Partial liquid ventilation combined with kinetic therapy in acute respiratory failure in piglets

OBJECTIVE: To investigate the effect of the combination of kinetic therapy (KT) with partial liquid ventilation (PLV) on gas exchange, lung mechanics and hemodynamics in acute lung injury (ALI). DESIGN: Prospective, randomized, controlled pilot study. SETTING: University research laboratory. SUBJECTS: Eleven piglets weighing 8.3+/-0.9 kg. INTERVENTION: ALI was induced by the infusion of oleic acid (0.08 ml/kg) and repeated lung lavages with 0.9% NaCl (20 ml kg(-1)). Thereafter the animals were randomly assigned either for PLV or a combination of PLV with KT (PLV/KT). The dose of perfluorocarbon administered was 30 ml/kg, evaporative losses were substituted with 5 ml/kg per h. MEASUREMENTS AND MAIN RESULTS: Airway pressures, tidal volumes, dynamic compliance (Cdyn), expiratory airway resistance and arterial blood gases were measured. Hemodynamic monitoring included right atrial, mean pulmonary artery, pulmonary capillary wedge and mean systemic arterial pressures, and continuous flow recording of the pulmonary artery. In both groups the induction of ALI significantly reduced PaO2/FIO2 Cdyn and cardiac output, and significantly increased pulmonary artery pressure. After the initiation of PLV there was a significant increase of PaO2/FIO2, and Cdyn, and a significant decrease of pulmonary artery pressure in both groups. Except the PaCO2, which showed significantly lower values in the PLV/KT group, no variables showed any differences between the two groups. CONCLUSION: The additional use of KT did not show beneficial effects on oxygenation and lung mechanics during PLV. However, at constant minute ventilation PaCO2 levels were significantly lower during PLV/KT, indicating some positive influence on the ventilation/perfusion distribution within the lung. Extreme body positions during PLV/KT did not show any significant hemodynamic side effects.     

Inhaled endothelin A antagonist improves arterial oxygenation in experimental acute lung injury

OBJECTIVES: To study the effects of an inhaled endothelin A (ET(A)) receptor antagonist on hemodynamics and pulmonary gas exchange in experimental acute lung injury (ALI). DESIGN AND SETTING: Prospective, randomized, and controlled study in a university laboratory. PARTICIPANTS AND INTERVENTIONS: Sixteen pigs were ventilated in a volume controlled mode during general anesthesia. ALI was induced by surfactant depletion using repetitive lung lavages until the PaO2/FIO2 ratio was below 100 mmHg. The animals were then randomly assigned to receive either a nebulized ET(A) receptor antagonist (LU-135252, 3 mg/kg, inhaled over 1 h; LU group) or nebulization of saline (5-10 ml inhaled over 1 h) with no further intervention (controls). MEASUREMENTS AND RESULTS: Parameters of hemodynamics and gas exchange were measured for 6 h after induction of ALI. In the LU group intrapulmonary right-left shunting (QS/QT) decreased from 58 +/- 8% at the onset of ALI to 27 +/- 12% 3 h and 24 +/- 9% 6 h after ALI (p < 0.05); PaO2 increased from 55 +/- 12 to 257 +/- 148 mmHg 3 h and 270 +/- 136 mmHg 6 h after ALI. (p < 0.05), whereas in controls QS/QT and PaO2 did not improve over the 6 h after onset of ALI. In the LU group mean pulmonary artery pressure was stable for 6 h after ALI (26-29 mmHg), while in controls it increased from 28 +/- 2 to 41 +/- 2 mmHg (p < 0.05). Inhaled LU-135252 reduced cardiac output by 31 +/- 11% (p < 0.05) and increased systemic vascular resistance by 60 +/- 29 % (p < 0.05), while these parameters remained stable in controls. CONCLUSION: In this porcine model of ALI the inhalation of an ET(A) receptor antagonist improved arterial oxygenation and maintained a stable pulmonary artery pressure without inducing systemic vasodilatation.     

"Ideal PEEP" is superior to high dose partial liquid ventilation with low PEEP in experimental acute lung injury

OBJECTIVE: To determine the effects of a high dose partial liquid ventilation (PLV) approximating the amount of the functional residual capacity (FRC) with low levels of positive end-expiratory pressure (PEEP) compared to a lung-protective strategy with volume-controlled mechanical ventilation (vcMV) with a PEEP level above the lower inflection point (LIP) on pulmonary gas exchange, haemodynamics, respiratory mechanics and lung injury in an experimental model of acute lung injury (ALI). DESIGN: Prospective, randomised, controlled study. METHODS: Twenty-four anaesthetised, tracheotomised and mechanically ventilated (FIO(2) 1.0) pigs underwent induction of ALI by repeated saline wash-out of surfactant. Animals were randomly assigned to receive either PLV ( PLV, n=8) with 30 ml/kg of perfluorocarbons (PF 5080, 3 M, Germany) and a PEEP level of 5 cmH(2)O, to receive vcMV with a PEEP level of 1 cmH(2)O above the LIP ( (ideal) PEEP, n=8), or to receive vcMV with a PEEP level of 5 cmH(2)O ( Controls, n=8). MEASUREMENTS AND RESULTS: Measurements of pulmonary gas exchange, respiratory mechanics and haemodynamics were performed hourly for a 6 h period. In the (ideal) PEEP group, intra-pulmonary shunt (Qs/Qt) decreased from 55+/-5% after induction of ALI to 10+/-3% ( p<0.05 versus Controls and versus PLV) and PaO(2) increased from 52+/-4 to 566+/-19 mmHg after 6 h of treatment ( p<0.05 versus Controls and versus PLV). In the PLV group, Qs/Qt decreased from 50+/-5% after induction of ALI to 24+/-3% ( p<0.05 versus Controls) and PaO(2) increased from 59+/-5 to 306+/-35 mmHg after 6 h of treatment ( p<0.05 versus Controls). In the PLV group and in Controls, mean pulmonary artery pressure (MPAP) was significantly increased from 27+/-2 to 38+/-2 mmHg and from 29+/-1 to 40+/-1 mmHg, respectively, 6 h after induction of ALI ( p<0.05 versus (ideal) PEEP), while in the (ideal) PEEP group, MPAP was maintained between 26+/-1 and 31+/-2 mmHg for 6 h after ALI. Cardiac output (CO) decreased significantly in the (ideal) PEEP group compared to Controls ( p<0.05), while CO did not change in the PLV group and in Controls. The compliance of the respiratory system (C(RS)) increased in the (ideal) PEEP group after induction of ALI from 11+/-2 to 22+/-5 ml/mbar ( p<0.05 versus Controls and versus PLV) and in the PLV group from 10+/-2 to 13+/-3 ml/mbar after 6 h of treatment ( p<0.05 versus Controls). On histological examination, the highest total injury scores were found in animals of the PLV group ( p<0.05 versus Controls and versus (ideal) PEEP), while the lowest total lung injury score was found in the dependent lung regions of the (ideal) PEEP group ( p<0.05 versus Controls). CONCLUSION: In this porcine model of ALI, vcMV with a PEEP level of 1 cmH(2)O above the LIP was superior to high dose PLV with a PEEP of 5 cmH(2)O in improving gas exchange and lung mechanics. In terms of lung damage, the treatment in the (ideal) PEEP group resulted in the lowest total lung injury scores.     

Effect of inhaled nitric oxide in combination with almitrine on ventilation-perfusion distributions in experimental lung injury

Objective: To investigate a possible additive effect of combined nitric oxide (NO) and almitrine bismesylate (ALM) on pulmonary ventilation-perfusion (V˙._A/Q˙) ratio.¶Design: Prospective, controlled animal study.¶Setting: Animal research facility of a university hospital.¶Interventions: Three conditions were studied in ten female pigs with experimental acute lung injury (ALI) induced by repeated lung lavage: 1) 10 ppm NO, 2) 10 ppm NO with 1 μg/kg per min ALM, 3) 1 μg/kg per min ALM. For each condition, gas exchange, hemodynamics and V˙._A/Q˙ distributions were analyzed using the multiple inert gas elimination technique (MIGET).¶Measurement and results: With NO + ALM, arterial oxygen partial pressure (PaO₂) increased from 63 ± 18 mmHg to 202 ± 97 mmHg while intrapulmonary shunt decreased from 50 ± 15 % to 26 ± 12 % and blood flow to regions with a normal V˙._A/Q˙ ratio increased from 49 ± 16 % to 72 ± 15 %. These changes were significant when compared to untreated ALI (p < 0.05) and NO or ALM alone (p < 0.05), although improvements due to NO or ALM also reached statistical significance compared to ALI values (p < 0.05).¶Conclusions: We conclude that NO + ALM results in an additive improvement of pulmonary gas exchange in an experimental model of ALI by diverting additional blood flow from non-ventilated lung regions towards those with normal V˙._A/Q˙ relationships.     

Acute myocardial infarction with normal coronary arteries during septic shock from Neisseria meningitidis

Objective: To investigate a possible additive effect of combined nitric oxide (NO) and almitrine bismesylate (ALM) on pulmonary ventilation-perfusion (?^·V_A/?^·Q) ratio.¶Design: Prospective, controlled animal study.¶Setting: Animal research facility of a university hospital.¶Interventions: Three conditions were studied in ten female pigs with experimental acute lung injury (ALI) induced by repeated lung lavage: 1) 10 ppm NO, 2) 10 ppm NO with 1 μg/kg per min ALM, 3) 1 μg/kg per min ALM. For each condition, gas exchange, hemodynamics and?^·V_A/?^·Qdistributions were analyzed using the multiple inert gas elimination technique (MIGET).¶Measurement and results: With NO + ALM, arterial oxygen partial pressure (PaO₂) increased from 63 ± 18 mmHg to 202 ± 97 mmHg while intrapulmonary shunt decreased from 50 ± 15 % to 26 ± 12 % and blood flow to regions with a normal?^·V_A/?^·Qratio increased from 49 ± 16 % to 72 ± 15 %. These changes were significant when compared to untreated ALI (p < 0.05) and NO or ALM alone (p < 0.05), although improvements due to NO or ALM also reached statistical significance compared to ALI values (p < 0.05).¶Conclusions: We conclude that NO + ALM results in an additive improvement of pulmonary gas exchange in an experimental model of ALI by diverting additional blood flow from non-ventilated lung regions towards those with normal?^·V_A/?^·Qrelationships.     

Effects of prolonged partial liquid ventilation, high frequency ventilation and conventional ventilation on gas exchange and lung pathology in newborn surfactant-depleted piglets

Partial liquid ventilation (PLV) improves oxygenation in various animal models of respiratory insufficiency. The aim of this study was to compare the effects of conventional ventilation (CV), high frequency oscillatory ventilation (HFOV), and PLV combined with CV or HFOV on gas exchange and histopathology. Thirty anaesthetised newborn piglets (mean weight 1.94 kg, age 1-3 days) were randomized in five groups of six animals: CV, CV + surfactant (S), HFOV+S, PLV/CV, and PLV/HFOV. Thirty min after lung injury had been induced with repeated saline lavage, specific ventilatory treatment was initiated. Three animals of the CV group died within the 24 h study period, whereas none died in any of the other groups. The oxygenation index (OI) and the PaO2/FIO2 ratio improved significantly within 30 min in all groups, but not in the CV group. After 24 h all oxygenation parameters were better in the PLV groups than in CV or CV+S (P < 0.05). No differences in gas exchange were noted between HFOV+S and PLV/CV. The combination of PLV with HFOV led to an increased PaO2/FIO2 ratio when compared with PLV/CV and with HFOV+S (P < 0.05). All PLV treated animals had significantly less lung injury in the upper and lower lobes compared with gas-ventilated animals by histologic semi-quantitative lung injury score (P < 0.01) and in the lower lobes by morphometry (P < 0.001). In conclusion, HFOV+S and PLV either with CV or HFOV are effective techniques to provide adequate gas exchange in S-deficient lungs compared with CV with and without S. However, lung injury was significantly improved in both PLV treated groups compared with HFOV+S and the CV groups.     

Pulmonary administration of prostacyclin (PGI2) during partial liquid ventilation in an oleic acid-induced lung injury: inhalation of aerosol or intratracheal instillation?

OBJECTIVE: The purpose of this study was to investigate the effects of aerosolized prostacyclin (A-PGI2) and intratracheally instilled prostacyclin (I-PGI2) during partial liquid ventilation (PLV) on gas exchange and pulmonary circulation in rabbits with acute respiratory distress. DESIGN: Prospective control study. SETTING: A research laboratory at a university medical centre. SUBJECTS: Sixty-nine Japanese white rabbits. INTERVENTION: Lung injury was induced by oleic acid and the animals were divided into five groups of ten each: a mechanical gas ventilation (GV) group, an A-PGI2 group, a PLV group, an A-PGI2+PLV group and an I-PGI2+PLV group. PLV, A-PGI2+PLV and I-PGI2+PLV groups received 15 ml/ kg perflubron intratracheally while receiving mechanical GV. A-PGI2 and A-PGI2+PLV groups received aerosolized PGI2 (50 ng/kg/min) in combination with GV or PLV, respectively. The I-PGI2+PLV group was instilled 50 ng/kg/min PGI2 intratracheally in combination with PLV. RESULT: After lung injury, all animals developed hypoxia, hypercarbia and pulmonary hypertension. The improvement of partial pressure of arterial oxygen (PaO2) in the A-PGI2 and PLV groups was transient, whereas the A-PGI2+PLV and I-PGI2+PLV groups showed consistent improvement throughout the experiment. The PaO2 values of the I-PGI2+PLV group were significantly higher than those of the other groups 120 min after treatment. The mean pulmonary artery pressure (PAP) significantly decreased after treatment in the A-PGI2, APGI2+PLV and I-PGI2+PLV groups. CONCLUSIONS: The results suggest that both aerosolized and intratracheally instilled PGI2 improve oxygenation and reduce PAP during PLV in oleic acid lung injury.     

The effect of positive end-expiratory pressure during partial liquid ventilation in acute lung injury in piglets.

OBJECTIVES: To investigate the effects of positive end-expiratory pressure (PEEP) application during partial liquid ventilation (PLV) on gas exchange, lung mechanics, and hemodynamics in acute lung injury. DESIGN: Prospective, randomized, experimental study. SETTING: University research laboratory. SUBJECTS: Six piglets weighing 7 to 12 kg. INTERVENTIONS: After induction of anesthesia, tracheostomy, and controlled mechanical ventilation, animals were instrumented with two central venous catheters, a pulmonary artery catheter and two arterial catheters, and an ultrasonic flow probe around the pulmonary artery. Acute lung injury was induced by the infusion of oleic acid (0.08 mL/kg) and repeated lung lavage procedures with 0.9% sodium chloride (20 mL/kg). The protocol consisted of four different PEEP levels (0, 5, 10, and 15 cm H2O) randomly applied during PLV. The oxygenated and warmed perfluorocarbon liquid (30 mL/kg) was instilled into the trachea over 5 mins without changing the ventilator settings. MEASUREMENTS AND MAIN RESULTS: Airway pressures, tidal volumes, dynamic and static pulmonary compliance, mean and expiratory airway resistances, and arterial blood gases were measured. In addition, dynamic pressure/volume loops were recorded. Hemodynamic monitoring included right atrial, mean pulmonary artery, pulmonary capillary wedge, and mean systemic arterial pressures and continuous flow recording at the pulmonary artery. The infusion of oleic acid combined with two to five lung lavage procedures induced a significant reduction in PaO2/FI(O2) from 485 +/- 28 torr (64 +/- 3.6 kPa) to 68 +/- 3.2 torr (9.0 +/- 0.4 kPa) (p < .01) and in static pulmonary compliance from 1.3 +/- 0.06 to 0.67 +/- 0.04 mL/cm H2O/kg (p < .01). During PLV, PaO2/FI(O2) increased significantly from 68 +/- 3.2 torr (8.9 +/- 0.4 kPa) to >200 torr (>26 kPa) (p < .01). The highest PaO2 values were observed during PLV with PEEP of 15 cm H2O. Deadspace ventilation was lower during PLV when PEEP levels of 10 to 15 cm H2O were applied. There were no differences in hemodynamic data during PLV with PEEP levels up to 10 cm H2O. However, PEEP levels of 15 cm H2O resulted in a significant decrease in cardiac output. Dynamic pressure/volume loops showed early inspiratory pressure spikes during PLV with PEEP levels of 0 and 5 cm H2O. CONCLUSIONS: Partial liquid ventilation is a useful technique to improve oxygenation in severe acute lung injury. The application of PEEP during PLV further improves oxygenation and lung mechanics. PEEP levels of 10 cm H2O seem to be optimal to improve oxygenation and lung mechanics.     

Inhaled nitric oxide in acute respiratory distress syndrome with and without septic shock requiring norepinephrine administration: a dose–response study

BACKGROUND: The aim of this prospective study was to assess whether the presence of septic shock could influence the dose response to inhaled nitric oxide (NO) in NO-responding patients with adult respiratory distress syndrome (ARDS). RESULTS: Eight patients with ARDS and without septic shock (PaO2 = 95 +/- 16 mmHg, PEEP = 0, FiO2 = 1.0), and eight patients with ARDS and septic shock (PaO2 = 88 +/- 11 mmHg, PEEP = 0, FiO2 = 1.0) receiving exclusively norepinephrine were studied. All responded to 15 ppm inhaled NO with an increase in PaO2 of at least 40 mmHg, at FiO2 1.0 and PEEP 10 cmH2O. Inspiratory intratracheal NO concentrations were recorded continuously using a fast response time chemiluminescence apparatus. Seven inspiratory NO concentrations were randomly administered: 0.15, 0.45, 1.5, 4.5, 15, 45 and 150 ppm. In both groups, NO induced a dose-dependent decrease in mean pulmonary artery pressure (MPAP), pulmonary vascular resistance index (PVRI), and venous admixture (QVA/QT), and a dose-dependent increase in PaO2/FiO2 (P 相似文献   

Selective tracheal gas insufflation during partial liquid ventilation improves lung function in an animal model of unilateral acute lung injury.

OBJECTIVE: During unilateral lung injury, we hypothesized that we can improve global lung function by applying selective tracheal gas insufflation (TGI) and partial liquid ventilation (PLV) to the injured lung. DESIGN: Prospective, interventional animal study. SETTING: Animal laboratory in a university hospital. SUBJECTS: Adult mixed-breed dogs. INTERVENTIONS: In six anesthetized dogs, left saline lung lavage was performed until PaO(2)/FiO(2) fell below 100 torr (13.3 kPa). The dogs were then reintubated with a Univent single-lumen endotracheal tube, which incorporates an internal catheter to provide TGI. In a consecutive manner, we studied 1) the application of 10 cm H(2)O of positive end-expiratory pressure (PEEP); 2) instillation of 10 mL/kg of perflubron (Liquivent) to the left lung at a PEEP level of 10 cm H(2)O (PLV+PEEP 10 initial); 3) application of selective TGI (PLV+TGI) while maintaining end-expiratory lung volume (EELV) constant; 4) PLV+TGI at reduced tidal volume (VT); and 5) PLV+PEEP 10 final. MEASUREMENTS AND MAIN RESULTS: Application of PLV+PEEP 10 initial did not change gas exchange, lung mechanics, or hemodynamics. PLV+TGI improved PaO(2)/FiO(2) from 189 +/- 13 torr (25.2 +/- 1.7 kPa) to 383 +/- 44 torr (51.1 +/- 5.9 kPa) (p <.01) and decreased PaCO(2) from 55 +/- 5 torr (7.3 +/- 0.7 kPa) to 30 +/- 2 torr (4.0 +/- 0.3 kPa) (p <.01). During ventilation with PLV+TGI, reducing VT from 15 mL/kg to 3.5 mL/kg while keeping EELV constant decreased PaO(2)/FiO(2) to 288 +/- 49 torr (38.4 +/- 6.5 kPa) (not significant) and normalized PaCO(2). At this stage, end-inspiratory plateau pressure decreased from 19.2 +/- 0.7 cm H(2)O to 13.6 +/- 0.7 cm H(2)O (p <.01). At PLV+PEEP 10 final, measurements returned to those observed at previous baseline stage (PLV+PEEP 10 initial). CONCLUSIONS: During unilateral lung injury, PLV with a moderate PEEP did not improve oxygenation, TGI superimposed on PLV improved gas exchange, and combination of TGI and PLV allowed a 77% reduction in VT without any adverse effect on PaCO(2).     

High-frequency oscillatory ventilation and partial liquid ventilation after acute lung injury in premature lambs with respiratory distress syndrome

OBJECTIVE: Conventional mechanical ventilatory support (CV) contributes to lung injury in premature lambs with respiratory distress syndrome, a disease that is characterized by progressive deterioration of gas exchange and increased lung inflammation. Lung recruitment strategies, such as high-frequency oscillatory ventilation (HFOV) and partial liquid ventilation (PLV), improve gas exchange and attenuate lung inflammation when instituted immediately after birth. However, whether these recruitment strategies are effective as rescue treatment after established lung injury is unknown. To determine the separate and combined effects of HFOV and PLV when initiated after the establishment of acute lung injury in severe respiratory distress syndrome, we studied the effects of these strategies on gas exchange and histologic signs of acute lung injury in premature lambs. DESIGN: Animals were intubated, treated with surfactant and ventilated with 1.00 FIO2 for 4 hrs. After 2 hrs, animals were either continued on CV (controls) or treated with one of three strategies: HFOV; CV + PLV; or HFOV + PLV. The response to low-dose inhaled nitric oxide (5 ppm) was measured in each group at the end of the study. SETTING: An animal laboratory affiliated with University of Colorado School of Medicine. SUBJECTS: A total of 20 premature lambs at 115-118 days of gestation (term = 147 days). MEASUREMENTS AND MAIN RESULTS: In comparison with control animals, each of the rescue therapies improved PaO2 after 1 hr of treatment. The HFOV and HFOV + PLV groups had higher PaO2 than CV + PLV or CV alone (p < .05). Mean airway pressure (Paw) was lower in the PLV groups during CV or HFOV compared with their controls (p < .05). Inhaled NO improved PaO2 in all groups; however, the increase in PaO2 was greatest in the HFOV + PLV group (p < .05). Histologic examination and myeloperoxidase assay were not different between groups. CONCLUSION: We conclude that each lung recruitment strategy improved oxygenation in premature lambs with established lung injury.     

Right ventricular response to high-dose almitrine infusion in patients with severe hypoxemia related to acute respiratory distress syndrome

OBJECTIVE: To evaluate the effects of high-dose almitrine infusion on gas exchange and right ventricular function in patients with severe hypoxemia related to acute respiratory distress syndrome (ARDS). DESIGN: Prospective study. SETTING: Medicosurgical intensive care department (ten beds). PATIENTS: Nine patients with ARDS and severe hypoxemia (PaO2/FIO2 ratio, <150 torr [20 kPa]). INTERVENTION: High-dose almitrine infusion (16 microg/kg/min for 30 mins). MEASUREMENTS AND MAIN RESULTS: Gas exchange and hemodynamic parameters were recorded before and after almitrine infusion. Right ventricular function was evaluated by using a fast response thermistor pulmonary artery catheter that allowed measurement of right ventricular ejection fraction and calculation of right ventricular end-diastolic and end-systolic volumes. Almitrine did not significantly alter arterial oxygenation and intrapulmonary shunt. Almitrine increased mean pulmonary arterial pressure (MPAP) from 31 +/- 4 to 33 +/- 4 mm Hg (p < .05), pulmonary vascular resistance index from 353 +/- 63 to 397 +/- 100 dyne x sec/ cm5 x m2 (p < .05), and right ventricular end-systolic volume index from 71 +/- 22 to 77 +/- 21 mL/m2 (p < .05); almitrine decreased right ventricular ejection fraction from 36% +/- 7% to 34% +/- 8% (p < .05). Stroke volume index and cardiac index did not change. The almitrine-induced changes in right ventricular ejection fraction were closely correlated with the baseline MPAP (r2 = .71, p < .01). CONCLUSION: In patients with severe hypoxemia related to ARDS, high-dose almitrine infusion did not improve arterial oxygenation and impaired the loading conditions of the right ventricle. The decrease in right ventricular ejection fraction induced by almitrine was correlated with the baseline MPAP. Thus, high-dose almitrine infusion may be harmful in ARDS patients with severe hypoxemia and pulmonary hypertension.     

Partial liquid ventilation shows dose-dependent increase in oxygenation with PEEP and decreases lung injury associated with mechanical ventilation

PURPOSE: The purpose of this article is to evaluate the effect of positive end-expiratory pressure (PEEP) during partial liquid ventilation (PLV) and to investigate if lung damage associated with mechanical ventilation can be reduced by PLV. MATERIALS AND METHODS: Twenty-two New-Zealand white rabbits were ventilated in pressure-controlled mode maintaining constant tidal volume (10 mL/kg). Lung injury was induced by repeated saline lavage (PaO2 < 100 mm Hg).Two incremental PEEP steps maneuvers (IPSMs) from 2 to 10 cm H2O in 2 cm H2O steps were performed sequentially. The control group received the first IPSM in the supine position and were turned prone for the second IPSM. In the PLV group (n = 7), 12 mL/kg of perfluorodecalin was instilled after lung injury before the two IPSMs. The early prone group (n = 7) received both IPSMs in the prone position. Parameters of gas exchange, lung mechanics, and hemodynamics as well as pathology were examined. RESULTS: During the first IPSM, the PLV group showed a significant increase in PaO2 after instillation of perfluorodecalin (P < .05) and then showed a dose-dependent increase in PaO2 with PEER. The control and EP groups showed improvement in PaO2 only at higher PEEP, eventually showing no intergroup differences at PEEP of 10 cm H2O. During the second IPSM only the PLV group retained its ability to increase PaO2 to the level obtained during the first IPSM (P < .05 compared with control and EP groups). During the first IPSM all three groups showed increasing trend in static compliance (Cst) with PEEP peaking at PEEP of 8 cm H2O. During the second IPSM, only the PLV group showed increase in static compliance with PEEP (P < .05 compared with other groups). Lung histology revealed significantly less hyaline membrane formation in the PLV group (P < .05). CONCLUSION: PLV shows dose-dependent increase in oxygenation with PEEP and may reduce lung damage associated with mechanical ventilation.     

Effects of single and multiple doses of perfluorocarbon in comparison with continuous partial liquid ventilation on gas exchange and lung pathology in newborn surfactant-depleted pigs

OBJECTIVE: To compare the efficacy of single, multiple, and continuous application of perfluorocarbon (PFC) FC-77 on gas exchange and lung pathology in a prolonged 24-hr study. DESIGN: Controlled animal trial. SETTING: Research laboratory in a university setting. SUBJECTS: Twenty-one newborn piglets (mean weight 1.94 kg). INTERVENTIONS: After intubation and instrumentation, the anesthetized animals were randomized in three groups: a) animals receiving one 1-hr session of partial liquid ventilation (PLV) followed by 23 hrs of conventional ventilation (CV), designated as the single PLV (S-PLV) group; b) animals receiving multiple 1-hr sessions of PLV with intermittent CV, designated as the multiple PLV (M-PLV) group; and c) animals receiving continuous PLV over 24 hrs, designated as the continuous PLV (C-PLV) group. After lung injury was induced with repeated saline lavage, specific ventilatory treatment was initiated. The oxygenation index, Pao2/Fio2 ratio, and ventilatory efficacy index were determined before and after lung injury and during the 24-hr course. After 24 hrs, the lungs were removed for histopathologic examination. MEASUREMENTS AND MAIN RESULTS: Gas exchange variables improved within 60 mins in all groups after the initiation of the specific ventilatory treatment (p < .01). The best outcome was observed in the C-PLV group, which provided a continuously stable gas exchange over the 24-hr period. S-PLV initially improved gas exchange, but after 6 hrs all variables were impaired when compared with C-PLV (p < .01). M-PLV transiently improved gas exchange variables after each PFC application; however, M-PLV was associated with a significant deterioration of all pulmonary variables during the 24-hr course. The lungs of the animals in the M-PLV group demonstrated an increased lung injury score (p < .01) and increased morphometric values (p < .05) when compared with C-PLV. CONCLUSIONS: In surfactant deficient lungs, single and multiple applications of PFC only transiently improved oxygenation. Multiple PFC fillings with intermittent gas ventilation led to a deterioration of gas exchange during the 24-hr study and severe lung damage. Continuous PLV provides the best gas exchange and the most favorable histopathologic outcome.     

Segmental hemodynamics during partial liquid ventilation in isolated rat lungs

Partial liquid ventilation (PLV) is a means of ventilatory support in which gas ventilation is carried out in a lung partially filled with a perfluorocarbon liquid capable of supporting gas exchange. Recently, this technique has been proposed as an adjunctive therapy for cardiac arrest, during which PLV with cold perfluorocarbons might rapidly cool the intrathoracic contents and promote cerebral protective hypothermia while not interfering with gas exchange. A concern during such therapy will be the effect of PLV on pulmonary hemodynamics during very low blood flow conditions. In the current study, segmental (i.e. precapillary, capillary, and postcapillary) hemodynamics were studied in the rat lung using a standard isolated lung perfusion system at a flow rate of 6 ml/min ( approximately 5% normal cardiac output). Lungs received either gas ventilation or 5 or 10 ml/kg PLV. Segmental pressures and vascular resistances were determined, as was transcapillary fluid flux. The relationship between individual hemodynamic parameters and PLV dose was examined using linear regression, with n=5 in each study group. PLV at both the 5 and 10 ml/kg dose produced no detectable changes in pulmonary blood flow or in transcapillary fluid flux (all R(2) values<0.20). CONCLUSION: In an isolated perfused lung model of low flow conditions, normal segmental hemodynamic behavior was preserved during liquid ventilation. These data support further investigation of this technique as an adjunct to cardiopulmonary resuscitation.     

Additive effect on gas exchange of inhaled nitric oxide and intravenous almitrine bismesylate in the adult respiratory distress syndrome

Objective To assess the additive effect of inhaled nitric oxide (NO) and intravenous almitrine bismesylate (ALM) on gas exchange.Design Prospective self-controlled study.Setting 3 medico-surgical intensive care units.Patients 17 patients with severe hypoxemia (PaO₂/FIO₂ ratio: 88±30mmHg, venous admixture: 47±7%) and elevated mean pulmonary artery pressure (MPAP: 30±5mmHg) due to adult respiratory distress syndrome (ARDS).Interventions 5 conditions were studied: 1) baseline, 2) 5 to 10ppm of NO during 30min, 3) discontinuation of NO during 30min, 4) ALM infusion (0.5mg/kg) during 30min, 5) ALM infusion (0.5mg/kg) during 30min in combination with 5 to 10ppm of NO.Measurement and results The PaO₂/FIO₂ ratio rose from 88±30 to 98±37mmHg (NS) with NO alone, and from 92±25 to 130±56mmHg (p<0.01) with NO+ALM (p<0.05 vs NO alone). Seven patients were considered as NO-responders (rise in PaO₂/FIO₂ ratio of 10mmHg or more with NO); in this subgroup the PaO₂/FIO₂ ratio rose from 87±30 to 128±39mmHg (p<0.05) with NO alone, and from 93±20 to 169±51mmHg (p<0.01) with NO+ALM (p<0.05 versus NO alone). MPAP decreased from 30±5 to 26±5mmHg (p<0.01) with NO alone, increased slightly from 28±5 to 31±5mmHg (NS) with ALM alone and decreased to 27±5mmHg (p<0.05) with NO+ALM.Conclusions NO+ALM had additive effects on gas exchange while decreasing MPAP in patients with ARDS. The effects of NO alone were small and non significant, except in a subgroup of 7 patients in whom the combination of both therapies had the more pronounced results.     

Effects of milrinone on pulmonary vasculature in normal dogs and in dogs with pulmonary hypertension

OBJECTIVE: To study the effects of milrinone on pulmonary vasculature. BACKGROUND: It has been suggested that bipyridines or their derivatives may have a selective pulmonary vasodilation effect. METHODS: Preliminary study: milrinone administration to 12 normal dogs (low dose [bolus 75 micrograms/kg for 5 min followed by a continuous infusion at 0.75 micrograms/kg.min, n = 6]; high dose [bolus 150 micrograms/kg for 5 min followed by continuous infusion at 1.5 micrograms/kg.min, n = 6]). Main study: milrinone administration to 18 dogs with pulmonary hypertension due to pulmonary embolism induced by a massive injection of autologous muscle cubes. The pulmonary hypertension dogs were divided into three groups: a) group E (n = 6) received embolization only, as control; b) group L (n = 6) received low-dose milrinone; and c) group H (n = 6) received high-dose milrinone, equivalent to the preliminary study group. Hemodynamic measurements and blood samplings were obtained at baseline and at 15, 30, and 60 min after start of milrinone infusion. RESULTS: Milrinone did not change mean pulmonary artery pressure (MPAP) in normal dogs. Milrinone decreased MPAP significantly in dogs with pulmonary hypertension. Pulmonary vascular resistance index remained at an almost constant level in normal dogs, but decreased significantly in dogs with pulmonary hypertension. Mean arterial pressure was maintained at a constant level in all groups. High-dose milrinone administration decreased systemic vascular resistance index (SVRI) significantly; low-dose milrinone administration decreased SVRI slightly. CONCLUSIONS: Milrinone may have a selective pulmonary vasodilatory effect only in dogs with pulmonary hypertension. The mechanism that produced a selectivity on pulmonary vasculature in dogs with pulmonary hypertension is unknown. However, an inhibition of platelet aggregation may decrease the MPAP resulting from an increase in cAMP caused by milrinone. Further studies are needed to resolve the pulmonary vasodilatory effect of milrinone in dogs with pulmonary hypertension.     

Effect of high-dose prednisolone on lung fluid in patients with non-cardiogenic lung edema

The influence of high-dose prednisolone on extravascular lung water (EVLW) was studied in a randomized trial in patients with noncardiac pulmonary edema. The patients were treated every 6 hours for 48 hours with 2 g of prednisolone-hemisuccinate or placebo. In the prednisolone-group (n = 7) EVLW decreased from 16.4 +/- 6.2 before to 11.8 +/- 5.1 ml/kg after treatment (p less than 0.05). Additionally alveolar-arterial oxygen gradient (AaDO2/FiO2), pulmonary vascular resistance and heart rate decreased, while arterial oxygen tension (PaO2/FiO2) and mean arterial pressure increased (p less than 0.05). In the placebo-group (n = 7) EVLW increased slightly from 17.5 +/- 3.1 before to 19.3 +/- 10.3 ml/kg after treatment. Additionally all other parameters did not change significantly in this group. Although no statistical significant difference was found between the two groups of treatment, a decrease in EVLW was observed in all prednisolone-treated patients, whereas a pronounced increase in EVLW was found in 3 placebo-treated patients. Probably, those patients would have benefited from high-dose prednisolone treatment. High-dose prednisolone reduced EVLW and improved hemodynamics and gas exchange in patients with noncardiac pulmonary edema, whereas placebo did not achieve comparable effects. Therefore, high-dose prednisolone appears beneficial in noncardiac pulmonary edema in respect of EVLW, hemodynamics, and gas exchange.     

Combining partial liquid ventilation with nitric oxide to improve gas exchange in acute lung injury

Objective: To assess the effects of increasing concentrations of inhaled nitric oxide (NO) during incremental dosages of partial liquid ventilation (PLV) on gas exchange, hemodynamics, and oxygen transport in pigs with induced acute lung injury (ALI). Design: Prospective experimental study. Setting: Experimental intensive care unit of a university. Subjects: 6 pigs with induced ALI. Interventions: Animals were surfactant-depleted by lung lavage to a partial pressure of oxygen in arterial blood (PaO₂) < 100 mmHg. They then received four incremental doses of 5 ml/kg perflubron (LiquiVent). Between each dose the animals received 0, 10, 20, 30, 40, and 0 parts per million (ppm) NO. Measurements and main results: Blood gases, hemodynamic parameters, and oxygen delivery were measured after each dose of perflubron as well as after each NO concentration. Perflubron resulted in a dose-dependent increase in PaO₂. At each perflubron dose, additional NO inhalation resulted in a further significant (ANOVA, p < 0.05) increase in PaO₂, with a maximum effect at 30 ± 10 ppm NO. The 5 ml/kg perflubron dose led to a significant decrease in mean pulmonary artery pressure, which decreased further with higher NO concentrations. Conclusions: PLV can be combined with NO administration and results in a cumulative effect on arterial oxygenation and to a decrease in pulmonary artery pressure, without having any deleterious effect on measured systemic hemodynamic parameters. Received: 29 April 1996 Accepted: 24 October 1996     

Partial liquid ventilation with surfactant: effects on gas exchange and lung pathology in surfactant-depleted piglets

Objective: To evaluate the effects of 24 h partial liquid ventilation (PLV) with and without surfactant (S) treatment on gas exchange and lung injury in a newborn animal model of S deficiency.¶Design: A prospective, controlled, in vivo animal laboratory study.¶Setting: Research laboratory in a university setting.¶Subjects: Twenty-four pathogen-free, male piglets (mean weight 1.9 kg, age 1–3 days).¶Interventions: The animals were randomised in four groups: PLV with FC-77 combined with conventional ventilation (PLV/CV) versus S + PLV/CV and PLV combined with high frequency oscillatory ventilation (PLV/HFOV) versus S + PLV/HFOV. The piglets were anaesthetised, intubated and instrumented with vascular catheters. Thirty minutes after lung injury had been induced with repeated saline lavage, S animals received natural S. Thirty minutes after surfactant substitution PLV with FC-77 was started. The oxygenation index (OI), PaO₂/FIO₂ ratio, PaCO₂ and the ventilatory efficacy index were determined before and during PLV. After 24 h the lungs were removed for histopathological examination.¶Measurements and main results: Within 60 min after the initiation of PLV, all animals demonstrated improvements of the OI and PaO₂/FIO₂ ratio compared to the values after lung injury. However, at 18 and 24 h of PLV, the OI and PaO₂/FIO₂ ratio were significantly worse in the S + PLV/CV and S + PLV/HFOV groups compared to the groups without S. PaCO₂ was higher at 18 and 24 h when S was used in PLV/HFOV (p < 0.05). A semi-quantitative lung injury score revealed most severe lung damage in the S + PLV/HFOV group.¶Conclusion: The combination of S and PLV with FC-77 led to an impaired gas exchange and did not further protect the animal from lung injury.