need for oxygen enrichment in myogardial infarction, shock and following cardiac arrest

NEED F O R OXYGEN E N R I C H M E N T I N MYOCARDIAL INFARCTION, SHOCK AND

FOLLOWING CARDIAC ARREST

JAN SMITH, JEAN J. PENNINCKX, STEPHAN KAMPSCHULTE and PETER SAFAR

The abundance of data of the systemic circulation in various types of shock and following cardiac arrest is contrasted by a surprising lack of information on pulmonary changes. We have seen hypoxemia in most patients with clinically reduced cardiovascular function, calling for respiratory care. Maximal arterial oxygen content is needed for maintaining oxygen delivery to tissues in conditions of reduced blood flow. Universal acceptance of exhaled-air ventilation and bag-mask-air ventilation has created the impression that oxygen enrichment is not required. The observations by others and ourselves to be reported indicate that an early switch to ventilation with increased oxygen concentrations is called for.

We like to define shock as “the clinical picture of inadequate total tissue perfusion.” The pathogeneses are based on one or a combination of the following: (1) oligemia; (2) systemic vasodilation; (3) pump failure (reduced cardiac contractility); and (4) increased pulmonary vascular resistance from embolization or spasm. Any one of these factors may lead to a vicious cycle of metabolic acidosis, cardiac failure, refractory hypotension and irreversible tissue damage.

The management of shock states must support oxygen transport to the organism, and not merely arterial pressure (Tabel 1). Oxygen transport (oxygen delivery, oxygen availability) equals blood flow times arterial oxygen content. The normal 70 kg resting adult thus has about 1 liter of oxygen per minute supplied to his systemic capillaries with a cardiac output of about 5 liters per minute and an arterial oxygen content of about 20 volumes percent. 250 ml of oxygen are used for metabolism under resting conditions. A reduction of oxygen delivery to the capillary bed may be the result of decreased blood flow, loss of hemoglobin and/or

Department of Anesthesiology, University of Pittsburgh School of Medicine and Presbyterian-University Hospital, Pittsburgh, Pennsylvania, U. S. A.. Supp~rted by U. S. Army Contract *DA-40-193-MD-2160.

128

Table 1 .

0 2 Transport - - bT X Ca02*)

( 0 2 Delivery) Cardiac Arterial ( 0 2 Availability) output 0 2 Content Approx. normal values 1000 ml/min - 5000 ml/min x 20 -

100 m1 -

*) CaOr = 1.34 ml Odg Hb -t 0.3 ml Od100 mm Hg PaOd100 ml blood.

inadequate saturation of hemoglobin secondary to reduced PaO2, all of which may result in tissue oxygen debt and possibly irreversible damage.

Raising Pa02 over 100 mm Hg increases arterial oxygen content (CaOe) only slightly, namely by 0.3 volumes percent of oxygen for every 100 mm Hg Pa02 rise. Nevertheless, it would be of interest to study whether a greatly increased Pa02 could promote diffusion of oxygen from capillaries to mitochondria through tissue which is often edematous in post- hypoxic states. While Pa02 values of 100400 mm Hg seem to be safe and may be helpful, Pa02 values below 50 mm Hg are undesirable since they reduce SaO2 below 75 %. In addition, hypoxia and the resulting acidosis cause pulmonary vasospasm.

I. OBSERVATIONS ON PATIENTS The records of patients with myocardial infarction, shock or following

cardiac resuscitation admitted to the intensive care unit of Presbyterian- University Hospital during an arbitrarily selected 6-month period were reviewed (Table 2 ) . Periodic blood-gas determinations were available in 48 patients. This review preceded the recent introduction of more de- tailed patient studies which will permit correlation of cardiac output, oxygen consumption, total blood volume, acid-base status, physiologic dead space and shunting with and without therapeutic measures, such as intermittent positive-pressure breathing (assisted respiration, IPPB) ; intermittent positive-pressure ventilation (controlled ventilation, IPPV) ; blood- volume expansion and cardiotonic and vasopressor drugs.

Arterial blood samples were collected anaerobically in heparihed glass syringes and immediately analyzed with an Instrumentation Laboratory’s triple electrode unit for POP, pCO2 and pH. Bicarbonate and base excess were calculated. In most patients, sampling was via an arterial catheter left in place for periods of up to one week. Whenever possible, determina-

129

Diagnosis (Groups)

Number of patients

Total I Survived I Died

tions were first made during spontaneous breathing of room air which, however, was not possible in all cases due to the severity of the patient’s clinical condition. Measurements were then made during spontaneous breathing of 100 @ oxygen (tight-fitting face mask, cuffed tracheal tube or cuffed tracheostomy tube; non-rebreathing valve; reservoir bag; warm mist). This was followed by administration of 100 @ oxygen with IPPB and finally with IPPV, using large tidal volumes (approximately 15 mlhg) to determine the reversibility of the shunt effect by deep lung inflations. IPPB or IPPV/oxygen was administered by Bird, Bennett, Emer- son or Engstrom ventilators.

The following cases are only examples of hypoxemia in one representa- tive case of each group listed in Table 2.

Uncomplicated myocardial infarction.-All of the eight patients re-

Table 3. Myocardial infarction uncomplicated.

8 patients-all recovered Case No. 1

100% 0 2

Pa02 mm Hg .......... 55 295 430 PaC02 mm Hg . . . . . . . . . . 38 40 26 pHa ................... 7.38 7.35 7.49 Bicarb. mEq/l .......... 22 21.5 19.5

130

Table 4. Myocardial infarction with pulmonary edema.

5 patients-all died. Case No. 2

100% 0 2

Spont. R. 1 IPPB I IPPV

Pa02 mm Hg . . . . . . . . . . . 50 71 210

pHa . . . . . . . . . . . . . . . . . . . 7.5 7.57 7.6 Bicarb. mEq/l . . . . . . . . . . . 11 16 14

PaC02 mm Hg . . . . . . . . . . 15 18 15

CVP . . . . . . . . . . . . . . . .; . . . 25 16 15

covered. Patient * 1 (Table 3) was a 69-year-old man brought to the hospital following chest pain. He was normotensive and his lungs were clear. Initial ECG showed acute anterior wall myocardial infarction. Chest X- ray showed cardiomegaly with left ventricular prepondenance. SGOT and LDH values were elevated. While breathing room air spontaneously, he had a Pa02 of 55 mm Hg. His ventilation volumes were adequate and there was no metabolic acidosis. The Pa02 rose to 295 mm Hg during inhalation of 100 % oxygen. This indicates only mild shunting which was partially reversible by IPPB. After episodes of ventricular tachycardia, which were controlled, he recovered.

Myocardial infarction with pulmonary edema.-All five patients developed shock and died. Patient * 2 (Table 4) was a 67-year-old woman. She developed cyanosis and dyspnea 12 hours following resection of an abdominal aortic aneurysm. ECG showed a fresh posterior-wall myocardial infarction. She was normotensive, had tachycardia, peripheral venous dis- tension, a central venous pressure of 25 cm H20, and left ventricular gallop. Soon she was coughing up pink, frothy mucus. Rales were present throughout both lung fields. While breathing 100 % oxygen spontaneously, she had a Pa02 of only 50 mm Hg. Her PC02 and pH values indicated hyperventilation and metabolic acidosis. Administration of IPPB/lOO % 0 2 increased the Pa02 to only 71 mm Hg, while pH and PC02 values remained unchanged, but central venous pressure decreased. Since she became somnolent, her trachea was intubated and, under curarkation, her ventilation controlled. This resulted in marked improvement in her clinical condition. Her Pa02 rose to 210 mm Hg, while the central venous pressure decreased to 15 cm H20 without a decrease in arterial pressure. Subsequently, she deteriorated and died in shock.

131

Table 5. Myocardial infarction shock.

6 patients 4 died-2 recovered

Case No. 6

100% 0 2

Pa02 mm Hg . . . . . . . . . . PaC02 mm Hg . . . . . . . . . .

.. pHa . . . . . . . . . . . . . . . . . . . Bicarb. mEq/l . . . . . . . . . . . CVP . . . . . . . . . . . . . . . . . . .

Spont. R. IPPB IPPV 6 hr. 1 5 hr. 1 8 hr.

63 135 175 30 19 20

7.39 7.47 7.56 17 13 17 15 21 11

Recovered

Myocardial infarction with shock.-Shock was defined as arterial systolic pressure below 100 mm Hg, cold and clammy periphery, and oliguria. None of these patients had clinical evidence of pulmonary edema (lungs clear, roentgenograms normal). Four of these six patients died and two recovered. Patient"6 (Table 5) was a 60-year-old man who became hypotensive following a hiatal hernia repair. ECG was suggestive of an anterior-wall myocardial infarction. Central venous pressure was 15 mm Hg. His arterial pressure was maintained at normotensive levels by an intravenous infusion of metaraminol: Pa02 was 63 mm Hg while breathing 100 % oxygen spontaneously. PaC02 and pHa values showed slight hyperventilation and metabolic acidosis. Vital capacity was reduced. Be- cause of deterioration of his condition his trachea was intubated. Assisted respiration with 100 "/o 0 2 increased the PaO2. This increase was more sustained when controlled ventilation was instituted. Later 50 "/o inhaled oxygen was sufficient to maintain Pa02 over 80 mm Hg, but only when administered by IPPB. After digitalization he could be weaned from metaraminol and controlled ventilation over a period of 7 days. During weaning, spontaneous alveolar ventilation was adequate, but progressive shunting was the problem. He recovered and is doing well.

Comment: Since this review, two additional patients with cardiogenic shock recovered after treatment with IPPV/O2 via tracheal tube, stabiliza- tion with relaxants or narcotics, pHa, Pa02 and PaCOo control, and titra- tion of arterial and central venous pressures by isoproterenol and norepinephrine infusion.

132

Table 6. Myocardial infarction cardiac arrest post resuscitation.

15 patients. 10 died-5 recovered, no CNS damage.

Case No. 15: CPR for 1 hour, epin., NaHCOs, lidocaine, defibrillation

1 Spont. R. 1 IPPV

Pa02 mm Hg . . . . . . . . . . 1-5 day

PaC02 mm Hg . . . . . . . . . . :1-5 day

pHa . . . . . . . . . . . . . . . . . . . 1-5 day

9 day

9 day

9 day

9 day Bicarb. mEq/l . . . . . . . . . . . 1-5 day

- 40-200

- 18-44

- 7.27-7.52

- 11-22

140 300

17 12

7.45 7.57

11 10

Recovered

Cardiac arrest following myocardial infarction.-Fifteen patients suffered cardiac arrest in the wards and were taken to the intensive care unit for post-resuscitation care. Ten died and five recovered with intact central nervous system function. These five and ten others make a total of fifteen patients with coronary artery disease, discharged from our hospital with intact CNS in a five-year period (1962 to 1967) following proven cardiac arrest outside the operating suite. There were none with prolonged coma because efforts were discontinued when biologic death was evident.

Patient * 15 (Table 6) was a 61-year-old man who was brought to the emergency room with substernal pain, dyspnea and sweating. He had a cardiac arrest in the emergency room which was immediately treated and diagnosed as ventricular fibrillation. Only after numerous external electric countershocks and 600 mg of lidocaine during 60 minutes of external cardiac compression was spontaneous circulation restored. He also received 6 mg of epinephrine, 300 mEq of NaHCOs and 3 grams of calcium glu- conate. He was then taken to the intensive care unit and received controlled ventilation with 100 % oxygen with the aid of partial curarization. Acute anteriolateral myocardial infarction was confirmed by ECG and elevated blood enzyme levels.

Marked hypoxemia was present shortly after the return of spontaneous circulation although the lungs were clear and there was no evidence of aspiration. Concomitantly with recovery of his cardiovascular state, Pa02

133

. . . . . . . . . . . . Pa02 mm Hg

.. . . . . . . . . . PaC02 mm Hg

pHa . . . . . . . . . . . . . . . . . . .

Bicarb. mEq/l . . . . . . . . . . .

Table 7. Cardiac arrest (non-M.I.) post resuscitation.

7 patients. 6 died-1 recovered.

Blood gas values variable. Case No. 5: Trauma, aspiration, epin., NaHCOs

10 min 35 200

’ 10 min 25 1 7

1 day

1 day ’ 10 min 7.3

1 day 7.5 ’ 10 min 1 1

12 1 day

I IPPV/lOO% 0,

Died

values rose to 200 and then 300 mm Hg during IPPV/Oe. On the ninth day during spontaneous breathing of 100 % oxygen PaOe was 140 mm Hg. The expected metabolic acidosis was controlled with NaHCOs. He recovered with no CNS deficit.

Cardiac arrest without myocardial infarction.-Of the seven patients in this group, six died and one recovered without CNS deficit.

Hypoxemia following restoration of spontaneous circulation was variable, but always present. As demonstrated by the patient shown in Table 7, the lowest PaOe values were seen in patients who had aspirated gastro- intestinal contents. Only the combined application of IPPV/Oe 100 %, steroids, bronchodilators, and tracheobronchial lavage resulted in the reversal of this severe shunt effect. ,

Oligemic shock.-Most patients with acute oligemia were treated promptly with volume replacement and showed no severe hypoxemia. In two patients with prolonged oligemic shock, hypoxemia was severe. The patient shown in Table 8 was a 28-year-old man admitted 48 hours after an automobile accident. He had suffered a fractured pelvis and intra- abdominal bleeding which on laparotomy proved to be a large retroperito- neal hematoma. On transfer to our hospital he was found to be in clinical shock (cold, clammy, apprehensive, with tachycardia and tachypnea) in spite of an arterial pressure of 140/80 mm Hg. The hemoglobin was 10 grams percent and the central venous pressure was low. During spontane-

134

Admission I 7 hrs.

Table 8. Oligemic shock.

2 patients. 1 died-1 recovered.

Case No. 4: Trauma, shock for 48 hrs., oliguria

8 hrs.

I 100% o p

I Spont. Resp. 1 IPPB 1 Spont. Resp.

2 hrs. I 3 hrs. 1 4 hrs.

after infusion Admission

Pa02 mm Hg . . . . . 69 250 I40 350 PaCO2 mm Hg . . . 25 25 27 35 pHa . . . . . . . . . . . . . 7.44 7.36 7.37 7.37 Bicarb. mEqfl . . . . . 17 14 14 19 Art. Pr.-H.R. . . . . . . 140/80-100 120/80-142 140/110-120 140/110-80 CVP . . . . . . . . . . . . . 2 12 12 -

Recovered

ous breathing of 100 % 0 2 , Pa02 was 69 mm Hg, indicating severe shunting. The shunt effect was partially reversible by IPPV/Op and completely reversible (even during spontaneous breathing) by correction of the oligemic state. Vital capacity was over 2 liters, which indicates that diffuse atelectasis was not a causative factor.

Septic shock.-In both patients with septic shock the most severe shunt-

Table 9. Septic shock. 2 patients.

1 died-1 recovered. Case No. 3: Pseudomonas, steroid, NaHCOs infusion

Died

135

ing was observed. The patient shown in Table 9 was a 60-year-old woman admitted stuporous with hyperthermia, severe hypotension and cyanosis. She had chronic leukemia and subsequently blood cultures revealed pseudomonas. She was cooled to normothermia and treated with steroids, NaHCOs, antibiotics, and norepinephrine infusion. Her trachea was intubated and she received IPPV/lOO "/o 0 2 . Nevertheless her Pa02 was only 40 mm Hg. There was severe metabolic acidosis. The shunt was not reversible by IPPV and she died. The other patient who recovered and two additional survivors of septic shock since this review were treated similarly but recieved, in addition, isoproterenol. In all three, correction of hypoxemia and reduced vital capacity by IPPVIOr was considered important in the patient's survival.

11. STUDIES IN DOGS The common occurrence of hypoxemia following CPR in man stimulated

a controlled experiment in animals to elucidate its pathogenesis. Lightly anesthetized dogs were ventilated with IPPV/air. Parameters

monitored included arterial pH, PC02, POP, hematocrit and base excess; cardiac output (dye-dilution method with sampling from ascending aorta) ; central blood volume (calculated from dye-dilution curves) ; EKG; aortic pressure; right ventricular pressure; mixed exhaled volumes, PCOa and POa; physiologic dead space (Bohr equation) ; and physiologic shunting (shunt equation).

Ventricular fibrillation was induced electrically. The trachea was clamped in expiration to simulate upper airway obstruction in coma. After 2 minutes of ventricular fibrillation, IPPV/air and 'external cardiac compression were started. After 3 and 6 minutes of CPR blood samples were drawn. After 8 minutes of CPR the dogs were defibrillated (AC external countershock of 350 volts, increasing to 650 volts). When the first series of countershocks was not successful, 1 mg of epinephrine was given i. v. and the countershock series repeated. No alkalinizing drugs were used. Blood samples were drawn after 3, 15, 60 and 240 minutes following restoration of spontaneous circulation.

Preliminary data of the first series of dogs ventilated with air are sum- marized in Table 10. All ten dogs could be successfully defibrillated. Five dogs needed epinephrine and repeated countershocks. Pa02 values were moderately low during and following CPR. Physiologic shunting increased inconsistently and could not fully explain the degree of hypoxemia. Physiologic dead space was only slightly increased.

Tabl

e 10

. C

ircu

lato

ry a

nd r

espi

rato

ry p

aram

eter

s fo

llow

ing

card

iac

arre

st a

nd r

esus

cita

tion

(10

dogs

).

Mea

n va

lues

(R

ange

s)

EC

C +

IPP

V/a

ir

3’ s

pont

. 15

’ spo

nt.

60’

spon

t. 24

0’ s

pont

. 1 3

’ E

CC

I 6

’ E

CC

I cir

cula

tion

I cir

cula

tion

1 cir

cula

tion

I cir

cula

tion

C

ontr

ol

PaO

p m

m H

g ..

....

...

86

67

61

69

72

82

PaC

02 m

m H

g ..

....

..

30

25

29

40

44

31

(7

2-1

0 1 )

(4

9-82

) (4

7-72

) (4

8-89

) (6

4-91

) ..

(49-

1 04

) -

(20-

42)

(12-

57)

(1M

6)

(23-

55)

(32-

68)

(21-

38) -

(7.3

5-7.

52)

(7.2

2-7.

53)

(7.1

C7.

49)

(6.8

2-7.

30)

(6.8

2-7.

20)

(6.8

0-7.

38) -

pHa*

) ..

....

....

....

. 7.

40

7.37

7.

31

7.09

7.

07

7.18

QT

I/min

% af c

ontr

ol .

. 10

0 %

44

%

58 %

68

%

- - -

-

~ _

_

QsI

QT

% .

....

....

...

11.4

%

19.2

%

13.9

% -

Vd

VT

% .

....

....

...

46 %

57

%

48 %

-

- -

__

*)

No

alka

liniz

atio

n us

ed.

137

Cardiac output was greatly reduced following successful restoration of spontaneous circulation, in spite of normal arterial pressure in all dogs. The decrease in pH and that in cardiac output seemed to show some correlation.

The hypoxemia following CPR seemed to have been the result of combination of reduced venous oxygen content (decreased cardiac output), increased shunting and ventilation-perfusion mismatch.

Uncompensated metabolic acidosis persisted for over one hour in spite of the brevity of arrest, demonstrating the need for continuous alkaliniza- tion beyond the immediate resuscitative period. These observations also indicate need for IPPV/O2, and inotropic sympathomimetic amines in the post-resuscitation period.

111. COMMENTS Most previous studies on respiratory changes in shock have revealed an

increased physiologic dead space (VD/VT) (Table 11). One of the first, by Gerst, Rattenborg and Holaday ( 1 ) using anesthetized dogs in oligemic shock under controlled ventilation, found increased VD/VT presumably from closure of portions of the pulmonary vascular bed; and in addition decreased shunting Total lung/thorax compliance was decreased probably as a result of increased bronchomotor tone and alveolar collapse. Cahill (2 ) found during hypovolemic shock in dogs increased compliance and decreased airway resistance. Pulmonary blood flow and diffusion capacity were reduced. Freeman and Nunn ( 3 ) confirmed the increase in VD/VT in oligemic shock in dogs and could increase survival rate by moderate oxygen enrichment. They concluded that deoxygenation

Table 11. Physiological deadspace in shock.

Authors Subjects VDIVT (per cent)

Normal Cournand et al. (1943) Gerst et al. ( 1959) Freeman and Nunn ( 1963) Askrog et al. (1964) McNichol et al. ( 1964) Penninckx and Smith (1966)

Kampschulte and Penninckx (1966)

- Oligemic shock, man Oligemic shock, dog Oligemic shock, dog Vasodilation, hypotension, man Cardiogenic shock (5) , man Cardiogenic shock ( Z ) , man

Post-card. arrest and CPR, dog

33 55-64

55 78

45 (IPPV) 42-75

45-52 (Spont. R.) 50-55 (IPPV) 36-69 (IPPV)

138

was the result of VlQ mismatching. Nunn also analyzed Cournand's data of oligemic patients from 1943 which also showed an increase in VD/VT in oligemia. An increase in tidal volume and minute volume thus is not only necessary to compensate for the developing metabolic acidosis (4) but also to compensate for the increase in V&T. Askrog and Eckenhoff (5) showed an increase in VD/VT plus an increase in P A - ~ O ~ in patients under deliberate hypotension with vasodilator agents and the head-up posi- tion.

MacKenzie and associates (6) found in five patients with cardiogenic shock low Pa02 values (mean 49 mm Hg) during air breathing. The degree of hypoxemia could be related to the reduction in cardiac output, metabolic acidosis, increased right atrial pressure, increased central blood volume and increased shunting (Qs/QT 22 %). PaC02 values were variable. Breathing approximately 100 76 oxygen increased Pa02 only slightly (to mean 119 mm Hg). He did not study the effects of IPPV, which we found to reverse the shunt effect.

McNicol and associates (7 ) found increased VD/VT, decreased FEV and hypoxemia in patients with cardiogenic shock and hypoxemia, even in patients with uncomplicated myocardial infarction. The hypoxemia could be partially reversed by diuretics. Of 23 patients with SaO2 below 85 %, 56 "/o died, whereas of 65 patient with SaO2 above 85 % only 19 "/o died. Other studies (8, 9) showed similar changes and indicated a relationship between acidosis and mortality.

Myocardial infarction is sometimes complicated by pulmonary edema. Miller and Sproule (10) showed in pulmonary edema that the severe reduction in SaO2 (presumably due to venous admixture) could be partially or completely reversed by IPPB/O2. He attributed the beneficial effects of IPPB in pulmonary edema to the following: improved ventilation and gas distribution; decreased work of breathing; deceased transcapillary pressure gradient; and reduced venous return.

Septic shock in animals is associated with tachypnea, increased airway resistance and reduction in lung compliance ( 2 ) . In dogs and sheep endo- toxin produces hypoxemia, spasm of pulmonary venules and bronchospasm (1 1, 12). The fall in cardiac output is thought to be partially due to the rise in pulmonary vascular resistance. The organ congestion resulting from dilation of arterioles and constriction of venules in prolonged local acidosis, as seen in the systemic circulation also occurs in the lungs (13). Isoproterenol relieves bronchoconstriction and pulmonary and systemic vaso- constriction, which, in addition to its cardiac inotropic effect, aids in increasing cardiac output.

139

Pulmonary thrombo-embolism (14) and fat embolism (15), both common in traumatic shock (16), are associated with diffuse pulmonary physiologic dead space and increased capillary shunting with hypoxemia. The influence of humoral agents on the pathogenesis of pulmonary changes observed during shock, especially during septic and embolic shock, is now more than a matter of speculation. The agent or agents responsible are known to produce acute cor pulmonale and bronchiolar closure ( 11 ).

The lung in shock has been studied histologically and usually a combination of the following was found : intra-alveolar edema; interstitial edema; intra-alveolar and intrabronchial hemorrhages with fibrin deposits; vascular engorgement; emboli; thrombi (12, 13, 16, 17). Burn shock is also often associated with pulmonary insufficiency, even when there are no obvious airway burns ( 12, 18).

The respiratory insufficiency following cardiopulmonary bypass ( 19) is similar to rhat in shock and also still poorly understood.

Following cardiac resuscitation the variable degree of hypoxemia seen by us was also observed by Gilston (20). This may be the result of the following: pulmonary contusion from external cardiac compression; pulmonary congestion from left ventricular failure; aspiration; and bone marrow and fat emboli into the lungs (20, 21 ) .

Following cardiac resuscitation in our previously healthy dogs the prolonged and severe acidosis and reduction in cardiac output in spite of normal arterial pressure was striking. Controlled hyperventilation following cardiopulmonary resuscitation, therefore, seems indicated to compensate for the metabolic acidosis and increased V&T, to blow off CO2 following NaHCOs administration and to reduce shunting.

Controlled hyperventilation must be conducted cautiously and under PaCOa and pHa control since it may reduce venous return in patients with low cardiac output and reduce brain blood flow to dangerous levels when PaC02 is reduced below 20 mm Hg. In critically ill patients with increased work of breathing, a change from spontaneous breathing to controlled ventilation may result in a greater reduction in oxygen consumption than in cardiac output, with the net result being a beneficial one (22, 23).

The difficulty in oxygenation observed may call for prolonged administration of 100 "/o oxygen. Pulmonary oxygen toxicity is related to P102 and time (24). FIOP of 1 at 1 ATA has resulted after 12 hours in substernal distress in healthy volunteers (25); and after 50 hours in death from pulmonary edema in dogs (26), even when controlled ventilation was used. Even when Pa02 values are very low, we suspect that open alveoli

140

can be poisoned by F10e values over 0.7 (25, 26, 27). Brief periodic interruptions of oxygen administration by inflations with air (as used by us routinely for “sighing”) may prolong the safe period of 0. administration (24). Although F102 of 0.5 at 1 ATA was used continuously for months without producing lethal damage (29), subtle tissue changes with very prolonged administration of FIOZ between 0.21 and 0.5 cannot be ruled out at this time. If possible, FIOZ should be adjusted to keep Pa02 between 100 and 200 mm Hg and FIOZ of over 0.7 should be avoided for periods longer than 6 to 12 hours.

PaOe values of less than 50 mm Hg should be avoided as they produce reduction in CaOz, pulmonary vasospasm and possibly hypoxic acidosis, which reduces myocardial contractility. I n patients with myocardial infarction even mild degrees of hypoxemia (Pa02 50-80 mm Hg) should be avoided because the possibility of hypoxemia being arrhythmogenic has not been ruled out. The ideal. Pa02 value for the patient in need of arrhythmia control is not known.

IV. CONCLUSIONS Observations on patients and animals reported in the literature and by

the authors indicate that full saturation of hemoglobin with oxygen during spontaneous breathing or air in myocardial infaction, shock and following cardiac arrest cannot be assumed. The pulmonary changes are complex. The hypoxemia observed seems to be the result of a variable combination of the following factors: ( 1 ) increased VD/VT, predominant in oligemic and vasodilation hypotension. ( 2) V/Q mismatch, presumably from ( 1 ) reduced blood pressure causing under-perfusion of upper lung areas and over-perfusion of dependent lung areas; and (b) from pulmonary embolic phenomena. (3 ) An actual increase in Qs/QT due to ( 1 ) pulmonary congestion (alveolar collapse), (b) pulmonary edema, ( c ) miliary atelectasis from hypoventilation (pain, opiates) ; or (d ) bronchospasm (predominant in embolic phenomena). (4) Reduced cardiac output per se, resulting in low C;Oe, which increases PA-aOz without an increase in Q~/QT. The increase of PA-aOz by reduction of cardiac output per se without an increase in shunt has not been sufficiently appreciated and was calculated by Kelman and associates (28).

Hypoxemia caused by an increase in V&T or by V/Q .mismatching can be corrected by moderate oxygen enrichment (F10e = 0.25-0.5) and/or increasing ventilation volumes. Hypoxemia caused primarily by shunting may require an F102 of 1.0, which should be lowered to 0.7 (or better

141

0.5) after 6-12 hours. I n addition, IPPV or IPPB was shown to reduce the shunt effect. Hypoxemia primarily caused by decrease in cardiac output should also be treated by measures to increase cardiac output. If IPPV with 100 "/o 0 2 and attempts at increasing cardiac output fail to raise Pa02 over 50 mm Hg, hypothermia should be considered to reduce oxygen demand.

Because of the complex interrelationships of factors probably causing reduction in oxygen transport, the following therapeutic measures are sug- gested for the management of critically ill patient (29, 30, 31) : stabiliza- tion of the patient with IPPB or IPPV with 0 2 , if necessary via a tracheal tube; control of Pa02, PaCO2, PHa, FlO2, arterial pressure and central venous pressure, facilitated by prolonged arterial and central venous (preferably right auricular) catheterization; and guidance of therapy by measurements of cardiac output and oxygen comsumption.

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2. Cahill, J. M., Jouasset-Strieder, D., and Byrne, J. J.: Lung Function in Shock. A m . 3. Surg. 1965, 110, 324.

3. Freeman, J., and Nunn, J. F.: Ventilation/Perfusion Relationships After Hemor- rhage. Clin. Sc. 1963, 24, 135.

4. Weidner, M. G., and Simeone, F. A.: Physiology of Prolonged Oligemic Hypo- tension: Investigation of Pulmonary Function. Ann. Surg. 1962, 156, 493.

5. Askrog, V. F., Pender, J. W., and Eckenhoff, J. E.: Changes in Physiologic Dead Space During Deliberate Hypotension. Anesthesiology, 1953, 25, 744.

6. MacKenzie, G. J., Flenley, D. C., and Taylor, S. H.: Circulatory and Respiratory Studies in Myocardial Infarction and Cardiogenic Shock. Lancet, 1964, ii, 825.

7. McNicol, M. W., e t al.: Pulmonary Function in Acute Myocardial Infarction. Brit. Med. J. 1965, 2, 1270.

8. Valentine, P. A., et al.: Blood-gas Changes After Acute Myocardial Infarction. Lancet, 1966, ii, 837.

9. Kirby, B. J., and McNichol, M. W.: Acid-Base Status in Acute Myocardial In- farction. Lancet 1966, ii, 1054.

10. Miller, W. F., and Sproule, B. I.: Studies on the Role of Intermittent Inspiratory Positive Pressure Oxygen Breathing in the Treatment of Pulmonary Edema. Dis. Chest. 1959, 35, 469.

11. Halmagyi, D. F., Homer, G. J., and Starzecki, B.: Acute Cor Pulmonale and Shock. Med. 3. Aust. 1965, 2, 141.

12. Aviado, D. M.: T h e Lung Circulation (Volumes I and 11). Pergammon Press, 1965.

13. Lillehei, et al.: Shock and Hypotension; Pathogenesis and treatment. Twelfth Hahnemann Symposium. Editors: Mills, L. C. and Moyer, J. H., New York, Grune and Stratton, 1965.

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14. Sasahara, A. A., and Stein, M.: Symposium on Pulmonary Embolic Disease. Boston, 1964. Grune and Stratton, 1965.

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Catheterization for Sampling and Pressure Monitoring (in preparation).

DISCUSSION

Thomas: As Dr. Safar said, arterial hypoxia is extremely common in patients

with acute cardiac infarction. We have studied this subject over about four years and also noted that arterial PO2 is commonly low even in patients who have a relatively uncomplicated disease, without shock and without pulmonary oedema. Dr. Brenda Higgs in our department in particular made respiratory studies and showed also that this was ba- sically a shunting phenomenon. More recently, we have been measuring

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the pulmonary artery pressure in association with arterial blood-gas measurements and serial observations of X-ray appearances in patients who have pulmonary oedema.

It’s quite remarkable that as the radiological evidence of pulmonary oedema disappears, so the pulmonary artery pressure comes down, but it may take many weeks for the arterial PO2 to return to normal. So it seems that it’s rather unlikely that shunting is the whole basis of arterial hypoxia, and perhaps we have to think in terms of a change of the alveolar membrane as a whole. Since we know that the pulmonary oedema is an albumenous fluid, and I suppose not necessarily complete re- absorbed, it’s quite possible that there is some residual diffusion defect.

With respect to oxygen therapy as a whole, we routinely give our patients oxygen by a face mask; really on the basis of clinical prejudice that this is in favour of the infarction itself and the surrounding ischaemic heart muscle, and supposing that if the peripheral circulation became inadequate for tissue metabolism as a whole, increased arterial PO2 would be useful. But, unfortunately, oxygen itself has pharmacological effects, and the most embarrassing of these is that it drops the cardiac output. We studied this about three years ago and found that the average fall in cardiac output was about 17 %, which is very much greater than is seen in patients with a normal circulation. While this isn’t terribly important for some-one with a good cardiac output, it may not be entirely innocuous in a patient with a failing cardiac output. So against the possibility of increasing the oxygenation in the tissues by means of im- proving the arterial PO2, you have this possibility of reducing blood flow on account of the pharmacological effects.

With respect to cardiac arrhythmias, I think this is an open question. We have not made any controlled study, but with on/off experiments in patients who have multiple ectopic beats, there doesn’t seem to be any constant relationship between giving oxygen and the number of ectopics.

Nolte: Dr. Safar, did you see any harmful effects of administering 100 % oxygen

for several days?

Safar: We are not using 100 70 oxygen for several days. Even with low Pa02

values we assume that lung areas exposed to p O 2 values of over 400 mm Hg for 24 hours may be damaged. Pautler in our laboratory studied dogs with spontaneous versus controlled ventilation, breathing air versus

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oxygen. (Acta anaesth. Scandinav., Suppl. 24; 51, 1966). After about 50 hours, both groups showed some non-specific changes, but only the oxygen group showed liver-like pulmonary consolidation with pulmonary oedema. There was no absorption atelectasis.

holrndahl: True shunting and a diffusion block certainly calls for oxygen breathing.

At an early stage of hypovolaemic or cardiogenic shock it may not be true shunting, but ventilation-perfusion disturbances that cause a decrease in Pa02 during air breathing. Overventilation of some parts of the lung results in increased physiological : dead space, and over-perfusion of under- ventilated areas of the lung results in a decreased PaO2. The uneven pulmonary blood flow distribution starts a vicious circle as the under- perfused areas of the lung will be more compliant and therefore take more and more of the tidal volume. 'Even a slight oxygen enrichment of the inhaled atmosphere can correct a fall in Pa02 due solely to under- ventilation of some areas where there is still no true shunting.

Modell: I don't think any of us will argue with the fact that immediately one

should try to achieve the highest inspired oxygen concentration possible, but later it does not seem that it would be of any benefit to raise the arterial pO2 above 150 mm Hg, inasmuch as this is the point where the haemoglobin is completely saturated with oxygen. Therefore, I think the proper approach would be to increase the inspired oxygen concentration by use of oxygen enrichment rather than by strict 100 % oxygen inhalation according to the arterial oxygen tension. I n this way I think you will stand less danger of oxygen toxicity.

Keszler : Mali, Pautler and Pultr from our department studied oxygen toxicity

histologically in 32 patients who were to undergo thoracotomy. The concentration of oxygen was from 80 to 90 % and the average duration 3 to 24 hours prior to operation. There were 14 controls and 18 patients who inhaled oxygen. With these concentrations and the times mentioned, there did not seem to be any histological difference between the two groups.

We were also interested in oxygen therapy and its influence on tissue oxygen tensions under conditions of an emergency distribution of the blood. We started with haemorrhagic shock in dogs. VrAnovi studied tissue oxygen tensions in muscle, liver and brain. In averages from 10 experiments

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during a control period, inhalation of oxygen caused considerable increase in tissue oxygen tension in the muscles. During haemorrhagic shock (arterial pressure of 40 mm Hg for about 90 minutes) the inhalation of oxygen did not cause any increase in tissue oxygen tension, while the arterial oxygen tension increased considerably. We could not confirm that arterial oxygen tension is diminished in haemorrhagic shock.

Giving oxygen under the same conditions but with an oxygen electrode in the brain showed that while in the muscle 0 2 inhalation had no effect on the tissue oxygen tension, inhalation of 100 "/o oxygen returned brain oxygen tension practically to normal values.

Zngvar : I am very much impressed with Dr. Keszler's experiments on the effect

of administering oxygen in shock. In our experience, the brain oxygen tension is again a matter of auto-regulation of the cerebral vessels. With auto-regulation existing you can administer oxygen and the cerebral tissue oxygen tension does not change very much from the normal, that is around 20-30 mm Hg. But if the regulation is impaired, as occurs with cerebral hypoxia, and 40, 50 or 60 % oxygen is administered, the oxygen tension of the brain may rise to very high levels.

need for oxygen enrichment in myogardial infarction, shock and following cardiac arrest

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