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Intracaval devices for the prevention of pulmonary embolism
lntracaval Devices for the Prevention of Pulmonary Embolism SAMIR
R. NEIMAT,
DONALD
Ligation or compartmentation of the inferior vena cava in patients with pulmonary embolism, uncontrolled by anticoaguIation, may be a life-saving procedure. However, the mortality of the operation in poor risk patients is reported to be high and stands as a significant deterrent to the use of the procedure in this group of patients [j-3]. A promising solution to this problem appears in the development of occlusive or filtering devices which may be introduced into the inferior vena cava via a peripheral vein with the avoidance of major surgery. The ingenious work of MobinUddin in the design and application of the intracaval umbrella is supported by significant experimental as well as clinical evidence [.4-r]. Alternative intracaval devices reported by Eichelter and Schenk [B], Pate, Melvin, and Cheek [9], and Hunter, Sessions, and Buenger [IO] have shown promise in the experimental laboratory but have not had wide human application. The simplicity and early success of intracaval devices suggest the need for a comparative study of their merits. With this in mind the following project was undertaken. Material and Methods Medium sized mongrel dogs under light anesthesia (Nembutala administered intravenously) were subjected to insertion of an intracaval device into the inferior vena cava via a peripheral vein (femoral or jugular). The device was positioned in the cava with the aid of fluoroscopy, angiography, or a small abdominal incision. In the latter case intracaval pressures were measured on the caudal and cephalad aspects of the device. Specific placement of the devices immediately caudal to the renal veins was accomplished in certain groups of animals whereas more random positioning in the infrarenal portion of the inferior vena cava was the objective in other groups. The intracaval devices studies were : (1) Silastic@balloons, (2) Dacron@-covered springs (Pate), and (3) umbrella filter (MobinUddin) . (Figure 1.) From the Department of Surgery, Tufts University School of Medicine, and The Surgical Service of the Boston Veterans Administration Hospital, Boston, Massachusetts. Reprint requests may be addressed to Dr Nabseth. Chief, Surgical Service. Boston Veterans Administration Hospital, 150 South Hunting. ton Avenue. Boston, Massachusetts 02130. Presented at the Fifty-First Annual Meeting of the New England Surgical Society, West Harwich, Massachusetts, October 1-3. 1970.
442
MD,
C. NABSETH,
Boston, MD,
Massachusetts
Boston,
Massachusetts
Silmtic Balloons. In a series of twenty-one dogs (group I) specially constructed Silastic balloons* (measuring 1.5 cm in diameter in the nondistended state) were inserted into the infrarenal portion of the inferior vena cava via the exposed right femoral vein. In all instances the balloon was passed in the collapsed position with an introducer fashioned from a plastic catheter. When the desired level of the cava was reached the balloon was extruded from the introducer by means of a smaller catheter placed in the introducer. This was followed by removal of catheters from the vein. Inflation of the balloon with 5 cc of Renografinm (meglumine diatrizoate) was accomplished by injection through the small Silastic tube attached to the balloon. This tube was ligated to the femoral vein and acted as an intraluminal anchor for the inflated balloon. Further fixation of the balloon resulted from friction at the site of placement since the balloon was always distended to the point of complete occlusion of the cava. Dacron-Covered Springs. A series of seventeen dogs (group II) received intracaval springs via the femoral vein. The springs were constructed (by method of Pate) from a piece of spring steel music wire measuring 0.024 inch in diameter and 12 cm in length. A loop was formed in the midportion of the wire and each arm extending out from the loop was bent back on itself in the midportion of the arm to an acute angle of approximately 30 degrees. The device was fashioned so that the distance between the midportion of each arm (at the point of acute angulation) was 3 cm and the maximal distance between the limbs on each side of the loop was 1.8 cm. This resulted in a device which, in medium-sized dogs, converted the cross section of the inferior vena cava from a circular to a slit-like structure measuring 3 mm, at the wide point of the slit. In five animals the spring was gold-plated and wrapped with unspun Dacron thread. In the remaining animals the wire was not gold-plated. In six of the latter the device was wrapped with unspun Dacron thread and in five the device was encased in a specially knitted small Dacron tube.? All springs were folded into the lumen of a thin-walled plastic catheter measuring l/8 inch ID which served as an introducer. When the device was properly positioned, an internal pIunger was used to
* Specially fabricated and supplied by Dow Corning Cor-
poration
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f Specially fabricated Sidebotham sylvania.
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lntracaval
extrude it from the tip of the introducer. A suture passed through the loop of the spring was used as an aid in control of the device at the time of positioning. This suture was finally removed by simply pulling on one end. Accurate positioning of all intracaval springs immediately caudal to both renal veins was accomplished by observing the introducer through a small vertical right-sided abdominal incision. By this exposure it was also possible to measure caval pressures on each side of the device. A series of eight dogs (group III) Umbrella Filter. received sieve type umbrella filters designed by MobinUddin. The smaller dogs received prostheses measuring 12 mm in diameter with 1.5 mm perforations in the silicone rubber. Four larger dogs deceived prostheses 23 mm in diameter with 3 mm perforations. All umbrella filters were introduced through the exposed jugular vein by the method of Mobin-Uddin which utilizes a specially designed applicator within which the filter is compressed until ejected into the infrarenal portion of the inferior vena cava. Positioning of filter was accomplished by fluoroscopic control after an intravenous pyelogram was taken for accurate delineation of the renl pelvis of each kidney. Occasional difficulty in passing the capsule beyond the right atrium was solved by placing the dog in a lateral reclining position with the left side down. In all instances caval pressure proximal and distal to the filter was measured immediately after placement by means of a small abdominal incision. At periods varying from two to eight months the animals were restudied. Blood was drawn for culture and chest roentgenograms were taken. Angiograms of the inferior vena cava and collateral venous circulation were obtained by injecting 30 cc of Renografin into one of the femoral veins. Through a venotomy in the left femoral vein experimental thrombi were introduced through a catheter into the left common iliac vein. These thrombi were produced by the method of Sheil and Sabiston [Ill. Five separate emboli cut to the size of 3 by 3 mm were introduced into each animal in an effort to test the effectiveness of the device in preventing pulmonary embolism. Finally the area of the cava bearing the prosthesis was exposed and venous pres-
sures were measured proximal and distal to the device. The status of the device was further assessed by observing surrounding tissue reaction, presence or absence of neointimal coverings, and potency of the cava. The lungs were removed and extensively sectioned in search for emboli. Results
At the time of exGroup I: Silastic Balloons. amination, which varied from one day to eight months after introduction of the balloon, all balloons were intact and inflated. Mortality: Four of the twenty-one animals died during the first two postoperative days. One animal died of multiple pulmonary emboli, one died of aspiration pneumonia, and ,two died of unknown Volume 121, April
1971
Devices Preventing
Figure 1. The three balloon, Dacron-covered
Pulmonary
Embolism
intracaval devices studied: Silastic spring, and sieve type umbrella filter.
causes. Three animals died at one month. One died of heart worms and two died of multiple pulmonary embolism. In one of the latter animals the balloon was found displaced above the renal veins with thrombosis of the cava for a short distance proximal and distal to the balloon. All other animals survived until sacrifice at one, two, or three months (eight animals) and seven to eight months (six animals). Pulmonary embolism: As mentioned previously there were three animals dying of pulmonary embolism in this group. In addition there was one other nonfatal pulmonary embolus (measuring 2 by 3 mm) found in the right lower lobe at the time of sacrifice eight and a half months after insertion of the balloon, In all of these animals thrombosis was found occupying the cava caudal to the balloon whereas only one in four showed any evidence of thrombosis cephalad to the device. Since the balloons were completely occluding the cava, it was difficult to determine the precise source of the organized thrombus found in the lungs. Thrombosis of the cava caudal to the balloons may have embolized through the enlarged collateral venous channels developing after caval occlusion. All experimental emboli introduced into the left femoral vein were effectively prevented from reaching the lung by the intracaval device. (Figure 2A.) In two instances in which the balloon was displaced into the right iliac vein the cava remained completely patent and allowed the experimental emboli to pass into the lungs. Because of the sudden death of three of the four animals found with pulmonary embolism, the testing with experimental emboli was not possible in these instances. In Local thrombosis and neointimal formation: all animals except those dying within the first two days the balloon was found well encased in a smooth glistening covering of neointima which isolated the balloon in a cyst-like cavity. In fifteen of seventeen animals there was no evidence of 443
Neimat and Nabseth
A, angiogram revealing Figure 2. farge collateral venous circulation developing after eight months of caval occlusion by Silastic balloon. 8, radiograph showing all radiopaque experimental emboli lodging in the left iliac vein after introduction into the left femoral vein.
thrombosis proximal to the balloon with a smooth layer of neointima covering the dome of the balloon immediately caudal to the renal veins. In two instances in which the balloon was displaced 3 to 4 cm caudal to the renal veins an organized thrombus was found which extended up to the renal veins. In neither of these animals was there evidence of pulmonary embolism. Those balloons displaced to the bifurcation of the inferior vena cava into the right iliac vein were not found to have thrombosis proximally. The majority of cavas contained partial or complete thrombosis of the vessel caudal to the balloon although in four animals the cavas were completely patent proximal and distal to the device without evidence of thrombus formation. There was little tissue reaction in the region of the balloons and no evidence of infection. Blood culture : All blood cultures taken were reported as showing no growth. Angiography: Inferior vena cavagrams, performed by the injection of contrast media into the left femoral vein, revealed complete occlusion in all instances except those in which the balloon was displaced into the right iliac vein. Moderate to marked collateral venous circulation was demonstrated to exist around the site of caval occlusion. (Figure 2B.) The most prominent collateral channels were seen in the region of the gonadal, intervertebral, and abdominal wall venous plexuses. Group II: Dacron-Covered Springs. Mortality: Two of seventeen dogs in this group died during the immediate postoperative period. One animal died the night of operation and was found to have acute thrombotic occlusion of the device with marked swelling of the hind limbs. The second animal died on the second postoperative day and was found to have diffuse bronchopneumonia without evidence of pulmonary embolism. One animal died 444
weeks of multiple pulmonary emboli. One death occurred at one month and autopsy failed to reveal the cause. Pulmonary embolism was not present. All other animals (thirteen) were followed for periods of three months (three animals), four months (two), five months (seven), and seven months (one). Pulmonary embolism: There were three instances of pulmonary embolism in this group. One animal died at two weeks of multiple pulmonary emboli and two animals were found to each have a small old pulmonary embolus in the left lower lobe at the time of sacrifice five months after insertion of the device. It is of interest to note that the latter animals were found to have patency of the cava at the site of the device without evidence of thrombosis in the region. Experimental emboli were injected into the left femoral vein in all animals at the time of scrifice. One small (3 by 3 mm) thrombus in one animal was found in the lung. In the others all experimental emboli were found to be trapped in the cava immediately caudal to the device (Figure 3.) It should be noted that the intracaval spring was designed to create a 3 mm slit in the cava and the experimental emboli were 3 by 3 mm in size. It is apparent that this provided a critical test for the device and allowed little margin of protection against the passage of emboli. Patency and thrombus formation: Fourteen of the seventeen animals maintained patency of the cava and the device as determined by angiography and direct examination at time of sacrifice. Only two of thirteen long-term animals were found,with organized thrombus formation completely occluding the slit created by the spring. In the majority of the patent devices there was excellent coverage of the Dacron-covered spring with neointima and
at two
The American
Journal
of Surgery
lntracaval Devices Preventing only minimal evidence of organized thrombus in the area. Occasional small recesses in the region of the deformed cava were occupied by organized thrombus. Four of five springs with gold plating were patent although one patent device was associated with a nonfatal pulmonary embolus. Five of six springs covered with unspun Dacron but not gold-plated maintained patency and were not associated with pulmonary embolism. Four of five springs covered with knitted Dacron tubing maintained patency but were associated with two instances of pulmonary embolism. Venous presure measurements: Intracaval pressures proximal and distal to the device at the time of insertion were not found to be significantly different with a maximal gradient of 1 cm H,O. These pressure relationships were found to be maintained at the time of sacrifice in all animals with patent devices. In those with occluded devices the venous pressure distal to the device was approximately twice the intracaval pressure cephalad to the spring. Inf e&ion: Blood cultures taken at the time of sacrifice revealed growth ‘of pathogenic bacteria in five animals. Organisms cultured were Streptococcus fecalis, Escherichia coli, Beta Streptococci, and Staphylococcus aureus, coagulase-positive. All animals appeared to be in good general health and there was no instance of local infection at the site of implantation of the spring. Group III: Umbrella Filters. Mortality: A group of eight animals were followed for periods varying from one day to six months prior to study and sacrifice. One animal died of intussusception on the first postoperative day. The remaining animals all survived and were studied at one week (one animal) six weeks (two), two months (three), and six months (one).
Pulmonary
Embolism
Pulmon.ary embolism: There was no instance of pulmonary embolism in this group of animals. All injected experimental emboli in each animal were trapped in the inferior vena cava caudal to the umbrella. Six of eight Patency and thrombus formation: umbrellas remained at least partially patent during the follow-up period. Two were completely closed. In most animals the majority of perforations in the umbrellas were sealed with a smooth glistening layer of neointima with only two or three openings remaining patent. Angiography in this instance always resulted in the demonstration of good filling of the cava above and below the device and was somewh,at misleading in judging the degree of partial obstruction. (Figure 4.) All six animals followed for six weeks or longer were found to have organized thrombus within the concavity of the umbrella on the cephalad aspect of the device. This thrombus formation was tightly fixed to the device and peeled away with difficulty. There was a small amount of thrombus formation found in the cava caudal to the filter and was most extensively developed in the completely occluded animals. Venous pressure measurements: In the animals with partially patent umbrella filters, there was no significant difference between caval pressures above and below the device. However, in the presence of complete occlusion the distal pressure was found to be increased over the proximal pressure by threefold in one animal and fourfold in the other. Infection: Blood cultures sacrifice revealed no growth nisms. There was no instance the site of implantation of the
taken at the time of of pathogenic orgaof local infection at umbrella filter.
Figure
3. A, angiogram revealing caval patency at site of Dacron-covered spring. Note complete absence of collateral circulation. B, angiogram after introduction of experimental emboli into the left femoral vein. Note negative shadows within the spring. Volume
121,
April
1971
445
Neimat and Nabseth
Figure 4. A, ing sieve type 6, angiogrem several of the brella.
Comments
This investigation was designed to study some of the differences between various intracaval devices for the prevention of pulmonary embolism. On the basis of these results and the results of others the following comments seem appropriate. Balloon occlusion of the inferior vena cava provides a reliable and immediate barrier to the further caval passage of thrombi to the lungs. Utilizing a Silastic balloon as described herein or the ingenious balloon developed by Hunter and associates [IO], it is apparent that the device is well tolerated by the body and that neointima formation occurs around it. However, in our series of twentyone animals with intracaval balloons, there were four instances of pulmonary embolism. This may be related to relatively high incidence of thrombosis caudal to the balloon in association with the anchoring and inflating tube which extended to the right femoral region. Increased collateral venous circulation consistently observed after complete caval occlusion may have provided the pathway for recurrent emboli from the thrombus formation distal to the balloon. This postulate is supported by the fact that there was only rare evidence of thrombosis on the cephalad aspect of the balloon. Furthermore, Hunter reported no pulmonary emboli associated with free balloons placed in the inferior vena cava of dogs via the jugular vein. Balloon occlusion of the cava, as any sudden occlusion of the vessel, has the theoretic disadvantage of causing a rapid rise in venous pressure distal to the point of occlusion and possibly initiating a serious pooling of blood and fluid in the pelvis and lower extremities. This phenomenon, however, was not observed in this study. In addition, complete caval occlusion stimulates the development of collateral channels which may contribute to further pulmonary embolism. The Dacron-covered intracaval spring described by Pate and associates [9] was associated with a 446
roentgenogram showumbrella filter in situ. showing patency of openings in the um-
high patency rate in our experimental group of animals. In addition, the device was found to be very efficient in trapping experimental emboli introduced through the femoral vein. Of a total of sixty-five experimental emboli used in thirteen long-term animals in this group only one embolus managed to pass to the lung. Three instances of pulmonary embolism independant of experimental emboli were observed in this group. This was not easily explained in view of the high patency rate of the device and the paucity of thrombus formation in the region of and caudal to the spring. Gold plating of the steel wire did not appear to be advantageous in this study. Similarly, various forms of Dacron covering of the wire were not significantly different in behavior. A disturbing evidence was the finding of several positive blood cultures in the animals with intracaval springs although there was no local evidence of infection. The true significance of this is not clear from these experiments. The unique sieve type umbrella filter of MobinUddin was not associated with pulmonary embolism in any instance in this study. All experimental emboli were prevented from reaching the lungs. Although most of the perforations were found to be occluded at the time of sacrifice and organized thrombus was consistently found on the cephalad aspect of the device, the umbrella filter appeared to be a well tolerated and effective means of preventing pulmonary embolism. Although the finding of proximal thrombosis in cup-like concavity of the device suggests a potential danger, the absence of pulmonary embolism in our experimental animals as well as those reported by MobinUddin is substantial evidence against the possibility of genesis of emboli from the device. It is apparent from this study and the reports of MobinUddin that the mapority of sieve type umbrella filters will close and become completely occluded in time. The sieve has the apparent advantage of gradual occlusion eliminating the danger of acute distal pooling of blood. The American
Journal
of Surgery
lntracaval Devices Preventing Pulmonary Embolism
It is difficult to see how the occluded caval device will differ from caval ligation in respect to the subsequent development of large collateral channels and the development of occasional recurrent pulmonary embolism from distal unresolved sites of thrombophlebitis. Solution to this problem is not simple since it is apparent that an ideal intracaval filtering device, without tendency towards occlusion would become a completely occlusive influence at the time of arresting the first major thrombus. Summary
Intracaval occlusion for the prevention of pulmonary embolism was studied in a series of fortysix mongrel dogs. Partial or complete occlusion of the inferior vena cava was achieved by the use of Silastic balloons, Dacron-covered springs, and sieve type umbrella filters. The animals were studied by angiography, venous pressure measurements, blood cultures, roentgenograms of the lung, and the introduction of experimental emboli. The balloon and spring devices were associated with the development of pulmonary embolism in some of the animals. This was not true of the umbrella filter. All devices proved to be very efficient at arresting experimental thrombi. The spring device maintained a high incidence of patency, whereas most of the sieve openings in the umbrella filter became occluded. Considering all aspects the umbrella filter appeared as the safest and most consistently reliable device under study. References 1. Crane C: Femoral vs caval interruption for venous thromboembolism. New Eng J Med 270: 819,1964. 2. Nabseth DC, Moran JM: Reassesment of the role of the inferior vena cava ligation in venous thromboembolism. New Eng J Med 273: 1250.1965. 3. Mazes M, Adar R, Bogokowsky H, Agmon M: Vein ligation in treatment of pulmonary embolism. Surgery 55: 621,1964. 4. Mobin-Uddin K, Smith PE, Martinez LD, Lombard0 CR, Jude JR: A vena caval filter for the prevention of pulmonary embolus. Surg Forum 18: 269, 1967. 5. Mobin-Uddin K. McLean R. Bolooki H. Jude JR: Caval interruption ‘for prevention of pulmonary embolism. Arch Surg 99: 711. 1969. 6. Mobin-Uddin K, McLean R, Jude JR: A new catheter technique of interruption of inferior vena cava for prevention of pulmonary embolism. Amer Surg 35: 889, 1969. 7. Mobin-Uddin K, Blooki H, Jude JR: Intravenous caval interruption for pulmonary embolism in cardiac dis‘ease. Circulation 41 (suppl 2): 153, 1970. 8. Eichelter P, Schenk WG Jr: A new experimental approach to prophylaxis of pulmonary embolism. Rev Surg 24: 455,1967. 9. Pate JW, Melvin 0, Cheek RC: A new form of vena caval interruption. Ann Surg 169: 873, 1969. 10. Hunter JA, Sessions R, Buenger ‘R: Experimental balloon obstruction of inferior vena cava. Ann Surg 171: 315, 1970. Volume 121, April 1971
11. Sheil AGR, Sabiston DC: Experimental venous thrombosis
and thrombectomy. Arch Surg 87: 408, 1963.
Discussion C. CRANE (Boston, Mass) : Doctors Neimat and Nabseth have presented to us a very complete and careful study of three different types of intracaval antiembolism devices in dogs, all passed in from the periphery. I think that the evidence is convincing that these devices are very effective in preventing the transportation of clot from the femoral vein up to the pulmonary artery. They have shown us that thrombosis on the north side of these devices is rare which is the thing that we would all worry about. On the other hand, it is not desirable to have a large intraluminal foreign body lying in the low pressure, low tlow inferior vena cava. One would prefer an externally applied clip which, in dogs, can be removed in six months after which the cava will spring out and be quite normal. However, we are impressed by what we have seen of the intimal surface of the dog’s cava after the balloon is removed. It looks free of clot above the balloon and the same is true of the other devices. We agree 100 per cent with the authors that there is a large segment of patients with late stage right heart failure who are too sick to have caval ligation. We have avoided using this operation in these patients for the last few years and here an intracaval device might be very useful. One can pick out other groups of very ill patients having major embolism in whom heparinization at a high dosage level is contraindicated. Here again this sort of device would be useful. One question is: would not the authors rather pass this device down from the jugular vein rather than up from the femoral? Secondly, if a very sick patient, so treated, did very well and the bulk of his problems were reversed, would not the surgeon reoperate two or three months later, take out the device, and tie the vena cava? JOHN M. MORAN (Boston, Mass) : Doctor Nabseth has given a great deal of thought to the problem of intracaval occlusive devices. Personally, I would prefer a device such as the one he has developed to the MobinUddin umbrella on the grounds that it seems less injurious to the cava. The main objective of all such devices should be to prevent pulmonary emboli with minimal caval injury, and ideally without total occlusion. In a series of six large dogs we inserted “humansized” umbrella filters in the inferior vena cava with radiographic control. Autopsies were performed at intervals ranging from twenty-four hours to three weeks. [Slide.] This is the inferior cava from a dog autopsied at twenty-four hours. Note the massive clotting both below and above the umbrella. A large saddle embolus was recovered from the pulmonary artery. Although nonlethal, it was impressive in size and had clearly detached from the clot above the umbrella. These are the lungs from an autopsy three weeks after insertion of the umbrella filter [slide]. There is a large recent embolus in the right lower lobe, and scattered emboli of 447
Neimat and Nabseth all ages elsewhere in both lungs. Similar pulmonary emboli were found in all six dogs, including two which were heparinized, both of which developed massive retroperitoneal and intra-abdominal bleeding, fatal in one. Although this data may not be transferable to human subjects, our single case illustrated some similarities to the experience in dogs. A twenty-four year old man with Wilson’s disease attempted suicide by jumping from the fifth floor of the hospital. He suffered multiple fractures of both legs and skull, and was comatose. Ten days later episodes suggestive of pulmonary emboli developed, but he did not seem a candidate for caval surgery. Pulmonary emboli were demonstrated by angiography, and the umbrella was placed just below the renal veins. Within the next week he was again having similar episodes of tachycardia, tachypnea, and cyanosis. He developed an acute abdomen, and a cavagram was obtained showing a large clot sitting on the cephalad aspect of the umbrella. At operation, after a perforated duodenal ulcer was plicated, the cava was examined, and firm clot was felt above the umbrella and adherent to it. A Teflon clip was placed above it for further protection. At autopsy ten days later, multiple pulmonary emboli of all ages were found in both lungs, but none could be specifically identified as arising from the umbrella. I am not condemning the umbrella filter but suggesting that its use be confined to well selected cases until more information is available about its natural history.
448
I hope that Dr Nabseth and others will continue developing noninjurious means of partial intracaval interruption. JOHN J. BYRNE (Boston, Mass) : I believe there is a definite place for this device in the critically ill patient. It can be inserted quite easily under local anesthesia. DONALD C. NABSETH (closing) : I wish to thank the discussers for their remarks. In answer to Dr Crane’s question about reoperation, I would not reoperate unless there was specific reason to believe that the device was contributing to the further pulmonary emboli or some other problem. I agree with the disadvantages of placing an intraluminal foreign body in a venous system. This is one of the critical aspects of the use of intracaval devices. I believe that the jugular vein is the route of choice since one does not have to worry about the problem of phlebitis and the possible dislodgment of clots that may be in the iliac or femoral veins at the time of introduction. I cannot explain the difference between Dr Moran’s experience with dogs and ours, unless it may have been the size of the umbrella filter that was used. I think that this is very valuable information and is the type of evidence that must be gathered and weighed over the years to come, if we are to know the true place for the use of intracaval devices. It seems to me that we have to balance the mortality and morbidity ,of the operative caval procedure that we presently use against whatever disadvantages come from the intravacal devices. Herein lies the answer, and only further experience will give this to us.
The
Amerlcen Journal
of
Surgery
R. NEIMAT,
DONALD
Ligation or compartmentation of the inferior vena cava in patients with pulmonary embolism, uncontrolled by anticoaguIation, may be a life-saving procedure. However, the mortality of the operation in poor risk patients is reported to be high and stands as a significant deterrent to the use of the procedure in this group of patients [j-3]. A promising solution to this problem appears in the development of occlusive or filtering devices which may be introduced into the inferior vena cava via a peripheral vein with the avoidance of major surgery. The ingenious work of MobinUddin in the design and application of the intracaval umbrella is supported by significant experimental as well as clinical evidence [.4-r]. Alternative intracaval devices reported by Eichelter and Schenk [B], Pate, Melvin, and Cheek [9], and Hunter, Sessions, and Buenger [IO] have shown promise in the experimental laboratory but have not had wide human application. The simplicity and early success of intracaval devices suggest the need for a comparative study of their merits. With this in mind the following project was undertaken. Material and Methods Medium sized mongrel dogs under light anesthesia (Nembutala administered intravenously) were subjected to insertion of an intracaval device into the inferior vena cava via a peripheral vein (femoral or jugular). The device was positioned in the cava with the aid of fluoroscopy, angiography, or a small abdominal incision. In the latter case intracaval pressures were measured on the caudal and cephalad aspects of the device. Specific placement of the devices immediately caudal to the renal veins was accomplished in certain groups of animals whereas more random positioning in the infrarenal portion of the inferior vena cava was the objective in other groups. The intracaval devices studies were : (1) Silastic@balloons, (2) Dacron@-covered springs (Pate), and (3) umbrella filter (MobinUddin) . (Figure 1.) From the Department of Surgery, Tufts University School of Medicine, and The Surgical Service of the Boston Veterans Administration Hospital, Boston, Massachusetts. Reprint requests may be addressed to Dr Nabseth. Chief, Surgical Service. Boston Veterans Administration Hospital, 150 South Hunting. ton Avenue. Boston, Massachusetts 02130. Presented at the Fifty-First Annual Meeting of the New England Surgical Society, West Harwich, Massachusetts, October 1-3. 1970.
442
MD,
C. NABSETH,
Boston, MD,
Massachusetts
Boston,
Massachusetts
Silmtic Balloons. In a series of twenty-one dogs (group I) specially constructed Silastic balloons* (measuring 1.5 cm in diameter in the nondistended state) were inserted into the infrarenal portion of the inferior vena cava via the exposed right femoral vein. In all instances the balloon was passed in the collapsed position with an introducer fashioned from a plastic catheter. When the desired level of the cava was reached the balloon was extruded from the introducer by means of a smaller catheter placed in the introducer. This was followed by removal of catheters from the vein. Inflation of the balloon with 5 cc of Renografinm (meglumine diatrizoate) was accomplished by injection through the small Silastic tube attached to the balloon. This tube was ligated to the femoral vein and acted as an intraluminal anchor for the inflated balloon. Further fixation of the balloon resulted from friction at the site of placement since the balloon was always distended to the point of complete occlusion of the cava. Dacron-Covered Springs. A series of seventeen dogs (group II) received intracaval springs via the femoral vein. The springs were constructed (by method of Pate) from a piece of spring steel music wire measuring 0.024 inch in diameter and 12 cm in length. A loop was formed in the midportion of the wire and each arm extending out from the loop was bent back on itself in the midportion of the arm to an acute angle of approximately 30 degrees. The device was fashioned so that the distance between the midportion of each arm (at the point of acute angulation) was 3 cm and the maximal distance between the limbs on each side of the loop was 1.8 cm. This resulted in a device which, in medium-sized dogs, converted the cross section of the inferior vena cava from a circular to a slit-like structure measuring 3 mm, at the wide point of the slit. In five animals the spring was gold-plated and wrapped with unspun Dacron thread. In the remaining animals the wire was not gold-plated. In six of the latter the device was wrapped with unspun Dacron thread and in five the device was encased in a specially knitted small Dacron tube.? All springs were folded into the lumen of a thin-walled plastic catheter measuring l/8 inch ID which served as an introducer. When the device was properly positioned, an internal pIunger was used to
* Specially fabricated and supplied by Dow Corning Cor-
poration
Medical
Products
Plant, Hemlock, Michigan. and generously supplied by John &‘I?’ Griscom Street, Philadelphia, Penn-
f Specially fabricated Sidebotham sylvania.
Inc.,
The
American
Journal
of
Surgery
lntracaval
extrude it from the tip of the introducer. A suture passed through the loop of the spring was used as an aid in control of the device at the time of positioning. This suture was finally removed by simply pulling on one end. Accurate positioning of all intracaval springs immediately caudal to both renal veins was accomplished by observing the introducer through a small vertical right-sided abdominal incision. By this exposure it was also possible to measure caval pressures on each side of the device. A series of eight dogs (group III) Umbrella Filter. received sieve type umbrella filters designed by MobinUddin. The smaller dogs received prostheses measuring 12 mm in diameter with 1.5 mm perforations in the silicone rubber. Four larger dogs deceived prostheses 23 mm in diameter with 3 mm perforations. All umbrella filters were introduced through the exposed jugular vein by the method of Mobin-Uddin which utilizes a specially designed applicator within which the filter is compressed until ejected into the infrarenal portion of the inferior vena cava. Positioning of filter was accomplished by fluoroscopic control after an intravenous pyelogram was taken for accurate delineation of the renl pelvis of each kidney. Occasional difficulty in passing the capsule beyond the right atrium was solved by placing the dog in a lateral reclining position with the left side down. In all instances caval pressure proximal and distal to the filter was measured immediately after placement by means of a small abdominal incision. At periods varying from two to eight months the animals were restudied. Blood was drawn for culture and chest roentgenograms were taken. Angiograms of the inferior vena cava and collateral venous circulation were obtained by injecting 30 cc of Renografin into one of the femoral veins. Through a venotomy in the left femoral vein experimental thrombi were introduced through a catheter into the left common iliac vein. These thrombi were produced by the method of Sheil and Sabiston [Ill. Five separate emboli cut to the size of 3 by 3 mm were introduced into each animal in an effort to test the effectiveness of the device in preventing pulmonary embolism. Finally the area of the cava bearing the prosthesis was exposed and venous pres-
sures were measured proximal and distal to the device. The status of the device was further assessed by observing surrounding tissue reaction, presence or absence of neointimal coverings, and potency of the cava. The lungs were removed and extensively sectioned in search for emboli. Results
At the time of exGroup I: Silastic Balloons. amination, which varied from one day to eight months after introduction of the balloon, all balloons were intact and inflated. Mortality: Four of the twenty-one animals died during the first two postoperative days. One animal died of multiple pulmonary emboli, one died of aspiration pneumonia, and ,two died of unknown Volume 121, April
1971
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Figure 1. The three balloon, Dacron-covered
Pulmonary
Embolism
intracaval devices studied: Silastic spring, and sieve type umbrella filter.
causes. Three animals died at one month. One died of heart worms and two died of multiple pulmonary embolism. In one of the latter animals the balloon was found displaced above the renal veins with thrombosis of the cava for a short distance proximal and distal to the balloon. All other animals survived until sacrifice at one, two, or three months (eight animals) and seven to eight months (six animals). Pulmonary embolism: As mentioned previously there were three animals dying of pulmonary embolism in this group. In addition there was one other nonfatal pulmonary embolus (measuring 2 by 3 mm) found in the right lower lobe at the time of sacrifice eight and a half months after insertion of the balloon, In all of these animals thrombosis was found occupying the cava caudal to the balloon whereas only one in four showed any evidence of thrombosis cephalad to the device. Since the balloons were completely occluding the cava, it was difficult to determine the precise source of the organized thrombus found in the lungs. Thrombosis of the cava caudal to the balloons may have embolized through the enlarged collateral venous channels developing after caval occlusion. All experimental emboli introduced into the left femoral vein were effectively prevented from reaching the lung by the intracaval device. (Figure 2A.) In two instances in which the balloon was displaced into the right iliac vein the cava remained completely patent and allowed the experimental emboli to pass into the lungs. Because of the sudden death of three of the four animals found with pulmonary embolism, the testing with experimental emboli was not possible in these instances. In Local thrombosis and neointimal formation: all animals except those dying within the first two days the balloon was found well encased in a smooth glistening covering of neointima which isolated the balloon in a cyst-like cavity. In fifteen of seventeen animals there was no evidence of 443
Neimat and Nabseth
A, angiogram revealing Figure 2. farge collateral venous circulation developing after eight months of caval occlusion by Silastic balloon. 8, radiograph showing all radiopaque experimental emboli lodging in the left iliac vein after introduction into the left femoral vein.
thrombosis proximal to the balloon with a smooth layer of neointima covering the dome of the balloon immediately caudal to the renal veins. In two instances in which the balloon was displaced 3 to 4 cm caudal to the renal veins an organized thrombus was found which extended up to the renal veins. In neither of these animals was there evidence of pulmonary embolism. Those balloons displaced to the bifurcation of the inferior vena cava into the right iliac vein were not found to have thrombosis proximally. The majority of cavas contained partial or complete thrombosis of the vessel caudal to the balloon although in four animals the cavas were completely patent proximal and distal to the device without evidence of thrombus formation. There was little tissue reaction in the region of the balloons and no evidence of infection. Blood culture : All blood cultures taken were reported as showing no growth. Angiography: Inferior vena cavagrams, performed by the injection of contrast media into the left femoral vein, revealed complete occlusion in all instances except those in which the balloon was displaced into the right iliac vein. Moderate to marked collateral venous circulation was demonstrated to exist around the site of caval occlusion. (Figure 2B.) The most prominent collateral channels were seen in the region of the gonadal, intervertebral, and abdominal wall venous plexuses. Group II: Dacron-Covered Springs. Mortality: Two of seventeen dogs in this group died during the immediate postoperative period. One animal died the night of operation and was found to have acute thrombotic occlusion of the device with marked swelling of the hind limbs. The second animal died on the second postoperative day and was found to have diffuse bronchopneumonia without evidence of pulmonary embolism. One animal died 444
weeks of multiple pulmonary emboli. One death occurred at one month and autopsy failed to reveal the cause. Pulmonary embolism was not present. All other animals (thirteen) were followed for periods of three months (three animals), four months (two), five months (seven), and seven months (one). Pulmonary embolism: There were three instances of pulmonary embolism in this group. One animal died at two weeks of multiple pulmonary emboli and two animals were found to each have a small old pulmonary embolus in the left lower lobe at the time of sacrifice five months after insertion of the device. It is of interest to note that the latter animals were found to have patency of the cava at the site of the device without evidence of thrombosis in the region. Experimental emboli were injected into the left femoral vein in all animals at the time of scrifice. One small (3 by 3 mm) thrombus in one animal was found in the lung. In the others all experimental emboli were found to be trapped in the cava immediately caudal to the device (Figure 3.) It should be noted that the intracaval spring was designed to create a 3 mm slit in the cava and the experimental emboli were 3 by 3 mm in size. It is apparent that this provided a critical test for the device and allowed little margin of protection against the passage of emboli. Patency and thrombus formation: Fourteen of the seventeen animals maintained patency of the cava and the device as determined by angiography and direct examination at time of sacrifice. Only two of thirteen long-term animals were found,with organized thrombus formation completely occluding the slit created by the spring. In the majority of the patent devices there was excellent coverage of the Dacron-covered spring with neointima and
at two
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lntracaval Devices Preventing only minimal evidence of organized thrombus in the area. Occasional small recesses in the region of the deformed cava were occupied by organized thrombus. Four of five springs with gold plating were patent although one patent device was associated with a nonfatal pulmonary embolus. Five of six springs covered with unspun Dacron but not gold-plated maintained patency and were not associated with pulmonary embolism. Four of five springs covered with knitted Dacron tubing maintained patency but were associated with two instances of pulmonary embolism. Venous presure measurements: Intracaval pressures proximal and distal to the device at the time of insertion were not found to be significantly different with a maximal gradient of 1 cm H,O. These pressure relationships were found to be maintained at the time of sacrifice in all animals with patent devices. In those with occluded devices the venous pressure distal to the device was approximately twice the intracaval pressure cephalad to the spring. Inf e&ion: Blood cultures taken at the time of sacrifice revealed growth ‘of pathogenic bacteria in five animals. Organisms cultured were Streptococcus fecalis, Escherichia coli, Beta Streptococci, and Staphylococcus aureus, coagulase-positive. All animals appeared to be in good general health and there was no instance of local infection at the site of implantation of the spring. Group III: Umbrella Filters. Mortality: A group of eight animals were followed for periods varying from one day to six months prior to study and sacrifice. One animal died of intussusception on the first postoperative day. The remaining animals all survived and were studied at one week (one animal) six weeks (two), two months (three), and six months (one).
Pulmonary
Embolism
Pulmon.ary embolism: There was no instance of pulmonary embolism in this group of animals. All injected experimental emboli in each animal were trapped in the inferior vena cava caudal to the umbrella. Six of eight Patency and thrombus formation: umbrellas remained at least partially patent during the follow-up period. Two were completely closed. In most animals the majority of perforations in the umbrellas were sealed with a smooth glistening layer of neointima with only two or three openings remaining patent. Angiography in this instance always resulted in the demonstration of good filling of the cava above and below the device and was somewh,at misleading in judging the degree of partial obstruction. (Figure 4.) All six animals followed for six weeks or longer were found to have organized thrombus within the concavity of the umbrella on the cephalad aspect of the device. This thrombus formation was tightly fixed to the device and peeled away with difficulty. There was a small amount of thrombus formation found in the cava caudal to the filter and was most extensively developed in the completely occluded animals. Venous pressure measurements: In the animals with partially patent umbrella filters, there was no significant difference between caval pressures above and below the device. However, in the presence of complete occlusion the distal pressure was found to be increased over the proximal pressure by threefold in one animal and fourfold in the other. Infection: Blood cultures sacrifice revealed no growth nisms. There was no instance the site of implantation of the
taken at the time of of pathogenic orgaof local infection at umbrella filter.
Figure
3. A, angiogram revealing caval patency at site of Dacron-covered spring. Note complete absence of collateral circulation. B, angiogram after introduction of experimental emboli into the left femoral vein. Note negative shadows within the spring. Volume
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Figure 4. A, ing sieve type 6, angiogrem several of the brella.
Comments
This investigation was designed to study some of the differences between various intracaval devices for the prevention of pulmonary embolism. On the basis of these results and the results of others the following comments seem appropriate. Balloon occlusion of the inferior vena cava provides a reliable and immediate barrier to the further caval passage of thrombi to the lungs. Utilizing a Silastic balloon as described herein or the ingenious balloon developed by Hunter and associates [IO], it is apparent that the device is well tolerated by the body and that neointima formation occurs around it. However, in our series of twentyone animals with intracaval balloons, there were four instances of pulmonary embolism. This may be related to relatively high incidence of thrombosis caudal to the balloon in association with the anchoring and inflating tube which extended to the right femoral region. Increased collateral venous circulation consistently observed after complete caval occlusion may have provided the pathway for recurrent emboli from the thrombus formation distal to the balloon. This postulate is supported by the fact that there was only rare evidence of thrombosis on the cephalad aspect of the balloon. Furthermore, Hunter reported no pulmonary emboli associated with free balloons placed in the inferior vena cava of dogs via the jugular vein. Balloon occlusion of the cava, as any sudden occlusion of the vessel, has the theoretic disadvantage of causing a rapid rise in venous pressure distal to the point of occlusion and possibly initiating a serious pooling of blood and fluid in the pelvis and lower extremities. This phenomenon, however, was not observed in this study. In addition, complete caval occlusion stimulates the development of collateral channels which may contribute to further pulmonary embolism. The Dacron-covered intracaval spring described by Pate and associates [9] was associated with a 446
roentgenogram showumbrella filter in situ. showing patency of openings in the um-
high patency rate in our experimental group of animals. In addition, the device was found to be very efficient in trapping experimental emboli introduced through the femoral vein. Of a total of sixty-five experimental emboli used in thirteen long-term animals in this group only one embolus managed to pass to the lung. Three instances of pulmonary embolism independant of experimental emboli were observed in this group. This was not easily explained in view of the high patency rate of the device and the paucity of thrombus formation in the region of and caudal to the spring. Gold plating of the steel wire did not appear to be advantageous in this study. Similarly, various forms of Dacron covering of the wire were not significantly different in behavior. A disturbing evidence was the finding of several positive blood cultures in the animals with intracaval springs although there was no local evidence of infection. The true significance of this is not clear from these experiments. The unique sieve type umbrella filter of MobinUddin was not associated with pulmonary embolism in any instance in this study. All experimental emboli were prevented from reaching the lungs. Although most of the perforations were found to be occluded at the time of sacrifice and organized thrombus was consistently found on the cephalad aspect of the device, the umbrella filter appeared to be a well tolerated and effective means of preventing pulmonary embolism. Although the finding of proximal thrombosis in cup-like concavity of the device suggests a potential danger, the absence of pulmonary embolism in our experimental animals as well as those reported by MobinUddin is substantial evidence against the possibility of genesis of emboli from the device. It is apparent from this study and the reports of MobinUddin that the mapority of sieve type umbrella filters will close and become completely occluded in time. The sieve has the apparent advantage of gradual occlusion eliminating the danger of acute distal pooling of blood. The American
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lntracaval Devices Preventing Pulmonary Embolism
It is difficult to see how the occluded caval device will differ from caval ligation in respect to the subsequent development of large collateral channels and the development of occasional recurrent pulmonary embolism from distal unresolved sites of thrombophlebitis. Solution to this problem is not simple since it is apparent that an ideal intracaval filtering device, without tendency towards occlusion would become a completely occlusive influence at the time of arresting the first major thrombus. Summary
Intracaval occlusion for the prevention of pulmonary embolism was studied in a series of fortysix mongrel dogs. Partial or complete occlusion of the inferior vena cava was achieved by the use of Silastic balloons, Dacron-covered springs, and sieve type umbrella filters. The animals were studied by angiography, venous pressure measurements, blood cultures, roentgenograms of the lung, and the introduction of experimental emboli. The balloon and spring devices were associated with the development of pulmonary embolism in some of the animals. This was not true of the umbrella filter. All devices proved to be very efficient at arresting experimental thrombi. The spring device maintained a high incidence of patency, whereas most of the sieve openings in the umbrella filter became occluded. Considering all aspects the umbrella filter appeared as the safest and most consistently reliable device under study. References 1. Crane C: Femoral vs caval interruption for venous thromboembolism. New Eng J Med 270: 819,1964. 2. Nabseth DC, Moran JM: Reassesment of the role of the inferior vena cava ligation in venous thromboembolism. New Eng J Med 273: 1250.1965. 3. Mazes M, Adar R, Bogokowsky H, Agmon M: Vein ligation in treatment of pulmonary embolism. Surgery 55: 621,1964. 4. Mobin-Uddin K, Smith PE, Martinez LD, Lombard0 CR, Jude JR: A vena caval filter for the prevention of pulmonary embolus. Surg Forum 18: 269, 1967. 5. Mobin-Uddin K. McLean R. Bolooki H. Jude JR: Caval interruption ‘for prevention of pulmonary embolism. Arch Surg 99: 711. 1969. 6. Mobin-Uddin K, McLean R, Jude JR: A new catheter technique of interruption of inferior vena cava for prevention of pulmonary embolism. Amer Surg 35: 889, 1969. 7. Mobin-Uddin K, Blooki H, Jude JR: Intravenous caval interruption for pulmonary embolism in cardiac dis‘ease. Circulation 41 (suppl 2): 153, 1970. 8. Eichelter P, Schenk WG Jr: A new experimental approach to prophylaxis of pulmonary embolism. Rev Surg 24: 455,1967. 9. Pate JW, Melvin 0, Cheek RC: A new form of vena caval interruption. Ann Surg 169: 873, 1969. 10. Hunter JA, Sessions R, Buenger ‘R: Experimental balloon obstruction of inferior vena cava. Ann Surg 171: 315, 1970. Volume 121, April 1971
11. Sheil AGR, Sabiston DC: Experimental venous thrombosis
and thrombectomy. Arch Surg 87: 408, 1963.
Discussion C. CRANE (Boston, Mass) : Doctors Neimat and Nabseth have presented to us a very complete and careful study of three different types of intracaval antiembolism devices in dogs, all passed in from the periphery. I think that the evidence is convincing that these devices are very effective in preventing the transportation of clot from the femoral vein up to the pulmonary artery. They have shown us that thrombosis on the north side of these devices is rare which is the thing that we would all worry about. On the other hand, it is not desirable to have a large intraluminal foreign body lying in the low pressure, low tlow inferior vena cava. One would prefer an externally applied clip which, in dogs, can be removed in six months after which the cava will spring out and be quite normal. However, we are impressed by what we have seen of the intimal surface of the dog’s cava after the balloon is removed. It looks free of clot above the balloon and the same is true of the other devices. We agree 100 per cent with the authors that there is a large segment of patients with late stage right heart failure who are too sick to have caval ligation. We have avoided using this operation in these patients for the last few years and here an intracaval device might be very useful. One can pick out other groups of very ill patients having major embolism in whom heparinization at a high dosage level is contraindicated. Here again this sort of device would be useful. One question is: would not the authors rather pass this device down from the jugular vein rather than up from the femoral? Secondly, if a very sick patient, so treated, did very well and the bulk of his problems were reversed, would not the surgeon reoperate two or three months later, take out the device, and tie the vena cava? JOHN M. MORAN (Boston, Mass) : Doctor Nabseth has given a great deal of thought to the problem of intracaval occlusive devices. Personally, I would prefer a device such as the one he has developed to the MobinUddin umbrella on the grounds that it seems less injurious to the cava. The main objective of all such devices should be to prevent pulmonary emboli with minimal caval injury, and ideally without total occlusion. In a series of six large dogs we inserted “humansized” umbrella filters in the inferior vena cava with radiographic control. Autopsies were performed at intervals ranging from twenty-four hours to three weeks. [Slide.] This is the inferior cava from a dog autopsied at twenty-four hours. Note the massive clotting both below and above the umbrella. A large saddle embolus was recovered from the pulmonary artery. Although nonlethal, it was impressive in size and had clearly detached from the clot above the umbrella. These are the lungs from an autopsy three weeks after insertion of the umbrella filter [slide]. There is a large recent embolus in the right lower lobe, and scattered emboli of 447
Neimat and Nabseth all ages elsewhere in both lungs. Similar pulmonary emboli were found in all six dogs, including two which were heparinized, both of which developed massive retroperitoneal and intra-abdominal bleeding, fatal in one. Although this data may not be transferable to human subjects, our single case illustrated some similarities to the experience in dogs. A twenty-four year old man with Wilson’s disease attempted suicide by jumping from the fifth floor of the hospital. He suffered multiple fractures of both legs and skull, and was comatose. Ten days later episodes suggestive of pulmonary emboli developed, but he did not seem a candidate for caval surgery. Pulmonary emboli were demonstrated by angiography, and the umbrella was placed just below the renal veins. Within the next week he was again having similar episodes of tachycardia, tachypnea, and cyanosis. He developed an acute abdomen, and a cavagram was obtained showing a large clot sitting on the cephalad aspect of the umbrella. At operation, after a perforated duodenal ulcer was plicated, the cava was examined, and firm clot was felt above the umbrella and adherent to it. A Teflon clip was placed above it for further protection. At autopsy ten days later, multiple pulmonary emboli of all ages were found in both lungs, but none could be specifically identified as arising from the umbrella. I am not condemning the umbrella filter but suggesting that its use be confined to well selected cases until more information is available about its natural history.
448
I hope that Dr Nabseth and others will continue developing noninjurious means of partial intracaval interruption. JOHN J. BYRNE (Boston, Mass) : I believe there is a definite place for this device in the critically ill patient. It can be inserted quite easily under local anesthesia. DONALD C. NABSETH (closing) : I wish to thank the discussers for their remarks. In answer to Dr Crane’s question about reoperation, I would not reoperate unless there was specific reason to believe that the device was contributing to the further pulmonary emboli or some other problem. I agree with the disadvantages of placing an intraluminal foreign body in a venous system. This is one of the critical aspects of the use of intracaval devices. I believe that the jugular vein is the route of choice since one does not have to worry about the problem of phlebitis and the possible dislodgment of clots that may be in the iliac or femoral veins at the time of introduction. I cannot explain the difference between Dr Moran’s experience with dogs and ours, unless it may have been the size of the umbrella filter that was used. I think that this is very valuable information and is the type of evidence that must be gathered and weighed over the years to come, if we are to know the true place for the use of intracaval devices. It seems to me that we have to balance the mortality and morbidity ,of the operative caval procedure that we presently use against whatever disadvantages come from the intravacal devices. Herein lies the answer, and only further experience will give this to us.
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