Clinical evaluation of prolonged ambulatory oxygen therapy in chronic airway obstruction

Clinical Evaluation of Prolonged Ambulatory Oxygen Therapy in Chronic Airway Obstruction* THOMAS L . PETTY,

M .D .

and MICHAEL M . FINIGAN,

M .D .

Denver, Colorado

Twenty patients with chronic airway obstruction have received continuous portable oxygen therapy on a home basis for from six to twenty-five months ; improvement in activity level has been observed in all . Secondary polycythemia has been reversed in those with an elevated hematocrit level . A gain in dry weight was observed in most patients . The data reported suggest that oxygen is safe when used in a controlled fashion by nasal prongs with sufficient flows to bring the arterial oxygen pressure (pO2) to normal . The practicality and economics of continuous home oxygen therapy are discussed . XYGEN has been established as a useful therapeutic agent in the care and rehabilitation of patients with chronic lung diseases, particularly emphysema and chronic bronchitis [1-5] . Objective hemodynamic improvement by reduction of pulmonary artery pressures by the acute [6] or chronic use of oxygen [1] in hypoxemic subjects has been reported . In addition, a reversal of hypoxelniainduced secondary polycythemia by continuous oxygen therapy has been demonstrated [7] . The value of chronic oxygen administration to support exercise in many rehabilitation progrants has been emphasized previously [1-3] . These studies were primarily hospital-based rehabilitation programs . The fear of possible oxygen toxicity remains a matter of concern for clinicians who care for patients with chronic respiratory disease when oxygen therapy is required [8] . The economics of continuous oxygen therapy also remains a burden [9] . Recent developments of oxygen equipment have provided the means for ambulatory oxygen therapy utilizing portable oxygen equipment which is practical for use outside the hospital . f

This equipment has provided a new dimension of activity for respiratory cripples . The present study was designed to (1) gain insight into the utility of continuous ambulatory oxygen therapy used in the home for respiratory cripples, (2) establish the safety of continuous prolonged oxygen therapy, and to (3) study some of the long-term physiologic effects of chronic oxygen administration in respiratory cripples .

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MATERIALS AND METHODS

Patients were selected on the basis of marked disability, with inability to exercise without the aid of supplemental oxygen . Many patients had severe hypoxemia with secondary polycythemia and pulmonary hypertension with cor pulmonale and repeated bouts of recurrent congestive right heart failure (bronchitis type of chronic airway obstruction [70]) . Several additional patients had relatively normal blood gases at rest and no pulmonary hypertension, large lung volumes, but marked disability (emphysema type of chronic airway obstruction [70]) . The majority of the patients within the series were patients in an organized pulmonary rehabilitation program . In all patients convincing evidence of disability had been observed by us for weeks or months prior to the trial of continuous oxygen therapy . Serial physiologic observations were made at intervals at the beginning of the study and when appro-

f Lindc Division of Union Carbide, New York .

" From the Department of Medicine, Respiratory Care Laboratory, and the Webb Waring Institute for Medical Research, Univcnity of Colorado Medical Center, Denver, Colorado . This study was supported in part by PHS Contract No . PH 108-66-227, U .S . Department of Health, Education and Welfare . Requests for reprints should be addressed to Thomas L. Petty, M .D ., University of Colorado Medical Center, 4200 East Ninth Avenue, Denver, Colorado 80220 . Manuscript received July 24, 1967 . 242

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B

Fte . 1 , , patient (Case 2) filling portable walke om larger canister . The walker contains two to four hours supply (total weight 7) pounds) and home cannister two to four days supply . B, patient ambulating with the assistance of supplemental oxygen . From the Rocky Mountain M . .1 . priate because of the addition of oxygen therapy, intercurrent illness or the introduction of another form of therapy . Ventilation tests including vital capacity (VC), forced expiratory volume in one second (l'FV,), maximum mid-expiratory flow (MMEF) and maximum voluntary ventilation (MVV) were performed with a 13 .5 L . Collins spirometer or a 9 L . Stead-l-yells spirometer when the patient was in a clinical steady state and had not taken an inhaled bronchodilator . Arterial pH analyses were performed with a glass electrode (Radiometer Co .) and carbon dioxide tension (pCO,) was estimated by the Astrup tonometric method using the Siggaard-Anderson nomogram or by the Severinghaus electrode . Oxygen saturation was calculated, using the Severinghaus curve, from the pH and pO z obtained on the Clark electrode, in most cases, or in the higher ranges of saturation by a dual beam hemoreflecting oximeter (American Optical Co . Diffusion tests were performed by the steady .) state carbon monoxide uptake method of Filley et al . [71] . Serial determinations of ventilation and blood gases at rest and exercise were made during the more than two years encompassed by the study but not all the data will be recorded here . Ventilation tests and blood gas analyses are reported only if the patient was in a clinical steady state free of intercurrent illness_ sot. . 45,

Arnttsi -

1

9GN

Right-sided cardiac catheterization ,vas performed in two patients at the onset and at an interval after continuous oxygen therapy (one and six and a half months, respectively) . The patents received a fairly standard treatment regimen designed to promote physical reconditioning and pulmonary rehabilitation, The treatment program both before and during oxygen always included a bronchial hygiene program encompassing inhaled bronchodilator (isoprotcrenol or racemic epinephrine) followed by steam inhalation, followed by expulsive coughing maneuvers to clear the airways . All patients received an oral ephedrine-containing drug three times daily . All patients received breathing retraining and were urged and encouraged to maintain a high level of activity with graded physical exercises such as walking and stair climbing whenever possible . Cardiac glycosides and occasionally diuretic agents were used to manage congestive right heart failure . Phlebotomy was performed when hematocrit levels were greater than 60 per cent. All the patients in this study were living at home . Patients were supervised by repeat clinic: visits and at home by a public health nurse trained in respiratory care . The public: health nurse aided in the estimation of the patient's daily activities employing standard questionnaires as well as visits to the home to decide the patient's level of activity .



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Two of the patients who died after one and two months of continuous oxygen therapy were examined at autopsy in order to estimate the degree of emphysema, bronchitis and hronchiolitis . and to search for the lesion of so-called oxygen toxicity [8] . One lung was fixed in the distended state by either formalin fumes or liquid formalin . The degree of emphysema was estimated by a semiquantitative gross analysis of the departitioning present in the lesions of mucous gland hyperplasia and bronchiolitis were identified [101 . The contralateral lung was studied with thin fine microsections stained with hernatoxylin and eosin . All the patients in the study were observed by one or both of us throughout the period of observation . Data from twenty patients with chronic airway obstruction receiving continuous oxygen therapy for periods ranging from six to eighteen months are included in this report. PORTABLE OXYGEN EQUIPMENT

Recently, the availability of portable oxygen equipment has made continuous ambulatory oxygen therapy a reality . In brief, a patient maintains a home reservoir which contains three

to four days of liquid oxygen supply . A 6 .5 pound cannister is filled with two to four hours oxygen supply by the patient in the home (Fig . 1 a) . Liquid oxygen is constantly being converted into gaseous oxygen which is consumed by the patient with flow rate control at 2 to 4 L . per minute . This equipment allows the patient to ambulate free of the confinements of conventional oxygen equipment (Fig . 1B) . We had previously determined that most patients with chronic airways obstruction and hypoxemia require an average of 2 L . per minute at rest 1/2] . In each case an attempt was made to maintain oxygen saturation at near normal levels for Denver (88 to 92 per rent) . Observations were made in each case to determine what level of flow was necessary to provide adequate oxygenation during slow exercise . The average patient required 2 to 4 L . per minute during exercise . RESULTS

In Table i are listed the background factors including duration of oxygen therapy, dry

TABLE I PROLONGED CONTINUOUS OXYGEN THERAPY IN CHRONIC AIRWAY OBSTRUCTION CLINICAL AND PHYSIOLOGIC OBSERVATIONS IN FIFTEEN SURVIVING PATIENTS)

Case No . Patient

Age (yr .) and Sex

Months of Os HematThe, Weight ocnr apy (lb.) (%)

Arterial Blood Gases Ventilation Tests SAO, VC

FEV, MMF MVV

pH

PLO,

(%)

Clinical Steady State

Activity Level and Remarks

Patimh with Secondary Pafycythsnsis Rrguirina Phlrhwomia 1

B .G.

38, Al

Pre 0s Post Os

8

173

65

2 .08

1 .27

0 .59

173

55

1 .67

1 .20

1 .29

50

7 .38

52

75

49

7 .42

47

91

Room air, rest Os at 2 ./min L ., rest

2

J .H.

64, M

Pre 0,

Post 0,

3

O.H .

56,M

Pre Os Postos

4

G .B .

67, M

D.M .

6

Pre Os

Post 0-

5

6

10

56, M Pre Os Post 02

6

142

67

2 .02

0 .46

0 .19

19

7 .32

70

55

Room air, rest

153

43

1 .85

0 .63

0 .20

24

7 .38

48

84

7 .36

50

98

Room air, rest 0, at 2 L ./min ., rest Room air, rest Room air, rest

152

61

2 .85

0 .95

0 .46

23

7 .38

44

79

156

47

2,93

0 .70

0 .78

32

7,41

42

85

168

65

4 .02

0 .64

0,29

33

7,37

47

76

Room air, rest

165

52

3 .09

0 .56

0 .20

22

7 .33

68

90

220

61

3 .91

1 .61

0 .47

74

7 .41

52

50

240

57

3 .03

1 .29

0 .47

52

7 .33

54

89

Os at 2 L,/min, rest Room air, rest .16 0, L,/min ., rat

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Housebound ; ram,, us phlebotomies Full independent activitv including outdoors ; no phlebntRespiratory failure ; numerousphiebotomiea ; working part time with ,,.d,,I deterioration Working full time withalgnificantly enhanced activity; no phlebotomies Huusebuund ; few phebotomies Full independence ; limited outdoor activity ; no phlebotomies Housebound with limited outdoor activity ; many phlebotomies Full independence ; works 4 hr./day ; no pldebotomies Housebound ; ownera pblebotomie, Full daily activity ; moderate outdoor amhulatinn ; I phlebutumy in 6 ma.

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Prolonged Oxygen Therapy- -1'rtG' . Fmigm) TABLE I

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(Cost'd)

PROLONCLII C' IN TlSOOOS OXYGEN 'THERAPY IN CHRONIC AIRWAY OBSTRUCTION (CLINICAL AND PFIPS?05 0GIC (-fI1F RV '1]'[0 Ns IN FIFr'EEN SURVIVING PATIENTS)

Cxss No . Patient

Months of Os Heo,ntThrr- Weight ocrir apy (Ib.) (A)

a,d S,x

Vev5lntinnTests -VC FEV2 MMF MVV

Arteria . Blood Gases -SAO 5 pii pCO 2 Y'))

Clinical Stcndv Slate

.AOticit3 Level and Raru,da

Padientr mu ."tSernndan PsIycythenia 6

WA .

66. M

Pre 0s

Post Os

7

E .E.

62-"

Pre Os

9

W .C.

1 .. P.

49,M

74, M

89

48

3 .30

0 .52

0 30

38

126

39

3 .69

0 .75

0 .30

33

103

45

2 .21

0 .63

0 .22

24

7 .38

50

77

68

55

37

76 fig

106

43

1,68

0 .37

0 .13

15

7,32

Pre Os

132

50

1 .34

0 .46

0 .27

18

7 .29 7 .38

72 30

91 81

Poet 0s

132

47

2 .06

0 .40

0 .16

19

7,40

54

68

7 .40

52

88

85

Post Os

8

10

7 .46

120

7

Pre 0s

147

51

4 .18

0 .95

0 .47

29

7 .45

38

138

51

4 .52

1 .04

0 .45

32

7 .43

39

85

118

45

1 .46

0 .57

0 .21

22

7,43

49

72

78 Post O2

10

C .T.

68, M

6

Pre 02

58 Past Os

11

K.V .

62, M

Pre 0s Post 0,

12

63, 5

F .F .

M .S .

62, M

7

Pre 0,

Post 0a

13

8

18

128

2 .78

0 .87

0 .27

39

7 .41

44

52

1 .50

0 .36

0 .14

14

7 .38

48

86

124

50

2,62

0 .36

0 .18

16

7 .34

62

92

97

49

1,78

0 .49

0 .19

23

7 .47

45

81

7 .45

44

91

7 .39

53

59

7 .40

60

92

7 .42

46

82

103

42

14

H .P .

78, M

8

Pre 0s Post Os

7

rest Room air . at Room a exercise Room air, rest Room air, rest Room

L ./nun, rest Room air, rest 0,,,,2 rest Room air, st Os at 2 LI rcat m Room J, rest Osat2

158

48

2 .58

0 .59

0 .22

27

7 .42

38

94

122

48

2 .34

1 .13

0 .44

42

7 .32

49

75

127

44

1 .81

0 .97

0 .45

30

7 .34

4 .5

77

at Roam air. rest Ron 2 Oa at L./mist, cst Room air, rest Room air,

7 35

46

89

Os

rest Rome air, rest

54

2 .72

0 .94

0 .30

38

76 Post Os

Os at 2

96

121

143

Pre Os

49

0,12 Bed m chair s . . . . I"', hosp,tnlised for 2 7_ :Snm., o st Exe Room s'jr . P, dl iadeprmla,e.r : rest arthclationlorludes 815 stairs s .nh t gen Roon, air, IIousrhnund st O s at6 Fvll nsdependeore at home wish Iinuted ou :door ;nnh,daficn Exercise Room air. llom,ebound st Room

,11

15

E .E .

42, F

Pre Os

Post Os

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160

56

1 .99

0 .84

0 .40

44

7, 36

49

r.

139

55

2,71

0,86

0 .32

36

7 .35

45

90

1,

2

O, at 2 L,/nun ., rest

Iteesebound

Moderntr, outdoor arbully including fishing Bed-chair existence ; respiratory failure 2 imer Full independent am. bnlaums Cnnline,lie whalchair Independent home activiq; limito) 0551door ambulation Bad-chair existence

Full ird,pradaad0, hamcertiSle

I horehound

Full independent acttvfty with n,oderate outdoor activity TTonsebound Null independent a, tisity wiW limited nn'd<,nr ."Mr,

Housebound ; 8 too . i n hospital for rebabiliration Null independeneq able m do most of household duties



246

Prolonged Oxygen Therapy-Petty, Finigan

FIG. 2 . Hematocrit change during period of continuous oxygen therapy comparing hematocrit levels of patients with previous phlebotomies versus those not requiring phlebotomies . Broken line represents history of phlebotomies and solid line no precious phlebotomies. weight, hernatocrit, ventilation tests, arterial blood gases on room air and on oxygen, and the activity level of fifteen patients before and after the institution of oxygen therapy. The duration of oxygen therapy ranged from six to eighteen months (average 8 .1 months) . An improvement in arterial oxygen saturation on oxygen breathing was demonstrated in every case . In only four patients (Cases 4, 7, 11 and 12) was there a significant elevation in arterial pCO2 during the period of observation on oxygen . In three of these (Cases 7, 11 and 12) the initial maximal breathing capacities were less than 25 L . and in the fourth (Case 4, Table i) there was a drop in maximal breathing capacity from 240 230 220 - 180 170 m 160 ~. 150 140 130 120 110 100 90

1 2 3 4 5 6 7 8 9 10 M ..Ih . . . o .yy . .

/18

Fio . 3. Weight change during period of continuous oxygen therapy .

33 to 22 L . during the period of observation . It was our clinical impression that these four patients demonstrated deterioration consistent with their previous clinical course, but that they were able to remain comfortable and active only with supplemental oxygen . Ventilation tests showed variable changes probably due to the day to day changes in ability to perform standard ventilation tests [131 . For example, the MVV change ranged from an increase of 11 L . to a decrease of 22 L . per minute during the period of observation (mean change 3 .3 L . per minute) . A reduction in hematocrit was observed in almost all the patients (Fig . 2) . All patients with a history of secondary polycythemia and frequent phlebotomies (Cases 1, 2, 3, 4 and 5) had a significant reduction in hematocrit while receiving continuous oxygen therapy . And the need for phlebotomy in all these cases was nearly eliminated by oxygen therapy . The remaining patients without secondary polycytheinia also showed a slight reduction in their hematocrit during the period of oxygen administration . It is also noteworthy that ten of fifteen patients exhibited a slight to moderate gain in dry weight during the period of oxygen administration (Fig. 3) . There was only one with a modcrate weight loss (Case 9) . Every patient in the study achieved an improved level of functional activity . In almost every instance this allowed the patient to be much more independent than previously, and in three cases (Cases 2, 4 and 8) a return to gainful employment was possible . Since the oxygen reservoir is portable, it is possible to have a reservoir in the place of business and at home . One of the two female patients (Case 15) also demonstrated a significant increase in activity allowing her to perform almost all of her household duties . In Table it are listed the clinical data on three patients who died during the period of observation . Autopsies were performed on two of them and the findings are listed . It is emphasized that a careful study of the autopsy material, including whole lung and standard sections, failed to reveal any evidence of oxygen toxicity [8] . The results of the steady state diffusion tests performed at varying months after the initiation of oxygen therapy are given in Table m . No significant changes were observed although all determinations were quite low, a frequent finding in severe chronic airway obstruction . AMERICAN JOURNAL OF MEDICINE



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Prolonged Oxygen Therapy-Petty,

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TABLE It CLINICAL, PHYSIOLOGIC AND AUTOPSY OBSERVATIONS (THREE DEATHS)

Case No . Patient 1

C . C.

Age (Ym) and Sex

Months of 0, Ventilation Tests Ther- -- VC FF.V, spy MMF MBC

39, M

Pre Ot

post 0,

2 .64

0 .34

0,17

17

11

Arterial

pH

pCO,

SAO,

7,43

49

79

. .36

57

Clime,,I stead y Scam

Activity Level and Remarks

Room sir, rest Roam air, exercise

lines, xnd 'ha hound, no to ernce Fuliindependence at home with todera outdoor activity

0,a12 rest

2

H .P .

60,M

Pie Os

1 .57

0 .49

0 .19

25

Post 0,

3

W j.

71, M Prc Os

2 .62

0 .94

0 .33

30

7 .45

48

7A

Room air, rest

7 .30

54

93

0 , at 2 L . . mn. .

7 .42

41

70 64

Post 0,

15

ILLUSTRATIVE CASES

Details from two additional patients not included in Tables i and it are reviewed in order to cite additional clinical and physiologic features associated with continuous oxygen therapy . A sixty-one year old white man (W .M ., CGH No . 165963), was first admitted to the Colorado General Hospital in March 1965 because of chronic and acute respiratory failure . He had a history of forty individual hospital admissions over the preceding sixteen years, always for problems related to silicosis, pulmonary fibrosis and chronic bronchitis, severe secondary polycythemia and cor pulmonale . The patient had been a hard rock miner for thirty years until 1950 and had had shortness of breath for over twenty years. At the time of admission he complained of dyspnea at rest and was nearly bed bound . Paroxysmal nocturnal dyspnea approximately three to four times a night was reported . A chronic cough produced about a half cup of white sputum each day . Several episodes of pneumonia had occurred in the past . Recurrent chest infections and intermittent ankle edema were prominent features of his history . At least 175 phleVOL .

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7 .41

40

87

Limited actidty at h"' ., Full independente at home

t¢ Peat nied after 11 . Autopsy d w closed Kiehaiella pncu,nonia .t,u16pie "'Imon vabscesses. severechrnniv hronchi'is, end-slagnncn+rilohnlar mphvse Died nfter7 mo . Autopsy di, doa;i sascre re panacioaT uuplrc , tedial Prvperraphv polmo-

diced nmrinsrlero. . chronic passive r esNon of lira Room vin Housebound ; Died ,her 13 rest difficulty suddenly Room air, with self athome t on .tops. ' 0,,12 Full indepen;cocadence I'll plet, outdo" attendance at social and sporting events

botomies were required for a hematocrit of greater than 60 per cent over the previous eight years, with poor control of his polycythemia . The electrocardiographic reports revealed evidence of right axis deviation, right ventricular enlargement, right atrial enlargement and digitalis effect . A chest roentgenogram revealed some bullous emphysema and rather moderate diffuse pulmonary fibrosis . The clinical impression was chronic obstructive lung disease, chronic bronchitis, bullous emphysema and silicosis with diffuse pulmonary fibrosis, with complicating secondary polycythemia and cor pulmonale . TABLE In EFFECT OF PROLONGED CONTINUOUS OXYGEN 'raIERAPY ON DIFFUSION TEST AT REST

Patient W .A .

Months of Os Therapy 10 -

E. R.

7

W. C. L .P. 0 .11 .

7

6 6

Diffusion Test Results Pre Os -

6 3 6 5 3

Post O,

.3 -_ ~ 5 8 .9 2 .9 .2 6 .5 .0 5 .5 .9 4 .5

.

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Prolonged Oxygen Therapy-Petty, Finigan

The patient was initially admitted to the Clinical Research Ward where a rehabilitation program was initiated, including bronchial hygiene using inhaled Isoproterenol ® followed by steam and in turn followed by expulsive coughing efforts three times a day together with daily training in abdominal diaphragmatic breathing and graded exercises [t] . Cardiac catheterization was performed in May 1965 (Table iv) . The hematocrit was 65 per cent, white blood cells 8,000 per cu . mm. with a normal differential and chromium 51 red cell mass 62 cc . per kg . Ventilation tests revealed a VC of 3 .37 (87 per cent of predicted), FEV, or 1 .38 L . (41 per cent of VC), MMEF of 0.45 L . per second (3 .12 f 0 .80 L. per second predicted), and MVV of 47 L . per minute (40 per cent of predicted) . The arterial pH was 7 .27, pCO, was 75 mm . Hg (normal 34 to 38 mm . Hg), pO, was 32 mm . Hg (normal 65 to 75 mm . Hg) and SAO 5 was 53 per cent (normal 92 to 94 per cent) . The mean pulmonary artery pressure at rest was 42 mm . Hg . Following one month of intensive efforts at pulmonary rehabilitation without oxygen, continuous oxygen therapy was begun. After one month of continuous oxygen therapy, the hematocrit was 48 per cent, red cell mass 33 cc . per kg. and mean pulmonary artery pressure at rest 28 mm . Jig . The need for phlebotomies ceased and the patient's exercise tolerance improved markedly. When last seen, twenty-five months after the initiation of continuous oxygen therapy, the patient was living with his invalid wife and doing all the housework and gardening . He had had an increase in his hematocrit when he became careless about mainLaining continuous oxygen therapy and was breathing room air ranging from one to four hours a day . On resuming continuous oxygen therapy, his hematocrit control was achieved . Continuous oxygen therapy for Comment : twenty-five months has been highly effective in providing for a high level of functional activity, complete elimination of hospitalizations for exacerbations of disease, and adequate control of congestive right heart failure and secondary polycythemia . The need for continuous oxygen administration is emphasized by the patient's clinical deterioration and worsening polycythemia during periods of oxygen discontinuance, even for a few hours each day . A thirty-four year old white, divorced mother of three with a long history of repeated chest infections and a ten year history of smoking (S.B ., CGH No . 40972) was first admitted to the Colorado General Hospital in 1956 because of shortness of breath, cough and excessive sputum production (Fig . 1) . At that time a diagnosis of bronchiectasis of the lower lobe

of the left lung was based on a bronchogram and a left lower lobectomy was performed . Her condition improved slightly during the following six years but she continued to smoke heavily . In July 1963 she was admitted to the hospital for the sixth time for recurrent cor pulmonale and was treated with digitalis and diuretics, with improvement . Her electrocardiogram demonstrated right axis deviation and right ventricular enlargement . Her ventilation tests revealed a vital capacity of 1 .71, an FEV, of 0 .80, an MMF of 0.47 and an MVV of 25 L . per minute . Because of secondary polycythemia with hematocrit concentrations ranging from 61 to 65 per cent, the patient had required numerous phlebotomies in the past . In June 1964 she was again admitted with cor pulmonale and was described as having "end-stage lung disease ." Her MVV was reduced to 17 L . per minute and the arterial oxygen saturation at rest ranged between 59 and 67 per cent . In March 1965 she was hospitalized for the thirteenth time because of recurrent infection . At that time the attending physician did not think that anything more in the way of therapy was likely to bring about improvement . During these months she had had oxygen at home and had used it intermittently for attacks of dyspnea but never on a continuous basis . In November 1965 she was readmitted for the sixteenth time with respiratory failure and cor pulmonale with congestive heart failure. Her hematocrit of 67 per cent was managed by three successive venesections of 500 cc . each during the first week of care . Ventilation tests demonstrated a vital capacity of 1 .81 (53 per cent of normal), FEV, of 43 per cent of VC (normal more than 75 per cent of VC), MMF of 0.27 (normal 3 .77 y 0 .88 L. per second), and MVV of 17 L. (19 per cent of normal) . The arterial pCO, ranged from 50 to 70 mm . Hg on numerous occasions and the arterial oxygen saturation at rest was 61 per cent . Cardiac catheterization (Table tv) had been performed one year earlier, revealing resting mean pulmonary artery pressure of 61, right ventricular pressure of 96/9-13, arteriovenous difference of 5 .05, total pulmonary resistance of 1,365, and pulmonary arteriolar resistance of 1,075 . No pulmonary artery pressure gradient was found . The cardiac index was 3 .6 Ms . BSA .* The patient was discharged in November 1965 on a regimen of continuous oxygen therapy, using the portable oxygen walker for the first time . She had no further hospitalizations until March 1966 when she was admitted for elective cardiac catheterization . At that time her hematocrit was 43 per cent, and she had not required any phlebotomies during the previous five months of oxygen therapy . * Courtesy of Henry Beckwitt, M.D ., General Rose Memorial Hospital, Denver, Colorado . AMERICAN JOURNAL OF MEDICINE

Prolonged Oxygen Therapy-Pelly, 11inigon Ventilation test results were unchanged and the arterial blood gases showed a pCO 2 of 62 and an oxygen saturation at rest on room air of 50 per cent . Oxygen saturation during continuous oxygen therapy ranged from 85 to 92 per cent. An electrocardiogram showed significant improvement in the right ventricular enlargement pattern (Fig. 4) . Repeat cardiac cathe lei ization showed a right ventricular pressure of 76/0-9 . (Attempts to enter the pulmonary artery w . unsuccessful and thus right ventricular pressures were taken as an index of pulmonary hypertension . This is justifiable since no gradient across the pulmonic valve was demonstrated previously .) The calculated right ventricular work was decreased by 18 per cent (Table iv) . The patient was discharged on portable oxygen to be used at rest, during sleep and exercise, i .e ., twenty-four hours a day . In August 1966 she was admitted for the eighteenth tune because of a 15 per cent pneumothorax . Her hematocrit was 42 per cent and her oxygen saturation while receiving oxygen via nasal prongs at 2 L . per minute was 94 per cent, Her pCO, ranged from 51 to 60 . She was again discharged after brief hospitalization with resolution of the pneumothorax . Site has been observed in the Outpatient Clinic and has been comfortable and active to date . At her last clinic appointment on June 25, 1967, she had remained relatively well with continuous oxygen therapy . Laboratory determinations revealed a hematocrit of 40 per cent, vital capacity of 1 .74, FLV 1 of 0 .36, MMF of 0 .14 and MBC of 14 L . Arterial blood gases while receiving 2 L . of oxygen by nasal prongs demonstrated an oxygen saturation of 92 per cent, pH of 7 .40 and pCO i of 66 . Comment : A list of this patient's hospitalizations before and after continuous oxygen therapy appears in Table v . From the hospital records it is quite clear that her attending physicians thought in the fall of 1964 and in early 1965 that death was irnminent . The patient has remained fully ambulatory on oxygen and is able to do her housework and shopping . ECONOMICS OF CONTINUOUS OXYGEN THERAPY

In our recent experience, we have observed that the average cost of continuous oxygen therapy, whether conventional or ambulatory, ranges from $80 to $180 per month [14] . This is a considerable economic burden to those already disabled . One way to identify the value of continuous oxygen is to compare the economics of respiratory care supported by oxygen with the cost of an equal period when oxygen was not given . In Case 2, an analysis of the number of vor, . 45, AT! GUST 1968

249

FIG . 4. Regression of right ventricular enlargement by chronic oxygen therapy . Change in cardiogram following continuous oxygen therapy for six month duration . (Courtesy of Henry Beckwitt, M .D ., General Rose Memorial Hospital .) hospital days, clinic visits and emergency room visits was made (Table vi) . An eighteen month period without oxygen was compared to the subsequent eighteen month period when oxygen therapy was used continuously . A careful review of the records indicates that no other major change in drug therapy was made . This patient was cared for by the same physicians and nurses throughout both periods . It is apparent that oxygen drastically reduced the number of necessary hospital days and clinic visits . When one compares the expense of oxygen added to the necessary hospitalizations during oxygen therapy and the cost of clinic visits, it becomes TABLE R' RIGHT-SDJED CARDIAC C .A'ITIETERIZA'1ION DETERMINA'rIONS ONE YEAR BEFORE AND SIX MONTHS AFTER INITIATION OF CONTINUOUS OXYGEN THERAPY Rest Studies Right ventricular systolic pressure (mnl . Hg) Mean pulmonary artery pressure (mm . Ilg) Arterial oxygen saturation (~ . ) Arterial venous oxygen content difference (vol . %) Cardiac index (L ./min./Ms .) Right ventricular work

11/19/64

3/24/66*

96/9-13

76/0-9

61 51 .1

48 .8

5 .05 3 .6

4 .35 3 .6

4 .56

3 .72

* Continuous oxygen therapy began on 11/15/ 65 . NOTE : This table is reproduced through the courtesy of Henry J . Beckwitt, M .D ., General Rose Memorial Hospital, Denver, Colorado .



Prolonged Oxygen Therapy

250

Petty, Finigan

TABLE V IMPORTANCE OF OXYGEN IN RECURRENT RESPIRATORY AND CARDIAC FAILURE

Data

Days

Hematocrit

Phlehominy

58 55 50 48 47,50 49 63 58 67

+ + 0 0 0 0 + + +

40,43 43 42 43

0 0 0 0

7th admission 4/14/64 11 6/15/64 (H) 17 12 9/9/64 (H) 11/18/64 (H) 3 12/22/64 (H) 9 2/17/65 (H) 9 5/1/65 (H) 8 6 7/12/65 (H) 10/4/65 (H) 8 Continuous oxygen added 4/1/66 (C) 6/1/66 (C) 8/3/66 (H) 0 4/1/67 (C)

POI

Electrocardiographic Findings

pCO s

3

58

33 29 33

51 54 62

50-60 70 63

48-63 50 61

Right axis, RVH, Right axis, RVH, Right axis, RVH, Right axis, RVII, Right axis, RVH, Right axis, RVH, Right axis, RVH, Right axis, RVH, Right axis, RVH, Norm Norm Norm Norm

axis axis axis axis

rtward rtward rtward rtward

RAH RAH RAH RAH RAH RAH RAH RAH RAH

term term term term

vector vector vector vector

NOTE : H = hospital observation . C = clinical observation . RVH = right ventricular hypertrophy . RAH = right atrial hypertrophy . Norm axis rtward term vector = normal axis rightward terminal vector .

apparent that oxygen therapy, despite its considerable cost, was nevertheless less expensive than the cost of hospitalizations and clinic visits during the previous period . When oxygen can return the patient to gainful employment, additional economic gains are made . The value of home living versus hospital or nursing home care is another obvious advantage . In addition to the patients with chronic airway obstruction, ten other patients with pulmonary fibrosis from extensive tuberculosis, cosinophilia granuloma, idiopathic fibrosis as well as pneumoconiosis have been managed on continuous oxygen for an average of eleven months . These patients have also experienced

TABLE VI ECONOMICS OF CONTINUOUS OXYGEN THERAPY VERSUS COST OP HOSPITALIZATIONS BEFORE AND AFTER OXYGEN

D a As hospital patient Hospital days Cost As outpatient Clinic visits Cost Emergency room Cost Oxygen cost Total costs (excluding drugs)

18 Mo.

No Os

79

18 Mo . it

$2,938 33

$ 597 13

$ 165 5

Continuous Os

$

$

65

50 $2,034

$3,153

$2,696

clinical benefits . Thus, it is likely that continuous oxygen therapy will be of therapeutic value for all disabled hypoxemic subjects whatever the underlying disease may be . INDICATIONS FOR CONTINUOUS OXYGEN THERAPY IN PATIENTS WITH CHRONIC AIRWAY OBSTRUCTION

A listing of all the clinical indications for oxygen therapy is beyond the scope of this paper . In chronic airway obstruction with hypoxemia and disability, oxygen therapy has been demonstrated to improve exercise tolerance, ameliorate pulmonary hypertension and help control congestive right heart failure and secondary polycythemia. These benefits of continuous oxygen therapy must be weighed against the inconvenience of carrying the oxygen walker at all times, alternate modes of therapy for secondary polycythemia such as phlebotomy, and congestive right heart failure with cardiac glycosides and diuretic agents, the psychologic burden of displaying something new and slightly curious to society, and the expense of continuous oxygen therapy . Our present day experience suggests that oxygen therapy is clearly indicated in those who have severe exercise intolerance, repeated bouts of congestive right heart failure and uncontrollable secondary polycytheria . These people should be chosen on the basis of their willingness to stop smoking and those who are psychologically sound so as not to be unduly concerned about the use of an obvious physiologic crutch . AMERICAN

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Prolonged Oxygen Therapy-Petty, Finigan The most controversial application of oxygen is in the respiratory cripple with almost true emphysema who has marked obstructive airway disease, profound disability in terms of limited exercise tolerance and normal or near normal blood gas determinations at rest. Experience thus far has demonstrated that these people can improve their exercise tolerance with oxygensupported exercise to a somewhat lesser degree than hypoxemic subjects previously described . ']'be role of oxygen in this group of patients is a subject of current study [151 but at the present time the use of oxygen in this group of patients remains empirical, useful for those patients who cannot exercise without oxygen but who can with the administration of this drug . Thus far in our experience, when congestive right heart failure occurs in the emphysema or "pink puffer" type of chronic airway obstruction, oxygen may be valuable in allowing for a comfortable existence and control in congestive right heart failure which is usually a terminal event in this type of patient [15] . It should be stressed that oxygen therapy is not intended to replace all other modalities of therapy in disabled patients with respiratory insufficiency . The usefulness of cardiac glycosides, diuretic agents, salt restriction, necessary phlebotomy and a graded exercise program with or without oxygen has been well established in this spectrum of diseases . COMMENTS

That oxygen therapy can improve the activity level in patients with respiratory insufficiency seems well established from the data here recorded and from other reports [1,2] . In hypoxemic subjects, oxygen therapy can effectively reverse pulmonary hypertension and secondary polycythemia . In addition, oxygen therapy has been shown to improve renal plasma flow in hypoxemic subjects and thus improve urine flow ram [/0'] . The application of continuous oxygen therapy may have beneficial effects other than correction of hypoxemia . Oxygen therapy has been shown to reverse the excessive susceptibility of hypoxemic experimental animals to infection [17] . Many of the patients in our series have contracted fewer deep chest infections during the period of oxygen therapy than during an equal time previously without oxygen . Oxygen therapy has also been reported to reverse hypoxemia-induced increased airway resistance vor . . 45,

AUGUST

1968

251

[18] . In our series, standard ventilation tests have riot demonstrated a significant improvement, but perhaps the more sensitive detertninations of airflow might have brought out small differences due to oxygen therapy . Whereas the rationale for the use of oxygen in hypoxemic subjects seems clear, the inechanism of observed improvementt in patients with relatively normal arterial saturations during rest but with marked disability without oxygen remains unexplained . Oxygen may prevent the hypoxemia that would develop on exercise and thus allow for exercise to take place . In addition . slight increases in oxygen content may improve tissue oxygen transport to the extent that exercise is possible . The final mechanism for the observed clinical improvement in disabled but not hypoxemic emphysema patients by oxygen should he aa subject of further study . Certainly, the psychologic effects of supplemental oxygen may well contribute to some of the improvement . Fears of oxygen toxicity have led to slow acceptance of (his drug in the rehabilitation of respiratory cripples . The administration of oxygen in excess causes damage to the alveolar membrane [1 .91 and is associated with oxidative hemolytic anemia, serum enzyme changes and cerebral changes [20] . These findings occur only during excessive oxygenation . Arterial pO,'s in excess of 250 mm . Hg for prolonged periods are probably dangerous 1211 and the safe level of arterial pO s may be less than 200 urn . IIg. Thus far when oxygen has been used in the manner we have described, we have failed to observe any clinical, physiologic, roentgenographic or pathologic evidence of oxygen toxicity . Since our therapeutic aim is to return the arterial pO ; to the normal range, it would be highly unlikely that oxygen toxicity should occur . Said another way, oxygen given in physiologic doses should be no more toxic than oxygen obtained by normal patients breathing ambient air . The improved control of congestive right heart failure during continuous oxygen therapy may help combat the relatively poor prognosis of patients with chronic airways obstruction and cor pulmonate living at altitude [21] . .A large number of people will have to be evaluated for prolonged periods to sec if the prognosis is actually altered. The gain in dry weight further suggests objective improvement and perhaps improved prognosis . An inexorable loss of weight has been

252

Prolonged Oxygen Therapy-Petty,

correlated with exceedingly poor prognosis in emphysema and chronic bronchitis [22], The risk

of

carbon dioxide retention on

oxygen breathing can be largely eliminated by controlled

low flow

oxygen and by observations

of arterial blood gas analysis . In our experience, carbon dioxide retention occurs only in a few patients with acute respiratory failure or in those who have received sedatives or high flow, uncontrolled oxygen or terminally in patients with insufficient pulmonary parenchyma

to

support life . ADDENDUM The two patients described herein were still living as of June

Acknowledgment : Broughton,

A.

M .D .,

1, 1968 . The assistance of Joseph Philip Corsello,

Lindesmith, M .D ., Louise

M.

0.

M .D ., Larry

Nett, R .N . and

Susan W . Tyler, B .5 . is gratefully acknowledged . REFERENCES 1 . LEviNE, B. E ., BIGELOw, D . B ., HAMSTRA, R . D ., BECKWITT, 1"1. J ., MITCHELL, R . S ., NETT, L. M ., STEPHEN, T . A . and PETTY, T . L. The role of long term continuous oxygen administration in patients with chronic airway obstruction with hypoxemia . Ann . Int . Med., 66 : 639, 1967 . 2 . MILLER, W. F. and TAYLOR, H . F . Exercise training in the rehabilitation of patients with severe respiratory insufficiency due to pulmonary emphysema : the role of oxygen breathing . South . M . J., 55 : 1216, 1962. 3 . COTES, J. E . and GILSON, J . C . Effect of oxygen on exercise ability in chronic respiratory insufficiency : use of portable apparatus . Lancet, 1 : 877, 1956 . 4. CAMPBELL, E . 1 . M . Oxygen therapy in diseases of the chest . Brit . J. Dis . Chest, 58 : 149, 1964. 5 . PETTY, T . L ., BURTIS, B . B. and BmELow, D . B . Oxygen, an important pharmacologic agent . Rocky Mountain M . J., 64 : 66, 1967, 6 . CoEss, J . E ., PISA, Z . and THOMAS, A . J . Effect of breathing oxygen upon cardiac output, heart rate, ventilation, systemic and pulmonary blood pressure in patients with chronic lung disease . Clin . Sc., 25 : 305, 1963 . 7 . CHAMBERLAIN, D . A. and MILLARD, F, J . C . The treatment of polycythemia secondary to hypoxic

Finigan

lung disease by continuous oxygen administration . Quart. J . Med ., 32 : 341, 1963 . 8 . PRATT, P . C . The reaction of the human lung to enriched oxygen atmosphere . Ann . Pew York Acad. Sc ., 121 : 809, 1964. 9 . PETTY, T. L ., FINIGAN, M . M . and NErr, L . M . Can We Help Them Breathe? Yes! IOTA Bulletin 3, February 1967. 10 . MITCHELL, R . S ., VINCENT, T . N ., RYAN, S . and FILLEV, G . F . Chronic obstructive bronchopulmonary disease . Iv . The clinical and physiological differentiation of chronic bronchitis and emphysema. Am . J. M. Se ., 247 : 513, 1964 . 11 . FILLEY, G . F ., MACINrOSCII, A. J . and WRIGHT, G . W . Carbon monoxide uptake and pulmonary diffusing capacity in normal subjects at rest and during exercise . J. Clin. Invest ., 33 : 530, 1954 . 12 . BIGELOW, D . B ., PETTY, T. L ., LEVINE, B . E ., FILLEY, G . F . and FINIGAN, M. M . The effect of oxygen breathing in arterial blood gases in patients with chronic airway obstruction living at 5200 feet . Am . Rev . Resp . Dis ., 96 : 28, 1967 . 13 . SPICER, W . S . Variation in respiratory function . Arch . Enviran . Health, 12 : 217, 1966 . 14 . PETTY, T. L . and NET l, L . M . Records of the Respiratory Care Laboratory, University of Colorado Medical Center, Denver, Colorado, 1965-67 . 15 . PETTY, T . L. The role of continuous ambulatory oxygen therapy in the pulmonary cripple without significant hypoxemia at rest . In preparation . 16 . DINER, H . and GRANBERG, P . Effect of induced hypoxia on renal function in man . Acta chit . scandinav ., 125 : 253, 1963 . 17 . GREEN, G . Resistance to bacterial infection in experimental simulated respiratory insufficiency . Clin. Res., 15 : 345, 1967 . 18 . AsTIN, T . W . and PENMAN, W. B . Airway obstruction due to hypoxemia in patients with chronic lung disease . Am. Rev . Resp . Dis ., 95 : 567, 1967 . 19 . CALDWELL, P . R . B ., LEE, W . J ., SCHILDKRAUT, H . S . and ARCHIB .ALD, E . R . Changes in lung volume, diffusing capacity and blood gases in men breathing oxygen. J. Appl. Phyriol., 21 : 1477, 1966 . 20 . ROTH, E . M . Gas physiology in spore . operations . New England J. Med., 275 : 144, 1966 . 21 . RENZETTI, A . D ., MCCLEMENT, J. H . and LITT, B. D . The veterans administration cooperative study of pulmonary function . In . Mortality in relation to respiratory function in chronic obstructive pulmonary disease. Am . J. Med., 41 : 115, 1966 . 22 . VAN DR WORSTIJNE, K . P. and GYSELEN, A . Weight changes in the terminal stages of chronic obstructive lung disease . Relation to respiratory function and prognosis . Am . Rev . Resp . Dis ., 95 : 556, 1967 .

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