Benefits, Complications, and Care of Implantable Infusion Devices in 31 Children With Cancer

By Jutie Wallace and Paul M. Zeltzer

San Antonio, Texas

�9 This retrospective study of 31 pediatric oncology patients with subcutaneously implanted infusion devices details the required care and demonstrates the benefits and complications of the system. The Port-a-cath device was used in 29 patients; one had an Infuse-a-port, and two had Medlports. Ages of the patients ranged from 5 months to 16 years. The average time of catheter function was more than 163 +_ 149 days and the total experience was 5,208 patient catheter days. In all, five catheters were removed, one fo r suspected and one for proven infection, two with extravasations, and one patient had spontaneous extrusion and thrombosis. These totally implanted devices allowed safe administration of blood products, antibiotics, short-term hyperalimentation, and sclerosing chemothera- peutic agents to pediatric oncology patients with previ- ously compromised venous access. �9 1987 by Grune & Stratton. Inc.

INDEX WORDS: Implantable infusion devices.

V 'ENOUS ACCESS for pediatric patients and especially those with cancer can be a difficult

problem. Access has been improved by the use of transcutaneous catheters of the Hickman and Broviac type, ~ but several disadvantages are inherent in these systems. One study found that catheter-related com- plications requiring catheter removal was 19%. 2 There are stringent maintenance requirements. Heparin flushes must be performed once daily with dressing changes three to four times per week) Leaks and tears in the catheters may require frequent repairs' or replacement, 3 and the open skin penetration site pre- vents bathing or swimming. Thus, while they may be useful in the critically ill patient, excessive mainte- nance is necessary for out patient or less intensive use.

Totally implantable venous access systems share with transcutaneous catheters the advantages of decreased venipunctures, easier administration of medications and fluids, and support of the patient's nutritional needs, which may improve the tolerance to antitumor therapy. 2"+

Several advantages accrue to a closed implantable device: (1) minimal maintenance requiring a heparin flush only once every 4 weeks; (2) an apparent decreased risk of infection, which may be secondary to the natural skin barrier inhibiting access of bacteria to the blood streamS; and (3) possible decreased removal rate of implantable venous systems due to infections. 6 Our data on this large study population suggest that this device provides safe convenient central venous

access with an acceptable complication rate for pediat- ric oncology patients.

MATERIALS AND METHODS

Surgical Placement The Port-a-cath system (PAC; Pharmaeia Laboratories, Piscata-

way, NJ) was implanted by two pediatric surgeons in 28 of 31 children at the Santa Rosa Children's Hospital in San Antonio, TX. Two Mediports (Cormed Ine, Medina, NY) and one Infuse-a-port (Infusaid Corp, Norwood, MA) 7 were also implanted under the skin using general anesthesia. The catheter was usually placed into the common facial vein or jugular vein by venous cutdown and then threaded into the right atrium of the heart. Another subcutaneous incision was placed in the chest over the nipple area near the fourth and fifth intercostal spaces. This provides a pocket to hold the portal chamber. A tunnel was then made subcutaneously between the two incisions and the catheter was threaded to the portal chamber. The catheter was attached to the portal chamber by a metal slip ring for the PAC. The system was flushed with a saline-heparin solution for potency. Intraoperative c-arm fluoroscopy was employed to ascer- tain correct placement of the catheter into the right atrium; then the incisions were sutured and dressed. The system was then flushed with 5 mL (100 ,u/mL) heparin solution for three consecutive days postoperatively to maintain continued patency. It was used for access 24 hours after surgery when necessary.

Routine Care

Prior to access, the area was cleansed with a Betadine solution and then with alcohol. Sterile gloves were worn and the maintenance of a sterile field was essential. Only Huber point needles were used, as they have a solid core tip and side opening to prevent coring of the rubber septum. The Hubcr needle used for one time medication delivery was usually a straight one; whereas for continuous delivery of fluids, a needle with a 90 ~ bend was used. For accurate insertion, the needle was inserted perpendicular to the septum after careful palpation of the device) Correct placement of the needle into the portal chamber of the septum was ascertained with aspiration of blood prior to any infusion. To prevent tearing of the septum, care was taken to prevent rocking or tilting of the needle by using two 2 x 2 gauze sponges under the needle. The needle was then secured by an occlusive dressing. The surgical technique has been reported. 9

From The University o f Texas Health Science Center at San Antonio, San Antonio, TX.

Supported in part by NCl Grant No. CA 36004-03 and the Robert J. and Helen C. Kleberg Foundation.

Presented in part at the Nursing Symposium of the Childrens . Cancer Study Group, Atlanta, Georgia, April 20, 1986.

Address reprint requests to Paul 3t. Zeltzer, MD, Division of llematology/Oncology, Children's Hospital of Los Angeles, PO Box 54700, Los Angeles, CA 90054-0700.

�9 1987 by Grune & Stratton. Inc. 0022-3468/87/2209-0013503.00/0

Journal of Pediatric Surgery, Vol 22, No 9 (September), 1987: pp 833-838 833

834 WALLACE AND ZELrZER

To flush the system, 5 mL normal saline was infused before and after each medication, while 10 to 20 mL was used after each blood sampling or infusion of blood products? This flushing procedure was to prevent thrombus formation, provide a check for adquate flow, and act as a buffer between medications, except where contraindi- cated as with amphotericin B. If slight resistance was felt when flushing after blood products, a 2 mL heparin flush (100 p/mL) was used. j~ If strong resistance was felt, alternating heparin flush and aspiration was used to remove a thrombus. If the system was occluded, 1 mL urokinase (Abbokinase, Abbott Laboratories, Chi- cago, IL) or streptokinase (Streptase, Hoechst Roussel, Sommer- rifle, N J: 5,000 IU per vial) was instilled by a physician to clear the catheter. 9'1~ If infusion and withdrawal were still impaired after this procedure, the catheter qualified as an "occluded catheter" and was removed. Routinely, the system was flushed once a month with heparin (100 p/mL) to maintain patency (5 mL in the PAC and 3 mL in the other two ports). Positive pressure was applied with the heparin flush as the needle was withdrawn to prevent reflux of blood into the catheter with each heparinization.

RESULTS

The ages of the patients ranged from 5 months to 16 years of age at the time of implantation.(Table 1). Of

the 31 patients, 17 had acute leukemia; five had histiocytosis X; one had osteosarcoma; two had rhab- domyosarcoma; two had Wilms' tumors; and four had brain tumors. Eighteen patients had the catheter placed in the right anterior chest, 13 had left anterior chest placement, and one patient (no. 2) had place- ment in the mid chest; one patient (no. 2) had two catheters. Sixteen patients are alive with the devices still in use. Deaths of the other 15 patients were due to disease progression and were not catheter-related.

The average time for functional catheter use was more than 163 ___ 149 days with the total being 5,208 patient catheter days.

Blood products and antibiotics were the most fre- quent nonchemotherapy agents infused. A large num- ber of different classes of chemotherapy agents also were infused. Of the several sclerosing-type chemo- therapy agents, neither obvious extravasation, tissue necrosis, nor pain at the site occurred with these agents (Table 2). Probable thrombus formation occurred in

Table 1. Patient Characteristics and Catheter Status and Complications

Complications Catheter Time Catheter Not Necessarily Requiring Catheter

Patient Age Sex Diagnosis in Days Status Re: to Catheter Removal

1 * 5 mo F BT 3 0 + P/A None No

2 t 8 mo F Hx 41 P/A Postoperative infection Yes Septicemia, S aur-

eus

ANC > 5 0 0 2 15 mo F Hx 35 P/D None No 3 10 mo M BT 155+ P/A None No 4 12 mo M ALL 9 0 + P/A None No

5 13 mo M ANLL 215 P/D Septicemia, S epi No BMT (cleared)

ANC <500, thrombus

(spontaneous extru-

sion] 6 13 mo M Rhab 196 P/D Thrombus, streptoki- Yes BMT

nase x 2 (persistent

clot) 7 14 mo M VVT 5 1 5 + P/A None No

8 14 me M ALL 300 + P/A None No

9 18 mo F Hx 515 + P/A Thrombus, heparin No

flush x 1 10 19 mo M Hx 90 P/D None No

11 22 mo F Hx 50 O/A Neck extravasation Yes 12 2 yr 4 mo F Hx 20 P/D None No 13 2 yr 6 mo M ANLL 190 P/D None No

14:1: 3 yr I mo M ALL 3 0 + P/A None No 15 3 yr 2 mo M W'l- 365 + P/A Septicemia, C fetus je- No

junii (cleared) ANC > 500

16~ 3 yr 4 mo M ALL 3 0 + P/A None No 17 3 yr 6 rno M BT 2 1 0 + P/A None No

18 5 yr F BT 150+ P/A Septicemia, S. viridans No

(cleared) ANC >

500

INFUSION DEVICES IN CHILDREN WITH CANCER

Table 1. Patient Characteristics and Catheter Status and Complications (Cont'd)

835

Complications Catheter Time Catheter Not Necessarily Requiring Catheter

Patient Age Sex Diagnosis in Days Status Re: to Catheter Removal

19 4 yr 8 me F ANLL 488 O/A Septicemia, S viridans Yes BMT

thrombus (cleared) streptok x 1, extra- vasation in neck

20 4 yr 8 me F Rhab 180 P/D Polymicrobial infec- No

tions K pneumo B fragilis ANC > 500

21 4 yr 8 me M ALL 75 P/D Septicemia, S aureus No (cleared) ANC 500*

22 6 yr M ALL 17 P/D Fever ANC < 500 No 23 6 yr 9 me F ANLL 3 9 5 + P/A None No

24 6 yr 7 me M ANLL 150+ P/A Septicemia, Sepi No

fever, ANC < 500 No 25 7 yr M ANLL 112 P/D Septicemia, S mitis Yes, BMT

(cleared) ANC <

500, persistent fe- ver

26 8 yr 1 me M ALL 3 0 + P/A None No

27 10 yr F Osteo 60 P/D Fever, ANC > 500 No 28 11 yr M ALL 120+ P/A None No

29 12 yr F ALL 4 P/D Fever, ANC < 500 No

30 12 yr M ALL 180 P/D Polymicrobial infec- No tions, septicemia E

cofi and S epi ANC

< 500, thrombus (cleared) hep flush

31 16 u 3 me M ANLL 180+ P/A Multiple fevers, ANC No

> 500

Mean, 163 -+ 149. Total patient catheter days, 5,208. SD, 149. SE, 26.

Abbreviations: ALL, acute lymphocytic leukemia; ANLL, acute nonlymphocytic leukemia; BT, brain tumor; Osteo, osteosarcoma; WT, Wilms" tumor; Hx, histiocytosis X; Rhab, rhabdomyosarcoma; P, patient; A, alive; D, deceased; O, occluded; BMT, bone marrow transplant; ANC, absolute neutrophil count.

�9 Infuse-a-port device. t Device removed after 41 days and replaced for another 35 days. .1;Medipor t device.

five of 31 (16%) patients, with only one patient requir- ing catheter removal due to the occlusion. Four of the five catheter occlusions were corrected with either heparin and/or streptokinase solution.

Six of 31 (19%) patients had positive blood cultures associated with an absolute neutrophil count (ANC) below 500 ~tL. Only one catheter was removed because of persistent infection that could not be cleared with antimicrobial agents (3%) and one device was removed because of suspected infection after marrow transplan- tation. The others were treated with appropriate anti- biotics through the system with complete recovery. Two other patients experienced fevers with an ANC <500/t~L. Three patients had positive blood cultures and one patient had polymicrobial sepsis with the ANC above 500//~L.

Two of 31 patients experienced extravasations in the neck with subsequent removal of the catheters. One catheter was instilled with urokinase for 20 minutes

then flushed with normal saline with resultant neck edema. Findings on removal of this catheter showed no catheter leakage or tear at the chamber. The other catheter was removed after radiographs demonstrated extravasation of contrast at the catheter hub. The characteristics, advantages, and disadvantages of three of the commonly used devices are listed in Table 3. The visual features for the three devices and their connec- tions can be appreciated in Figs 1 and 2.

The approximate cost of the system is as follows: infusion device, $350; operating room, $390; surgeon and anesthesiologist fee, $1,100; semiprivate room for 3 days, $550, totaling $2,390.

DISCUSSION

Our clinical experience confirms the benefits of the totally implantable venous access devices, u'ta Our patient population and devices differed from those other studies that used Infuse-a-ports in adult

836 WALLACE AND ZEL'fZER

Table 2. Agents Infused in Access Systems

Nonchemotherapy Chemotherapy

Fluids 31 t Packed red blood cells 16 Antibiotics 15 Platelets 14 Hyperslimentation 7 Amphotericin B 5 Albumin 2

Vincristine* 15 ARA C 14 Cytoxan 9 VP-16 7 Cisplatin 6 Adriamycin* 4 Methylprednisolone 4 Vinblastine* 3 BCNU 3 Daunomycin* 3 Nitrogen mustard* 2 Methotrexate 2 5 Azacytidine 2 AMSA* 2 DTIC 2 VM-26 1

*Represents vesicants infused. ~Numbers represent number of patients receiving these products.

patients. 6 We found also a 19% infection rate, but our data demonstrate a low incidence of complications and infection-related removal. 6

One of the major risks associated with prolonged central venous access is the development of infection. The published data are difficult to compare with this study. Six of 92 patients (median 127 patient catheter days) had infections with one catheter removed due to septicemia. 6 Bothe et a115 reported catheter-related sepsis in two of 74 patients (average 29 days of continuous drug delivery per patient); seven catheters required removal. Merritt et al 2 reported four of 21 Hickman catheters were removed due to infection or clotting with an average of 433 patient catheter days.

Our study showed that six of 31 patients (mean 163+ patient catheter days) had positive blood cul- tures. But importantly, five of six patients were treated successfully with appropriate antimicrobial therapy with complete clearing of their infections. All the above patients had myelosuppression (ANC <500/~L) at the time of their positive blood cultures. Therefore, the 3% infection removal rate of catheters and the 19% positive blood cultures were not necessarily related to catheter infection itself, but rather they were probably due to the underlying disease and/or myelosuppressive treatment in this high-risk population. One of the two catheters was removed after 41 days because of fever and persistent S at treus septicemia present since the

Table 3. Trouble Shooting "Occluded Catheters"

Turn patient's head Move arms up and down Turn patient side to side Replace Huber needle Heparin flush and aspiration Streptokinase or urokinase

Q I

Fig 1. Top and frontal v iews of Mediport, Infus-a-port, and Port-a-cath devices. For reference, base diameter of the Port- a-cath is 2.54 cm.

time of surgery. The same patient had a second Port- a-eath device implanted 7 months later at the age of 15 months but expired 35 days later due to progressive disease. An autopsy was not permitted, but all blood cultures were negative up until death. One other catheter was removed after bone marrow transplanta- tion (BMT) due to persistant fevers with negative blood cultures. The other positive blood cultures were prior to BMT and were treated successfully with complete recovery. At time of removal cultures were negative. Thus, the only proven catheter sepsis that persisted was in patient 2 (Table 1).

The other major catheter complication was occlu- sion by thrombus. Lokich reported 15 of 92 (16%) catheter thromboses with ten necessitating removal. 6 He cited decreased venous flow, intrapulmonary or metastatic disease, chemotherapy agents, and large bore catheter size as contributing causes. Merritt et al 2 reported two Hickman catheters removed due to occlu- sion. Of the 32 catheters in this study, five were occluded as defined by either difficulty in withdrawal of blood and/or in forward flushing. Four of the five occlusions were successfully cleared with either hepa- rin and/or streptokinase. One catheter was removed at another institution due to occlusion. This catheter was patent for 196 days before removal. Patient 5 had his thrombus cleared, but the device was extruded sponta- neously following BMT.

Of the six catheters removed, three were following BMT. BMT patients have prolonged neutropenia with numerous infections and fevers, and according to pres-

~L Fig 2. Side view of the three devices. Height of the Mediport

(1.1 cm in Table 3) is f rom the top of the base to the septum.

INFUSION DEVICES IN CHILDREN WITH CANCER 837

ent protocols, require catheters with either double or triple lumens to accommodate intense antimicrobial therapy and longer term nutritional support. The PAC devices were left in three patients but Hickman cathe- ters were placed to provide additional access. There- fore, when a patient is considered for BMT, the implantable infusion devices may not be as desirable as the Hickman or Broviac catheters.

Aspirating blood from the catheter was a common problem. Sometimes this was due to positioning rather than thrombus formation. Positional problems can be detected by turning the patient's head, moving the arms up and down, or by turning the patient from side to side. If the needle has been in place for more than 2 weeks, a small clot may collect at the needle tip and a new Huber needle should be reinserted. This will sometimes result in a blood return. Thus, the different correctable causes should be considered before the catheter is removed for suspected thrombosis (Table 3).

The factors that favor the use of one device over the other relate to local availability, unique characteristics of the patient and device, and the surgeon's experience (Table 4). Considerations should be given to using a catheter that can be threaded into the common facial vein. 9 This should preserve internal jugular venous return, should reinsertion on the coutralateral side become necessary. A larger sized catheter usually

must be threaded directly into the internal jugular vein and thence to the superior vena cava or heart. This usually results in permanent occlusion of the internal jugular. The Infuse-a-port has a small catheter avail- able for use in infants, but small catheters have not been easily obtainable for the other devices. Though the baseplate of the Infuse-a-port is large, necessitat- ing a larger pocket, tight skin tenting has not been a problem. Both the Mediport and Infuse-a-port have small septae and may be more difficult to puncture. The Mediport developed septal leaks in two cases not reported in this series.

The PAC has the largest septum. Its catheter con- nects by a slip ring to the port and requires skill and experience by the surgeon to ensure a permanent, nonleaking connection. The other devices have a sealed connection.

The site of placement of the implantable infusion device is of major importance, but this factor is not discussed in the literature. The patients with left anterior chest wall placement had difficulty with echo- cardiographic and nuclear scan evaluations of anthra- cycline toxicity. Thus, placement in the right anterior chest wall should be considered in consultation with the surgeon. Another placement concern is the possible interference of breast bud development in girls. Again, there is no data on interference of breast development in the literature.

Table 4. Comparison of Implantable Venous Access Systems ~ �9

Infuse-a-port Mediport Port-a-cath

Reservoir Base diameter (cm)

Height (cm)

Catheter Length (cm) Lumen diameter (mm)

Weight (g) Volume

Septum Diameter Maximum no. of punc-

tures Advantages

Disadvantages

Company

4.76 3.5 2.54

1.58 1.1 1.35

50.8 50.0 0.6 or 1.0 1.0, 1.5

13 15

0.2 mL in port 0.0032 mL/cm 1 .O mL in port with In 0.6 mm catheter 1.0 mm catheter 0.0081 mL/cm 1.5 mL in port with In 1.O mm catheter 1.5 mm catheter 0.25" (7 ram) 0.3" (8 mm)

1,O00-2,000 1,500-2,000

Sealed connection to catheter Low profile Small catheter for infants Sialastic mesh baseplate Lightest of 3 for sutures

Sealed connection to catheter

Small septum Small septum Large baseplate ? septum rupture on

older models

Infusaid Corp, Norwood, MA Cormed, Inc, Medina, NY

76.2 1.02

28 0.4 mL in port

0.6 mL in 1.02 mm catheter

0.45" (11.4 ram)

1,000-2,000

Largest septum excellent for larger children

Manual connection to catheter (slip ring)

Higher profile No small catheter available Pharmacia Nu Tech, Piecata-

way, NJ

Adapted with permisslon, t~

838 WALLACE AND ZEL"rZER

The access systems were effective in our populat ion. O u r young pat ients requi red frequent inpat ien t and ou tpa t i en t infusions o f blood products and mul t ip le chemothe rapy agents with several being vesicants. These agents were infused without the risk o f ext ravas- a t ion for well over 1 yea r in five patients , Ampho te r i c in B, an i r r i tant and sclerosing agent in per iphera l veins, also was infused without difficulty.

Severa l advantages accrue in compar ing the closed ca the t e r systems with o ther ca the te rs and o ther s tud- ies. ~6"~7 T h e y inc lude (1) m i n i m a l m a i n t e n a n c e required by the family of the pat ients; (2) absence of body image a l te ra t ion reflected in a high level of pa t ien t acceptabi l i ty ; (3) no in ter ference with clothing, p laying, or swimming; and (4) an appa ren t decreased risk of complicat ions compared with o ther ca the te r systems. 6.~s Our results confirm these advantages .

In summary , the to ta l ly implan ted infusion devices provide an a l te rna te means for consis tent centra l venous access in pat ients with compromised veins.

Wi th pedia t r ic oncology pat ients , this closed sys tem provided for admin i s t r a t ion of blood products , ant ib i - otics, shor t - te rm hypera l imenta t ion , and chemother - apy agents with some o f these substances del ivered s imultaneously. ~9'2~ These ports also can a c c o m m o d a t e two needles s imul taneous ly to deliver compa t ib le sub- stances. Though es t ima ted cost of the imp lan tab l e device with hospi ta l iza t ion is approx ima te ly $2,390, the el igible pat ients had no real a l ternat ives . This system m a y be useful not only for oncology pat ients , but possibly for others who need long- term venous access such as h e m o p h i l i a c and cys t ic f ibros is pat ients . ~z

ACKNOWLEDGMENT

We acknowledge the critical review and discussions on surgical considerations with Dr I. Ratner and Dr B. McGovern, and the helpful suggestions of John Drake, RN, MSN, Sylvia Brown, RN, and Janine Primomo, RN.

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