Neutrophil accumulation is reduced during partial liquid ventilation

OBJECTIVE: This study evaluates the ability of perflubron to inhibit pulmonary neutrophil accumulation during partial liquid ventilation (PLV) in the setting of acute lung injury. DESIGN: Randomized, controlled, nonblinded study. SETTING: Research laboratory at a university. SUBJECTS: Male, Sprague-Dawley rats (n = 120, 506 +/- 42 g). INTERVENTIONS: Animals were divided into eight groups (n = 15 in each group, of which n = 12 for myeloperoxidase content and n = 3 for histologic neutrophil counting): a) GV-CVF group, animals received gas ventilation (GV) with the induction of lung injury using cobra venom factor (CVF); b) PLV-CVF group, animals received partial liquid ventilation before the induction of lung injury; c) PEEP-CVF group, animals received positive end-expiratory pressure (PEEP) before the administration of cobra venom factor; d) CVF-PLV group, animals received partial liquid ventilation after cobra venom factor; e) CVF-PEEP group, animals received PEEP after cobra venom factor; f) PLV only group, animals received partial liquid ventilation only; g) GV only group, animals received gas ventilation only; and h) NVSBA group, nonventilated spontaneous breathing animals. MEASUREMENTS AND MAIN RESULTS: After the experimental period, total lung myeloperoxidase content was significantly decreased in the PLV-CVF (0.29 +/- 0.08, p = .02) and PEEP-CVF (0.34 +/- 0.04, p = .01) groups when compared with the GV-CVF group (0.62 +/- 0.07). When compared with the GV-CVF group, a trend toward a reduction in myeloperoxidase was observed in the CVF-PLV (0.42 +/- 0.05, p = .07) and the CVF-PEEP (0.39 +/- 0.06, p = .07) groups. When compared with the cobra venom factor only group (GV-CVF 47 +/- 2 neutrophils/high-power field), reductions in neutrophil count were observed in all groups (neutrophils/high-power field): PLV-CVF (20 +/- 2, p = .009); PEEP-CVF (24 +/- 1, p = .01); CVF-PLV (30 +/- 2, p = .03); and CVF-PEEP (37 +/- 1, p = .04). CONCLUSION: These data suggest that both partial liquid ventilation and PEEP result in a reduction in neutrophil accumulation in the setting of acute lung injury.     

Continuous low-flow tracheal gas insufflation during partial liquid ventilation in rabbits

BACKGROUND: Both partial liquid ventilation (PLV) and tracheal gas insufflation are novel techniques for mechanical ventilation. In this study we examined whether PLV superimposed by continuous low-flow tracheal gas insufflation (TGI) offers any advantage to the blood gases and lung mechanics in normal-lung rabbits compared to the use of PLV only. METHODS: Eighteen anesthetized, paralyzed and mechanically ventilated rabbits were used. After obtaining a baseline PaCO2 value between 29 and 39 mmHg (3.9 and 5.2 kPa), the animals were assigned to three equal groups according to the ventilation they received--A group: PLV superimposed by TGI; B group: PLV only; and C group: continuous mandatory ventilation (CMV) superimposed by TGI. Serial arterial blood gases, pH and lung mechanics were measured. RESULTS: The animals in each group were hemodynamically stable. In the case of the A group, PaO2 continuously increased, and PaCO2 stabilized around 40.8 +/- 5.5 mmHg (5.4 +/- 0.7 kPa, mean +/- SD, NS). In the B group, the tendency for PaO2 to increase was not as definite; PaCO2 continuously increased from 35.2 +/- 2.3 mmHg (4.7 +/- 0.3 kPa) to 56.3 +/- 12.7 mmHg (7.5 +/- 1.7 kPa, P < 0.05) at the end of the experiment. In the C group, PaO2 and PaCO2 were stable during the observation period. The superimposition of TGI on PLV did not decrease the airway pressures compared to PLV alone. CONCLUSION: In summary, continuous low-flow TGI superimposed on PLV can decrease and stabilize the PaCO2 elevation caused by the initiation of PLV.     

Pulmonary function in patients with trophoblastic disease treated with low-dose methotrexate

The Sheffield Trophoblastic Disease Centre treats about 25 patients with persistent trophoblastic disease each year. A total of 75% of patients are classified as low risk according to the Charing Cross Hospital prognostic scoring system and receive methotrexate (MTX) 50 mg, i.m., on days 1, 3, 5, 7 with folinic acid 7.5 mg orally 24 h after each methotrexate injection. There is a 7-day rest between treatment cycles. Remission is achieved in 85% of cases. Approximately 20% of patients experienced pleuritic chest pain and dyspnoea. We have evaluated prospectively lung function in 16 low-risk patients receiving methotrexate. All patients had pulmonary function tests [spirometry-forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), and transfer factor - TLCO, kCO] performed before and after completed treatment. A mean of 7.5 cycles of MTX were administered (range 4-11). There was a significant reduction in the mean TLCO (mean pre/post 8.15/7.38 mmol min-1 kPa-1, P = 0.01), but there were no other statistically significant changes. Three patients experienced respiratory symptoms and were found to have a 39%, 28%, and 11% reduction in TLCO from baseline, improving on follow up to pretreatment levels. Low-dose MTX is an effective therapy but may cause troublesome pulmonary toxicity.     

High-frequency partial liquid ventilation in respiratory distress syndrome: hemodynamics and gas exchange

Partial liquid ventilation using conventional ventilatory schemes improves lung function in animal models of respiratory failure. We examined the feasibility of high-frequency partial liquid ventilation in the preterm lamb with respiratory distress syndrome and evaluated its effect on pulmonary and systemic hemodynamics. Seventeen lambs were studied in three groups: high-frequency gas ventilation (Gas group), high-frequency partial liquid ventilation (Liquid group), and high-frequency partial liquid ventilation with hypoxia-hypercarbia (Liquid-Hypoxia group). High-frequency partial liquid ventilation increased oxygenation compared with high-frequency gas ventilation over 5 h (arterial oxygen tension 253 +/- 21.3 vs. 17 +/- 1.8 Torr; P < 0.001). Pulmonary vascular resistance decreased 78% (P < 0.001), pulmonary blood flow increased fivefold (P < 0.001), and aortic pressure was maintained (P < 0.01) in the Liquid group, in contrast to progressive hypoxemia, hypercarbia, and shock in the Gas group. Central venous pressure did not change. The Liquid-Hypoxia group was similar to the Gas group. We conclude that high-frequency partial liquid ventilation improves gas exchange and stabilizes pulmonary and systemic hemodynamics compared with high-frequency gas ventilation. The stabilization appears to be due in large part to improvement in gas exchange.     

Pulmonary abscess treated with postural drainage

Case record of patients with lung abscess treated by postural drainage is presented in this paper. In young man with multiple explosive injuries lung abscess was formed two months after injury. A postural drainage with parenteral application of antibiotics has been performed. The expectoration was painful. At the seventh day there was no temperature, ESR was described at the tenth day. The general status was becoming better. At the seventeenth day patient was discharged from Hospital. Rig imaging was shown nearly completely resolution of lung abscess. Postural drainage was effective because of favorable localisation of abscess near the large bronchus and basely part of the lung.     

Severe measles-associated pneumonia treated with assisted ventilation

Measles-associated pneumonia, which was severe enough to require mechanical ventilation, caused a mortality of 64%. The main indications for special respiratory care were severe infection and hypoxaemia. Complications of the disease occurred in 78% of the patients. The commonest were anaemia, enteritis and cardiac failure, and they contributed to the grave prognosis. Viral pneumonia was present in most of the patients who died; superinfection was rare. The characteristics of measles virus was present in 30% and of adenovirus in no less that 40%.     

Transesophageal echocardiography in patients treated with ventilation at a polyvalent intensive care unit

Transthoracic echocardiography (TTE) has a definite role in general ICUs where its indications are now generally accepted. Transesophageal echocardiography (TEE) has widened the diagnostic scope of ultrasonic and doppler technology, partly by resolving the physical limitations of TTE. In this article the authors comment on their series of TTEs and TEEs, pointing out advantages, the diagnostic and therapeutic implications, especially in artificially ventilated patients. They conclude by emphasising the need to establish TEE as a routine diagnostic tool in general ICUs.     

Surfactant replacement increases compliance in premature lamb lungs during partial liquid ventilation in situ

Treatments available to improve compliance in surfactant-deficient states include exogenous surfactant (ES) and either partial (PLV) or total liquid ventilation (TLV) with perfluorochemical (PFC). Because of the additional air-lung and air-PFC interfaces introduced during PLV compared with TLV, we hypothesized that compliance would be worse during PLV than during TLV. Because surfactant is able to reduce interfacial tension between air and lung as well as between PFC and lung, we further hypothesized that compliance would improve with surfactant treatment before PLV. In excised preterm lamb lungs, we used Survanta for surfactant replacement and perflubron as the PFC. Compliance during PLV was intermediate between TLV and gas inflation, both with and without surfactant. Surfactant improved compliance during PLV, compared with PLV alone. Because of the force-balance equation governing the behavior of immiscible droplets on liquid surfaces, we predict that PFC droplets spread during PLV to cover the alveolar surface in surfactant-deficient lungs during most of lung inflation and deflation but that the PFC would retract into droplets in surfactant-sufficient lungs, except at end inspiration.     

Renal fibromuscular dysplasia treated with partial nephrectomy

We report a previously undescribed ultrastructural calcification of glomerular immune complex depositions in a patient with lupus nephritis. Such processes give rise to a distinctive ultrastructural calcified microspheriol in electron-dense immune deposits, and were associated with hypercalcemia and nephrocalcinosis. The cause of hypercalcemia in this patient was uncertain, but related to a granulomatous inflammation and abscess of the breast. Whereas ultrastructural microcalcification was associated with hypercalcemia, its distribution in the segmental glomerular lesions suggests that an inflammatory process was contributory. The clinical follow-up indicates that the microcalcifications of immune complexes have not affected the outcome of nephritis and renal function.     

Partial liquid ventilation]

Partial liquid ventilation (PLV) is a relatively new therapeutic approach to acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). The idea of combining the intrapulmonary application of an oxygen-carrying substance and positive pressure ventilation was introduced by Fuhrman in 1991 and originally called perfluorocarbon-associated gas exchange (PAGE). Nowadays, the technique is mostly known as partial liquid ventilation (PLV). The efficacy of PVL treatment has been demonstrated in numerous animal studies in different models of lung injury. The results of those studies led to multicenter phase I-II studies in patients of all age groups in the United States and Canada. Recently, the first randomized, controlled study in 90 adult patients suffering from ALI and ARDS was completed and first results have been published. Comparison of overall mortality and number of ventilator-free days (VFD's) in a 28-day period showed no differences between PLV and conventionally treated patients. A post-hoc stratification by age (< 55 years) demonstrated a tendency to lower mortality (PLV 25.6%; CMV 36.8%) and a significant increase of VFD (PLV 8.95 days; CMV 4.11 days; p = 0.03) in PLV when compared to conventionally treated patients. Perfluorocarbons (PFCs) are chemically stable and inert. They are mostly eliminated via exhalation (> 99%). The unique physicochemical properties of PFCs permit access to atelectatic, non-ventilated lung areas, enhance gas exchange and decrease inflammation. The dense PFCs prevent the endexpiratory collapse of alveoli and reestablish functional residual capacity (FRC). Comparable to positive endexpiratory pressure (PEEP), these effects have been described as "liquid or fluid PEEP". These properties offer a new approach to the underlying pathophysiology of ALI and ARDS. In addition, the combination with other therapeutic approaches to ALI and ARDS like high-frequency oscillations (HFO), inhaled nitric oxide (NO) therapy, and surfactant replacement can be considered and is already the subject of recent publications. However, combination therapy is still experimental and further investigation is necessary to evaluate efficacy and potential risks. Many questions still exist which need to be answered by experimental as well as human pilot studies. Based on these studies, the results of ongoing human trials can be assessed properly and new multicenter trials can be planned effectively.     

Distribution of pulmonary blood flow and total lung water during partial liquid ventilation in acute lung injury

BACKGROUND: Gas exchange is improved during partial liquid ventilation (PLV) with perfluorocarbon in animal models of acute lung injury. The mechanisms are not fully defined. We hypothesize that redistribution of pulmonary blood flow (PBF) along with redistribution of, and decrease in, total lung water (TLW) during PLV may improve oxygenation. METHODS: We characterized PBF and TLW in anesthetized adult dogs by using positron emission tomography with H2(15)O. Measurements of gas exchange, PBF, and TLW were made before and after acute lung injury was induced with intravenous oleic acid. The same measurements were made during PLV (with 30 ml/kg perfluorocarbon) and compared with gas ventilated (GV) controls. RESULTS: Oxygenation was significantly improved during PLV. PBF redistributed from the dependent zone of the lung to the nondependent zones, thus potentially improving ventilation/perfusion relationships. However, a similar pattern of PBF redistribution was observed during GV such that there was no significant difference between groups. TLW redistributed in a similar pattern during PLV. By quantitative measurements, PLV ameliorated the continued accumulation of TLW compared with GV animals. CONCLUSIONS: We conclude that PBF and TLW redistribution and attenuation of increases in TLW may contribute to the improvement in gas exchange during PLV in the setting of acute lung injury.     

Chemical paralysis reduces energy expenditure in patients with burns and severe respiratory failure treated with mechanical ventilation

Predictive formulas often overestimate energy requirements, particularly in patients being treated with mechanical ventilation, resulting in significant overfeeding. The purpose of this study was to quantify the effect of chemical paralysis on energy expenditure in patients with burn injuries receiving ventilation treatment, and compare measured energy expenditure with estimates of energy expenditure based on predictive formulas. The study was a retrospective review of 14 patients with burn injuries treated with mechanical ventilation that required chemical paralysis to reduce inspiratory pressures or improve oxygenation. Indirect calorimetry was performed before, during, and after paralysis. Measured energy expenditure (MEE) was compared with the energy predictions of the Harris-Benedict (HBEE) and Curreri (CEE) estimates. During paralysis, mean MEE was significantly lower than pre- or postparalysis (19.65 +/- 1.65 versus 26.00 +/- 2.42 and 29.49 +/- 2.83 kcal/kg/24 hr, respectively). Mean HBEE (2031 +/- 145 kcal/24 hr) approximated MEE pre-(1989 +/- 350 kcal/24 hr) and postparalysis (2237 +/- 269 kcal/24 hr), but overestimated MEE during paralysis (1532 +/- 208 kcal/24 hr; p < 0.05). Mean CEE (2957 +/- 229 kcal/ 24 hr) estimates significantly overestimated MEE before, during, and after paralysis (1989 +/- 350, 1532 +/- 208, and 2237 +/- 269, respectively p < 0.05). Predictive formulas significantly overestimate measured energy requirements in these patients. Indirect calorimetry should guide nutrition support in patients requiring prolonged mechanical ventilation.     

Effects of partial liquid ventilation with perfluorocarbons on pressure-flow relationships, vascular compliance, and filtration coefficients of isolated blood-perfused rabbit lungs

OBJECTIVES: The density of perfluorocarbons is almost twice that of blood. Therefore, we hypothesized that partial liquid ventilation with these fluids markedly affects pulmonary hemodynamics and filtration coefficients. To test these hypotheses we studied pressure-flow relationships, vascular compliances, capillary pressures, and filtration coefficients in normal and perfluorocarbon-ventilated rabbit lungs. DESIGN: Controlled animal study with an ex-vivo isolated lung preparation. SETTING: Research laboratory for experimental anesthesiology at the Heinrich-Heine-University of Düsseldorf. SUBJECTS: Fourteen New Zealand White rabbits. INTERVENTIONS: The lungs were perfused under zone 3 flow conditions with autologous blood at various flow rates (50 to 250 mL/min, closed circuit, roller pump, 37 degrees C) and ventilated with 5% CO2 in air (positive end-expiratory pressure: 2 cm H2O, tidal volume: 10 mL/kg, respiratory rate: 30 breaths/min) without (control group, n=7) and with (n=7) perfluorocarbon administered intratracheally (15 mL/kg). MEASUREMENTS AND MAIN RESULTS: Pulmonary arterial, left atrial, and airway pressures, as well as blood reservoir volume (reflecting changes in pulmonary blood volume) and lung weight, were measured continuously. Inconsistent with our hypothesis, we found no significant differences between both groups in the slopes and intercepts of the pressure-flow relationships. There were no significant differences in capillary pressures determined by double occlusion (6.7+/-1.2 vs. 6.3+/-1.3 cm H2O for control group, p=.53), vascular compliances (0.51+/-0.10 vs. 0.47+/-0.09 mL/cm H2O for control group, p=.38), and filtration coefficients (0.33+/-0.06 vs. 0.37+/-0.07 mL/min/mm Hg/100 g wet weight for control group, p=.80, Mann-Whitney). CONCLUSIONS: Partial liquid ventilation with perfluorocarbons has no relevant effects on pulmonary filtration coefficients and global hemodynamic variables of isolated zone 3 lungs. These findings suggest that right ventricular afterload is not changed with partial liquid ventilation. It is likely, however, that intrapulmonary blood flow is redistributed toward less-dependent regions, although relevant global hemodynamic changes are absent during partial liquid ventilation.     

Partial liquid ventilation decreases the inflammatory response in the alveolar environment of trauma patients

BACKGROUND: Perflubron is a perfluorocarbon with unique physical characteristics. It has twice the density of water, allows free diffusion of O2 and CO2, is easily dispersed, and is insoluble. Thus, it can act as "liquid positive end-expiratory pressure" to recruit collapsed alveoli and improve oxygenation. Results of laboratory studies suggest that perflubron exerts an anti-inflammatory effect on alveolar cells. Limited clinical data in neonates and adults with severe acute respiratory distress syndrome are promising. We present a single institution's experience with partial liquid ventilation (PLV) in trauma patients compared with conventional mechanical ventilation (CMV) with particular attention to the alveolar inflammatory response. METHODS: Ventilated patients with bilateral lung injury and PaO2/FIO2 < 300 were eligible in this prospective multicenter trial. Perflubron was administered by means of the endotracheal tube to fill up to functional residual capacity (approximately 30 mL/kg), followed by supplemental doses up to 96 hours. At this institution, bronchoscopy with bronchoalveolar lavage was performed serially for white blood cell count, protein, interleukin (IL)-1, IL-6, IL-8, and IL-10, and analyzed as early (< 48 hours) and late (48-96 hours). Clinical response was defined as a sustained 10% increase in PaO2/FIO2 at 48 hours. RESULTS: 16 patients were enrolled: 12 PLV patients and 4 CMV patients. There were no differences between groups relative to sex, Injury Severity Score, or initial PaO2/FIO2. There were no major outcome differences between groups in this pilot study relative to pneumonia (50% PLV and 75% CMV), deaths (one death in each group caused by multiple organ failure), or for oxygenation after 5 days. Eight PLV patients were responders (PLV-R) compared with four patients who did not (PLV-NR). The main differences between these subgroups was time from injury to study (1.8 days for PLV-R vs. 5.8 for PLV-NR, p < 0.02) and age (30 years for PLV-R vs. 42 years for PLV-NR, p < 0.04). Both white blood cell count and protein were higher in CMV, suggesting a greater inflammatory response. Neutrophils were significantly higher in CMV, despite equal IL-8 levels in both PLV and CMV. The inflammatory cytokines IL-1 and IL-6 were greater in CMV, and the anti-inflammatory IL-10 was lower in PLV. CONCLUSION: Early institution of partial liquid ventilation is effective at reducing the alveolar inflammatory response. Perflubron exhibits an anti-inflammatory effect in the alveolar environment with reduction of proinflammatory IL-1 and IL-6 (possibly removing a stimulus for IL-10), white blood cell count, and protein capillary leak. PLV also reduces alveolar neutrophils independent of IL-8. Further characterization of this altered inflammatory response is necessary.     

Pulmonary thrombo-embolism in nephrotic syndrome treated with tissue plasminogen activator

We describe the case of a boy with steroid sensitive nephrotic syndrome and left pulmonary artery thrombo-embolism. clinical presentation initially suggested sepsis and respiratory signs were minor. Treatment with tissue plasminogen activator infused into the pulmonary artery was successful. CONCLUSION: Pulmonary thrombo-embolism should be considered in unwell children with nephrotic syndrome.