Percutaneous hepatic perfusion (PHP)

Percutaneous hepatic perfusion (PHP) is a procedure which utilizes veno-veno bypass to isolate the liver circulation and deliver high dose chemotherapy to treat non-operable liver metastases. The blood returning to the patient from the hepatic circulation goes through a filter which removes the chemotherapeutic agent, sparing the patient from systemic chemotherapy. The isolation of the liver circulation with balloons in the vena cava and the inflammatory response to the filter cause significant hemodynamic shifts that require high dose vasopressors, as well as potentially causing coagulopathy.

This procedure is performed as a combined procedure with IR, surgical oncology, and perfusion in a hybrid OR. The patients undergo a screening process to ensure cardiopulmonary fitness to undergo the procedure.

Percutaneous hepatic perfusion (PHP)

Anesthesia type	General
Airway	ETT
Lines and access	PIV Central line Arterial line Bypass cannulas
Monitors	Standard ABP
Primary anesthetic considerations
Preoperative	Cardiopulmonary fitness Team coordination (Oncology, VIR, perfusion, pharmacy)
Intraoperative	Decreased preload on balloon inflation Massive vasodilation on filter initiation
Postoperative	Coagulopathy, resuscitation
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Overview

Indications

PHP is indicated, by the FDA, for adult patients with uveal melanoma complicated by unresectable hepatic metastases affecting less than 50% of the liver and no extrahepatic disease or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation.

The procedure has been used for other types of non-operable metastases in Europe.

Surgical procedure

Currently the only commercially available PHP system in the United States is the Hepzato Kit™. The process is well described by Burgmans et al

Access

The first step of the procedure is accessing all necessary vessels.

• Left/right radial artery - arterial catheter - blood pressure monitoring
• Left IJ - central line - vasoactive infusions and intravenous access
• Right IJ - 10 French sheath - bypass outflow cannula
• Left femoral artery - 5 French sheath - chemotherapy delivery
• Right femoral vein - 18 French - bypass inflow cannula, introduction of balloon catheter

Isolation and bypass

The next step is to isolate the liver circulation and initiate veno-veno bypass. The inflation of balloons and inflammatory response to the bypass circuit can cause significant hypotension.

• Hepatic angiograms are obtained, and the tip of a microcatheter is then placed into the hepatic artery at the intended location of infusion

• 300U/kg of heparin is administered with a goal ACT >400 prior to introduction of balloon catheter
• 16-F double-balloon catheter (Hepzato Kit) is inserted via the right CFV and positioned with its tip in the right atrium
• Veno-veno bypass (flow of 600-800ml/min managed by perfusion) is initiated by connecting the catheter to an extracorporeal circulation system consisting of a centrifugal pump and two drug filtration activated carbon, aspirating blood through catheter fenestrations in a segment between the two balloons, and actively pumping through the filtration system until it returns through the sheath in the right IJ

• The cranial balloon of the catheter is then inflated in the right atrium and retracted into the inferior caval vein (ICV). The caudal balloon is inflated in the IVC below the level of the hepatic veins and above the level of the renal veins
• A venogram is obtained by hand injection of a contrast to ensure adequate positioning of the double-balloon catheter and isolation of the venous hepatic circulation

Filtration and chemotherapy

The next step is delivery of the chemotherapy and filtering it out of the returning blood. This is the most critical portion of the procedure. The filters cause a massive inflammatory response and also filter catecholamines from the blood which leads to impressive hypotension. Expect your SBP to decrease by ~100-130 quickly after the filters are primed. The removal of catecholamines from the blood requires much higher than usual pressors; it is not unusual for all 3 of your vasopressors to be above the pump's "normal limit."

• The hemofiltration filters are brought online one by one
• Once the cartridges are completely filled with blood, the bypass line is closed
• When the hemofiltration circuit is running sufficiently and hemodynamic stability is achieved intra-arterial infusion of chemotherapeutic drugs may be started using a pump injector. Before and during the infusion, hepatic angiograms are obtained to ensure that hepatic blood flow is not compromised
• After the infusion, extracorporeal filtration is continued for 30 min (‘washout period’) to allow clearance of chemotherapeutics from the liver

Emergence

The final step is reversal of heparinization, managing ongoing resuscitation, assessing and managing coagulopathy, extubation, and transporting the patient to recovery.

• Heparin is reversed 1:1 with protamine
• CBC, INR, Fibrinogen, +/- thromboelastogram/ROTEM
• Sheaths will remain in place until normal coagulation is demonstrated; generally removed in recovery unit/ICU
• Unless contraindicated, patient is extubated at the end of the procedure

Preoperative management

Patient evaluation

Neurologic	Intracranial metastases or brain lesions with a propensity to bleed are a contraindication to PHP
Cardiovascular	Patient should be evaluated for CAD, valulopathies, arrythmias, and heart failure prior to undergoing procedure. Screening dictated by institution, but should be a thorough investigation; likely an EKG, echocardiogram, +/- left heart catheterization to ensure cardiopulmonary fitness for hemodynamic stress of procedure
Pulmonary	Standard evaluation
Gastrointestinal	Patient should be evaluated for signs of liver disease prior to undergoing the procedure (encephalopathy, portocaval hypertension, jaundice, etc.). Concerns for liver dysfunction are a contraindication to PHP
Hematologic	Chronic disease and active malignancy can cause anemia, leukopenia, and thrombocytopenia. Liver metastases can cause coagulopathy. Baseline coagulation should be assessed prior to procedure
Renal	Standard evaluation
Endocrine	Inflammatory response to bypass circuit can cause hyperglycemia that may be more pronounced in diabetic patients

Labs and studies

• CBC
• CMP
• INR
• Fibrinogen
• Type and screen
• EKG
• Cardiac evaluation likely including TTE

Operating room setup

• Arterial catheter and transducer
• Central line
• Hotline on fluid warmer
• 4+ infusion pumps
• Norepinephrine, epinephrine, and vasopressin on pump
• Push dose pressors drawn up
• Heparin and protamine

Intraoperative management

Monitoring and access

• PIV
• Standard monitors
• Post induction radial arterial line
• Attach sterile tubing from VIR placed central line to bolus line and infusions

Induction and airway management

• Standard

Positioning

• Supine with arms tucked
• Neck and groins are prepped, forced air warmer must be placed on mid abdomen prior to draping
• Consider an underbody warming blanket

Maintenance and surgical considerations

• Standard maintenance, patient usually maintained chemically paralyzed for potential breath holds needed for fluoroscopy
• Patient may need "anti-anesthetic" vasopressor infusion during access stage due to low surgical stimulation (vessels accessed with needles under local anesthesia)
• Use and encourage closed loop communication between all teams. Ask for "5 minute heads up" prior to bypass initiation, balloon inflation, and filter initiation. There are many teams involved and effective coordination is absolutely required for a successful procedure
• Start vasoactive infusions a few minutes prior to balloon inflation. Target a SBP ~180 prior to inflation
• Following inflation of balloons there will be a brief time when the proceduralists will test balloons, during this time you will want to prepare for filter initiation by once again increasing your SBP. Target a SBP ~200 prior to initiation. Strategies vary, but norepinephrine 0.1mcg/kg/min, epinephrine 0.1mcg/kg/min, and vasopressin 0.06units/min would not be an unusual place to start
• On filter initiation, titrate infusions and use push dose pressors to stabilize patient. After the initial hypotension from the filters, you will usually decrease your infusions, though they will still be high doses
• When the filters go offline and v-v bypass ends, pressors can usually be drastically and quickly deescalated with the goal of being completely off by procedure end
• Send labs to prepare to correct coagulopathy, though that is usually done in recovery

Emergence

• Standard extubation criteria
• Sheaths will stay in place until coagulation is corrected; preoperatively counsel the patient that they will need to keep their legs flat postoperatively

Postoperative management

Disposition

• Depends on local practice concerning vascular sheath management

Pain management

• Pain is generally mild and related to lying flat for hours

Potential complications

• Cardiac collapse from severe hypotension
• Coagulopathy
• Vessell rupture, retroperitoneal bleeding
• Standard risks of general anesthesia