key: cord-0837303-a56qpiio authors: Nicolai, Laura; Adornetto, Raffaele; Bianchini, Roberta; Carrer, Floriana; dal Borgo, Chiara; Doro, Stefano; Masotti, Daniele; Puglisi, Cristina; Turini, Letizia; Wohlauer, Max; Galeazzi, Edoardo title: Distal AV Fistula to Preserve Patency in COVID-19-associated Acute Limb Ischemia date: 2021-09-05 journal: Semin Vasc Surg DOI: 10.1053/j.semvascsurg.2021.08.006 sha: 103bf082d8455ea52e5d20a451d788eb84bab700 doc_id: 837303 cord_uid: a56qpiio The purpose of this study was to report our institutional experience with patients with COVID-19 who developed acute limb ischemia during hospitalization and to determine the characteristics and clinical outcomes. Between March 2020 and January 2021, we treated 3 patients who were COVID-19-positive and developed acute limb ischemia after they received thromboprophylaxis. We performed an embolectomy by exposing the popliteal artery below the knee to treat an occlusion of the popliteal and tibial arteries. An infusion of unfractionated heparin was initiated immediately after surgery, maintaining a partial thromboplastin time ratio > 2.5 times the normal value and transferred the patients to the intensive care unit. However, after these patients developed recurrent acute limb ischemia in the same leg, we decided to perform an embolectomy of popliteal and tibial arteries at the ankle and created an arteriovenous fistula (AVF) with tibial veins using polypropylene 7-0. The first patient died from pneumonia after 3 weeks in the intensive care unit; at that time, the foot was viable with triphasic flow in the distal posterior tibial artery and the AVF was patent. The second and third patients are doing well, they can walk without any problems, and the tibial arteries and AFV were patent on duplex ultrasound after 6 months. The AVF allowed part of the flow of tibial arteries to divert into the small veins of the foot that have a low resistance to maintain patency of tibial vessels, despite a hypercoagulable state and extensive thrombotic microangiopathy in patients with COVID-19. The emergence of the novel coronavirus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), in late 2019, and the resulting illness, COVID-19 (coronavirus disease, 2019), was declared a pandemic by World Health organization on March 11, 2020. 1 Coagulopathy, in the form of venous and arterial thromboembolism is emerging as one of the most severe sequelae of the disease. This phenomenon has been shown to present even in the presence of anticoagulation and has been prognostic of worse outcomes. 2 The incidence of arterial thrombosis in patients with COVID-19 who require hospitalization ranges between 3-15%, based on a systematic review of literature. 3 Reports of arterial thrombosis manifesting as ischemic strokes, myocardial infarction, aortic thrombus, acute limb ischemia as well as arterial thrombi in unusual sites resulting in acute mesenteric ischemia and splenic infarct have been described. 4, 5, 6, 7 Several pathophysiologic mechanisms have been implicated in the hypercoagulable state which leads to diffuse thrombosis, including direct viral-related endothelial injury, viral invasion of endothelial cells via angiotensin-converting enzyme 2 (ACE2) receptors, excessive cytokine release is postulated to cause the severe illness and activation of endothelium, monocytes and neutrophils; leukocyte-and cytokine-mediated platelet activation, unchecked complement activation and more recently, elevated Von Willebrand factor antigen to ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity ratio. 8, 9, 10, 11 Several clinical reports have demonstrated evidence of a thrombotic microangiopathy associated with COVID-19 infection. Acute limb ischemia (ALI) is defined as a sudden decrease in arterial perfusion of an extremity associated with a threat to the viability of the affected extremity. ALI is a surgical emergency and may cause major tissue or limb loss, or death if not promptly recognized. 6,7 ALI occurs in approximately 1.5 cases per 10,000 persons per year. In a report from New York City during the COVID-19 pandemic, ALI occurred five times more frequently in COVID-positive patients compared to patients who were COVID-negative. 5 Characteristics associated with patients with COVID-19 who present with acute limb ischemia include male preponderance, presence of at least one cardiovascular risk factor, including hypertension, diabetes, obesity, and cigarette smoking. 12, 13, 14 The purpose of this study is to report a surgical technique for management of acute limb ischemia associated with COVID-19 infection. Between March 2020 and January 2021, three consecutive patients hospitalized with COVID-19 at Treviso Hospital that presented ALI during hospitalization, despite antithrombotic prophylaxis, were treated with thromboembolectomy and distal arterio-venous fistula (AVF). All three patients presented with thrombosis of the popliteal and tibial arteries in the setting of Rutherford IIb acute limb ischemia. 15 An urgent embolectomy was performed by exposing the popliteal artery below the knee. Drawing from experience that several patients with COVD-19 developed recurrent ALI requiring reoperation, we thought to perform a distal arterio-venous fistula (AVF) on tibial arteries and veins at the ankle in addition to performing transpopliteal and tibial embolectomy at the ankle. The AVF is an establish technique for improving bypass patency when small tibial vessels are heavily diseased and anastomosis of a bypass graft to these vessels is associated with diminished graft patency rates. 16, 17, 18, 19, 20 The failure mode in this situation is thought to be related to the high resistance, low flow state seen in the bypass which contributes to graft occlusion. The fashioning of an AVF at the distal anastomosis is hypothesized to counteract this flow limiting state. 21, 22 Likewise, we hypothesized that extensive thrombotic microangiopathy at the foot causes high peripheral resistance leading to re-occlusion following open thrombectomy in patients with COVID-19 associated acute limb ischemia. For creating the AVF, we used the "common ostium" technique, mobilizing approximately 2 cm of the (anterior and/or posterior) tibial artery and vein, performing a parallel arteriotomy and venotomy about 6-7mm. The side-to side anastomosis of the artery to the vein is established with a continuous 7-0 polypropylene suture. The time to perform the AVF is about 10-15 minutes and is necessary that the diameter of tibial vein at least 2 mm in diameter. The first COVID-19 patient with ALI was a male in his 60's with hypertension and an otherwise unremarkable past medical history. He presented with acute right leg pain, cyanosis of the forefoot, with motor and sensory impairment and was found to have acute occlusion of popliteal and tibial arteries (Rutherford score IIb). An embolectomy was performed by exposing the popliteal artery below the knee, removing fresh thrombus. Anterior and posterior tibial pulses were restored at the end of the case. An infusion of unfractionated heparin was initiated immediately after surgery, maintaining a PTT ratio greater than 2.5 the normal value. Two days later, the patient was transferred to the intensive care unit (ICU) because of worsening of COVID-19 pneumonia, during which time he developed recurrent ALI in the same leg despite being therapeutic on anticoagulation. Thus, we performed a cut-down and embolectomy on the popliteal and tibial arteries. Palpable pulses were present at the end of the operation and heparin infusion was initiated after surgery. Eight hours later, however, the patient developed recurrent ALI for a third time, again involving the popliteal and tibial arteries. With a working diagnosis of no-reflow phenomenon (due to thrombosis of the small vessels of the foot), we decided to create a distal AVF at the same time as repeating embolectomy of the popliteal and tibial arteries. We prepared the posterior tibial artery and vein at the ankle, and performed an embolectomy of plantar arch and created an AVF with tibial vein, using 7-0 polypropylene. It wasn't possible to perform AVF on anterior tibial artery and vein, because the patient's respiratory status was deteriorating and he required an immediate transfer from the operating room to ICU. Therapy with heparin was continued peri-operatively. Unfortunately, the patient died after 3 weeks in the ICU from COVID-19 pneumonia. At the time of his death, the foot was viable with triphasic flow in the distal posterior tibial artery and the AVF was patent based on duplex. The second COVID-19 patient with ALI was an obese male in his 50's who presented with pneumonia and acute right leg ischemia with rest pain, cyanosis of the forefoot and with motor and sensory impairment three days after hospitalization (Rutherford score IIb). He underwent a transpopliteal embolectomy, below the knee of the left leg pulling out fresh thrombus and, at the end of the surgery, had triphasic flow in the tibial arteries on duplex ultrasound. He was transferred to the ICU because of worsening of COVID-related pneumonia and therapy with unfractionated heparin was started. The day after surgery, recurrent ALI on the same leg recurred. This time, it wasn't possible to perform surgery because he was critically ill from pneumonia. After a two-day delay the patient's clinical situation improved, and he underwent a transpopliteal embolectomy below the knee, embolectomy of the tibial arteries at the ankle, embolectomy of the pedal arteries of the foot, and an AVF between both the anterior tibial vein an artery and posterior tibial vein and artery at the ankle. Unfractionated heparin was continued through surgery with the addition of an Iloprost infusion for 7 days, after which unfractionated heparin was replaced with LMWH and Iloprost continued for three weeks. The patient was discharged from the ICU after three weeks, and ultimately discharged from the hospital after two months on ASA 100mg monotherapy. At the time of discharge, the foot was viable with triphasic flow in the distal anterior and posterior tibial arteries on duplex ultrasound. . He developed a foot drop related to peroneal nerve injury. The ulcers of the forefoot, developed due to protracted ischemia, healed within two months. At 3 month clinic follow up, he was walking without a brace, the wounds healed and the AVF patent on duplex (Figure 1 ). The third COVID-19 patient with ALI was a male in his 70's who was an active smoker but had no other risk factors. He presented with ALI of right leg a few days after admission for COVID-19 despite receiving prophylaxis with LMWH, presenting with pain and motor and sensory impairment of the toes (Rutherford score IIb). He underwent a thromboendarterectomy for in-situ thrombosis of the superficial femoral artery. The soft clot removed was more consistent with a hypercoagulable state than traditional atherosclerotic disease. A transpopliteal embolectomy was performed below the knee along with an embolectomy of the posterior tibial artery at the ankle, retrieving fresh thrombus. At the end of the surgery, he had a palpable posterior tibial artery pulse and was started on therapeutic LMWH. Five days later, he developed recurrent ALI with popliteal occlusion affecting the same leg. We performed a popliteal embolectomy below the knee and posterior tibial artery at the ankle. We also explored the anterior tibial artery at the ankle, but it was chronically occluded, so we performed an AVF between the posterior tibial artery and vein. We discharged the patient after 10 days with warfarin. The patient had triphasic flow in the distal posterior tibial arteries, and the AVF patent on duplex at the time of his discharge and at clinic follow up. with ALI has been reported due to the systemic illness, hypercoagulable state, and extensive thrombotic microangiopathy that involves extrapulmonary organs. 23 Patients with ALI do not have typical causes of ALI, and the vessels at the surgery tend to be relatively healthy with no atherosclerotic disease. 2 Treatment methods for ALI in general include surgical treatment (such as thromboembolectomy and bypass surgery), endovascular treatment (such as catheter-directed thrombolysis, percutaneous thrombus aspiration, and stent placement), and hybrid treatment that combines both therapies. A meta-analysis of randomized controlled trials performed in 2018 investigated whether surgical or endovascular treatment (catheter-directed thrombolysis) should be performed as the first-line of treatment for ALI. While there was no significant difference between the two groups in terms of limb salvage and mortality rates, the endovascular treatment group showed a significantly higher incidence of stroke and bleeding within 30-days of treatment. 24 Furthermore, while thrombolysis using t-PA remains an effective treatment option for patients presenting with lower extremity mild and moderate ALI by Rutherford classification, patients with poor pedal outflow may benefit from alternative revascularization strategies. 25 Our three patients presented with Rutherford IIb ALI, and we performed emergent surgical embolectomy to resolve the ischemia. Our group in Treviso is very comfortable with surgical revascularization techniques and we sought to avoid catheter-directed thrombolysis (CDT) given the current paucity of high quality data to support CDT in the COVID-19 population. The usual indications for creating an adjunct AVF is the use of prosthetic or non-autologous biological graft, to perform femorotibial reconstructions for atherosclerotic disease. If a borderline saphenous vein is used and whenever the runoff is poor or otherwise compromised, the use of an AVF may also beneficial. 18 Contraindications for performing AVF includ undersized venous comitantes (smaller than the artery) and a poor deep venous system such as phlebosclerosis and/or deep vein thrombosis. The location of the fistula is most frequently performed in the middle and distal third of the limb to any one of the tibial vessels, although exceptions are possible. The AV fistula enables the modulation of blood inflow into high resistance-low capacitance circulatory bed. As a consequence of the additional flow into the low resistance-high capacitance venous circulation, augmentation of blood flow (volume and velocity) occurs above the critical thrombotic threshold velocity level of the bypass. Mean estimated blood flow through the bypass during the immediate postoperative period was 264ml/min, the AVF is 157ml/min and the distal artery was 19ml/min. Unlike an AVF created at the level of the distal bypass anastomosis, a remote distal AVF not only increases graft blood flow but also augments native arterial blood flow and thus improve distal perfusion. A study used capillary microscopy to allow an objective evaluation of clinical outcome on follow-up. In a patient with an AFV, the red blood cell (RBC) velocity, peak RBC velocity and time to peak RBC velocity are significantly higher compared to values in patients without an AVF. In addition, the individual data showed that microcirculatory blood flow correlated with patency of the graft. 26 We applied our experience using AVF to improve patency of peripheral femorotibial bypass to patients with COVID-19-associated ALI with no-reflow phenomenon. The AVF performed at the ankle diverts tibial artery flow into small veins of the foot that have a low resistance, which helps maintain patency when runoff is compromised as occurs with COVID-19 related microangiopathy. Our small case series reports anecdotal success with distal AVF in the setting of recurrent COVID-19 ALI. Based on our early success with this technique, we believe that creation of an arteriovenous fistula may be considered as an adjunctive option to maintain arterial patency in patients with COVID-19-associated acute limb ischemia. The authors have no conflict of interest to declare in relation to the this work. COVID-19 versus HIT hypercoagulability The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management Managing Vascular Surgery Emergencies and Referrals During the COVID-19 Pandemic at a Tertiary Centre in Oman Acute limb ischemia in patients with COVID-19 pneumonia The impact of the COVID-19 pandemic on cerebrovascular disease Early Left Ventricular Thrombus Formation in a COVID-19 Patient with ST-Elevation Myocardial Infarction A review of acute limb ischemia in COVID-positive patients Imbalance of von Willebrand factor and ADAMTS13 axis is rather a biomarker of strong inflammation and endothelial damage than a cause of thrombotic process in critically ill COVID-19 patients A mild deficiency of ADAMTS13 is associated with severity in COVID-19: comparison of the coagulation profile in critically and noncritically ill patients COVID-19-Associated Coagulopathy: An Exacerbated Immunothrombosis Response Acute Arterial Thromboembolism in Patients with COVID-19 in the New York City Area Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System Acute arterial and deep venous thromboembolism in COVID-19 patients: Risk factors and personalized therapy AHA/ACC Guide-line on the Management of Patients With Lower Extremity American College of Cardiology/Ameri-can Heart Association Task Force on Clinical Practice Guidelines Infrapopliteal prosthetic graft patency by use of the distal adjunctive arteriovenous fistula Distal vein patch with an arteriovenous fistula: a viable option for the patient without autogenous conduit and severe distal occlusive disease Improved method to create the common ostium variant of the distal arteriovenous fistula for enhancing crural prosthetic graft patency Remote distal arteriovenous fistula to improve infrapopliteal bypass patency Remote arteriovenous fistula with infrapopliteal polytetrafluoroethylene bypass for critical ischemia The use of arteriovenous fistula as an adjunct to peripheral arterial by-pass: a systematic review and metaanalysis Update on the role of the distal arteriovenous fistula as an adjunct for improving graft patency and limb salvage rates after crural revascularization Thromboembolic events in patients with SARS-CoV-2 Acute Limb Ischemia Contemporary outcomes of endovascular interventions for acute limb ischemia Creation of a distal arteriovenous fistula improves microcirculatory hemodynamics of prosthetic graft bypass in secondary limb salvage procedures