Increasing inspiratory time exacerbates ventilator-induced lung injury during high-pressure/high-volume mechanical ventilation

INTRODUCTION: Ventilator-induced lung injury may be caused by overdistension of alveoli during high-pressure ventilation. In this study, we examined the effects of increasing inspiratory time on ventilator-induced lung injury. METHODS: Sprague-Dawley rats were divided into four different groups with ten animals per group. Each group was then ventilated for 30 mins with one of four ventilator strategies. All groups were ventilated with an Fio2 of 1.0 and a positive end-expiratory pressure of 0 cm H2O. Group LoP was the negative control group and was ventilated with low pressures (peak inspiratory pressure = 12 cm H2O, rate = 30, and inspiratory time = 0.5 secs). Groups iT = 0.5, iT = 1.0, and iT = 1.5 were the experimental groups and were ventilated with high pressures (peak inspiratory pressure = 45 cm H2O, rate = 10, and inspiratory times = 0.5 secs, iT = 1.0 sec, and iT = 1.5 secs, respectively). Outcome measures included lung compliance, Pao /Fio ratio, wet/dry lung weight, and dry lung/body weight. RESULTS: Final static lung compliance (p =.0002) and Pao2/Fio2 (p =.001) decreased as inspiratory time increased. Wet/dry lung weights (p <.0001) and dry lung/body weights (p <.0001) increased as inspiratory time increased. Light microscopy revealed evidence of intra-alveolar edema and hemorrhage in the iT = 1.0 and iT = 1.5 animals but not the LoP and iT = 0.5 animals. CONCLUSION: Increasing inspiratory time during high-pressure/high-volume mechanical ventilation is associated with an increase in variables of lung injury.     

Repetitive high-pressure recruitment maneuvers required to maximally recruit lung in a sheep model of acute respiratory distress syndrome

OBJECTIVE: To compare the effects of two different recruitment maneuvers repeated multiple times on gas exchange lung injury, hemodynamic, and lung mechanics. DESIGN: Randomized prospective comparison. SETTINGS: Animal research laboratory. SUBJECT: Nineteen fasted Hampshire sheep. INTERVENTIONS: In 15 27-kg sheep with saline lavage lung injury, we compared the effects of two recruitment maneuvers: 40 cm H2O continuous positive airway pressure for 60 secs and 40 cm H2O positive end-expiratory pressure with 20 cm H2O pressure control, rate 10 breaths/min, inspiratory to expiratory ratio 1:1 for 2 mins. Each recruitment maneuver was repeated four times, every 30 mins after a 30-sec ventilator disconnection. An additional group received no recruitment maneuvers. Animals were assigned randomly to the three groups and ventilated with 20 cm H2O positive end-expiratory pressure, pressure control 15 cm H2O, rate 20 breaths/min, inspiratory to expiratory ratio 1:1, and Fio2 1.0 between recruitment maneuver periods. MEASUREMENTS AND MAIN RESULTS: Significant and marked increases in Pao2 were observed in the pressure control recruitment maneuver group but only after the second recruitment maneuver. In both the control group and continuous positive airway pressure groups, Pao2 did not significantly increase after any recruitment maneuver compared with baseline injury. There was a significant decrease in cardiac output immediately after some continuous positive airway pressure recruitment maneuvers and a significant increase in mean pulmonary artery pressure in both continuous positive airway pressure and pressure control groups immediately after recruitment maneuvers, but these changes resolved within 10 mins. There were no marked histologic differences between groups and no volutrauma. CONCLUSION: In this model, maximal lung recruitment was obtained with 40 cm H2O positive end-expiratory pressure and 20 cm H2O pressure control applied repetitively every 30 mins for 2 mins without physiologic or histologic harm. Multiple recruitment maneuvers in some animals were required for maximum effect.     

Effects of sustained inflation and postinflation positive end-expiratory pressure in acute respiratory distress syndrome: focusing on pulmonary and extrapulmonary forms

OBJECTIVE: To investigate whether the response to sustained inflation and postinflation positive end-expiratory pressure varies between acute respiratory distress syndrome with pulmonary (ARDS(exp)) and extrapulmonary origin (ARDS(exp)). DESIGN: Prospective clinical study. SETTING: Multidisciplinary intensive care unit in a university hospital. PATIENTS: A total of 11 patients with ARDS and 13 patients with ARDS. INTERVENTIONS: A 7 ml/kg tidal volume, 12-15 breaths/min respiratory rate, and an inspiratory/expiratory ratio of 1:2 was used during baseline ventilation. Positive end-expiratory pressure levels were set according to the decision of the primary physician. Sustained inflation was performed by 45 cm H2O continuous positive airway pressure for 30 secs. Postinflation positive end-expiratory pressure was titrated decrementally, starting from a level of 20 cm H2O to keep the peripheral oxygen saturation between 92% and 95%. Fio2 was decreased, and baseline tidal volume, respiratory rate, inspiratory/expiratory ratio were maintained unchanged throughout the study period. MEASUREMENTS AND MAIN RESULTS: Blood gas, airway pressure, and hemodynamic measurements were performed at the following time points: at baseline and at 15 mins, 1 hr, 4 hrs, and 6 hrs after sustained inflation. After sustained inflation, the Pao2/Fio2 ratio improved in all of the patients both in ARDS(p) and ARDS(exp). However, the Pao2/Fio2 ratio increased to >200 in four ARDS(p) patients (36%) and in seven ARDS(p) patients (54%). In two of those ARDS patients, the Pao2/Fio2 ratio was found to be <200, whereas none of the ARDS(p) patients revealed Pao2/Fio2 ratios of <200 at the 6-hr measurement. Postinflation positive end-expiratory pressure levels were set at 16.7 +/- 2.3 cm H O in ARDS(p) and 15.6 +/- 2.5 cm H2O in ARDS. The change in Pao /Fio ratios was found statistically significant in patients with ARDS(p) (p =.0001) and with ARDS(p) (p =.008). Respiratory system compliance increased in ARDS patients (p =.02), whereas the change in ARDS was not statistically significant. CONCLUSIONS: Sustained inflation followed by high levels of postinflation positive end-expiratory pressure provided an increase in respiratory system compliance in ARDS; however, arterial oxygenation improved in both ARDS forms.     

Lethal systemic capillary leak syndrome associated with severe ventilator-induced lung injury: an experimental study

OBJECTIVE: We report the evolution of severe ventilator-induced lung injury associated with lethal systemic capillary leak syndrome, when sheep were ventilated at a peak inspiratory pressure of 50 cm H2O, at a respiratory rate of 8 breaths.min, with an inspiratory time of 2.5 secs. DESIGN: A prospective laboratory animal study. SETTING: Experimental animal research laboratory. SUBJECTS: Mixed breed sheep. INTERVENTIONS: Sheep were anesthetized, paralyzed, and mechanically ventilated. MEASUREMENTS AND MAIN RESULTS: This sheep model was characterized by a rapidly evolving massive anasarca, hemoconcentration, cardiac dysfunction, multiple system organ failure, and severe ventilator-induced lung injury. Cardiovascular changes and profound hemoconcentration developed within 6 hrs from the start of mechanical ventilation, along with a major decline in pulmonary compliance and deterioration in arterial blood gases. When total static lung compliance decreased to 0.15 mL (cm H2O)(-1) x kg(-1) (7-30 hrs), the sheep were randomized to two groups. Group I received high (recruitive) positive end-expiratory pressure (9-20 cm H2O), adjusted as needed; group II received low (supportive) positive end-expiratory pressure (2-6 cm H2O). Sheep in both groups progressively deteriorated and died with cardiocirculatory failure and multiple system organ failure within 12-24 hrs from start of treatment. CONCLUSIONS: This model of lethal systemic capillary leak syndrome with multiple system organ failure differs greatly from our previous sheep model of acute ventilator-induced lung injury in which sheep were ventilated with a peak inspiratory pressure of 50 cm H2O, a respiratory rate of 4 breaths x min(-1), and an inspiratory time of 1.35 secs, without inducing capillary leak syndrome. The mere change of respiratory rate from 4 to 8 breaths x min(-1), with a near doubling of the inspiratory time to 2.5 secs, although maintaining eucapnia, resulted in lethal systemic capillary leak syndrome and multiple system organ failure with both gross and microscopic pathology of lungs greatly different from our previous model of mechanical ventilation-induced acute respiratory distress syndrome.     

Effect of different cycling-off criteria and positive end-expiratory pressure during pressure support ventilation in patients with chronic obstructive pulmonary disease

OBJECTIVE: During pressure support ventilation, ventilator inspiration ends when inspiratory flow drops to a given percentage of the peak inspiratory flow cycling-off criteria. This study evaluated the effect of two different cycling-off criteria on breathing pattern, respiratory effort, and gas exchange in patients with chronic obstructive pulmonary disease. DESIGN: Clinical study. PATIENTS: Thirteen mechanically ventilated patients with acute exacerbation of chronic obstructive pulmonary disease primarily due to pneumonia (PaO2/FIO2 291 +/- 114 mm Hg, PaCO2 53 +/- 19 mm Hg). INTERVENTIONS: Two cycling-off criteria (5% and 40% of the peak inspiratory flow) at two levels of pressure support (5 and 15 cm H2O) with and without the application of an external positive end-expiratory pressure (6 and 0 cm H2O) were applied. Measurement Patient-ventilator time delay of cycling-off was computed as the difference between the end of inspiratory flow and the lowest value of inspiratory esophageal pressure. Inspiratory effort was estimated by computing the work of breathing, the pressure time product partitioned into the total pressure time product, and the pressure time product due to the dynamic intrinsic positive end-expiratory pressure. RESULTS: At 5 and 15 cm H2O of pressure support ventilation, the cycling-off criteria 40% significantly reduced the patient-ventilator time delay of cycling-off from 0.40 +/- 0.20 secs to 0.29 +/- 0.16 secs and from 0.93 +/- 0.50 secs to 0.52 +/- 0.25 secs, respectively; the dynamic intrinsic positive end-expiratory pressure from 3.9 +/- 1.8 cm H2O to 3.1 +/- 2.1 cm H2O and from 2.4 +/- 2.0 cm H2O to 1.7 +/- 1.4 cm H2O, respectively; and the pressure time product due to the dynamic intrinsic positive end-expiratory pressure. At 5 cm H2O of pressure support, the cycling-off criteria 40% significantly reduced the tidal volume and the inspiratory effort. The modification of cycling-off criteria did not affect the gas exchange. CONCLUSION: The modification of cycling-off criteria may have a beneficial effect on reducing the dynamic hyperinflation and inspiratory effort in chronic obstructive pulmonary disease patients, especially at low levels of pressure support.     

Physiologic effects of transtracheal open ventilation in postextubation patients with high upper airway resistance

OBJECTIVE: To investigate whether transtracheal open ventilation (TOV), pressure control ventilation (PCV) through a minitracheotomy tube (internal diameter 4 mm), is an effective method of inspiratory assistance under high upper airway resistance in postextubation patients; to compare, in a lung model study, TOV with other methods. DESIGN: Clinical study: A prospective, controlled, crossover study. Lung model study: A prospective laboratory trial. SETTING: Clinical study: A six-bed general intensive care unit in a teaching hospital. Lung model study: Animal research laboratory. PATIENTS: Clinical study: Eleven postextubation patients, who had undergone minitracheotomy for sputum retention between January 1997 and December 1997. SUBJECT: Lung model study: Two-bellows-in-a-box lung model, which included ordinary and high levels of upper airway resistance. INTERVENTIONS: Clinical study: Ventilatory settings were: assist/control (A/C) mode, 2 breaths/min of A/C back-up rate, 35-40 cm H2O of PCV, 0.6-0.8 secs of inspiratory time, and 0 cm H2O of positive end-expiratory pressure. The ventilatory parameters of TOV were compared with those of spontaneous breathing (SB). Lung model study: Effect of TOV on inspiratory assistance was compared with those of SB, open minitracheotomy, 5 L/min of transtracheal gas insufflation, and 5 and 10 cm H2O of pressure support ventilation (PSV), which simulated noninvasive positive ventilation. TOV ventilatory settings were: A/C mode; 30, 40, and 50 cm H2O of PCV, 0.9 secs of inspiratory time, and 0 cm H2O of positive end-expiratory pressure. At each ventilatory setting, we adjusted the inspiratory effort of the model to give a tidal volume of 0.5 L. MEASUREMENTS AND MAIN RESULTS: Clinical study: TOV was performed for 76.6 +/- 38.6 hrs (mean +/- sd) over 5.6 +/- 2.6 days without major complication. Peak tracheal pressure, which was measured distal to the minitracheotomy tube in six patients by a catheter pressure transducer, was 4.33 +/- 0.59 cm H2O. Inspiratory tidal volume delivered by the ventilator was 0.51 +/- 0.06 L. Respiratory rate during TOV was lower than during SB. According to esophageal pressure and respiratory inductive plethysmography, TOV reduced the patient's inspiratory work and improved the breathing pattern. Lung model study: Mean tracheal pressure during TOV and 10 cm H2O of PSV were positive values and they had larger inspiratory assistance according to the pressure-time product of pleural pressure. Although high upper airway resistance reduced the inspiratory assistance of PSV, it did not change the effects of TOV. CONCLUSIONS: TOV effectively reduced patient's inspiratory work and was more useful than open minitracheotomy and transtracheal gas insufflation. TOV also improved the breathing pattern. TOV may be useful for resolving some postextubation respiratory problems and avoiding the need for reintubation.     

Effects of positive end-expiratory pressure on gas exchange and expiratory flow limitation in adult respiratory distress syndrome

OBJECTIVE: To assess the effects of different positive end-expiratory pressure (PEEP) levels (0, 5, 10, and 15 cm H2O) on tidal expiratory flow limitation (FL), regional intrinsic positive end-expiratory pressure (PEEPi) inhomogeneity, alveolar recruited volume (Vrec), respiratory mechanics, and arterial blood gases in mechanically ventilated patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective clinical study. SETTING: Multidisciplinary intensive care unit of a university hospital. PATIENTS: Thirteen sedated, mechanically ventilated patients during the first 2 days of ARDS. INTERVENTIONS: Detection of tidal FL and evaluation of total dynamic PEEP (PEEPt,dyn), total static PEEP (PEEPt,st), respiratory mechanics, and Vrec from pressure, flow, and volume traces provided by the ventilator. The average (+/-sd) tidal volume was 7.1 +/- 1.5 mL/kg, the total cycle duration was 2.9 +/- 0.45 secs, and the duty cycle was 0.35 +/- 0.05. MEASUREMENTS: Tidal FL was assessed using the negative expiratory pressure technique. Regional PEEPi inhomogeneity was assessed as the ratio of PEEPt,dyn to PEEPt,st (PEEPi inequality index), and Vrec was quantified as the difference in lung volume at the same airway pressure between quasi-static inflation volume-pressure curves on zero end-expiratory pressure (ZEEP) and PEEP. RESULTS: On ZEEP, seven patients exhibited FL amounting to 31 +/- 8% of tidal volume. They had higher PEEPt,st and PEEPi,st ( p<.001) and lower PEEPi inequality index ( p<.001) than the six nonflow-limited (NFL) patients. Two FL patients became NFL with PEEP of 5 cm H2O and five with PEEP of 10 cm H2O. In both groups, PaO2 increased progressively with PEEP. In the FL group, there was a significant correlation of PaO2 to PEEPi inequality index ( p=.002). For a given PEEP, Vrec was greater in NFL than FL patients, and a significant correlation of Pao to Vrec ( p<.001) was found only in the NFL group. CONCLUSIONS: We conclude that on ZEEP, tidal FL is common in ARDS patients and is associated with greater regional PEEPi inhomogeneity than in NFL patients. With PEEP of 10 cm H2O, flow limitation with concurrent cyclic dynamic airway compression and re-expansion and the risk of "low lung volume injury" were absent in all patients. In FL patients, PEEP induced a significant increase in PaO2, mainly because of the reduction of regional PEEPi inequality, whereas in the NFL group, arterial oxygenation was improved satisfactorily because of alveolar recruitment.     

Recruitment maneuver: does it promote bacterial translocation?

OBJECTIVE: High peak airway opening pressures (Pao) are used routinely during recruitment maneuvers to open collapsed lung units. High peak Pao, however, can cause lung injury as evidenced by translocation of intratracheally inoculated bacteria. In this study we explored whether recruitment maneuvers that used high Pao could cause translocation of the intratracheally inoculated from the alveoli into the systemic circulation. DESIGN: Prospective, randomized, animal study. SETTING: Experimental animal care laboratory. SUBJECTS: Eighteen male Sprague Dawley rats.INTERVENTIONS Rats were anesthetized, tracheostomized, and ventilated with 14 cm H2O peak Pao and 0 cm H2O positive end-expiratory pressure (PEEP) in pressure-controlled ventilation (frequency, 30 bpm; inspiratory/expiratory ratio, 1:2; Fio, 1). Intratracheal inoculation of 500 microL of saline containing 1 x 10 colony forming units/mL was performed before randomization into three groups (n = 6 in each): a low-pressure group (14 cm H2O peak Pao, 0 cm H2O PEEP), a high-pressure group (45 cm H2O peak Pao, 0 cm H2O PEEP), and a recruitment maneuver group (14 cm H2O peak Pao, 0 cm H2O PEEP, and a recruitment maneuver sustained inflation of 45 cm H2O continuous positive airway pressure for 30 secs every 15 mins). Blood samples for blood gas analysis were obtained before intratracheal instillation of bacteria and at the end of the experimental protocol (2 hrs). Blood cultures were obtained before and after bacterial instillation at 30-min intervals during the experiment. Blood samples were cultured directly in sheep blood, MacConkey, and Iso-Sensitest agars and were observed on the second day. Bacteremia was defined as the presence of one or more colonies of in 1 mL of blood. MEASUREMENTS AND MAIN RESULTS: The blood cultures were positive for in only six rats in the high-pressure group and remained negative throughout the study period in the low-pressure and recruitment maneuver groups. Oxygenation deteriorated in all groups after intratracheal instillation of bacteria. In the high-pressure group, oxygenation decreased from 417 +/- 67 mm Hg to 79 +/- 20 mm Hg ( p=.004), whereas in the low-pressure and recruitment maneuver groups PaO2 decreased from 410 +/- 98 mm Hg and 383 +/- 78 mm Hg to 287 +/- 105 mm Hg ( p=.031) and 249 +/- 59 mm Hg (p =.11), respectively. CONCLUSION: Intermittent recruitment maneuvers applied as a sustained inflation superimposed on low-pressure ventilation with 0 cm H2O PEEP did not cause translocation of intratracheally inoculated.     

Mechanistic scheme and effect of "extended sigh" as a recruitment maneuver in patients with acute respiratory distress syndrome: a preliminary study

OBJECTIVE: To devise a new form of sigh ("extended sigh") capable of providing a sufficient recruiting pressure x time, and to test it as a recruitment maneuver in patients with acute respiratory distress syndrome. DESIGN: Prospective uncontrolled clinical trial. SETTING: Medical intensive care unit of a university-affiliated hospital. PATIENTS: Twenty consecutive patients diagnosed with acute respiratory distress syndrome (18 men, 2 women, age 59 +/- 10 yrs). INTERVENTIONS: From baseline settings of tidal volume (Vt) 8 mL/kg and positive end-expiratory pressure (PEEP) 10 cm H2O on volume control mode with the high pressure limit at 40 cm H2O, the Vt-PEEP values were changed to 6-15, 4-20, and 2-25, each step being 30 secs (inflation phase). After Vt-PEEP 2-25, the mode was switched to continuous positive airway pressure of 30 cm H2O for a duration of 30 secs (pause), after which the baseline setting was resumed following the reverse sequence of inflation (deflation phase). This extended sigh was performed twice with 1 min of baseline ventilation between. MEASUREMENTS AND RESULTS: Airway pressures and hemodynamic parameters were traced at each step during the extended sigh. Arterial blood gases and physiologic parameters were determined before the extended sigh (pre-extended sigh), at 5 mins after two extended sighs (post-extended sigh), and then every 15 mins for 1 hr. In our average patient, the recruiting pressure x time of the inflation phase was estimated to be 32.8-35.4 cm H2O x 90 secs. Compared with the inflation phase, inspiratory pause pressure of the deflation phase was lower at Vt-PEEP 6-15 (28.9 +/- 2.7 cm H2O vs. 27.3 +/- 2.8 cm H2O) and 4-20 (31.8 +/- 2.9 cm H2O vs. 31.1 +/- 2.9 cm H2O; both p <.05). Compared with pre-extended sigh, Pao2 (81.5 +/- 15.3 mm Hg vs. 104.8 +/- 25.0 mm Hg; p <.001) and static respiratory compliance both increased post-extended sigh (27.9 +/- 7.9 mL/cm H2O vs. 30.2 +/- 9.7 mL/cm H2O; p =.009). Improvement in these parameters was sustained above pre-extended sigh for the duration of the study. Major hemodynamic or respiratory complications were not noted during the study. CONCLUSION: We present a new form of sigh (i.e., extended sigh) capable of achieving an augmented recruiting pressure x time through a prolonged inflation on a gradually increased end-expiratory pressure. In view of the sustained effect and absence of major complications in our patients, extended sigh could be a useful recruitment maneuver in acute respiratory distress syndrome.     

Intratracheal pulmonary ventilation in a rabbit lung injury model: continuous airway pressure monitoring and gas exchange efficacy

OBJECTIVES: To compare carinal pressures vs. proximal airway pressures, and gas exchange efficacy with a constant minute volume, in lung-injured rabbits during conventional mechanical ventilation (CMV) and intratracheal pulmonary ventilation (ITPV); and to evaluate performance of a prototype ITPV gas delivery and continuous airway pressure monitoring system. DESIGN: Prospective controlled study. SETTING: Animal research laboratory at a teaching hospital. SUBJECTS: Sixteen adult female rabbits. INTERVENTIONS: Anesthetized rabbits were tracheostomized with a multilumen endotracheal tube. Anesthesia and muscle relaxation were maintained continuously throughout the study. Proximal airway pressures and carinal pressures were recorded continuously. The injection port of the multilumen endotracheal tube was used for the carinal pressure monitoring. To prevent obstruction of the port, it was flushed with oxygen at a rate of 11 mL/min. CMV was initiated with a pressure-limited, time-cycled ventilator set at an FiO2 of 1.0 and at a flow of 1.0 L/kg/min. The pressure limit of the ventilator was effectively disabled. A normal baseline for arterial blood gases was achieved by adjusting the inspiratory/expiratory time ratios. ITPV was established using a flow of 1.0 L/kg/min through a reverse thrust catheter, at the same baseline and inspiratory/expiratory ratio. Carinal positive end-expiratory pressure was maintained at a constant value of 2 cm H2O by adjusting the expiratory resistance of the ventilator circuit Lung injury was achieved over a 30-min period by three normal saline lavages of 5 mL/kg each. After lung injury, all animals were consecutively ventilated for 1 hr with CMV, for 1 hr with ITPV, and again for 1 hr with CMV. Six rabbits were ventilated at 30 breaths/min (group 1), and ten rabbits were ventilated at 80 breaths/min (group 2). Four rabbits in group 2 were subjected, 1 hr after return to CMV from ITPV, to another session of ITPV, with positive end-expiratory pressure gradually being increased to 4, 6, and 8 cm H2O for 15 mins each. RESULTS: No significant differences were observed in carinal peak inspiratory pressure between CMV and ITPV modes, at both low and high frequencies of breathing, indicating that the inspired tidal volume remained constant during both modes of ventilation. Significant gradients were noted between proximal airway and carinal peak inspiratory pressure during ITPV but not during CMV. Initiation of ITPV, at a flow of 1.0 L/kg/min, required an increase in the ventilator expiratory resistance to maintain a constant level of positive end-expiratory pressure (2 cm H2O) as measured at the carina. During ITPV, the PaCO2 was significantly reduced by 20% at 30 breaths/min (p < .05) and by 22% at 90 breaths/min (p < .01), compared with CMV. Arterial oxygenation was significantly enhanced with a positive end-expiratory pressure of 6 and 8 cm H2O (p < .05 and .001, respectively), compared with a positive end-expiratory pressure of 2 cm H2O during ITPV. All components of the new prototype gas delivery and airway pressure monitoring system functioned without failure, at least for 3 hrs of the CMV, ITPV, and CMV trials. CONCLUSIONS: ITPV in saline-lavaged, lung-injured rabbits at breathing frequencies of 30 and 80 breaths/min, compared with CMV at the same minute ventilation, can improve CO2 exchange. During ITPV, significant pressure gradients can develop between carinal and proximal airway pressures. Continuous carinal pressure monitoring is therefore necessary for the safe clinical application of ITPV. Reliable carinal pressure monitoring can be achieved by adding a small bias flow through the carinal pressure monitoring port. Although ITPV can remove CO2 from injured lungs efficiently, simultaneous addition of positive end-expiratory pressure can further improve arterial oxygenation.     

A comparison of intratracheal pulmonary ventilation to conventional ventilation in a surfactant deficient animal model

OBJECTIVE: To compare intratracheal pulmonary ventilation (ITPV) with conventional ventilation in a rabbit model of surfactant deficiency. DESIGN: A prospective randomized animal study. SETTING: The Children's National Medical Center Research Animal Facility in Washington, DC. SUBJECTS: Adult male New Zealand white rabbits (n = 20), weighing 1.4-4.2 kg. INTERVENTIONS: After anesthesia and catheter placement, rabbits were tracheotomized, paralyzed, and placed on the conventional ventilator. We determined pulmonary functions at baseline. We washed surfactant out of the lungs by using serial bronchoalveolar lavages. Pulmonary function studies were determined after completion of the bronchoalveolar lavages and were used as an indication of severity of lung injury. Animals were randomized into two groups: We placed ten animals on ITPV, using the ITPV reverse thruster catheter designed by Kolobow and a prototype ITPV ventilator designed at Children's National Medical Center; we placed ten animals on conventional ventilation using the Sechrist iv-100 ventilator. Arterial blood gases were drawn every 15 mins, and the ventilator settings were adjusted to the minimal level that would maintain arterial blood gases in the following ranges: pH 7.35-7.45, PaCO2 30-40 torr (3.995.33 kPa), PaO2 50-70 torr (6.66-9.33 kPa). Animals were ventilated with the randomized ventilation techniques for 4 hrs. MEASUREMENTS AND MAIN RESULTS: Peak inspiratory pressure, mean airway pressure, and positive end-expiratory pressure were measured at the distal end of the endotracheal tube. We recorded these variables plus respiratory rate at baseline and every 30 mins for a total of 4 hrs of ventilation. Lung compliance did not differ between groups at the postlavage study period (ITPV, 0.56+/-0.13 mL/cm H2O/kg; conventional 0.49+/-0.15 mL/cm H2O/kg). At the end of the 4 hr study period, peak inspiratory pressure (ITPV, 26.2+/-4.6 cm H2O; conventional, 32.4+/-5.04 cm H2O, p = .007) and positive end-expiratory pressure (ITPV, 3.9+/-1.96 cm H2O; conventional, 6.3+/-1.42 cm H2O, p = .005) were lower in the ITPV ventilation group. Peak inspiratory pressure was significantly lower in the ITPV group by 2 hrs into the study. CONCLUSION: In this model of surfactant deficiency lung injury, ventilation and oxygenation were achieved at significantly lower ventilator settings using ITPV compared with conventional ventilation. Long-term studies are needed to determine whether this reduction in ventilation is maintained, and if so, if lung injury is reduced.     

Effects of different continuous positive airway pressure devices and periodic hyperinflations on respiratory function

OBJECTIVE: To compare the effect on respiratory function of different continuous positive airway pressure systems and periodic hyperinflations in patients with respiratory failure. DESIGN: Prospective SETTING: Hospital intensive care unit. PATIENTS: Sixteen intubated patients (eight men and eight women, age 54 +/- 18 yrs, PaO2/FiO2 277 +/- 58 torr, positive end-expiratory pressure 6.2 +/- 2.0 cm H2O). INTERVENTIONS: We evaluated continuous flow positive airway pressure systems with high or low flow plus a reservoir bag equipped with spring-loaded mechanical or underwater seal positive end-expiratory pressure valve and a continuous positive airway pressure by a Servo 300 C ventilator with or without periodic hyperinflations (three assisted breaths per minute with constant inspiratory pressure of 30 cm H2O over positive end-expiratory pressure). MEASUREMENTS AND MAIN RESULTS: We measured the respiratory pattern, work of breathing, dyspnea sensation, end-expiratory lung volume, and gas exchange. We found the following: a) Work of breathing and gas exchange were comparable between continuous flow systems; b) the ventilator continuous positive airway pressure was not different compared with continuous flow systems; and c) continuous positive airway pressure with periodic hyperinflations reduced work of breathing (10.7 +/- 9.5 vs. 6.3 +/- 5.7 J/min, p <.05) and dyspnea sensation (1.6 +/- 1.2 vs. 1.1 +/- 0.8 cm, p <.05) increased end-expiratory lung volume (1.6 +/- 0.8 vs. 2.0 +/- 0.9 L, p <.05) and PaO2 (100 +/- 21 vs. 120 +/- 25 torr, p <.05) compared with ventilator continuous positive airway pressure. CONCLUSIONS: The continuous flow positive airway pressure systems tested are equally efficient; a ventilator can provide satisfactory continuous positive airway pressure; and the use of periodic hyperinflations during continuous positive airway pressure can improve respiratory function and reduce the work of breathing.     

Partial liquid ventilation in severely surfactant-depleted, spontaneously breathing rabbits supported by proportional assist ventilation

OBJECTIVE: We hypothesized that partial liquid ventilation (PLV) would improve oxygenation in nonparalyzed, surfactant-deficient rabbits breathing spontaneously while supported by proportional assist ventilation (PAV). This ventilation mode compensates for low pulmonary compliance and high resistance and thereby facilitates spontaneous breathing. DESIGN: Randomized trial. SETTING: University animal research facility. SUBJECTS: Twenty-six anesthetized New Zealand white rabbits weighing 2592 +/- 237g (mean +/- sd). INTERVENTIONS: After pulmonary lavage (target Pao2 <100 mm Hg on mechanical ventilation with 6 cm H2O of positive end-expiratory pressure [PEEP] and an Fio2 of 1.0), rabbits were randomized to PAV (PEEP of 8 cm H2O) with or without PLV. PLV rabbits received 25 mL/kg of perfluorocarbon by intratracheal infusion (1 mL/kg/min). Pao2, Paco2, tidal volume, respiratory rate, minute ventilation, mean airway pressure, arterial blood pressure, heart rate, pulmonary compliance, and airway resistance were measured. Evaporated perfluorocarbon was refilled every 30 mins in PLV animals. After 5 hrs, animals were killed and lungs were removed. Lung injury was evaluated using a histologic score. MAIN RESULTS: Pao2 and compliance were significantly higher in PLV rabbits compared with controls (p <.05, analysis of variance for repeated measures). All other parameters were similar in both groups. CONCLUSIONS: PLV improved oxygenation and pulmonary compliance in spontaneously breathing, severely surfactant-depleted rabbits supported by PAV. The severity of lung injury by histology was unaffected.     

A comparative evaluation of three neonatal ventilators

The comparative reliability of three neonatal ventilators was evaluated using an infant model lung to simulate airway resistance and lung compliance. The ventilators tested were the Bourns BP200, the Healthdyne TI-11, and a positive-pressure ventilator called the PREEMIE (not commercially manufactured) used in several neonatal units in the Milwaukee area. The Bourns and Healthdyne ventilators generated similar airway and alveolar pressures while the PREEMIE produced alveolar, peak inspiratory, and positive end-expiratory pressures that exceeded the respective ventilator pressure settings by up to 11 cm H2O. The simple method described here should be generally useful for the evaluation of neonatal ventilator output.     

Airway pressure as a measure of gas exchange during high-frequency jet ventilation

Airway pressure during high-frequency jet ventilation (HFJV) reflects safety, ventilator performance, and gas exchange. The value of airway pressure as a monitoring and control variable for predicting the effectiveness of gas exchange was examined in 2 studies using healthy dogs. In the first study, HFJV was delivered to the airway via an extra lumen in the wall of an endotracheal tube, at a frequency of 150 cycle/min and 30% inspiratory time. Airway pressures (peak, mean, trough) were measured at various locations, from 5 cm below to 30 cm above the jet port. Pressures measured above the jet were misleading, but the proper measurement distance below the jet remains uncertain. The second study used the same ventilator settings but varied the airway pressure difference between peak and end-expiratory pressures (2, 4, or 6 cm H2O), and either the mean airway pressure (6 or 10 cm H2O) or the positive end-expiratory pressure (0, 5, 10, or 15 cm H2O). The airway pressure difference correlated strongly with efficiency of gas exchange for both CO2 elimination and oxygenation. Mean and end-expiratory pressures showed little influence over moderate ranges, but use of 15 cm H2O of PEEP decreased efficiency of both CO2 elimination and oxygenation, presumably due to increased dead space because of lung overdistension. We conclude that the airway pressure difference, measured as far distal in the airway as is safe and practical, can be useful for monitoring and controlling HFJV.     

Evaluation of inspiratory rise time and inspiration termination criteria in new-generation mechanical ventilators: a lung model study

INTRODUCTION: Inspiratory rise time adjustment during pressure ventilation and inspiration termination criteria adjustment during pressure support ventilation are available on some of the newest mechanical ventilators. Both are designed to improve patient-ventilator synchrony. However, the function of these adjuncts during pressure ventilation on these ventilators has not been evaluated. METHODS: Three inspiratory rise times (minimum, medium, and maximum) were evaluated in 5 new-generation mechanical ventilators (Hamilton Galileo, Siemens 300A, Puritan Bennett 840, BEAR 1000, and Dr?ger Evita 4) during pressure support and pressure assist/control. Three inspiration termination criteria settings (minimum, medium, and maximum) were also evaluated in 2 mechanical ventilators (Hamilton Galileo and Puritan Bennett 840) during pressure support. All evaluations were performed with a spontaneous breathing lung model (compliance 50 mL/cm H2O, resistance 8.2 cm H2O/L/s, respiratory rate 12 breaths/min, inspiratory time 1.0 s, and lung model peak inspiratory flow 60 L/min). Throughout the evaluation, inspiratory pressure was set at 15 cm H2O and positive end-expiratory pressure at 5 cm H2O, resulting in a peak airway pressure of 20 cm H2O. RESULTS: Significant (p < 0.05) and important (> 10%) differences were found among the ventilators at similar rise times (minimum, medium, and maximum) and for each ventilator as rise time was varied. Also, significant (p < 0.05) and important (> 10%) differences were observed between ventilators and within each ventilator when inspiration termination criteria were varied. There were significant (p < 0.05) differences between pressure support and pressure assist/control, but most were < 10%, except those associated with expiration. CONCLUSIONS: Major differences exist for each ventilator as rise time or inspiration termination criteria are varied and among ventilators at similar settings. Inspiration termination criteria adjustment markedly affects transition to exhalation in the Puritan Bennett 840.     

Pulmonary surfactant is altered during mechanical ventilation of isolated rat lung

OBJECTIVE: To test the hypothesis that the lung injury induced by certain mechanical ventilation strategies is associated with changes in the pulmonary surfactant system. DESIGN: Analysis of the pulmonary surfactant system from isolated rat lungs after one of four different ventilatory strategies. SETTING: A research laboratory at a university. SUBJECTS: A total of 45 Sprague-Dawley rats. INTERVENTIONS: Isolated lungs were randomized to either no ventilation (0-TIME) or to ventilation at 40 breaths/min in a humidified 37 degrees C chamber for either 30 mins or 120 mins with one of the following four strategies: a) control (CON, 7 mL/kg, 3 cm H2O positive end-expiratory pressure); b) medium volume, zero end-expiratory pressure (MVZP, 15 mL/kg, 0 cm H2O end-expiratory pressure); c) medium volume, high positive end-expiratory pressure (MVHP, 15 mL/kg, 9 cm H2O positive end-expiratory pressure); and d) high volume, zero end-expiratory pressure (HVZP, 40 mL/kg, 0 cm H2O end-expiratory pressure). MEASUREMENTS: Pressure-volume curves were determined before and after the ventilation period, after which the lungs were lavaged for surfactant analysis. MAIN RESULTS: Compared with 0-TIME, 30 mins of ventilation with the HVZP strategy or 120 mins of ventilation with CON and MVZP strategies caused a significant decrease in compliance. Groups showing a decreased compliance had significant increases in the amount of surfactant, surfactant large aggregates, and total lavage protein compared with 0-TIME. CONCLUSIONS: A short period of injurious mechanical ventilation can cause a decrease in lung compliance that is associated with a large influx of proteins into the alveolar space and with alterations of the pulmonary surfactant system. The changes of surfactant in these experiments are different from those seen in acute lung injury, indicating that they may represent an initial response to mechanical ventilation.     

A simple method for the measurement of intrinsic positive end-expiratory pressure during controlled and assisted modes of mechanical ventilation.

OBJECTIVE: To evaluate a new and simple method for the measurement of intrinsic positive end-expiratory pressure during controlled and assisted modes of mechanical ventilation. DESIGN: Prospective study. SETTING: Three university hospital medical ICUs. PATIENTS: A total of 13 intubated, mechanically ventilated patients with severe airway obstruction. INTERVENTIONS: Airway occlusions reproducibly timed to occur coincidently with end-expiration were obtained by: a) manipulation of a three-way manual valve placed in the inspiratory limb of the external ventilator circuit (manual valve method) and b) activation of the expiratory pause hold function of the mechanical ventilator (Siemens 900C). MEASUREMENTS AND MAIN RESULTS: Airway pressure, flow, and volume were recorded during controlled and assisted modes of mechanical ventilation. Intrinsic positive end-expiratory pressure was determined from the plateau in airway pressure, which was developed during end-expiratory occlusions. For controlled mechanical ventilation, intrinsic positive end-expiratory pressure averaged 11.42 +/- 0.77 (SEM) cm H2O with the manual valve method, compared with 11.38 +/- 0.70 cm H2O, using the ventilator expiratory pause hold function. There was close correlation between results over the wide range of intrinsic positive end-expiratory pressure observed, which varied from approximately 5 to 22 cm H2O (y = 1.08x - 0.92; r2 = .99). Values of intrinsic positive end-expiratory pressure were comparable for the two methods during assist-control ventilation, pressure support ventilation, and spontaneous breathing through the ventilator circuit. The manual valve method was also effective when tested with different mechanical ventilators using a mechanical lung model. CONCLUSIONS: The manual valve method can be used to determine intrinsic positive end-expiratory pressure during controlled and assisted modes of ventilatory support with current ventilators. The availability of such an approach should facilitate the routine monitoring of intrinsic positive end-expiratory pressure in mechanically ventilated patients, thereby aiding clinical decision-making and management in these critically ill individuals.     

Effects of cyclic opening and closing at low- and high-volume ventilation on bronchoalveolar lavage cytokines

OBJECTIVE: To examine the mechanisms of ventilator-induced lung injury at low and high lung volumes. DESIGN: Prospective, randomized, laboratory study. SETTING: University research laboratory. SUBJECTS: Eighty-eight adult male Sprague-Dawley rats. INTERVENTIONS: Mechanical ventilation using low and high lung volumes. MEASUREMENTS AND MAIN RESULTS: An ex vivo rat lung model was used. In study I (ventilation at low lung volumes), rat lungs (n = 40) were randomly assigned to various modes of ventilation: a) opening and closing with positive end-expiratory pressure (PEEP; control): tidal volume 7 mL/kg and PEEP 5 cm H2O; b) opening and closing from zero end-expiratory pressure (ZEEP): tidal volume 7 mL/kg and PEEP 0; or c) atelectasis. Peak inspiratory pressure was monitored at the beginning and end of 3 hrs of ventilation. At the end of 3 hrs of ventilation, the lungs were lavaged, and the concentrations of tumor necrosis factor-alpha, macrophage inflammatory protein-2, and interleukin-6 cytokines were measured in the lavage. In study II (ventilation at high volumes), rat lungs (n = 45) were randomly assigned to a) cyclic lung stretch: pressure-controlled ventilation, peak inspiratory pressure 50 cm H2O, and PEEP 8 cm H2O; b) continuous positive airway pressure at 50 cm H2O (CPAP50); or c) CPAP at the mean airway pressure of the cyclic stretch group (CPAP 31 cm H2O). Bronchoalveolar lavage cytokine concentrations (tumor necrosis factor-alpha, macrophage inflammatory protein-2, and interleukin-6) were measured at the end of 3 hrs of ventilation. In the low volume study, there was no difference in bronchoalveolar lavage cytokine concentrations between the PEEP group and the atelectatic group. All cytokines were significantly higher in the ZEEP group compared with the atelectasis group. Macrophage inflammatory protein-2 was significantly higher in the ZEEP group compared with the PEEP group. Lung compliance, as reflected by change in peak inspiratory pressure, was also significantly worse in the ZEEP compared with the PEEP group. In the high-volume study, tumor necrosis factor-alpha and interleukin-6 were significantly higher in the cyclic stretch group compared with the CPAP 31 group. There was no significant difference between the cytokine concentrations in the cyclic stretch group compared with the CPAP 50 group. CONCLUSION: We conclude that at low lung volumes, cyclic opening and closing from ZEEP leads to greater increases in bronchoalveolar lavage cytokines than atelectasis. With high-volume ventilation, over time, the degree of overdistension is more associated with increases in bronchoalveolar lavage cytokines than cyclic opening and closing alone.     

Compression volume during mechanical ventilation: comparison of ventilators and tubing circuits

Four ventilators (Puritan-Bennett MA-1 and MA-2, Emerson, and Bear I) and four commercially available disposable and nondisposable tubing circuits (Bennett nondisposable, Becton-Dickinson, Inspiron, and Life-line) were tested on a lung analog for differences in inspiratory-circuit compression volume. The compression ratio (Rc), equal to the gas volume compressed per cm H2O peak airway pressure, was calculated for each combination of ventilator and circuit at each of four compliance settings (0.15, 0.10, 0.05, 0.01 L/cm H2O) on the analog. Rc values ranged from 0.3 to 4.5 ml/cm H2O at the highest and lowest compliance settings, respectively, accounting for a reduction in delivered tidal volume of up to 20%. The Emerson ventilator with all tubing systems and the Bennett nondisposable circuit with each ventilator demonstrated slightly smaller compression volumes. Application of an inspiratory pause on the Bear I ventilator did not affect its compression characteristics. The clinical importance of compression volume and data from other ventilation systems are reviewed.