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 Article References 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 Hypoxemia Hypoxemia 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 tha increases t 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 1 Effect Respiratory Ventilation Cardiovascular HR & Stroke Vol Hematologic Erythropoetin & Hb concentration Possible Benefits PaO2 Improve Ventilation Perfusion matching PaO2 & O2 delivery O2 carrying capacity Negative consequence work of breathing


Pulmonary artery pressure myocardial work

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

Unfortunately. oxygen supplementation improves survival. III or aVF) *Erythrocythemia (Hematocrit >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. six months of oxygen significantly improved pulmonary-artery pressure. the pressure improved in 12 of the patients. just before. During five years of follow-up. Survival Long-term oxygen therapy improves survival. patients were randomly assigned to either 12 or 24 hours of daily oxygen therapy. After 26 months. Indications for LTOT Continuous Oxygen Resting Pa O2 55mmHg or O2 saturation 88% Resting Pa O2 56-59 mmHg or O2 saturation of 89% in the presence of any of the following: *Dependent oedema suggesting CHF *P pulmonale on the ECG (P wave >3mm in II. daytime somnolence & cardiac arrhythmias. In a study by the British Medical Research Council. patients with hypoxemia were randomly assigned to receive 15 hours of continuous oxygen or no oxygen. there was a mean (±SD) yearly increase in the pulmonary-artery pressure of 1. and stroke volume at rest and during exercise. Table 1. cor pulmonale. Patients receiving long-term oxygen therapy should be reevaluated within two months to assess whether hypoxemia persists. 19 of 42 patients treated with oxygen died.9 In the Nocturnal Oxygen Therapy Trial (NOTT). pulmonary hemodynamics. or polycythemia should also receive long-term oxygen therapy. In the NOTT study. and 31 months after oxygen therapy. attempts to correlate short-term hemodynamic responses to oxygen with long-term survival have not succeeded.6 The condition of many patients worsens despite supplemental oxygen. Up to 40 percent of treated patients have sufficient improvement after one month to make continued supplemental oxygen unnecessary.).8 Because the improvement in survival with long-term oxygen therapy seems to be proportional to the number of hours of therapy.4 mm Hg. After supplemental oxygen therapy. mortality in the continuoustreatment group was half that in the 12-hour group.8. exercise capacity. such as . as compared with 30 of 45 controls. Patients with a PaO2 of 56 to 59 mm Hg or an oxygen saturation of 89 percent. It may also decrease the oxygen cost of breathing and improve the quality of sleep.12. the current recommendation for patients with hypoxemia (defined as a PaO2 of <55 mm Hg or an oxygen saturation of <88 percent) is continuous 24-hour-a-day oxygen (Table 1Table 1Indications for LongTerm Oxygen Therapy. peripheral vascular resistance.47±2.3 mm Hg. with a mean annual decrease of 2. Right heart catheterization was performed in 16 patients who had hypoxemia with chronic obstructive 7 pulmonary disease 41 months before.6.13 The use of noninvasive methods to predict the response to oxygen.15±4. and neuropsychological performance. Early identification of these patients would allow them to avoid the cost and inconvenience of therapy.In patients with hypoxemia. Before therapy.11 Pulmonary Hemodynamics Supplemental oxygen can improve pulmonary hemodynamics and reduce cardiac work.

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. The Work of Breathing 2 Supplemental oxygen decreases minute ventilation and the oxygen cost of breathing. and short-term memory in young men. measures of exercise endurance.37 This factor may be particularly important in patients with severe obstruction.38 There may be an association between nocturnal oxygen desaturation and pulmonary hypertension in patients with chronic obstructive pulmonary disease and a daytime PaO above 60 2 . 2-25 but the mechanisms by which it does so are not clear.31 Both these studies demonstrated an increase in the frequency of neuropsychological deficits as the PaO 2 decreased. since some benefit is possible and other options are limited. motor speed.19.29 The NOTT investigators studied neuropsychological performance in 203 patients with a mean PaO2 of 51 mm Hg. 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. phenomena best explained by rapid.35.oxygen uptake during maximal exercise12 or the change in the right ventricular ejection fraction after oxygen therapy. but not their emotional state or the quality of their lives.36 During rapid-eye-movement sleep. and hand grip. reductions in functional residual capacity. Therefore. dyspnea. Currently.16 Supplemental oxygen also reduces minute ventilation and the respiratory rate for a given workload. breathing becomes more variable. and oxygen saturation falls. increased oxygen saturation does not predict improved exercise performance. Exercise Capacity Ventilatory rather than circulatory factors limit exercise in many patients with airflow obstruction.25. learning. and alterations in ventilation perfusion matching. Neuropsychological Effects Hypoxemia (PaO2.15 Supplemental oxygen increases the distance patients can walk and their endurance in tests on a treadmill or a bicycle. supplemental oxygen increases oxygen delivery and its utilization by muscles during exercise. >60 mm 2 Hg) to 61 percent in those with severe hypoxemia (PaO2.18 Currently. 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. shallow breathing.21 Supplemental oxygen may also decrease dyspnea and improve endurance by directly reducing chemoreceptor activity. The incidence ranged from 27 percent in patients with mild hypoxemia (PaO . six months of supplemental oxygen improved the participants' general alertness. the contribution of the rib cage to ventilation decreases.30 whereas the Canadian Intermittent Positive Pressure Breathing Trial included 100 patients with less severe hypoxemia (mean PaO2. sleep is associated with hypoxemia and retention of carbon dioxide. 66 mm Hg). long-term oxygen therapy is indicated for all patients who have hypoxemia as defined above.14 have been disappointing.32 In the NOTT study.17 In addition.28. episodes of hypopnea. <50 mm Hg).27 It also decreases neuropsychological performance in patients with chronic obstructive pulmonary disease. as a consequence of hypotonia.20 However. hypoventilation. who greatly depend on the accessory muscles of respiration for breathing.34 In chronic obstructive pulmonary disease. In the future. Sleep During rapid-eye-movement sleep.33 Supplemental oxygen should not currently be prescribed for the sole purpose of trying to improve a patient's mental function. a desire to decrease the work of breathing is not an accepted indication for the long-term administration of oxygen.16-18 In patients with hypoxemia and those who have oxygen desaturation with exercise. 45 to 60 mm Hg) impairs judgment. and ventilatory-muscle fatigue may serve as criteria for prescribing supplemental oxygen.

and during sleep. the airlines have different policies regarding patients traveling with oxygen. Systems of Oxygen Delivery Long-term oxygen therapy can be administered from an oxygen concentrator or in the form of compressed gas or liquid oxygen (Table 2Table 2Modes of Oxygen Delivery. and their oxygen requirements assessed. patients with nocturnal desaturation (oxygen saturation. but a single policy that will make traveling easier is being studied. during exercise. but this measurement is less precise. Prescribing Oxygen Guidelines for prescribing oxygen are listed in Table 1. or cardiac arrhythmias.2 Determining the Need for Oxygen The need for supplemental oxygen should be determined by obtaining arterial blood gas values.43 At present. measurement of oxygen saturation is adequate to adjust treatment. regression formulas may be helpful in that assessment.2. measured by finger or ear oximetry.42 It is unclear whether supplemental oxygen improves the quality of sleep. In the United States. <88 percent) should receive supplemental oxygen if they have complications attributable to hypoxemia during sleep. blood gases should be monitored whenever oxygen therapy is adjusted in patients with hypercapnia. In addition. a certificate of medical necessity for home oxygen therapy must be completed. Airline travel is safe for most patients with chronic obstructive pulmonary disease. .42 Patients who have hypoxemia while awake should receive supplemental oxygen during sleep. and the flow rate at rest. In general.22 Oxygen saturation. correlates with PaO2. Patients with hypoxemia should be evaluated clinically.mm Hg. such as pulmonary hypertension.40 Patients with chronic obstructive pulmonary disease have poor-quality sleep41 and frequent arousals during periods of desaturation.41. patients receiving oxygen should be instructed to increase the flow by 1 to 2 liters per minute during the flight. Table 2 Modes of Oxygen delivery System Advantages Gas Moderate cost Wide availability Fair portability Little need for maintenance Liquid Light weight Excellent portability Ease of refilling O2 concentrator Low cost Good availability Ease of use Disadvantages Heavy weight Difficulty of refilling Need frequent refills High cost Incompatibility of parts among vendors Pressure venting Need moderate maintenance Heavy weight Relatively poor portability Need regular maintenance Because home oxygen therapy is supplied under a fixed-reimbursement policy regardless of the system used. the type of delivery system. For patients who do not have hypercapnia. The prescription should include the source of supplemental oxygen. Supplemental oxygen should be administered to increase the PaO2 to no less than 60 mm Hg or the oxygen saturation to 90 percent or more. daytime somnolence.44 vendors in the United States provide the least expensive system unless the physician requests otherwise. To avoid excessive retention of carbon dioxide. It is therefore important that the prescription clearly specify the desired oxygendelivery system.39.).

arterial oxygen pressure may return to levels higher than 60 mm Hg after prolonged therapy.3-kg) and 6. this method is inefficient. In some patients higher oxygen flows may induce some retention of carbon dioxide. 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. Compressed gas or liquid oxygen can be portable sources of oxygen. thereby delivering supplemental oxygen to the patient while returning nitrogen to the atmosphere.5 vs.4 kg). Supplemental oxygen is a fire hazard.4 days.2 Although effective. Oxygen stored at temperatures below -183°C becomes a liquid. The liquid-oxygen tanks also need pressure-relief venting as the tanks warm up and the gas expands. 16.2 hours. Although liquid oxygen is more portable and containers are easier to refill than highpressure cylinders. and 3 lb (91. physicians (sometimes pressed by the patients) are tempted to discontinue the oxygen. respectively. fearing that it may cause addiction. 7. patients should have both stationary and mobile systems of oxygen delivery. A study comparing two types of portable oxygen systems. The portable 9. found that patients used liquid oxygen more hours per day (23. 5. Unless they are immobile or confined to bed. In such cases. 10) and left their houses for more hours per week (19. If this is done. are quite portable and. 2 hours. standard sizes are 200.5-lb (4. Patients may want to avoid continuous oxygen therapy. Compressed oxygen is provided in high-pressure cylinders. Oxygen-Administration Devices Patients usually receive oxygen through a nasal cannula. 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. coupled with electronic oxygenconserving devices. a container of liquid oxygen of equivalent weight will last four times longer at a given flow rate. Concentrators are relatively inexpensive ($1. These cylinders provide oxygen at a flow rate of 2 liters per minute for 2. 15. the movement of oxygen to the lungs occurs only during early inhalation one sixth of the cycle. and 1. In the United States. Liquid oxygen is particularly desirable for active patients.500) and require little maintenance. Tanks should be stored away from heaters and furnaces. respectively.5-lb (3-kg) containers provide oxygen for eight and four hours.2 hours. and 1. 9. gaseous and liquid. and coupling devices for stationary and portable systems made by different manufacturers may not be compatible. as compared with $350 for a compressed-oxygen tank). to prevent both disconnection of the regulator and explosion if the tank falls. In some patients. because their condition frequently deteriorates to a point at which supplemental oxygen is again needed. but occasional patients report local irritation in the nose and eyes. The smaller units. they are used as a fixed source of oxygen. 4. During the respiratory cycle. however. The volume of liquid oxygen is less than 1 percent of the volume of a comparable amount of atmospheric oxygen. Because the concentrators weigh about 35 lb (16 kg) and require wall current to operate. Temporary oxygen is indicated during sleep and exercise when hypoxemia is present only during those activities. may deliver oxygen for as long as eight hours.5 vs. Oxygen concentrators are electrical devices that use a molecular sieve to separate oxygen from air. Liquid oxygen has a higher cost ($3. Tanks should be safely secured to a wall.Most patients require a stationary source of supplemental oxygen. Education about the difference between an addictive substance and a necessary one frequently resolves the problem. this process wastes unused oxygen. there are several disadvantages. usually an oxygen concentrator. the patients should be closely followed. Alveolar ventilation does not occur . As compared with oxygen in the form of a compressed gas.45 Misconceptions and Hazards There is no place in medical care for the administration of short courses of oxygen. Cylinders are bulky and require frequent refills. Patients must abstain from smoking something that will also help their lung disease. at the same flow rate. Low-flow supplemental oxygen has been remarkably free of important side effects. Oxygen at a flow rate of 2 liters per minute increases the fraction of inspired oxygen from 21 percent to approximately 27 percent.5).500 for a stationary system.

include subcutaneous emphysema. bronchospasm. Therefore.22. such as sleep. the results may modify the current indications for oxygen therapy.).22 Electronic demand devices sense the beginning of inspiration and deliver a pulse of oxygen during early inhalation. requires special care High.22 Only oxygen flowing during early inspiration gets to the alveoli. Coupled with better electrical oxygen-conserving devices.47-49 The implantation procedure is usually performed by a pulmonologist or otolaryngologist.22 Transtracheal catheters improve oxygen delivery by bypassing anatomical dead space and using the upper airways as a reservoir for oxygen during end-expiration. auricular.46 Transtracheal oxygen is delivered directly into the trachea. stomal infections.50 Future Directions Lighter and longer-lasting portable oxygen-delivery systems are becoming available. these systems will increase the mobility of patients now restricted to a limited lifest. these devices decrease oxygen waste by a facto of two r to four. work of breathing They include reservoir nasal cannulas..47 Rates of acceptance by patients range from 80 to 96 percent. which may be fatal. easy to initiate use Saves the most O2 Disadvantges Poor appearance Mechanical failure possible. To improve the efficiency of oxygen delivery. and procedurerelated complications. which occur in 3 to 5 percent of cases. The hollow catheter is surgically implanted under local anesthesia between the second and third tracheal rings.g.2.during late inspiration and exhalation. and electronic demand devices. or facial irritation. several devices have been designed (Table 3 Table 3 Oxygen-Conserving Devices. the remainder is wasted. including cost of procedure Good appearance. mucus plugs). Late complications include dislodged catheters. which are frequent with the transtracheal catheter.2. Reimbursement to suppliers of the oxygen-delivery equipment is tied to the flow rate of oxygen. The use of oxygen for patients with temporary decreases in oxygen saturation during certain activities. and the infrequency of displacement of the catheter during exercise or sleep. Table 3 Oxygen Conserving Devices Type Mechanism Reservoir Stores O2 in exhalation Demand Delivers at beginning of inhalation Transtracheal Bypasses dead space Cost Low Substantial Advantages Reliable. the lack of nasal. oxygen flow at rates below 1 liter per minute. and mucous balls. excellent compliance. Other advantages of transtracheal oxygen include its inconspicuousness. 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. and paroxysmal coughing. . complicated Important complications (e. As compared with conventional nasal cannulas. transtracheal catheters. Both the catheter and the procedure are covered by Medicare. discourages the provision of these devices by the suppliers of medical equipment. is being tested.2.

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