OBJECTIVE: To compare the physiologic and pathologic effects of conventional ventilation (CV) and high-frequency ventilation (HFV) during partial liquid ventilation (PLV) with perflubron after surfactant treatment with the results of HFV plus surfactant in an animal lung-injury model created by saline lavage. We also studied the dose effects of perflubron during HFV. DESIGN: Randomized experimental study. SETTING: Research animal laboratory. SUBJECTS: A total of 32 newborn piglets. INTERVENTIONS: After lung injury was induced, the animals were randomized to one of four groups: a) CV + surfactant + perflubron to functional residual capacity (FRC); b) HFV + surfactant + perflubron to FRC; c) HFV + surfactant + 10 mL/kg perflubron; and d) HFV + surfactant. All then received intratracheal surfactant. After 30 mins, perflubron was administered to the PLV groups. The animals underwent ventilation for 20 hrs. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases and hemodynamic variables were continuously monitored. Pulmonary histologic and morphometric analyses were performed after death or euthanasia at 20 hrs. All animals had sustained improvements in arterial/alveolar oxygen ratios, and no differences were observed among groups. All HFV groups required higher mean airway pressures to maintain oxygenation (p <.05). Hemodynamics did not differ among groups. Pathologic analysis demonstrated decreased lung injury in both cranial-dorsal (nondependent) and caudal-ventral (dependent) lobes of all animals treated with PLV when compared with those treated with HFV + surfactant (p <.05). CONCLUSIONS: After surfactant treatment, physiologic support over 20 hrs was similar during HFV with or without perflubron and CV with perflubron. All PLV modalities improved lung pathologic factors uniformly to a greater degree than did HFV + surfactant. A lower treatment volume of perflubron during HFV produced physiologic and pathologic results similar to those produced by perflubron with respect to FRC during either CV or HFV.

High Frequency Oscillatory and Conventional Ventilation, Exogenous Surfactant, and Partial Liquid Ventilation: Effect of Prolonged Treatment on Lung Pathology in an Animal Lung Injury Model

Positive End-Expiratory Pressure during Partial Liquid Ventilation: Impact on Lung Volume Recruitment and Gas Exchange

We hypothesized that during partial liquid ventilation (PLV) with perflubron in spontaneously breathing lung injured animals, a fully-synchronized mode of ventilation, assist-control (A/C), would reduce subject effort when compared to IMV and SIMV. Ten newborn piglets(1.19±0.40 kg) with saline lavage-induced lung injury (PaO2<100 torr at FiO2 1.0) were randomized to sequential 30 minute periods of PLV during IMVSIMVA/C, or A/CSIMVIMV. Piglets were ventilated using time-cycled, pressure limited, volume targeted (15 cc/kg) ventilation(Drager Babylog®). Respiratory rate (RR) and minute ventilation (Ve) were determined as 1 minute moving averages every 15 seconds; tidal volume(Vt), mean airway presure (MAP), and an esophageal pressure-time index(PE·RR) to estimate subject, not mechanical, work of breathing were determined for all breaths. PE·RR was defined as the area below baseline of the esophageal pressure-time curve × RR, and was recorded using a computer-assisted lung mechanics analyzer (VenTrak®). Blood gases were recorded every 30 seconds using an in-line continuous blood gas analyzer(Paratrend 7®); a/A was calculated. Vt variation was assessed using the coefficient of variation (V; SD/mean × 100). Data analysis used paired t-tests with Bonferroni correction. Wilcoxon rank-sum test was used for nonparametric data. Results: Subject work, estimated by PE·RR, was significantly lower with A/C vs SIMV during PLV (A/C vs IMV, p=0.06). pH was higher and a/A was significantly improved using A/C. Ve and MAP increased during A/C. RR was significantly less in AC vs SIMV, and trended lower in A/C vs IMV (p=0.07). Vt was always more consistent during A/C.Conclusion: In spontaneously breathing animals, fully-synchronized PLV using A/C, which required the least patient effort, increased pH, Ve, and a/A at the lowest RR and least variable Vt. These data suggest substantial physiologic benefit from A/C during PLV in nonparalyzed subjects. Perflubron provided by Alliance Pharmaceutical Corp./Hoechst Marion Roussel. VenTrak provided by Novametrix Medical Systems. Babylog provided by Drager Inc. Table

We hypothesized that a fully-synchronized patient triggered mode of ventilation, assist-control (A/C), would reduce subject effort when compared to IMV and SIMV. Ten newborn piglets (1.9±0.40 kg) with saline lavage-induced lung injury (PaO2<100 torr at FiO2 1.0) were randomized to sequential 30 minute periods of IMVSIMVAC (n=5), or ACSIMVIMV (n=5) using time-cycled, pressure limited, volume targeted (15 mL/kg) ventilation (Drager Babylog®). Respiratory rate(RR) and minute ventilation (Ve) were determined as 1 minute moving averages every 15 seconds; tidal volume (Vt), mean airway pressure (MAP), and an esophageal pressure-time index (PE·RR) to estimate subject, not mechanical, work of breathing were determined for all breaths. PE·RR was defined as the area below baseline of the esophageal pressure-time curve× RR, and was recorded using a computer-assisted lung mechanics analyzer(VenTrak®). Blood gases were recorded every 30 seconds using an in-line continuous blood gas analyzer (Paratrend 7®); a/A was calculated. Vt variation was assessed using the coefficient of variation (V; SD/mean × 100). Data analysis used paired t-tests with Bonferroni correction. Wilcoxon rank-sum test was used for nonparametric data.Results: Subject work, estimated by PE·RR, was significantly lower with A/C. Statistically significant differences in A/C vs IMV and SIMV included higher pH, lower RR, and increased Ve and MAP. No differences in a/A were seen. Vt was always less variable during A/C. Conclusion: Fully-synchronized A/C ventilation produced the highest Ve and pH, and the most consistent Vt, with the lowest subject effort as estimated by PE·RR. This data suggests A/C is more efficient during spontaneous respiration than either IMV or SIMV, as it provides improved gas exchange with less inspiratory effort, Table

SummaryA laboratory evaluation was performed to evaluate the performance characteristics of a new veterinary ventilator. The ventilator studied was configured according to manufacturer's directions and attached to a test lung via a pneumotachograph and differential pressure transducer interfaced to a pulmonary mechanics analyzer system. Constant resistance (R=10 cm H2O/L/sec) and compliance (C=3 ml/cm H2O) factors were maintained for all trials. The ventilator operated at the manufacturer's preprogrammed parameters. In the first trial, body weight was the only variable. In the second trial, an endotracheal tube was placed in series between the ventilator's breathing circuit and the pneumotachograph. Body weights from 1–20 kgs were evaluated. Mean values for respiratory rate (RR), minute ventilation (VE), inspiratory time (Ti), peak inspiratory pressure (PIP), and peak inspiratory flow (Fpki) displayed on the ventilator control panel; tidal volume (VT), calculated from the displayed minute volume, and identical parameters measured by the pulmonary mechanics system at each body weight, were compared using a two factor analysis of variance. Significant differences (P< 0.05) were found between mean displayed and measured values for RR, PIP, and Fpki.

Objective: To test the hypothesis that high-frequency ventilation (HFV), when compared with conventional techniques, enhances respiratory gas exchange during partial liquid ventilation (PLV),Design: A four-period crossover design,Setting: Animal research laboratory of Children's Health Care-St. Paul,Subjects: Thirty-two newborn piglets, weighing 1.40 +/- 0.39 kg.Interventions: Animals were divided into four groups of eight animals: a) PLV with high-frequency jet ventilation; b) PLV with jet ventilation using a background intermittent mandatory Ventilation (IMV) rate; c) PLV with high-frequency oscillation; or d) PLV with high frequency flow interruption using a background IMV rate, After anesthesia, paralysis, and tracheotomy, a normal saline wash procedure produced lung injury. Perfluorocarbon was then instilled via the endotracheal tube in an amount estimated to represent functional residual capacity, Animals received randomly either PLV using conventional techniques or PLV using the selected HFV technique as initial treatment, Then, animals were crossed over to the alternative treatment at equal mean airway pressure, as measured at the endotracheal tube tip, This sequence was repeated for a total of four crossover periods, such that all animals were treated twice with PLV using conventional techniques and twice with PLV using HFV,Measurements and Main Results: We measured airway pressures at the endotracheal tube tip, aortic and central venous blood pressures, arterial blood gases, and respiratory system mechanics at baseline, after induction of lung injury, and at specified intervals throughout the experiment, Measurements were made before and 15 mins after crossovers, then ventilators were adjusted to normalize gas exchange, Measurements were again made 30 mins later, at the end of the treatment period, All types of PLV provided adequate gas exchange, Only PLV using jet ventilation with IMV produced gas exchange equal to that seen during PLV using conventional techniques at equivalent mean airway pressure, By the end of the treatment periods, only PLV using high frequency oscillation continued to require higher airway pressure than PLV using conventional techniques for equivalent gas exchange,Conclusions: Gas exchange was not enhanced during PLV-HFV, Application of HFV with PLV provides no clear acute physiologic advantages to PLV using more conventional techniques.

Surfactant (surf, Survanta®) followed by partial liquid ventilation(PLV) with perflubron (LiquiVent®) improves lung mechanics and oxygenation more than S only, PLV only, or PLV followed by S (Peds Res 1996:39;343A). Histologic and morphometric analysis was performed on slides from the upper anterior and lower posterior lobes of 32 newborn piglets (1.7±0.8 kg) with saline lavage-induced lung injury (PaO2<60 torr, FiO2 1.0) after randomization into 4 groups and treatment for 2 hours with: 1) surf only (S; n=8); 2) PLV only (PLV; n=8); 3) PLV followed by surf (PLV-S; n=8 and 4) surf followed by PLV (S-PLV; n=8). Ventilators were adjusted to maintain tidal volume of 15 cc/kg; FiO2 was 1.0. Histologic variables (alveolar, interstitial inflammation; alveolar, interstitial hemorrhage; edema; atelectasis; necrosis) were scored on a 0-4 point scale (no injury = 0, injury in 25% of field = 1, injury in 50% of field = 2, injury in 75% of field = 3, and injury throughout field = 4). Morphometric analysis on trichrome-stained slides analyzed total cellular to air space, expressed as percent tissue area (% tissue area =[cellular area/total area] × 100). Kruskal-Wallis, Wilcoxin, and paired t-tests with Bonferroni correction (p<0.05) were used to assess differences. Table

High Frequency Oscillation After Surfactant and Perfluorocarbon in an Animal Model of RDS. † 1549

Objective To test the hypothesis that high-frequency ventilation (HFV), when compared with conventional techniques, enhances respiratory gas exchange during partial liquid ventilation (PLV). Design A four-period crossover design. Setting Animal research laboratory of Children's Health Care-St. Paul. Subjects Thirty-two newborn piglets, weighing 1.40 +/- 0.39 kg. Interventions Animals were divided into four groups of eight animals: a) PLV with high-frequency jet ventilation; b) PLV with jet ventilation using a background intermittent mandatory ventilation (IMV) rate; c) PLV with high-frequency oscillation; or d) PLV with high-frequency flow interruption using a background IMV rate. After anesthesia, paralysis, and tracheotomy, a normal saline wash procedure produced lung injury. Perfluorocarbon was then instilled via the endotracheal tube in an amount estimated to represent functional residual capacity. Animals received randomly either PLV using conventional techniques or PLV using the selected HFV technique as initial treatment. Then, animals were crossed over to the alternative treatment at equal mean airway pressure, as measured at the endotracheal tube tip. This sequence was repeated for a total of four crossover periods, such that all animals were treated twice with PLV using conventional techniques and twice with PLV using HFV. Measurements and Main Results We measured airway pressures at the endotracheal tube tip, aortic and central venous blood pressures, arterial blood gases, and respiratory system mechanics at baseline, after induction of lung injury, and at specified intervals throughout the experiment. Measurements were made before and 15 mins after crossovers, then ventilators were adjusted to normalize gas exchange. Measurements were again made 30 mins later, at the end of the treatment period. All types of PLV provided adequate gas exchange. Only PLV using jet ventilation with IMV produced gas exchange equal to that seen during PLV using conventional techniques at equivalent mean airway pressure. By the end of the treatment periods, only PLV using high-frequency oscillation continued to require higher airway pressure than PLV using conventional techniques for equivalent gas exchange. Conclusions Gas exchange was not enhanced during PLV-HFV. Application of HFV with PLV provides no clear acute physiologic advantages to PLV using more conventional techniques. (Crit Care Med 1997; 25:1179-1186)

We tested the hypothesis that partial liquid ventilation (PLV) with perflubron (LiquiVent®) in spontaneously breathing (SB) animals would increase respiratory rate (RR), minute ventilation (Ve), and work of breathing when compared to animals treated with gas ventilation (GV). We studied 8 newborn piglets after sedation with ketamine, intubation, and placement of catheters and an esophageal balloon. CPAP was initially used, then animals were randomized to sequentially receive different modes of ventilation during GV (Drager Babylog): IMV-SIMV-AC, or AC-SIMV-IMV. We then instilled perflubron to FRC and repeated the sequence during PLV. Animals returned to CPAP during PLV at the end of the experiment. Each treatment lasted 30 minutes. Ventilator rate during IMV and SIMV, and backup rate during AC, was 10/minute. RR, Ve, and pressure- time product (PTP=ΔPes·Ti, by flow) were measured for all spontaneous and triggered breaths. Standardized PTP•RR is an index of work of breathing. Blood gases were measured and OI calculated every 15 minutes. Reported values are means for the treatment periods. Data analysis used paired t-tests (p<0.05).Table

PARTIAL LIQUID VENTILATION AND SURFACTANT: INTERACTION AND ADMINISTRATION ORDER EFFECTS. † 2040