Relationship between Improvement in Exercise Performance with Supplemental Oxygen and Hypoxic Ventilatory Drive in Patients with Chronic Airflow Obstruction

doi:10.1378/chest.95.4.751

Chest

Volume 95, Issue 4, April 1989, Pages 751-756

https://doi.org/10.1378/chest.95.4.751 Get rights and content

The purpose of this study was to determine if there is a relationship between improvement in exercise capacity with supplemental oxygen and the magnitude of hypoxic ventilatory drive in patients with CAO. We hypothesized that those patients with the highest hypoxic drives would be the most likely to have increased exercise tolerance with supplemental oxygen. Seventeen patients with CAO (mean FEV₁ = 0.99 ±0.45 L) underwent identical maximal cycle ergometry exercise tests on two occasions 45 minutes apart while breathing either air or 30 percent oxygen in a randomized single-blind fashion. With supplemental oxygen, the ventilation decreased and the PaCO₂ increased significantly at rest. The patients had a significantly greater exercise tolerance on supplemental oxygen (76.7 vs 69.1 watts, p<0.005) but no increase in the maximal ventilation. When the nine patients who improved were compared to the eight patients who did not improve, the two groups were basically identical. Specifically, there were no significant differences in the mean ventilatory or mouth occlusion responses to hypoxia or in the blood gases. The patients who did improve tended to have a greater reduction in their ventilatory response to exercise while exercising on oxygen as compared to when they were exercising on room air. From this study, it was concluded that measurements of hypoxic ventilatory drive are not helpful in predicting which patients with CAO are likely to have improved exercise capability while breathing supplemental oxygen.

Section snippets

Subjects

To be included in the study, patients were required to have a FEV₁ less than 2.5 L and to have a FEV₁/FVC less than 60 percent. In addition, their exercise tolerance had to be limited by shortness of breath. The characteristics of the 17 study patients are summarized in Table 1. All but one were men. Patients with a wide range of severity of airflow obstruction were evaluated. Patients who were taking oral theophylline and inhaled beta-adrenergic agents continued taking these medications during

Hypoxic Responses

Our patients had a broad range of hypoxic responses. The ventilation vs SaO₂ slopes varied between –0.12 and –0.66 with a mean±SD of –0.35±0.17 L/min/%SaO₂/m². The mouth occlusion pressure vs SaO₂ slopes varied between –0.02 and –0.69 with a mean of –0.24 ±0.17 cm H₂O/%SaO₂.

Resting Data

As expected, the mean PaO₂, SaO₂, and PaCO₂ were significantly higher and the $\dot{V} E$ significantly lower when the patients were breathing 30 percent oxygen as compared to room air (Table 2). When we attempted to predict

DISCUSSION

The present study confirms previous studies2, 3, 4, 5, 6, 7, 8, 9, 10, 11 which have documented that the exercise tolerance of at least some patients with CAO is improved with supplemental oxygen. At rest, the administration of oxygen to patients with CAO resulted in a significantly lower $\dot{V} E$ and a significantly higher PaCO₂ as had been reported previously.¹¹

As reported in previous studies,1, 2, 3, 7, 10 the PaCO₂ was significantly higher and the pH was significantly lower at maximum

ACKNOWLEDGMENTS

The writers thank Marian Berman for her graphics and Dr. Catherine Sassoon for her careful review of the manuscript.

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Breathlessness and portable oxygen in chronic obstructive airways disease
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Cited by (26)

Mechanisms of non-pharmacologic adjunct therapies used during exercise in COPD
2012, Respiratory Medicine
Citation Excerpt :
With these factors compounding the effects of hyperinflation, it becomes evident that the hypoxemic patient with COPD is especially susceptible to lactic acidosis, muscle fatigue and reduce exercise capacity.112,169 Administration of supplemental O2 during exercise to patients with COPD who are hypoxemic at rest and/or who desaturate with exercise has been shown to reduce VE170, RR and ventilatory drive171–173 for a given exercise work load. The lower VE which occurs secondary to a lower RR, has been reported to promote a reduction in dynamic hyperinflation,172 thus placing the diaphragm on a more optimal contractile portion of its length–tension curve.
Individuals with chronic obstructive pulmonary disease (COPD) are often limited in their ability to perform exercise due to a heightened sense of dyspnea and/or the occurrence of leg fatigue associated with a reduced ventilatory capacity and peripheral skeletal muscle dysfunction, respectively. Pulmonary rehabilitation programs have been shown to improve exercise tolerance and health related quality of life. Additional therapeutic approaches such as non-invasive ventilatory support (NIVS), heliox (He–O₂) and supplemental oxygen have been used as non-pharmacologic adjuncts to exercise to enhance the ability of patients with COPD to exercise at a higher exercise-intensity and thus improve the physiological benefits of exercise. The purpose of the current review is to examine the pathophysiology of exercise limitation in COPD and to explore the physiological mechanisms underlying the effect of the adjunct therapies on exercise in patients with COPD. This review indicates that strategies that aim to unload the respiratory muscles and enhance oxygen saturation during exercise alleviate exercise limiting factors and improve exercise performance in patients with COPD. However, available data shows significant variability in the effectiveness across patients. Further research is needed to identify the most appropriate candidates for these forms of therapies.
Does correction of exercise-induced desaturation by O<inf>2</inf> always improve exercise tolerance in COPD? A preliminary study
2008, Respiratory Medicine
Citation Excerpt :
Nevertheless, evidence has also accumulated suggesting that mere methodological considerations are probably insufficient to explain these different responses to acute oxygen supplementation. Even in studies in which subjects have undergone the same procedures,6,8,14,15 differential behaviors were sometimes observed. Notably, in a recent study of desaturation during an exercise test in COPD patients, Jolly et al.8 showed marked differences in individual response during oxygen supplementation.
This study sought to investigate whether correction of exercise-induced desaturation by oxygen supply (O₂) systematically improves exercise tolerance and cardiorespiratory adaptations in COPD patients.
Twenty-five COPD patients [FEV₁ = 52 ± 2.5% pred] exhibiting exercise-induced desaturation performed cyclo-ergometer endurance exercise at 60%of their maximal workload in two randomized conditions: air vs. O₂. O₂ was adjusted to ensure 90 ≤ SpO₂ ≤ 95%. Endurance time (Tlim), dyspnoea, ventilation ( ${\dot{V}}_{E}$ ), breathing frequency (fb), tidal volume (V_T), cardiac output (CO), heart rate (HR) and arterio-venous difference in oxygen (AVD) were compared between conditions.
The comparison of whole group performance between conditions revealed no differences, but individual analysis showed that O₂ increased Tlim for 14 patients [+68%; p < 0.01; (positive responders)], decreased it for seven [−36%; p < 0.05; (negative responders)] and induced no change for four (non-responders). For positive responders, improved performance was supported by reduced dyspnoea, ${\dot{V}}_{E}$ , fb, HR and CO and increased AVD. For negative responders, hyperoxia resulted in increased dyspnoea and fb without change in ${\dot{V}}_{E}$ or cardiovascular parameters.
For comparable correction of exercise desaturation, O₂ does not induce similar effects on exercise responses in all patients. These results were confirmed in complementary study with 11 consecutives patients at higher exercise intensity. For R+, we recorded the classic and expected O₂ effects on cardiorespiratory adaptations (i.e. reduced ventilatory demand and cardiac output). In the other group, exercise breathing frequency and dyspnoea were paradoxically increased despite desaturation correction. However, this study must be considered as pilot study, which will need to be confirmed in future studies conducted on a larger case series.
Detecting oxygen desaturation in patients with COPD: Incremental versus endurance shuttle walking
2008, Respiratory Medicine
Citation Excerpt :
We acknowledge that some patients may benefit from a higher flow rate. Leach et al.8 found that patients improved their walking distance by 67.7% whilst breathing oxygen at 4 l/min−1 compared to air. Practically this flow rate is difficult to administer as the cylinders last approximately for 20 min at a flow rate of 4 l/min−1 compared with 2 h at a flow rate of 2 l/min−1.
There has been no direct comparison between an incremental and endurance walking test to detect the relative oxygen desaturation in patients with chronic obstructive pulmonary disease (COPD). This is of some importance as current guidelines have suggested that ambulatory oxygen should only be prescribed after a standard assessment and desaturation documented. No clear advice about the nature of the required exercise task is given. This study therefore compared the relative desaturation between the incremental shuttle walking test (ISWT) and the constant speed walking test (ESWT) and response to ambulatory oxygen.
Forty-one patients (29 male), mean (SD), age 71.18 (7.48) yrs, FEV₁ 0.85 (0.29) l with stable COPD were recruited after completion of a 7-week pulmonary rehabilitation programme. Patients completed a baseline (without carrying a cylinder) ISWT and ESWT and then, in random order in double blind fashion, completed the walk tests with a cylinder of air or a cylinder of oxygen. Measurements included distance walked, oxygen saturation, heart rate, perceived breathlessness and exertion (Borg scale).
All patients desaturated (<4% below 90%). There was no significant difference in desaturation between the ISWT and the ESWT. There was a significant improvement in performance with supplementary oxygen compared to cylinder air (p < 0.05) for both tests. However, compared to the baseline walk, supplementary oxygen did not enhance the distance walked for either test. There was a significant decrease in walking performance on both the ISWT and the ESWT when carrying an air cylinder compared with the control walk. When comparing the percentage difference between oxygen and air for responders (i.e. those that achieve a 10% or more increase), the ESWT showed a greater percentage change 42.1% compared to 26.1% for the ISWT.
This study identifies that incremental and endurance walking provokes significant desaturation and that there is a short-term benefit of oxygen versus air in enhancing exercise performance. There was no significant difference in the level of desaturation between tests. Therefore the ISWT is a suitable exercise test that can be used to evaluate desaturation and is practically more realistic.
A systematic review of randomized controlled trials examining the short-term benefit of ambulatory oxygen in COPD
2007, Chest
Citation Excerpt :
Figure 1summarizes the trial flow and the metaanalysis profile as outlined in the QUOROM statement7for reporting of systematic reviews. Thirty-one studies9–39(contributing 33 data sets) with a total of 534 participants met the inclusion criteria for this review. Sample size varied from 5 to 41.
Aim:To systematically review the short-term efficacy of ambulatory oxygen from single-assessment studies in COPD.
Methods:Searches for relevant randomized controlled trials using predefined search terms were conducted on the Cochrane Airways Group Specialized Register of RCTs, the Cochrane Central Register of Controlled Trials, and other electronically available journals, databases, and search engines. All databases were searched from their inception until December 2004. Two reviewers (J.B., B.O.) independently assessed eligibility and extracted data. All trial data were combined using RevMan analyses 4.2.8 (Cochrane Collaboration;). Due to the crossover design of the studies, data were entered using the generic inverse variance method. Fixed-effect or random-effect models were used depending on the level of statistical heterogeneity observed.
Results:Thirty-one studies (33 data sets; 534 participants) met the inclusion criteria of the review. Oxygen improved the primary outcomes relating to endurance and maximal exercise capacity. For the secondary outcomes of breathlessness, arterial oxygen saturation (Sao₂), and minute ventilation (Ve), comparisons were made at isotime. Oxygen improved breathlessness, Sao₂/Pao₂, and Veat isotime with endurance exercise testing. For maximal exercise testing, data were not available in a format suitable for metaanalysis for breathlessness, but the improvement in Sao₂/Pao₂and Veat isotime was significant.
Conclusion:This review provides evidence from single-assessment studies that ambulatory oxygen improves exercise performance in COPD; however, the clinical importance of this size of improvement is unclear. Prior to widespread prescription of ambulatory oxygen, future research is required to establish the net long-term benefit of ambulatory oxygen in patients with different levels of hypoxemia or exercise-induced desaturation.
Enhancement of exercise performance in COPD patients by hyperoxia: A call for research
2002, Chest
Citation Excerpt :
The endurance time for cycling at a constant workload was increased by 51% at an O2 flow rate of 2 L/min, by 88% at 4 L/min, and by 80% at 6 L/min. Light et al15 studied the relationship between improvement in exercise performance on O2 supplementation therapy and the magnitude of hypoxic ventilatory drive in 17 patients with COPD (ie, mean FEV1, 0.99 L) and mild hypoxemia (ie, mean Pao2, 68.7 mm Hg). Identical maximal cycle ergometer exercise was carried out breathing air or 30% O2.
This essay summarizes 16 reports, published since 1956, that describe the effects of hyperoxia on exercise endurance in persons with COPD who have severe airflow obstruction (ie, FEV₁ < 1.0 L or < 39% of predicted) and mild hypoxemia at rest (ie, Pao₂ > 62 mm Hg or arterial oxygen saturation [Sao₂] measured by pulse oximetry of > 91%). The term hyperoxia is used because, in a proportion of study participants, oxygen administration increased exercise endurance in a dose-dependent fashion, up to a fraction of inspired oxygen of 0.5 or a flow of 100% O₂ of 6 L/min. The process appears to be dependent on an increase in Pao₂ rather than on the restoration of Sao₂ to normal levels. The results of pulmonary function tests were not predictive of response. Increased exercise performance was associated with a decrease in dyspnea, respiratory frequency, and minute ventilation. The slowing of respiratory frequency and the decrease in pulmonary air trapping likely accounted for the decrease in dyspnea. Slowing of the respiratory rate, which occurred at the expense of the retention of CO₂, is most likely due to a hyperoxia-induced decrease in chemoreceptor ventilatory drive from the aortic and carotid bodies. Research is called for to determine the following: (1) the prevalence of COPD patients who have severe airflow limitation accompanied by mild hypoxemia; (2) the proportion of these patients who show improvements in exercise performance during a test of hyperoxic exercise; and (3) whether enhanced exercise performance during a brief test translates into a meaningful increase in the ability to perform the activities of daily living.
Effect of 30 mg of morphine alone or with promethazine or prochlorperazine on the exercise capacity of patients with COPD
1996, Chest
We have shown that the administration of 0.8 mg/kg of morphine (M) to patients with COPD resulted in a 20% increase in the maximum oxygen consumption ( ${\dot{V} o}_{2} max$ ) but was associated with significant drowsiness and euphoria. The objective of the present study was to ascertain whether lower doses of M alone or in combination with prochlorperazine (PC) or promethazine (P) could elicit significant increases in exercise tolerance.
The exercise capacity, psychological status, and reaction times were assessed before and 60 min after the patients received placebo (PLAC), 30 mg M orally, 30 mg M plus 10 mg PC (M-PC), or 30 mg M plus 25 mg P (M-P) in a randomized double-blind crossover study. In a secondary study, nine patients were tested on three separate days before and after receiving PLAC, 25 mg P, or 30 mg M plus 25 mg P.
Seven COPD patients (FEV₁=0.99 ±0.30 L, ${\dot{V} o}_{2} max$ max=990±315 mL/min) who were ventilatory-limited.
Veterans Affairs medical center.
After the patients ingested M-P, the increase in the ${\dot{V} o}_{2} max$ max (129.0±104 mL/min), the workload (10.0 ±6.5 W) and the maximum minute ventilation (4.0±3.9 L/min) were significantly greater (p<0.05) than after PLAC ingestion (-4.8±79 mL/min, 1.4±6.9 W, and −1.6±2.4 L/min, respectively). Changes after the ingestion of M, P, or M-PC were intermediate. The M-PC combination adversely affected the patient's reported mental status (Bond visual analog scale) more than the M-P or M regimens. No regimen significantly affected the reaction time.
We conclude that the administration of 30 mg of M plus 25 mg of P significantly improves the exercise tolerance of patients with COPD, without significantly impairing the mental capabilities of the subjects. The utility of this regimen over longer time periods needs to be evaluated.

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: Manuscript received April 29; revision accepted August 12.

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Chest

Clinical InvestigationsRelationship between Improvement in Exercise Performance with Supplemental Oxygen and Hypoxic Ventilatory Drive in Patients with Chronic Airflow Obstruction

Section snippets

Subjects

Hypoxic Responses

Resting Data

DISCUSSION

ACKNOWLEDGMENTS

Lancet

Lancet

Chest

Exercise tolerance breathing a low density gas mixture, 35% oxygen and air in patients with chronic obstructive bronchitis

Clin Science

Response to patients with chronic airway obstruction

Am Rev Respir Dis

Oxygen-assisted exercise in chronic obstructive lung disease

Am Rev Respir Dis

Effects of dihydrocodeine, alcohol, and caffeine on breathlessness and exercise tolerance in patients with chronic obstructive lung disease and normal blood gases

N Engl J Med

Effect of oxygen on breathing during exercise in patients with chronic obstructive lung disease

Eur J Respir Dis

Breathlessness and portable oxygen in chronic obstructive airways disease

Thorax

Clinical Investigations
Relationship between Improvement in Exercise Performance with Supplemental Oxygen and Hypoxic Ventilatory Drive in Patients with Chronic Airflow Obstruction