Isolated Limb Perfusion of Upper Limb: How I Do It

Isolated Limb Perfusion of Upper Limb

The limb salvage rates for extremity soft tissue sarcomas (STSs) are over 90% (1, 2). Amputation however is still performed for 10% of patients. Indications include (a) locally advanced soft tissue sarcomas (LSTS) and recurrent sarcomas treated with curative intent, and (b) palliative amputations in metastatic sarcoma (3). Management of LSTS is challenging. The only upfront surgical option for them would be an amputation. Amputation undoubtedly provides the best local control rates for LSTS (4). Most patients are apprehensive and decline amputation and want their limbs preserved. Data on efficacy of neo-adjuvant radiation in downstaging LSTS to permit limb salvage is scarce. The role of chemotherapy (CT) in STS is evolving (5, 6). The response rates of CT are inferior to that of ILP. Literature review reveals isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNFα) + melphalan can salvage 50–80% of limbs in locally advanced STSs (7–11).

ILP for upper limb is challenging as compared to ILP of the lower limb. Although the vessels can be accessed easily in the axilla, application of the esmarch bandage, achieving desired flow rates, and double vein canulation are demanding. Literature on technique of lower limb ILP is available in abundant; however, the technique of ILP in upper limb (UL) is usually mentioned as a passing note. In this article we describe the technique of upper limb ILP in detail.

Indications of ILP

1. Multifocal primary tumors

2. Multiple recurrent tumors

3. Secondary angiosarcoma in a lymphedematous limb

4. Tumor recurrences in previously irradiated areas

5. Single tumors with fixation to or invasion into the neurovascular bundle and/or bone

6. Unresectable tumors that do not respond to neoadjuvant therapy

Contraindications of ILP

1. Fungating tumor

2. Severe cardiopulmonary disease

3. Uncontrolled infections

4. Organ transplants

5. Concurrent immunosuppressive therapy

6. Concurrent chemotherapy, immunotherapy, radiation therapy

7. Coagulation disorder

8. Severe obliterative peripheral arteriosclerosis

9. Severe lymphedema in the extremity (not in a secondary angiosarcoma setting)

Anesthetic Management

The patient will undergo thorough preoperative evaluation with emphasis on cardiovascular reserve and coagulation profile. Along with the standard monitors such as the pulse oximetry, non-invasive blood pressure, electrocardiogram, end tidal carbon dioxide, temperature, and entropy, continuous cardiac output monitoring is necessary to assess the fluid and hemodynamic status. The blood products, crystalloids, and colloids are stacked in operating room. The availability of warming blankets and rapid fluid infuser system is ensured.

The procedure is done under general anesthesia. After orotracheal intubation, nasogastric tube, invasive arterial, central venous cannula, and urinary catheter should be inserted. Two large bore peripheral intravenous cannulation is necessary for volume replacement.

The goals would be to maintain mean arterial pressure (MAP) > 70 mmHg, avoid hypothermia, and maintain higher systemic blood pressure than the limb pressure to keep it isolated and prevent spill of chemotherapy agent into systemic circulation.

The baseline activated clotting time (ACT) is recorded before systemic heparinization. Heparin 300 IU/kg body weight (BW) is given through the central venous cannula to achieve target ACT more than 480 s. Three minutes after heparin dose, the axillary artery and vein are cannulated. ACT is monitored every 30 min from the systemic and isolated limb venous circulation. Heparin may be repeated half of the initial dose to maintain the target ACT.

ABG is monitored throughout the duration of hyperthermic isolated limb perfusion (HILP) from the systemic and limb samples simultaneously. Oxygen, carbon dioxide, hemoglobin, electrolytes, glucose, bicarbonate, and lactate levels are maintained accordingly. Pressors, fluids, blood products, and bicarbonates would be necessary to prevent reperfusion-induced hemodynamic instability before unclamping the isolated limb. Protamine after the test dose of 1 mg is given at the dose of 1 mg/100 units of heparin to fully reverse heparinization. ACT is done finally to confirm normalization.

At the end of the procedure, after ensuring hemodynamic stability and reversal of neuromuscular blocker and tracheal extubation, the patient is transferred and monitored in intensive care unit.

ILP Procedure

Patient is in supine position with arm abducted to 90° on an arm table. The entire UL is free draped. During ILP the axillary artery and vein are clamped in the axilla; collateral vessels are ligated. Arteriotomy and venotomy are done. Vessels are cannulated with appropriately sized catheters (Medtronic, cannula SS venous), and the tip is positioned in the proximal brachial artery, position checked with intraoperative C-arm fluoroscopy imaging. Usually, a 12 French catheter is used for the vein and a 10 French catheter for the axillary artery. Shanz screw is inserted into the head of the humerus and an Esmarch rubber bandage is wrapped proximal to the screw and twisted around the root of the limb, in axilla. The rubber bandage should be proximal to the site of arteriotomy and venotomy. After placement of the catheters and application of torniquet, the isolated limb is perfused by extracorporeal circulation that is oxygenated and propelled by a hyperthermic perfusion system (Rand Performer HT, Italy) (Fig. 1).

Fig. 1.

Simplified circuit of ILP of upper limb with techniques to increase flow rate

The ILP consists of 90-min-long perfusion with 13 mg/L volume of melphalan at mild hyperthermia (39–40 °C). We use water displacement method to measure the volume of limb; other methods such as standardized limb circumference measurement or CT scan volumetry may also be followed (12). Composition of the perfusate will include the following: priming volume of 700 mL consisting of 500 mL normal saline, 200 mL of colloid, and 1 mL (5000 IU) heparin. Priming is done till target temperature of 40 °C is reached and is dependent on the rate. With appropriate flow rates, priming must take less than 30 min. TNFα is unavailable in India and our protocol is to use only melphalan. However, if TNFα is available, 3 mg of TNFα is to be injected as a bolus into the arterial line when limb tissue temperature is > 38 °C. Melphalan is administered 30 min later at limb temperatures between 39 and 40 °C.

Throughout the perfusion period, any potential leakage of the drugs is monitored using a radioactive tracer. Four to five millicurie of Technetium 99 m pertechnetate is injected into the perfusion machine apparatus. Continuous monitoring is performed with a precordial gamma probe. Systemic leakage is expressed quantitatively as a percentage. More than 10% detection in the precordium will be considered a leak.

During ILP, adequate tissue temperatures are achieved and maintained by heating the heparinized perfusate and by the application of a sterile warm blanket around the limb. If necessary, the temperature of the operating room is increased to facilitate early achievement of desired limb temperatures.

Flow rates during the perfusion are kept at physiologic levels of 40 to 50 mL/minute/L limb volume. Reduced venous return leading to reduced flow rates is a common problem encountered during UL ILP. The flow rates can be reduced provided the oxygen saturation of the perfusate is > 65%. The basilic vein may also be cannulated to increase the venous return thereby increasing the flow rates, in which case a Y connector is needed to incorporate both the limbs of the venous outflow (13). Hyperthermia and melphalan may result in vasospasm and reduced flow rates; stellate ganglion block to increase flow rates by causing vasodilation may also be used (14). Flow rates alter with change in position of the limb. That position of limb in which the flow rates are maximum is preferred. Perfusate blood gas levels are monitored every 20 min. There is continuous monitoring of the temperature in the subcutaneous and intramuscular distal and proximal compartments of the limb using thermistor needle probes. Continuous monitoring of activated clotting time is done.

At the end of ILP, the limb is washed with normal saline, till fluid is clear in venous cannula, which will require 2–3 L of normal saline. The circuit is disconnected, catheters are removed, and vessels are sutured and would be closed in layers over a drain. We do not routinely perform prophylactic fasciotomy.

Regional toxicity is scored according to Wieberdink et al., and for systemic toxicity, common toxicity criteria v5.0 is used (15).

Postoperative Care

1. Limb elevation—the importance of limb elevation cannot be overemphasized.

2. Look for skin changes—most of the patients develop blisters which may be due to ILP or heat induced, which spontaneously resolves.

3. Monitor vital parameters.

4. Monitor distal pulses and nerve function.

5. Blood transfusion—due to loss of volume from one limb.

6. Monitor urine output, creatine kinase.

7. Look for acidosis.

8. Watch for compartment syndrome.

9. Anticoagulation protocol—6 h after the procedure if there are no bleeding complications, 5000 IU of Inj. Dalteparin is given subcutaneously 12th hourly and Tab. aspirin 75 mg once daily till discharge. From discharge for a period of 3 months, the patient receives 75 mg of aspirin daily along with 110 mg dabigatron twice daily.

The tumor is reassessed at 6 to 8 weeks for response. RECIST 1.1 criteria are used for radiological evaluation of the tumor (16). Surgery is performed 8 to 12 weeks following ILP based on the response. The goal is to achieve a locally radical, complete resection after ILP, and if this is not considered possible after ILP without severely compromising limb function, then amputation/repeat ILP is performed.

Unlike amputations in the lower limb for which prosthesis is used successfully, amputations of the upper limb usually leave the patient disabled. ILP may benefit patients by salvaging their limbs and may result in a better functional and psychological outcome without compromising on their oncological outcomes (17). Some hand is better than no hand (18). ILP should be considered in the armamentarium while managing tumors of the UL.

Declarations

Conflict of Interest

The authors declare no competing interests.