Improvement In Arterial Oxygenation Research Articles

Response to Recruitment Maneuver Influences Net Alveolar Fluid Clearance in Acute Respiratory Distress Syndrome

Alveolar fluid clearance is impaired in the majority of patients with acute respiratory distress syndrome (ARDS). Experimental studies have shown that a reduction of tidal volume increases alveolar fluid clearance. This study was aimed at assessing the impact of the response to a recruitment maneuver (RM) on net alveolar fluid clearance. In 15 patients with ARDS, pulmonary edema fluid and plasma protein concentrations were measured before and after an RM, consisting of a positive end-expiratory pressure maintained 10 cm H2O above the lower inflection point of the pressure-volume curve during 15 min. Cardiorespiratory parameters were measured at baseline (before RM) and 1 and 4 h later. RM-induced lung recruitment was measured using the pressure-volume curve method. Net alveolar fluid clearance was measured by measuring changes in bronchoalveolar protein concentrations before and after RM. In responders, defined as patients showing an RM-induced increase in arterial oxygen tension of 20% of baseline value or greater, net alveolar fluid clearance (19 +/- 13%/h) and significant alveolar recruitment (113 +/- 101 ml) were observed. In nonresponders, neither net alveolar fluid clearance (-24 +/- 11%/h) nor alveolar recruitment was measured. Responders and nonresponders differed only in terms of lung morphology: Responders had a diffuse loss of aeration, whereas nonresponders had a focal loss of aeration, predominating in the lower lobes. In the absence of alveolar recruitment and improvement in arterial oxygenation, RM decreases the rate of alveolar fluid clearance, suggesting that lung overinflation may be associated with epithelial dysfunction.

Treatment of severe meconium aspiration syndrome with porcine surfactant: A multicentre, randomized, controlled trial

A randomized, controlled clinical trial was performed in 19 Chinese neonatal intensive care units to evaluate the safety and efficacy of exogenous surfactant replacement therapy for severe meconium aspiration syndrome (MAS) in term and near-term neonates. Sixty-one term infants with severe MAS were randomly assigned to either a surfactant or a control group within 36 h after birth. The infants in the surfactant group (n=31) received an initial dose of porcine lung-derived surfactant (Curosurf) at 200 mg/kg, and repeated doses of 200, 100 and 100 mg/kg were given at 6-12 h intervals to a maximum of four doses if oxygenation index (OI) deteriorated by >2 from baseline. The primary outcomes were a reduction of OI to less than 10 and an increase of the pre-treatment a/A PO(2) ratio of 100% over baseline 24 h after surfactant treatment. The secondary outcomes were duration of mechanical ventilation, incidence of complications and survival to discharge from hospital. The general demographic characteristics of the study subjects were similar. There was a trend for surfactant-treated infants to have an improvement in arterial oxygenation compared to the control group. In comparison with the control group at 24 h, the surfactant group had a lower mean OI (8.1 vs 10.9), more infants with a 100% increase of a/A PO(2) (83% vs 48%, p<0.01) over baseline, and a larger area under the curve for PaO(2)/FiO(2) over baseline (3762+/-1877 vs 2715+/-1644 mmHg(.)h, p<0.05). Repeated measures of these parameters were also in favour of the surfactant group during 24 h to 3 and 7 d compared to the baseline (p<0.05). No differences were found in mean duration of mechanical ventilation, incidence of major complications and number of survivors between the two groups. Surfactant replacement therapy improved oxygenation in the study subjects, suggesting that surfactant may have a role in the treatment of severe MAS in term and near-term infants.

Almitrine bismesylate treatment in patient with chronic obstructive pulmonary disease and moderate chronic respiratory failure. Open prospective multicentre trial

The efficacy and safety of almitrine bismesylate treatment was assessed in COPD patients in 6 month open prospective multicentre trial. 77 COPD patients with moderate hypoxemia were included (males / females — 57 / 20, mean age 63.2 ± 9.7 years; mean FEV1 0.95 ± 0.38 L, mean PaO2 63.3 ± 5.4 mmHg, mean PaСO2 44.1 ± 7.3 mmHg). We used an intermittent regime of almitrine administration: 1 mg / kg / day, for 3 months, then a "window" of 1 month, and again active therapy for 2 months. Almitrine therapy resulted in improvement of РаО2: rise after 1 month to 71.5 ± 10.6 mmHg, after 3 month — to 70.3 ± 8.3 mmHg, and after 6 month — to 72.5 ± 14.2 mmHg (р &lt; 0.001). There was a significant fall in dyspnea during daily life activities (MRC score): from 3.5 ± 0.9 to 3.0 ± 0.9 (1 month), 2.8 ± 0.9 (3 month), 2.6 ± 0.7 (6 month) (р &lt; 0.001). The distance during 6 minute walk test (6 MWT) increased from 334 ± 108 m to 371 ± 101 m (1 month), 377 ± 88 m (3 month), 398 ± 104 m (6 month) (р &lt; 0.001). The levels of desaturation and Borg dyspnea score during 6 MWT significantly decreased (both р &lt; 0.001). During almitrine treatment an improvement in almost all domains of SF 36 quality of life questionnaire was noted. 58 COPD patients completed the study. The most common adverse effects were parasthesia (6.4 %) and worsening of dyspnea (5 %), pulmonary artery pressure did not change during study. Conclusions: almitrine treatment in COPD patients with moderate hypoxemia resulted in improvement of arterial oxygenation, reduction of dyspnea during daily life activities and exercise, increase of physical capacity and improvement of health related quality of life.

Differences in hemodynamic and oxygenation responses to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension

Objectives We sought to compare the short-termimpact of three different phosphodiesterase-5 (PDE5) inhibitors on pulmonary and systemic hemodynamics and gas exchange parameters in patients with pulmonary arterial hypertension (PAH). Background The PDE5 inhibitor sildenafil has been reported to cause pulmonary vasodilation in patients with PAH. Vardenafil and tadalafil are new PDE5 inhibitors, recently being approved for the treatment of erectile dysfunction. Methods Sixty consecutive PAH patients (New York Heart Association functional class II to IV) who underwent right heart catheterization received short-term nitric oxide (NO) inhalation and were subsequently assigned to oral intake of 50 mg sildenafil (n = 19), 10 mg (n = 7) or 20 mg (n = 9) vardenafil, or 20 mg (n = 9), 40 mg (n = 8), or 60 mg (n = 8) tadalafil. Hemodynamics and changes in oxygenation were assessed over a subsequent 120-min observation period. Results All three PDE5 inhibitors caused significant pulmonary vasorelaxation, with maximum effects being obtained after 40 to 45 min (vardenafil), 60 min (sildenafil), and 75 to 90 min (tadalafil). Sildenafil and tadalafil, but not vardenafil, caused a significant reduction in the pulmonary to systemic vascular resistance ratio. Significant improvement in arterial oxygenation (equally to NO inhalation) was only noted with sildenafil. Conclusions In PAH patients, the three PDE5 inhibitors differ markedly in their kinetics of pulmonary vasorelaxation (most rapid effect by vardenafil), their selectivity for the pulmonary circulation (sildenafil and tadalafil, but not vardenafil), and their impact on arterial oxygenation (improvement with sildenafil only). Careful evaluation of each new PDE5 inhibitor, when being considered for PAH treatment, has to be undertaken, despite common classification as PDE5 inhibitors.

Ventilator strategies for posttraumatic acute respiratory distress syndrome: airway pressure release ventilation and the role of spontaneous breathing in critically ill patients

Patients who experience severe trauma are at increased risk for the development of acute lung injury and acute respiratory distress syndrome. The management strategies used to treat respiratory failure in this patient population should be comprehensive. Current trends in the management of acute lung injury and acute respiratory distress syndrome consist of maintaining acceptable gas exchange while limiting ventilator-associated lung injury. Currently, two distinct forms of ventilator-associated lung injury are recognized to produce alveolar stress failure and have been termed low-volume lung injury (intratidal alveolar recruitment and derecruitment) and high-volume lung injury (alveolar stretch and overdistension). Pathologically, alveolar stress failure from low- and high-volume ventilation can produce lung injury in animal models and is termed ventilator-induced lung injury. The management goal in acute lung injury and acute respiratory distress syndrome challenges clinicians to achieve the optimal balance that both limits the forms of alveolar stress failure and maintains effective gas exchange. The integration of new ventilator modes that include the augmentation of spontaneous breathing during mechanical ventilation may be beneficial and may improve the ability to attain these goals. Airway pressure release ventilation is a mode of mechanical ventilation that maintains lung volume to limit intra tidal recruitment /derecruitment and improves gas exchange while limiting over distension. Clinical and experimental data demonstrate improvements in arterial oxygenation, ventilation-perfusion matching (less shunt and dead space ventilation), cardiac output, oxygen delivery, and lower airway pressures during airway pressure release ventilation. Mechanical ventilation with airway pressure release ventilation permits spontaneous breathing throughout the entire respiratory cycle, improves patient comfort, reduces the use of sedation, and may reduce ventilator days.

Differences in hemodynamic and oxygenation responses to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertensionA randomized prospective study

We sought to compare the short-termimpact of three different phosphodiesterase-5 (PDE5) inhibitors on pulmonary and systemic hemodynamics and gas exchange parameters in patients with pulmonary arterial hypertension (PAH). The PDE5 inhibitor sildenafil has been reported to cause pulmonary vasodilation in patients with PAH. Vardenafil and tadalafil are new PDE5 inhibitors, recently being approved for the treatment of erectile dysfunction. Sixty consecutive PAH patients (New York Heart Association functional class II to IV) who underwent right heart catheterization received short-term nitric oxide (NO) inhalation and were subsequently assigned to oral intake of 50 mg sildenafil (n = 19), 10 mg (n = 7) or 20 mg (n = 9) vardenafil, or 20 mg (n = 9), 40 mg (n = 8), or 60 mg (n = 8) tadalafil. Hemodynamics and changes in oxygenation were assessed over a subsequent 120-min observation period. All three PDE5 inhibitors caused significant pulmonary vasorelaxation, with maximum effects being obtained after 40 to 45 min (vardenafil), 60 min (sildenafil), and 75 to 90 min (tadalafil). Sildenafil and tadalafil, but not vardenafil, caused a significant reduction in the pulmonary to systemic vascular resistance ratio. Significant improvement in arterial oxygenation (equally to NO inhalation) was only noted with sildenafil. In PAH patients, the three PDE5 inhibitors differ markedly in their kinetics of pulmonary vasorelaxation (most rapid effect by vardenafil), their selectivity for the pulmonary circulation (sildenafil and tadalafil, but not vardenafil), and their impact on arterial oxygenation (improvement with sildenafil only). Careful evaluation of each new PDE5 inhibitor, when being considered for PAH treatment, has to be undertaken, despite common classification as PDE5 inhibitors.

Differences in hemodynamic and oxygenation responses to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension: A randomized prospective study

We sought to compare the short-term impact of three different phosphodiesterase-5 (PDE5) inhibitors on pulmonary and systemic hemodynamics and gas exchange parameters in patients with pulmonary arterial hypertension (PAH). The PDE5 inhibitor sildenafil has been reported to cause pulmonary vasodilation in patients with PAH. Vardenafil and tadalafil are new PDE5 inhibitors, recently being approved for the treatment of erectile dysfunction. Sixty consecutive PAH patients (New York Heart Association functional class II to IV) who underwent right heart catheterization received short-term nitric oxide (NO) inhalation and were subsequently assigned to oral intake of 50 mg sildenafil (n = 19), 10 mg (n = 7) or 20 mg (n = 9) vardenafil, or 20 mg (n = 9), 40 mg (n = 8), or 60 mg (n = 8) tadalafil. Hemodynamics and changes in oxygenation were assessed over a subsequent 120-min observation period. All three PDE5 inhibitors caused significant pulmonary vasorelaxation, with maximum effects being obtained after 40 to 45 min (vardenafil), 60 min (sildenafil), and 75 to 90 min (tadalafil). Sildenafil and tadalafil, but not vardenafil, caused a significant reduction in the pulmonary to systemic vascular resistance ratio. Significant improvement in arterial oxygenation (equally to NO inhalation) was only noted with sildenafil. In PAH patients, the three PDE5 inhibitors differ markedly in their kinetics of pulmonary vasorelaxation (most rapid effect by vardenafil), their selectivity for the pulmonary circulation (sildenafil and tadalafil, but not vardenafil), and their impact on arterial oxygenation (improvement with sildenafil only). Careful evaluation of each new PDE5 inhibitor, when being considered for PAH treatment, has to be undertaken, despite common classification as PDE5 inhibitors.

Difference of Short Term Survival in Patients with ARDS According to Responsiveness to Alveolar Recruitment

Background : Lung protective strategies, using low tidal volume in ARDS, improve survival rate in ARDS. However, low tidal volume ventilation may promote alveolar de-recruitment. Therefore, alveolar recruitment is necessary to maintain arterial oxygenation and to prevent repetitive opening and closure of collapsed alveoli in lung protective strategies. There has been a recent report describing improvement in arterial oxygenation with use of recruitment maneuver. However, impact of recruitment on outcome of ARDS is unknown. We evaluated whether short-term survival difference existed in patients with ARDS, who were performed alveolar recruitment maneuver(ARM) and prone position, according to response of alveolar recruitment or not. Methods : All patients who were diagnosed with ADRS and received mechanical ventilation were included. ARM were sustained inflation( CPAP for 30-40 sec.) or increasing level of PEEP. If these methods were ineffective, alveolar recruitment with prone position was done for at least 10 hours. (P/F) ratio was determined before and at 0.5 and 2 hours after ARM. We defined a responder if the P/F ratio was increased over 50% of baseline value. We compared 10-days and 30-days survival rate between responders and non-responders. Results : 20 patients(M:F=12:8, ) were included. Among them, 12 patients were responders and 8 patients were non-responders. In responders, P/F ratio was increased from to . In non-responders, P/F ratio increased from to . Among non-responders, P/F ratio was improved over 50% in 2 patients after prone position. Overall, 14 patients were responders after ARM and prone position. The 10-days and 30-days survival rate in responders was significantly higher than in non-responders(86%, 57% in responders and 33%, 0% in non-responders)(p, ), lung injury score(, ), simplified acute physiology score(SAPS) II (, ), positive end-positive pressure level(, ). Conclusion : ARM may improve arterial oxygenation in some patients with ARDS. These responders in patients with ARDS showed significant higher 10-days and 30-days survival rate than non-responders patients with alveolar recruitment.

Lung recruitment maneuver in patients with cerebral injury: effects on intracranial pressure and cerebral metabolism.

To investigate the effects of a lung recruitment maneuver on intracranial pressure (ICP) and cerebral metabolism in patients with acute cerebral injury and respiratory failure. Prospective investigation. Ten-bed intensive care unit of a university hospital. Eleven patients with acute traumatic or non-traumatic cerebral lesions, who were on mechanical ventilation with acute lung injury. Hemodynamics, ICP, cerebral perfusion pressure (CPP), jugular venous oxygen saturation (SJO(2)), and arterial minus jugular venous lactate content difference (AJDL) were measured before, during and after a volume recruitment maneuver (VRM), which included a 30-s progressive increase in peak pressure up to 60 cmH(2)O and a sustained pressure at the same level for the next 30 s. At the end of VRM, ICP was elevated (16+/-5 mmHg vs 13+/-5 mmHg before VRM, P<0.05) and mean arterial pressure was reduced (75+/-10 vs 86+/-9 mmHg, P<0.01), which resulted in a decrease of CPP (60+/-10 vs 72+/-8 mmHg, P<0.01). SJO(2) deteriorated at the end of the procedure (59+/-7 vs 69+/-6%, P<0.05), AJDL was not altered. In the following period all parameters returned to normal values. An improvement in arterial oxygenation was observed at the end, but not in the period after the maneuver. Our VRM reduced cerebral hemodynamics and metabolism. We conclude that our VRM with high peak pressure effects only a marginal improvement in oxygenation but causes deterioration of cerebral hemodynamics. We therefore cannot recommend this technique for the ventilatory management of brain-injured patients.

Outpatient inhaled nitric oxide in a patient with idiopathic pulmonary fibrosis: a bridge to lung transplantation

Inhaled nitric oxide (INO) has been shown to improve oxygenation and decrease intrapulmonary shunt and pulmonary hypertension in various lung diseases. In this study we report a patient with end-stage idiopathic pulmonary fibrosis and pulmonary hypertension who received INO after coronary artery bypass surgery, with significant improvement in arterial oxygenation and pulmonary arterial pressure. Using a pulsing delivery system, the patient continued to receive outpatient INO for 30 months while waiting for lung transplantation. Exercise study and two-dimensional echocardiogram, after 3 months of inhaled NO, demonstrated continued benefits of INO for improvement of arterial oxygenation, pulmonary arterial pressure and exercise tolerance. Inhaled nitric oxide (INO), a selective pulmonary vasodilator, has been shown to improve arterial oxygenation and pulmonary hypertension in the short term in patients with idiopathic pulmonary fibrosis. 1,2 However, long-term use of INO in these patients has not been reported previously. We report here the successful long-term outpatient administration of INO in a patient with idiopathic pulmonary fibrosis and secondary pulmonary hypertension, using a simple pulsed delivery system. The patient demonstrated significant improvement in oxygenation, pulmonary hypertension and exercise tolerance during treatment, allowing him to function independently while awaiting lung transplantation.

Non-invasive pressure support ventilation in severe community-acquired pneumonia.

Objective: To explore three aspects of non-invasive pressure support ventilation (NIPSV) applied by face mask to patients with acute respiratory failure (ARF) due to severe community-acquired pneumonia (CAP): (1) the initial acute effects on respiratory rate, gas exchange and hemodynamics, (2) the clinical course and outcome during ICU and hospital stay, (3) the nursing workload as measured by the daily PRN 87 (Project Research in Nursing) score. Setting: Medical ICU, University Hospital. Design: Prospective, observational study. Patients: Patients without any prior history of chronic lung disease, consecutively admitted to the ICU to receive NIPSV for ARF due to severe CAP. Measurements and results (means ± SD): Twenty-four patients aged 49±17 years, admission APACHE II 13±5, were included. Admission PaO2/FIO2, alveolar-arterial oxygen difference (DA-aO2) and PaCO2 were 104±48, 447±120 and 40±10 mmHg, respectively. All patients were normotensive. During the initial NIPSV trial respiratory rate decreased from 34±8 to 28±10 breaths/min (p<0.001) and arterial oxygenation improved (PaO2/FIO2 104±48 vs 153±49, DA-aO2 447±120 vs 370±180 mmHg, p<0.001) while PaCO2 remained unchanged. There were no hemodynamic effects. Subsequently, a total of 133 NIPSV trials were performed (median duration 55 min, range 30–540 min) over 1–7 days. No complication occurred during NIPSV. Sixteen patients were intubated (66%) 1.3±1 days after inclusion. Upon inclusion, the patients who were subsequently intubated were older (55±15 vs 37±12 years) and more severely hypoxemic (63±11 vs 80±15 mmHg, p<0.05) than those not requiring intubation. Eight patients died (33%), all in the intubated group. Median lengths of stay in the ICU and hospital were longer in intubated patients (ICU 16 days, range 3–64 vs 6 days, range 3–7, p<0.05; hospital 23 days, range 9–77 vs 9.5 days, range 4–42, p<0.05). Mean daily total PRN points were stable throughout the NIPSV period and were not different between the groups. Only 14% of PRN points resulted from respiratory therapy interventions. PRN score was higher during the first 24 h following intubation than during the first 24 h of NIPSV (278±55 vs 228±24 points, p<0.05). Conclusion: Despite initial improvement in arterial oxygenation with NIPSV in patients with ARF due to severe CAP, the intubation rate is high. However, the more favorable outcome and shorter ICU and hospital stays when intubation is avoided, as well as the short delay required to assess the success or failure of NIPSV warrants a trial of NIPSV in this setting. The nursing workload remains stable during NIPSV and does not result predominantly from respiratory therapy interventions.

Randomized Controlled Trial of Domiciliary Noninvasive Positive Pressure Ventilation and Physical Training in Severe Chronic Obstructive Pulmonary Disease

The addition of noninvasive positive pressure ventilation (NPPV) to an exercise training (ET) program in severe chronic obstructive pulmonary disease (COPD) may produce greater benefits in exercise tolerance and quality of life than after training alone. Forty-five patients with severe stable COPD-mean (SD) FEV(1) 0.96 (0.31) L, Pa(O(2)) 65.4 (9.07) mm Hg, Pa(CO(2)) 45.6 (7.89) mm Hg-were randomized to domiciliary NPPV + ET (n = 23) or ET alone (n = 22). Exercise capacity and health status were assessed at baseline and after an 8-wk training program. There was a significant improvement in mean shuttle walk test (SWT) in the NPPV + ET group: from 169 (112) to 269 (124) m (p = 0.001), compared with the ET group: 205 (100) to 233 (123) m (p = 0.19); mean difference (95% confidence interval [CI]): 72 (12.9 to 131) m. Repeated measures analysis of variance (ANOVA) showed that the differences between the two groups became evident only in the final 4 wk of the training program with a mean end study difference (95% 1CI) of 65.8 (17.1 to 114) m. There was a significant improvement in the Chronic Respiratory Disease Questionnaire (CRDQ) of mean (SD) 24.0 (17.4) (p = < 0.001) in the NPPV + ET group and 11.8 (15.8) (p = 0.003) points in the ET group; mean difference: 12.3 (1.19 to 23.4). Only the NPPV + ET group demonstrated a significant improvement in arterial oxygenation; mean difference: 3.70 mm Hg (0.37 to 7.27). This study suggests that domiciliary NPPV can be used successfully to augment the effects of rehabilitation in severe COPD.

Time-dependency of improvements in arterial oxygenation during partial liquid ventilation in experimental acute respiratory distress syndrome.

The mechanisms by which partial liquid ventilation (PLV) can improve gas exchange in acute lung injury are still unclear. Therefore, we examined the time- and dose-dependency of the improvements in arterial oxygen tension (PaO2) due to PLV in eight pigs with experimental lung injury, in order to discriminate increases due to oxygen dissolved in perfluorocarbon before its intrapulmonary instillation from a persistent diffusion of the respiratory gas through the liquid column. Application of four sequential doses of perfluorocarbon resulted in a dose-dependent increase in PaO2. Comparison of measurements 5 and 30 min after instillation of each dose revealed a time-dependent decrease in PaO2 for doses that approximated the functional residual capacity of the animals. Although oxygen dissolved in perfluorocarbon at the onset of PLV can cause a short-term improvement in arterial oxygenation, diffusion of oxygen through the liquid may not be sufficient to maintain the initially observed increase in PaO2.

Milrinone improves arterial oxygenation in dogs with acute lung injury induced by oleic acid.

The aim of the study was to investigate effects of milrinone on pulmonary permeability in dogs with acute lung injury induced by oleic acid. To induce acute lung injury, we administered 0.08 mg/kg of oleic acid to 19 adult mongrel dogs and then measured hemodynamic parameters and performed blood gas analysis. An injection of oleic acid depressed the mean arterial pressure, cardiac index, and arterial oxygenation. Dogs were divided into three groups: six received a bolus of milrinone (50 microg/kg) followed by a continuous (0.5 microg/kg/min, low-dose), seven received a bolus (100 microg/kg) followed by a continuous (1.0 microg/kg/min; i.e., a low-dose twice; high-dose), and six no milrinone (control). Milrinone administration improved the cardiac index and arterial oxygenation and simultaneously depressed the intrapulmonary shunt fraction and the extravascular thermal lung water as extravascular water content of the lung. These changes produced by milrinone are different according to the doses. In conclusion, milrinone acts on the capillary endothelium and inhibits an accumulation in the extravascular water content of the lung, which may induce an improvement in arterial oxygenation. Milrinone may also improve arterial oxygenation through an inhibition of platelet aggregation and chemical mediators that are released from platelets. The latter mechanism also may improve arterial oxygenation, and the exact property responsible for causing the effect of milrinone has not yet been identified.

Nitric oxide inhalation in pulmonary hypertension and severe respiratory failure.

Inhalation of nitric oxide (NO) can cause selective pulmonary vasodilation in aerated lung regions; thus, it may be of benefit in the treatment of various forms of pulmonary hypertension and respiratory distress due to a mismatch of pulmonary ventilation and perfusion. The specific characteristics of inhaled NO exclude long-term treatment, but NO has been successfully used as a test substance to screen patients for response to oral vasodilators. Furthermore, inhalation of NO has been shown to improve gas exchange and right ventricular performance and to reduce the need for other, more invasive therapies in various settings of acute pulmonary hypertension. However, the improvement of arterial oxygenation seen in patients with the acute respiratory distress syndrome does not result in increased survival, questioning the future importance of inhaled NO in the treatment of this pulmonary disorder.

The cardiopulmonary effects of clenbuterol when administered to dorsally recumbent halothane-anaesthetised ponies — failure to increase arterial oxygenation

Clenbuterol (0·8 μg kg −1 intravenously) was investigated in ponies (small horses) anaesthetised with acepromazine, detomidine and thiopentone, then halothane in oxygen alone (hyperoxic group) or with nitrous oxide (hypoxic group). Following instrumentation, ponies were placed in dorsal recumbency for 60 minutes, clenbuterol (both groups) or a saline control (hyperoxic group) given, and cardiopulmonary parameters monitored for a further 60 minutes. In the hyperoxic group, clenbuterol administration resulted in a transitory (<five minutes) 15 per cent fall in arterial blood pressure and 78 per cent rise in intramuscular blood flow. Heart rate increased from a mean of 42 (SD 4) to 54 (12) beats per minute, the rise being significant for 15 minutes. Cardiac index increased from 2·1 (0·7) to 3·-9 (0·7) litres m −2 and remained significantly elevated for the remainder of the measurement period. Cardiovascular changes in the hypoxic group were similar. 30 minutes after clenbuterol administration, PaO 2 had changed non-significantly from 32·.3 (19·2) to 33·.4 (17) kPa in the hyperoxic group and from 7·9 (1·8) to 8·.6 (1·3) kPa in the hypoxic group. The study concludes that under these experimental conditions, clenbuterol does not cause significant improvement in arterial oxygenation, but its cardiovascular effects are minimal or advantageous.

Treatment of hepatopulmonary syndrome with Allium sativum L. (garlic): a pilot trial.

No medical therapy exists for subjects with hepatopulmonary syndrome (HPS). A patient with HPS was reported to have improvement in arterial oxygenation while self-administering garlic. Our goal was to determine whether a standardized garlic powder improves arterial oxygenation and dyspnea in subjects with HPS. A prospective, open label uncontrolled pilot study in 15 subjects with HPS were administered garlic powder capsules daily for a minimum of 6 months. Arterial blood gases were determined every 4-8 weeks, in the same position on room air, and a subjective dyspnea transition index was reported. Six of 15 subjects (40%, confidence interval: 0.15-65) had at least a 10 mmHg increase in the P(O2) or decrease in the alveolar-arterial gradient. The mean pre- and postarterial difference in these patients were: P(O2) (14+/-4 mmHg) and alveolar-arterial gradient (18+/-5 mmHg). All 6 subjects who responded to garlic had less dyspnea on exertion. Garlic improved arterial oxygenation in younger subjects (mean 40 versus 56 years old; p = 0.021) or those with lower macroaggregated albumin shunt fractions (mean 21 versus 44%, p = 0.058). Garlic may improve arterial oxygenation and symptoms in patients with hepatopulmonary syndrome and warrants further investigation.

The Utility of Nitric Oxide in the Postoperative Period

Inhaled nitric oxide (iNO) is a pulmonary-selective vaso dilator with minimal bronchodilator activity in humans. NO also inhibits platelet and neutrophil activation and adhesion and inhibits ischemia-reperfusion injury. The pulmonary vasodilatory property of iNO causes a reduc tion in pulmonary vascular resistance and improvement in arterial oxygenation in a wide spectrum of diseases characterized by pulmonary hypertension and hypox emia. Promising examples of diseases for which NO may provide beneficial physiologic effects are primary and secondary pulmonary hypertension, right ventricu lar failure, cardiac transplantation, pulmonary embo lism, protamine reactions, acute respiratory distress syndrome, lung transplantation and, perhaps, chronic obstructive airways disease. The usefulness of iNO may be improved by concomitant therapy with pulmonary- selective intravenous vasoconstrictors (eg, Almitrine; Vectarian, Neuilly, France) and cGMP phosphodiester ase V inhibitors (eg, Zaprinast; Research Biochemicals International, Natick, MA). Almitrine improves oxygen ation, synergistically with iNO, and may be useful in disease states characterized primarily by hypoxemia. Zaprinast may be useful for weaning iNO and avoidance of rebound pulmonary hypertension.

Comparison of volume controlled with pressure controlled ventilation during one-lung anaesthesia

Pressure controlled ventilation (PCV) is an alternative mode of ventilation which is used widely in severe respiratory failure. In this study, PCV was used for one-lung anaesthesia and its effects on airway pressures, arterial oxygenation and haemodynamic state were compared with volume controlled ventilation (VCV). We studied 48 patients undergoing thoracotomy. After two-lung ventilation with VCV, patients were allocated randomly to one of two groups. In the first group (n = 24), one-lung ventilation was started by VCV and the ventilation mode was then switched to PCV. Ventilation modes were performed in the opposite order in the second group (n = 24). We observed that peak airway pressure (P = 0.000001), plateau pressure (P = 0.01) and pulmonary shunt (P = 0.03) were significantly higher during VCV, whereas arterial oxygen tension (P = 0.02) was significantly higher during PCV. Peak airway pressure (Paw) decreased consistently during PCV in every patient and the percentage reduction in Paw was 4-35% (mean 16.1 (SD 8.4) %). Arterial oxygen tension increased in 31 patients using PCV and the improvement in arterial oxygenation during PCV correlated inversely with preoperative respiratory function tests. We conclude that PCV appeared to be an alternative to VCV in patients requiring one-lung anaesthesia and may be superior to VCV in patients with respiratory disease.

OPC-6535, a Superoxide Anion Production Inhibitor, Attenuates Acute Lung Injury

A large body of evidence has demonstrated that inhibition of the neutrophil's oxidant burst attenuates sepsis-induced acute lung injury. The present study sought to evaluate the ability of OPC-6535, a superoxide anion production inhibitor, to attenuate sepsis-induced acute lung injury. Four groups of swine were anesthetized, ventilated, and studied for 5 hr. Following surgical preparation, control (n= 10) and OPC-control (n= 2) animals received a 1-hr infusion of sterile saline. Sepsis was induced with a 1-hr intravenous infusion of livePseudomonas aeruginosa.Untreated septic animals (n= 10) received no treatment. Animals treated with OPC-6535 (n= 6) received a 1 mg/kg bolus of OPC-6535 15 min prior to initiation of the bacterial infusion. Changes in systemic and pulmonary hemodynamics, arterial oxygen tension, bronchoalveolar lavage protein and neutrophil content, neutrophil integrin expression, neutrophil oxidant burst, and lung myeloperoxidase content were used as outcome measures. Treatment with OPC-6535 significantly reduced acute lung injury, as indicated by improved bronchoalveolar lavage protein and neutrophil content, resulting in a significant improvement in arterial oxygenation. Treatment with OPC-6535 failed to prevent the development of pulmonary hypertension and systemic hypotension. Neutrophils from animals with both treated and untreated sepsis exhibited significant up-regulation of CD18 and production of increased levels of oxidants, indicating significant activation when compared to neutrophils from control animals. Although animals treated with OPC-6535 produced 25% less superoxide anion than untreated septic animals, this decrease was not statistically significant. Treatment of animals with OPC-6535 prior to the onset of sepsis produced significant protection against acute lung injury but failed to attenuate hemodynamic derangements associated with sepsis.