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.     

Kinematic analysis of patients with spinal muscular atrophy during spontaneous breathing and mechanical ventilation

Dinoseb is a herbicide known to inhibit photosystem II electron transfer like DCMU, triazine and phenolic-type herbicides. The mutant Din7 of the cyanobacterium Synechocystis sp. PCC 6803, selected for resistance to dinoseb, and the mutant Ins2, constructed by the insertion of the kanamycin resistance cassette into the drgA gene, were cross-resistant to other nitrophenolic herbicides (DNOC, 2,4-dinitrophenol) and to the cell inhibitor metronidazole but not to the photosystem II inhibitors DCMU or ioxynil. The Din7 mutant had the same characteristics of photosystem II inhibition by dinoseb as the wild type. This result suggested the existence of another site for dinoseb inhibition. The wild type cells modified dinoseb to a non-toxic product that gave an absorption spectrum similar to that of dithionite treated dinoseb containing reduced nitro groups. In contrast, the Din7 mutant did not modify dinoseb. These phenomena were controlled by the drgA gene encoding a protein which showed similarity to several enzymes having nitroreductase activity. The addition of superoxide dismutase to the medium relieved the toxic effect of dinoseb in wild type cells but not in Din7. It is proposed that in wild type cells of Synechocystis sp. PCC 6803 the DrgA protein is involved in detoxification of dinoseb via the reduction of the nitro group(s) and this process is accompanied by the formation of toxic superoxide anions. Mutations blocking the activity of the DrgA protein lead to the development of resistance to nitrophenolic herbicides and metronidazole.     

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.     

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.     

Pulmonary pathology of patients treated with partial liquid ventilation

Adsorption and size exclusion in starch and cross-linked dextran were phenomena discovered in Uppsala in the 1950s [Porath (1979), Biochem. Soc. Trans. 7, 1197; Porath (1981), Current Content 19, 21; Porath (1981), J. Chromatogr. 218, 241; Janson (1987), Chromatographia 23, 361; Laurent (1993), J. Chromatogr. 633, 1]. These discoveries were the background to the development of a variety of affinity chromatographic methods. At present attempts are being made to combine size exclusion chromatography (SEC) with adsorption into a single operation that we call adsorptive SEC (AdSEC).     

The effect of sedation on oxygen uptake during spontaneous breathing

Sedation may be used in intensive care and emergency medicine to improve the oxygen demand/delivery ratio. The influence of sedation has most frequently been investigated in a dose-related manner. The aim of the present study was to determine the effect-related influence of different sedatives on oxygen uptake (VO2) in relation to defined resting conditions. METHODS. Forty ASA I patients who had to undergo a minor surgical procedure were investigated 1.5 h before surgery at basal energy-expenditure measurement conditions. One of the following substances was given with a preset bolus rate in a double-blind, randomised order until a defined level of sleep or side effects was encountered: propofol (n = 8), midazolam (n = 8), thiopentone (n = 8), sodium chloride (n = 8), and fentanyl (n = 8). The sleep level was defined as sluggish response to a loud voice or tapping on the forearm. The variables VO2, carbon dioxide elimination (VCO2), end tidal CO2 (p(et)CO2), oxygen saturation (SaO2), heart rate, systemic blood pressure, skin temperature, and skin resistance on the sole of the foot were documented on-line on a computer. All variables were compared using differences of averages from 10-min periods before and after sedation during which the VO2 was minimal. RESULTS. The mean VO2 before sedation was 264 +/- 60 ml/min, and the measured energy expenditure did differ by -0.2% (+/- 14%) from mean predicted values using the Harris-Benedict equation. The VO2 was reduced by 15 +/- 2% with propofol, by 12 +/- 8% with midazolam, and by 10 +/- 5% with thiopentone. This was statistically significant compared to placebo treatment, as was the difference between propofol and thiopentone effects. All patients in these groups reached the defined sleep level, which was not achieved by the placebo and fentanyl groups. Placebo treatment changed the VO2 by 0.1% (+/- 2%). Fentanyl increased the VO2 by 5% (+/- 8%), which did not reach significance. In the fentanyl group the bolus application had to be stopped at a p(et)CO2 of 50 mm Hg in all patients. In the propofol, midazolam, and thiopentone groups the phasic changes of skin resistance were reduced to zero and the skin temperature increased from 27 +/- 2 degrees C to 32 +/- 2 degrees C. The fentanyl group showed an increase in changes of skin resistance without changes in temperature. CONCLUSIONS. Sleep induced by propofol, midazolam, or thiopentone to a clinically maximal desirable level in spontaneously breathing patients reduced VO2 by 10% to 15%. This level of sedation did not induce a relevant change in P(et)CO2 or SaO2. The effect of propofol appeared to be the most pronounced and least variable. This may be attributable to a more pronounced reduction in single-organ VO2 or to an undetected difference in level of sedation. Fentanyl did, in contrast to most publications on opioid effects, seem to increase VO2. Underlying mechanisms may be sought in an increased rate-pressure product and sympathetic activity on the basis of hypercapnia and changes in muscle tension.     

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.     

A simple breathing circuit minimizing changes in alveolar ventilation during hyperpnoea

Many clinical and research situations require maintenance of isocapnia, which occurs when alveolar ventilation (V'A) is matched to CO2 production. A simple, passive circuit that minimizes changes in V'A during hyperpnoea was devised. It is comprised of a manifold, with two gas inlets, attached to the intake port of a nonrebreathing circuit or ventilator. The first inlet receives a flow of fresh gas (CO2=0%) equal to the subject's minute ventilation (V'E). During hyperpnoea, the balance of V'E is drawn (inlet 2) from a reservoir containing gas, the carbon dioxide tension (PCO2) approximates that of mixed venous blood and therefore contributes minimally to V'A. Nine normal subjects breathed through the circuit for 4 min at 15-31 times resting levels. End-tidal PCO2 (Pet,CO2) at rest, 0, 1.5 and 3.0 min were (mean+/-SE) 5.1+/-0.1 kPa (38.1+/-1.1 mmHg), 4.9+/-0.1 kPa (36.4+/-1.1 mmHg), 5.0+/-0.2 kPa (37.8+/-1.6 mmHg) and 5.0+/-0.2 kPa (37.6+/-1.4 mmHg) (p=0.53, analysis of variance (ANOVA)), respectively; without the circuit, Pet,CO2 would be expected to have decreased by at least 2.7 kPa (20 mmHg). Six anaesthetized, intubated dogs were first ventilated at control levels and then hyperventilated by stepwise increases in either respiratory frequency (fR) from 10 to 24 min(-1) or tidal volume (VT) from 400 to 1,200 mL. Increases in fR did not significantly affect arterial CO2 tension (Pa,CO2) (p=0.28, ANOVA). Only the highest VT decreased Pa,CO2 from control (-0.5 +/- 0.3 kPa (-3.4 +/- 2.3 mmHg), p<0.05). In conclusion, this circuit effectively minimizes changes in alveolar ventilation and therefore arterial carbon dioxide tension during hyperpnoea.     

Susceptibility to periodic breathing with assisted ventilation during sleep in normal subjects

Assisted ventilation with pressure support (PSV) or proportional assist (PAV) ventilation has the potential to produce periodic breathing (PB) during sleep. We hypothesized that PB will develop when PSV level exceeds the product of spontaneous tidal volume (VT) and elastance (VTsp . E) but that the actual level at which PB will develop [PSV(PB)] will be influenced by the DeltaPCO2 (difference between eupneic PCO2 and CO2 apneic threshold) and by DeltaRR [response of respiratory rate (RR) to PSV]. We also wished to determine the PAV level at which PB develops to assess inherent ventilatory stability in normal subjects. Twelve normal subjects underwent polysomnography while connected to a PSV/PAV ventilator prototype. Level of assist with either mode was increased in small steps (2-5 min each) until PB developed or the subject awakened. End-tidal PCO2, VT, RR, and airway pressure (Paw) were continuously monitored, and the pressure generated by respiratory muscle (Pmus) was calculated. The pressure amplification factor (PAF) at the highest PAV level was calculated from [(DeltaPaw + Pmus)/Pmus], where DeltaPaw is peak Paw - continuous positive airway pressure. PB with central apneas developed in 11 of 12 subjects on PSV. DeltaPCO2 ranged from 1.5 to 5.8 Torr. Changes in RR with PSV were small and bidirectional (+1.1 to -3.5 min-1). With use of stepwise regression, PSV(PB) was significantly correlated with VTsp (P = 0.001), E (P = 0.00009), DeltaPCO2 (P = 0.007), and DeltaRR (P = 0.006). The final regression model was as follows: PSV(PB) = 11.1 VTsp + 0.3E - 0.4 DeltaPCO2 - 0.34 DeltaRR - 3.4 (r = 0.98). PB developed in five subjects on PAV at amplification factors of 1.5-3.4. It failed to occur in seven subjects, despite PAF of up to 7.6. We conclude that 1) a PCO2 apneic threshold exists during sleep at 1.5-5.8 Torr below eupneic PCO2, 2) the development of PB during PSV is entirely predictable during sleep, and 3) the inherent susceptibility to PB varies considerably among normal subjects.     

Partial liquid ventilation protects lung during resuscitation from shock

Preliminary animal experience with partial liquid ventilation (PLV) suggests that this therapy may diminish neutrophil invasion and capillary leak during acute lung injury. We sought to confirm these findings in a model of shock-induced lung injury. Sixty anesthetized rats were studied. After hemorrhage to an arterial pressure of 25 mmHg for 45 min, animals were resuscitated with blood and saline and treated with gas ventilation alone or with 5 ml/kg of intratracheally administered perflubron. Myeloperoxidase activity was used to measure lung neutrophil content. A permeability index (the bronchoalveolar-to-blood ratio of 125I-labeled albumin activity) quantified alveolar leak. Injury caused an increase in myeloperoxidase that was reversed by PLV (injury = 0.837 +/- 0.452, PLV = 0.257 +/- 0.165; P < 0.01). Capillary permeability also increased with hemorrhage, with a strong trend toward improvement in the PLV group (permeability indexes: injury = 0.094 +/- 0.102, PLV = 0.045 +/- 0.045; 95% confidence interval for injury--PLV: -0.024, 0.1219). We conclude that PLV is associated with a decrease in pulmonary neutrophil accumulation and a trend toward decreased capillary leak after hemorrhagic shock.     

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.     

Negative pressure ventilation vs. spontaneous assisted ventilation during rigid bronchoscopy. A controlled randomised trial

BACKGROUND: Ventilation during interventional rigid bronchoscopy (IRB) under general anaesthesia (jet ventilation, positive pressure ventilation and spontaneous assisted ventilation) may offer some difficulties. This study compares the effectiveness during IRB of intermittent negative pressure ventilation (INPV) and spontaneous assisted ventilation (SAV). METHODS: Thirty-eight patients submitted to IRB were randomised into two groups: SAV or INPV. All patients received a total intravenous anaesthesia; INPV patients were paralysed. Pre- and intra-operative arterial blood gases and O2 flow through a rigid bronchoscope were assessed. The endoscopist applying a subjective score evaluated the operating conditions. RESULTS: Patients of the INPV group, as compared to the SAV group, required a lower dosage of fentanyl (2.6 +/- 1.8 micrograms.kg-1.h-1 vs. 6.6 +/- 4.8 micrograms.kg-1.h-1), a lower O2 supply (3.3 +/- 2.8 l/min vs. 11.6 +/- 3.4 l/min), a shorter recovery time (5.4 +/- 2.9 min vs. 9.8 +/- 7.1 min) and no manually assisted ventilation (0 +/- 0 vs. 1 +/- 1.1 n degree/procedure). Intraoperative PaCO2 was higher in the SAV (8.1 +/- 1.3 kPa) than in the INPV group (5.0 +/- 1.6 kPa) and intraoperative pH differed in the two groups (7.26 +/- 0.05, SAV vs. 7.47 +/- 0.08, INPV). Operating conditions, as assessed by a subjective score, were considered better with INPV than with SAV (4.9 vs. 4.3). CONCLUSIONS: As compared to SAV, INPV in paralysed patients during IRB reduces administration of opioids, shortens recovery time, prevents respiratory acidosis, excludes the need for manually assisted ventilation, reduces O2 need and affords optimal surgical conditions. INPV appears a safe, non-invasive and effective ventilatory management during IRB.     

Dynamics of lung collapse and recruitment during prolonged breathing in porcine lung injury

Oleic acid (OA) injection, lung lavage, and endotoxin infusion are three commonly used methods to induce experimental lung injury. The dynamics of lung collapse and recruitment in these models have not been studied, although knowledge of this is desirable to establish ventilatory techniques that keep the lungs open. We measured lung density by computed tomography during breath-holding procedures. Lung injury was induced with OA, lung lavage, or endotoxin in groups of six mechanically ventilated pigs. After a stabilization period, repetitive computed tomography scans of the same slice were obtained during prolonged expirations with and without positive end-expiratory pressure and during prolonged inspirations after 5 and 30 s of expiration. Lung collapse and recruitment occurred mainly within the first 4 s of breath-holding procedures in all three lung injury models, and some collapse and recruitment occurred even within 0.6 s. OA-injured lungs were significantly more unstable than lungs injured by bronchoalveolar lavage or endotoxin infusion. In this experimental setting, expiration times <0.6 s are required to avoid cyclic alveolar collapse during mechanical ventilation without extrinsic positive end-expiratory pressure.     

Effects of mechanical ventilation on control of breathing

The presence of thermotolerant Campylobacter in rivers and lakes of Warsaw region was examined with the detectability of 1 c.f.u./ml. Samples were taken from depth of water and from the surface of different objects deposited on the bottom. The results indicate that about 70% of water samples are contaminated with Campylobacter, whereas the contamination of the underwater objects is less prevalent. The species distribution was as follows: C. jejuni-65%, C. coli-22%, C. lari-13%. In vitro experiment was also performed to test the ability of Campylobacter to create biofilms on the surface of wood, metal and plastic, however no such property was revealed. From the analysis of presented results it was established that localization of the highest contamination is connected mainly with presence of municipal sewage and in less extent with the presence of the droppings of wild animals. The samples of water give the better reflection of the examined reservoir contamination than solid samples.     

Influence of drive and timing mechanisms on breathing pattern and ventilation during mental task performance

Assessment of multiple respiratory measures may provide insight into how behavioral demands affect the breathing pattern. This is illustrated by data from a study among 44 subjects, in which tidal volume, respiration rate, minute ventilation and indices of central drive and timing mechanisms were assessed via inductive plethysmography, in addition to end-tidal PCO2. After a baseline, three conditions of a memory comparison task were presented. The first two conditions differed only with regard to the presence or absence of feedback of performance (NFB and FB). In the third 'all-or-nothing' (AON) condition, subjects only received a monetary bonus, if their performance exceeded that of the previous two conditions. Minute ventilation increased from baseline to all task conditions, and from NFB and FB to AON. Respiration rate increased in all task conditions, but there were no differences between task conditions. Tidal volume decreased during NFB, but was equal to baseline during FB and AON. Of the respiratory control indices, inspiratory flow rate covaried much more closely with minute ventilation than duty cycle. The task performance induced a minor degree of hyperventilation. The discussion focusses on how behavioral demands affect respiratory control processes to produce alterations in breathing pattern and ventilation.     

Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation. Spanish Lung Failure Collaborative Group

The duration of spontaneous breathing trials before extubation has been set at 2 h in research studies, but the optimal duration is not known. We conducted a prospective, multicenter study involving 526 ventilator-supported patients considered ready for weaning, to compare clinical outcomes for trials of spontaneous breathing with target durations of 30 and 120 min. Of the 270 and 256 patients in the 30- and 120-min trial groups, respectively, 237 (87.8%) and 216 (84.8%), respectively, completed the trial without distress and were extubated (p = 0.32); 32 (13.5%) and 29 (13.4%), respectively, of these patients required reintubation within 48 h. The percentage of patients who remained extubated for 48 h after a spontaneous breathing trial did not differ in the 30- and 120-min trial groups (75.9% versus 73.0%, respectively, p = 0.43). The 30- and 120-min trial groups had similar within-unit mortality rates (13 and 9%, respectively) and in-hospital mortality rates (19 and 18%, respectively). Reintubation was required in 61 (13.5%) patients, and these patients had a higher mortality (20 of 61, 32.8%) than did patients who tolerated extubation (18 of 392, 4.6%) (p < 0.001). Neither measurements of respiratory frequency, heart rate, systolic blood pressure, and oxygen saturation during the trial, nor other functional measurements before the trial discriminated between patients who required reintubation from those who tolerated extubation. In conclusion, after a first trial of spontaneous breathing, successful extubation was achieved equally effectively with trials targeted to last 30 and 120 min.     

Respiratory pattern and rebreathing in the Mapleson A, C and D breathing systems with spontaneous ventilation. A theory

A theoretical analysis is presented of the Mapleson A, C and D breathing systems when used in spontaneous respiration. The influence of the respiratory pattern is explained diagrammatically. Simple equations are derived, predicting the fresh gas flow required to prevent rebreathing with different respiratory patterns. Further equations allow the degree of rebreathing caused by inadequate fresh gas flow to be quantified. These are used to examine the effects of different respiratory patterns on the efficiency of the three systems. It is demonstrated that the single most important determinant of efficiency is the duration of the expiratory pause. The nature of the inspiratory and expiratory waveforms is less important and the I:E ratio far less important. The analysis suggests that the Mapleson A system will always be the most efficient of the three systems. The Mapleson C system will be efficient if inspiration is long and the expiratory pause is minimal. The Mapleson D system will be efficient if the expiratory pause is sufficiently long.     

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.     

Expiratory flow limitation during spontaneous breathing: comparison of patients with restrictive and obstructive respiratory disorders

BACKGROUND AND STUDY OBJECTIVES: Comparison of tidal and forced expiratory flow-volume (V-V) curves has inherent technical problems in the characterization of expiratory flow limitation. In addition, patients with neuromuscular disorders may be unable to perform forced expiratory maneuvers because of muscle weakness or poor coordination. A recently developed simple, noninvasive technique that avoids these problems was used to detect expiratory flow limitation at rest in 19 seated patients with restrictive respiratory (13 with musculoskeletal) disorders (RD) and 20 with chronic obstructive airway disease (COAD). SETTING: A large rehabilitation hospital for the care of patients with chronic musculoskeletal and respiratory disorders. INTERVENTIONS AND MEASUREMENTS: The method consisted of applying negative pressure of about 5 cm H2O at the airway opening during expiration and comparing the ensuing V-V curve to the preceding tidal V-V curve. RESULTS: While nine patients with COAD demonstrated flow limitation, only one patient with RD did so. Patients with expiratory flow limitation exhibited various contours of the control tidal expiratory V-V curve. Thus, inspection of the tidal V-V curve is not a reliable means of detecting expiratory flow limitation. CONCLUSIONS: We conclude that expiratory flow limitation during resting breathing is common in patients with COAD but not in patients with RD.