A double-blind, randomised, controlled Phase II trial of Heliox28 gas mixture in lung cancer patients with dyspnoea on exertion. Ambulatory oxygen therapy in stable kyphoscoliosis. Contribution of peripheral chemoreceptors to ventilation and the effects of their suppression on exercise tolerance in chronic heart failure. Ambulatory oxygen in chronic heart failure. Effects of oxygen on dyspnoea in hypoxaemic terminal-cancer patients. Does oxygen help dyspnea in patients with cancer? A randomized controlled trial of supplemental oxygen versus air in cancer patients with dyspnea.
Helium has a low density and the potential of reducing the work of breathing and improving alveolar ventilation when replacing nitrogen in air. A Phase II, double-blind, randomised, prospective, controlled trial was undertaken to assess whether Heliox28 (72% He/28% O(2)) compared with oxygen-enriched air (72% N(2)/28% O(2)) or medical air (78.9% N(2)/21.1% O(2)) could reduce dyspnoea and improve the exercise capability of patients with primary lung cancer and dyspnoea on exertion (Borg >3). A total of 12 patients (seven male, five female patients, age 53-78) breathed the test gases in randomised order via a facemask and inspiratory demand valve at rest and while performing 6-min walk tests. Pulse oximetry (SaO(2)) was recorded continuously. Respiratory rate and dyspnoea ratings (Borg and VAS) were taken before and immediately post-walk. Breathing Heliox28 at rest significantly increased SaO(2) compared to oxygen-enriched air (96+/-2 cf. 94+/-2, P<0.01). When compared to medical air, breathing Heliox28 but not oxygen-enriched air gave a significant improvement in the exercise capability (P<0.0001), SaO(2) (P<0.05) and dyspnoea scores (VAS, P<0.05) of lung cancer patients. Patients with chronic obstructive pulmonary disease (COPD) may benefit from ambulatory oxygen; however, the effect of exercise on arterial oxygen saturation (Sa,O2) in patients with kyphoscoliosis and of correction with ambulatory oxygen have not been previously reported. Twelve patients with stable kyphoscoliosis (mean (SD) Cobb angle 79 (26) degrees) were studied, with mean (SD) arterial oxygen tension (Pa,O2) 8.96 (0.93) kPa, arterial carbon dioxide tension (Pa,CO2) 6.52 (0.66), forced expiratory volume in one second (FEV1) 0.90 (0.15) L, forced vital capacity (FVC) 1.34 (0.46) L. Six-minute walking tests with oximetry and visual analogue scores (VAS) for breathlessness were performed on air (baseline), and with cylinders containing air and oxygen at 2 L-min-1. Cylinder walks were in random order, with patients blinded to cylinder content. Patients showed oxygen desaturation at each stage of the study. At baseline, oxygen desaturation during exercise was correlated with deterioration in VAS breathlessness scores. Ambulatory oxygen produced significant improvements in desaturation, breathlessness scores and recovery time compared to baseline and air cylinder walks. There was no relationship between baseline desaturation and changes in walking distance. Although exercise desaturation, breathlessness and recovery times were significantly improved with ambulatory oxygen at 2 L.min-1, walking distance was unaffected. We conclude that patients with moderate to severe kyphoscoliosis have significant oxygen desaturation on exercise and should thus routinely receive oximetry on exercise and assessment for ambulatory oxygen therapy. To assess the contribution of peripheral chemoreceptors to ventilation and the effects of continuous inspired oxygen on exercise tolerance in chronic heart failure patients. The role of peripheral chemoreceptors in mediating hyperpnoea in chronic heart failure is unknown. Hyperoxia is known to suppress the peripheral chemoreceptor drive. The magnitude of decrease in ventilation with transient inhalations of oxygen thus provides a measure of the contribution of the peripheral chemoreceptors to ventilation.
                Tertiary specialist hospital.
                Three breaths of 100% oxygen were given at rest and also during cycle ergometry at 25 W to 8 healthy controls (age 52.0 (4.7) (SEM) years) and 13 patients with chronic heart failure (age 60.5 (2.1) years (P = NS); radionuclide left ventricular ejection fraction 25.5 (4.3)%). The peripheral chemoreceptor sensitivity was also measured by assessing the ventilatory response to hypoxia using transient inhalations of pure nitrogen. Another group of 12 patients with chronic heart failure (age 65.5 (1.5) years; left ventricular ejection fraction 21.3 (3.0)%) underwent treadmill exercise testing on 2 occasions, breathing air or 100% oxygen in a randomised single-blind manner, to examine the effects of continuous inspired oxygen on exercise tolerance.
                The reduction in ventilation with transient hyperoxia was 18.1 (2.9)% v 17.9 (2.6)% (P = NS) at rest and 20.4 (2.8)% v 21.0 (1.6)% (P = NS) during cycle ergometry, for controls and patients respectively. The hypoxic chemosensitivity was higher in patients (0.232 (0.022) v 0.572 (0.082) 1/min/%SaO2; P = 0.002). Continuous inspired oxygen increased exercise time (517 (31) v 455 (27) seconds; P = 0.003), and a trend towards a reduction in the ventilatory response to exercise, characterised by the regression slope relating ventilation to carbon dioxide output, was evident (31.27 (2.60) v 34.19 (2.35); P = 0.08).
                Despite an increased peripheral chemoreceptor sensitivity, the proportionate contribution of peripheral chemoreceptors to ventilation remained similar in heart failure patients (about 20%). This suggests that the peripheral chemoreceptors are not the main mediator of increased ventilation and there are other non-peripheral chemoreceptor-mediated mechanisms involved. Hyperoxia reduced ventilation at rest and during cycle ergometry. The increase in exercise duration with continuous inspired oxygen that was associated with a reduction in exercise ventilatory response suggests that suppression of the peripheral chemoreceptors may improve exercise tolerance; the effects of possible reduced skeletal muscle anaerobiosis cannot be excluded, however. Ambulatory oxygen therapy may be of benefit in bicycle exercise tests. We have assessed the effects of ambulatory oxygen during walk tests in 12 patients with chronic heart failure. In 6 min walks with the patient breathing air, mean (SD) arterial oxygen saturation (SaO2) fell from 94.4 (3.7)% at rest to 90.1 (6.1)% (p = 0.014) on exercise. 21/min oxygen increased resting SaO2 from 93.7 (4.0)% (air cylinder) to 96.5 (3.0)% (p < 0.001) with no effect on minimum SaO2, distance, or breathlessness. During endurance walks, 4 l/min oxygen increased minimum SaO2 from 90.4 (5.6)% to 93.5 (4.7)% (p = 0.011) but also had no effect on breathlessness or distance. Ambulatory oxygen in currently available cylinders cannot be recommended for patients with chronic heart failure. Dyspnoea is a frequent and devastating symptom of advanced cancer. The purpose of this prospective, double-blind, crossover trial was to assess the effects of supplemental oxygen on the intensity of dyspnoea. 14 patients with hypoxaemic dyspnoea due to advanced cancer were randomised to receive either oxygen or air; the gases were delivered at 5 L/min by mask. After 5 min of stable oxygen saturation (pulse oximetry), patients were crossed over to receive the other treatment. The crossover was repeated twice. Dyspnoea was assessed with a visual analogue scale (O = no dyspnoea, 100 = worst dyspnoea). Mean difference in dyspnoea visual analogue scale between air and oxygen treatment was 20.5 (95% confidence interval 13.5 to 27.6). 12 patients consistently preferred oxygen to air; similarly, the investigator consistently chose oxygen for the same 12 patients. In a global rating questionnaire, patients reported little or no benefit during the air phase compared with moderate to much benefit during the oxygen phase. We conclude that oxygen is beneficial to patients with hypoxia and dyspnoea at rest. Dyspnea in patients with advanced cancer is a common symptom that is difficult to treat. This study investigated whether oxygen helps to relieve rest dyspnea in patients with advanced cancer. In a single-blind controlled trial, oxygen and air were administered in random order to hospice patients reporting dyspnea at rest. Measurements of arterial oxygen saturation, lung function, and dyspnea (using a visual analogue scale [VAS] and Borg score) were made before and after each gas had been given for 15 min. Data from 38 patients were used: analysis of variance revealed that mean VAS levels during baseline conditions, breathing room air (59 mm), were significantly reduced after administration of either air (48 mm; p < 0.001) or oxygen (45 mm; p < 0.001); there was no significant difference for the mean VAS scores between oxygen and air administration. There was no statistically significant order of treatment effect. There was no difference in the response to oxygen or air in patients with a history of cardiopulmonary disease. The improvement in dyspnea with oxygen could not be predicted from a subject's initial level of hypoxia. Results suggested that benzodiazepines may potentiate the effect of oxygen. The overall conclusion is that oxygen and air can have a significant effect in reducing dyspnea at rest in patients with advanced cancer. The symptomatic benefits of oxygen in patients with cancer who have nonhypoxic dyspnea are not well defined.
                To determine whether or not oxygen is more effective than air in decreasing dyspnea and fatigue and increasing distance walked during a 6-minute walk test.
                Patients with advanced cancer who had no severe hypoxemia (i.e., had an O2 saturation level of > or = 90%) at rest and had a dyspnea intensity of > or = 3 on a scale of 0-10 (0 = no shortness of breath, 10 = worst imaginable shortness of breath) were recruited from an outpatient thoracic clinic at a comprehensive cancer center. This was a double-blind, randomized crossover trial. Supplemental oxygen or air (5 L/min) was administered via nasal cannula during a 6-minute walk test. The outcome measures were dyspnea at 3 and 6 minutes, fatigue at 6 minutes, and distance walked. We also measured oxygen saturation levels at baseline, before second treatment phase, and at the end of study.
                In 33 evaluable patients (31 with lung cancer), no significant differences between treatment groups were observed in dyspnea, fatigue, or distance walked (dyspnea at 3 minutes: P = 0.61; dyspnea, fatigue, and distance walked at 6 minutes: P = 0.81, 0.37, and 0.23, respectively).
                Currently, the routine use of supplemental oxygen for dyspnea during exercise in this patient population cannot be recommended.
The failure to demonstrate a beneficial effect for oxygen breathing over air breathing in cancer or cardiac failure was limited by the small volume of research studies available for inclusion, the small numbers of participants and by the methods used in the studies.