Peripheral Arterial Disease (PAD), Including the Diabetic Foot

Treatment for peripheral arterial disease (PAD) include angiography, with or without intervention; hybrid procedures (endarterectomy, with endovascular intervention); and open revascularization (bypass or endarterectomy with autogenous, prosthetic or bioprosthetic material).

Patient History & Physical Examination  

The SVS clinical practice guidelines recommends against invasive treatments for peripheral arterial disease (PAD) in the absence of symptoms.⁴³ Conducting a complete history and physical examination of patients with PAD is important, and focusing on the legs, as well as systemic risk factors and comorbidities, is essential. The manifestations of chronic lower extremity ischemia often include pain produced by varying degrees of ischemia, ranging from no or atypical leg symptoms to typical exertional muscular pain (intermittent claudication [IC]) to ischemic rest pain.⁴³ 

The target population of patients includes adults with claudication or critical limb threatening  ischemia (CLTI), defined as a patient with objectively documented and any of the following clinical symptoms or signs: Ischemic rest pain with confirmatory hemodynamic studies, diabetic foot ulcer (DFU) or any lower limb ulceration present for at least two weeks and gangrene involving any portion of the lower limb or foot.⁴³ For patients with CLTI, the one year risk of  requiring major amputation is 30% and 1-year mortality risk is 25%.⁴⁴ 

Imaging 

The SVS guidelines recommend using the ankle brachial index (ABI) as the first-line noninvasive  test to establish diagnosis.⁴³ 

For patients who are being considered for revascularization, physiologic noninvasive studies, such as segmental pressures and pulse volume recordings, aid in the quantification of arterial insufficiency and help localize the level of obstruction.⁴³ 

The SVS also recommends obtaining high-quality angiographic imaging with dedicated views of the ankle and foot arteries to permit anatomic staging and procedural planning in all CLTI  patients who are candidates for revascularization.⁴³ The use of an integrated limb-based staging system (Global Limb Anatomical Staging System) to define the anatomic pattern of disease and preferred target artery path in all CLTI can be considered.⁴³ Another commonly used risk  stratification scoring system to rate the need for revascularization or potential need for amputation  is the Wound, Ischemia and Foot Infection (WIFI).⁴⁵ 

Other studies that should be considered for planning revascularization, and not for routine screening, are arterial duplex ultrasound, CTA, magnetic resonance angiography (MRA), and contrast arteriography. The SVS guidelines recommend either axial imaging (e.g., CTA, MRA)  or catheter-based angiography.⁴³

In high-volume expert centers and especially for patients with recurrent disease the arterial duplex  US is considered in place of axial imaging. 

Medical Management and Lifestyle Changes  

• Smoking cessation: A multidisciplinary comprehensive smoking cessation approach should be utilized until tobacco use has been stopped.  
• Exercise: Supervised exercise therapy⁴⁶, now reimbursed by Centers for Medicare and Medicaid  Services (CMS), is a first-line indication for patients with claudication; it includes walking a  minimum of 3 times per week (30-60 min/session) for at least 12 weeks. Home-based exercise⁴⁷can be done when a supervised program is unavailable.⁴³ 
• Diabetes: For patients with PAD, it is important to optimize diabetes control (hemoglobin  A1c goal of <7.0) without hypoglycemia. 
• The SVS recommends therapy with aspirin (75-325 mg daily). Clopidogrel is  recommended (75 mg daily) as an alternative to aspirin for antiplatelet therapy.⁴⁸ Dual antiplatelet therapy, with aspirin and Plavix, is not better than aspirin alone.^{48, 49} 
• In patients with claudication without heart failure, a 3-month trial of cilostazol (100 mg twice daily) is recommended, with dose reduction to 50 mg twice daily for patients with side effects. Those who cannot tolerate or are ineligible for cilostazol can try pentoxifylline (400 mg, 3 times daily). Clinicians should consider using reduced dose  Rivaroxaban for those patients with PAD and low bleeding risk.^{43, 50} 
• Hypertension: Anti-hypertensive control should be focused on a goal blood pressure of less than 140/90, with ACE inhibitors⁵¹ and ARB⁵² recommended as first line. The use of  beta blockers (hypertension, cardiac indications), should be considered if symptoms are  due to atherosclerosis 
• Dyslipidemia: For patients with dyslipidemia, treatment with a statin to achieve a target  low-density lipoprotein cholesterol (LDL-C) level of <70 mg/dL is recommended.⁵³ If  LDL-C goal is not achieved by statin therapy, then PCSK9i should be considered. Even if  LDL-C is at goal, statin therapy should be initiated and continued due to its overall pleiotropic beneficial effects. 

Risk Stratification  

Because cardiac disease is so prevalent among patients with peripheral vascular disease, ECG  should be performed in all patients. Chest radiography may be helpful in some patients if  undiagnosed underlying disease is suspected on the basis of the history and physical examination.  In select patients, more advanced testing may be appropriate, such as cardiac stress testing or pulmonary function evaluation when cardiac or pulmonary disease is suspected. The associated comorbidities and risk factors, including smoking cessation, should be managed optimally before  revascularization, similar to patients undergoing any major vascular surgical procedures. There  are well-accepted, published guidelines from most of the medical subspecialties to guide the preoperative evaluation, including those from the American Heart Association and the American  College of Cardiology for the optimal preoperative cardiac evaluation for patients undergoing major noncardiac surgery.³¹ 

A multidisciplinary approach to care can optimize outcomes. Medical specialists and team members can assist patients with risk factor modification, such as smoking cessation, maintaining glycemic control, normalizing blood pressure and lipid levels, maintaining antiplatelet therapy and fostering participation in exercise programs, thereby promoting a positive patient experience.  Discharge planning should also be considered at time of surgical planning.⁵⁴ 

Preoperative Labs 

A complete blood count should be obtained to screen for the presence of infection, to ensure an adequate red blood cell volume, and to rule out a serious hematologic abnormality. Serum electrolyte concentrations should be evaluated and corrected when abnormalities exist. Of special importance are serum potassium, calcium, and magnesium levels because if they are abnormal and not corrected, they can lead to deleterious cardiac effects.¹⁷ 

Furthermore, because renal disease is prevalent in patients with vascular disease and some vascular interventions may compromise renal function, a baseline creatinine level should be obtained. All patients should also have serum glucose concentration measured, and in diabetic patients, glucose levels and HbA1c should be controlled before, during, and after intervention.  

Measures of coagulation, such as the prothrombin time and international normalized ratio, should be determined to identify coagulation abnormalities, and in patients taking warfarin or other anticoagulants, an appropriate anticoagulation scheme should be decided on before surgery. 

Preoperative Medication Adjustment 

It is important to take into consideration medications due the administration of radiocontrast material that may lead to acute kidney injury.  

• Perioperative antibiotics: Prophylactic antibiotics for open procedure should be considered perioperatively as for any other surgery, and for endovascular interventions on a case-by-case basis.¹⁷ 
• Anticoagulation and its reversal: oral anticoagulation should be discontinued preoperatively to minimize bleeding complication. Direct oral anticoagulants  (DOACs) should be held for 48-72 hours before procedure. Warfarin should be discontinued 3-5 days in advance. Consider bridging with parenteral anticoagulation  (unfractionated heparin [UFH] or LMWH) in appropriate patients with high thrombosis risk.¹⁷ 
• Nephropathy: Techniques to minimize contrast nephropathy for endovascular procedures in patients with CKD should be utilized. While many different agents have been studied with varying success, only fluid loading has been consistently reported to be associated with better renal outcomes. If there is no contraindication fluid administration pre, intra and post operatively is recommended. The issue to hold ACEs and ARBs is still not resolved and more research is needed. CO2 digital angiography should also be considered in patient with CKD. The advantages include no allergic potentiation and no renal metabolism of CO2, because CO2 is cleared by the lungs and does not recirculate.¹⁷ 
• ACE Inhibitors: If significant volume depletion is anticipated, it is suggested to hold ACE  inhibitors and angiotensin receptor antagonists on the morning of surgery and restarting these agents after the procedure, once euvolemia has been achieved.¹⁷ 
• Diabetes Mellitus: It is suggested to hold metformin at the time of administration of contrast material among patients with an eGFR of <60 mL/min or up to 48 hours before administration of contrast material if the eGFR is <45 mL/min and restarting no sooner than 48 hours after administration of contrast material as long as renal function has remained stable. Diabetic patients who receive intermediate or long-acting insulin should receive half the scheduled dose when nil per os (NPO) in preparation for surgery.  Glycemic control should be considered per the current guidelines of the American  Diabetes Association.^{18, 31}

Anesthesia Management 

a) Anesthesia Techniques 

PAD procedures can be safely performed under local, regional, neuraxial, and general anesthesia,  or a combination of the three, depending on the local clinical practice as well as patient  preferences.^55-58 The question regarding safest anesthetic modality for PAD surgery remains controversial, with inconsistent results regarding the incidence of perioperative complications.^59-61Having said this, studies reported a decreased incidence of postoperative pneumonia, myocardial infarction, and graft failure with neuroaxial (NA) compared to general anesthesia (GA).^61-66Currently, the choice of anesthetic technique reflects patient-specific factors as well as procedure specific factors (e.g., anticipated duration).  

i) Open Procedures  

Lower extremity bypass may need to be performed under general endotracheal anesthesia.  Maintenance of anesthesia can be accomplished using volatile anesthetics, such as sevoflurane and desflurane, or with a propofol drip. Opioids (i.e., fentanyl or sufentanil) can be used for intraoperative pain control. Non-steroidal drugs, such as ketorolac or ibuprofen, may need to be avoided depending on the risk of kidney injury. 

ii) Endovascular Procedures 

The majority of lower extremity endovascular interventions can be performed under local anesthesia and sedation. 

Other approaches can be considered on a case-by-case basis. General endotracheal anesthesia may be best-suited if prolonged episodes of apnea to improve imaging quality are warranted.  Depending on the percutaneous or cut-down approach, endovascular procedures can be performed under local anesthesia; regional anesthesia with a nerve plexus block, such as ilioinguinal plexus block; or neuraxial anesthesia in the form of epidural or spinal anesthesia.^{55-58, 61} 

The ilioinguinal nerve plexus block can be performed by the surgeon in the sterile field. 

Both the iliohypogastric and the ilioinguinal nerves originate from the nerve root of L1 and perforate the transverse abdominis muscle near the anterior part of the iliac crest. In the anterior abdominal wall, the nerves travel between the transverse abdominis and the internal oblique muscles. The nerve bundle can be visualized using ultrasounds and the injection of 10-20 ml of local anesthetic (e.g., mepivacaine, ropivacaine or bupivacaine) will anesthetize the groin area, as well as the lower portion of the abdominal wall and the upper thigh.⁶¹ 

Local anesthesia or regional anesthesia technique can be supplemented with mild to moderate sedation with a propofol or dexmedetomidine drip for patient comfort. 

b) Monitoring and Access 

Standard monitoring of SaO2, EKG, non-invasive blood pressure and temperature.⁶⁷ 

• Invasive Arterial blood pressure monitoring : Placement of an arterial catheter may be necessary due to cardiac comorbidities. Arterial access also allows for intraoperative blood draws for ACT measurements. 
• Central venous catheter: The use of vasoactive drugs for tight blood pressure control may require the placement of a central venous catheter after induction of anesthesia. 
• Large bore intravenous access: The possibility of acute intraoperative blood loss requires large bore IV access for volume resuscitation. 

c) Intraoperative Concerns 

Notably, up to 55% of patients with PAD were found to display severe, asymptomatic CAD.⁶⁸Consequently, blood pressure should be maintained within 20% of the preoperative baseline value  (with mean arterial pressure >65 mmHg). Severe hypertension or hypotension should be avoided as it may result in myocardial ischemia. Thermoregulation becomes impaired with aging.^{69, 70} 

Thus, temperature regulation should be aggressively managed using different modalities such as  heated mattresses, bear huggers, warm intravenous fluid infusion, and warm ambient room  temperature.⁷ 

d. General & Procedure-Specific Concerns 

General intraoperative concerns: Skin preparation (CHG wipe timeout for three minutes to dry),  Foley placed by trained staff, shaving performed with clippers, normothermia.⁷¹

Steps Prior to Discharge 

Open Procedures 

• Patients might require a stay in the ICU or telemetry unit in order to be monitored for cardiopulmonary complications. 
• Monitoring for patency of the revascularization should be continued throughout the hospital stay. 
• Wound care should be continued in patients with tissue loss.  
• Physical therapy and pain control should be initiated. 

Endovascular Procedures 

• These procedures can be done on an outpatient basis, or with overnight observation,  depending on the patient’s need for hydration and the type of access or need for site observation.  

Steps After Discharge 

• Follow-up: Follow up call within the first week after surgery.  
• Office / Telehealth Visit: Follow-up within a month postoperative, unless indicated sooner.
  • For endovascular lower extremity procedures, the SVS recommends clinical examination, ABI, and DUS within the first month to provide a post-treatment baseline and evaluate for residual stenosis. For open lower extremity procedures, the SVS recommends clinical exam and ABI, with or without the addition of duplex ultrasound, in the early postoperative period to provide a baseline for further follow-up. This is usually within a month from discharge. 
  • Clinical exam and ABI/ pulse volume recording (PVR) with or without the additions of DUS should be performed at 6 and 12 months and then annually as long as there are no new signs or symptoms.⁴³ Specific duplex US velocity criteria should be used to diagnose a hemodynamically significant stenosis post stenting as well as for graft stenosis following bypass.  
• Medications:  
  • The use of long-term medications can be coordinated with the patient’s primary care physician and can include the use of statins or a PCSK9 inhibitor in order to achieve optimal LDL control.⁶¹ In addition, anti-platelet agents, anti-hypertensive agents,  and agents for glycemic control should be prescribed, as indicated.  
  • In patients undergoing infrainguinal endovascular intervention, it is recommended to treat with aspirin and clopidogrel for at least 30 days.⁴⁸ Options for antiplatelet treatment include ASA 81 mg/day or Clopidogrel 75 mg/day or DAPT w ASA +  Clopidogrel for at least 30 days in some patients with stenting (MIRROR trial).⁷²The combination of aspirin with low-dose Rivaroxaban has shown some benefit  following endovascular intervention and can be be considered if not contraindicated(VOYAGER trial).⁷³ In patients with resistance to Clopidogrel, the  use of an alternative agent such as Ticagrelor (Brilinta) is indicated.³¹

References