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Fibrin Sleeve Formation on Indwelling Subclavian Central Venous CathetersVerne L. Hoshal, Jr., MD; Robert G. Ause, MD; and Phillip A. Hoskins, MD, Ann Arbor, Michigan Arch Surg 1971;102(Apr):353-357. Fifty five subclavian veins with previous indwelling catheters were dissected at autopsy. Two groups of subclavian catheters injected with contrast material during removal were studied by cinefluoroscopy. Group 1 consisted of 25 patients with indwelling Teflon and polyethylene catheters. Group 2 comprised six patients with indwelling graphite benzakonium chloride-heparin sodium (GBH) bonded polyethylene catheters. The vein dissections and the cinefluoroscopic studies in group 1 revealed that totally circumferential fibrin sleeves consistently and extensively formed on indwelling subclavian catheters. They developed on polyethylene, Teflon, nylon, and siliconized rubber catheters. These fibrin sleeves were noted at dissection on catheters within 24 hours after insertion. Two associated thrombi were discovered. Cinefluoroscopy detected one additional thrombus. These findings are an undesirable potential hazard and concern of thromboembolism is certainly warranted. Methods to eliminate fibrin sleeves seem justified. Evidence suggests that GBH-bonded catheters significantly inhibit fibrin sleeve formation. The use of indwelling percutaneous subclavian central venous catheters has recently gained widespread acceptance. A variety of complications has been associated with their use including pneumothorax, hemothorax, hydrothorax, air embolism, catheter embolism, subclavian artery puncture, mediastinal infiltration, brachial plexus injury, hematoma formation, and dermatocellulitis.1-l4 Subclavian catheters have reportedly been bacteriologically safe over an extended indwelling period if meticulous care of the catheter has been observed.15 Significantly, the complications of thrombosis and thromboembolism have usually been dismissed by authors writing on subclavian vein catheterization. However, a case of superior vena caval thrombosis and obstruction has recently been reported.l6 This paper presents our investigations over the past 12 months which have consistently detected the formation of totally circumferential fibrin sleeves on indwelling subclavian catheters. The purpose of this report is threefold: to primarily document the presence of these fibrin sleeves, then to consider their significance, and finally to review our efforts to date in preventing their formation.
Methods and MaterialsAutopsy Dissections. Fifty-five patients who had indwelling subclavian catheters were autopsied. The catheters were indwelling from 24 hours to 76 days. Catheter materials studied were Teflon and polyethylene. In most cases the subclavian catheter was left in place after death. Bilaterial subclavian vein dissections were carried out in each instance with careful notation made of any thrombosis, phlebitis, and other adverse findings. Cinefluoroscopic Injections. Under fluoroscopic control, subclavian vein catheters were slowly removed while simultaneously injecting 50 mm of iothalamate sodium 66.8% (Conray 400) through the catheter. Group 1 consisted of 25 patients who had four different types of indwelling catheters: polyethylene, Teflon, nylon, and siliconized rubber. These catheters were indwelling from 7 to 54 days. Group 2 comprised six patients who had indwelling heparin-bonded polyethylene catheters. Catheters in this group were indwelling 3 to 32 days. These catheters were coated consecutively with colloidal graphite, benzalkonium chloride, and heparin sodium (GBH) by a modified method of Gott et al.l7 This procedure has consisted of the following: (1) fine sand-papering of polyethylene catheter surface followed by a xylene wipe; (2) dip once in a 4:1 dilution of alkyd resin colloidal graphite and xylene; (3) air dry for one hour and polish to a glistening smooth surface; (4) soak for 24 hours in an aqueous solution of benzalkonium chloride 1:1000; (5) rinse in normal saline; (Q soak for four hours in a 6 mg/ 100 cc of heparin sodium solution; (7) rinse in normal saline and air dry; and (8) gas sterilize.
ResultsAutopsy Dissections. Totally circumferential fibrin sleeves develop around each subclavian catheter studied. Figure 1 shows a 1.5-cm fibrin sleeve encompassing a Teflon catheter (5 1/4 inches long) indwelling only 24 hours. In Figure 2 the venous system behind the left clavicle is exposed. A probe is placed in a fibrin sleeve which developed around and to the tip of a polyethylene catheter (5 1/2 inches long) indwelling for ten days. The sleeve is folded up accordion style on the probe. A tangential view of a polyethylene catheter with fibrin sleeve indwelling 21 days is demonstrated in Figure 3. The catheter with its fibrin sleeve bridges the vein from the point of entrance to the area of tip contact on the intima of the innominate vein. Figure 4 depicts the persistence of fibrin sleeves even though the catheter had been removed many days previously. In this dissection both right and left venous systems are preserved. There is a sleeve on the right side which formed around a polyethylene catheter indwelling 45 days, but removed 23 days prior to the patient's death. The sleeve is still virtually intact. On the left side, portions of a sleeve which developed around a polyethylene catheter indwelling for 23 days and in at the time of death are apparent. Microscopic sections of these sleeves verify their fibrin composition. Figure 5 is a microscopic cross section of a sleeve adherent to a vein wall showing fibrin deposition with no evidence of endothelization or organization. There is also subendothelial proliferation of the vein wall adjacent to the adherent fibrin sleeve. A totally unexpected finding in two of the 55 dissections was the presence of significant thrombosis of the subclavian vein, innominate vein, and superior vena cava. One of these (Figure 6 ) occurred in a 64-year-old man with abdominal carcinomatosis, who died of massive pulmonary embolism. A careful search for pelvic and lower extremity venous thrombosis was unrewarding, leaving the superior vena caval thrombus as the only obvious source of embolism. The other thrombus was located in the left subclavian, internal jugular, and innominate veins, causing left upper extremity edema. Interestingly, Staphylococcus aureus was found in this thrombus. Cinefluoroscopic Injections. The catheters studied in group 1 reveal conclusively the consistent presence of fibrin sleeves. These fibrin sleeves which formed on all tested catheter materials are readily demonstrated (Figure 7 Figure 8 Figure 9 Figure 10 ). In each illustration the extent of the sleeve is clearly seen between the arrow markers. The removed catheter tip is similarly indicated. Especially note the presence of a left internal jugular vein thrombus in Figure 7. The fibrin sleeves on the group 2 GBH-bonded catheters are definitely smaller, both in length and in thickness. The extent of the fibrin sleeve on a 32-day indwelling GBH-bonded catheter which was studied is very minimal ( Figure 11 and Figure 12 ). Contrasted to those catheters in group 1, there is a dramatic reduction in the amount of fibrin sleeve formation. Click on image to see enlarged view
CommentIt is evident from these studies that fibrin sleeves consistently form around indwelling catheters regardless of the type of catheter material. They vary in extent and configuration, and as documented are associated with venous thrombosis not apparent clinically. To our knowledge, this is the first report in the English literature describing these findings. The French literature in 1964 contained the first report of fibrin sleeve formation on indwelling subclavian polyethylene catheters.18 The authors described autopsy dissection findings similar to those in this study. Of the 154 patients studied, three were autopsied. There was no evidence of pulmonary embolism at autopsy, and associated catheter venous thrombosis was not mentioned. They did not clinically observe any venous thrombus obstruction of the upper extremities, any pulmonary embolism, or any electrocardiogram changes. The authors did express concern for the fate of the fibrin sleeves in patients when the catheter was removed. Comparable findings were reported recently in the German literature.19 The authors described 17 autopsy cases with "small and insignificant partial thrombi" in the subclavian vein associated with indwelling catheters. Thrombi were located at the angle formed by the venous wall and the catheter entering the vessel seven times. Eleven thrombi of very small size were found where the tip of the catheter was touching the intima. There was "no massive thrombosis." Pulmonary embolism was present in three cases, but the authors found no evidence to suggest subclavian vein origin. Pulmonary infarcts in one case were regarded as originating in the femoral and iliac veins. Interestingly, fibrin sleeve formation was not discussed. We have not agreed with these authors that these findings are to be considered as "insignificant." A critical analysis of inert materials introduced into vascular channels of patients in the intensive care unit has revealed some startling findings.20 The investigators encountered three cases of thrombosis into the great veins of the neck and superior vena cava from a central venous pressure (CVP) catheter introduced into the superior vena cava via the basilic vein. In their study nine patients with cardiac pacemakers came to autopsy. Seven of these were permanent pacemakers. The intracardiac portion of the pacemaker catheter was segmentally enveloped in "sleeve thrombi." Additionally, the superior vena cava was occluded from extensive thrombus in three patients. Out of nine patients three showed multiple small pulmonary thromboemboli. The authors aptly termed these grave occurrences as "the pathology of progress." The problem of thrombosis with percutaneous catheter arteriography has been reported. A recent paper noted a 54% incidence of thrombus formation in 93 diagnostic arterial catheterizations.2l Polyethylene, Teflon, and siliconized polyurethane catheters were used. The frequency of clot formation was much higher in the Teflon catheter group. The mechanism of fibrin sleeve formation is intriguing. Propagation of the sleeve originates from two points of intimal injury. The most common is the point where the catheter enters the vessel. Fibrin deposition occurs from the area of intimal injury and propagates down and around the catheter. The other point of fibrin formation is located where the catheter tip touches on the intima. Fibrin propagates retrograde from this area. Within at least five to seven days the entire length of the catheter is encased in this way by the fibrin. Much of the safety of indwelling subclavian vein catheters is attributed to large vessel size and laminar blood flow characteristics.22 Allegedly, phlebitis does not occur because of this. We believe that this is incorrect unless a very flexible catheter material is used, such as siliconized rubber. Almost invariably, stiffer catheter materials (polyethylene, Teflon, and nylon) contact the vein along the greater portion of their length. Even more important the tip of the catheter is frequently positioned directly against the intima of the innominate vein or upper superior vena cava. At this area of intimal contact, from our observations, significant phlebitis develops. It is understandable why this happens. An undiluted flow of hyperosmolar acidic solution streams directly at a few millimeters of intima; a perfect situation for the development of phlebitis.23 Turbulence around the catheter is also an etiological factor.24 We consider these fibrin sleeves as an undesirable potential hazard. Contrary to general acceptance, concern for occult thrombosis and thromboembolism is certainly warranted. This is suggested by three cases of thrombosis presented in this report. Microembolism is also a distinct possibility as evidenced by our cinefluoroscopic observations of fibrin sleeve breakage during catheter removal. Even the accuracy of CVP readings are possibly affected by these sleeves. Perhaps reconsideration of the bacteriological safety of long-term indwelling subclavian catheters is in order. It is conceivable that these fibrin sleeves alone may become infected. Ideally, two criteria must be attained to eliminate fibrin sleeve formation. The length of the catheter intravenously must be short and not in contact with the intima of the vein. A truly nonthrombogenic plastic catheter material must be developed. It seemed plausible that a heparin coating bonded to catheter materials might inhibit the formation of fibrin sleeves and decrease thrombosis. Studies with a GBH coating previously reported as preventing thrombosis on intravascular plastics were encouraging.25 We utilized a modification of this coating method as outlined earlier in this study. Attempts to coat Teflon catheters (5 1/4 inches) failed despite etching. The coating readily flaked off with rubbing and bending of the catheter. An adherent stable coating was ultimately obtained using polyethylene catheters (5 l/2 inches). This coating remained intact when placed intravascularly. Other methods of bonding heparin to plastic materials have become available since the initial work with GBH-bonded plastics.26 27 28 Several of these procedures have been investigated in arterial catheters.29 We have not used any of these as yet, but plan to do so. A recently reported heparin wipe solution for arterial catheters may also be applicable to indwelling venous catheters and merits investigation.21 Our GBH-bonded polyethylene catheters appear to significantly inhibit fibrin sleeve formation even if indwelling for 32 days. The cinefluoroscopic studies detect only a minimal fibrin sleeve adherent to the vein wall at the catheter puncture site. As discussed above, the catheter tip is most likely against the intima of the vein and phlebitis occurs. Interestingly, there is no retrograde propagation of fibrin deposition from the catheter tip in the six patients studied. This indicates that there is some degree of nonthrombogenicity in the GBH-bonded polyethylene catheters. Suffice to say we are gratified by our initial results to date and are continuing these studies. The alkyd resin colloidal graphite used in coating the polyethylene catheters was developed as DAG 35 by the Acheson Colloids Co., Port Huron, Mich. Angiocath polyethylene and Teflon catheters used in this investigation were manufactured by Desert Pharmaceutical Co., Sandy, Utah. Arch Surg 1971;lO2(Apr):353-357. Copyright 1971, American Medical Association.
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