Translational Respiratory Medicine

Translational Respiratory Medicine Cover Image
Editorial
Open Access

The effect of high concentration oxygen therapy on PaCO2 in acute and chronic respiratory disorders

Translational Respiratory Medicine20131:8

https://doi.org/10.1186/2213-0802-1-8

©  Pilcher et al.; licensee Springer. 2013

Received: 19 March 2013

Accepted: 19 March 2013

Published: 4 April 2013

Abstract

There is evidence that the potential for high concentration oxygen therapy to increase PaCO2 is not limited to stable and acute exacerbations of COPD, but also to other acute respiratory disorders with abnormal gas exchange such as asthma and pneumonia, and chronic respiratory conditions with hypercapnia such as obesity hypoventilation syndrome. This evidence forms the basis of consensus guidelines which recommend that oxygen therapy is titrated in COPD and other respiratory conditions, to ensure the maximal benefits of oxygen therapy are achieved while reducing the potential for harm due to hyperoxia.

Introduction

The risks associated with high concentration oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease (COPD) were reported over 50 years ago [1]. Since then it has been demonstrated that high concentration oxygen therapy can cause an increase in PaCO2 in both stable COPD and exacerbations of COPD, and that in some patients the effect can be both rapid and marked with an increase in PaCO2 of >20 mmHg within 60 minutes [2]. The clinical significance of this effect is evident from the recent randomised controlled trial (RCT) which demonstrated that in acute exacerbations of COPD, high concentration oxygen therapy in the pre-hospital setting significantly increases mortality compared with a titrated regimen to achieve arterial oxygen saturations between 88% and 92% [3]. In patients with confirmed COPD who received oxygen therapy treatments as per protocol, the PaCO2 was 34 mmHg higher in the high concentration oxygen therapy group (Table  1).
Table 1

High concentration versus titrated oxygen therapy in the pre-hospital setting in patients with confirmed COPD

 

High concentration

Titrated

Relative risk (95% CI)

Difference

P Value

Mortality

9%

2%

0.22 (0.5 to 0.91)

 

0.04

Ventilation

14%

10%

0.67 (0.29 to 1.54)

 

0.34

Arterial blood gases†

     

 Mean (SD) pH

7.29 (0.15)

7.41 (0.09)

 

0.12

0.01

 Mean (SD) PaCO2 (mmHg)

76.5 (50.2)

42.9 (14.2)

 

−33.6

0.02

 Mean (SD) PaO2 (mmHg)

98.4 (46.1)

81.5 (30.9)

 

−16.9

0.46

† Treatment per protocol analysis.

Reproduced with modification from reference [3].

The main mechanisms responsible for the increase in PaCO2 with high concentration oxygen therapy are a reduction in respiratory drive and worsening ventilation/perfusion mismatch due to release of hypoxic pulmonary vasoconstriction [2, 4–7]. Ventilation-perfusion mismatch is also a predominant gas exchange abnormality in other acute respiratory disorders such as asthma and pneumonia, with the degree of mismatch worsening with the administration of oxygen [8–14]. As a result it would be expected that high concentration oxygen therapy would cause an increase in PaCO2 in severe asthma and pneumonia, similar to its administration in acute exacerbations of COPD.

Recently a series of RCTs has demonstrated that high concentration oxygen treatment results in a significant increase in PaCO2 or transcutaneous carbon dioxide tension (PtCO2) in patients presenting with severe exacerbations of asthma [15–17]. The clinical significance of this physiological effect is suggested by the observation that 10% of patients randomised to high concentration oxygen therapy had an increase in PtCO2 of ≥10 mmHg and a PtCO2 ≥45 mmHg after 60 minutes of treatment, whereas no patients receiving titrated oxygen therapy to maintain the arterial oxygen saturations between 93 and 95% had this response (Figure 1) [15]. In a similar RCT, high concentration oxygen therapy was also shown to increase the PtCO2 in patients presenting with community-acquired pneumonia when compared with the titrated oxygen regimen which avoided both hypoxia and hyperoxia [18]. The three- and six-fold relative risks of an increase in PtCO2 of at least 4 mmHg and at least 8 mmHg respectively, suggest that this effect may potentially be of both physiological and clinical significance (Table  2).
Figure 1

The transcutaneous partial pressure of carbon dioxide (PtCO 2 ) levels at baseline and after 60 min of high concentration (open circles) or titrated (filled circles) oxygen in patients presenting to the Emergency Department with a severe exacerbation of asthma. Reproduced from reference [15].

Table 2

The proportion of patients with community-acquired pneumonia with a rise in PtCO 2 from baseline after 60 minutes of high concentration or titrated oxygen therapy

 

High concentration

Titrated

Relative risk

P value

 

n (%)

n (%)

(95% CI)

 

Change in PtCO2 ≥4 mmHg

36 (50%)

11 (14.7%)

3.4 (1.9 to 6.2)

<0.001

Change in PtCO2 ≥8 mmHg

11 (15.3%)

2 (2.7%)

5.7 (1.3 to 25.0)

0.007

Reproduced with modification from reference [18].

Chronic respiratory failure may also occur in other chronic respiratory disorders such as obesity hypoventilation syndrome [19], so it might be expected that high concentration oxygen therapy could cause CO2 retention in this condition, similar to stable COPD. This physiological effect has recently been demonstrated in a randomised placebo-controlled trial of 100% oxygen and room air in patients with obesity hypoventilation syndrome and baseline hypercapnia (Figure 2) [20]. The main mechanism responsible for the worsening hypercapnia when breathing 100% oxygen was a reduction in minute ventilation, leading to alveolar hypoventilation. The clinical significance of this physiological effect was suggested by the requirement to terminate the study in one in eight of the patients studied, due to an increase in PtCO2 ≥10 mmHg within 20 minutes of receiving 100% oxygen therapy.
Figure 2

The change in PtCO 2 (mmHg) from baseline following breathing 100% oxygen or room air in subjects with obesity hypoventilation syndrome. The vertical lines are the mean (central horizontal line) ±1 SD for 20 min PtCO2 minus baseline. Reproduced from reference [20].

Thus there is evidence that the potential for high concentration oxygen therapy to increase PaCO2 is not limited to stable and acute exacerbations of COPD, but also to other acute respiratory disorders with abnormal gas exchange such as asthma and pneumonia, and chronic respiratory conditions with hypercapnia such as obesity hypoventilation syndrome. This evidence forms the basis of consensus guidelines [21] which recommend that oxygen therapy is titrated in COPD and other respiratory conditions, to ensure the maximal benefits of oxygen therapy are achieved while reducing the potential for harm due to hyperoxia.

Declarations

Acknowledgements

JP is a Health Research Council of New Zealand Clinical Research Training Fellow.

Authors’ Affiliations

(1)
Medical Research Institute of New Zealand
(2)
Wellington Regional Hospital, Capital & Coast District Health Board
(3)
School of Biological Sciences, Victoria University of Wellington

References

  1. Campbell EJ: Respiratory failure: the relation between oxygen concentrations of inspired air and arterial blood. Lancet 1960, 2: 10–11.PubMedView ArticleGoogle Scholar
  2. Murphy R, Driscoll P, O'Driscoll R: Emergency oxygen therapy for the COPD patient. Emerg Med J 2001, 18: 333–339. 10.1136/emj.18.5.333PubMed CentralPubMedView ArticleGoogle Scholar
  3. Austin MA, Wills KE, Blizzard L, Walters EH, Wood-Baker R: Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ 2010, 341: c5462. 10.1136/bmj.c5462PubMed CentralPubMedView ArticleGoogle Scholar
  4. Aubier M, Murciano D, Milic-Emili J, Touaty E, Daghfous J, Pariente R, Derenne J-P: Effects of the administration of O 2 on ventilation and blood gases in patients with chronic obstructive pulmonary disease during acute respiratory failure. Am Rev Respir Dis 1980, 122: 747–754.PubMedGoogle Scholar
  5. Dick C, Liu Z, Sassoon C, Berry RB, Mahutte CK: O 2 -induced change in ventilation and ventilatory drive in COPD. Am J Respir Crit Care Med 1997, 155: 609–614. 10.1164/ajrccm.155.2.9032202PubMedView ArticleGoogle Scholar
  6. Robinson TD, Freiberg DB, Regnis JA, Young IH: The role of hypoventilation and ventilation-perfusion redistribution in oxygen-induced hypercapnia during acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000, 161: 1524–1529. 10.1164/ajrccm.161.5.9904119PubMedView ArticleGoogle Scholar
  7. Sassoon CS, Hassell KT, Mahutte CK: Hyperoxic-induced hypercapnia in stable chronic obstructive pulmonary disease. Am Rev Respir Dis 1987, 135: 907–911.PubMedGoogle Scholar
  8. Ballester E, Reyes A, Roca J, Guitart R, Wagner PD, Rodriguez-Roisin R: Ventilation-perfusion mismatching in acute severe asthma: effects of salbutamol and 100% oxygen. Thorax 1989, 44: 258–267. 10.1136/thx.44.4.258PubMed CentralPubMedView ArticleGoogle Scholar
  9. Corte P, Young IH: Ventilation-perfusion relationships in symptomatic asthma. Response to oxygen and clemastine. Chest 1985, 88: 167–175. 10.1378/chest.88.2.167PubMedView ArticleGoogle Scholar
  10. Field GB: The effects of posture, oxygen, isoproterenol and atropine on ventilation-perfusion relationships in the lung in asthma. Clin Sci 1967, 32: 279–288.PubMedGoogle Scholar
  11. Rodriguez-Roisin R, Ballester E, Roca J, Torres A, Wagner PD: Mechanisms of hypoxemia in patients with status asthmaticus requiring mechanical ventilation. Am Rev Respir Dis 1989, 139: 732–739. 10.1164/ajrccm/139.3.732PubMedView ArticleGoogle Scholar
  12. Gea J, Roca J, Torres A, Agusti AG, Wagner PD, Rodriguez-Roisin R: Mechanisms of abnormal gas exchange in patients with pneumonia. Anesthesiology 1991, 75: 782–789. 10.1097/00000542-199111000-00009PubMedView ArticleGoogle Scholar
  13. Light RB: Pulmonary pathophysiology of pneumococcal pneumonia. Semin Respir Infect 1999, 14: 218–226.PubMedGoogle Scholar
  14. Rodriguez-Roisin R, Roca J: Update ’96 on pulmonary gas exchange pathophysiology in pneumonia. Semin Respir Infect 1996, 11: 3–12.PubMedGoogle Scholar
  15. Perrin K, Wijesinghe M, Healy B, Wadsworth K, Bowditch R, Bibby S, Baker T, Weatherall M, Beasley R: Randomised controlled trial of high concentration versus titrated oxygen therapy in severe exacerbations of asthma. Thorax 2011, 66: 937–941. 10.1136/thx.2010.155259PubMedView ArticleGoogle Scholar
  16. Chien JW, Ciufo R, Novak R, Skowronski M, Nelson J, Coreno A, McFadden ER Jr: Uncontrolled oxygen administration and respiratory failure in acute asthma. Chest 2000, 117: 728e33.View ArticleGoogle Scholar
  17. Rodrigo GJ, Rodriquez Verde M, Peregalli V, Rodrigo C: Effects of short-term 28% and 100% oxygen on PaCO2 and peak expiratory flow rate in acute asthma: a randomized trial. Chest 2003, 124: 1312e17.View ArticleGoogle Scholar
  18. Wijesinghe M, Perrin K, Healy B, Weatherall M, Beasley R: Randomized controlled trial of high concentration oxygen in suspected community-acquired pneumonia. J R Soc Med 2012, 105: 208–216. 10.1258/jrsm.2012.110084PubMed CentralPubMedView ArticleGoogle Scholar
  19. Nowbar S, Burkart KM, Gonzales R, Fedorowicz A, Gozansky WS, Gaudio JC, Taylor MR, Zwillich CW: Obesity-associated hypoventilation in hospitalized patients: prevalence, effects, and outcome. Am J Med 2004, 116: 1–7.PubMedView ArticleGoogle Scholar
  20. Wijesinghe M, Williams M, Perrin K, Weatherall M, Beasley R: The effect of supplemental oxygen on hypercapnia in subjects with obesity-associated hypoventilation: a randomized, crossover clinical study. Chest 2011, 139: 1018–1024. 10.1378/chest.10-1280PubMedView ArticleGoogle Scholar
  21. O’Driscoll BR, Howard LS, Davison AG: British Thoracic Society guideline for emergency oxygen use in adult patients. Thorax 2008,63(Suppl 6):vi1–68.PubMedGoogle Scholar

Copyright

© Pilcher et al.; licensee Springer. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.