7/27/2019 COPD Schmidt Hall

1/2

Oxygen therapy and hypoxic drive to breathe: is there danger in the patient with COPD?Schmidt GA, Hall JB. Critical Care Digest 1989;8:52-53.

Acute deterioration of chronic obstructive pulmonary disease (COPD) is marked by a rising PaCO2

and hypoxemia. This hypoxemia can lead to end-organ dysfunction including mental impairment and

myocardial ischemia. Since much of the hypoxemia of COPD is due to mismatching of ventilation

and perfusion, it is substantially relieved by oxygen enrichment of inspired air.1

Physicians who first began to give oxygen therapy to patients with exacerbations of COPD made

two observations that became causally linked. First, the partial pressure of arterial CO2 often rose after

oxygen was applied. Second, some patients became progressively obtunded, eventually requiring

mechanical ventilation. A theory arose proposing that patients with a chronically elevated PaCO2received their drive to breathe largely from hypoxia. Relief of hypoxemia abolished drive, causing

hypoventilation, elevation of PaCO2 and CO2 'narcosis'.

A high art developed around the proper means to administer very low flow or carefully controlled

oxygen. Special masks were designed that could give a known and fixed inspired oxygen concen-

tration, based on the Venturi principle. E.J.M. Campbell directed his J Burns Amberson Lecture at

teaching pulmonary physicians how to avoid doing harm with oxygen.2

Several generations of

medical students were inculcated with the dangers of oxygen therapy, and this notion found a place inmany textbooks of general and pulmonary medicine.

Of interest, limited attention was paid to testing this hypothesis by giving oxygen and

simultaneously measuring ventilation. Pain, Read and Read3

gave oxygen to patients with

obstructive lung disease and found that the rise in PaCO2 could not be accounted for by

hypoventilation. In a follow up study, Lee and Read4 found that in some patients ventilation

decreased, in some it was unchanged, and in the rest, ventilation increased. The commonest pattern

was of early hypoventilation followed by a return to baseline. Lee and Read attributed the rise inPaCO2 to an increase in the dead space to tidal volume ratio consequent to oxygen therapy, though the

mechanism for this change is unclear.

Aubier and colleagues gave oxygen to twenty patients with acute on chronic respiratory failure,raising their PaO2 to an average of 120 mm Hg.5 Minute ventilation fell 14% on average, but was not

correlated with the rise in PaCO2. Despite the abolition of any hypoxic stimulus in most patients,

respiratory drive assessed by mouth occlusion pressure (P 0.l) was three times normal after

oxygen. In a subsequent study6 100% oxygen was given to twenty-two patients, and again the rise in

PaCO2 could not be accounted for by hypoventilation. Aubier et al also attributed this to worsening of

ventilation-perfusion matching.

Stradling has criticized this work, speculating that hypoventilation due to abolition of drive does

account for the hypercapnia, even using the data of Aubier et al.7,8

He has argued that when the

alveolar volume of each breath is very small and the dead space is very high and largely fixed, minor

decrements in tidal volume can lead to large proportional changes in alveolar ventilation, and

therefore in PaCO2.In reply, Aubier et al have given further data that convincingly support their

contention.9

In eleven of their twenty-two patients tidal volume increasedwith oxygen therapy anaverage of 37cc. The PaCO2 rose in this subset by 25mm Hg, an amount even greater than in the

eleven patients whose tidal volume fell. In yet another study, Sassoon has confirmed Aubier's findings

in patients with stable COPD, also concluding that impairment of gas exchange, not

hypoventilation, accounts for the hypercapnia of oxygen therapy.10

This debate has become important in view of hypotheses regarding the central role of diaphragm

fatigue in the pathogenesis of ventilatory failure. New investigations suggest that when the energy

demands of the inspiratory muscles exceed the energy supply, fatigue ensues leading to

7/27/2019 COPD Schmidt Hall

2/2

respiratory failure. The oxygen cost of breathing is known to be high in ill patients with COPD.11

Reduced oxygen supply to respiratory muscles is implicated in the genesis of ventilatory failure in

experimental animals.12

In this formulation, patients with COPD may be perched on a precipice,

with respiratory muscle demand nearly outstripping supply. Small increments in demand, such as

worse bronchospasm, new infection, and even splinting due to rib fracture, will precipitate respiratory

failure. One might predict that patients with COPD would also be particularly sensitive to decrements

in the supply of oxygen to their respiratory muscles. Parsimony in the application of oxygen mightthen contribute to ventilatory failure. We believe that the risks of oxygen therapy in patients with

COPD are typically overblown in the clinical literature. The purportedly devastating hypoventilation

after oxygen is, in fact, trivial and of no demonstrated relevance. Until further data support a

detrimental effect, we conclude that adequate oxygenation is critical, not only for respiratory muscle

function, but also for optimal cardiac and neurologic function. Withholding of sufficient oxygen, in an

attempt to maintain ventilatory drive, is ill-advised and may cause harm. Of course, some patients

with acute or chronic respiratory failure will progress to ventilatory failure despite, not because of

oxygen therapy, and require mechanical ventilation. Whilst the average rise in PaCO2in Aubier'sstudy6 was from 65 ( 30mmHg breathing air to 88 (5) mm Hg breathing oxygen, there is no level of

PaCO2 we would regard as unacceptable per se since we have seen several patients with COPD with a

PaCO2 > 150mm Hg, who were awake, alert and stable.We prefer to manage these patients by

clinical assessment (mentation, work of breathing) rather than by arbitrary laboratory values.

In a practical sense, we are advocating no great change in the way patients are managed. All

physicians make adequate oxyhemoglobin saturation a treatment goal. Since ninety percent

saturation of hemoglobin requires a PaO2 of only about 60 mmHg, we are not suggesting large

increments in inspired oxygen. Our guiding principle of oxygen therapy is different, however.

Oxygen is good and necessary, particularly in incipient ventilatory failure, not a treacherous

commodity to be sparingly meted out. In the early titration of therapy we take care to provide

enough of this essential nutrient, rather than to excessively 'toe the line' of just tolerable oxygenation.

Our patients will benefit if we reconsider the way we teach the oxygen management of patients with

COPD.

Gregory A. Schmidt, M.D.Assistant Professor of Medicine.Section of Pulmonary and Critical Cure Medicine.Department of Medicine.The University of Chicago

Jesse B. Hall, M.D.Associate Professor of Medicine.Section of Pulmonary and Critical Care MedicineDepartment of MedicineThe University of Chicago

1. Wagner P, Dantzker D, Dueck D, et al. Ventilation-perfusion inequality in chronic obstructive pulmonary disease.J.ClinInvest1977;59:203-16.2. Campbell EJM. The J Burns Amberson Lecture. The management of acute respiratory failure in chronic bronchitis and emphysema.Am Rev Respir Dis1967; 96: 626-39.3. Pain MCF, Read DJC, Read J. Changes of arterial carbon dioxide tension in patients with chronic lung disease breathing oxygen.Aust Ann Med1965;

14: 195.4. Lee J, Read J . Effect of oxygen breathing on distribution of pulmonary blood flow in chronic obstructive lung disease.Am Rev Respir Dis1967; 96:1173-80.5. Aubier M, Murciano D, Fournier M et al. Central respiratory drive in acute respiratory failure of patients with chronic obstructive pulmonary disease.Am Rev Respir Dis 1980; 122: 191-9.6. Aubier M, Murciano D, Millic-Emili J, et al. Effects of the administration of O2 on ventilation and blood gases in patients with chronic obstructivepulmonary disease during acute respiratory failure. Am Rev Respir Dis 1980; 122: 747-54.7. Stradling JR. Hypercapnia during oxygen therapy in airways obstruction: a reappraisal. Thorax 1986; 41: 897-902.8. Stradling J. Effects of the administration of O2 on ventilation and blood gases in patients with chronic obstructive pulmonary disease during acute

respiratory failure (letter).Am Rev Respir Dis 1987; 135:274.9. Aubier M, Murciano D, Millic-Emili J, et al. Effects of the administration of O2 on ventilation and blood gases in patients with chronic obstructivepulmonary disease during acute respiratory failure (letter).Am Rev Respir Dis 1987; 135: 274.10. Sassoon CSH, Hassell KT, Mahutte CK. Hyperoxic-induced hypercapnia in stable chronic obstructive pulmonary disease.Am Rev Respir Dis 1987;

135:907-11.11. Field S, Kelly S, Macklem PT. The oxygen cost of breathing in patients with cardio-respiratory disease.Am Rev Respir Dis 1982; 126: 9-13.12. Aubier M, Trippenbach T, Roussos C. Respiratory muscle fatigue during cardiogenic shock. J Appl Physiol1981; 51: 496-508.