Design and Use of a Pump-Oxygenator

Design and Use of a Pump . Oxygenator ELTON WATKINS, JR., M.D. ALEXANDER C. HERING, CAPT. (MC) USN* HERBERT D. ADAMS, M.D.

WITHIN the past decade the medical profession has seen a remarkable application of biophysical and engineering principles to surgery in the development of hElart-lung machines for temporary bypass of the central circulation. A diseased heart or aorta, quiet and empty of blood, may now be opened for purposes of performing definitive surgical procedures. Certain anatomic defects which hitherto were untreatable by direct attack can be repaired, and a variety of other lesions, treated in the past with only partial success by "blind" methods, can now be visualized and corrected in a precise fashion. Moreover, there is evidence to indicate that this technique has applications in other fields than cardiovascular surgery. Partial bypass has proved useful in the perfusion of isolated segments of the body so that high concentrations of cancer chemotherapeutic agents may be confined to the perfused segment. 6 It is possible that the circulation may be supported successfully to tide the body over severe transient circulatory derangements such as the shock of coronary thrombosis. 22 Our experience in this field has led us to develop certain perspectives concerning the technique of extracorporeal perfusion and to apply these concepts in the design of a pumpoxygenator (Fig. 1).

From the Department of Surgery, Lahey Clinic, the Surgical Research Laboratory and Surgical Service, U.S. Naval Hospital, Chelsea, Massachusetts and the Surgical Service, New England Deaconess Hospital. With the technical assistance of Ralph W. Sommers, Joel A. Johns and Mary Ann Dalton, R.N. Aided by Grants from the National Heart Institute, U.S. Public Health Service (H-3803) , The Lahey Foundation, and American Proctologic Research Foundation. The Surgical Research Laboratory of the U.S. Naval Hospital, Chelsea, is also supported by grant funds from the Office of Naval Research. This article expresses the personal opinions of the authors and does not necessarily reflect the official opinion of the United States Navy.

* Head of Thoracic Surgery, U.S. Naval Hospital, Chelsea, Massachusetts.

609

610

WATKINS, HERING, ADAMS

Fig. 1. Our current pump-oxygenator utilizing gravity venous drainage, a disc oxygenator and DeBakey type pumps.

A pump may be purchased easily on the open market. However, the institution acquiring such a device must weld together a smooth operating team. For this purpose an experimental surgical laboratory is essential. After the clinical phase is initiated in a pump project, the laboratory must continue to function actively since each operation should introduce new possibilities for improvement which are best tested on animals before further clinical work is done. Lack of emphasis upon the problem of poor animal tolerance is unfortunate. The considerably greater tolerance of humans to extracorporeal circulation may be based upon a species variation of response to blood trauma inflicted by pumping. Better understanding of the mechanisms that lead to a high dog mortality during bypass would permit minimization of trauma responses having significance in extension of the technique into longer periods of human bypass. Sources of Information on Pump-Oxygenators

The current surgical literature contains numerous excellent articles on pump techniques--too many to list adequately in this report,

Design and Use of a Pump-Oxygenator

611

Representative articles of general interest are noted in the bibliography.2-5, 7, 8,12,14-16 A valuable reference book was the outcome of the Extracorporeal Circulation Conference sponsored by the U.S. Public Health Service, National Institutes of Health in 1957.1 Where possible, we have attempted to conform in this report to the nomenclature set forth by the nomenclature committee at that Conference. 10 Principles of Extracorporeal Circulation Technique

Certain principles appear to be common to all successful systems of extracorporeal circulation. Among these principles are the provision of an adequate flow rate for the time required for total cardiac bypass, the simulation of arterial blood gas concentrations in blood passing from the oxygenator to the arterial tree of the patient, minimal trauma to blood, and reliable operation of the mechanical system. BYPASS FLOW IN RELATION TO TIME REQUIRED FOR EXTRACORPOREAL CIRCULATION. The flow through the heart-lung machine should be adequate to meet body needs for long periods of bypass. On the basis of studies of oxygen depletion of mixed venous blood, a flow on the order of 2300 to 2500 cc. per minute per square meter of the body surface area would meet such a requirement. We have utilized the nomograms shown in Figure 2 to compute the body surface area in humans or dogs.* Pump operation is regulated to obtain a flow to the body tissues of 2500 mI. per minute per square meter as a minimum. Where a lesion is present which increases ineffective bronchial or AV shunt blood flow (which does not exchange gases), pump flow must be increased above the minimum figure. In this situation, we arbitrarily increase pump flow and measure evidences of adequate body flow as shown by arterial pressures, mixed venous oxyhemoglobin saturation and measurements of organ function (electroencephalography, radioiodine Diodrast clearance,25 and so forth). REPRODUCTION OF PHYSIOLOGIC ARTERIAL GAS TENSIONS. There is considerable evidence to indicate that inadequate oxygenation of blood in a mechanical apparatus results in a deleterious deficiency of tissue oxygen tension with resulting metabolic acidosis. Such a deficiency of oxygenation is aggravated by inadequate blood flow, which results in an excessive depletion of oxygen from mixed venous blood. Tissue oxygen tension is closely related to mixed venous blood oxygen tension

* The human body surface area nomogram is modified from the data of Talbot et al.23 The nomogram for dog body surface area is modified from the equation of Cowgill and Drabkin. 4 BSA in M2 = 0.2864 (wt. kg.)O.367(L meters) It should be noted that this equation in the Report of the Committee on Definition and Conformity of Nomenclature and Measurements in Extracorporeal Circulation10 is reproduced without exponent due to typographical error.

612

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B Fig. 2. Nomograms for computation of body surface area from height and weight in adults, children and dogs. The minimum pumping rate through the machine is set to give a minimum body flow of 2500 m!. per minute per square meter of body surface. A, Adults, children and infants; B, dogs.

Design and Use of a Pump-Oxygenator

613

so that reductions of mixed venous blood oxygen tension reflect degrees of tissue anoxia. Although hemoglobin gives up oxygen more easily at lower oxygen tensions, it is not apparent that such a facilitation of oxyhemoglobin dissociation is advantageous in view of the fact that considerable tissue anoxia must be present before facilitation may occur. Evidence also exists showing that excessively high blood oxygen tensions induced by over-oxygenation of blood in a mechanical lung are deleterious. It is not clear whether this is due to an ill-defined direct "toxic effect" of high oxygen tension in tissue or is more simply due to the persistence of minute oxygen bubbles in the blood stream following passage of supersaturated blood through orifices where cavitation may occur (jet effect at cannulas, and so forth). We have preferred to simulate closely the normal arterial blood oxygen tension on the order of 100 mm. of mercury. This gas tension is equivalent to an oxyhemoglobin saturation of 95 per cent. The more closely arterial and mixed venous blood oxygen tensions during bypass simulate intact basal conditions, the less likely are derangements of acid-base balance to occur. The underlying basis for such an alteration of acid-base balance is the development of metabolic acidosis due to an accumulation of anions ("fixed acids") during anoxic perfusions. Although acid-base derangements are buffered in the physiologic range by changes in the blood bicarbonate buffer system, it does not follow that extreme derangements resulting from anion excess should be corrected by extreme alterations of blood carbon dioxide tension. Extreme reductions of blood carbon dioxide tension (shifting blood hydrogen ion concentration from uncompensated acidosis toward the normal range) are accompanied by vasomotor changes and cation shifts which later aggravate the basic underlying defect of anion excess. 19 As a consequence, we have avoided hyperventilation prior to bypass and have adjusted the carbon dioxide tension within the gas phase of the oxygenator so that arterial blood carbon dioxide tension is simulated. We rely upon adequate blood oxygenation and flow to minimize metabolic acidosis. OTHER REQUIREMENTS FOR SUCCESSFUL BYPASS. Blood may be damaged by passage through unsuitable channels within the heart-lung machine. These channels should be designed to eliminate constrictions in tubing and excessive turbulence of blood flow. The necessity for reliable operation of the apparatus is obvious, as is the necessity for complete elimination of gas bubbles in blood passing back to the patient. Our Current Preferences as to the Type of Mechanical System

Although we were convinced from experience that the type of machine to be used was of less importance than a thorough understanding of perfusion principles, the generally satisfactory results obtained with certain types of oxygenators and pumps and our previous experience

614

WATKINS, HERING, ADAMS

with such types led us to select them for current usage. We have adhered to a gravity siphonage system for venous drainage, a disc type of oxygenator, and nonocclusive pumps of the DeBakey type. The gravity type of venous collection system, wherein siphonage effects are utilized to drain the venous blood from the occluded cavae into the machine, has the virtue of simplicity. No type of continuous monitoring or feedback control of venous inflow is necessary. Although monitoring devices and feedback controls may appeal to workers in this field, it is safer to avoid such controls where automatic functioning based upon design of the mechanical device permits elimination of a complex monitoring mechanism. Undoubtedly feedback controls are necessary for uniformly safe operation of low-prime machines at adequate flow volumes. The disc type of oxygenator presents the advantages of minimal trauma to blood, the lack of necessity for tricky foaming procedures and for refilming of the exposed blood surfaces if a film is lost during perfusion. With adjustment of ambient gas tensions, gas exchange is satisfactory. We prefer a roller pump of the DeBakey type because the low amplitude pulsations of such a pump produce less pulse recoil of small bore cannulas passing to the arterial tree. With high amplitude pulsation, we have seen trauma to arteries inflicted by vigorous pulse recoil at the cannula. It is quite possible that production of vigorous pulsatile action in a small volume regional chemotherapy perfusion may enhance the passage of toxic chemical agents from the perfused region to the general circulation. The blood channels within the machine should be designed to minimize turbulence and flow impedance. An effort should be made to keep the physical arrangement of pumps and oxygenator on the cabinet surface to such a location that a minimum circuit distance is produced consistent with easy sterile assembly. The component parts should be arranged conveniently so that the operator may visualize and adjust any part of the pumping circuit easily during conduct of bypass. CURRENT PUMP-OXYGENATOR

With this background in mind, a pump-oxygenator has been fabricated.* Various units of the extracorporeal circuit are located at a convenient table top level on a sturdy stainless steel cabinet. Such an arrangement permits the operator to work in a comfortable position and yet provides adequate siphonage for venous drainage into the single collecting chamber. The stainless steel cabinet, containing pump motors and electrical circuits, is pressurized by a blower fan connected

* Produced by Edward A. Olson of Ashland, Massachusetts. Engineer: Alexander M. Duncan.

De8ign and Use of a Pump-Oxygenator

615

to a snorkel tube with air inlet above the 5 foot level. Major high voltage electrical circuits are energized after pressurization of the cabinet. Although it is not obligatory that a pump-oxygenator thus meet specifications for operation in a hazardous gas atmosphere (apparatus such as electrocautery used in open heart surgery contraindicates the use of explosive anesthetic gases), we felt that it would be advisable to meet these requirements to minimize any peculiar medicolegal problems that might arise in the future directly concerning the pump-oxygenator. All blood contacting surfaces in the apparatus are fashioned of Pyrex glass or polished stainless steel. Each surface is coated with a longacting silicone resin. 27 The successive channels through which blood passes are as follows (Fig. 3).

Fig. 3. Assembly for total cardiac bypass. e, Venous cannulas and stainless steel Y tube for collection of venous blood from the obstructed cavae; V, venous chamber; 0, long oxygenator containing 64 stainless steel discs; R, radiant blood heater beneath oxygenator; P, arterial pump; F, arterial filter; S, suction pump for withdrawing blood from the endocardial cavity and delivering it to the venous chamber; M, gas flowmeter; B, gas bacterial filter; W, gas humidifier; se, snorkel tube for pressurization of cabinet; GS, general suction unit mounted on flexible metal frame at rear of the oxygenator.

Venous Chamber Venous blood is collected through cannulas placed in the obstructed cavae, passing by way of a stainless steel Y tube and large bore Tygon plastic tube to a venous collecting chamber. Blood enters the bottom of this chamber through a large bore orifice at the apex of a stainless steel cone. Observation of the channel flowing over the top of this cone permits one to monitor venous input at all

616

WATKINS, HERING, ADAMS

Fig. 4. Method of adjusting the degree of occlusion of plastic tubing by pump rollers. The vernier adjustment in the central shaft of the pump roller mechanism is rotated to give a measured degree of lumen clearance with each new lot of plastic tubing. The degree of clearance (in 0.001 inch increments) may be measured by the use of a feeler gauge inserted in the lumen of the tube as it is compressed in the pump track by the roller. times during bypass. The glass cylinder of the chamber is etched with two horizontal rings 2.5 cm. apart. The fluid volume contained between the rings is known. By obstructing the outflow beyond the venous collecting chamber and measuring the rate of rise between these two rings with a stopwatch, it is possible to compute the rate of flow (from 0 to 8 liters per minute) at any time during the bypass without interruption of flow to the patient. The upper compartment of the venous chamber serves as a defoaming and collecting channel for blood aspirated from the heart. A stopcock in the venous chamber outlet permits sterile withdrawal of venous blood for chemical studies. Oxygenator Blood flows from the venous chamber to the oxygenator through a large bore Tygon tube. For total cardiac bypass in adults, the oxygenator is fitted with a glass cylinder 18 inches in length. Within this cylinder, 64 discs are mounted on a sturdy steel shaft with thin spacers between the discs. Each flat, thin, stainless steel disc is coated with silicone grease during assembly. (In our experience, Teflon coated discs have flaked.) As the discs rotate and dip into blood flowing in the bottom of the cylinder, a constantly changing thin film of blood on each disc is presented for gas exchange and returned to the fluid pool. We have found it unnecessary to vary the number of discs used for perfusion on adults and larger children. During human perfusions from 2 to 6 liters per minute we have consistently produced effluent blood oxyhemoglobin saturations of 94 to 96 per cent by rotating 64 discs from 80 to 110 rpm. The discs are rotated by a variable speed alternating current motor contained within the pressurized cabinet and connected to the oxygenator disc shaft by a clutch mechanism.

Design and Use of a Pump-Oxygenator

617

The other end of the disc shaft may be fitted with a hand crank for emergency operation. For perfusion of small subjects and for regional chemotherapy perfusions, we use an 8 inch cylinder and shaft bearing 23 discs. This oxygenator circuit requires a smaller priming blood volume and is satisfactory for low flow perfusions. The same oxygenator end plates may be used in either the small oxygenator or large oxygenator. A different length disc shaft, glass cylinder, spanning rods and gas manifold are required for each size oxygenator. Arterial Pump

From the oxygenator, blood flows to the DeBakey type arterial pump mounted in front of the oxygenator. Tygon tubing leading from the oxygenator is held firmly in position in the U-shaped track of the pump by clamps mounted at either end of the track. Pump rollers milk blood along the tubing to propel it into the body at arterial pressure. We have found that reproducible roller pump function cannot be obtained unless the degree of occlusion of the tubing by the milking rollers can be adjusted and maintained accurately. Since successive lots of plastic tubing may vary in wall thickness from 0.002 to 0.003 inches, we have found it necessary to measure accurately the degree of roller occlusion for each lot of tubing. The adjustment is made to produce 0.010 inch tubing lumen clearance beneath the roller (Fig. 4). The pump rotor shaft is connected to a reduction gear powered by a third horsepower direct current electric motor. Pump revolution rate is governed by a variable control located immediately beneath the pump on the front surface of the cabinet. A small electric generator is geared to the pump rotor shaft and wired to a voltmeter mounted on the front of the cabinet. This meter registers the revolution rate of the pump whether it is driven by electric motor or by hand crank at times of power failure. Hand cranks for pumps and oxygenator are mounted in a recess in the side of the cabinet. Arterial Filter Blood flows from the arterial pump to a large capacity filter where it passes through a 40 mesh stainless steel screen before return to the patient. A stopcock is mounted in the filter for venting, sampling arterial blood, or injecting drugs into the arterial line. A second vent may also be tapped to give blood for hypothermic regional perfusions. Suction Pump Blood within the opened heart is aspirated into the oxygenator circuit by a second roller pump mounted near the venous chamber. Two suction lines are connected through the tracks of this pump so that two separate sump aspirators27 may be used in different regions of the endocardial cavity. The suction lines are connected to the inlet at the top of the venous chamber through a Tygon Y connector. Within the upper compartment of the venous chamber, this blood is defoamed by passing through a series of coarse mesh stainless steel screens very lightly coated with antifoam spray. Oxygenator Gas Supply In our experience, the most suitable gas mixture is a combination of 98 per cent oxygen and 2 per cent carbon dioxide. Large cylinders of this mixture are prepared and subjected to gas analysis prior to use. Gas is conducted to the cabinet through a pressure line at 60 psi passing to a gas flowmeter mounted conveniently on the surface of the cabinet. Following regulation of the rate of flow, the gas passes through a bacterial filter and humidifier before entering a manifold

618

WATKINS, HERING, ADAMS

within the oxygenator. Here the gas is directed through multiple small holes to blow directly on each rotating disc. Excess gas escapes through a vent in one end of the oxygenator. To achieve adequate oxygenation in adult total perfusions, a gas flow rate of 10 liters per minute is maintained. In regional perfusions and low flow perfusions with the small oxygenator, a gas flow rate of 5 liters per minute is adequate. Blood Temperature Control

We have avoided generalized blood hypothermia because of the added inherent complexities. Blood is warmed to normal or hyperpyrexic levels by a radiant heater located beneath the Pyrex glass cylinder of the oxygenator. Since blood temperature has not been variable enough to warrant direct coupling of thermostatic controls to a blood temperature measuring device, the heater level is adjusted by a variable resistance control mounted on the front of the oxygenator cabinet. The radiant reflector has interchangeable short or long plug-in heater coils for use with the short or long oxygenator. Blood temperature is monitored through a thermocouple placed in a well within the outlet line from the oxygenator and by means of a similar thermocouple which may be inserted in a body cavity of the patient and plugged into the cabinet of the oxygenator. The two temperature meters are mounted in the front panel of the oxygenator. Commercial temperature meters have been modified so that they may be calibrated without disconnecting the thermocouple lines. Each temperature meter may be removed from the oxygenator for use in other studies or in postoperative care on the wards. Electrical Circuits

Electrical power in the form of 110 volt 60 cycle alternating current is delivered to the side of the cabinet through an explosion-proof connection. The standard reverse-service connector has been modified to permit locking of the plug into the cabinet during operation to prevent inadvertent disconnection of the line during operation. The blower-fan motor, which pressurizes the cabinet, is of the shaded-pole type without brushes and starts immediately when the power cable is plugged into the cabinet. Other high voltage circuits are activated by switches following pressurization. Operation of these circuits is indicated by signal lights. Alternating current at 110 volts is used to power the oxygenator heater, the disc drive motor control and the pressure-fan motor. Electrical power for the arterial and suction pumps is converted to direct current by heavy-duty selenium rectifiers. In the armature circuit, a variable output transformer is placed ahead of the rectifier to govern pump rotation rate. A choke coil follows the armature rectifier to filter out pulsations and provide even gradation of pump revolution rate. To maintain constant torque at all revolution rates, the field voltage of each pump motor is held constant by passage through a separate constant voltage transformer and rectifier circuit. The armature circuits are protected by circuit breakers so arranged that the alternating current supply to the motor is interrupted when armature current flow reaches an abnormally high value. Such a situation is likely to develop in instances of jamming of the pump rotor and may cause damage to the electrical coils of the motor if persistent. Circuit breakers are utilized to eliminate the necessity for changing fuses in an emergency situation. Selenium rectifiers were used instead of an electronic tube thyratron circuit to convert alternating to direct current. With selenium rectifiers there is no danger of vacuum tube failure during a crucial phase of pump operation, and no warm-up time is necessary; thus, the pumps are available for immediate operation once

619

Design and Use of a Pump-Oxygenator

the electrical circuits are activated. There has been no measurable temperature rise within the cabinet during operation. The pump revolution rate may be varied smoothly from 0 to 400 rpm with measurement of the actual mechanical rate of pump-shaft rotation by the shaft tachometer.

Flexiframe A flexible metal laboratory frame mounted at the rear of the cabinet is useful for supporting our general suction unit conveniently and in providing suitable laboratory clamps holding the arterial lines, suction lines and venous connectors.27 BLOOD TRAUMA WITH THIS APPARATUS

Care was taken in design of the machine to minimize factors causing Table 1. Blood Findings During Recirculation Through the Pump-Oxygenator Time Min. Run Flow, ml./min. Pump, rpm Disc, rpm Blood Temp., C.

1400

1401

1430

1500

1530

1600

1630

1700

0

1

30

60

90

120

150

180

2700

2700

2560

7500

7500

220

220

215

90

90

90

30.5°

30.5°

33.0°

2560 2700 to 7500 220 220 to 220 400+ (max.) 90 to 90 90 110 34.0° 34.8° 35.8° to 33.5° 44.0 45.0 45.0 132.5 145.0 175.0 2560

44.5 44.5 Hematocrit 43.5 Plasma Hemoglo- 21.0 22.75 66.5 bin Observed, mg. % mg. 11.38 33.25 66.25 72.5 %/2X 10.5 prime 19.42 19.25 Oxygen Capacity, vol. % 20.2 Oxygen Content, 19.40 20.5 vol. % 103.9 OxyHb. Satura- 100.8 106.5 tion, % 19.9 16.5 G0 2 Content, 20.7 mm./L. 7.29 7.37 pH 7.27 42.5 Bb+, mm./L. 42.5 42.5 pC0 2, mm.Hg. 46.9 33.0 51.0 178,000 152,000 Platelets, per cu. 256,000 mm. 142 142 Na+, mEq./L. 4.3 3.9 K+, mEq./L. 96.5 101.5 Cl-, mEg./L. 0.243 Fibrinogen, 0.233 0.236 gm./100 ml. Filter deposit, 0 mg.

87.5

400+ 400+ (max.) (max.) 110

110

36.2°

37.7°

45.0 205.0

45.0 230.0

102.5

115.0

19.24

18.5

99.2

95.2

13.7

8.75

7.43 41.0 24.8 134,000

7.56 38.5 12.7 96,000

147 4.8 101.5 0.253

140 6.0 102.7 0.246 1150

620

WATKINS, HERING, ADAMS

200

300

400

500

700

.,.. CIRCUITS .. LITERS TOTAL FLOW Fig. 5. Change of rate of production of free plasma hemoglobin with consecutive varying degrees of roller compression of pump tubing. Fresh ACD blood, 1000 mI., was pumped at 28° C. through a circuit consisting of pump tubing, filter and arterial cannula passing to the bottom of a siliconized Kelley flask. Tubing compression was varied and pump revolution rate altered to give a constant flow rate. Rate of free hemoglobin production declines in all successive periods except the period of occlusive pumping. However, all degrees of compression give easily tolerable plasma hemoglobin levels. Because of considerations, such as minimization of tubing wear and avoidance of high line pressures, nonocclusive 0.010 inch pumping is preferred to occlusive pumping. In a study of hemolysis rates, the fact must be considered that the more fragile elements of the red cells will be broken down at an increased rate early in the experiment. The rate of change for hemoglobin concentration is corrected to that occurring in twice the priming volume of 3000 mI.lO

excessive trauma to blood during its passage through the foreign environment. The minimal derangements observed during in vitro studies indicate the success of such precautions (Table 1). The studies were done under aseptic conditions with 3000 ml. of freshly drawn Type 0 heparinized blood (40 mcg. per milliliter) in the machine. The circuit shown in Figure 3 was used. Attention is directed to the maintenance of adequate platelet concentrations and the minimal plasma hemoglobin values despite protracted pumping-two hours at 2.5 liters per minute followed by one hour at 7.5 liters per minute. We hope that similar reports with other types of pump-oxygenators will be forthcoming so that a critical comparative evaluation of various machines can be made. Continuing improvement of the design of our machine will facilitate extension of the pump-oxygenator technique to prolonged circulatory support and to the fascinating field of suprabasal perfusion. A DeBakey pump used asa completely occlusive pump is not significantly more traumatic to blood than it is when operated as a nonocclusive pump, with a slight residual lumen remaining in the tubing during roller compression (Fig. 5). However, cannula pulsations are more

Design and Use of a Pump-Oxygenator

621

vigorous with occlusive pumping, the pump tubing becomes fatigued and may break after several hours of testing and tremendous pressures can build up when a line is clamped beyond the pump. As a consequence, we prefer a nonocclusive setting of the verniers of the rollers (Fig. 4). We have found 0.010 inch lumen clearance useful. This degree of occlusion gives a moderately nonlinear relationship between pump revolution rate and flow under operating conditions (Fig. 6). Since the relationship FLOW

(Liters/min.) 9

8 7

6 5 4

3

50

100

Fig. 6. Pump output with varying degrees of roller occlusion. The theoretical maximum output is computed from measurements of the quantity of fluid contained within the plastic tubing on the pump track multiplied by the rotation rate. The observed outputs of the pump are given for varying degrees of occlusion. Pumping against a 4 mm. arterial cannula and 100 mm. of mercury pressure head.

between revolution rate and flow need not be known during bypass (pump revolutions being governed in each instance by the desired flow as actually measured during the bypass), nonlinearity in the relationship between revolution rate and flow is not an undesirable feature of the pump mechanism. USE OF THE PUMP-OXYGENATOR

Sterilization and Assembly of the Apparatus After use, all blood contacting parts are completely dismantled, rinsed, soaked in Hemosol detergent, and then washed with hot tap

622

WATKINS, HERING, ADAMS

water through all cycles in a commercial home dishwasher. The parts are then rinsed twice with glass-distilled water in the dishwasher and cycled twice through the drying stage. New plastic tubing (Tygon B-44-3) is cut to suitable lengths and soaked in detergent, soaked in hot running tap water and rinsed with running glass-distilled water. After cleaning, the parts are handled with rubber gloves only. The apparatus is wrapped for sterilization in the dismantled condition. The oxygenator disc shaft is assembled with the required number of discs lightly coated with silicone grease. The coarse mesh screens in the upper assembly of the venous collecting chamber and the cone within the venous collecting chamber are lightly sprayed with antifoam and wiped with lint-free cloth prior to sterilization. Glass and metal parts of the apparatus are autoclaved at 2500 F. for 60 minutes. Plastic tubing is autoclaved at 2500 F. for 30 minutes followed by drying of the tubing for two hours with a steam-jacket cycle at atmospheric pressure. The tubing must be carefully placed on a form to prevent distortion during sterilization and drying. Blood contacting parts, gas channels, and the general suction unit are assembled under sterile operating room conditions. The venous and arterial lines are covered with Teflon plastic sleeves. The sleeve serves to maintain line sterility, being cut away just before transfer of the lines to the operating field. The laboratory flexiframe is assembled under sterile conditions with the blood lines and sterile general suction unit held in sterile laboratory clamps. The flexible frame is then covered completely with a sterile wrapper to maintain asepsis of the area until lines from the apparatus are to be connected to the patient. Priming the Apparatus

Fresh heparinized blood, 3000 mi., is used to prime the long oxygenator circuit. For regional perfusions and small flow perfusions with the short oxygenator, 1500 ml. is used. Although it is quite possible to conduct bypass with 2500 ml. of blood priming the long oxygenator or 1000 ml. of blood priming the short oxygenator, we prefer to have a larger volume present in the machine since any transient impedance of venous return or shifts of blood within the body reducing venous return to the machine may rapidly deplete an apparatus of blood when adequately high flow rates are being maintained. A level-sensing electronic control of pump output may minimize this hazard, but such controls may be harmful in reducing flow rates at a crucial point in the patient's adjustment. Consequently we prefer a large prime for maximal safety of operation. Thoracic surgery at the Lahey Clinic is customarily performed in the afternoon. We prefer that priming blood be drawn from walking donors

Design and Use of a Pump-Oxygenator

623

on the morning of a bypass, although blood drawn the evening before has been used without difficulty. The blood is collected in plastic bags or siliconized glass bottles to which heparin has been added at the factory. Intermatching is carried out by means of both high protein crossmatches and Coombs crossmatches between prime blood, transfusion blood, and the patient. All priming blood is refrigerated until placed in a 390 C. water bath one hour before introduction into the apparatus. Priming is carried out over the course of ten minutes as vessel cannulation is completed. Several extra transfusion sets are assembled and connected to orifices in the top of the venous chamber for immediate transfer of reserve blood into the machine should a need arise during bypass. Priming blood treated with the new chelating agent, Edglugate-Mg,21 has functioned quite satisfactorily in the laboratory but we have not had occasion as yet to utilize it during bypass in humans. At present, we are also carrying out an experimental study of the properties of frozen, glycerolized blood when used as a priming medium for this pump-oxygenator.* Preliminary investigations suggest that such blood will be the prime of choice for all types of bypass in the future. ls Control of Blood Coagulation

We administer heparin in concentrations of 40 mcg. per milliliter of priming blood and in concentrations of 20 mcg. per milliliter of blood volume to the patient just after introduction of the first cannula. Each kilogram of body weight is considered equivalent to 100 ml. of body blood volume for purposes of heparinization. Computations of heparin and heparin antagonist drug dosage are carried out in terms of the micrograms required per milliliter of blood, using this assumed blood volume at all times. We use Polybrenet to neutralize heparin effects.2o The Polybrene is administered after blood heparin activity is measured by determination of a Polybrene titration curve in the operating room. This titration is performed by the technique of Hurt, Perkins, Osborn and Gerbode. 13 Polybrene is preferred because it appears to give a firmer in vitro clot in titration studies. When arterial hypotension exists, it is necessary to administer Polybrene slowly in a small volume of diluting fluid to avoid further mild hypotensive effects of the agent. Techniques for Measuring the Status of the Patient

Arterial blood pressure and venous pressure are monitored continu-

* In collaboration with the Chelsea Naval Blood Preservation Laboratory and the Protein Foundation, Inc. t Kindly supplied by Abbott Laboratories, North Chicago, Illinois.

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Fig. 7. Introduction of arterial catheter for sampling and monitoring blood pressure. (1) The catheter is introduced through a small incision in the vessel wall and secured with a figure-of-eight silk suture. (2) The catheter is also secured to the skin edge.

ously during the course of operation. Suitable peripheral vessels are cannulated with fine plastic catheters connected through strain gages to a recording oscilloscope. These catheters may be introduced under local anesthesia; special cut-down trays are prepared for this purpose. The correct types of fine bulldog artery clamps, Adson dural forceps, and fine scissors facilitate prompt and atraumatic catheterization of small vessels (Fig. 7). We have stopped the routine measurement of blood hydrogen ion concentration during operation. On occasion, when the adequacy of flow or patient status is in question, we measure blood hydrogen ion concentration with an anaerobic glass electrode assembly at 38° C.* We perform occasional spot checks of blood carbon dioxide and oxygen concentration using conventional Van Slyke manometric techniques or occasionally monitor samples for blood oxyhemoglobin saturation with a cuvette oximeter.t 24 Hemostasis and Blood Loss

Although the thought has been advanced that all hemostasis problems • Model Gs pH Meter and Blood Electrode Model No. 290-31, Beckman Instruments, Inc., Fullerton, California. t Oximeter Galvanometer Model X-60A, Waters Conley Company, Rochester, Minnesota.

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in cardiac bypass stem from errors in surgical technique, it is apparent that the achievement of hemostasis in the wound of a patient undergoing cardiac bypass is far more difficult than the control of clotting in the wound of a patient undergoing other types of operation with or without heparinization. We hope that derangements of clotting of pumped heparinized blood within tissues will be better understood and corrected in the future. Until that time, certain technical precautions must be taken to minimize the possibility of serious, persistent oozing following closure of the incision. Hemostasis by coagulating electrocautery is an essential expedient in this type of procedure. We instruct our surgical assistants to use gauze sponges with a gentle wiping motion rather than the usual blotting action. We have observed no harm from this maneuver and feel that it better demonstrates bleeding points which may ooze after operation unless treated by cautery at the time of incision. Bleeding must be controlled by ligature or cautery rather than by the application of compresses to a bleeding area. Blood loss is measured by sponge weighing and by actual determinations of blood volume before and after operation. Rapid rough approximations of blood volume deficits may be made by weighing the patient before and after operation. Extracellular fluid loss is computed at the

Fig. 8. Method of weighing adult patient for approximation of shifts in blood volume during operative procedure. Blood pressure recording apparatus is shown in right edge of the photograph. ... Hydraulic Lifter with Scale and Stretcher, Hoyer Company, Oshkosh, Wisconsin

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3

Fig. 9. Insertion of arterial pump cannula. (1) A suitable length of artery is isolated and occluded with fine bulldog clamps. Heparin, 10 ml. (0.1 per cent), is injected into artery distal to site of occlusion. (2) Distal bulldog clamp is shifted downward to cover the needle hole and prevent leakage of heparin solution. A transverse incision is made in the excluded segment of artery and a curved stainless steel cannula introduced. (3) Cannula is held in place with a ligature encircling the vessel and cannula. On completion of perfusion, the transverse arterial incision is closed with interrupted fine silk sutures.

rate of 30 cc. per hour of operation per square meter of body surface. This value is subtracted from the difference between careful preoperative and postoperative weighings. The net change then gives an estimate of changes of blood volume. Adult patients are weighed on a stretcher with hydraulic lift (Fig. 8).* This scale has a maximum capacity of 160 kg. and is sensitive to 100 gm. in the average weight range of patients. A smaller, more sensitive scale may be used to weigh children.* The pediatric scale has a weight capacity of 51 kg. and is sensitive to 10 gm. Approaches

We prefer a midline sternotomy for cardiac procedures, excepting atrial septal defect repair and mitral valve operative manipulation. For the repair of atrial septal defects, an anterolateral right thoracotomy

* Clinical Scale,

Model 521, Continental Scale Corporation, Chicago 36, Illinois.

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is utilized, with resection of the fourth or fifth rib and costal cartilage. A right anterolateral thoracotomy is used in the presence of recurrent mitral stenosis and the left thoracotomy approach (with bypass from the pulmonary artery to the femoral artery) reserved for those mitral lesions in which the left pleural space has not been entered. In the performance of anterior sternotomy, we have preferred the Shoemaker sternum-splitting shears. Periosteal vessels in the sternotomy incision are carefully electrocoagulated, and bone wax is applied to the sternal marrow space. Repair of the sternal defect has been most satisfactory when number 5 braided silk sutures are passed through holes drilled at frequent intervals along the length of the sternum. Cannulation of Vessels

We prefer to cannulate the femoral artery in the groin for retrograde perfusion of the aorta during all total cardiac bypasses. In the older patient there is danger that a subclaviatr artery may bear a dominant vertebral branch so that damage to the central nervous system may result from its temporary occlusion by the arterial cannula. The groin is easy to approach and can be easily draped into the primary operating field so that all cannulas are under observation by the operating team during the period of bypass. The insertion technique is shown in Figure 9. . When the chest is open, the cavae are isolated by dissection in the avascular plane at the pericardial reflection and encircled with tourniquets of Nylon tape.* Care should be taken in encircling the cavae that anomalous pulmonary veins, the azygos vein, or high hepatic veins are not traumatized during the dissection. The venous drainage catheters to be passed into the cavae are introduced through purse-string incisions in the right atrium. We prefer Wasmuth Endotracheal Tubest for venous cannulas. These tubes are thin walled and yet show no tendency to kink when bent into sharp curves. The tip of the catheter bears an extra side hole, and the end of the catheter flares nicely to connect to a standard Y connector on the venous collecting tube of the oxygenator. Catheter sizes serially graded from French 16 to 30 are available. The tubes are inserted into the atrium through separate incisions. A purse-string suture is placed in the wall of the right atrium below the appendage and a suitable sized catheter introduced into the superior vena cava through this incision. The inferior caval cannula is then passed through a separate incision in the right atrial appendage tip. The catheter to be introduced is two-thirds to three-fourths the diameter of the vena cava. The tip of the catheter is located accurately by palpa-

* Gudelace H 1/8": Gudebrod Bros. Silk Co., Pottstown, Pa. t C. R. Bard, Inc., Summit, New Jersey.

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tion and the catheter is tied into position with the purse-string sutures. All sutures tied to plastic or metal tubes are secured with surgeon's knots because ordinary knots have a tendency to slip upon firm plastic or metal structures. We have observed that prolonged blockage of the inferior vena cava by a catheter before onset of the bypass has a tendency to diminish venous return for several minutes following the start of the bypass. Consequently, when the fit appears to be close, the catheter is introduced into the atrium, connected to the machine, and then passed into the vena cava as the last maneuver before initiation of bypass. Conduct of Bypass

Sterilization, assembly, and operation of the pump are carried out by one trustworthy technician. The individual must be trained to correct promptly any problems that might arise during bypass. We have been thoroughly satisfied with the manner in which nonprofessional technicians conduct bypasses once they are adequately trained and experienced in the use of the machine. The most important principles in the conduct of bypass are the prompt attainment of adequate flow and the assurance of faultless stable pump function. These conditions are met before the cavae are completely obstructed by tourniquet to divert all venous drainage to the machine. It has been our experience that venous flow is consistently adequate if blood volume replacement has been adequate before bypass is initiated. The flow is regulated to a point at or above the minimum flow requirement as estimated by the body surface area equation. The machine is then regulated so that this flow is maintained during the period of bypass and the blood content within the oxygenator is maintained 'at a constant level as determined by observation of a calibration mark taped to the oxygenator cylinder surface. During bypass the patient's lungs are held gently inflated with a mixture of helium and oxygen. Various precautions must be taken to avoid excess vascular overload of the lungs during operation. Check Lists and Recording of Data

Apparatus is cleaned and transported and the machine assembled by means of check-off lists. Special record sheets for flow data, blood replacement and coagulation control are maintained. These records are incorporated in the patient's chart, and duplicate copies are maintained in the laboratory for easy reference. Special Problems Arising in the Management of Intracardiac Lesions It is impossible to describe the numerous techniques utilized in repair of specific intracardiac defects. In general, we have utilized conventional

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reported methods for handling the various defects. Adequate exposure and lighting of the intracardiac lesion are essential. Campbell nerve root retractors and Baby Little retractors are most useful in spreading the walls of the heart and valves apart to expose defects. At the present time our studies center about the management of specific lesions since the conduct of bypass is now standardized. We are concerned about the hazards in all reported techniques of management of calcific aortic stenosis. Studies in progress indicate that calcific foci in these valves may be fragmented without tissue injury by the direct application of ultrasound energy.28 A definite sequence of operative manipulations should be carried out, using special rongeurs in conjunction with ultrasound fragmentation of calcific valve deposits. We have not yet attempted the placement of prosthetic valves. Citrate-induced or anoxic asystole is unsafe in the presence of left' ventricular hypertrophy and we prefer the technique of coronary artery cannulation with cooling of the coronary perfusate. Hypothermia is obtained by passage of blood from the arterial filter through an ice bath to metal cannulas introduced in the coronary ostia. The cannulas are incorporated in a self-retaining retractor frame and serve to hold open the walls of the aortotomy incision during manipulation of the aortic valve. Air embolization is prevented by careful refilling of the heart, the maintenance of adequate aortic pressures during intracardiac manipulations to avoid vicarious systolic ejection, and the use of the spiral spring described by Gott and Lillehei.ll This spiral is placed in the mitral valve orifice during the time the left ventricle is open to insure incompetency of the valve and to prevent thereby an effective systolic ejection. The nature of our patient population is such that postoperative heart block is not a frequent problem. In patients with conduction disturbance, a pacemaker-monitor is attached while the patient is in the operating room and its use is continued for a number of days following the operative procedure. 17 Substitute electronic conduction systems are currently under investigation. g • 26

APPLICATION OF THE PUMP-OXYGENATOR TO REGIONAL CANCER CHEMOTHERAPY PERFUSIONS

At the present time we are carrying out regional chemotherapy perfusions, using balloon catheters to isolate regional vascular beds for local circulation of high concentrations of nitrogen mustard. In these cases the malignant disease is far-advanced, nonresectable and unsuitable

W ATKINS,

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HERING, ADAMS

Fig. 10. Detail of interchangeable short oxygenator used for regional cancer chemotherapy. The oxygenator is viewed from rear of cabinet. Thermocouple line enters outlet port of oxygenator for measurement of effluent blood temperature. The interchangeable small plug-in electric coil is positioned in radiant heater. Support rod for venous chamber is positioned close to the oxygenator to minimize circuit distance. Sampling syringe is positioned in venous chamber outlet. Small orifices in venous chamber cover permit sterile infusion of reserve blood through standard transfusion sets. Hand crank for emergency manual operation is positioned on oxygenator disc shaft.

for x-ray therapy. The small oxygenator has proved most useful for this type of low-flow perfusion (Fig. 10). The present apparatus is so designed that it may be used with suitable venous chambers and filters for double perfusions of this type. Studies are currently in progress to document rapid, accurate methods for measurement of the volume of tissue perfused, and the amount of toxic agent leaking to the general circulation. SUMMARY

1. A remarkable application of basic science techniques to surgical therapy has resulted in the development of machines which may be used to shortcircuit the heart and lungs. The use of these apparatuses permits precise operative manipulations within the empty heart. Applications outside the field of cardiovascular surgery include perfusion of far-advanced malignancies with alkylating agents and the possibility of partial support of the failing circulation.

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2. Our experience has given us certain perspectives concerning the development of a pump-oxygenator program. These principles include: (a) the importance of interdisciplinary teams during engineering design of an apparatus; (b) the importance of a surgical research laboratory available to test continuing improvements of perfusion technique, and (c) the apparent emergence of certain principles of perfusion making for successful bypass. 3. The principles making for successful perfusion include: (a) adequate pump flow to permit prolonged total cardiac bypass; (b) simulation of arterial gas tensions; (c) prevention of gas emboli; (d) minimal blood trauma, and (e) stable machine function. 4. We have designed a pump-oxygenator with these principles in mind. Venous blood passes from the obstructed cavae to the apparatus by a simple nonturbulent siphonage system. Gas is exchanged in a rotating disc oxygenator. Arterial pumping and intracardiac suction are effected by nonocclusive DeBakey type pumps. 5. Minimal trauma is inflicted upon blood during prolonged passage through our apparatus. 6. Strict attention to numerous described details during the conduct of bypass has made for a successful procedure. Acknowledgments This work would not have been possible without the active support of Capt. Lewis L. Haynes, Chief of Surgery, U.S. Naval Hospital, Chelsea, Massachusetts. Although investigations of this complexity involved the labors of numerous unnamed individuals, we are particularly indebted to Dr. Michel Y. Peter, Dr. Thomas G. O'Brien, Cdr. Mary V. Sproule and Cdr. Helen Boyle. Studies of blood trauma were made possible by the active participation of the Chelsea Naval Blood Preservation Laboratory and the Protein Foundation, Incorporated.

REFERENCES 1. Allen, J. G., Editor: Extracorporeal Circulation. Springfield, Illinois, Charles C

Thomas, 1957, 518 pp. 2. Bjork, V. 0.: Brain perfusions in dogs with artificially oxygenated blood. Acta chir. scandinav. (suppl. 137) 96: 1-122, 1948. 3. Clowes, G. H. A., Jr., Hopkins, A. L. and Neville, W. E.: Artificial lung dependent upon diffusion of oxygen and carbon dioxide through plastic membranes. J. Thoracic Surg. 32: 630-637 (Nov.) 1956. 4. Cowgill, G. R. and Drabkin, D. L.: Determination of formula for surface area of dog together with consideration of formulae available for other species. Am. J. Physiol. 81: 36-61 (June) 1927. 5. Crafoord, C., Norberg, B. and Senning, A.: Clinical studies in extracorporeal circulation with a heart-lung machine. Acta chir. scandinav. 112: 220-245 (March 28) 1957. 6. Creech, O. J., Jr., Krementz, E. T., Ryan, R. F., Reemtsma, K., Elliot, J. L. and Winblad, J. N.: Perfusion treatment of patients with cancer. J.A.M.A. 171: 2069-2075 (Dec. 12) 1959. 7. DeWall, R. A. and others: Total body perfusion for open cardiotomy utilizing the bubble oxygenator; physiologic responses in man. J. Thoracic Surg. 32: 591-603 (Nov.) 1956.

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8. Ellis, F. H., Jr. and Kirklin, J. W.: The use of extracorporeal circulation in cardiac surgery. Dis. Chest 36: 173-178 (Aug.) 1959. 9. Folkman, M. J. and Watkins, E.: An artificial conduction system for the management of experimental complete heart block. S. Forum 8: 331-334, 1957. 10. Gerbode, F. L. A., Bahnson, H. T., Bentall, H. H., Clark, L. C., Jr., Dennis, C., Jones, R. E., Melrose, D. G., Perkins, J. F., Jr. and Watkins, E.: Report of committee on definition and conformity of nomenclature and measurements used in studies on extracorporeal circulation. In: Extracorporeal Circulation. Allen, J. G., Editor, Springfield, Illinois, Charles C Thomas, 1957, pp. 504-518. 11. Gott, V. L. and Lillehei, C. W.: An instrument for the prevention of air embolism during direct vision closure of atrial septal defects and mitral valvuloplasties. Surg. Gynec. & Obst. 108: 747-750 (June) 1959. 12. Gross, R. E.: Open-heart surgery for repair of congenital defects. New England J. Med. 260: 1047-1057 (May 21) 1959. 13. Hurt, R., Perkins, H. A., Osborn, J. J. and Gerbode, F.: Neutralization of heparin by protamine in extracorporeal circulation. J. Thoracic Surg. 32: 612-619 (Nov.) 1956. 14. Kay, E. B. and others: Certain clinical aspects of use of pump oxygenator. J.A.M.A. 162: 639-641 (Oct. 13) 1956. 15. Miller, B. J., Gibbon, J. H., Jr. and Gibbon, M. H.: Recent advances in development of mechanical heart and lung apparatus. Ann. Surg. 134: 694-708 (Oct.) 1951. 16. Newman, M. H. and others: Complete and partial perfusion of animal and human subjects with the pump-oxygenator; study of factors yielding consistent survival. Successful application to one case. Surgery 38: 30-37 (July) 1955. 17. Nicholson, M. J., Eversole, U. H., Orr, R. B. and Crehan, J. P.: A cardiac monitor-pacemaker: Use during and after anesthesia. Anesth. & Analg. 38: 335-347 (Sept.-Oct.) 1959. 18. O'Brien, R. G. and Watkins, E.: Unpublished data. 19. Pontius, R. G., Watkins, E., Manheim, B. S., Allen, R. G., Sauvage, L. R. and Gross, R. E.: Studies of acid-base derangement during total cardiac bypass. S. Forum 8: 393-397, 1957. 20. Preston, F. W., Hohf, R. and Trippel, 0.: Neutralization of heparin with Polybrene. Quart. Bull. Northwestern Univ. M. School 30: 138-143, 1956. 21. Smith, W. W., Brown, I. W., Jr., Young, W. G., Jr. and Sealy, W. C.: Studies of Edglugate-Mg: a new donor blood anticoagulant-preservative mixture for extracorporeal circulation. J. Thoracic & Cardiovasc. Surg. 38: 573-585 (Nov.) 1959. 22. Stuckey, J. H., Newman, M. M., Dennis, C., Berg, E. H., Goodman, S. E., Fries, C., Karlson, K. E., Blumenfeld, M., Weitzner, S. W., Binder, L. S. and Winston, A.: The use of the heart-lung machine in selected cases of acute myocardial infarction. S. Forum 8: 342-344, 1957. 23. Talbot, N. B., Sobel, E. H., McArthur, J. W. and Crawford, J. D.: Functional Endocrinology from Birth through Adolescence. Cambridge, Massachusetts, Harvard University Press, 1952,638 pp. 24. Watkins, E.: Rapid measurement of oxygen saturation of whole blood samples with Millikan oximeter. Proc. Soc. Exper. Biol. & Med. 72: 180-184 (Oct.) 1949. 25. Watkins, E.: Discussion. In: Extracorporeal Circu'ation. Allen, J. G., Editor. Springfield, Illinois, Charles C Thomas, 1957, p. 326. 26. Watkins, E.: Transistors for cardiac conduction system. IRE Tr. Med. Electronics ME-6: 36-38 (March) 1959. 27. Watkins, E. and Hering, A. C.: A suction apparatus for use during open cardiotomy. A.M.A. Arch. Surg. 79: 35-39 (July) 1959. 28. Watkins, E., Hovnanian, H. P., Hering, A. C. and Brennan, T.: Unpublished data.