部分液体通气用于家猪肺灌洗诱导的急性肺损伤的疗效观察

目的 对肺灌洗诱导的急性肺损伤家猪实施以氟碳（PFC）为媒介的部分液体通气（PLV）,观察其对肺气体交换及血液动力学的影响。方法 16头体重为（25±3）kg的健康幼猪,麻醉后经气管导管注入生理盐水反复肺内灌洗,直致动脉氧分压（PaO2）<100 mm Hg达1h,记录肺气体交换及血液动力学各参数作为肺损伤基值。随机分为PLV组及对照组。对照组以呼吸机仅行常规机械通气,PLV组动物经气管导管肺内灌以30ml/kgPFC,然后以与对照组同样的呼吸参数行机械通气,每小时补充4ml/kg的PFC以弥补蒸发损失量。每小时记录各肺气体交换及血液动力学参数的变化。结果 实施PLV1h后,PaO2即从 ALI的（53.2±10.81）mm Hg升高至（14.07±133.42）mmHg,4h后高达（318.51±108.97）mm Hg,显著高于对照组。实施PLV1h后Qs/Qt从ALI的57.10％±8.88％降至42.3％±12.78％,4h后降至26.05％±10.56,并于2h后显著低于对照组。与对照组比较,PLV组血液动力学无显著性的改变。结论 以PFC为媒介的PLC可明显地改善急性肺损伤的肺气体交换,对血液动力学无明显影响。     

Partial liquid ventilation for acute allograft dysfunction after canine lung transplantation

BACKGROUND: This study was designed to investigate the efficacy of partial liquid ventilation (PLV) on acute allograft dysfunction after lung transplantation. METHODS: The canine left lung allotransplantation model was used, with the graft preserved in 4 degrees C low-potassium dextran glucose solution for 18 hours. The control group (n = 6) had conventional mechanical ventilation, and the PLV group (n = 6) had perfluorooctylbromide instilled into the airway 30 minutes after reperfusion. For 360 minutes, allograft function and hemodynamics were evaluated. After the evaluation, myeloperoxidase activity of the graft tissue was assayed. RESULTS: All dogs survived for 360 minutes. In the PLV group, PaO2, shunt fraction, and alveolar to arterial gradient for O2 were significantly better than those in the control group after 120, 180, and 120 minutes, respectively (p < 0.05). After 240 minutes, peak airway pressure became significantly lower than that in the control group (p < 0.05). The PaO2 at 360 minutes was 102 +/- 55 mm Hg in the control group and 420 +/- 78 mm Hg in the PLV group (p < 0.0001), and the peak airway pressure was 21.4 +/- 4.1 mm Hg in the control group and 14.7 +/- 5.0 mm Hg in the PLV group (p < 0.05). Myeloperoxidase activity in the PLV group was lower than that in the control group. CONCLUSIONS: The study shows that PLV alleviated acute allograft dysfunction after lung transplantation.     

Combining partial liquid ventilation and prone position in experimental acute lung injury.

BACKGROUND: Partial liquid ventilation (PLV) and prone position can improve arterial oxygen tension (PaO2) in acute lung injury (ALI). The authors evaluated additive effects of these techniques in a saline lung lavage model of ALI. METHODS: ALI was induced in 20 medium-sized pigs (29.2+/-2.5 kg body weight). Gas exchange and hemodynamic parameters were determined in both supine and prone position in all animals. Thereafter, one group was assigned to PLV with two sequential doses of 15 ml/kg of perfluorocarbon (n = 10); the second group was assigned to gaseous ventilation (n = 10). Gas-exchange and hemodynamic parameters were determined at corresponding time points in both groups in prone and supine position. RESULTS: In the PLV group, positioning the animals prone resulted in an increase of PaO2 prior to PLV and during PLV with both doses of perfluorocarbon when compared to ALI. PLV in supine position was only effective if 30 ml/kg of perfluorocarbon was applied. In the gaseous ventilation group, PaO2 increased reproducibly compared with ALI when the animals were turned prone. A significant additive improvement of arterial oxygenation was observed during combined therapy with 30 ml/kg of perfluorocarbon and prone position in the PLV group compared with either therapy alone. CONCLUSIONS: The authors conclude that combining PLV with prone position exerts additive effects on pulmonary gas exchange in a saline lung lavage model of ALI in medium-sized pigs.     

Real-time visualization of partial liquid ventilation in a model of acute lung injury

BACKGROUND: To clarify the effects of partial liquid ventilation, we visualized and morphologically analyzed real-time alveolar recruitment in a model of acute lung injury. METHODS: Male Wistar rats were divided into 3 groups: a group that underwent hydrochloric acid aspiration and mechanical gas ventilation (ALI group, n = 15), a group that underwent acid aspiration and partial liquid ventilation beginning 90 minutes after acid aspiration (PLV group, n = 15), and a group that underwent mechanical ventilation without acid aspiration (control group, n = 5). The number of ventilated alveoli and the diameter of the largest ventilated alveolus in each of 10 high-power fields observed on fluorescence micrographs with a tracer of labeled albumin were determined and averaged from 90 to 210 minutes after acid aspiration. RESULTS: The number of alveoli in the PLV group significantly increased in comparison to that in the ALI group. The diameter of the largest alveolus in the PLV group decreased from 103.7 +/- 16.3 microm to 76.3 +/- 6.5 microm until the end of the experiment. This diameter was equivalent to that in the control group. CONCLUSIONS: The excellent alveolar recruitment suggests that liquid ventilation ameliorates ventilator-associated lung injury.     

部分液体通气对急性肺损伤兔肺表面活性物质的影响

目的 研究部分液体通气(PLV)对油酸诱导的急性肺损伤肺表面活性物质的影响。方法 24只健康成年日本大白兔随机分成三组,每组8只:正常对照单纯机械通气组(C组);油酸肺损伤机械通气组(MV组)和油酸肺损伤部分液体通气组(PLV组)。中心静脉滴注油酸150μg/kg诱导急性肺损伤(ALI)模型,1h后当PaO_2/FiO_2<300时,认为造模成功,再连续通气4h,用多导生理监测仪连续记录血压和心率的变化,并测定基础、肺损伤及治疗后1、2、4h动脉血气。治疗4h立即处死动物,描记肺的压力-容积曲线,行右肺支气管灌洗,测量灌洗液中双饱和磷脂酰胆碱(DPPC)、肺表面活性物质相关蛋白A(SP-A)、总蛋白(TP)的浓度。结果 PLC组经PLV治疗后,PaO_2提高(P<0.01),各时段PaO_2高于MV组(P<0.01);PLV组PaCO_2逐渐降低,治疗后4h,PaCO_2与MV组差异有显著性(P<0.05)。PLV组灌洗液中DPPC、SP-A的含量高于MV组(P<0.01),而TP的含量低于MV组(P<0.01)。PLV组肺的顺应性较MV组提高。结论 PLV可增加油酸性急性肺损伤肺泡Ⅱ型上皮细胞分泌肺泡表面活性物质,改善肺功能。     

New aspects of ventilation in acute lung injury

Recent recognition that artificial ventilation may cause damage to the acutely injured lung has caused renewed interest in ventilation techniques that minimise this potential harm. Many ventilation techniques have proved beneficial in small trials of very specific patient groups, but most have subsequently failed to translate into improved patient outcome in larger trials. An exception to this is 'protective ventilation' using reduced tidal volumes (to lower airway pressure) and increased PEEP (to reduce pulmonary collapse). Results of trials of protective ventilation have been encouraging, and the technique should now be adopted more widely. High frequency ventilation, inverse ratio ventilation, prone positioning and inhaled nitric oxide are all techniques that may be considered when, in spite of optimal artificial ventilation, the patient's gas exchange remains dangerously poor. Under these circumstances, the choice of technique is dependent on their availability, local expertise and individual patient needs.     

部分液体通气对吸入性损伤犬的研究

目的 观察部分液体通气(PLV)对吸人性损伤犬呼吸力学、氧合和血流动力学参数的影响.方法 16条健康杂种犬经蒸气吸人造成重度吸入性损伤模型,随机分为对照组和实验组(n=8).实验组经气管导管缓慢注入氟碳液体(12ml/kg体重)行PLV治疗,治疗后30、60、90 min时测定两组犬血气、气道阻力、肺顺应性及血流动力学参数.结果 实验组Pa02呈进行性上升,在各时点与致伤后60 min比较差异有统计学意义(P＜0.05).与对照组比较,实验组各时点的PaO2稍有升高(P＞0.05).两组气道阻力、肺顺应性和血流动力学参数比较,差异均无统计学意义(P＞0.05).结论 PLV有利于吸入性损伤犬的动脉氧合,对血流动力学无明显不利影响.     

Factors predicting successful noninvasive ventilation in acute lung injury

PURPOSE: Noninvasive ventilation (NIV) has been successfully used to treat various forms of acute respiratory failure. It remains unclear whether NIV has potential as an effective therapeutic method in patients with acute lung injury (ALI). The aims of this study were to determine factors predicting the need for endotracheal intubation in ALI patients treated with NIV, and to promote the selection of patients suitable for NIV. METHODS: We conducted a retrospective study of all patients admitted to the intensive care unit (ICU) of the Nippon Medical School Hospital from 2000 to 2006 with a diagnosis of ALI, in whom NIV was initiated. RESULTS: A total of 47 patients with ALI received NIV, and 33 patients (70%) successfully avoided endotracheal intubation. Patients who required endotracheal intubation had a significantly higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and a significantly higher Simplified Acute Physiology Score (SAPS) II, and a significantly lower arterial pH. The respiratory rate decreased significantly within 1 h of starting NIV only in patients successfully treated with NIV. An APACHE II score of more than 17 (P = 0.022) and a respiratory rate of more than 25 breaths x min(-1) after 1 h of NIV (P = 0.024) were independent factors associated with the need for endotracheal intubation. Patients who avoided endotracheal intubation had a significantly lower ICU mortality rate and in-hospital mortality rate than patients who required endotracheal intubation. CONCLUSION: We determined an APACHE II score of more than 17 and a respiratory rate of more than 25 breaths x min(-1) after 1 h of NIV as factors predicting the need for endotracheal intubation in ALI patients treated with NIV.     

Changes in pulmonary blood flow during gaseous and partial liquid ventilation in experimental acute lung injury

BACKGROUND: It has been proposed that partial liquid ventilation (PLV) causes a compression of the pulmonary vasculature by the dense perfluorocarbons and a subsequent redistribution of pulmonary blood flow from dorsal to better-ventilated middle and ventral lung regions, thereby improving arterial oxygenation in situations of acute lung injury. METHODS: After induction of acute lung injury by repeated lung lavage with saline, 20 pigs were randomly assigned to partial liquid ventilation with two sequential doses of 15 ml/kg perfluorocarbon (PLV group, n = 10) or to continued gaseous ventilation (GV group, n = 10). Single-photon emission computed tomography was used to study regional pulmonary blood flow. Gas exchange, hemodynamics, and pulmonary blood flow were determined in both groups before and after the induction of acute lung injury and at corresponding time points 1 and 2 h after each instillation of perfluorocarbon in the PLV group. RESULTS: During partial liquid ventilation, there were no changes in pulmonary blood flow distribution when compared with values obtained after induction of acute lung injury in the PLV group or to the animals submitted to gaseous ventilation. Arterial oxygenation improved significantly in the PLV group after instillation of the second dose of perfluorocarbon. CONCLUSIONS: In the surfactant washout animal model of acute lung injury, redistribution of pulmonary blood flow does not seem to be a major factor for the observed increase of arterial oxygen tension during partial liquid ventilation.     

Prevention of ventilator-induced lung injury with partial liquid ventilation

BACKGROUND/PURPOSE: Pulmonary injury from mechanical ventilation has been attributed to application of excess alveolar pressure (barotrauma) or volume (volutrauma). The authors questioned whether partial liquid ventilation (gas ventilation of the perfluorocarbon filled lung, PLV) would reduce ventilator-induced lung injury. METHODS: A tracheostomy tube and carotid artery catheter were placed in anesthetized Sprague-Dawley rats (500 +/- 50 g). Bovine serum albumin (BSA) labeled with Iodine (I) 125 was administered intraarterially. Ventilation with tidal volume (TV) of 5 mL/kg was initiated. The rats were then selected randomly to a 30-minute experimental period of one of the following ventilation protocols: continued atraumatic gas ventilation (GV, TV, 5 mL/kg; n = 10); atraumatic gas ventilation combined with intratracheal administration of 10 mL/kg perfluorocarbon (GV-PLV, TV, 5 mL/kg, n = 10); barotrauma (BT, peak inspiratory pressure [PIP], 45 cm H(2)O; n = 10); barotrauma with PLV (BT-PLV, PIP, 45 cm H(2)O; n = 8); volutrauma (VT, TV, 30 mL/kg; n = 8); or volutrauma with PLV (VT-PLV, TV, 30 mL/kg; n = 10). Animals were killed and the amount of radiolabeled BSA in both lungs was measured and normalized to the counts in 1 mL of blood from that animal (injury index). Data were analyzed by analysis of variance (ANOVA) with post-hoc t test comparison between groups. RESULTS: There was a significant difference in the (125)I-BSA injury index when all groups were compared (P <.001 by ANOVA). Post-hoc analysis showed a significant decrease in the injury index when comparing BT versus BT-PLV (P =.024) and VT versus VT-PLV (P =.014). CONCLUSION: (125)I-BSA leak produced during high-pressure or high-volume mechanical ventilation is reduced by partial liquid ventilation.     

Effect of increasing perfluorocarbon dose on VA/Q distribution during partial liquid ventilation in acute lung injury

BACKGROUND: Although gas exchange during partial liquid ventilation (PLV) depends on perfluorocarbon liquid, the effect of perfluorocarbon dose on the ventilation-perfusion (VA/Q) distribution is not known. This study investigated how VA/Q distribution of an acutely injured lung is affected during PLV at increasing perfluorocarbon dose. METHODS: In eight rabbits (3.2 +/- 0.1 kg), acute lung injury (ALI) was created by repeated saline lavage (arterial oxygen partial pressure/fraction of inspired oxygen, 37 +/- 11 mm Hg). Three different doses of perfluorodecalin (9 ml/kg = low dose; 13.5 ml/kg = medium dose; 18 ml/kg = functional residual capacity [FRC] dose) were applied in random order during PLV. VA/Q distribution at different doses was evaluated by multiple inert gas elimination technique. RESULTS: Inert gas shunt (63 +/- 21% at ALI) decreased with increasing perfluorocarbon dose (43 +/- 21% at low dose, 29 +/- 10% at medium dose, 11 +/- 9% at FRC dose; P = 0.022). Compared with ALI (0%), the proportion of low VA/Q units was higher at all tested doses (19 +/- 10, 25 +/- 12, and 34 +/- 18%, respectively; all P < 0.05). Compared with ALI (27 +/- 14%), the proportion of normal VA/Q units was not increased at low or medium doses but was increased only at the FRC dose (45 +/- 13%; P = 0.027). CONCLUSIONS: With increasing perfluorocarbon dose during PLV, shunt was reduced from a small dose. The majority shunt units were converted to units showing low VA/Q ratios rather than normal VA/Q ratios. The presence of considerable amount of low VA/Q units across the varying doses of perfluorocarbon suggested that additional measures are necessary during PLV to augment its effect on gas exchange.     

Partial liquid ventilation with perfluorodecalin following unilateral canine lung allotransplantation in non-heart-beating donors.

BACKGROUND: The purpose of this study was to evaluate canine lungs obtained from non-heart-beating donors after unilateral lung transplantation subjected to partial liquid ventilation with perfluorodecalin. METHODS: Twelve donor dogs were killed and kept under mechanical ventilation for 3 hours. Heart-lung blocks were harvested after retrograde pulmonary hypothermic flush with Perfadex. Left lung grafts were randomly transplanted into 12 weight-matched recipient animals. Animals were divided into 2 groups: control (standard mechanical ventilation, n = 6) and PLV (partial liquid ventilation, n = 6). Forty-five minutes after transplantation, the animals in the PLV group received perfluorodecalin (15 ml/kg) via orotracheal tube. All animals received volume-controlled ventilation (FIO2) 1.0, PEEP 5 cm H(2)O) over 6 consecutive hours. Thereafter, blood-gas analysis, ventilatory mechanics and hemodynamics were registered at 30-minute intervals. After 6 hours of reperfusion the animals were killed and the transplanted lungs were extracted to obtain the wet/dry weight ratio. RESULTS: There were significant differences in pulmonary arterial pressure, which were higher in control group animals (p < 0.009). The control animals also showed higher arterial PaO(2) than those in the PLV group (p < 0.00001), but lower PaCO(2) (p < 0.008). The peak and plateau pressures were higher in the PLV group (p < 0.00001). Neither static compliance nor wet/dry weight ratios were different in between groups. CONCLUSIONS: PLV with perfluorodecalin yields functional results compatible with life in this model. Nonetheless, pulmonary gas exchange and mechanics were superior after reperfusion in animals given conventional mechanical ventilation up to 6 hours after left lung allotransplantation.     

Comparison of exogenous surfactant therapy, mechanical ventilation with high end-expiratory pressure and partial liquid ventilation in a model of acute lung injury

We have compared three treatment strategies, that aim to prevent repetitive alveolar collapse, for their effect on gas exchange, lung mechanics, lung injury, protein transfer into the alveoli and surfactant system, in a model of acute lung injury. In adult rats, the lungs were ventilated mechanically with 100% oxygen and a PEEP of 6 cm H2O, and acute lung injury was induced by repeated lung lavage to obtain a PaO2 value < 13 kPa. Animals were then allocated randomly (n = 12 in each group) to receive exogenous surfactant therapy, ventilation with high PEEP (18 cm H2O), partial liquid ventilation or ventilation with low PEEP (8 cm H2O) (ventilated controls). Blood-gas values were measured hourly. At the end of the 4-h study, in six animals per group, pressure-volume curves were constructed and bronchoalveolar lavage (BAL) was performed, whereas in the remaining animals lung injury was assessed. In the ventilated control group, arterial oxygenation did not improve and protein concentration of BAL and conversion of active to non-active surfactant components increased significantly. In the three treatment groups, PaO2 increased rapidly to > 50 kPa and remained stable over the next 4 h. The protein concentration of BAL fluid increased significantly only in the partial liquid ventilation group. Conversion of active to non-active surfactant components increased significantly in the partial liquid ventilation group and in the group ventilated with high PEEP. In the surfactant group and partial liquid ventilation groups, less lung injury was found compared with the ventilated control group and the group ventilated with high PEEP. We conclude that although all three strategies improved PaO2 to > 50 kPa, the impact on protein transfer into the alveoli, surfactant system and lung injury differed markedly.      

The use of prone ventilation in acute lung injury and acute respiratory distress syndrome

Prone positioning has been suggested since 1974 as a ventilatory strategy to improve oxygenation and pulmonary mechanics in patients with acute lung injury and acute respiratory distress syndrome. Although this mode of ventilation can improve gas exchange, the optimal role of the prone position is uncertain. The aim of this article is to examine the evidence in support of this mode of ventilation in adult patients with acute lung injury and acute respiratory distress syndrome. Limitations of the currently available evidence upon which the recommendations are made must be recognized. With these limitations in mind, however, the available evidence has been considered and conclusions presented. Considerable clinical experience confirms that prone ventilation can improve oxygenation in the majority of patients. It is difficult to predict which patients will respond. There are few contraindications and with experienced staff it can be achieved safely. Most patients should therefore be considered for a trial of prone positioning. Prolonged and repeated prone ventilation may be more effective. Whether the improvement in physiological parameters translates into improved clinical outcomes is less certain and well-designed randomized controlled trials will be required to address this issue.