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Long term o2 therapy

http://www.nejm.org/doi/full/10.1056/NEJM199509143331107

Long-Term Oxygen Therapy

Stephen P. Tarpy, M.D., and Bartolome R. Celli, M.D.

N Engl J Med 1995; 333:710-714September 14, 1995

ArticleReferences

Citing Articles (25)

The concept of oxygen as a therapeutic agent was introduced in the 1920s by Alvin Barach.1 Since

then, a better understanding of the effects of hypoxemia, and of their reversal with oxygen

supplementation, has enhanced the treatment of patients with pulmonary diseases. There are close

to 800,000 patients receiving long-term oxygen therapy in the United States, at a yearly cost of $1.8

billion.2,3 We need to understand the effects of oxygen therapy, the indications for it, and its modes

of delivery in order to make the most appropriate use of this effective therapeutic resource. In this

article, we discuss long-term oxygen therapy, emphasizing its use in the care of patients with chronic

obstructive pulmonary disease, the application that has been most carefully studied.4-9 Some of the

same principles may apply to the treatment of patients with interstitial and neuromuscular diseases.

Physiologic Responses to HypoxemiaHypoxemia induces several physiologic responses designed to maintain adequate oxygen delivery to

the tissues. At a partial pressure of arterial oxygen (PaO2) below 55 mm Hg, ventilatory drive

increases, leading to a higher PaO2 and a lower partial pressure of carbon dioxide (PaCO2). The

vascular beds supplying hypoxic tissue dilate, inducing a compensatory tachycardia that increases

cardiac output and improves oxygen delivery. The pulmonary vasculature constricts in response to

alveolar hypoxia, thereby improving the match between ventilation and perfusion in the affected

lung. Subsequently, the secretion of erythropoietin by the kidney causes erythrocytosis, thus

increasing the oxygen-carrying capacity of the blood and oxygen delivery. These early benefits may

have detrimental long-term effects, however (Figure 1Figure 1Short-Term and Long-Term Effects of

Hypoxemia on the Respiratory, Cardiovascular, and Hematologic Systems.).

Figure 1Effect Possible Benefits Negative consequence

Respiratory

Hypoxemia

Ventilation PaO2 work of breathing

Cardiovascular

HR & Stroke

Vol

Improve Ventilation

Perfusion matching

PaO2 & O2 delivery

Pulmonary artery

pressure

myocardial workHematologic

Erythropoetin

& Hb

concentration

O2 carrying capacity

Prolonged vasoconstriction, erythrocytosis, and increased cardiac output cause pulmonary

hypertension, right ventricular failure, and often death.4-9 The cost of breathing in terms of

increased ventilation and oxygen demand may contribute to chronic malnutrition in patients with

severe obstructive pulmonary disease.10

Effects of Long-Term Oxygen Therapy

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In patients with hypoxemia, oxygen supplementation improves survival, pulmonary hemodynamics,

exercise capacity, and neuropsychological performance. It may also decrease the oxygen cost of

breathing and improve the quality of sleep.

Survival

Long-term oxygen therapy improves survival. In a study by the British Medical Research Council,

patients with hypoxemia were randomly assigned to receive 15 hours of continuous oxygen or nooxygen. During five years of follow-up, 19 of 42 patients treated with oxygen died, as compared with

30 of 45 controls.9 In the Nocturnal Oxygen Therapy Trial (NOTT), patients were randomly assigned

to either 12 or 24 hours of daily oxygen therapy. After 26 months, mortality in the continuous-

treatment group was half that in the 12-hour group.8 Because the improvement in survival with

long-term oxygen therapy seems to be proportional to the number of hours of therapy, the current

recommendation for patients with hypoxemia (defined as a PaO2 of 56%)

Resting Pa O2 >59 mmHg or O2 saturation >89%

Reimbursable only with additional documentation justifying the O2 prescription & a summary of

more conservative therapy that has failed

Non Continuous Oxygen

O2 flow rate & no of hours per day must be specified

*During exercise: PaO2 55 mmHg or O2 saturation 88% with a low level of exertion

*During sleep: PaO2 55 mmHg or O2 saturation 88% with associated complications such as

pulmonary hypertension, daytime somnolence & cardiac arrhythmias.

Patients with a PaO2 of 56 to 59 mm Hg or an oxygen saturation of 89 percent, cor pulmonale, or

polycythemia should also receive long-term oxygen therapy.

Patients receiving long-term oxygen therapy should be reevaluated within two months to assess

whether hypoxemia persists. Up to 40 percent of treated patients have sufficient improvement after

one month to make continued supplemental oxygen unnecessary.8,11

Pulmonary Hemodynamics

Supplemental oxygen can improve pulmonary hemodynamicsand reduce cardiac work. Right heart

catheterization was performed in 16 patients who had hypoxemia with chronic obstructive

pulmonary disease 41 months before, just before, and 31 months after oxygen therapy.7 Before

therapy, there was a mean (SD) yearly increase in the pulmonary-artery pressure of 1.472.3 mmHg. After supplemental oxygen therapy, the pressure improved in 12 of the patients, with a mean

annual decrease of 2.154.4 mm Hg. In the NOTT study, six months of oxygen significantly improved

pulmonary-artery pressure, peripheral vascular resistance, and stroke volume at rest and during

exercise.6

The condition of many patients worsens despite supplemental oxygen. Early identification of these

patients would allow them to avoid the cost and inconvenience of therapy. Unfortunately, attempts

to correlate short-term hemodynamic responses to oxygen with long-term survival have not

succeeded.6,12,13 The use of noninvasive methods to predict the response to oxygen, such as

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oxygen uptake during maximal exercise12 or the change in the right ventricular ejection fraction

after oxygen therapy,14 have been disappointing. Therefore, long-term oxygen therapy is indicated

for all patients who have hypoxemia as defined above, since some benefit is possible and other

options are limited.

Exercise Capacity

Ventilatory rather than circulatory factors limit exercise in many patients with airflow obstruction.15Supplemental oxygen increases the distance patients can walk and their endurance in tests on a

treadmill or a bicycle.16-18 In patients with hypoxemia and those who have oxygen desaturation

with exercise, supplemental oxygen increases oxygen delivery and its utilization by muscles during

exercise.19,20 However, increased oxygen saturation does not predict improved exercise

performance.16 Supplemental oxygen also reduces minute ventilation and the respiratory rate for a

given workload.17 In addition, it improves ventilatory-muscle function during exercise by postponing

the onset of respiratory-muscle fatigue and improving the capacity of the diaphragm to sustain

work.21 Supplemental oxygen may also decrease dyspnea and improve endurance by directly

reducing chemoreceptor activity.18 Currently, supplemental oxygen during exercise should be

prescribed for patients with a documented PaO2 of 55 mm Hg or less or oxygen saturation of 88

percent or less during exercise. In the future, measures of exercise endurance, dyspnea, and

ventilatory-muscle fatigue may serve as criteria for prescribing supplemental oxygen.

The Work of Breathing

Supplemental oxygen decreases minute ventilation and the oxygen cost of breathing,22-25 but the

mechanisms by which it does so are not clear.25,26 The beneficial effect of oxygen on ventilation

and the work of breathing may help explain the decreased sensation of dyspnea that patients with

mild hypoxemia experience when given oxygen. Currently, a desire to decrease the work of

breathing is not an accepted indication for the long-term administration of oxygen.

Neuropsychological Effects

Hypoxemia (PaO2, 45 to 60 mm Hg) impairs judgment, learning, and short-term memory in young

men.27 It also decreases neuropsychological performance in patients with chronic obstructive

pulmonary disease.28,29 The NOTT investigators studied neuropsychological performance in 203patients with a mean PaO2 of 51 mm Hg,30 whereas the Canadian Intermittent Positive Pressure

Breathing Trial included 100 patients with less severe hypoxemia (mean PaO2, 66 mm Hg).31 Both

these studies demonstrated an increase in the frequency of neuropsychological deficits as the PaO2

decreased. The incidence ranged from 27 percent in patients with mild hypoxemia (PaO2, >60 mm

Hg) to 61 percent in those with severe hypoxemia (PaO2,

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mm Hg.39,40

Patients with chronic obstructive pulmonary disease have poor-quality sleep41 and frequent

arousals during periods of desaturation.42 It is unclear whether supplemental oxygen improves the

quality of sleep.41,42 Patients who have hypoxemia while awake should receive supplemental

oxygen during sleep. In addition, patients with nocturnal desaturation (oxygen saturation,

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Most patients require a stationary source of supplemental oxygen, usually an oxygen concentrator.

Concentrators are relatively inexpensive ($1,500) and require little maintenance. Oxygen

concentrators are electrical devices that use a molecular sieve to separate oxygen from air, thereby

delivering supplemental oxygen to the patient while returning nitrogen to the atmosphere. Because

the concentrators weigh about 35 lb (16 kg) and require wall current to operate, they are used as a

fixed source of oxygen.

Unless they are immobile or confined to bed, patients should have both stationary and mobilesystems of oxygen delivery. Compressed gas or liquid oxygen can be portable sources of oxygen.

Compressed oxygen is provided in high-pressure cylinders. In the United States, standard sizes are

200, 16, 9, and 3 lb (91, 7, 4, and 1.4 kg). These cylinders provide oxygen at a flow rate of 2 liters per

minute for 2.4 days, 5.2 hours, 2 hours, and 1.2 hours, respectively. Cylinders are bulky and require

frequent refills. The smaller units, however, are quite portable and, coupled with electronic oxygen-

conserving devices, may deliver oxygen for as long as eight hours.

Oxygen stored at temperatures below -183C becomes a liquid. The volume of liquid oxygen is less

than 1 percent of the volume of a comparable amount of atmospheric oxygen. Stationary units of

liquid oxygen typically weigh 240 lb (109 kg) and provide seven days of continuous oxygen at a flow

rate of 2 liters per minute. The portable 9.5-lb (4.3-kg) and 6.5-lb (3-kg) containers provide oxygen

for eight and four hours, respectively, at the same flow rate. As compared with oxygen in the form of

a compressed gas, a container of liquid oxygen of equivalent weight will last four times longer at agiven flow rate. Although liquid oxygen is more portable and containers are easier to refill than high-

pressure cylinders, there are several disadvantages. Liquid oxygen has a higher cost ($3,500 for a

stationary system, as compared with $350 for a compressed-oxygen tank), and coupling devices for

stationary and portable systems made by different manufacturers may not be compatible. The

liquid-oxygen tanks also need pressure-relief venting as the tanks warm up and the gas expands; this

process wastes unused oxygen.

Liquid oxygen is particularly desirable for active patients. A study comparing two types of portable

oxygen systems, gaseous and liquid, found that patients used liquid oxygen more hours per day

(23.5 vs. 10) and left their houses for more hours per week (19.5 vs. 15.5).45

Misconceptions and Hazards

There is no place in medical care for the administration of short courses of oxygen. Temporaryoxygen is indicated during sleep and exercise when hypoxemia is present only during those activities.

Patients may want to avoid continuous oxygen therapy, fearing that it may cause addiction.

Education about the difference between an addictive substance and a necessary one frequently

resolves the problem. In some patients, arterial oxygen pressure may return to levels higher than 60

mm Hg after prolonged therapy. In such cases, physicians (sometimes pressed by the patients) are

tempted to discontinue the oxygen. If this is done, the patients should be closely followed, because

their condition frequently deteriorates to a point at which supplemental oxygen is again needed.

Supplemental oxygen is a fire hazard. Patients must abstain from smoking something that will also

help their lung disease. Tanks should be safely secured to a wall, to prevent both disconnection of

the regulator and explosion if the tank falls. Tanks should be stored away from heaters and furnaces.

Low-flow supplemental oxygen has been remarkably free of important side effects, but occasional

patients report local irritation in the nose and eyes. In some patients higher oxygen flows may

induce some retention of carbon dioxide. This hazard is best avoided by careful adjustment of the

flow rate of supplemental oxygen to maintain the PaO2 between 60 and 65 mm Hg.

Oxygen-Administration Devices

Patients usually receive oxygen through a nasal cannula. Oxygen at a flow rate of 2 liters per minute

increases the fraction of inspired oxygen from 21 percent to approximately 27 percent.2 Although

effective, this method is inefficient. During the respiratory cycle, the movement of oxygen to the

lungs occurs only during early inhalation one sixth of the cycle. Alveolar ventilation does not occur

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during late inspiration and exhalation.2,22 Only oxygen flowing during early inspiration gets to the

alveoli; the remainder is wasted.

To improve the efficiency of oxygen delivery, several devices have been designed (Table 3 Table 3

Oxygen-Conserving Devices.).

Table 3 Oxygen Conserving Devices

Type Mechanism Cost Advantages DisadvantgesReservoir Stores O2 in

exhalation

Low Reliable, easy to

initiate use

Poor appearance

Demand Delivers at beginning

of inhalation

Substantial Saves the most O2 Mechanical

failure possible,

complicated

Transtracheal Bypasses dead space High, including

cost of

procedure

Good appearance,

excellent

compliance,

work of breathing

Important

complications

(e.g., mucus

plugs), requires

special care

They include reservoir nasal cannulas, transtracheal catheters, and electronic demand devices. Ascompared with conventional nasal cannulas, these devices decrease oxygen waste by a factor of two

to four. The reservoir nasal cannula has a pouch that stores 20 ml of oxygen during expiration and

delivers this oxygen as a bolus at the onset of inspiration.2,22 Electronic demand devices sense the

beginning of inspiration and deliver a pulse of oxygen during early inhalation.2,22

Transtracheal catheters improve oxygen delivery by bypassing anatomical dead space and using the

upper airways as a reservoir for oxygen during end-expiration.22,46 Transtracheal oxygen is

delivered directly into the trachea. The hollow catheter is surgically implanted under local anesthesia

between the second and third tracheal rings. Both the catheter and the procedure are covered by

Medicare. Reimbursement to suppliers of the oxygen-delivery equipment is tied to the flow rate of

oxygen. Therefore, oxygen flow at rates below 1 liter per minute, which are frequent with the

transtracheal catheter, discourages the provision of these devices by the suppliers of medical

equipment. Other advantages of transtracheal oxygen include its inconspicuousness; the lack ofnasal, auricular, or facial irritation; and the infrequency of displacement of the catheter during

exercise or sleep.47 Rates of acceptance by patients range from 80 to 96 percent.47-49 The

implantation procedure is usually performed by a pulmonologist or otolaryngologist, and procedure-

related complications, which occur in 3 to 5 percent of cases, include subcutaneous emphysema,

bronchospasm, and paroxysmal coughing. Late complications include dislodged catheters, stomal

infections, and mucous balls, which may be fatal.50

Future Directions

Lighter and longer-lasting portable oxygen-delivery systems are becoming available. Coupled with

better electrical oxygen-conserving devices, these systems will increase the mobility of patients now

restricted to a limited lifest. The use of oxygen for patients with temporary decreases in oxygen

saturation during certain activities, such as sleep, is being tested; the results may modify the currentindications for oxygen therapy.