Management of Access Site and Systemic Complications of Percutaneous Coronary and Peripheral Interventions

ABSTRACT: The role of endovascular therapy for the treatment of coronary and peripheral vascular diseases (including carotid, renal and lower extremity arteries) is expanding. The steady growth in the volume of endovascular procedures is likely to result in an absolute increase in the incidence of procedural complications. Knowledge of common and specific procedural complications and their management are critical to successful outcomes. Complications can be classified as (i) access site-related and (ii) systemic.

J INVASIVE CARDIOL 2008;20:463–469


The role of endovascular therapy for the treatment of coronary and peripheral vascular diseases (including carotid, renal and lower extremity arteries) is expanding. Knowledge of common and specific procedural complications and their management are critical to successful outcomes. Complications can be classified as (i) access site related and (ii) systemic.

1. Access Site-Related Complications

A. Pseudoaneurysm

A pseudoaneurysm (PSA) is defined as an arterial rupture of one or more layers of its walls, contained by overlying fibromuscular tissue, which communicates with an artery by a neck or sinus tract1 (Figure 1). Pseudoaneurysms occur in up to 7.5% of femoral artery catheterizations and can result in distal embolization, extrinsic compression on neurovascular structures, rupture and hemorrhage.2 Clinically the patient may complain of pain in the groin. A pulsatile groin mass with or without an audible bruit may be present on physical examination. Duplex ultrasound may provide evidence of extra-arterial flow or there may be classic “to-and-fro” Doppler waveform in the neck of the PSA (Figure 1).

Before 1985, the treatment of PSA was surgical repair.3 Reports of the natural history of unrepaired PSA indicate that spontaneous closure can occur, especially with small PSAs. Large PSA (> 3 cm) that are symptomatic, expanding or those associated with large hematomas are generally thought the most prone to rupture.2,4

Ultrasound-guided compression was the treatment of choice for PSA in the 1990s.5,6 The procedure is successful in up to 90% of cases. Although the procedure is noninvasive, it has many disadvantages including prolonged compression time (up to 120 minutes), patient discomfort, early recurrence of PSA and limited success in treating large PSA.6,7

Ultrasound-guided thrombin injection for PSA of the iliac, femoral and peroneal arteries was pioneered by Cope and Zeit.8,9 Thrombin injection is safe, effective, associated with few complications and has emerged as the preferred treatment modality for pseudoaneurysms occurring as a result of percutaneous femoral arterial interventions.10,11 The procedure should be carried out by a physician with an ultrasonographer to enable continuous visualization of the PSA. Thrombin is introduced into the sac of the PSA away from the neck under direct ultrasound guidance (Figure 1).

Small aliquot is given at a time and monitored for abolishment of spontaneous flow.12,13 Based on results from animal studies14,15 and indeed injecting of esophageal and gastric varices,16 thrombin injection of 0.5–2 ml at 1000 U/ml is considered a safe and effective dose range for PSA.17 A recent study of 274 patients with iatrogenic femoral PSA post-catheterization demonstrated ultrasound-guided thrombin injection was successful in 97% of cases.11 Complex PSA may require more than one injection of thrombin.18 Mohler et al have shown that the preferred approach for treating a PSA with multiple sacs is initial injection of the sac closest to the skin followed by injections of the deeper sacs.19 Potential complications of thrombin injection include leakage of thrombin causing thrombosis of the femoral artery and distal embolization.20 Contraindication for thrombin injection includes PSA with a wide, short neck, and associated arteriovenous fistula.

B. Access site vessel occlusion

In the event of acute vessel occlusion, the patient may complain of pain, pallor, parenthesis or decreased movement in the respective limb. Clinical examination may reveal a cold ischemic limb with absent pulses. An ankle-brachial index (ABI) < 0.5, flat pulse-volume-recording tracing or absent color flow and Doppler waveform on duplex ultrasound in the index artery are important pointers to this diagnosis. The use of a vascular closure device should also prompt attention to the fact that the closure device itself may have occluded and/or subsequently caused thrombosis in the access site vessel.

Angiography of the affected artery via a retrograde approach from the contralateral common femoral artery should be performed with a view to an endovascular therapeutic intervention (Figure 2). Urgent surgical exploration is indicated for a threatened limb and when a percutaneous approach is not feasible.

C. Hematomas

i) Localized hematoma

Painful swelling of the groin and indurated tissue around the access site is often associated with hematoma formation which is usually treated with manual compression and analgesia. Duplex ultrasound of the groin should be performed if the hematoma is pulsatile, expansile, has a bruit or exquisitely tender to exclude a PSA or arteriovenous fistula.

ii) Retroperitoneal hematoma

Hypotension after an endovascular intervention should always include the differential diagnosis of retroperitoneal bleeding. Clinical signs that may point toward the diagnosis of a retroperitoneal hemorrhage include hypotension, lower abdominal or flank pain, acute drop in hematocrit and a high puncture at the site of arterial access (typically above the inguinal ligament) which predispose to a higher risk of retroperitoneal bleeding. Review of angiographic images may reveal a high common femoral artery access above the inguinal ligament denoted by the origin of the inferior epigastric artery.

Retroperitoneal hemorrhage can be confirmed on CT scan of the abdomen and pelvis (Figure 3). Stable patients can be managed conservatively including blood transfusion to maintain stable hematocrit, reversal of heparin with intravenous protamine and close monitoring of the blood pressure. However, if the patient is hemodynamically unstable, in addition to volume resuscitation, the patient should be taken for urgent angiography to localize the site of retroperitoneal bleeding by obtaining vascular access via a retrograde approach using the contralateral common femoral or brachial artery. In addition to identifying the site of blood loss, hemostasis can be achieved with balloon inflation as a temporary measure while awaiting surgical repair or as a definitive treatment.21 Covered stent and intra-arterial thrombin injection have been described to seal the site of extravasation.22 Surgical exploration and decompression is indicated for severe, continuous bleeding, development of abdominal compartment syndrome and compression of adjacent intra-abdominal organs as a result elevated intra-abdominal pressure.23

D. Arteriovenous fistula

The incidence of post-catheterization femoral arteriovenous fistulas (AVF) varies from 0.006% to 0.88%.24–26 The diagnosis of femoral AVF can be made by palpation, auscultation and imaging techniques. A high clinical index of suspicion is warranted in patients with a new femoral bruit, thrill, fresh hematoma or pain in the lower limbs on the following day after sheath removal. Suspected clinical femoral AVF can be confirmed by color Doppler ultrasonography demonstrating an AVF with continuous systolic and diastolic flow27 (Figure 4). The prognosis of an uncomplicated AVF is usually good. Spontaneous closure is the rule for the majority of AVF, and therefore this lesion can be safely observed. Serious complications such as high output cardiac failure due to large AVF, aneurysmal degeneration of the artery and limb edema have been described but are extremely rare consequences of AVF.28–32

Simple observation and ultrasound guided compression have been suggested as first line therapies in the management of post-catheterization femoral AVF because of their noninvasive nature33,34 However, spontaneous closure or successful compression/obliteration of an iatrogenic AVF is less likely in patients who are on anticoagulation and antiplatelet therapy.35,36 Contraindications for conservative management include associated large PSA, hemorrhage, expanding mass, compromised cardiac output, arterial or venous occlusion, and leg edema. Surgical ligation of the AVF can be performed under local anesthesia. Implantation of covered stents into the common femoral artery is still under clinical investigation and is not suitable for all cases such as lesions at the femoral arterial bifurcation.37 Prolonged compression and bandaging has also been shown to be associated with a high closure rate of AVF.

E. Deep venous thrombosis

Deep venous thrombosis is an important clinical diagnosis to remember in patients presenting with lower limb pain and swelling having recently undergone endovascular intervention. Compression of the common femoral vein by instrumentation of the common femoral artery may predispose to thrombus formation. Clinical suspicion should be followed by venous ultrasonography of the lower limb to assess for presence of deep venous thrombosis (Figure 5).

F. Neurogenic etiology

Transfemoral artery endovascular intervention can lead to neurogenic complications due to the proximity of the femoral nerve and the more laterally located lateral cutaneous nerve of the thigh to the common femoral artery. Symptoms such as hypoesthesia, dysesthesia and hypalgesia of the thigh can be caused by compression of either of the above two nerves as a result of hematoma from the femoral artery access site. Symptoms usually subside over a number of days but symptoms have been reported up to 6 months.38

2. Systemic

A. Atheromatous embolization syndrome

Atheromatous embolization or cholesterol embolization syndrome (CES) is due to the release of cholesterol emboli from ulcerated atheromatous plaques usually caused by endovascular instrumentation. Emboli range in size from 100–200 µm and can cause downstream arteriole occlusion of different organs. The process is identified with increasing frequency after any arterial manipulation (i.e., aortography or aortic intervention, lower extremity angiography or intervention, percutaneous coronary angiography or intervention and indeed cardiac surgery). The syndrome can also arise spontaneously in elderly patients with severe aortic atherosclerotic disease (“the shaggy aorta”) and after anticoagulant or fibrinolytic therapy.39

Clinical consequences of the embolization syndrome vary considerably, from being completely asymptomatic to acute multi-organ failure with mortality rates between 16–90% depending on the degree of multiorgan damage.40–42 The kidneys, abdominal organs and skin of the lower limbs are the most frequently involved organs and can present as rapidly progressive renal failure, cutaneous livido reticularis and acrocyanosis (Figure 6). The distal limb or digit may be cold (“blue toe syndrome”) and digital gangrene may also be present. Symptoms may also appear in the brain, skeletal muscles and retina.39,43 The syndrome occurs more frequently in patients with generalized atherosclerosis such as multivessel coronary disease and cerebrovascular disease.

An elevated white cell count, C-reactive protein, ESR and transient hypocomplementemia or eosinophilia may be present with CES. These laboratory parameters reflect the course of the disease with an immediate acute phase and a subacute phase in the following weeks, caused by an inflammatory response to the cholesterol emboli.40,43 Serum creatine and urea are helpful parameters for monitoring renal function in the presence of renal atheroembolization. Elevated creatine phosphokinase and myoglobin levels can suggest myositis secondary to cholesterol emboli. Ankle-brachial index and duplex ultrasound of the distal vessel of the affected limb may be helpful in assessing patients with predominantly lower limb involvement. Skin or renal biopsy can confirm the diagnosis by demonstrating characteristic cholesterol crystals but it is important to remember that the biopsy can be falsely negative if the segment biopsied is spared of cholesterol emboli.

There is no proven specific therapy for CES. There are no large trials evaluating any medical therapies for the treatment of patients with CCE. Steroid treatment is controversial. There are equivocal reports concerning the use of steroid therapy for specific patients with CES.44 There are also isolated reports suggesting LDL apheresis45 may be useful for patients with CES following invasive procedures. Current treatment is mainly supportive. This includes control of hypertension and heart failure, adequate nutrition and hydration, and support of renal function with dialysis if necessary. Analgesia and optimal wound care are essential management components. Surgical treatment (removal of diseased vessel wall) may be curative, but is associated with a prohibitively high mortality rate.

Iloprost, a stable prostacyclin analog with strong vasodilating and anti-platelet aggregating effects, has been shown to be highly effective in treating many diseases, including peripheral vascular disease, pulmonary hypertension and Raynaud’s phenomenon.46 In a series of 10 patients with systemic sclerosis and elevated resistance index of renal vessels, iloprost administration reduced the resistance index after both acute and chronic drug administration.47 Elinav and colleagues described a series of four cases of cholesterol emboli treated with iloprost. The main observations were improvement in distal extremity ischemia in all cases and improvement in renal function in the one patient with acute renal impairment.48 CES remains a serious complication of endovascular intervention with a high morbidity and mortality rate.

B. Contrast-induced nephropathy

Contrast-induced nephropathy (CIN) is the third leading cause of acute kidney injury in hospitalized patients and is associated with significant patient morbidity. CIN is usually defined as an increase in serum creatine concentration of > 25% above baseline or > 0.5 mg/dl within 48 hours after radiocontrast media administration.49–52 Factors that have been identified to be associated with the development of CIN include: preexisting renal impairment, diabetes mellitus, advanced age, periprocedural intravascular depletion, congestive heart failure, volume and type of contrast administered, and concomitant use of other nephrotoxic drugs.53–55 The impairment tends to be non-oliguric and transient, with the peak serum creatine usually occurring around day 3 and returning to normal in the majority of cases within 2 weeks. Some patients may develop more severe renal failure, with approximately 1% of this group requiring dialysis. Although small in number, the morbidity and mortality rates in this group are alarmingly high, with an in-hospital mortality rate of up to 30% and an 80% 2-year mortality rate.55

The impairment of renal function after radiocontrast media exposure is multifactorial. Two predominant pathophysiological mechanisms proposed include contrast induced direct cytotoxic effects and vasoconstriction followed by either regional hypoxic damage or ischemia/reperfusion injury.56

Hydration as a prophylactic measure has a beneficial effect especially if the fluid load is given before the procedure.57 There are currently no studies of the optimal rate of prehydration, but most of the studies used a rate of 1–2 ml/kg/hr, for 6–12 hours preprocedure. Prehydration with normal saline has also been shown to be better than 0.45% saline, especially in women, diabetics, and patients receiving 250 ml or more of contrast.58 The use of isotonic sodium bicarbonate as a preventative measure for CIN has also been questioned and recent studies have suggested that bicarbonate alone may be associated with an increased risk of CIN.59

N-Acetylcysteine is the acetylated form of the amino acid L-cysteine and has long been established clinically as a mucolytic and as a treatment for acetaminophen overdose. Having antioxidant properties combined with a vasodilatory effect on the renal medullary circulation has led to studies evaluating its effects on CIN.60,61 Unfortunately no randomized trials exist but meta-analyses have shown that N-acetylcysteine significantly reduces the incidence of CIN, particularly when used with pre-hydration.61–63 A single trial has demonstrated significant beneficial effects from the use of another antioxidant, ascorbic acid, in patients with renal insufficiency undergoing coronary angiography.6465 Other agents including adenosine antagonists,65 calcium channel antagonists,66 dopamine67 and fenoldopam68 in preventing CIN have all yielded equivocal results.

The specific contrast agent used is also of importance in catheterization studies. Numerous studies, including a meta-analysis of 31 trials, have shown low-osmolar contrast media (LOCM) to be associated with significantly less CIN than high-osmolar contrast media in patients with renal impairment and/or diabetes.2 There has been considerable refinement during the past decades from ionic high-osmolar, to nonionic low-osmolar, and finally to nonionic iso-osmolar contrast media (IOCM). In patients with diabetes and/or chronic kidney disease, studies have shown that there may be a decrease in the postprocedural rise in creatine with the use of the iso-osmolar agent iodixanol compared to LOCM.69–71 However, it is unclear if this benefit translates into clinical outcomes, such as rehospitalization for renal failure or requiring hemodialysis, which actually favored the use of LOCM from registry data.72,73

Basic prophylactic measures include identifying those patients at risk, performing preprocedure assessment with a focus on volume status, identifying and withholding potentially nephrotoxic agents and drugs that may accumulate with reduced renal function such as aminoglycosides, nonsteroidal anti-inflammatory drugs (NSAID), metformin and digoxin.

C. Acute stroke following cardiac catheterization

Although strokes after cardiac catheterization are relatively rare, reported rates including both ischemic and hemorrhagic subtypes, range widely from 0.07% to 7.0%. Large contemporary registries of exclusively diagnostic and invasive coronary procedures report rates from 0.07% to 0.38%, and smaller studies of other invasive studies have reported higher rates.74 The etiology of ischemic stroke in this context can be dislodged aortic arch plaque which is calcified and fibrin-dense and therefore not amenable to lysis. Alternatively, calcific thrombi might partially lyse, leading to downstream emboli.75 Recent studies have shown a statistically and clinically significant early improvement in stroke severity in NIHSS score by 24 hours and indeed similar improvements were observed from baseline to 7 days in patients with acute stroke after cardiac catheterization treated with early thrombolysis.76 Low rates of intracranial and systemic hemorrhage were also noted in this study. Future large, prospective registries to further characterize this population are needed.

Conclusion
The steady growth in the volume of endovascular procedures is likely to result in an absolute increase in the incidence of procedural complications. Competent operators must have a broad knowledge of potential systemic and vascular access complications as well as an understanding of the management of these complications (Table 1).