Dennis R. Bing

Prolonged partial liquid ventilation using conventional and high-frequency ventilatory techniques: gas exchange and lung pathology in an animal model of respiratory distress syndrome.

OBJECTIVE To evaluate the effect of prolonged partial liquid ventilation with perflubron (partial liquid ventilation), using conventional and high-frequency ventilatory techniques, on gas exchange, hemodynamics, and lung pathology in an animal model of lung injury. DESIGN Prospective, randomized, controlled study. SETTING Animal laboratory of the Infant Pulmonary Research Center, Childrens Health Care-St. Paul. SUBJECTS Thirty-six newborn piglets. INTERVENTIONS We studied newborn piglets with lung injury induced by saline lavage. Animals were randomized into one of five treatment groups: a) conventional gas ventilation (n = 8); b) partial liquid ventilation with conventional ventilation (n = 7); c) partial liquid ventilation with high-frequency jet ventilation (n = 7); d) partial liquid ventilation with high-frequency oscillation (n = 7); and e) partial liquid ventilation with high-frequency flow interruption (n = 7). After induction of lung injury, all partial liquid ventilation animals received intratracheal perflubron to approximate functional residual capacity. After 30 mins of stabilization, animals randomized to high-frequency ventilation were changed to their respective high-frequency modes. Hemodynamics and blood gases were measured before and after lung injury, after perflubron administration, and then every 4 hrs for 20 hrs. Histopathologic evaluation was carried out using semiquantitative scoring and computer-assisted morphometric analysis on pulmonary tissue from animals surviving at least 16 hrs. MEASUREMENTS AND MAIN RESULTS All animals developed acidosis and hypoxemia after lung injury. Oxygenation significantly (p < .001) improved after perflubron administration in all partial liquid ventilation groups. After 4 hrs, oxygenation was similar in all ventilator groups. The partial liquid ventilation-jet ventilation group had the highest pH; intergroup differences were seen at 16 and 20 hrs (p < .05). The partial liquid ventilation-oscillation group required higher mean airway pressure; intergroup differences were significant at 4 and 8 hrs (p < .05). Aortic pressures, central venous pressures, and heart rates were not different at any time point. Survival rate was significantly lower in the partial liquid ventilation-flow interruption group (p < .05). All partial liquid ventilation-treated animals had less lung injury compared with gas-ventilated animals by both histologic and morphometric analysis (p < .05). The lower lobes of all partial liquid ventilation-treated animals demonstrated less damage than the upper lobes, although scores reached significance (p < .05) only in the partial liquid ventilation-conventional ventilation animals. CONCLUSIONS In this animal model, partial liquid ventilation using conventional or high-frequency ventilation provided rapid and sustained improvements in oxygenation without adverse hemodynamic consequences. Animals treated with partial liquid ventilation-flow interruption had a significantly decreased survival rate vs. animals treated with the other studied techniques. Histopathologic and morphometric analysis showed significantly less injury in the lower lobes of lungs from animals treated with partial liquid ventilation. High-frequency ventilation techniques did not further improve pathologic outcome.

Partial liquid ventilation : A comparison using conventional and high-frequency techniques in an animal model of acute respiratory failure

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 Childrens 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.

Randomized Controlled Trial of Volume-Targeted Synchronized Ventilation and Conventional Intermittent Mandatory Ventilation Following Initial Exogenous Surfactant Therapy

We set out to evaluate the impact of volume‐targeted synchronized ventilation and conventional intermittent mandatory ventilation (IMV) on the early physiologic response to surfactant replacement therapy in neonates with respiratory distress syndrome (RDS). We hypothesized that volume‐targeted, patient‐triggered synchronized ventilation would stabilize minute ventilation at a lower respiratory rate than that seen during volume‐targeted IMV, and that synchronization would improve oxygenation and decrease variation in measured tidal volume (Vt). This was a prospective, randomized study of 30 hospitalized neonates with RDS. Infants were randomly assigned to volume‐targeted ventilation using IMV (n = 10), synchronized IMV (SIMV; n = 10), or assist/control ventilation (A/C; n = 10) after meeting eligibility requirements and before initial surfactant treatment. Following measurements of arterial blood gases and cardiovascular and respiratory parameters, infants received surfactant. Infants were studied for 6 hr following surfactant treatment.

High-frequency oscillation versus conventional ventilation following surfactant administration and partial liquid ventilation

Surfactant followed by partial liquid ventilation (PLV) with perfluorocarbon (PFC; LiquiVent®) improves oxygenation, lung compliance, and lung pathology in lung‐injured animals receiving conventional ventilation (CV). In this study, we hypothesize that high‐frequency oscillation (HFO) and CV will provide equivalent oxygenation in lung‐injured animals following surfactant repletion and PLV, once lung volume is optimized. After saline‐lavage lung injury during CV, newborn piglets were randomized to either HFO (n = 10) or CV (n = 9). HFO animals were stabilized over 15 min without optimization of lung volume; CV animals continued treatment with time‐cycled, pressure‐limited, volume‐targeted ventilation. All animals then received 100 mg/kg of surfactant (Survanta®). Thirty minutes later, all received intratracheal PFC to approximate functional residual capacity. Thirty minutes after PLV began, mean airway pressure (MAP) in both groups was increased to improve oxygenation. MAP was directly adjusted during HFO; PEEP and PIP were adjusted during IMV, maintaining a pressure sufficient to deliver 15 mL/kg tidal volume. Animals were treated for 4 h.

Perfluorocarbon priming and surfactant: physiologic and pathologic effects.

OBJECTIVE To test the hypothesis that perfluorocarbon (PFC) priming before surfactant administration improves gas exchange and lung compliance, and also decreases lung injury, more than surfactant alone. DESIGN Prospective, randomized animal study. SETTING Animal research laboratory of Childrens Hospital of St. Paul. SUBJECTS Thirty-two newborn piglets, weighing 1.55 +/- 0.18 kg. INTERVENTIONS We studied four groups of eight animals randomized after anesthesia, paralysis, tracheostomy, and establishment of lung injury using saline washout to receive one of the following treatments: a) surfactant alone (n = 8); b) priming with the PFC perflubron alone (n = 8); c) priming with perflubron followed by surfactant (n = 8); and d) no treatment (control; n = 8). Perflubron priming was achieved by instilling perflubron via the endotracheal tube in an amount estimated to represent the functional residual capacity, ventilating the animal for 30 mins, and then removing perflubron by suctioning. After all treatments were given, animals were mechanically ventilated for 4 hrs. MEASUREMENTS AND MAIN RESULTS We evaluated oxygenation, airway pressures, respiratory system compliance, and hemodynamics at baseline, after induction of lung injury, and at 30-min intervals for 4 hrs. Histopathologic evaluation was carried out using a semiquantitative scoring system and by computer-assisted morphometric analysis. After all treatments, animals had decreased oxygenation indices (p < .001) and increased respiratory system compliance (p < .05). Animals in PFC groups had similar physiologic responses to treatments as animals treated with surfactant only; both the PFC-treated groups and the surfactant-treated animals required lower mean airway pressures throughout the experiment (p < .001) and had higher pH levels at 90 and 120 mins (p < .05) compared with the control group. Pathologic analysis demonstrated decreased lung injury in surfactant-treated animals compared with animals treated with PFC or the controls (p < .02). CONCLUSIONS Priming the lung with PFC neither improved the physiologic effects of exogenous surfactant nor improved lung pathology in this animal model.

Dynamics of spontaneous breathing during patient-triggered partial liquid ventilation

This study evaluates different ventilator strategies during gas (GV) and partial liquid ventilation (PLV) in spontaneously breathing animals. We hypothesized that during PLV, spontaneously breathing animals would self‐regulate respiratory parameters by increasing respiratory rate (RR) and minute ventilation (V′E) when compared to animals mechanically ventilated with gas, and further that full synchronization of each animals effort to the ventilator cycle would decrease RR at stable tidal volumes (VT). We studied 12 newborn piglets (1.54 ± 0.24 kg) undergoing GV and PLV in 3 different modes: intermittent mandatory ventilation (IMV), synchronized IMV (SIMV), and assist control ventilation (AC). Modes occurred sequentially in random order during GV first, with the same order then repeated during PLV. Animals initially received continuous positive airway pressure (CPAP) and returned to CPAP during PLV at the end of the experiment. Pressure‐limited, volume‐targeted ventilation was used with a tidal volume goal of 13 cc/kg. Rate was set at 10/min during IMV and SIMV, with a back‐up rate of 10/min during AC. RR, V′E, mechanical (VT) and spontaneous tidal volumes (sVT) were measured breath‐to‐breath using a computer‐assisted lung mechanics analyzer; mean values were determined over 30‐min periods. Data analysis used paired t‐tests with Bonferroni correction as needed (P < 0.05).

Lower respiratory rates without decreases in oxygen consumption during neonatal synchronized intermittent mandatory ventilation

Objective: We tested the hypothesis that synchronization to patient effort during intermittent mandatory ventilation (SIMV), when compared to conventional unsynchronized intermittent mandatory ventilation (IMV), will decrease energy

Surfactant and partial liquid ventilation via conventional and high-frequency techniques in an animal model of respiratory distress syndrome.

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.

PARTIAL LIQUID VENTILATION VS GAS VENTILATION: HISTOLOGIC DIFFERENCES USING HIGH FREQUENCY AND CONVENTIONAL TECHNIQUES. † 2083

PARTIAL LIQUID VENTILATION VS GAS VENTILATION: HISTOLOGIC DIFFERENCES USING HIGH FREQUENCY AND CONVENTIONAL TECHNIQUES. † 2083

Volume Targeted Patient Triggered Ventilation: Decreased Subject Effort and Improved Efficiency in an Animal Model of Respiratory Distress Syndrome|[dagger]| 1611

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