Cancer Cytogenetics and Molecular Oncology Program, Oncology Research ... Can J Vet Res 1992; 56: 382-386. 382 ... the Canadian Council on Animal Care.
The Use of an Implantable Central Venous (Hickman) Catheter for Long-term Venous Access in Dogs Undergoing Bone Marrow Transplantation Anthony C.G. Abrams-Ogg, Stephen A. Kruth, Ronald F. Carter, Victor E.O. Valli, Suzanne Kamel-Reid and Ian D. Dube
ABSTRACT
Methods were developed for the insertion and maintenance of longterm central venous catheters in dogs in order to provide reliable venous access during bone marrow transplantation. Single-lumen, 9.6 Fr Hickman catheters with a VitaCuff were used. The catheter was inserted into the jugular vein via a surgical cut-down, and tunnelled subcutaneously to exit over the thoracic spine. Fluoroscopic guidance was necessary to ensure proper positioning of the catheter tip in the right atrium. The catheter was secured at the venous entrance site with a grommet and at the cutaneous exit site with a finger-cuff suture. The exit site was bandaged; dressings were changed daily. Five dogs were studied. Catheter insertion and maintenance techniques were developed using two dogs. For the other three dogs, which developed 7 wk of profound myelosuppression induced by total body irradiation, the catheters were used for blood sampling and infusions of antibiotics, fluids, and blood products. For these three dogs there were 261 total catheterdays. Complete catheter obstruction did not occur. Partial obstruction (inability to withdraw blood) occurred for 13 days with one catheter. The tip of this catheter was in the cranial vena cava. One irradiated dog had a staphylococcal exit site infection for several days after catheter insertion, which
resolved with antibiotic therapy. Infections of the subcutaneous tunnel, and catheter associated bacteremia, were not identified. Infectious and hemorrhagic complications of myelosuppression were less severe than in six other dogs where intermittent venipuncture was used for vascular access during radiation induced myelosuppression. In conclusion, long-term central venous catheterization is feasible in dogs during profound myelosuppression and markedly facilitates patient management.
RESUME
Une methode d'insertion et de maintien de catheters veineux centraux a ete developpee afin de permettre un acces veineux continuel au cours d'experiences de transplantation de moelle osseuse chez le chien. Des catheters a canal unique, 9,6 Fr Hickman avec 1.0 x 109/L was achieved. Additional therapy was given during neutropenic febrile episodes with ,B-lactam antibiotics, intravenously three times a day (7). The catheter was removed at the end of the study period by applying steady traction, and the catheter tip and exit site were cultured for bacteria and fungi. (Dog 3 pulled out its catheter on day 97; the contaminated tip was not cultured. The catheter of dog 4 was very secure, and removal required dissection to the level of the Dacron cuff.) The grommet was not removed. 384
Six catheters were inserted. (Dog 1 was used for catheter insertion twice; the right jugular vein was used the second time.) The ideal position of the catheter tip (at the junction of the cranial vena cava and right atrium) was achieved in only three insertions by estimating the required catheter length. Correct catheter positioning was reliably achieved, however, with fluoroscopic guidance. A retention grommet was not used with the first catheter in dog 1. It migrated out of the jugular vein within 48 h, and all subsequent catheters were secured with grommets. Exit site retention sutures were not used with the first two catheters. This resulted in skin movement back and forth over the catheter and contamination of the cuffs and tunnel. Tissue glue (Vetbond, 3M Canada) was unable to secure the catheter at the exit site, necessitating the use of retention sutures. The catheters continuously exerted pressure to extrude, and when the finger-cuff suture was continuous with the pursestring suture, the latter became drawn too tightly, resulting in pressure necrosis at the exit site. Separate finger-cuff and purse-string sutures resulted in the best catheter retention with minimal tissue strangulation. A percutaneous insertion technique, using a guide-wire and peel-away vessel dilator/catheter introducer (Davol 60146, Bard Canada Inc.), was used to place two catheters in order to avoid the larger skin incision and dissection required for venotomy. This technique was abandoned because of difficulty introducing the vessel dilator into the
vein and the need to dissect the vein in order to suture the retention grommet in place. Table I summarizes catheter duration and patency for the three irradiated dogs. The catheters functioned well for the purposes of blood sampling and intravenous infusion. Catheter thrombosis was a minor, but frequent occurrence, even when dogs were thrombocytopenic. It was most prevalent when catheters were not heparin locked. Obstructive complications were most pronounced in dog 3, possibly because the catheter tip was not properly located near the right atrium (8). Obstruction was treated by repetitive flushing and aspiration, and by transiently increasing the strength and frequency of the heparin lock. Cardiopulmonary embolization probably occurred when partially obstructed catheters were cleared (9), but this was not associated with clinical signs. No differences were noted between hematological and biochemical test results determined on blood samples obtained concurrently from the catheter and by right jugular venipuncture. Partial thromboplastin time (PTT) was variably prolonged, following a 10 mL discard, when the catheter had been heparin locked. The PTT was 20.4- > 120 s with a 1000 U/mL heparin lock, 16.2-33.5 s with a 100 U/mL lock, and 19.8-22.6 s with a 1 U/mL lock. The PTT for samples obtained by venipuncture was 16.2- 22.3 s (reference limit < 20 s). Prothrombin time (PT) determined on samples obtained by venipuncture, and following 1 U/mL and 100 U/mL heparin locks, was
TABLE I. Duration and function of Hickman catheters for support of three dogs folowing total body irradiation
Dog 3 4 Sa Total catheter-days 97 118 46 0 0 Days complete obstructionb 0 Days partial obstructionC 13 0 0 1 8 Days transient partial obstructiond 5 0 2 Days clots aspirated from catheter 2 7 20 Catheter-days prior to irradiation 10 34 27 Catheter-days with neutrophils < 0.5 x 109/L 24 7 7 Catheter-days with pyrexia 18 55 65 Catheter-days with antibiotic therapy 40 48 61 Catheter-days with platelets < 50 x 109/Le 28 aDog 5 died 36 days after iffadiation from anaphylaxis following blood transfusion. The catheter was still in place blnability to flush or withdraw blood from the catheter Clnability to withdraw blood from the catheter dlnability to withdraw blood from the catheter which resolved after flushing eDogs were transfused as necessary to maintain the platelet count > 20 x 109/L. Dog 5 died prior to platelet recovery
6.5-8.3 s. The PT appeared to be mildly increased with 1000 U/mL heparin locks (9.3-13.7 s), but remained within the reference limit (< 14 s). Although the risk of catheterassociated infection increases with severity and duration of neutropenia (10), infectious complications of catheterization were minimal for the three irradiated dogs. A small volume of purulent exudate was noted at the exit site during the first week after insertion in dogs 3 and 5; Staphylococcus aureus was isolated from the latter. The dogs were treated with enrofloxacin and the inflammation resolved. All catheter blood cultures were negative except for dog 5, where Clostridium perfringens was cultured on one occasion when the dog was neutropenic and febrile. This was considered to be an unusual isolate from a long-term central venous catheter (11), and bacteremia was suspected of being intestinal in origin. Catheter tip and exit site cultures were negative at catheter removal except with dog 4, where Staphylococcus haemolyticus was isolated. This probably represented contamination at the time of catheter removal. Staphylococcus haemolyticus is part of the normal cutaneous flora of human beings and has been rarely isolated from nonprimate species (12). No signs of infection were present prior to catheter removal. In general, the dogs in this report had shorter and less severe febrile episodes, and reduced periods of inactivity and anorexia, compared to six dogs supported during myelosuppression with intermittent venipuncture (7). In spite of prolonged thrombocytopenia, hemorrhagic complications of catheterization did not occur, other than minor cutaneous hemorrhages associated with bandaging. A hematoma formed at the venotomy site eight days after insertion in dog 5. The dog was not thrombocytopenic at the time. A pressure bandage was applied and hemorrhage resolved. Venous thrombosis is a frequent complication of Hickman catheterization in human patients, which can result in clinically significant central venous obstruction and cardiopulmonary embolism (13). Jugular thrombosis was not noted in this study, but thrombosis without clinical signs may have
been present (13). Risk factors for thrombosis include thrombotic tendencies associated with neoplasia, and chemotherapy induced venous injury (14). These factors were not present in the dogs in this study. The jugular vein was patent in all dogs following catheter removal, and the grommet did not interfere with subsequent venipuncture. Preserving the jugular vein for continued access was desirable, in the event that the catheter had to be removed during myelosuppression. Necropsy was performed on dog 5, which died of a transfusion reaction. A fibrous sheath extended from the exit site to the venotomy site. Histologically the sheath was composed of bands of collagenous fibers with no evidence of inflammation. No pathological changes were noted in the jugular vein, cranial vena cava or right atrium. Pathological changes have been reported, however, in 880o of dogs in one study following central venous catheterization for four to nine weeks (6). The principal complication in this study was catheter damage from biting. The external portion of the catheter was 20-25 cm long, and constant vigilance was required to keep it coiled and secured to the body. All dogs bit their catheters at some point. Damage was successfully repaired using a catheter repair kit (Davol 60162, Bard Canada Inc.). Alternatives for reducing the risks of bite damage which were not pursued in this study include: 1) modifying the repair kit to electively shorten the external portion of the catheter, 2) fabricating jackets of sturdy material with a pocket to hold the coil, and 3) extending the catheter with additional tubing through a protective tether to the top of the cage (6). The latter technique also permits the catheter to be used for continuous infusion (6). The use of Hickman catheters markedly facilitated supportive care of dogs with severe radiation induced myelosuppression. Catheter obstruction occurred occasionally, but venous access was generally reliable. Our findings are preliminary, but long-term catheterization did not appear to increase the risk of sepsis or hemorrhage, although the origin of bacteremia in dog 5 was not determined. To date, vascular access devices implanted
in animals have been used primarily for research purposes. Hickman catheters may be utilized more frequently in dogs as this species continues to be a useful model for human marrow transplantation (15). Such devices will also probably become more popular in clinical veterinary medicine as familiarity with them develops. They have application wherever long-term vascular access is necessary. We have, for example, used a similar catheter to support and regulate a diabetic acromegalic cat treated by hypophysectomy. However, the greatest need for these catheters is probably in veterinary oncology, especially as veterinarians become more involved in clinical marrow transplantation. ACKNOWLEDGMENTS We thank Dr. K. Mathews for technical advice. The assistance of Diane Leger, Vicky Abrams-Ogg and Amanda Hathway with catheter insertion and care is gratefully acknowledged. Necropsy and histopathology services were provided by Dr. D. Percy. Dr. K. Welch supplied Fig. 1.
REFERENCES 1. PETZ LD, SCOTT EP. Supportive care. In: Blume KG, Petz LD, eds. Clinical Bone Marrow Transplantation. New York: Churchill Livingstone, 1983: 177-214. 2. APPELBAUM FR, HERZIG GP, GRAW RG, BULL MI, BOWLES C, GORIN NC, DEISSEROTH AB. Study of cell dose and storage time on engraftment of cryopreserved autologous bone marrow in a canine model. Transplantation 1978; 26: 245-248. 3. WALMA EP, VRIESENDORP HM, ZURCHER C, VAN BEKKUM DW. Engraftment of stem-cell enriched bone marrow fractions in MHC-identical dogs after fractionated total-body irradiation. Transplantation 1987; 43: 818-823. 4. STEAD RB, KWOK WW, STORB R, MILLER AD. Canine model for gene therapy: inefficient gene expression in dogs reconstituted with autologous marrow infected with retroviral vectors. Blood 1988; 77: 742-747. 5. CARTER RF, ABRAMS-OGG ACG, DICK JE, KRUTH SA, VALLI VE, KAMEL-REID S, DUBE ID. Autologous transplantation of canine long-term marrow culture cells genetically marked by retroviral vectors. Blood 1992; 79: 356-364. 6. MESFIN GM, HIGGINS MJ, BROWN WP, ROSNICK D. Cardiovascular complications of chronic catheterization of the jugular vein in the dog. Vet Pathol 1988; 25: 492-502.
385
7. ABRAMS-OGG ACG. Autologous Bone Marrow Transplantation Using Long-term Marrow Culture in Dogs: Clinical Investigations. University of Guelph, Doctor of Veterinary Science thesis, 1991. 8. STANISLAV GV, FITZGIBBONS RL, BAILEY RT, MAILLARD JA, JOHNSON PS, FEOLE JB. Reliability of implantable central venous access devices in patients with cancer. Arch Surg 1987; 122: 1280-1283. 9. ANDERSON AJ, KRASNOW SJ, BOYER MW, RAUCHEISEN ML, GRANT CE, GASPER OR, HOFFMANN JK, COHEN MH. Hickman catheter clots: a common occurrence despite daily heparin flushing. Cancer Treat Rep 1987; 71: 651-653.
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10. WURZEL CL, HALOM K, FELDMAN JG, RUBIN LG. Infection rates of BroviacHickman catheters and implantable venous devices. Am J Dis Child 1988; 142: 536-540. 11. PRESS OW, RAMSEY PG, LARSON EB, FEFER A, HICKMAN RO. Hickman catheter infections in patients with malignancies. Medicine 1984; 63: 189-200. 12. KLOOS WE, SCHLEIFER KH. Genus IV: Staphylococcus Rosenbach 1884. In: Smith PHA, ed. Bergey's Manual of Systematic Bacteriology. Vol 2. London: Williams and Wilkins, 1986: 1013-1035. 13. HAIRE WD, LIEBERMAN RP, LUND GB, EDNEY JA, KESSINGER A,
ARMITAGE JO. Thrombotic complications of silicone rubber catheters during autologous marrow and peripheral stem cell transplantation: prospective comparison of Hickman and Groshong catheters. Bone Marrow Transplant 1991; 7: 57-59. 14. CONLAN MG, HAIRE WD, LIEBERMAN RP, LUND G, KESSINGER A, ARMirAGE JO. Catheter-related thrombosis in patients with refractory lymphoma undergoing autologous stem cell transplantation. Bone Marrow Transplant 1991; 7: 235-240. 15. LADIGES WC, STORB R, THOMAS ED. Canine models of bone marrow transplantation. Lab Anim Sci 1990; 40: 11-15.
