Airway pressure release ventilation

BACKGROUND: Elevated airway pressures during mechanical ventilation are associated with hemodynamic compromise and pulmonary barotrauma. We studied the cardiopulmonary effects of a pressure-limited mode of ventilation (airway pressure release ventilation) in patients with the adult respiratory distress syndrome. METHODS: Fifteen patients requiring intermittent mandatory ventilation (IMV) and positive end-expiratory pressure (PEEP) were studied. Following measurement of hemodynamic and ventilatory data, all patients were placed on airway pressure release ventilation (APRV). Cardiorespiratory measurements were repeated after a 2-hour stabilization period. RESULTS: During ventilatory support with APRV, peak inspiratory pressure (62 +/- 10 vs 30 +/- 4 cm H2O) and PEEP (11 +/- 4 vs 7 +/- 2 cm H2O) were reduced compared with IMV. Mean airway pressure was higher with APRV (18 +/- 5 vs 24 +/- 4 cm H2O). There were no statistically significant differences in gas exchange or hemodynamic variables. Both cardiac output (8.7 +/- 1.8 vs 8.4 +/- 2.0 L/min) and partial pressure of oxygen in arterial blood (79 +/- 9 vs 86 +/- 11 mm Hg) were essentially unchanged. CONCLUSIONS: Our results suggest that while airway pressure release ventilation can provide similar oxygenation and ventilation at lower peak and end-expiratory pressures, this offers no hemodynamic advantages.     

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.     

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.     

Arterial oxygenation and shunt fraction during one-lung ventilation: a comparison of isoflurane and sevoflurane

The aim of this study was to evaluate the effect of isoflurane and sevoflurane on oxygenation and shunt fraction during one-lung ventilation (OLV). Twenty patients undergoing lobectomy for lung cancer and scheduled for long-term OLV were enrolled in this study. Patients were allocated to treatment with either isoflurane or sevoflurane. Arterial oxygenation, shunt fraction, and hemodynamics were evaluated at the end of two-lung ventilation; 20 min after the initiation of OLV; 20 min after the application of 4-cm positive end-expiratory pressure (PEEP) to the dependent lung; 20 min after 8-cm PEEP; and 20 min after the conversion from OLV to two-lung ventilation. There was no significant difference between isoflurane and sevoflurane with regard to oxygenation, shunt fraction, or hemodynamics during OLV. PaO2 values after the application of 4-cm PEEP increased from 131.1 +/- 11.8 mm Hg to 190.6 +/- 22.9 mm Hg in the isoflurane group (P < 0.05) and from 127.2 +/- 14.3 mm Hg to 192.4 +/- 26.9 mm Hg in the sevoflurane group (P < 0.05). The selection of either isoflurane or sevoflurane for OLV was made without regard to arterial oxygenation and shunt fraction. PEEP application to the dependent lung is useful for improving oxygenation during OLV, but 8-cm PEEP had no added effect compared with 4-cm PEEP. Implications: We compared the effects of isoflurane and sevoflurane on oxygenation, hemodynamics, and shunt fraction during one-lung ventilation in 20 patients undergoing scheduled lobectomy for lung cancer. There was no significant difference between isoflurane and sevoflurane with regard to oxygenation, shunt fraction, and hemodynamics during one-lung ventilation. The application of 4-cm positive end-expiratory pressure increased the partial pressure of arterial oxygen during one-lung ventilation.     

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.     

Out-of-hospital ventilation: bag--valve device vs transport ventilator

OBJECTIVE: To examine the patterns of out-of-hospital airway management and to compare the efficacy of bag-valve ventilation with that of the use of a transport ventilator for intubated patients. METHODS: A prospective, nonrandomized, convenience sample of 160 patients requiring airway management in the out-of-hospital urban setting was analyzed. A survey inquiring about airway and ventilatory management was completed by emergency medical services (EMS) personnel, and arterial blood gas (ABG) samples were obtained within 5 minutes of patient arrival in the ED. The ABG parameters were compared for patients grouped by different airway techniques and presence or absence of cardiac arrest (systolic blood pressure < 50 mm Hg) upon ED presentation. RESULTS: Over a one-year period, 160 surveys were returned. The majority (62%) of the patients were men; the population mean age was 61 +/- 19 years. Presenting ABGs were obtained for 76 patients; 17% (13/76) had systemic perfusion and 83% (63/76) were in cardiac arrest. There was no difference in ABG parameters between the intubated cardiac arrest patients ventilated with a transport ventilator (pH 7.17 +/- 0.17, PaCO2 37 +/- 20 torr, and PaO2 257 +/- 142 torr) and those ventilated with a bag-valve device (pH 7.20 +/- 0.16, PaCO2 42 +/- 21 torr, and PaO2 217 +/- 138 torr). The patients ventilated via an esophageal obturator airway (EOA) device had impaired gas exchange, compared with the groups who had endotracheal (ET) intubation (pH 7.09 +/- 0.13, PaCO2 76 +/- 30 torr, and PaO2 75 +/- 35 torr). The intubated patients not in cardiac arrest had similar ABG parameters whether ventilated manually with a bag-valve device or with a transport ventilator. Endotracheal intubation was successfully accomplished in 93% (123/132) of attempted cases. CONCLUSIONS: In this sample, ET intubation was the most frequently used airway by EMS providers. When ET intubation was accomplished, adequate ventilation could be achieved using either bag-valve ventilation or a transport ventilator. Ventilation via the EOA proved inadequate.     

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.     

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.     

ANP and bradycardic reflexes in hypertensive rats: influence of cardiac hypertrophy

OBJECTIVES: Beta2-integrin (CD11b/CD18) expression, an indicator of neutrophil activation, has been associated with the development of acute respiratory distress syndrome. Leumedins act directly on leukocytes to inhibit the up-regulated expression of beta2-integrins involved in leukocyte adhesion. We examined the effect of such a new anti-inflammatory agent, NPC 15669 (N-[9H-(2,7-dimethylfluorenyl-9-methoxy)-carbonyl]-L-leucine), on neutrophil-mediated acute lung injury in an animal model. DESIGN: Prospective, randomized, blinded, controlled animal study. SETTING: An animal laboratory in a university setting. SUBJECTS: Adult New Zealand rabbits. INTERVENTIONS: After repeated lung lavages with normal saline to induce acute lung injury, anesthetized rabbits were randomly assigned to one of two groups (n = 6 per group): a) treatment group (pretreated with NPC 15669 [10 mg/kg i.v. bolus] 30 mins before lavage, followed by a continuous infusion [5 mg/kg/hr] for the duration [4 hrs] of the experiment); or b) control group (pretreatment and continuous infusion with placebo). All animals were mechanically ventilated with identical pressure settings over 4 hrs and were killed at the end of the experiment. MEASUREMENTS AND MAIN RESULTS: PaO2, PaCO2, and tidal volumes were repeatedly measured and airway pressure settings were noted every 30 mins. At the end of the experiment, lungs were taken out for measurements of the myeloperoxidase content, for conventional histology (hematoxylin and eosin staining), and for intracellular adhesion molecule-1 immunohistostaining. Pretreatment with NPC 15669 profoundly improved oxygenation from a PaO2 of 52 +/- 5 torr (6.9 +/- 0.7 kPa) to 250 +/- 161 torr (33.3 +/- 21.5 kPa) within 60 mins after lung lavage (p < .05). Oxygenation continued to improve throughout the study, reaching a maximal PaO2 value of 395 +/- 98 torr (52.7 +/- 13.1 kPa) at 4 hrs. In the control group, oxygenation remained poor throughout the observation period. PaO2 values differed significantly (51 +/- 20 torr [6.8 +/- 2.7 kPa] vs. 306 +/- 126 torr [40.8 +/- 16.8 kPa], p < .005) at 90 mins and at all subsequent measurements from those values in the NPC 15669 group. Dynamic lung compliance improved significantly 60 to 90 mins after repeated lung lavage. Histology demonstrated markedly less lung damage (hyaline membrane formation and leukocyte infiltration) in treated animals (p < .05) than in controls. CONCLUSIONS: NPC 15669 seems to block inflammatory reactions by inhibiting the sequestration of neutrophils in acute, ventilator-associated lung injury. As a result, gas exchange and total lung compliance improve. Application of this and similar compounds affecting neutrophil adhesion warrants further investigation as a treatment modality for acute lung injury.     

Gastric versus duodenal feeding and gastric tonometric measurements

OBJECTIVE: To compare the influence of gastric and postpyloric enteral feeding on the gastric tonometric PCO2 gap (tonometric PCO2 - PaCO2). DESIGN: A prospective, clinical trial. SETTING: Two intensive care units in a university hospital. PATIENTS: Twenty patients undergoing mechanical ventilation and enteral feeding without catecholamines, sepsis, or sign of hypoxia. INTERVENTIONS: Patients were randomized to receive feeding through the tonometer (gastric group), or through a postpyloric tube (postpyloric group). MEASUREMENTS AND MAIN RESULTS: The patients received tube feeding at a rate of 50 mL/hr during 4 hrs. Baseline measurements included: mean arterial pressure, heart rate, tonometric parameters, arterial gases, and arterial lactate concentration. Except for lactate concentration, these measurements were repeated after 1 and 4 hrs of enteral feeding and 2 hrs after stopping enteral feeding. During the study, arterial pH and PaCO2 did not change. During enteral feeding, the PCO2 gap increased in the gastric group from a mean of 7+/-5 to 17+/-14 (SD) torr (0.9 0.7 to 2.3+/-1.9 kPa) (p< .O01) and did not change in the postpyloric group (5+/-5 to 3+/-1 torr [0.7+/-0.7 to 0.4+/-0.1 kPa]). Two hours after stopping enteral feeding, the PCO2 gap was still increased in the gastric group (15+/-9 vs. 7+/-5 torr [2.0+/-1.2 vs. 0.9+/-0.7 kPa]) (p < .01). CONCLUSION: The results indicate that gastric enteral feeding increased the PCO2 gap. However, postpyloric enteral feeding does not interact with gastric tonometric measurements and should be used when using gastric tonometry in enterally fed patients.     

Neutrophil accumulation is reduced during partial liquid ventilation

OBJECTIVE: This study evaluates the ability of perflubron to inhibit pulmonary neutrophil accumulation during partial liquid ventilation (PLV) in the setting of acute lung injury. DESIGN: Randomized, controlled, nonblinded study. SETTING: Research laboratory at a university. SUBJECTS: Male, Sprague-Dawley rats (n = 120, 506 +/- 42 g). INTERVENTIONS: Animals were divided into eight groups (n = 15 in each group, of which n = 12 for myeloperoxidase content and n = 3 for histologic neutrophil counting): a) GV-CVF group, animals received gas ventilation (GV) with the induction of lung injury using cobra venom factor (CVF); b) PLV-CVF group, animals received partial liquid ventilation before the induction of lung injury; c) PEEP-CVF group, animals received positive end-expiratory pressure (PEEP) before the administration of cobra venom factor; d) CVF-PLV group, animals received partial liquid ventilation after cobra venom factor; e) CVF-PEEP group, animals received PEEP after cobra venom factor; f) PLV only group, animals received partial liquid ventilation only; g) GV only group, animals received gas ventilation only; and h) NVSBA group, nonventilated spontaneous breathing animals. MEASUREMENTS AND MAIN RESULTS: After the experimental period, total lung myeloperoxidase content was significantly decreased in the PLV-CVF (0.29 +/- 0.08, p = .02) and PEEP-CVF (0.34 +/- 0.04, p = .01) groups when compared with the GV-CVF group (0.62 +/- 0.07). When compared with the GV-CVF group, a trend toward a reduction in myeloperoxidase was observed in the CVF-PLV (0.42 +/- 0.05, p = .07) and the CVF-PEEP (0.39 +/- 0.06, p = .07) groups. When compared with the cobra venom factor only group (GV-CVF 47 +/- 2 neutrophils/high-power field), reductions in neutrophil count were observed in all groups (neutrophils/high-power field): PLV-CVF (20 +/- 2, p = .009); PEEP-CVF (24 +/- 1, p = .01); CVF-PLV (30 +/- 2, p = .03); and CVF-PEEP (37 +/- 1, p = .04). CONCLUSION: These data suggest that both partial liquid ventilation and PEEP result in a reduction in neutrophil accumulation in the setting of acute lung injury.     

Extended preservation of ischemic pulmonary graft by postmortem alveolar expansion

BACKGROUND: If lungs could be retrieved for transplantation from non-heart-beating cadavers, the shortage of donors might be significantly alleviated. METHODS: Peak airway pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and wet to dry weight ratio were measured during delayed hypothermic crystalloid flush in rabbit lungs (n = 6) at successive intervals after death comparing cadavers with lungs left deflated (group 1), inflated with room air (group 2) or 100% oxygen (group 4), or ventilated with room air (group 3), or 100% nitrogen (group 5), or 100% oxygen (group 6). RESULTS: There was a gradual increase in mean pulmonary artery pressure and pulmonary vascular resistance with longer postmortem intervals in all study groups (p = not significant, group 1 versus group 2 versus group 3). There was also a gradual increase in peak airway pressure and wet-to-dry weight ratio over time in all groups, which reflected edema formation during flush (airway pressure, from 14.5 +/- 1.0 cm H2O to 53.7 +/- 12.2 cm H2O, and wet-to-dry weight ratio, from 3.6 +/- 0.1 to 11.5 +/- 1.2, in group 1 at 0 and 6 hours postmortem, respectively; p < 0.05). Compared with group 1, however, the increase in groups 2 and 3 was much slower (airway pressure, 20.9 +/- 0.5 cm H2O and 18.8 +/- 1.2 cm H2O, and wet-to-dry weight ratio, 5.2 +/- 0.3 and 4.6 +/- 0.4 at 6 hours postmortem, respectively; p < 0.05 versus group 1 and p = not significant, group 2 versus group 3). Airway pressure and wet-to-dry weight ratio did not differ between groups 2 and 4 or between groups 3, 5, and 6. CONCLUSIONS: These data suggest that (1) pulmonary edema will develop in atelectatic lungs if hypothermic flush is delayed for 2 hours after death, (2) postmortem inflation is as good as ventilation in prolonging warm ischemic tolerance, (3) inflation with oxygen or ventilation with nitrogen or oxygen is no different from that with room air, and (4) therefore, prevention of alveolar collapse appears to be the critical factor in protecting the lung from warm ischemic damage independent of continued oxygen delivery.     

Effects of partial liquid ventilation on lung injury in a model of acute respiratory failure: a histologic and morphometric analysis

OBJECTIVE: To compare the histopathologic changes observed in a sheep model of oleic acid-induced acute respiratory failure during partial liquid ventilation with perflubron with gas ventilation. DESIGN: Randomized, controlled study. SETTING: Animal laboratory and pathology laboratories of a university hospital. SUBJECTS: Fourteen healthy adult sheep, weighing 64.9 +/- 6.4 kg. INTERVENTIONS: Lung injury was induced with oleic acid (0.15 mL/kg). A tracheostomy tube was inserted, along with systemic and pulmonary artery monitoring catheters. Animals were randomized to undergo either partial liquid ventilation (n = 7) or gas ventilation (n = 7). Animals underwent euthanasia at the end of the 90-min study period, after which the endotracheal tube was clamped with the lungs in expiratory hold at a positive end-expiratory pressure of 5 cm H2O. En bloc excision of the heart and lungs was performed by thoracotomy. Perfusion of the isolated lung vasculature with 2.5% paraformaldehyde and 0.25% glutaraldehyde in a 0.1-M phosphate buffer was performed. Histologic analysis followed. MEASUREMENTS AND MAIN RESULTS: Gas exchange increased markedly in the animals that underwent partial liquid ventilation compared with the gas-ventilated animals (PaO2 at 90 mins: gas ventilation-treatment group, 40 +/- 8 torr [5.3 +/- 1.1 kPa]; partial liquid ventilation-treatment group, 108 +/- 60 torr [14.4 +/- 8.0 kPa]; p = .004). Lung histologic analysis demonstrated a better overall diffuse alveolar damage score (partial liquid ventilation-treatment group, 12.4 +/- 1.4; gas ventilation-treatment group, 15.0 +/- 1.7; p = .01). In the partial liquid ventilation-treatment group, we observed an increase in mean alveolar diameter (partial liquid ventilation-treatment group, 82.4 +/- 2.9 microm; gas ventilation-treatment group, 67.7 x 3.9 microm; p = .0022) and a decrease in the number of alveoli per high-power field (partial liquid ventilation-treatment group, 25.7 +/- 0.9, gas ventilation-treatment group, 31.4 +/- 2.5; p = .0022), in septal wall thickness (partial liquid ventilation-treatment group, 6.0 +/- 0.6 microm; gas ventilation-treatment group, 8.3 +/- 1.0 microm; p = .0033), and in mean capillary diameter (partial liquid ventilation-treatment group, 13.0 +/- 0.8 microm; gas ventilation-treatment group, 19.9 +/- 1.4 microm; p = .0022). CONCLUSIONS: Partial liquid ventilation is associated with notable improvement in gas exchange and with a reduction in the histologic and morphologic changes observed in an oleic acid model of acute lung injury.     

The laryngeal mask airway and positive-pressure ventilation

BACKGROUND: The utility of the laryngeal mask airway during positive-pressure ventilation has yet to be determined. Our study was designed to assess whether significant leaks occurred with positive-pressure ventilation and if leaks were associated with gastroesophageal insufflation. METHODS: Forty-eight patients undergoing elective surgery were studied. After induction of anesthesia and paralysis, controlled ventilation was used with four different peak pressure settings in each patient (15, 20, 25, and 30 cmH2O). The order of ventilator pressure settings was assigned from a randomized block schedule. Data collected included inspiratory and expiratory volumes, qualitative assessments of gastroesophageal insufflation, and leak at the neck. After data collection during laryngeal mask use, the anesthesiologist intubated the trachea and measurements were repeated for tracheal tube ventilation. Leak was calculated by subtracting the expiratory from the inspiratory volume and expressed as a fraction of the inspiratory volume. RESULTS: Ventilation with the laryngeal mask airway was adequate at all ventilation pressures and comparable with tracheal tube ventilation. Leak fraction (mean +/- SD) at 15, 20, 25, and 30 cmH2O for laryngeal mask ventilation were 0.13 +/- 0.15, 0.21 +/- 0.18, 0.25 +/- 0.16 and 0.27 +/- 0.17, respectively, and 0.03 +/- 0.03, 0.05 +/- 0.03, 0.05 +/- 0.03 and 0.04 +/- 0.03, respectively, for tracheal tube ventilation. Leak fractions for ventilation with the laryngeal mask were consistently greater than those measured for tracheal tube ventilation at similar ventilation pressures. Leak fraction with laryngeal mask ventilation increased with increasing airway pressures, whereas leak with tracheal tube ventilation remained unchanged. The frequency of gastroesophageal insufflation ranged from 2.1% at a ventilation pressure of 15 cmH2O to 35.4% at 30 cmH2O. CONCLUSIONS: Ventilation using the laryngeal mask appears to be adequate if airway resistance and pulmonary compliance are normal. Gastroesophageal insufflation of air will become a problem in the presence increased ventilation pressure.     

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.     

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.     

Predictors of extubation success and failure in mechanically ventilated infants and children

OBJECTIVE: To predict extubation success and failure in mechanically ventilated infants and children using bedside measures of respiratory function. DESIGN: Prospective collection of data. SETTING: A university-affiliated children's hospital with a 51-bed critical care unit. PATIENTS: All infants and children who were mechanically ventilated for at least 24 hrs, except neonates < or = 37 wks gestation and patients with neuromuscular disease. INTERVENTIONS: Bedside measurements of cardiorespiratory function were obtained immediately before extubation. MEASUREMENTS AND MAIN RESULTS: Extubation failure was defined as reintubation within 48 hrs of extubation in the absence of upper airway obstruction. Failure rates were calculated for different ranges (selected a priori) of preextubation measures of breathing effort, ventilatory support, respiratory mechanics, central inspiratory drive, and integrated indices useful in adults. Effort of spontaneous breathing was assessed by the respiratory rate standardized to age, the presence of retractions and paradoxical breathing, inspiratory pressure, maximal negative inspiratory pressure (maximal negative inspiratory pressure), inspiratory pressure/maximal negative inspiratory pressure ratio, and tidal volume indexed to body weight of a spontaneous breath. Ventilatory support was measured by the fraction of inspired oxygen (F10(2)), mean airway pressure, oxygenation index, and the fraction of total minute ventilation provided by the ventilator. Respiratory mechanics were assessed by determination of peak ventilatory inspiratory pressure and dynamic compliance. Central inspiratory drive was assessed by mean inspiratory flow. Frequency to tidal volume ratio and the compliance, rate, oxygenation, and pressure indexed to body weight, the integrated indices useful in predicting extubation failure in adults, were also calculated. Thirty-four of the 208 patients who were studied were reintubated for an overall failure rate of 16.3% (95% confidence interval 11.3% to 21.4%). The reasons for reintubation were poor effort (n = 8), excessive effort (n = 14), altered mental status or absent airway reflexes (n = 2), cardiovascular instability (n = 3), inadequate oxygenation (n = 3), respiratory acidosis (n = 3), and undocumented (n = 1). Extubation failure increased significantly with decreasing tidal volume indexed to body weight of a spontaneous breath, increasing F10(2), increasing mean airway pressure, increasing oxygenation index, increasing fraction of total minute ventilation provided by the ventilator, increasing peak ventilatory inspiratory pressure, or decreasing mean inspiratory flow (p < .05). Dynamic compliance showed a trend of increasing failure rate with decreasing dynamic compliance but did not reach statistical significance (p = .116). Respiratory rate standardized to age, inspiratory pressure, maximal negative inspiratory pressure, inspiratory pressure/maximal negative inspiratory pressure ratio, frequency to tidal volume ratio, and compliance, rate, oxygenation, and pressure did not show any trend in failure rate with increasing or decreasing values. Threshold values that defined a low risk (< or = 10%) and a high risk (> or = 25%) of extubation failure could be determined for tidal volume indexed to body weight of a spontaneous breath, F10(2), mean airway pressure, oxygenation index, fraction of total minute ventilation provided by the ventilator, peak ventilatory inspiratory pressure, dynamic compliance, and mean inspiratory flow. Neither a low nor a high risk of failure could be defined for frequency to tidal volume ratio or the compliance, rate, oxygenation, and pressure (CROP) index. CONCLUSIONS: Bedside measurements of respiratory function can predict extubation success and failure in infants and children. Both a low risk and a high risk of failure can be determined using these measures. Integrated indices useful in adults do not reliably predict extubation success or failure in     

A prospective, randomized, and controlled study of fluid management in children with severe head injury: lactated Ringer's solution versus hypertonic saline

OBJECTIVES: Resuscitation in severe head injury may be detrimental when given with hypotonic fluids. We evaluated the effects of lactated Ringer's solution (sodium 131 mmol/L, 277 mOsm/L) compared with hypertonic saline (sodium 268 mmol/L, 598 mOsm/L) in severely head-injured children over the first 3 days after injury. DESIGN: An open, randomized, and prospective study. SETTING: A 16-bed pediatric intensive care unit (ICU) (level III) at a university children's hospital. PATIENTS: A total of 35 consecutive children with head injury. INTERVENTIONS: Thirty-two children with Glasgow Coma Scores of <8 were randomly assigned to receive either lactated Ringer's solution (group 1) or hypertonic saline (group 2). Routine care was standardized, and included the following: head positioning at 30 degrees; normothermia (96.8 degrees to 98.6 degrees F [36 degrees to 37 degrees C]); analgesia and sedation with morphine (10 to 30 microg/kg/hr), midazolam (0.2 to 0.3 mg/kg/hr), and phenobarbital; volume-controlled ventilation (PaCO2 of 26.3 to 30 torr [3.5 to 4 kPa]); and optimal oxygenation (PaO2 of 90 to 105 torr [12 to 14 kPa], oxygen saturation of >92%, and hematocrit of >0.30). MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and intracranial pressure (ICP) were monitored continuously and documented hourly and at every intervention. The means of every 4-hr period were calculated and serum sodium concentrations were measured at the same time. An ICP of 15 mm Hg was treated with a predefined sequence of interventions, and complications were documented. There was no difference with respect to age, male/female ratio, or initial Glasgow Coma Score. In both groups, there was an inverse correlation between serum sodium concentration and ICP (group 1: r = -.13, r2 = .02, p < .03; group 2: r = -.29, r2 = .08, p < .001) that disappeared in group 1 and increased in group 2 (group 1: r = -.08, r2 = .01, NS; group 2: r = -.35, r2 =.12, p < .001). Correlation between serum sodium concentration and cerebral perfusion pressure (CPP) became significant in group 2 after 8 hrs of treatment (r = .2, r2 = .04, p = .002). Over time, ICP and CPP did not significantly differ between the groups. However, to keep ICP at <15 mm Hg, group 2 patients required significantly fewer interventions (p < .02). Group 1 patients received less sodium (8.0 +/- 4.5 vs. 11.5 +/- 5.0 mmol/kg/day, p = .05) and more fluid on day 1 (2850 +/- 1480 vs. 2180 +/- 770 mL/m2, p = .05). They also had a higher frequency of acute respiratory distress syndrome (four vs. 0 patients, p = .1) and more than two complications (six vs. 1 patient, p = .09). Group 2 patients had significantly shorter ICU stay times (11.6 +/- 6.1 vs. 8.0 +/- 2.4 days; p = .04) and shorter mechanical ventilation times (9.5 +/- 6.0 vs. 6.9 +/- 2.2 days; p = .1). The survival rate and duration of hospital stay were similar in both groups. CONCLUSIONS: Treatment of severe head injury with hypertonic saline is superior to that treatment with lactated Ringer's solution. An increase in serum sodium concentrations significantly correlates with lower ICP and higher CPP. Children treated with hypertonic saline require fewer interventions, have fewer complications, and stay a shorter time in the ICU.     

A tube in the pharynx for emergency ventilation

BACKGROUND: If the endotracheal placement of a nasal advanced tube fails, ventilation via this tube could bridge the time until a fibreoptic bronchoscope is available. This study investigates the efficiency of ventilation via a tube resting with its tip in the pharynx near the glottis. METHODS: In 20 patients respiratory data during ventilation via a pharyngeally placed tube were recorded by means of pulse oximetry, capnometry and side-stream spirometry. Results were compared with those measured previously in the same patients during conventional facemask ventilation. RESULTS: Oxygen saturation and end-tidal carbon dioxide concentration remained unchanged using ventilation via facemask (SO2 98.5 +/- 0.9%, FECO2 4.5 +/- 0.7 vol%) or pharyngeal tube (SO2 98.6 +/- 0.7%, FECO2 4.8 +/- 0.4 vol%). No significant differences were found between the two groups with regard to peak airway pressure, tidal volume leakage, compliance and resistance of the respiratory system. CONCLUSIONS: Our results suggest an effective ventilation and oxygenation via a tube placed with its tip in the pharynx. This technique may be helpful during difficult and prolonged nasal intubation.     

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.