.3 to 14.8 +/- 5.8 L/min (p = .02). Cardiac index slightly decreased, but hemodynamic values were otherwise stable. Only three of the 14 study patients survived. CONCLUSIONS: These data demonstrate that oxygenation is primarily a function of mean airway pressure, and that longer inspiratory times can be used as an alternative to applied PEEP to increase this oxygenation. If no air trapping develops, lung inflation pressures and delivered volumes remain constant with this approach. Because the technique was used only in patients refractory to conventional techniques, the poor outcome is not surprising.     

Increasing tidal volumes and pulmonary overdistention adversely affect pulmonary vascular mechanics and cardiac output in a pediatric swine model

OBJECTIVES: In a pediatric swine model, the effects of increasing tidal volumes and the subsequent development of pulmonary overdistention on cardiopulmonary interactions were studied. The objective was to test the hypothesis that increasing tidal volumes adversely affect pulmonary vascular mechanics and cardiac output. An additional goal was to determine whether the effects of pulmonary overdistention are dependent on delivered tidal volume and/or positive end-expiratory pressure (PEEP, end-expiratory lung volume). DESIGN: Prospective, randomized, controlled laboratory trial. SETTING: University research laboratory. SUBJECTS: Eleven 4- to 6-wk-old swine, weighing 8 to 12 kg. INTERVENTIONS: Piglets with normal lungs were anesthetized, intubated, and paralyzed. After median sternotomy, pressure transducers were placed in the right ventricle, pulmonary artery, and left atrium. An ultrasonic flow probe was placed around the pulmonary artery. MEASUREMENTS AND MAIN RESULTS: The swine were ventilated and data were collected with delivered tidal volumes of 10, 15, 20, and 25 mL/kg and PEEP settings of 5 and 10 cm H2O in a random order. Pulmonary overdistention was defined as a decrease in dynamic compliance of > or =20% when compared with a compliance measured at a baseline tidal volume of 10 mL/kg. At this baseline tidal volume, airway pressure-volume curves did not demonstrate pulmonary overdistention. Tidal volumes and airway pressures were measured by a pneumotachometer and the Pediatric Pulmonary Function Workstation. Inspiratory time (0.75 sec), FIO2 (0.3), and minute ventilation were held constant. We evaluated the pulmonary vascular and cardiac effects of the various tidal volume and PEEP settings by measuring pulmonary vascular resistance, pulmonary characteristic impedance, and cardiac output. When compared with a tidal volume of 10 mL/kg, a tidal volume of 20 mL/kg resulted in a significant decrease in dynamic compliance from 10.5 +/- 0.9 to 8.4 +/- 0.6 mL/cm H2O (p = .02) at a constant PEEP of 5 cm H2O. The decrease in dynamic compliance of 20% indicated the presence of pulmonary overdistention by definition. As the tidal volume was increased from 10 to 20 mL/kg, pulmonary vascular resistance (1351 +/- 94 vs. 2266 +/- 233 dyne x sec/cm5; p = .004) and characteristic impedance (167 +/- 12 vs. 219 +/- 22 dyne x sec/cm5; p = .02) significantly increased, while cardiac output significantly decreased (951 +/- 61 vs. 708 +/- 48 mL/min; p = .001). Each of these effects of pulmonary overdistention were further magnified when the tidal volume was increased to 25 mL/kg. The tidal volume-induced alterations in pulmonary vascular mechanics, characteristic impedance, and cardiac output occurred to a greater degree when the PEEP was increased to 10 cm H2O. Pulmonary vascular resistance and characteristic impedance were significantly increased and cardiac output significantly decreased for all tidal volumes studied at a PEEP of 10 cm H2O as compared with 5 cm H2O. CONCLUSIONS: Increasing tidal volumes, increasing PEEP levels, and the development of pulmonary overdistention had detrimental effects on the cardiovascular system by increasing pulmonary vascular resistance and characteristic impedance while significantly decreasing cardiac output. Delivered tidal volumes of >15 mL/kg should be utilized cautiously. Careful monitoring of respiratory mechanics and cardiac function, especially in neonatal and pediatric patients, is warranted.     

Does alveolar recruitment occur with positive end-expiratory pressure in adult respiratory distress syndrome patients?

We studied the effects of positive end-expiratory pressure (PEEP) (2 to 14 cm H2O) on alveolar recruitment (Vrec), static respiratory compliance, and end-expiratory lung volume (EELV) in nine sedated, paralyzed, mechanically ventilated adult respiratory distress syndrome patients. Positive end-expiratory pressure was applied in increasing and decreasing steps of 2 cm H2O. Flow, tidal volume, and airway pressure were measured. We used the rapid airway occlusion technique to determine static end-inspiratory elastic recoil pressure of the respiratory system (Pst, rs) and intrinsic PEEP (PEEPi). The changes in EELV were measured with respiratory inductive plethysmography. Alveolar recruitment was estimated as the difference in lung volume between PEEP and zero end-expiratory pressure (ZEEP) for the same end-inspiratory Pst, rs (20 cm H2O). We found that (1) Vrec with PEEP up to 14 cm H2O was in general rather small and was absent in two patients; (2) all patients exhibited PEEPi at ZEEP (5.6 +/- 1.0 cm H2O) and little change in EELV and Vrec was achieved until the external PEEP exceeded PEEPi; (3) if end-inspiratory Pst, rs is high at ZEEP, there is little or no alveolar recruitment with PEEP; and (4) Vrec and EELV were slightly higher during stepwise deflation than stepwise inflation with PEEP, except at ZEEP where EELV did not change after inflation-deflation runs with PEEP.     

Evaluation of lung function after intratracheal perfluorocarbon administration in healthy animals

OBJECTIVES: To investigate the effects of partial liquid ventilation (i.e., mechanical ventilation in combination with intratracheal administration of perfluorocarbon) on lung function, with particular attention to the integrity of the alveolocapillary membrane in healthy adult animals. DESIGN: Prospective, randomized, controlled study. SETTING: Laboratory at the Department of Experimental Anesthesiology, Erasmus University Rotterdam. SUBJECTS: Ten adult male New Zealand rabbits. INTERVENTIONS: Five rabbits were intratracheally treated with 12 mL/kg of perfluorocarbon while conventional mechanical ventilation (volume-controlled, tidal volume of 12 mL/kg, respiratory rate of 30 breaths/min, inspiration/expiration ratio of 1:2, positive end-expiratory pressure of 2 cm H2O, and an FIO2 of 1.0) was applied for 3 hrs. To assess the permeability of the alveolocapillary membrane, pulmonary clearance of inhaled technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) measurements were performed at 3 hrs and compared with data from the control group (n = 5) treated with mechanical ventilation only, using the same ventilatory parameters. MEASUREMENTS AND MAIN RESULTS: Pulmonary gas exchange and lung mechanical parameters were measured in both groups at 30-min intervals. Mean values for PaO2 in the perfluorocarbon group, although at adequate levels, were less than those values of the control group during the 3-hr study period (370 +/- 44 vs. 503 +/- 44 torr at 3 hrs [49.3 +/- 5.9 vs. 67.1 +/- 5.9 kPa]). Peak and mean airway pressures were higher in the perfluorocarbon group (ranging from 1.9 to 3.4 cm H2O and 0.7 to 1.3 cm H2O, respectively) compared with the control group, while end-inspiratory airway pressure was similar in both groups. The half-life of 99mTc-DTPA was 83.7 +/- 24.5 mins in the control group, which was significantly longer (p < .01) than in the perfluorocarbon group (49.8 +/- 6.1 mins). CONCLUSIONS: These findings suggest that partial liquid ventilation with perfluorocarbons lowers pulmonary gas exchange in healthy animals, and the increased pulmonary clearance of 99mTc-DTPA after 3 hrs of this type of ventilatory support may reflect minimal reversible changes in the lung surfactant system.     

Effects of partial liquid ventilation with perfluorocarbons on pressure-flow relationships, vascular compliance, and filtration coefficients of isolated blood-perfused rabbit lungs

OBJECTIVES: The density of perfluorocarbons is almost twice that of blood. Therefore, we hypothesized that partial liquid ventilation with these fluids markedly affects pulmonary hemodynamics and filtration coefficients. To test these hypotheses we studied pressure-flow relationships, vascular compliances, capillary pressures, and filtration coefficients in normal and perfluorocarbon-ventilated rabbit lungs. DESIGN: Controlled animal study with an ex-vivo isolated lung preparation. SETTING: Research laboratory for experimental anesthesiology at the Heinrich-Heine-University of Düsseldorf. SUBJECTS: Fourteen New Zealand White rabbits. INTERVENTIONS: The lungs were perfused under zone 3 flow conditions with autologous blood at various flow rates (50 to 250 mL/min, closed circuit, roller pump, 37 degrees C) and ventilated with 5% CO2 in air (positive end-expiratory pressure: 2 cm H2O, tidal volume: 10 mL/kg, respiratory rate: 30 breaths/min) without (control group, n=7) and with (n=7) perfluorocarbon administered intratracheally (15 mL/kg). MEASUREMENTS AND MAIN RESULTS: Pulmonary arterial, left atrial, and airway pressures, as well as blood reservoir volume (reflecting changes in pulmonary blood volume) and lung weight, were measured continuously. Inconsistent with our hypothesis, we found no significant differences between both groups in the slopes and intercepts of the pressure-flow relationships. There were no significant differences in capillary pressures determined by double occlusion (6.7+/-1.2 vs. 6.3+/-1.3 cm H2O for control group, p=.53), vascular compliances (0.51+/-0.10 vs. 0.47+/-0.09 mL/cm H2O for control group, p=.38), and filtration coefficients (0.33+/-0.06 vs. 0.37+/-0.07 mL/min/mm Hg/100 g wet weight for control group, p=.80, Mann-Whitney). CONCLUSIONS: Partial liquid ventilation with perfluorocarbons has no relevant effects on pulmonary filtration coefficients and global hemodynamic variables of isolated zone 3 lungs. These findings suggest that right ventricular afterload is not changed with partial liquid ventilation. It is likely, however, that intrapulmonary blood flow is redistributed toward less-dependent regions, although relevant global hemodynamic changes are absent during partial liquid ventilation.     

Serologic test for syphilis as a surrogate marker for human immunodeficiency virus infection among United States blood donors

OBJECTIVE: To determine the presence of tricuspid regurgitation (TR) in patients affected by acute lung injury (ALI) and the adult respiratory distress syndrome (ARDS) during mechanical ventilation with positive end-expiratory pressure (PEEP). DESIGN: A prospective clinical study. SETTING: 10-bed general intensive care unit in a University Hospital. PATIENTS: 7 consecutive patients an age 44.7 +/- 8.6 years with a diagnosis of ALI or ARDS were studied. All were on mechanical ventilation with PEEP. INTERVENTIONS: PEEP was increased in steps of 5 cm H2O until the appearance of TR or up to a limit of 20 cm H2O. MEASUREMENTS AND RESULTS: Right atrial pressure, pulmonary artery pressure, and wedge pressure were measured and cardiac output was determined by thermodilution. TR was graded from 0 to 3. Standard 2D echocardiographic and pulsed-wave images were obtained at each level of PEEP. PEEP was increased from 4 +/- 3 to 17 +/- 2 cm H2O. Mean PAP increased from 27.7 +/- 2.9 to 36.7 +/- 3.5 mm Hg (p < 0.02) when PEEP was increased. Five patients had competent valves and two had mild TR at baseline. In six out of the seven, TR either developed or increased when PEEP was increased. CONCLUSIONS: Our study demonstrated the development of TR after the use of PEEP in patients with ALI and ARDS as a consequence of pulmonary hypertension and right ventricular overloading. Since TR may randomly affect cardiac output values and derived parameters, the assessment of cardiac performance by some techniques such as thermodilution should be used with caution.     

Volume-controlled versus biphasic positive airway pressure ventilation in leukopenic patients with severe respiratory failure

OBJECTIVE: To study comparatively the effects of volume-controlled vs. biphasic positive airway pressure mechanical ventilation on respiratory mechanics and oxygenation in leukopenic patients with severe respiratory failure. DESIGN: Prospective, comparative study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Leukopenic (<1000 leukocytes/microliter) patients (n=20) after cytoreductive chemotherapy requiring mechanical ventilation for severe respiratory failure (Murray score of > 2.5). INTERVENTION: Patients were assigned in a consecutive, alternating manner to receive either volume-controlled or biphasic positive airway pressure mechanical ventilation, starting within 12 to 24 hrs after endotracheal intubation. MEASUREMENTS AND MAIN RESULTS: Tidal volume, inspiratory flow, peak inspiratory and positive end-expiratory pressures, FIO2, and arterial blood gas analyses were recorded hourly for a study period of 48 hrs. Biphasic positive airway pressure ventilation was associated with a significant reduction in peak inspiratory pressure (mean differences at 24, 36, and 48 hrs: 4.4, 3.4, and 4.2 cm H2O; p = .024, .019, and .013, respectively) and positive end-expiratory pressures (mean differences at 24, 36, and 48 hrs: 1.6, 1.4, and 1.5 cm H20; p = .023, .024, and .023, respectively) at significantly lower FIO2 (mean differences at 12, 24, 36, and 48 hrs; p = .007, .015, .016, and .011, respectively). PaO2/FIO2 ratios and CO2 removal were similar under ventilatory conditions. CONCLUSIONS: Biphasic positive airway pressure ventilation offers the advantage of significantly reduced peak inspiratory and positive end-expiratory pressures at a lower FIO2 and with at least similar oxygenation and CO2 removal as achieved by volume-controlled mechanical ventilation. Our results are in line with previous reports on nonleukopenic patients and suggest that the positive effects of pressure-limited mechanical ventilation are independent of circulating white blood cells. Further studies are mandatory to demonstrate clinical benefit in this critically ill patient population.     

Permissive hypercapnia with and without expiratory washout in patients with severe acute respiratory distress syndrome

BACKGROUND: Permissive hypercapnia is a ventilatory strategy aimed at avoiding lung volutrauma in patients with severe acute respiratory distress syndrome (ARDS). Expiratory washout (EWO) is a modality of tracheal gas insufflation that enhances carbon dioxide removal during mechanical ventilation by reducing dead space. The goal of this prospective study was to determine the efficacy of EWO in reducing the partial pressure of carbon dioxide (PaCO2) in patients with severe ARDS treated using permissive hypercapnia. METHODS: Seven critically ill patients with severe ARDS (lung injury severity score, 3.1 +/- 0.3) and no contraindications for permissive hypercapnia were studied. On the first day, hemodynamic and respiratory parameters were measured and the extent of lung hyperdensities was assessed using computed tomography. A positive end-expiratory pressure equal to the opening pressure identified on the pressure-volume curve was applied. Tidal volume was reduced until a plateau airway pressure of 25 cm H2O was reached. On the second day, after implementation of permissive hypercapnia, EWO was instituted at a flow of 15 l/min administered during the entire expiratory phase into the trachea through the proximal channel of an endotracheal tube using a ventilator equipped with a special flow generator. Cardiorespiratory parameters were studied under three conditions: permissive hypercapnia, permissive hypercapnia with EWO, and permissive hypercapnia. RESULTS: During permissive hypercapnia, EWO decreased PaCO2 from 76 +/- 4 mmHg to 53 +/- 3 mmHg (-30%; P < 0.0001), increased pH from 7.20 +/- 0.03 to 7.34 +/- 0.04 (P < 0.0001), and increased PaO2 from 205 +/- 28 to 296 +/- 38 mmHg (P < 0.05). The reduction in PaCO2 was accompanied by an increase in end-inspiratory plateau pressure from 26 +/- 1 to 32 +/- 2 cm H2O (P = 0.001). Expiratory washout also decreased cardiac index from 4.6 +/- 0.4 to 3.7 +/- 0.3 l.min-1.m-2 (P < 0.01), mean pulmonary arterial pressure from 28 +/- 2 to 25 +/- 2 mmHg (P < 0.01), and true pulmonary shunt from 47 +/- 2 to 36 +/- 3% (P < 0.01). CONCLUSIONS: Expiratory washout is an effective and easy-to-use ventilatory modality to reduce PaCO2 and increase pH during permissive hypercapnia. However, it significantly increases airway pressures and lung volume through expiratory flow limitation, reexposing some patients to a risk of lung volutrauma if the extrinsic positive end-expiratory pressure is not substantially reduced.     

Exogenous surfactant and positive end-expiratory pressure in the treatment of endotoxin-induced lung injury

OBJECTIVE: To evaluate the efficacy of treating endotoxin-induced lung injury with single dose exogenous surfactant and positive end-expiratory pressure (PEEP). DESIGN: Prospective trial. SETTING: Laboratory at a university medical center. SUBJECTS: Nineteen certified healthy pigs, weighing 15 to 20 kg. INTERVENTIONS: Pigs were anesthetized and surgically prepared for hemodynamic and lung function measurements. Animals were randomized into four groups: a) Control pigs (n = 4) received an intravenous infusion of saline without Escherichia colilipopolysaccharide (LPS); b) the LPS group (n = 5) received an intravenous infusion of saline containing LPS (100 microg/kg); c) the PEEP plus saline group (n = 5) received an intravenous infusion of saline containing LPS. Two hours after LPS infusion, saline was instilled into the lung as a control for surfactant instillation, and the animals were placed on 7.5 cm H2O of PEEP; d) the PEEP plus surfactant group (n = 5) received an intravenous infusion of saline containing LPS. Two hours following LPS infusion, surfactant (50 mg/kg) was instilled into the lung and the animals were placed on 7.5 cm H2O of PEEP. PEEP was applied first and surfactant or saline was instilled into the lung while maintaining positive pressure ventilation. All groups were studied for 6 hrs after the start of LPS injection. At necropsy, bronchoalveolar lavage was performed and the right middle lung lobe was fixed for histologic analysis. MEASUREMENTS AND MAIN RESULTS: Compared with LPS without treatment, PEEP plus surfactant significantly increased PaO2 (PEEP plus surfactant = 156.6 +/- 18.6 [SEM] torr [20.8 +/- 2.5 kPa]; LPS = 79.2 +/- 21.9 torr [10.5 +/- 2.9 kPa]; p<.05), and decreased venous admixture (PEEP plus surfactant = 12.5 +/- 2.0%; LPS = 46.9 +/- 14.2%; p< .05) 5 hrs after LPS infusion. These changes were not significant 6 hrs after LPS infusion. PEEP plus surfactant did not alter ventilatory efficiency index (VEI = 3800/[peak airway pressure - PEEP] x respiratory rate x PacO2), or static compliance as compared with LPS without treatment at any time point. Cytologic analysis of bronchoalveolar lavage fluid showed that surfactant treatment significantly increased the percentage of alveolar neutrophils as compared with LPS without treatment (PEEP plus surfactant = 39.1 +/- 5.5%; LPS = 17.4 +/- 6.6%; p< .05). Histologic analysis showed that LPS caused edema accumulation around the airways and pulmonary vessels, and a significant increase in the number of sequestered leukocytes (LPS group = 3.4 +/- 0.2 cells/6400 micro2; control group = 1.3 +/- 0.1 cells/6400 micro2; p < .05). PEEP plus saline and PEEP plus surfactant significantly increased the total number of sequestered leukocytes in the pulmonary parenchyma (PEEP plus surfactant = 8.2 +/- 0.7 cells/6400 micro2; PEEP plus saline = 3.9 +/- 0.2 cells/6400 micro2; p <.05) compared with the control and LPS groups. CONCLUSIONS: We conclude that PEEP plus surfactant treatment of endotoxin-induced lung injury transiently improves oxygenation, but is unable to maintain this salutary effect indefinitely. Thus, repeat bolus dosing of surfactant or bolus treatment followed by continuous aerosol delivery may be necessary for a continuous beneficial effect.     

Renal nerves are not involved in sodium and water retention during mechanical ventilation in awake dogs

BACKGROUND: The role of renal nerves during positive end-expiratory pressure ventilation (PEEP) has only been investigated in surgically stressed, anesthetized, unilaterally denervated dogs. Anesthesia, sedation, and surgical stress, however, decrease urine volume and sodium excretion and increase renal sympathetic nerve activity independent of PEEP. This study investigated in awake dogs the participation of renal nerves in mediating volume and water retention during PEEP. METHODS: Eight tracheotomized, trained, awake dogs were used. The protocol consisted of 60 min of spontaneous breathing at a continuous positive airway pressure of 4 cm H2O, followed by 120 min of controlled mechanical ventilation with a mean PEEP of 15-17 cm H2O (PEEP), and 60 min of continuous positive airway pressure. Two protocols were performed on intact dogs, in which volume expansion had (hypervolemic; electrolyte solution, 0.5 ml x kg(-1) x min(-1)) and had not (normovolemic) been instituted. This was repeated on the same dogs 2 or 3 weeks after bilateral renal denervation. RESULTS: Hypervolemic dogs excreted more sodium and water than did normovolemic dogs. There was no difference between intact and renal-denervated dogs. Arterial pressure did not decrease when continuous positive airway pressure was switched to PEEP. Plasma renin activity, aldosterone, and antidiuretic hormone concentrations were greater in normovolemic dogs. The PEEP increased aldosterone and antidiuretic hormone concentrations only in normovolemic dogs. CONCLUSIONS: In conscious dogs, renal nerves have no appreciable contribution to sodium and water retention during PEEP. Retention in normovolemic dogs seems to be primarily caused by an activation of the renin-angiotensin system and an increase in the antidiuretic hormone. Excretion rates depended on the volume status of the dogs.     

Determinants of nitric oxide in exhaled gas in the isolated rabbit lung

Nitric oxide concentrations in the exhaled gas (NOe) increases during various inflammatory conditions in humans and animals. Little is known about the sources and factors that influence NOe. NOe at end expiration was measured by chemiluminescence in an isolated, blood-perfused rabbit lung. The average end-expiratory concentration over 10 breaths was used. The effect of positive end-expiratory pressure (PEEP), flow rate, pH, hypoxia, venous pressure, and flow pulsatility on NOe were determined. At constant blood flow, increasing PEEP from 1 to 5 cm H2O elicited a reproducible increase in NOe from 49 +/- 7 to 53 +/- 8 parts per billion (ppb) (p < 0.05). When blood pH was increased from 7.40 to 7.74 by breathing low CO2 gas, NOe rose from 45 +/- 7 to 55 +/- 7 ppb (p < 0.001). Hypoxia caused a dose-dependent decrease in NOe from 37 +/- 3 during baseline to 23 +/- 2 during ventilation with 0% O2 (p < 0.01). Venous pressure elevation from 0 to 5 and 10 mm Hg decreased NOe from 32 +/- 5, to 26 +/- 5 and 24 +/- 5 ppb, respectively (p < 0.05). Switching from steady to pulsatile flow (same man flow) resulted in a small, albeit significant reduction in NOe; 30 +/- 4 to 28 +/- 4 ppb (p < 0.05). Changes in flow rate between 200 and 20 ml/min were associated with small changes in NOe; however, when flow was stopped, NOe rose substantially to 56 +/- 6 ppb (p < 0.05). The changes in NOe were rapid (1 to 2 min) and reversible. The results suggest that NOe is influenced by ventilatory and hemodynamic variables, pH, and hypoxia. We suggest that caution must be taken when interpreting changes in exhaled NO in humans or experimental animals. Changes in total and regional blood flow, capillary blood volume, ventilation, hypoxia, and pH should not be overlooked.     

Computer-controlled minute ventilation in preterm infants undergoing mechanical ventilation

INTRODUCTION: Computer-controlled minute ventilation (CCMV) continuously adjusts the ventilator rate to changes in spontaneous respiratory drive and pulmonary mechanics to maintain a preset total minute ventilation. HYPOTHESIS: We hypothesized that CCMV would maintain ventilation and oxygenation with fewer mechanical breaths than conventional intermittent mandatory ventilation in very low birth weight infants. METHODS: Very low birth weight infants in clinically stable condition who were undergoing mechanical ventilation were enrolled. The number of mechanical breaths, total and mechanical expiratory minute ventilation, mean airway pressure, oxygen hemoglobin saturation by pulse oximetry, and transcutaneous partial carbon dioxide and partial oxygen tensions were obtained during intermittent mandatory ventilation and CCMV (45 to 60 minutes) and compared by paired t test. RESULTS: Fifteen infants were studied. Birth weight (median, range) was 700 gm (550 to 1205 gm), gestational age 26 weeks (23 to 34 weeks), age 21 days (3 to 50 days). When switched from intermittent mandatory ventilation to CCMV, the number of mechanical breaths was reduced (15 +/- 2.8 to 8.6 +/- 2.9 breaths per minute, p < 0.001), leading to lower airway pressure (3.97 +/- 1.00 to 3.45 +/- 1.00 cm H2O, p < 0.001) and lower expiratory minute ventilation generated by the mechanical ventilator (116 +/- 31 to 65 +/- 28 ml/min per kilogram, p < 0.001), while total expiratory minute ventilation remained unchanged. Mean transcutaneous partial carbon dioxide and oxygen tensions, oxygen hemoglobin saturation, and the time spent within different oxygen hemoglobin saturation ranges did not differ between both ventilatory modes. CONCLUSION: CCMV maintained adequate ventilation and oxygenation with lower mechanical ventilatory support than IMV. CCMV may reduce barotrauma and chronic lung disease during long-term use.     

The fetal inflammatory response syndrome

A mathematical model of the ARDS lung, with simulated gravitational superimposed pressure, evaluated the effect of varying alveolar threshold opening pressures (TOP), PEEP and peak inspiratory pressure (PIP) on the static pressure-volume (PV) curve. The lower inflection point (Pflex) was affected by SP and TOP, and did not accurately indicate PEEP required to prevent end-expiratory collapse. Reinflation of collapsed lung units (recruitment) continued on the linear portion of the PV curve, which had a slope at any volume greater than the total compliance of aerated alveoli. As recruitment diminished, the reduced PV slope could produce an upper Pflex at 20 to 30 cm H2O pressure. An upper Pflex caused by alveolar overdistension could be modified or eliminated by recruitment with high TOP. With constant PIP as PEEP increased, and TOP range of 5 to 60 cm H2O, PEEP to prevent end-expiratory collapse was indicated by minimum PV slope above 20 cm H2O, minimum hysteresis, and maximum volume at a pressure of 20 cm H2O. With constant inflation volume as PEEP increased, the effect on PV slope was unpredictable. Although increased PV slope indicated recruitment, maximum PV slope usually underestimated PEEP required to prevent end-expiratory collapse. Therefore, with this model the PV curve did not reliably predict optimal ventilator settings.     

Effects of heat and moisture exchangers on minute ventilation, ventilatory drive, and work of breathing during pressure-support ventilation in acute respiratory failure

OBJECTIVES: To evaluate the effect of two commonly used heat and moisture exchangers on respiratory function and gas exchange in patients with acute respiratory failure during pressure-support ventilation. DESIGN: Prospective, randomized trial. SETTING: Intensive care unit of a university hospital. PATIENTS: Fourteen patients with moderate acute respiratory failure, receiving pressure-support ventilation. INTERVENTIONS: Patients were assigned randomly to two treatment groups, in which two different heat and moisture exchangers were used: Hygroster (DAR S.p.A., Mirandola, Italy) with higher deadspace and lower resistance (group 1, n = 7), and Hygrobac-S (DAR S.p.A.) with lower deadspace and higher resistance (group 2, n = 7). Patients were assessed at three pressure-support levels: a) baseline (10.3 +/- 2.4 cm H2O for group 1, 9.3 +/- 1.3 cm H2O for group 2); b) 5 cm H2O above baseline; and c) 5 cm H2O below baseline. Measurements obtained with the heat and moisture exchangers were compared with those values obtained using the standard heated hot water humidifier. MEASUREMENTS AND MAIN RESULTS: At baseline pressure-support ventilation, the insertion of both heat and moisture exchangers induced in all patients a significant increase in the following parameters: minute ventilation (12.4 +/- 3.2 to 15.0 +/- 2.6 L/min for group 1, and 11.8 +/- 3.6 to 14.2 +/- 3.5 L/min for group 2); static intrinsic positive end-expiratory pressure (2.9 +/- 2.0 to 5.1 +/- 3.2 cm H2O for group 1, and 2.9 +/- 1.7 to 5.5 +/- 3.0 cm H2O for group 2); ventilatory drive, expressed as P41 (2.7 +/- 2.0 to 5.2 +/- 4.0 cm H2O for group 1, and 3.3 +/- 2.0 to 5.3 +/- 3.0 cm H2O for group 2); and work of breathing, expressed as either power (8.8 +/- 9.4 to 14.5 +/- 10.3 joule/ min for group 1, and 10.5 +/- 7.4 to 16.6 +/- 11.0 joule/min for group 2) or work per liter of ventilation (0.6 +/- 0.6 to 1.0 +/- 0.7 joule/L for group 1, and 0.8 +/- 0.4 to 1.1 +/- 0.5 joule/L. for group 2). These increases also occurred when pressure-support ventilation was both above and below the baseline level, although at high pressure support the increase in work of breathing with heat and moisture exchangers was less evident. Gas exchange was unaffected by heat and moisture exchangers, as minute ventilation increased to compensate for the higher deadspace produced in the circuit by the insertion of heat and moisture exchangers. CONCLUSIONS: The tested heat and moisture exchangers should be used carefully in patients with acute respiratory failure during pressure-support ventilation, since these devices substantially increase minute ventilation, ventilatory drive, and work of breathing. However, an increase in pressure-support ventilation (5 to 10 cm H2O) may compensate for the increased work of breathing.     

Role of tidal volume, FRC, and end-inspiratory volume in the development of pulmonary edema following mechanical ventilation

Mechanical ventilation with high peak inspiratory pressure and large tidal volume (VT) produces permeability pulmonary edema. Whether it is mean or peak inspiratory pressure (i.e., mean or end-inspiratory volume) that is the major determinant of ventilation-induced lung injury is unsettled. Rats were ventilated with increasing tidal volumes starting from different degrees of FRC that were set by increasing end-expiratory pressure during positive-pressure ventilation. Pulmonary edema was assessed by the measurement of extravascular lung water content. The importance of permeability alterations was evaluated by measurement of dry lung weight and determination of albumin distribution space. Pulmonary edema with permeability alterations occurred regardless of the value of positive end-expiratory pressure (PEEP), provided the increase in VT was large enough. Similarly, edema occurred even during normal VT ventilation provided the increase in PEEP was large enough. Furthermore, moderate increases in VT or PEEP that were innocuous when applied alone, produced edema when combined. The effect of PEEP was not the consequence of raised airway pressure but of the increase in FRC since similar observations were made in animals ventilated with negative inspiratory pressure. However, although permeability alterations were similar, edema was less marked in animals ventilated with PEEP than in those ventilated with zero end-expiratory pressure (ZEEP) with the same end-inspiratory pressure. This "beneficial" effect of PEEP was probably the consequence of hemodynamic alterations. Indeed, infusion of dopamine to correct the drop in systemic arterial pressure that occurred during PEEP ventilation resulted in a significant increase in pulmonary edema. In conclusion, rather than VT or FRC value, the end-inspiratory volume is probably the main determinant of ventilation-induced edema. Hemodynamic status plays an important role in modulating the amount of edema during lung overinflation but does not fundamentally modify the characteristics of this edema which is consistently associated with major permeability alterations. These results may be relevant for ventilatory strategies during acute respiratory failure.     

A patient with WT syndrome and Castleman disease

We studied the mechanisms by which pulmonary solute clearance is affected by lung inflation. We examined the pulmonary clearance of inhaled technetium-99m diethylenetriaminepentaacetic acid (99mTc-DTPA) together with changes in lung volumes in healthy men after applying graded levels of continuous external negative pressure (CNP) and positive end-expiratory pressure (PEEP). The 99mTc-DTPA clearance increased from the baseline during -15 cm H2O CNP (p < 0.005) and during -20 cm H2O CNP (p < 0.001). The 99mTc-DTPA clearance increased during +15 cm H2O PEEP (p < 0.001). However, the changes during both -10 cm H2O CNP and +10 cm H2O PEEP did not differ from the baseline, indicating a threshold effect. On the other hand, changes in FRC during CNP were proportional to the applied pressures and were similar to those during PEEP with corresponding pressures. These results suggest that pulmonary vascular recruitment induced by CNP does not affect pulmonary 99mTc-DTPA clearance. This threshold effect suggests that the increased clearance is due to changes in membrane permeability rather than in the area of the alveolar-capillary interface or the lining layer thickness. We concluded that the effect of lung inflation on solute clearance may be mediated by the changes in membrane permeability.     

The influence of surveillance methods on surgical wound infection rates in a tertiary care spinal surgery service

We studied 13 consecutive infants admitted to our Neonatal Intensive Care Unit over 37 months from 1 June 1994 to 30 June 1997, who were diagnosed with severe persistent pulmonary hypertension (PPHN) meeting extracorporeal membrane oxygenation (ECMO) criteria as defined by Bartlett and/or Short. They were managed with conservative ventilation strategy, with emphasis on the use of moderate ventilatory pressures whilst avoiding paralysis. Peak inspiratory pressure (PIP) on intermittent mandatory ventilation was adjusted according to adequate chest excursion. High PIP was avoided. Two main ventilatory techniques were used: 1) low ventilatory rate < or = 40/min, PIP 20 to 30 cmH2O, inspiratory time (IT) 0.5 seconds, positive end-expiratory pressure (PEEP) 5 cmH2O, and 2) high ventilatory rate 100/min, PEEP 0 cmH2O, IT 0.3 seconds. The aim was to keep preductal PaO2 > or = 50 mmHg. We did not sought to achieve alkalotic pH or low PaCO2. When PIP requirements exceeded 30 to 35 cmH2O, the use of an alternative rescue therapy such as pulmonary vasodilator, high frequency ventilation and/or surfactant were considered. Only 1 infant died of PPHN. Low mortality due to PPHN can be achieved using this strategy. There is a need for a randomised controlled trial to compare this strategy with other alternative treatment strategies.     

Home versus intensive care pressure support devices. Experimental and clinical comparison

A bench study using an artificial lung model and a clinical study in patients were performed to evaluate six commercially available home pressure support devices. Six devices were tested in the in vitro study, including five designed for home use and one designed for use in intensive care units. Minimal positive end-expiratory pressure (PEEP) varied across home devices, from 0.5 cm H2O to 4.3 cm H2O. Work imposed during exhalation varied up to six-fold across devices. A substantial rebreathing volume has present for the three home devices with a common inspiratory and expiratory line. This rebreathing volume decreased with increasing PEEP level, as expected, but remained substantial at the widely used PEEP level of 5 cm H2O. Use of a non-rebreathing valve increased both the work imposed by the circuit during the exhalation phase and the time required to attain the relaxation equilibrium. Except for two home devices and a bilevel positive airway pressure (BiPAP) device equipped with a non-rebreathing valve, differences in inspiratory trigger sensitivities were small between home and intensive care devices. During pressure support, the total work performed by the machines did not differ by more than 15% between devices, whereas differences of more than 300% were observed in flow acceleration. Only one home device gave a flow acceleration similar to or better than that obtained with the intensive care device. In a randomized, crossover clinical study, we compared a home device to a device specially designed for intensive care use in seven intubated patients during weaning from mechanical ventilation. The main differences between the two devices were trigger sensitivity and initial flow acceleration. For the same level of pressure support, there were no significant differences in arterial PCO2, tidal volume, respiratory rate, or minute ventilation between these two devices. However, the esophageal pressure-time product was 30% higher with the home device (165 +/- 93 versus 119 +/- 80 cm H2O/min, p < 0.05). In conclusion, differences exist between devices in terms of occurrence of rebreathing, speed of attainment of stable pressure support level, and expiratory resistance. These differences characterizing the delivery of pressure support may have clinical impact on the inspiratory effort of patients.