Pulmonary function after emergence on 100% oxygen in patients with chronic obstructive pulmonary disease: a randomized, controlled trial.

BACKGROUND: During emergence from anesthesia, breathing 100% oxygen is frequently used to provide a safety margin toward hypoxemia in case an airway problem occurs. Oxygen breathing has been shown to cause pulmonary gas exchange disorders in healthy individuals. This study investigates how oxygen breathing during emergence affects lung function specifically whether oxygen breathing causes added hypoxemia in patients with chronic obstructive pulmonary disease. METHODS: This trial has been conducted in a parallel-arm, case-controlled, open-label manner. Fifty-three patients with chronic obstructive pulmonary disease were randomly allocated (computer-generated lists) to breathe either 100 or 30% oxygen balanced with nitrogen during emergence from anesthesia. Arterial blood gas measurements were taken before induction and at 5, 15, and 60 min after extubation. RESULTS: All participants tolerated the study well. Patients treated with 100% oxygen had a higher alveolar-arterial oxygen pressure gradient (primary outcome) compared with patients treated with 30% oxygen (25 vs. 20 mmHg) and compared with their baseline at the 60-min measurement (25 vs. 17 mmHg). At the 60-min measurement, arterial partial pressure of oxygen was lower in the 100% group (62 vs. 67 mmHg). Arterial partial pressure of carbon dioxide and pH were not different between groups or measurements. CONCLUSIONS: In this experiment, the authors examined oxygen breathing during emergence-a widely practiced maneuver known to generate pulmonary blood flow heterogeneity. In the observed cohort of patients already presenting with pulmonary blood flow disturbances, emergence on oxygen resulted in deterioration of oxygen-related blood gas parameters. In the perioperative care of patients with chronic obstructive pulmonary disease, oxygen breathing during emergence from anesthesia may need reconsideration.

Sildenafil and bosentan improve arterial oxygenation during acute hypoxic exercise: a controlled laboratory trial.

OBJECTIVES: Sildenafil and, recently, bosentan have been reported to increase arterial saturation and exercise capacity at altitude. The mechanisms behind this are still poorly defined but may be related to attenuation of hypoxic pulmonary vasoconstriction (HPV) and improved gas exchange. This study was designed to examine and compare the effect of sildenafil and bosentan on pulmonary gas exchange during acute hypoxic exercise in a controlled laboratory setting. METHODS: Sixteen athletic university students (8 males, 8 females) were examined during exercise in a hypoxic chamber (11% oxygen) before and after the administration of either sildenafil (n=10) or bosentan (n=6). Respiratory and metabolic measurements were taken at rest and during increasing exercise intensity (up to 90% of their individual maximal oxygen uptake [VO(2)max]) in concert with arterial blood gas sampling. RESULTS: Both drugs resulted in small, but significant increases in arterial PO(2) (2-3 Torr) and O(2) saturation (3-4%) at rest and during hypoxic exercise, in both men and women. No significant changes in arterial PCO(2) or ventilation were seen at rest or during exercise in hypoxia; however, heart rate (both at rest and during exercise) was increased with both sildenafil and bosentan in both men and women. CONCLUSIONS: These data demonstrate that sildenafil and bosentan equally improve arterial oxygenation in acute hypoxia in both men and women, which could account for improved physical performance at altitude.

Recombinant angiotensin-converting enzyme 2 improves pulmonary blood flow and oxygenation in lipopolysaccharide-induced lung injury in piglets.

OBJECTIVE: To study angiotensin-converting enzyme 2 in a piglet model with acute respiratory distress syndrome and to evaluate the therapeutic potential of this substance in a preclinical setting, as this model allows the assessment of the same parameters required for monitoring the disease in human intensive care medicine. The acute respiratory distress syndrome is the most severe form of acute lung injury with a high mortality rate. As yet, there is no specific therapy for improving the clinical outcome. Recently, angiotensin-converting enzyme 2, which inactivates angiotensin II, has been shown to ameliorate acute lung injury in mice. DESIGN: Prospective, randomized, double-blinded animal study. SETTING: Animal research laboratory. SUBJECTS: Fifteen anesthetized and mechanically ventilated piglets. INTERVENTIONS: Acute respiratory distress syndrome was induced by lipopolysaccharide infusion. Thereafter, six animals were assigned randomly into angiotensin-converting enzyme 2 group, whereas another six animals served as control. Three animals received angiotensin-converting enzyme 2 without lipopolysaccharide pretreatment. MEASUREMENTS AND MAIN RESULTS: Systemic and pulmonary hemodynamics, blood gas exchange parameters, tumor necrosis factor-alpha, and angiotensin II levels were examined before acute respiratory distress syndrome induction and at various time points after administering angiotensin-converting enzyme 2 or saline. In addition, ventilation-perfusion distribution of the lung tissue was assessed by the multiple inert gas elimination technique. Animals treated with angiotensin-converting enzyme 2 maintained significantly higher PaO2 than the control group, and pulmonary hypertension was less pronounced. Furthermore, angiotensin II and tumor necrosis factor-alpha levels, both of which were substantially increased, returned to basal values. Multiple inert gas elimination technique revealed a more homogeneous pulmonary blood flow after treatment with angiotensin-converting enzyme 2. In intergroup comparisons, there were no differences in pulmonary blood flow to lung units with subnormal ventilation/perfusion ratios. CONCLUSIONS: Angiotensin-converting enzyme 2 attenuates arterial hypoxemia, pulmonary hypertension, and redistribution of pulmonary blood flow in a piglet model of acute respiratory distress syndrome, and may be a promising substance for clinical use.

Intravenous tezosentan and vardenafil attenuate acute hypoxic pulmonary hypertension.

Excessive hypoxic pulmonary hypertension imposes right ventricular strain by increasing afterload that may lead to right heart failure and death. Increased phosphodiesterase activity, as well as increased levels of endothelin-1, has been discussed as molecular mechanisms. We investigated the hemodynamic and intrapulmonary effects of the intravenous dual endothelin A and B receptor blocker tezosentan, and of the phosphodiesterase-5 (PDE-5) antagonist vardenafil in a pig model of acute normobaric hypoxic pulmonary hypertension. Eighteen 4-week-old ventilated white farm pigs were exposed to normobaric hypoxia (FiO2 12%) and randomly assigned to three groups (n = 6) in order to receive either intravenous tezosentan or vardenafil or to serve as control. Arterial alveolar oxygen differences were the same with both drugs. After 90 min of treatment, pulmonary artery pressure and vascular resistance were significantly lower in both treatment groups when compared to controls (p < 0.001). Cardiac index increased significantly with vardenafil alone (2.8 l x min(-1) x m2 +/- 0.7 to 4.2 l x min x m2 +/- 0.7, p = 0.0003). Intravenous tezosentan, as well as vardenafil equipotently attenuate acute hypoxic pulmonary hypertension without afflicting pulmonary gas exchange. However, cardiac index increases with vardenafil only.

Intravenous tezosentan improves gas exchange and hemodynamics in acute lung injury secondary to meconium aspiration.

OBJECTIVE: Meconium aspiration induces acute lung injury (ALI) and subsequent pulmonary arterial hypertension (PAH) which may lead to right ventricular failure. Increase of endothelin-1, thromboxane-A, and phosphodiesterases are discussed molecular mechanisms. We investigated the intrapulmonary and hemodynamic effects of the intravenous dual endothelin A and B receptor blocker tezosentan and inhalational iloprost in a model of ALI due to meconium aspiration. DESIGN: Animal study. SETTING: University-affiliated research laboratory. SUBJECTS: White farm pigs. INTERVENTIONS: Acute lung injury was induced in 24 pigs by instillation of meconium. Animals were randomly assigned to four groups to receive either intravenous tezosentan, inhalational iloprost, or combined tezosentan and iloprost, or to serve as controls. MEASUREMENTS AND RESULTS: After meconium aspiration-induced lung injury each treatment increased oxyhemoglobin saturations (TEZO: 88 +/- 6% (p = 0.02), ILO: 85 +/- 13% (p = 0.05), TEZO-ILO: 89 +/- 6% (p = 0.02), control: 70 +/- 18%). TEZO but not ILO significantly decreased pulmonary arterial pressure and pulmonary vascular resistance (both p < 0.01). ILO alone decreased intrapulmonary shunt blood flow (p < 0.01). Compared with control, TEZO-ILO yielded the highest arterial partial pressure of oxygen (70 +/- 6 torr vs.49 +/- 9 torr, p = 0.04), although it decreased arterial blood pressure (change from 71 +/- 13 mmHg to 62 +/- 12 mmHg vs.85 +/- 14 mmHg to 80 +/- 11 mmHg (p = 0.01). CONCLUSIONS: Intravenous TEZO improves pulmonary gas exchange and hemodynamics in experimental acute lung injury secondary to meconium aspiration. Inhaled ILO improves gas exchange only, thereby reducing intrapulmonary shunt blood flow. Combination of TEZO and ILO marginally improves pulmonary gas exchange at the disadvantage of pulmonary selectivity.

Six-minute walk test in children and adolescents.

OBJECTIVE: To evaluate the 6-minute walking distance (6MWD) for healthy Caucasian children and adolescents of a population-based sample from the age of 3 to 18 years. STUDY DESIGN: Two hundred and eighty boys and 248 girls completed a modified test, using a measuring wheel as incentive device. RESULTS: Median 6MWD increased from the age of 3 to 11 years in boys and girls alike and increased further with increasing age in boys (from 667.3 m to 727.6 m), whereas it essentially plateaued in girls (655.8 m to 660.9 m). After adjusting for age, height (P = .001 in boys and P < .001 in girls) remained independently correlated with the 6MWD. In the best fitting and most efficient linear and quadratic regression models, the variables age and height explained about 49% of the variability of the 6MWD in boys and 50% in girls. CONCLUSION: This modified 6-minute walk test (6MWT) proved to be safe, easy to perform, and highly acceptable to children. It provides a simple and inexpensive means to measure functional exercise capacity in children, even of young age, and might be of value when conducting comparable studies.

Tezosentan decreases pulmonary artery pressure and improves survival rate in an animal model of meconium aspiration.

Acute pulmonary arterial hypertension in acute lung injury aggravates the clinical course and complicates treatment. Increased release and turnover of endogenous endothelin-1 is known to be a major determinant in the pathophysiology of pulmonary arterial hypertension of various etiologies. We tested whether intravenous tezosentan, a dual endothelin receptor antagonist, reduced pulmonary artery pressure in a pig model of acute lung injury induced by meconium aspiration. Acute pulmonary arterial hypertension was induced in 12 anesthetized and instrumented pigs by instillation of human pooled meconium in a 20% solution. Hemodynamic and gas exchange parameters were recorded every 30 min. Six animals received tezosentan 5 mg/kg after 0 and 90 min; six animals served as controls. Tezosentan led to a decrease of mean pulmonary artery pressure (PAP) from 33.4 +/- 4.0 mm Hg to 24.7 +/- 2.1 mm Hg and pulmonary vascular resistance (PVR) from 7.8 +/- 1.4 mm Hg.L(-1).min.m2 to 5.2 +/- 0.7 mm Hg.L(-1).min.m2. All animals treated with tezosentan survived, whereas in the control group four out of six animals died. Tezosentan improved survival and decreased pulmonary artery pressure in a porcine model of acute pulmonary arterial hypertension after meconium aspiration. Tezosentan has the potential for effective pharmacological treatment of pulmonary arterial hypertension following acute lung injury.

Administration of oxygen before tracheal extubation worsens gas exchange after general anesthesia in a pig model.

UNLABELLED: Administration of 100% oxygen before tracheal extubation is common clinical practice. We determined the effect of this technique on postoperative gas exchange in a porcine model using the multiple inert gas elimination technique. After general anesthesia with mechanical ventilation for a period of 30 min (inspiratory fraction of oxygen of 0.3), anesthesia was discontinued, and the pigs were randomized to an inspiratory fraction of oxygen of 0.3 or 1.0 until they could be safely extubated. Thirty minutes after extubation while breathing air, blood flow to poorly ventilated units had significantly increased in pigs that had been administered 100% oxygen as compared with those receiving 30% oxygen (17% +/- 15% versus 7% +/- 5%; P = 0.009). We conclude that exposure to 100% oxygen before extubation may cause an undesirable alteration in gas exchange. IMPLICATIONS: Blood flow to lung units with a low V(A)/Q ratio was significantly larger in pigs that had been exposed to 100% oxygen before extubation as compared with those exposed to 30% oxygen before extubation.

Decompression-triggered positive-pressure ventilation during cardiopulmonary resuscitation improves pulmonary gas exchange and oxygen uptake.

BACKGROUND: Intermittent positive-pressure ventilation (IPPV) is the "gold standard" of ventilation during cardiopulmonary resuscitation (CPR), but continuous positive airway pressure (CPAP) is increasingly discussed as an alternative. This study investigated hemodynamics and pulmonary gas exchange applying CPAP enhanced with pressure support ventilation (CPAP(PSV)) during CPR. METHODS AND RESULTS: Twenty-four pigs were subjected to ventricular fibrillation and CPR with CPAP(PSV), CPAP, or IPPV. Measurements were taken before (hemodynamics, blood gases, inert gas measurements) and 10 (hemodynamics, blood gases) and 20 (hemodynamics, blood gases, inert gas measurements) minutes after induction of ventricular fibrillation. Although no significant intergroup differences in hemodynamics were found, arterial partial pressure of oxygen (PaO(2)) was significantly higher during CPAP(PSV) compared with CPAP or IPPV (98+/-10, 61+/-27, and 71+/-30 mm Hg, respectively, P<0.05). CPAP(PSV) resulted in an alveolar-arterial partial pressure of oxygen difference of 56+/-17 mm Hg, whereas during CPAP, 83+/-21 mm Hg was detected, and during IPPV, 98+/-29 mm Hg was detected (P<0.05). Pulmonary blood flow to lung units with a normal VA/Q ratio in percent of cardiac output was 76+/-17% during CPAP(PSV), 61+/-21% during CPAP (P<0.01), and 54+/-13% during IPPV (P<0.01). Oxygen uptake (VO(2)) was significantly higher during CPAP(PSV) than with the other ventilation modes (P<0.05) and comparable to the baseline value in intragroup comparison. Return of spontaneous circulation was recorded in 8 of 8 animals in the CPAP(PSV) group, in 6 of 8 in the CPAP group, and in 3 of 8 in the IPPV group. CONCLUSIONS: CPAP(PSV) provides a straightforward and effective alternative to IPPV or CPAP during CPR that provides significantly higher PaO(2) and VO(2).

The influence of cuff volume and anatomic location on pharyngeal, esophageal, and tracheal mucosal pressures with the esophageal tracheal combitube.

BACKGROUND: The authors determined the influence of cuff volume and anatomic location on pharyngeal, esophageal, and tracheal mucosal pressures for the esophageal tracheal combitube. METHODS: Twenty fresh cadavers were studied. Microchip sensors were attached to the anterior, lateral, and posterior surfaces of the distal and proximal cuffs of the small adult esophageal tracheal combitube. Mucosal pressure for the proximal cuff in the pharynx was measured at 0- to 100-ml cuff volume in 10-ml increments, and for the distal cuff in the esophagus and trachea were measured at 0- to 20-ml cuff volume in 2-ml increments. The proximal cuff volume to form an oropharyngeal seal of 30 cm H2O was determined. In addition, mucosal pressures for the proximal cuff in the pharynx were measured in four awake volunteers with topical anesthesia. RESULTS: There was an increase in mucosal pressure in the trachea, esophagus, and pharynx at all cuff locations with increasing volume (all: P < 0.001). Pharyngeal mucosal pressures were highest posteriorly (50-ml cuff volume: 99 +/- 62 cm H2O; 100-ml cuff volume: 255 +/- 161 cm H2O). Esophageal mucosal pressures were highest posteriorly (10-ml cuff volume: 108 +/- 55 cm H2O; 20-ml cuff volume: 269 +/- 133 cm H2O). Tracheal mucosal pressures were highest anteriorly (10-ml cuff volume: 98 +/- 53 cm H2O; 20-ml cuff volume: 236 +/- 139 cm H2O). The proximal cuff volume to obtain an oropharyngeal seal of 30 cm H2O was 47 +/- 12 ml. Pharyngeal mucosal pressures were similar for cadavers and awake volunteers. CONCLUSION: We conclude that mucosal pressures for the esophageal tracheal combitube increase with cuff volume, are highest where the cuff is adjacent to rigid anatomic structures, and potentially exceed mucosal perfusion pressure even when cuff volumes are limited to achieving an oropharyngeal seal of 30 cm H2O.

Pulmonary gas exchange in coronary artery surgery patients during sevoflurane and isoflurane anesthesia.

UNLABELLED: As the surgical population ages, the number of patients presenting with coronary artery disease and age-related loss of pulmonary recoil will increase. Although their influence on gas exchange in this population remains unknown, sevoflurane and isoflurane are used for an increasing variety of surgical procedures. We examined pulmonary gas exchange (multiple inert gas elimination technique) in 30 patients presenting for coronary artery bypass grafting. After a baseline measurement taken during midazolam anesthesia, patients were continued on sevoflurane (n = 10), isoflurane (n = 10), or midazolam (n = 10) for 20 min, then a second measurement was taken. During sevoflurane and isoflurane anesthesia, blood flow to lung areas with a low ventilation/perfusion ratio (Va/Q) was significantly increased in comparison with control. During sevoflurane anesthesia, blood flow to lung areas with a normal Va/Q ratio (76 +/- 12 versus control: 89 +/- 5, mean +/- SD) and PaO(2) (138 +/- 31 versus control: 156 +/- 35 mm Hg, mean +/- SD) were depressed, whereas an increase in Va/Q-dispersion (log SD(Q)) was observed during isoflurane anesthesia. We conclude that both sevoflurane and isoflurane alter the distribution of perfusion in the lung, but only sevoflurane significantly depresses PaO(2). IMPLICATIONS: Both sevoflurane and isoflurane modified pulmonary blood flow in patients with coronary artery disease, but only sevoflurane depresses arterial oxygenation in this population.