Anticoagulants and Statins As Pharmacological Agents in Free Flap Surgery

Current Rationale

Adnan Pršić, MD; Elizabeth Kiwanuka, MD, PhD; Stephanie A. Caterson, MD; Edward J. Caterson, MD, PhD

Disclosures

ePlasty. 2015;15 

In This Article

Abstract and Introduction

Abstract

Microvascular free flaps are key components of reconstructive surgery, but despite their common use and usual reliability, flap failures still occur. Many pharmacological agents have been utilized to minimize risk of flap failure caused by thrombosis. However, the challenge of most antithrombotic therapy lies in providing patients with optimal antithrombotic prophylaxis without adverse bleeding effects. There is a limited but growing body of evidence suggesting that the vasoprotective and anti-inflammatory actions of statins can be beneficial for free flap survival. By inhibiting mevalonic acid, the downstream effects of statins include reduction of inflammation, reduced thrombogenicity, and improved vasodilation. This review provides a summary of the pathophysiology of thrombus formation and the current evidence of anticoagulation practices with aspirin, heparin, and dextran. In addition, the potential benefits of statins in the perioperative management of free flaps are highlighted.

Introduction

Free flaps have become a common technique to transfer tissue, such as skin, fat, fascia, muscle, and/or bone, together with its blood supply. Microvascular free-tissue transfers are often used in an attempt to restore complex congenital, ablative, and traumatic tissue defects, and the survival of the flap is highly dependent on the patency of the microvascular anastomosis.[1,2] During surgery, the arterial and venous blood flow is reconnected using microsurgical techniques. These techniques are based on standard vascular surgery principles, on a microscopic level. Murphy[3] performed the first successful vascular anastomosis as early as 1897. In 1902, Carrel[4] described the method for triangulation of blood vessels in arterial and venous repair, and in 1960, Jacobson and Suarez[5] created microsurgical anastomoses in laboratory animals, coining the term "microvascular surgery." Reconstructive microsurgery was born in the garage of Dr Harry Buncke in 1964, when he reported a successful replantation of a rabbit ear with 1-mm vessels.[6] Buncke, and his homemade instruments, unlocked the door to modern-day microsurgical techniques. Initially, free flap surgery was restricted by high failure rates, long operative times, and a limited number of trained surgeons, but advances in surgical techniques and equipment have decreased the rates of complications. However, despite the current reliability of microsurgical free-tissue transfers, flap failures still arise. Such failures are most commonly related to thrombosis occurring at the arterial or venous anastomosis, often resulting from technical errors. Approximately 10% of microvascular free flaps suffer complications, and flaps that undergo reexploration can be salvaged at a 50% to 80% success rate, making the overall success rate for free flaps up to 98% among experienced surgeons.[7–9] Nonetheless, anastomotic thrombosis still remains a major complication of microsurgical free-tissue transfers and total flap loss due to thrombi remains a significant concern.[10]

To inhibit the formation of microvascular thrombi, many surgeons routinely use preemptive anticoagulants and/or vasodilators.[1,11,12] Approximately 96% of surgeons reported use of some types of anticoagulation regimen, and the protocols vary widely among surgeons.[13] The most commonly used pharmacological agents are aspirin, heparin, and dextran, but their usage is often based on the surgeon's experience and without agreement in the timing or dosing. In fact, an early review of anticoagulation practices around the world point to anecdotal experience with more than 20 different agents used, most with very limited data supporting their benefit.[14] Although some of the pharmacological agents have been studied experimentally, most of the data come from animal studies or retrospective studies, with only a few prospective randomized trials. In addition, new drug such as statins have emerged as pharmacological agents that are used to prevent the formation of microvascular thrombosis. There is a growing body of evidence that suggest that the vasoprotective and anti-inflammatory actions of statins can be beneficial for free flap survival, but their role in preventing anastomotic thrombosis is not known. This article provides a summary of the pathophysiology of thrombus formation and reviews the current evidence of anticoagulation practices with aspirin, heparin, and dextran. We revisit the literature concerning the utility of pharmacological treatments used to improve free flap survival and review the utility of pharmacological agents not traditionally thought of as anticoagulants.

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