An isolated limb infusion technique: A guide for the perfusionist
Isolated limb perfusion with the administration of cytotoxic drugs has been successfully used to treat melanomas of the extremity since it was first introduced in 1958. The use of hyperthermia (40 degrees C) combined with chemotherapy agents, primarily melphalan, has resulted in greater cytotoxicity in laboratory studies, which led to the application of hyperthermia in clinical studies during the 1960s. The effectiveness of this regional technique and the absence of any good systemic therapy made hyperthermic-isolated limb perfusion (HILP) the main treatment for patients with regionally advanced melanoma. HILP involves open surgical dissection and cannulation of the peripheral vessels and is associated with moderate morbidity rates. Blood transfusions, systemic drug leak, infection, and damage to the blood vessels and nerves are all potential hazards associated with this technique. Recently, however, there has been increased interest in an alternative technique termed isolated limb infusion (ILI), which was first reported in 1994 from the Sydney Melanoma Unit in Australia. Based on a few single institution experiences, it was found that there are fewer morbidities associated with HILP than with ILI but no compromise in patient outcomes. ILI is a less invasive procedure involving the use of angiographically placed catheters inserted percutaneously through the femoral vessels that does not require blood donor exposure or use of a heart lung machine. Preliminary data suggest that the resultant local hypoxia and acidosis induced by this procedure potentiates the cytotoxic effects of melphalan. Response rates comparing ILI to HILP seem similar, and both are markedly better than systemic chemotherapy. ILI may be a more desirable option because morbidity is greatly reduced and outcomes appear similar. There is a potential role for the perfusionist in the application of ILI, an evolving area of cancer therapy.
Available from: PubMed Central
- "HILP is technically complex and demands close collaboration amongst surgeons, anesthesiologists, perfusionists and nurses. The procedure involves the use of an extracorporeal circuit, incorporating a blood pump and an oxygenator, to heat the perfusate and increase the oxygen tensions before delivery to the isolated limb [1,4,9]. During the HILP procedure, a dynamic fluid shift exists between the systemic vascular compartment and the vascular compartment of the isolated limb, especially when the patient is placed upon and disconnected from the extracorporeal circuit [2,4]. "
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ABSTRACT: Hyperthermic isolated limb perfusion (HILP) is used for patients with intractable or extensive in-transit metastatic melanoma of the limb to deliver high concentrations of cytotoxic agents to the affected limb and offers a treatment option in a disease stage with a poor prognosis when no treatment is given.
In a retrospective chart review of 17 cases, we studied the anesthetic and hemodynamic changes during HILP and its management.
HILP was well tolerated except in one case that is described herein. We present summary data of all cases undergoing upper and lower limb perfusion, discuss our current clinical practice of preoperative, perioperative and intraoperative patient care including the management of HILP circuit.
HILP is a challenging procedure, and requires a team effort including the surgical team, anesthesia care providers, perfusionists and nurses. Intraoperatively, invasive hemodynamic and metabolic monitoring is indispensable to manage significant hemodynamic and metabolic changes due to fluid shifts and release of cytokines.
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ABSTRACT: Two forms of regional chemotherapy for the treatment of advanced melanoma or sarcoma of the extremity are isolated limb perfusion (ILP) and the more recently described isolated limb infusion (ILI). Melphalan is the most commonly employed agent in both ILP and ILI, although it is often used in conjunction with other cytotoxic and/or biologic therapies. While ILP and ILI are far more effective for the treatment of extremity disease than is systemic therapy, there is still significant room for improvement in outcomes, from the standpoint of both response rate and toxicity. An understanding of the pharmacokinetics of regional chemotherapy would allow for the prediction of tumor response and toxicity and therefore patient outcomes. In addition, elucidating the mechanisms of drug resistance would lead to opportunities to develop effective chemo-modulators that enhance the effectiveness of ILP and ILI. This paper reviews progress in these two key areas of active investigation.
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ABSTRACT: Isolated limb infusion (ILI) for recurrent or in-transit melanoma is an accepted technique that allows high-dose chemotherapy to be delivered to an extremity with minimal systemic toxicity. Current infusion systems have relied on manual delivery of drugs and circulation of blood during the treatment. Herein, we document our initial results with an automated circuit for ILI as an alternative to the manual technique.
Patients undergoing ILI with an automated circuit for recurrent or advanced malignancy were identified. ILI was performed utilizing a Sarns 8000 roller pump attached to a Cobe 4:1 cardioplegia set with heat exchanger with a total priming volume of 80 ml. Melphalan (7.5 mg/L) and Dactinomycin (75 μg/L) doses which were corrected for ideal body weight were delivered via the infusion circuit after limb temperature reached 38 °C.
Fourteen lower extremity infusion procedures were performed in 10 patients. Successful infusion procedures were completed in all patients using the automated circuit. Constant flow rates of 50-70 cc/minute were achievable with the automated circuit. Acute toxicity and clinical results were similar to that reported with manual delivery systems.
ILI for advanced malignancy utilizing an automated circuit is feasible and safe. This automated system offers a safe and reliable alternative to the manual infusion technique.
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