Effectiveness of Venous Oxygenation during Progressive Hypoxia

EXPERIMENTAL APPROACHES

Effectiveness of Venous Oxygenation during Progressive Hypoxia* Monte Lichtiger, M.D.,o° Joanne McDermott, B.S.,t and Frank Collan, M.D.*

This study was undertaken to assess the effect of extracorporeal oxygenation on the heart and on gas exchange. In acute experiments on anesthetized, closed· chest greyhounds, venovenous shunting under puhatile pressure did not affect heart rate, cardiac output or arterial blood pressure. Then progressive hypoxia was produced by hypoventilation and the venous oxygen tension was raised by mechanical oxygenation. The magnitude of this effect was inversely related to the degree of existing hypoxia. With the blood Bow from a single cannula in a femoral vein and with an efficient oxygenator, a volume of oxygen amounting to half of the animal's consumption could be transferred.

Compared with the difficulty in assessing the benefit of assisted circulation in heart failure, the proposition to use oxygenating devices in respiratory failure is simple and obvious. Therefore, it is not surprising that the investigators who designed screen, 1 disc,2 bubble;{ and membrane oxygenators 4 almost two decades ago envisaged their first application in pulmonary insufficiency rather than in open heart surgery. Thus, one year before the first open cardiotomy under total cardiopulmonary bypass, the only well-documented clinical use of extracorporeal oxygenation in respiratory failure was described.1) For 75 minutes 1,300 ml of venous blood from a saphenous vein were drained into an oxygenator and pumped back into an antecubital vein. During perfusion the patient's cyanosis, dys-

pnea and orthopnea were relieved and the arterial oxygen saturation, carbon dioxide content and hydrogen ion concentration improved. Because of chronic pulmonary fibrosis the relief was only temporary. Since then investigators have explored the feasibility of prolonged oxygenation of venous blood, but excessive trauma to the blood and damage to the lungs 6 ' s prohibited human applications. Though it has been known for a long time that the damage to the blood cells and the lipoproteins of the plasma is caused by the open gas-toliquid interface, the industrial development of a separating, thin, sturdy and leakproof polycarbonate-silicone membrane is a recent development. 9 This has led to improved design and efficiency of membrane oxygenators which make atraumatic oxygenation for many days possible. 1 0.11 Thus, extracorporeal support of patients with pulmonary insufficiency holds more promise in the near future than in the preceding two decades. Because the variability of hypoxia, rate of flow, cardiac output and the oxygenating capacity of the various devices used precluded an evaluation of the efficacy of the procedure, we have undertaken

·From the departments of Anesthesiology and Surgery, University of Miami School of Medicine, and the Veterans Administration Hospital, Miami, Florida. This work was supported in part by USPHS NIGMS Research Training Grant 1 TOI GMOl714-01 and NIH Research Grant HE 09868-02.

··USPHS Postdoctoral Research Fellow in Anesthesiology. tResearch Associate, Veterans Administration Hospital. :j:Chief, Nuclear Medicine Service, Veterans Administration Hospital; Research Professor of Anesthesiology and Surgery, University of Miami School of Medicine, Miami, Florida.

284

285

VENOUS OXYGENATION DURING PROGRESSIVE HYPOXIA

controlled experiments on acute hypoventilation. METHODS

Greyhounds weighing between 20 and 31 kg were premedicated 1M with propiopromazine (2 mg/kg) and anesthetized with an intravenous injection of pentobarbital (45 mg/kg). The dogs were then intubated with cuffed intratracheal tubes and placed on a Harvard respirator. After the intravenous injection of 4 mg/kg of herparin a thin-walled polyvinyl cannula with multiple slits was introduced into a femoral vein and advanced into the thoracic cavity. Through this catheter venous blood was drained by gravity into a pump-oxygenator which had been primed with 1,200 ml Ringer's solution. Oxygenation of blood was accomplished by the dispersion of small oxygen bubbles through a ceramic microfilter. 3 The small amount of oxygen needed to saturate fully even severely hypoxic blood did not create the "dry" foam seen in oxygenators using a high flow or large oxygen bubbles. Although a larger defoaming area was needed to coalesce the small bubbles, the process was devoid of the vigorous bubbling so traumatic to blood. The oxygenated blood was then returned by a pneumatic ventricle pump12 into a jugular vein. Blood flow was monitored by an electromagnetic flowmeter probe in the venous drainage line. A thermoregulated electrode system was used to measure gas tensions and pH in blood samples withdrawn from a carotid artery and the right ventricle. Cardiac output was measured with the green dye dilution method. Hypoxia was produced by reducing the stroke volume of the respirator. This period obviously could not last long enough to establish a steady state, but was interrupted after a few minutes when two arterial p02 determinations showed similar values.

HYPOVENTILATION

mm Hg

RESULTS

In 11 artificially ventilated greyhounds of an average weight of 28 kg the procedure of venovenous pumping without oxygenation of about 1,400 ml of blood per minute was studied first. Since the pulsatile pumping did not affect cardiac output, stroke volume, mean arterial pressure, arterial p02 and pC0 2, we present the results in graphic fonn only (Fig 1). Then acute hypoventilation was produced and p02, pC0 2, pH and buffer base were measured in arterial and venous blood. The same measurements were repeated during venous oxygenation (Table 1 ). The rate of blood flow through the extracorporeal shunt was kept constant during this period. Hypoventilation produced an average arterial p02 of 45 mm Hg and an average venous p02 of about 20 mm Hg. Extracorporeal oxygenation produced in all instances an increase in venous, ie, right ventricular, and in arterial p02' Due to the short period of hypoventilation only mild hypercarbia developed, and therefore the average arterial and venous pC0 2 was only slightly reduced during the oxygenation of blood. A bar graph gives a clearer presentation of the marked p02 and the minor pC0 2 changes (Fig 2). The changes in pH were correspondingly small. The acidemia before and during venous oxygena-

HYPOVENTILATION & VENOUS OXYGENATION

100--------------------80 -

• ~

----------------80

ARTERIAL BLOOD RT. VENTRICULAR BLOOD

- ------- --

60 - - --

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40 - --

20 - -0-

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p0 2

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- ~ ~ - - 40

~~

-

-

p02

p C0 2

19

60

~ -l~~j-o

- - 20

FIGURE 1. Cardiac output, stroke volume, mean arterial pressure, arterial P02 and Pc<>:! of nornlally ventilated greyhounds before and during venovenous pumping without oxygenation.

CHEST, VOL. 59, NO.3, MARCH 1971

286

L1CHTIGER, MCDERMOTT AND GOLLAN

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50

80

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p 0 2 BEFORE FIGURE

80

60

100

Although previous investigations have shown that

CARDIAC OUTPUT

STROKE VOLUME

M.A.P.

liters/min.

cc/beat

mmHg

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CONTROL DURING BYPASS

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3.0

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120

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(mm Hg )

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p C0 2

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3. The relationship between the degree of hypoxemia and the efficacy of its treatment by venous oxygenation. FIGURE

50

ARTERIAL

100

160

56

20

all pump-oxygenators worthy of that name can increase the oxygenation of venous blood, the present study considers the hemodynamic and gas exchange effects separately. In dogs anesthetized with sodium pentobarbital, gravity drainage of about half of the venous return and pumping it back under pulsatile pressure into a vein, did not change heart rate, stroke volume, cardiac output, mean

125

40

1.0

p0 2

200

4.0

2.0

10

2. The effect of venous oxygenation on blood gas tensions of hypoventilated greyhounds.

DISCUSSION

•

0

(mm Hg)

tion was due to a loss of buffer base (Table 1). The increase in venous and in arterial p02 produced by extracorporeal oxygenation was inversely related to the degree of the previously induced hypoxemia (Fig 3).

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CHEST, VOL. 59, NO.3, MARCH 1971

VENOUS OXYGENATION DURING PROGRESSIVE HYPOXIA

287

Table 1 P02

PC02

A

A

Before

Before

Durin~

Durin~

Flow

ART

VEN

A-V

ART

VEN

A-V

ART

VEN

A-V

ART

VEN

A-V

1,050 1,070 910 1,250 1,714 1,500 1,200 1,200 1,200 1,714 1,714 1,260 1,500 1,400 1,040 2,300 1,300 1,400 1,600 Ave S.D.

42.0 52.0 32.2 8.0 53.5 76.2 28.7 70.5 59.8 25.0 29.0 14.0 64.5 76.0 37.5 77.0 23.0 40.0 55.0 45.5 21.6

30.8 30.7 18.0 8.0 30.7 30.8 19.0 30.0 31.7 7.0 14.0 8.0 23.0 21.0 16.5 17.5 9.0 10.0 18.0 19.7 8.98

11.2 21.3 14.2 0.0 22.8 45.4 9.5 40.5 28.1 18.0 15.0 6.0 41.5 55.0 21.0 59.5 14.0 30.0 37.0 25.8 16.7

67.5 77.2 66.8 37.5 72.2 112.0 103.8 102.1 92.8 92.0 87.0 64.0 108.5 110.5 56.5 92.0 73.0 78.0 79.0 82.8 12.2

42.2 46.2 36.7 36.7 46.2 42.2 43.9 49.0 49.0 76.0 62.0 41.0 32.5 44.2 38.0 47.5 48.0 48.3 33.5 45.4 10.1

25.3 31.0 30.1 0.8 26.0 69.8 59.9 53.1 43.8 16.0 25.0 23.0 76.0 63.5 18.5 44.5 25.0 29.7 45.5 37.2 20.1

35.9 33.2 58.3 38.0

41.8 42.9 62.4 47.2

5.9 9.7 4.1 9.2

2\1.l 26.7 44.6 31.4

41.8 37.3 51.0 40.4

2.7 10.6

43.2 44.2 39.6 78.5 26.0 37.0 23.6 34.5 65.0 29.3 50.0 17.5 26.0 58.8 41.0 15.9

57.8 52.3 53.8 80.2 34.5 43.5 32.2 49.4 67.5 42.0 57.0 25.5 34.5 74.0 49.9 14.8

14.6 8.1 14.2 1.7 8.5 6.5 8.6 14.9 2.5 12.7 7.0 8.0 8.5 15.2 8.9 4.1

52.5 49.8 47.2 46.6 20.2 32.5 22.6 33.2 50.0 26.0 64.0 16.5 27.5 43.5 36.9 1:l.2

60.2 54.6 54.0 62.6 34.2 45.5 33.0 46.5 48.0 41.0 79.0 27.5 40.0 52.8 47.2 12.4

7.7 4.8 6.8 16.0 14.0 13.0 10.4 13.3 2.0 15.0 15.0 11.0 12.5 \).3 10.0 4.2

pH

Buffer Base "-

A

Before

During

During

Before

A

A

Flow

ART

VEN

A-V

ART

VEN

A-V

ART

VEN

1,050 1,070 910 1,250 1,714 1,500 1,200 1,200 1,200 1,714 1,714 1,260 1,500 1,400 1,040 2,300 1,300 1,400 1,600 Ave S.D.

7.18 7.26 7.03 7.25 7.00 7.20 7.50 7.56 7.38 7.20 7.12 7.25 7.10 6.88 7.18 7.05 7.35 7.17 6.98 7.19 .17

7.16 7.19 6.97 7.22 6.99 7.16 7.42 7.53 7.11 7.14 7.11 7.20 7.04 6.88 7.12 7.03 7.25 7.14 6.94 7.14 .IS

0.02 0.07 0.06 0.03

7.25 7.26 7.11 7.33 7.05 7.16 7.51 7.53 7.48 7.27 7.13 7.29 7.07 6.98 7.22 6.88 7.34 7.50 7.03 7.23 0.19

7.19 7.19 7.11 7.27 7.04 7.15 7.47 7.48 7.45 7.21 7.05 7.21 7.05 6.96 7.14 6.83 7.23 7.07 7.00 7.16 0.17

0.06 0.07 0.00 0.06 0.01 0.01 0.04 0.05 0.02 0.06 0.08 0.08 0.02 0.02 0.08 0.05 0.11 0.43 0.03 0.07 0.09

-14.8 -11.5 -18.0 -10.2

-14.5 -12.3 -20.5 - 9.3

-11.2 +10.0 +12.0 +15.5 -16.8 -16.7 -15.8 -18.0 -22.0 -16.5 -16.7 -14.5 -18.3 -18.3 -11.2 11.3

- 9.8 + 7.5 +21.0 - 7.5 -16.5 -15.2 -14..5 -17.0 -21.5 -15.2 -16.2 -14.9 -16.7 -17.8 -11.7

om

0.04 0.08 0.03 0.27 0.06 0.01 0.05 0.06 0.00 0.06 0.02 0.10 0.03 0.04 0.06 0.06

6.4

9.0

arterial pressure or arterial p02 and pC0 2. In eventual human applications with different anesthetic agents the baroreceptors in the large veins and the right heart may respond to the high pulse pressure of a ventricle pump and changes in flow, pressure and heart rate may occur. The degree of prior hypoventilatiori evidently defines the extent to which extracorporeal oxygenation can increase the venous p02' 11 If the gradient

CHEST, VOL. 59, NO. 3, MARCH 1971

lOA

ART

VEN

0.3 0.8 2.5 0.9

-13.5 -14.0 -16.2 - 8.2

-12.7 -14.0 -14.8 - 8.3

0.8 0.0 1.4 0.1

1.4 2.5 9.0 23.0 0.3 1.5 1.3 1.0 0.5 1.3 0.5 0.4 1.6 0.5 2.7 5.S

-11.0 +13.8 +14.5 + 9.5 -16.5 -17.7 -14.4 -21.0 -20.0 -16.0 -22.2 -15.S - 0.8 19.2 -10.5 11.7

- 9.5 +13.0 +14.0 +15.0 -13.2 -180 -13.8 -17.2 -21.2 -14.8 -22.8 -15.0 -18.3 -18.5 -10.6 11.9

1.5 0.8 0.5 5.5 3.3 0.3 0.6 3.8 1.2 1.2 0.6 0.5 17.5 0.7 2.2 4.1

A-V

A-V

between venous and alveolar p02 is small, extracorporeal oxygenation has little to offer and little to accomplish. On the other hand, if the gradient is large, an efficient oxygenator may raise the venous p02 to the alveolar p02' The extent to which this can be accomplished depends on the rate of blood flow. In our experiments a large, thin-walled catheter with multiple holes shunted about half of the cardiac output from the right atrium into the

288

L1CHTIGER, MCDERMOn AND GOLLAN

oxygenator. Knowing the hematocrit, the p02' pH and temperature of blood entering and leaving the natural and the artificial lung, we calculated the rate of oxygen transfer of both gas exchangers. This amounted to an average of 140 mI O 2 per minute for the lungs and 74 mI O 2 per minute for the oxygenator. REFERENCES

2 3 4

5

Gibbon TH Jr: Artificial maintenance of circulation during experimental occlusion of pulmonary artery. Arch Surg 34:1105,1937 Bjork VO: An artificial heart or cardiopulmonary machine. Performance in animals. Lancet 1:491, 1948b Clark LC Jr, Gupta VB, Gollan F: Dispersion oxygenation for effecting survival of dogs breathing pure nitrogen for prolonged periods. Proc Soc Exp Bioi Med 74:268, 1950 Clowes GHA Jr, Hopkins AL, Newell WE: An artificial lung dependent upon diffusion of oxygen and carbon dioxide through plastic membranes. J Thorac Cardiovasc Surg 32:630, 1956 Helmsworth JA, Clark LC Jr, Kaplan S, et al: Clinical use of extracorporeal oxygenation with oxygenator-pump. JAM A 150:451, 1952

6 Krasna IH, Steinfeld L, Kreel I, et al: Prolonged venovenous perfusion with oxygenation in experimental hypoxia of respiratory origin. Surg Forum 11 :218, 1960 7 Zotti EF, Ikeda S, Lesage AM, et al: Prolonged venovenous perfusion with a membrane oxygenator for respiratory failure. J Thorac Cardiovasc Surg 51:383,1966 8 Robb WL: Thin silicone membranes-their permeation properties and some applications. General Electric Research and Development Center, Report No. 65-C-031, Schenectady, NY 1965 9 Kolobow T, Zapol W, Pierce JE, et al: Partial extracorporeal gas exchange in alert newborn lambs with a membrane artificial lung perfused via an A-V shunt for periods up to 96 hours. Trans Amer Soc Artif Intern Organs 14:328, 1968 10 Hill JD, Bramson ML, Hackel A, et al: Laboratory and clinical studies during prolonged partial extracorporeal circulation using the Bramson membrane lung. Circulation 37 (suppl 2) :139, 1968 11 Galetti PM, Brecher GA: Heart-lung Bypass. New YorkLondon, Grune and Stratton, Publishers, 1962, p 56 12 Hufnagel CA, McAlinden JD, Vardes A, et al: Simplified extracorporeal pumping system. Trans Amer Soc Artif Intern Organs 4:60, 1958 Reprint requests: Dr. Gollan, VA Hospital, Miami 33125

In Search of the Prehistoric Man The first fossil skull to arouse any interest in scientific circles was the one discovered in 1856 in the Feldhofer cave between Duesseldorf and Eberfeld in the side of a ravine called the Neanderthal. Actually the top of the cranium was discovered. A most English anatomist, King, saw in it an authentic ancestor of the human species: Homo neanderthalis. We had to wait until 1908 before the complete skeleton of the Neanderthal man was discovered in France. He had a large head on a small body and was only between 5 feet 1 inch and 5 feet 3 inches tall; although he stood upright, he walked with stoop, head thrust forward and knees bent. In Decemher 1891, Dubois of Holland discovered the top of the cranium of what was considered Pithecanthropus, on the island of Java. It characteristically combines the characteristics of ape and man. Of the ape it has the flat cranium, the bony excrescences above the orbits and that

of other excrescences above the nape; it also has ape-like teeth. The femur shows very little difference from the femur of modern man. We can fix the age of the Pithecanthropus between 100,000 and 300,000 years. On December 2, 1927, Black of Canada presented a report on Sinanthropus pekinensis. It had a low forehead, flat cranium, a ridge of bone above the orbits and occipital ridge of the nape; his teeth were intermediate between those of the anthropoid and those of modem man. Thus, 100,000 years ago there lived in South-west Asia manapes whose anatomic features were clearly intermediate between those of modern man and those of real anthropoids. Senet, A: Man in Search of his Ancestors, (translated by Barnes, M), McGraw-HilI, New York, 1956

CHEST, VOL. 59, NO.3, MARCH 1971