Background: The hepatic arterial infusion (HAI) pump is a treatment-delivery method based on the principle of targeting the tumor site directly and can be used alone or in combination with systemic chemotherapy.
Objectives: The intent of this article is to serve as a resource for oncology nurses to safely identify and manage HAI pump complications. These complications include seroma, flipped HAI pump, infection, changes in pressure and temperature, challenging access, dry pump, high residual volume, chemical hepatitis, risk of ulcer, and radiologic imaging considerations.
Methods: The authors performed a literature review to provide a foundation for nurses to be able to manage HAI pump infusions.
Findings: The literature review revealed minimal nursing resources to manage complications with an HAI pump. Resources to manage complications are crucial for safely administering medications and properly maintaining the function of the pump. Attention to patient education should be incorporated in nursing practice.
The liver is the dominant metastatic site for patients with colorectal cancer in the United States. Many patients initially present with liver metastases, and 50% develop liver metastases during the course of their disease (Groot Koerkamp et al., 2017). Multiple treatment options can be incorporated in the plan of care, including chemotherapy, radiation therapy, and surgery. Systemic chemotherapy is most common when surgery is not an initial option; however, surgical resection is preferred for curative intent. Hepatic arterial infusion (HAI) chemotherapy was developed to treat a metastatic site that is difficult to control. This modality has become an added treatment option for patients with unresectable liver metastases (Callahan & Kemeny, 2010) and can lead to rates of long-term disease-free survival because of control of the metastatic malignancies, allowing the option of resection, which would rarely occur with systemic chemotherapy alone (D’Angelica et al., 2015).
Despite being a treatment modality since the 1980s, a paucity of literature exists on the use of HAI, particularly literature geared toward nurses. A literature search revealed limited published articles about HAI treatment and management of complications. Martin (2002) discussed the variety of hepatic arterial catheters that have been used in the past and some of the risks and benefits of these delivery methods. A systematic literature review by Parks and Routt (2015) identified articles addressing use, procedures, and nursing care of patients with HAI pumps. Best practices have been identified through extrapolation from physician-specific literature and high volume of exposure to patients with HAI pumps at Memorial Sloan Kettering Cancer Center, a National Cancer Institute–designated cancer center in New York, New York, that cites more than 2,500 HAI treatments annually. This article provides an up-to-date overview of the HAI pump, the most common pump used to deliver treatment, and reviews pump management complications and strategies for nurses to address potential complications.
Hepatic Arterial Infusion
The HAI pump is a delivery method that directly targets the tumor site. The healthy liver receives its blood supply from the portal vein. The blood supply for hepatic metastases is derived from the hepatic artery; therefore, patients with liver metastases can benefit from the administration of chemotherapy via an HAI pump because it directly targets the source (Gyves et al., 1982).
HAI is a concept that has been used for many years. Early generation delivery methods included external devices connected to the hepatic artery and subcutaneous ports connected to a catheter and infused via the hepatic artery. These options required close monitoring and had significant complications, such as catheter-related thrombosis, migration, bleeding, and infection (Wickremesekera, Cannan, & Stubbs, 2000). The Codman® 3000 Infusion Pump referred to in this article is an implantable device that provides continuous chemotherapy infusions and does not require frequent access. With the use of the pump, no additional external equipment is needed.
Hepatic Arterial Infusion Pump
Prior to having an HAI pump placed, the patient must be deemed an appropriate candidate by having imaging to confirm the absence of extrahepatic disease and an arteriogram to identify any aberrant hepatic vessels. In the operating room, the surgeon creates a subcutaneous placement in the abdomen, referred to as the pump pocket, and sutures in the pump to the abdominal fascia (see Figure 1). Depending on the patient’s size and anatomy, pumps can be placed in the upper or lower quadrant on the right or left side. The catheter is inserted via the gastroduodenal artery to perfuse the hepatic artery, and aberrant vessels are tied off. A cholecystectomy is performed simultaneously to prevent cholecystitis from chemotherapy (Kanat, Gewirtz, & Kemeny, 2012).
Once placement is confirmed, the drug chamber is filled with heparin and normal saline to maintain patency, and the pump begins to flow. A hepatic perfusion scan is performed in nuclear medicine to verify placement and function prior to chemotherapy administration. Findings of abnormal perfusion (i.e., extrahepatic or one-sided perfusion) are addressed and corrected before initiating chemotherapy. A normal hepatic perfusion scan report should note “no extrahepatic perfusion.” Once discharged from the hospital, the patient must be followed as an outpatient by an interprofessional team. Communication, collaboration, and close monitoring are essential to ensure safe care is delivered.
The HAI pump is a circular, titanium device about 3 inches in diameter (see Figure 2). It includes a drug chamber and a charging chamber. The drug chamber contains a 30 ml reservoir where medication is stored. The charging chamber is located in the outer portion of the pump and has bellows and a propellant sealed inside (see Figure 3). The body temperature warms the propellant, which puts constant pressure on the bellows and forces the medication in the drug chamber through the catheter at a slow, continuous rate. Codman provides refill kits that contain supplies needed for the refill procedure.
A 1.5-inch, 22-gauge non-coring Huber needle is introduced by a clinician into the raised septum of the pump to empty and refill the drug chamber. The time frame for pump emptying and refilling is based on which medication is in the reservoir. By emptying the residual volume before refilling the drug chamber, an estimated individual flow rate can be calculated and used for precise drug dosing. A bolus injection pathway bypasses the drug reservoir and accesses the catheter directly for bolus infusions or catheter flushes. This is a vital component of the pump because it enables access to the catheter to inject radiopharmaceuticals in nuclear medicine to visualize accurate catheter perfusion and offers an access point to assess the patency with abnormal flow rates. The bolus injection pathway is accessed with a special bolus needle that has a closed tip with the hole in the shaft of the needle. It is tagged to prevent inadvertent use of the incorrect needle when accessing the pump for refill (see Figure 4). The pathway is flushed with normal saline 20 ml and heparin 1,000 U/10 ml. To avoid overpressurization, syringes smaller than 10 ml should not be used, and the lines should never be aspirated (Codman, 2002).
Floxuridine (FUDR®) is a pyrimidine antimetabolite that is converted to 5-fluorodeoxyuridine in the liver. Floxuridine has a high rate of hepatic extraction and low systemic exposures, making it optimal for hepatic infusion (Ensminger, 2002). It is instilled for a 14-day infusion with heparin and normal saline to prevent catheter clotting. The addition of HAI dexamethasone (Decadron®) with the floxuridine dose was studied by Kemeny et al. (1992), and patients randomized to receive the combination were found to have less biliary toxicity and tolerated higher doses of floxuridine. Therefore, best practice is to administer dexamethasone with each floxuridine dose. The drug dose is determined by the medical oncologist based on the patient’s weight, liver enzyme trends, and individualized flow rate calculation. Floxuridine, dexamethasone, heparin, and normal saline are alternated with heparin and normal saline every 14 days. Patients with a known heparin allergy can receive fondaparinux sodium (Arixra®) 5 mg as a substitute.
Glycerol is a viscous solution that can also be instilled into the pump every six to eight weeks. The thicker fluid viscosity infuses at a slower rate and is used to maintain catheter patency when the patient is not receiving chemotherapy for an extended period. This medication needs to be ordered from a compounding pharmacy that specializes in preparing personalized medications.
HAI is a complex regimen that can be accompanied by complications that require early assessment and intervention to ensure safe administration. Complications and management are often identified by oncology nurses. Because of the high volume of patients with HAI pumps in Memorial Sloan Kettering Cancer Center, nurses must complete a rigorous educational module and multiple return demonstrations to be deemed competent to access and administer medication via the HAI pump. Mismanaged and unaddressed complications can lead to complete pump malfunction, making it an unviable treatment option for the patient. Multiple return demonstrations can be difficult in institutions with low volume; therefore, each institution must develop policies and procedures to assist nurses in safe and effective management of the HAI pump complications. Management of these complications is based on management of the associated complications in other treatment types. For example, known best practices for seroma management can be applied to HAI-related seromas or management of infection while considering the unique complexities of the device and location.
A seroma is a postoperative complication characterized by a collection of fluid in the pump pocket. The seroma looks like a water balloon and makes the septum of the pump difficult to palpate and access; therefore, the fluid may need to be aspirated prior to refill. This is done by using sterile technique to insert a 1-inch, 21-gauge needle subcutaneously in the seroma and aspirating the fluid into a 20 ml syringe until the septum is palpable. The fluid is typically serosanguineous in color but can be blood that has accumulated in the pump pocket. A specimen is collected for culture and sensitivity if infection is suspected. It is common for seroma fluid to re-accumulate in the pump pocket shortly after being drained. As the pump pocket site heals, the body will slowly reabsorb the fluid. The rate of time will vary by patient, so draining the seroma may need to be performed at multiple visits over a period of time until resolution. Patients may be prescribed diuretics and instructed to wear an abdominal binder to increase the rate of fluid reabsorption.
The pump pocket should be assessed for signs and symptoms of infection, such as redness, warmth, or skin breakdown, and an antibiotic should be prescribed if infection is suspected. It is crucial for clinicians to access the pump using sterile technique. ChloraPrep® (chlorhexidine gluconate and isopropyl alcohol) or Betadine® (povidone-iodine) are appropriate antiseptic skin preparations to cleanse the site prior to pump access. If a pump pocket is infected and not resolving with oral antibiotics, then an IV antibiotic must be given, and the surgeon may consider surgical relocation or removal.
Removal of the pump is a last resort for persistent infection. When a pump is removed, the device is extracted from the pocket and the catheter is clipped, remaining in place. A catheter without fluid infusing will eventually form a clot and make it impossible for another pump to be connected. It is imperative that clinicians assess for signs of infection and treat accordingly to avoid pump removal.
Flipped Hepatic Arterial Infusion Pump
The HAI pump is positioned in the fascia of the abdomen and secured by four sutures. If the septum is unable to be palpated, the pump may be flipped. Typically, a distinct sound of the needle hitting metal is heard and felt when attempting to access it. This can occur if one or more of the sutures loosen and the pump has enough space for movement. A flipped pump is confirmed with an abdominal x-ray with cross-table lateral. On occasion, a clinician can manually manipulate the pump pocket and flip the pump back into position. If the pump is unable to be flipped manually or continues to flip positions, the surgeon may consider surgically reinforcing sutures. Patients who experience this complication should be instructed to wear an abdominal binder and avoid heavy lifting or jogging to help immobilize the pump.
Changes in Atmospheric Pressure and Increased Body Temperature
The rate of the HAI pump is increased by higher altitude and body temperature. The only indicator of the rate of infusion is measuring the residual volume. There are no alarms to alert the patient that the fluid level is getting low. This should be taken into consideration when patients are traveling or live at higher altitudes because drug doses and refill schedules need to be adjusted. Patients should be educated on the importance of maintaining normal body temperature and avoid using heating pads, electric blankets, saunas, or hot tubs. Scuba diving will affect the flow rate and should be avoided. Air travel is permitted with pressurized cabins. Some limitations of having an HAI pump can be frustrating for patients, requiring emotional support to understand the rationale for the restrictions. Patients who miss their scheduled appointments may be putting the pump at risk for running dry and becoming occluded.
Hepatic Arterial Infusion Pump With Challenging Access
Pump placement in the abdomen is dependent on the patient’s normal vascular anatomy. Patients with excessive abdominal adipose tissue should have their pump placed above the muscle layer near the ribs. The supine position is best for accessing pumps because a flatter position ensures easier septum palpation (see Figure 5). If the septum still remains difficult to find, a blind stick can be attempted by palpating and visualizing the outer perimeter of the pump, then marking with a pen where the center appears to be. Once the needle penetrates the skin, it is easier to feel the septum with the needle. The manufacturer prefilled kits include two 1.5-inch non-coring Huber needles; however, 2-inch needles should be available if needed. If these strategies are unsuccessful, the patient can be accessed under fluoroscopy for refill procedure by an interventional radiologist.
Dry Hepatic Arterial Infusion Pump
The HAI pump will continue to flow regardless of medication being instilled in the drug chamber; therefore, the main chamber needs to be maintained at specific time frames to avoid the pump going dry. Without medication infusing, blood in the hepatic artery could back up into the catheter and clot. Possible explanations for a dry pump include patient’s delayed return for pump maintenance, fevers, travel at high altitude, or use of heat on the pump, which increases the rate of infusion of medication.
Upon accessing a pump and noting no residual fluid, the nurse should reposition the needle. Another clinician can assist with repositioning and correcting needle placement. An additional technique to confirm needle placement is to attach and instill a 10 ml normal saline syringe. If the normal saline returns into the syringe when the plunger is released, it confirms that the needle position is accurate because the pressure in the pump is pushing the normal saline back, evidence of a dry pump.
To alleviate a dry pump, the drug chamber needs to be refilled with medication. The goal is to refill the reservoir to ensure fluid flow is reinitiated immediately. Because the duration of the pump being dry is unknown, the patency of the catheter should be confirmed by flushing the bolus pathway. If normal saline and heparin are injected with ease, patency is confirmed and treatment can proceed as scheduled. Notify the licensed independent practitioner (LIP) immediately if pain is noted in the abdomen or back when flushing the bolus pathway. Do not proceed because pain could be indicative of extrahepatic perfusion. A hepatic perfusion study should be ordered to evaluate catheter migration. If pain persists, the patient may need to be medicated until acute pain subsides. If resistance is met when flushing the bolus injection pathway, alteplase (Cathflo®) 2 mg can be instilled. If the bolus pathway cannot be flushed after attempts to restore patency, the LIP may determine that the catheter is clotted. Unfortunately, no further intervention exists to resolve this complication, and HAI treatment is no longer an option.
The only exception to allowing the pump to run dry is when the patient is at the end of life. When a patient is admitted to hospice and no further treatment is being considered, the pump may be left to run dry and not be refilled.
High Residual Pump Volume
Similar to how a dry pump can be detrimental to the catheter patency, a high residual volume can indicate a problem. With a reservoir chamber that holds 30 ml, a residual volume of 20 ml or greater should prompt the nurse to assess further. When high residual volume occurs, the patient may have returned sooner than anticipated for refill or may be an initial sign of catheter blockage. The nurse should access and flush the bolus injection pathway to assess patency. If there is resistance or pain, follow the steps listed previously for management of a dry pump.
Monitoring liver enzymes is crucial to safe care of patients with HAI pumps. This targeted therapy is delivered directly into the liver, which put these patients at higher risk for biliary toxicity. Liver enzymes (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, bilirubin) can become elevated, which will cause the patient to experience jaundice, generalized itching, dark urine, and light stools. The floxuridine dose may need to be decreased or temporarily held.
Medical management may include dexamethasone added to the maintenance drugs of heparin and normal saline to reduce biliary toxicity, which is tapered as liver enzymes normalize. Ursodiol (Actigall®) may also be prescribed to aid in managing the elevated liver enzymes. Liver function tests should be routinely monitored at least every two weeks to observe for rebound elevation.
As previously stated, a close proximity exists between the hepatic and gastroduodenal arteries, putting patients more at risk to develop ulcers (Kanat et al., 2012). A histamine-2 receptor antagonist, such as ranitidine (Zantac®), prescribed at the initiation of chemotherapy can decrease this risk. Patients should be instructed to avoid alcohol and to report signs of abdominal discomfort, diarrhea, and dark tarry stools because they could be indicative of a developing ulcer.
Security Screening and Radiologic Imaging
The Codman 3000 Infusion Pump is detectable with walk-through and handheld wand metal detectors. Patients are given an identification card from the manufacturer to present to security at screenings. The HAI pump is safe for use in all radiologic imaging machines, including magnetic resonance imaging, computed tomography, and x-ray.
Imaging studies are routinely performed to monitor treatment response and progression of disease. In some cases, the imaging will reveal other HAI pump complications, such as an aneurysm or a bleed at the tip of the catheter. An aneurysm is a dilation of the hepatic artery where the catheter lies. A bleed at the tip of the catheter can be visualized on the scan as a pooling of blood. The patient may present with weakness and low hemoglobin. Both complications require emergent intervention to embolize the artery. If embolization is unsuccessful, the pump may need to be permanently removed or emptied and not refilled to prevent further damage to the artery.
Patients with colorectal cancer are at higher risk of developing liver metastases, which could lead to increased mortality. The use of HAI is an additional treatment option for these patients. Good responses to HAI can lead to liver resection and cure for some patients. This article provides a resource for oncology nurses to safely manage HAI pump infusions and to address pump- or infusion-related complications. With individualized care and close collaboration between nurse and physician, this unique patient population can experience a low incidence of complications. Early intervention for most complications will result in retention of the pump.
About the Author(s)
Deborah Italiano, BSN, RN, OCN®, is an RN at Memorial Sloan Kettering Cancer Center in New York, NY. The author takes full responsibility for this content and did not receive honoraria or disclose any relevant financial relationships. The article has been reviewed by independent peer reviewers to ensure that it is objective and free from bias. Mention of specific products and opinions related to those products do not indicate or imply endorsement by the Oncology Nursing Society. Italiano can be reached at firstname.lastname@example.org, with copy to CJONEditor@ons.org. (Submitted August 2017. Accepted November 8, 2017.)
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