Materials and Methods

Dogs and cats referred to the Oncology Service at the Cornell University Hospital for Animals for chemotherapy or radiation therapy within a 1-year period (June 2005 through June 2006) were eligible for inclusion in the study. Client consent was obtained prior to inclusion.

A VAP^a catheter was surgically implanted into the left femoral vein of each patient (Figures 1 and 2). Location of the injection port was alternated between the caudal region of the left thoracic wall and the left ilial wing. Each patient was anesthetized, clipped, and prepared by use of standard aseptic technique and positioned in right lateral recumbency. A skin incision was made over the left femoral triangle, parallel to the femoral vein. The left femoral vein was isolated via blunt and sharp dissection. Three silk stay sutures were placed around the vein, 2 proximal and 1 distal to the proposed venotomy site. The length of catheter tubing required to reach the midabdominal level of the vena cava from the femoral vein was estimated, plus 3 to 5 cm of additional tubing to prevent excessive tension at the venotomy site. Excess tubing was removed with scissors. Depending on the predetermined injection port location, a vertical skin incision was made over the left ilial wing or caudal portion of the left thoracic wall and a deep subcutaneous pocket was created cranial to the skin incision. The catheter tubing was then tunneled beneath the skin to the port site by use of a tunneling trocar.^b The catheter was connected to the injection port, and the port was anchored to the underlying muscle fascia with 3-0 polypropylene sutures. The port was flushed with heparinized saline (0.9% NaCl) solution by use of a Huber needle and 12-mL syringe. With an assistant placing tension on the venous stay sutures to occlude blood flow, a small transverse incision was made into the femoral vein with iris scissors and the vascular access tubing was advanced proximally to the midabdominal level of the vena cava. The 2 proximal encircling stay sutures were tightened around the femoral vein and catheter. Care was taken not to occlude the catheter tubing with the ligature. The distal encircling stay suture was used to ligate the femoral vein distal to the venotomy site, then to transfix the catheter to the ligated vessel. The VAP was checked for patency by aspirating blood and flushing with sterile saline solution. A solution of heparinized saline solution (100 U/mL) was then administered. A standard 2-layer closure was performed at the venotomy and port sites. Operative time was defined as the interval in minutes from first skin incision to final suture placement. Length, in centimeters, of catheter tubing used was recorded for each patient. Cefazolin^c (22 mg/kg [10 mg/lb], IV, once) was given during surgery. Buprenorphine^d (0.01 mg/kg [0.045 mg/lb], SC, q 6 h) was given for 24 hours after surgery.

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Illustration depicting placement of a VAP in the left femoral vein of a cat with the injection port placed over the left ilial wing (viewed from left caudolateral aspect).

Citation: Journal of the American Veterinary Medical Association 231, 9; 10.2460/javma.231.9.1354

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Illustration depicting placement of a VAP in the left femoral vein of a cat with the injection port placed over the left thoracic wall (viewed from the left).

Citation: Journal of the American Veterinary Medical Association 231, 9; 10.2460/javma.231.9.1354

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Prior to each use, the skin over the injection port was prepared with 3 antiseptic and alcohol scrubs. Only Huber needles^e were used to access the VAP. The day following surgical placement, VAPs were flushed with 3 to 6 mL of sterile saline solution. At the conclusion of each port use, VAPs were injected with a solution of heparinized saline solution (100 U/mL); the volume of solution was determined for each patient on the basis of the length of catheter tubing implanted at the time of surgery.

The VAPs were used for administration of chemotherapy or sedation or for blood sampling. For administration of chemotherapy, patency of the VAP was first established by use of 1 to 3 mL of sterile saline solution, drugs were delivered, and the VAP was injected with heparinized saline solution. For each blood sample collection, 1.5 to 2 mL of blood was withdrawn into a 3mL syringe and discarded prior to obtaining the sample to be submitted. The VAP was flushed with 3 to 6 mL of sterile saline solution following blood sampling, then injected with heparinized saline solution. On occasion, patency was tested and recorded without drug administration or blood sampling.

Patients were evaluated 1 day after surgery by 1 surgeon (AKC) and at each port use by a licensed veterinary technician. The recheck schedule and protocol for VAP use were determined by the treatment protocol for each patient. The interval between recheck examinations and port use ranged from weekly to every 2 months. At each VAP use, the port site and catheter track site were assessed, a pain score was calculated, and infusion and aspiration of the port were evaluated (Appendix 1). Patients that received a pain score > 1 were treated for discomfort with opioids on an individual basis. Patients with signs of localized VAP-related infection (port or catheter track score > 2) were given cephalexin^f (22 mg/kg, PO, q 8 h) for 5 days or until resolution of clinical signs. Patients with signs of systemic illness or sepsis related to the VAP were treated with amoxicillin-clavulanic acid^g (30 mg/kg [13.6 mg/lb], IV, q 8 h), and the VAP was surgically removed and submitted for bacteriologic culture and susceptibility testing.

Questionnaires with 7 questions were given to owners at scheduled recheck visits to assess client satisfaction with VAP placement (Appendix 2). Observations and VAP function were evaluated for each patient. Duration of VAP observation was defined as the interval in days from VAP placement to data evaluation or VAP removal. Duration of successful aspiration was defined as the interval in days from VAP placement to data evaluation or irreversible failure of aspiration. Duration of successful infusion was defined as the interval in days from VAP placement to data evaluation or irreversible failure of infusion.

Results

Vascular access ports were successfully placed in the left femoral vein of 6 cats (median body weight, 5.1 kg [11.2 lb]; range, 3.4 to 8.1 kg [7.5 to 17.8 lb]) and 3 dogs (median body weight, 5.3 kg [11.7 lb]; range, 5.1 to 8.7 kg [11.2 to 19.1 lb]). Five injection ports were placed over the left ilial wing and 4 over the caudal portion of the left side of the thorax (Figure 3). Five-French-diameter catheters were used in 7 patients; 7-F-diameter catheters were placed in 2 cats. Median operative time was 75 minutes (range, 59 to 85 minutes). Median length of catheter tubing used was 30 cm (range, 18 to 35.5 cm). Median VAP (port hub plus catheter) luminal volume was 0.41 mL (range, 0.33 to 0.74 mL). Of the cats, 2 had vaccine-associated sarcomas, 2 had oral sarcomas, 1 had nasal lymphoma, and 1 had tonsillar carcinoma. Of the dogs, 1 had multicentric lymphoma, 1 had meningioma, and 1 had aural squamous cell carcinoma.

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Photograph of a dog undergoing blood withdrawal from a femoral VAP. The port hub has been placed over the caudal portion of the left thoracic wall. Inset: Huber needle with deflected tip.

Citation: Journal of the American Veterinary Medical Association 231, 9; 10.2460/javma.231.9.1354

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Signs of port-related pain or discomfort was recorded in 4 patients during 9 of 123 (7%) patient observations (Table 1). One animal had mild left hind limb lameness on 2 occasions, 1 had signs of pain over the injection port on 2 occasions, 1 had signs of injection port and catheter track pain on 3 occasions, and 1 had signs of injection port and catheter track pain on 2 occasions. All observations of signs of VAP-associated pain or discomfort occurred and then resolved within the first 2 weeks of surgery for VAP placement.

Table 1—

Maximum pain and inflammation scores for all 9 study animals (during 123 patient observations) by location of VAP.

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Injection port site and catheter track site inflammation scores represented the maximum score observed for each animal during the entire duration of VAP observation. No signs of inflammation (redness, swelling, heat, or discharge) were detected over the port site in 100 of 123 (81%) patient evaluations. During 23 evaluations, signs of inflammation at the port site were observed in 8 patients; signs were mild to moderate. In all but 1 patient, observations of inflammation associated with the port site occurred within the first 2 weeks after implantation. One cat had intermittent redness of the port site on days 11, 40, and 89. In 105 of 123 (85%) patient evaluations, no signs of inflammation over the catheter track site were detected. During 18 evaluations, signs of inflammation over the catheter site were observed in 6 patients. Most signs of inflammation occurred within the first 2 weeks after VAP placement.

Primary uses of the VAPs in this study were to provide sedation for radiation therapy in 3 patients and to administer sedative drugs and chemotherapeutic drugs in 6 patients. The VAPs were used for withdrawal of blood samples in 8 patients. In 4 patients, VAPs were used within 24 hours of surgical placement for vincristine^h administration (1 patient), propofolⁱ administration (2 patients), or blood withdrawal (1 patient). Median duration of VAP observation was 147 days (range, 65 to 370 days), with 7 of 9 VAPs still in place at the time of data analysis. Median duration of successful infusion was 147 days (range, 60 to 370 days), and 7 of 9 VAPs had successful infusion at the time of data analysis. Median duration of successful aspiration was 117 days (range, 10 to 271 days). Of 119 infusion attempts, 94 (79%) infusions were uncomplicated, 17 (14%) were positional, and 8 (7%) were unsuccessful. Infusion was positional on 1 or more occasions in 7 VAPs. One animal had unsuccessful infusion on days 77, 112, and 147, but infusion was categorized as uncomplicated on all subsequent attempts. Infusion was unsuccessful in 1 animal on day 124. Tissue plasminogen activator^j (2 mg in 2 mL of saline solution, IV) was infused into the port of 1 animal with no immediate change in port patency. At the following visit, day 152, the VAP was successfully infused but described as positional. Infusion was unsuccessful again on day 201, but the VAP returned to positional infusion on day 243 without treatment. Infusion was unsuccessful in 1 animal on day 271 and in another on day 60. The VAPs in these 2 patients were surgically removed.

Of 119 aspiration attempts, 63 (53%) aspirations were uncomplicated, 20 (17%) were positional, and 36 (30%) were unsuccessful (Table 2). Aspiration was positional at least once in 7 VAPs. In 2 patients, the ability to withdraw blood returned after previous unsuccessful attempts. Complete function was restored in 1 animal after 1 unsuccessful aspiration attempt. In 1 animal, aspiration was unsuccessful on 5 occasions over the course of treatment, but the occlusions were transient and function returned after each unsuccessful attempt until irreversible failure at day 202. Two patients had successful aspiration until their final recheck, at which time aspiration was unsuccessful. Two patients had irreversible failure of aspiration, and their ports were surgically removed. Aspiration of the VAP in 1 animal failed after 10 days. An injection of iodinated contrast material and fluoroscopic evaluation revealed a filling defect, consistent with a thrombus in the caudal vena cava just distal to the catheter tip (Figure 4). However, infusion of the VAP in this cat was successful for 244 days (until the end of the study).

Table 2—

Maximum infusion and aspiration scores (for all 9 study animals) by location of VAP.

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Lateral fluoroscopic view of the abdomen of a cat in which a VAP had been placed in the left femoral vein. Iodinated contrast medium has been injected through the VAP, and a filling defect is observed in the caudal vena cava, at the tip of the VAP catheter.

Citation: Journal of the American Veterinary Medical Association 231, 9; 10.2460/javma.231.9.1354

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Drugs infused through the VAPs included propofol (36 times in 6 patients), ketamine^k (2 times in 2 patients), diazepam^l (2 times in 2 patients), doxorubicin^m (20 times in 6 patients), carboplatinⁿ (3 times in 2 patients), vincristine (8 times in 2 patients), and cyclophosphamide^o (4 times in 2 patients). No extravasation of drugs was observed. Thirty-five samples were obtained through the VAPs for CBC or other hematologic tests.

The VAPs were surgically removed in 2 patients. One patient was evaluated 271 days after VAP placement with clinical signs of lethargy, inappetance, and fever (rectal temperature, 40.6°C [105°F]). A CBC revealed moderate normocytic, normochromic anemia (Hct 27%; reference range, 42% to 57%); degenerative left shift with low segmented neutrophils (2.5 × 10³/μL; reference range, 3.3 to 9.3 × 10³/μL) and increased band neutrophils (2.9 × 10³/μL; reference range, 0 to 0.1 × 10³/μL); and monocytosis (3.5 × 10³/μL; reference range, 0.1 to 1 × 10³/μL). Results of serum biochemical analyses and urinalysis were unremarkable. Abdominal ultrasonography did not reveal any gross abnormalities. Supportive treatment included IV administration of fluids and amoxicillin-clavulanic acid (30 mg/kg, IV, q 8 h), and rectal temperature returned to reference limits. Upon surgical removal of the VAP, partial occlusion of the catheter tubing at the site of fixation to the femoral vein was detected and an associated thrombus was observed. The catheter was submitted for aerobic and anaerobic bacteriologic culture and susceptibility testing, with no bacterial growth reported. One day after VAP removal, increased neutrophils (32.6 × 10³/μL) and decreased band neutrophils (1.1 × 10³/μL) were detected. The dog recovered completely and was released to the care of the owner 1 day after surgery.

In 1 patient (a cat with nasal lymphoma that received radiation therapy and combination chemotherapy), the VAP could not be aspirated or flushed on day 60. On palpation of the injection port over the caudal portion of the thorax, the port appeared to have rotated within the subcutaneous tissues. Surgery to reposition the port was attempted on day 67. A kink in the catheter tubing causing partial to complete occlusion of the VAP was observed at the connection between the catheter tubing and the port hub, presumably caused by rotation of the port hub. After repositioning of the port hub, aspiration and infusion of the VAP remained unsuccessful. The VAP was removed, and a clot was identified within the catheter tubing (Figure 5). Recovery after VAP removal was uncomplicated.

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Photograph of a VAP catheter after surgical removal. The catheter tubing has been transected with scissors. The obstruction, a blood clot, was removed by forcefully flushing through the port.

Citation: Journal of the American Veterinary Medical Association 231, 9; 10.2460/javma.231.9.1354

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Evaluation of 39 client questionnaires (273 total questions) completed at scheduled patient rechecks revealed 132 strong positive responses, 84 positive responses, and 32 neutral responses. Negative responses (n = 17) and strong negative responses (8) were given by 3 owners and were related to the appearance of the port (1), perceived VAP-related discomfort (1), or VAP dysfunction (1).

Discussion

The VAP is designed to provide permanent, repeated vascular access. Median duration of VAP use in this study was 4.8 months, which is comparable to that reported in previous studies.^6,11 One study¹¹ that evaluated the use of femoral venous VAPs in 35 research cats found that they remained useful for 1 to 8 months, with loss of sampling ability in 1 venous VAP.Henry et al⁶ described the use of jugular VAPs in 14 cats; the VAPs in that study were functional for 2.5 months, and none lost sampling ability.⁶ A more recent study⁹ of the use of jugular VAPs in 4 feline blood donors found successful use of the VAPs for at least 6 months. In the present study, median duration of successful aspiration was 117 days (range, 10 to 271). Irreversible loss of sampling ability was confirmed in 8 of 9 patients. However, 2 of the 8 patients had VAPs with lost sampling ability at the last recheck examination and, for the purposes of this study, were considered to have irreversible loss of sampling ability. Similar to other patients, sampling ability may have returned at follow-up evaluations. Six of 9 VAPs were functional for longer than the 70-day period reported by Henry et al.⁶

It is unclear why some of the VAPs in our patients lost sampling ability. In human medicine, reported VAP-associated complications resulting in port occlusion include thrombus formation and the development of a fibrin sleeve at the catheter tip.¹⁴ However, the prevalence of these complications in humans is low. In a study¹⁵ of 300 human patients, prevalence of thrombus formation was 9.7%. Findings of a more recent study,¹⁶ which compared the use of subclavian VAPs with conventional vascular access in women with ovarian carcinoma, revealed partial port occlusion in 22.7% of cases and complete port occlusion in 9% of cases. Edema of the extremities is reported as a sequel to central venous thrombus in human patients.^13,14 In our study, limb edema was not observed. Thrombus formation in the caudal vena cava, at the tip of the VAP catheter, was detected in 1 cat by use of contrast fluoroscopy. Thrombus or fibrin sleeve formation at the tip of the catheter may be secondary to direct endothelial damage caused by the catheter or by repeated injection of chemotherapeutic or sedative drugs.¹⁷ The presence of a thrombus, acting as a ball valve or a fibrin sleeve from the catheter tip, is likely to result in partial VAP occlusion. Although it is possible that thrombus formation occurred specifically as a result of delivery of chemotherapeutic drugs through the VAP, the use of chemotherapy has not predisposed to thrombus formation in human studies.¹⁸ Both patients with complete VAP occlusion and surgical removal had thrombus formation within the catheter, associated in both cases with stenosis or kinking of the catheter tubing. Both patients were also treated with chemotherapy. Thrombus formation may also form more frequently in smalldiameter catheter tubing.³ However, Morrison et al⁹ reported successful use of VAPs with 5-F catheters for a 6-month period. Seven of the 9 VAPs in our study were 5-F catheters. Failure to maintain positive pressure while flushing the VAP, infrequent heparin locking, or inadequate heparin concentration within the flush solution might also predispose to thrombus formation. Obvious technical error was not observed in the study reported here.

Infection is one of the most common VAP-related complications reported in human literature.^18,19 In our study, 1 animal had signs of systemic illness including fever, lethargy, and inappetance, all of which resolved after antimicrobial administration and VAP removal. Neither bacteremia nor local bacterial infection of the VAP was detected in this case; however, WBC count and clinical signs were initially suggestive of bacteremia or sepsis. van Rooden et al¹⁸ have suggested a bidirectional association between thrombus formation and infection. Following thrombus formation, microorganisms may adhere to thrombin sheaths in minimally bacteremic patients. Conversely, localized VAP-related infection may induce an inflammatory response that predisposes to the formation of a thrombus. In the present study, 1 patient had signs of both infection and thrombus formation, although a correlation between the 2 was not definitively identified. Taurolidine-citrate, a solution with antimicrobial properties, has been used with human VAPs to minimize infection and may prove to be useful for veterinary patients.²⁰ Hyperosmotic glucose solution has been used for its bactericidal properties; however, it may also serve as a potential medium for bacterial growth.⁸

The use of fibrinolytic agents, such as streptokinase and urokinase, to treat VAP-associated thrombi (with varying success) has been reported in human and veterinary literature.^6,15 In our study, 1 patient was treated with tissue plasminogen activator through the VAP when both aspiration and infusion failed. At the following visit, the VAP was functional for infusion, but not aspiration.

Migration of the port hub with subsequent kinking of the catheter tubing was observed in 1 patient in this study. Care should be taken to suture the injection port to a layer of muscular fascia to avoid this complication. Anchoring the port may be more challenging in obese patients. Obesity may also result in difficult port palpation and isolation after surgery. Excision of a portion of the subcutaneous tissue may be required to facilitate port palpation. In addition, the silicone catheter tubing has the potential to be overtightened while being sutured to the femoral vein. Intraoperative flushing of the VAP following placement of the encircling ligature should be performed to confirm catheter patency. Ideal placement of the port hub is over a firm area that will provide counterpressure during placement of the Huber needle. In our study, we placed the port hub over the thoracic wall or the ilial wing. Both locations were acceptable for clinical use.

The femoral location might provide an acceptable alternative to jugular VAP placement. Patients undergoing surgery or radiation therapy in the region of the jugular vein might benefit from femoral VAPs. The femoral location provides a site that can be easily monitored or used in fractious patients. Overall, clients were satisfied with their decision to have femoral VAPs used in their pets. Study limitations included small sample size and the inability to determine specific causes of partial VAP occlusion in each case. Further studies with larger numbers of clinical patients are necessary to determine the success of femoral venous VAPs as well as the preferred port hub location. Further studies might also include more use of diagnostic imaging, surgery, or necropsy to determine the cause of partial or complete port occlusion and to determine the prevalence of thrombus, infection, and other complications of VAPs in the femoral location.