Given that there is often a significant zone of vascular injury associated with amputations, interposition vein grafts are often necessary to reconstruct vessel loss from injury or debridement. Bony shortening can be an option to avoid such grafting, but the amount of shortening tolerated is dependent upon the level of injury. Concern has arisen historically that two anastomoses “in sequence” may be at higher risk of complication or thrombosis. However, when faced with the option of placing a single anastomosis under tension (or not debriding questionably damaged vessel) versus a vein graft, vein grafts provide superior outcomes. No difference in patency rates have been found retrospectively in cases necessitating vein grafts versus those that do not, whether the grafts are used for arterial or venous reconstruction or both [3].

In any case where the possible need for vein grafts is anticipated, a suitable donor site should be prepped into the sterile field. In the case of a digital, hand, or distal forearm amputation, the most optimal donor site is the ipsilateral forearm. An upper arm tourniquet should be placed and inflated above arterial pressure without exsanguinating so as to fill the veins for visualization. Marking pens are used to draw marks of varying diameter, coinciding with the diameter of the visible superficial veins. Particular attention is paid to branching points, which may be useful in certain situations, such as reconstructing the branching of the palmar arch or simultaneously reconstructing both radial and ulnar digital arteries.

To optimally match the length and diameter, the deficit to be grafted should be measured and a similar length of in situ graft harvested. If the graft is harvested, anastomosed either proximally or distally, and trimmed, and the second anastomosis performed; a significant difference in length, typically redundant, may be noted. All vein grafts should be reversed when utilized for arterial reconstruction, since even very small diameter veins have valves allowing one way flow, which can be present over any length of graft. If the vein can easily be flushed with heparinized saline in an in situ anterograde fashion, however, this may not be necessary.

A microvascular technique that is unique to vein grafting (or other situations where one vessel is highly mobile but rotating the vessels is difficult) is the “flipping” technique. In the case of the first anastomosis, whether proximal or distal, the anterior wall of the anastomosis is performed, and the free vessel flipped over the opposite to expose the back wall for completion of the anastomosis. The second anastomosis of the vein graft is performed utilizing standard techniques.

Venous flow through flaps can be utilized when there is a need for both vascular reconstruction and soft tissue coverage. Leaving vascular repairs uncovered or tenuously covered leads to likely desiccation, thrombosis, or leak. Venous flaps can be designed with a network of superficial veins with overlying subcutaneous fat and skin. By marking the superficial venous plexus preoperatively as described above (Fig. 8.2), the necessary veins, branching pattern, and skin paddle size can be found and utilized. The physiology that allows venous flaps to survive is not completely understood. Smaller, more distal grafts in the extremity have the advantage of a more complex venous network, multiple supplying and draining vessels, and fewer valves. This makes the volar wrist, dorsal hand, and dorsal foot reasonable donor sites that can often be closed primarily.

Heparin is used in many forms in replantation and microsurgery. It is used topically as heparinized saline irrigation intraoperatively and intravenously prior to anastomosis, as well as a postoperatively as an intravenous drip or subcutaneously for prophylactic anticoagulation. Its actions and effects on clotting are many. When used topically or intravenously, it binds to damaged endothelium, reversing the loss of normal negative charge. By doing so, platelet aggregation is inhibited. Heparin also decreases fibrinogen activity while decreasing blood viscosity. The clotting cascade is impaired at multiple points, clinically measured by a prolongation of the activated partial thromboplastin time (PTT), with a twofold prolongation considered therapeutic anticoagulation. The most significant effect on the clotting cascade is in activating antithrombin, which accelerates antithrombin’s inhibition of thrombin and factor Xa. The multiple actions of heparin make it the most utilized anticoagulant drug in microsurgery [5]. Given heparin’s interaction with plasma proteins, however, its dose-response curve is unpredictable, and activity levels must be followed clinically (PTT) to assess therapeutic level when used as a continuous drip. A continuous drip offers the flexibility of turning therapy on and off as needed based upon clinical circumstance, i.e., turning the drip off in the setting of bleeding.

Laboratory evidence supports the use of heparin intraoperatively. In a model of venous crush injury in the rat femoral vein, topical heparin yielded a 93 and 87 % patency rate at 1 h and 7 days post-anastomosis, compared to the use of saline irrigation, with a patency rate of 13 and 7 % at the same time points [6]. In a similar model of rat femoral artery crush, topical heparin and low-molecular-weight heparin (enoxaparin) both showed a significant improvement in patency rate at 1 and 7 days over saline and streptokinase [7]. The use of topical heparin is experimentally supported as an irrigant during the course of microvascular anastomosis, especially in the setting of crush injury.

Heparin use has also been substantiated in the case of post-replantation arterial thrombosis and venous insufficiency. Clinically, an 85 % overall survival rate was seen in a series of 13 replanted digits when 2,500–5,000 units of heparin was administered intravenously shortly after the development of arterial thrombosis. The same authors experimentally noted the intravenous bolus of heparin to affect the balance of coagulation and fibrinolysis, tipping the process in favor of fibrinolysis and increasing the recanalization rate [8]. In cases where a venous anastomosis could not be performed or when venous thrombosis occurs, an overall survival rate of 76 and 64 % has been shown, respectively. The approach utilizes a combination of external bleeding by paraungual incision and heparinized saline topical drip and intravenous heparin drip [9]. The use of intravenous heparin at the time of identification of arterial or venous thrombosis does not obviate the need for a return to the operating room for revision of anastomosis but can be used in the interim prior to returning to the operating room.

An intravenous bolus of heparin (40 units/kg) is typically given either prior to clamping and division of vessels in microsurgery or prior to release of clamps and reperfusion in replantation. This theoretically protects the anastomoses from a thrombotic tendency related to intimal damage, adventitial or foreign body (suture) exposure, or stasis related to vascular clamping. The use of heparin is not without possible complications, namely, the risk of bleeding or heparin-induced thrombocytopenia (HIT) and an antibody-mediated activation of platelet activity resulting in significant platelet consumption and thrombosis.

Low-molecular-weight heparins are derived from unfractionated heparin through hydrolysis into shorter polysaccharide fragments. These smaller molecules have been shown to have the same effect in inhibiting factor Xa but a weaker effect on thrombin. Enoxaparin and dalteparin are the two most commonly utilized and are once- or twice-daily dosed subcutaneously. LMWH has proven clinically useful due to its higher bioavailability, longer half-life, and steady dose-response relationship as compared to heparin. Because of this, prophylactic and therapeutic dosages are better defined, and laboratory values do not need to be followed to assess therapy. LMWH has less of an effect on PTT than heparin for a similar degree of anticoagulation. If clinically warranted, activity can be assessed by obtaining an anti-factor Xa assay.

Beyond the above advantages over heparin, it has also been shown to have similar anti-thrombotic effect, but no significant increase in bleeding complications [10, 11]. LMWH also has a significantly lower risk of heparin-induced thrombocytopenia. Due to the reliable dosing, it can be administered on an outpatient basis, which is a useful entity in either extending therapy or decreasing duration of hospitalization. Due to these advantages, we typically use subcutaneous LMWH postoperatively as an inpatient following free tissue transfer and replantation.

The antithrombotic activity of aspirin occurs via the irreversible inhibition of cyclooxygenase, an enzyme which acts to break arachidonic acid down to produce prostaglandins and thromboxane. This blocks thromboxane’s action as a potent vasoconstrictor and activator of platelet aggregation. Beyond this, aspirin has been shown to decrease thrombin production at the site of a vascular injury [12]. Given these and other downstream effects, aspirin has been shown to experimentally decrease thrombosis in rat models of microvascular injury, although the effect is less than that of heparin [13].

Multiple studies have examined the timing (pre-, intra-, and postoperative) and dosage of aspirin, mainly in rat models. In order to avoid complications both intraoperatively (bleeding) and longer term (systemic effects), the general recommendation has been to initiate low-dose aspirin therapy immediately postoperatively and return to routine general health recommendations for cardiovascular protection by 2–4 weeks postoperatively. The optimal dose has been shown to be approximately 3 mg/kg/day, which allows a decrease in thromboxane production while not significantly decreasing the protective effect of prostaglandin synthesis by endothelium [14]. We routinely utilize aspirin 325 mg rectally in the postanesthesia care unit, followed by daily low-dose therapy for a period of 1 month.

Dextran has a unique combination of effects that impart antithrombotic properties. Dextrans are polysaccharides synthesized by Leuconostoc mesenteroides streptococcus from sucrose. Dextran both reduces the activity of platelets and causes an increase in blood volume while decreasing viscosity. Dextran binds to platelets, erythrocytes, and endothelium, causing them to become electronegative and reducing aggregation and activation of platelets, which are further inhibited by dextran decreasing von Willebrand factor. When platelets do become activated, their distribution in the thrombus is more organized and diffuse, allowing thrombolysis to be a more orderly and efficient process [5]. Dextran has been utilized for its action as an osmotic agent in the setting of hypovolemia. This osmotic action increases blood volume and decreases blood viscosity, two properties that have shown to be beneficial in promoting vascular patency.

Dextrans come as varying size compounds, with the most commonly utilized being dextran-40 (molecular weight 40 k daltons). This is important, as at this molecular size, approximately 70 % is excreted by the kidneys in 24 h, with the remaining staying in the bloodstream for multiple days, prolonging both the beneficial and potentially harmful effects [15]. In a prospective, randomized study of head and neck microvascular reconstruction, Disa et al. showed that the use of dextran for 48 or 120 h had no clinical benefit over aspirin for 120 h postoperatively [16]. However, in this study, the rate of systemic complications compared to aspirin was 3.9 times higher with 48 h of infusion and 7.2 times higher at 120 h of infusion.

Serious, well-documented complications have been the consequence of the use of dextran. These include anaphylaxis, acute pulmonary edema, adult respiratory distress syndrome, cerebral edema, acute renal failure, and congestive heart failure. Despite the multiple mechanisms of action in decreasing thrombotic complications in microsurgery, these complications, in addition to the lack of definite clinical benefit, have made dextran fall out of favor with microvascular surgeons.

Papaverine is an opium alkaloid antispasmodic drug found in the opium poppy. Its pharmacologic uses include relieving spasm of the gastrointestinal tract, bile ducts, and ureter. In the vasculature, it is a smooth muscle relaxant, where applications include the therapy of subarachnoid hemorrhage in the cerebral vasculature and coronary artery disease in the internal mammary vessels during coronary artery bypass grafting. When used topically (30 mg/mL) directly on vessels during the course of a microvascular anastomosis, vasodilation and relief of vasospasm are seen [17].

In a rabbit model following microvascular anastomosis of the carotid artery, a significant increase in blood flow was seen following topical administration of papaverine. An added effect was noted with the use of papaverine in combination with either 2 or 20 % lidocaine. In an in vitro model, papaverine showed a dose-dependent reversal of the effect of norepinephrine [17].

Lidocaine is a commonly used anesthetic that acts as a stabilizer of cell membranes. Its mechanism of action on the vasculature has not been fully elucidated, but varying responses are seen based on the concentration utilized [18]. In the study that investigated the effect of papaverine, 2 % lidocaine caused augmented constriction of in vitro vessels pretreated with norepinephrine, while 20 % lidocaine reversed the norepinephrine effect. In the rabbit carotid artery model, 2 % lidocaine did not alter blood flow through anastomosed vessels, while 20 % lidocaine caused a significant increase in blood flow. It should be noted that prior studies of mechanical ischemia demonstrated initial vasodilation followed by a prolonged period of rebound vasoconstriction [19]; this effect was not seen in the above study following microvascular anastomosis with higher concentration of lidocaine.

The clinical use of 4 % lidocaine is common in microsurgery. The available literature supports the use of higher doses of lidocaine as a topical agent to promote vasodilation. While low-dose lidocaine does not relieve vasospasm, high-dose lidocaine (16–20 %) exerts high osmotic pressure and may damage vessel walls [20], not to mention the theoretical concern for systemic toxicity. Thus, the optimal concentration of lidocaine for use in microsurgery is 10 %.

Intra-arterial injections of urokinase, streptokinase, and tissue plasminogen activator (t-PA) have been utilized in the management of failing free tissue transfers or replantations due to thrombosis. Typically, t-PA is utilized in the case of a technically sound anastomosis without flow or when clot is noted at the anastomosis. In this case, it is assumed that distal embolization has occurred into the free flap or amputated part. Local use at recommended doses has been utilized safely without life-threatening bleeding complications being encountered, with many “saves” noted in the microsurgery literature [21].

Hirudin is a natural polypeptide of small size (7 kDa) produced by the leech Hirudo medicinalis. It is a natural direct thrombin inhibitor, without the additional effects seen with other anticoagulant medications. Recombinant forms, lepirudin and desirudin, have been produced with use as systemic anticoagulants in the setting of heparin-induced thrombocytopenia [22]. Hirudin’s use in replantation is limited to the use of leeches in the setting of venous insufficiency and rarely in the case of a patient with HIT.

Pain, anxiety, nausea, hypertension, and hypotension all have detrimental effects on the dynamics of microvascular blood flow in replantation and free tissue transfer. Routine postoperative care will prophylax against and treat these factors.

A critical aspect of postoperative care in extremity replantation is the avoidance of vasospasm. Many microsurgeons utilize routine postoperative strategies that are aimed at doing so. Dressings are soft, bulky, and non-circumferential to avoid compression (Fig. 8.3). These are typically left in place for the first 3–5 days, unless they are saturated, as dressing changes are often painful, anxiety-inducing events, and run the risk of mechanical damage to the replanted part. Warming of the patient’s room to above 74° (for many surgeons, above 78°) can increase the temperature of the part by causing peripheral vasodilation as well as decreasing the cooling effect of the ambient air. While many microsurgeons dispute the effect of ambient temperature on free flaps, replanted extremities are uniquely exposed to room air, as compared to free flaps on the body surface. More easily agreed upon is the fact that replanted parts are sensitive to acute changes in temperature and remain so for years, resulting acutely in vasospasm threatening perfusion and chronically in cold intolerance [23].

Patients must avoid ingestion of substances that can cause vasoconstriction. This includes caffeine, chocolate, and, most notably, nicotine. In a series of replantations performed at the Christine M. Kleinert Institute, a group of late failures were noted 2–3 weeks postoperatively. These coincided with a return to tobacco use. Smoking status was thought to be a contributor to early failure (0–3 days), but not causative [24]. Patients must be strongly counseled to avoid smoking upon discharge from the hospital given this risk.

It is necessary, both intraoperatively and postoperatively, to avoid physiologic responses leading to vasoconstriction, including hypovolemia, anemia, hypoxia, hyperoxia, hypoventilation, hyperventilation, and pain [25]. A balance of administration of isotonic fluids and blood products to maintain a hematocrit of 30 % will optimize viscosity and oxygen delivery. While vasopressors have been shown to be safe in breast and head and neck microsurgery, similar data has not been reported in replantation [26–28]. Vasopressors should be avoided in favor of fluid- and blood-based resuscitation when possible.

An indwelling brachial plexus blockade catheter has been shown to be effective in a number of ways. Although taking an average of 45 extra minutes preoperatively, a supraclavicular or axillary blockade catheter placement can be an effective method of intra- and postoperative pain control for 3–5 days. A continuous infusion of 0.125 % bupivacaine can help minimize pain and anxiety, as well as provide sympathetic blockade and subsequent decrease in vasospasm [29]. Utilization of a continuous brachial plexus blockade has shown a trend toward increase in surface temperature of the replanted part [30]. Smaller digital arteries are particularly prone to vasospasm, and thus, an indwelling catheter should be considered in both proximal and distal replantations. To be most effective, the catheter should be placed preoperatively to provide continuous sympatholytic effect and pain relief.