Shockwave Lithotripsy: Arterial Aneurysms and Vascular Complications

Experimental evidence

The lithotriptor causes stone fragmentation by generating external high-energy amplitudes of pressure that are transmitted through tissue and fluid until they encounter a boundary between two substances with different acoustic impedance, such as the renal calculi. ⁶ At the anterior boundary of the calculus, compressive stresses are generated, and at the posterior surface, energy is reflected that causes tensile stress and fragmentation. Shockwaves also generate bubble cavitation at the anterior surface of the calculi; this significantly contributes to disintegration of the stone. ⁷

The maximal energy generated by SWL is focused at a point defined as F2, but surrounding structures will also be subjected to energy from the shockwave. Estimation of the effective high pressure volume of the F2 point, however, is approximately 1.5 cc; outside this area, there is a rapid decrease to 20% of that at the focal point, ⁸ but pressure changes that extend beyond the F2 point up to 12 cm away have been recorded. ⁹ There is concern that energy outside the F2 point may cause injury to intra-abdominal organs and to the vascular tree, particularly in areas of calcification of an atherosclerotic plaque. To address the safety of SWL and the potential interaction with the vasculature, a small number of experimental studies have been performed—and specifically to investigate the affects on atherosclerotic arteries.

Energy from SWL is known to dissipate outside the F2 point, and this has been confirmed in animal studies. ⁸ In vitro study of the effects of SWL in the dog kidney have shown capillary rupture and resulting tissue hypoxia, ¹⁰ with similar results in a porcine model revealing extensive hemorrhage and vascular rupture both in the targeted kidney and outside the focus field. ¹¹ In rat kidneys prepared with casting material, SWL caused arterial injury, ranging from complete arcuate occlusion to small afferent arteriolar and glomerular capillary extravasation. ¹² Venous injury and thrombosis has been identified on histologic examination of dog kidneys that were exposed to SWL in vivo. ¹³ Cell injury has been shown by exposing human umbilical cord vein endothelial cells to shockwaves; this showed cell detachment and cell membrane damage with leak of the intracellular content. ¹⁴ From these studies, there is evidence to suggest that vascular injury can occur both within the kidney and in the surrounding tissue when subjected to SWL; therefore, the clinical reports of arteriovenous fistulation, ¹⁵ pseudoaneurysm, ¹⁶ and venous thrombosis ^{17 –19} may arise because of SWL.

Despite these data from animal models, studies on human artery specimens have failed to demonstrate any evidence to support SWL being causative to vascular injury or to support its causative affect on aneurysm rupture. Ex vivo study on canine and cadaveric human aorta and common iliac artery have been performed in which metal surgical clips were applied to vessel branches; the artery was then pressurized with methylene blue and subjected to SWL. No vascular rupture or injury was identified. ²⁰ Ex vivo study of calcified human aortic and iliac autopsy specimens have been performed in a model of SWL by subjecting calcified arterial specimens to SWL; no visible damage was identified when examined radiologically. ⁹ Similar study on resected AAA specimens, shown to be extensively calcified on CT, have been subjected to ex vivo SWL with no evidence of rupture seen nor any histologic difference in comparison with non-SWL specimens. ²¹ Although these studies have shown that SWL had no effect on healthy or calcified human arterial tissue, in vivo conditions are different, because the arterial wall is subjected to constant blood flow and blood components are present that may affect arterial plaque response to SWL.

In the reviewed literature, there was only a single experimental study on the effects of antiplatelet agents and SWL. In this study, rats were administered high- or low-dose aspirin or no medication before undergoing SWL; the authors showed no increased risk of hemorrhage. In addition, renal injury was identified with the electron microscope, but there was no difference in the degree of this. ²²

Successful SWL in AAA

Aneurysm of the abdominal aorta is a common pathology, found in the aging population, with an incidence of up to 5% at autopsy. ²³ Its incidence is increasing, and we are likely to encounter patients with the concomitant pathologies of urinary tract calculi and AAA. ²⁴ True aneurysms are defined by a diameter greater than 1.5 times the normal and with dilation of the intimal, medial, and adventitial walls of the vessel. ²⁵ The pathogenesis of AAA and rupture is still an area of research, but atherosclerosis is believed to be an important factor. Atherosclerosis occurs through lipid deposition beneath the intima, which is engulfed by macrophages causing an inflammatory response; myofibroblast infiltration follows, with proliferation and subsequent epithelialization. This inflammatory response leads to calcium and collagen deposition along with cholesterol crystals; this forms the atherosclerotic plaque.

In 1982, the first description of SWL treatment for renal tract calculi was published. ²⁶ It was not until 1991 that SWL was reported in a patient with a 5.1 cm AAA. ²⁷ In this first patient, the AAA had been diagnosed by CT, and calculi were found in the right ureter. There was no report on the F2 to AAA distance in this patient, although the authors state that the aneurysm was “adequately away from the F2 point.” During the procedure, the AAA was monitored with ultrasonography, but no mention of calcification of the aneurysm was made. A further 10 patients with AAA, in three different reports, have safely undergone SWL with no adverse effects or periprocedure monitoring of the aneurysm (Table 1). ^{28 –30} Of these cases, treatment with 2000 shocks was commonly described, but up to 2400 shocks have been used safely ²⁸ ; energy levels up to 24 kV have been delivered with no adverse effect ²⁷ ; a patient with an aneurysm as large as 5.5 cm has been treated ²⁹ ; also, three elderly patients older than age 70 had no complications. ³⁰

Rupture of AAA after SWL

Rupture of an AAA occurs most frequently into the retroperitoneal space rather than into the peritoneal cavity: In the former, a contained hemorrhage occurs and allows a delayed presentation; in the latter, rapid exsanguination into the peritoneal cavity is followed by death unless emergency surgery is successful. A large-scale randomized trial has shown that elective repair is only beneficial once an AAA has reached a diameter greater than 5.5 cm. ³¹

The first reported rupture of an AAA after SWL was in 1991 when an elderly patient with a large aneurysm of 10 cm presented 5 days after SWL; no operative management was sought, and the rupture proved fatal. ³² Initially, this patient had presented with left lower limb neurology 5 days after SWL before sudden onset back pain and cardiorespiratory collapse developed. In such a large aneurysm, correlation of SWL being causative to AAA rupture was presumed and the postmortem examination revealed a massive retroperitoneal hematoma. Since this first case, there have been a further five patients with ruptured AAA that has been attributed to SWL; in these other patients, emergency surgery was performed with successful repair (Table 1). ^{33 –35}

We would presume that injury to the wall of the aneurysm should occur at the time of SWL and that symptoms should develop acutely. In two patients who presented within 2 days of SWL, repair of the aorta was possible, although in these cases, no operative findings were discussed nor aneurysm size, site of rupture, or aneurysm to stone distance. ³³ Despite onset of pain after SWL, some patients may delay seeking medical opinion, and in a patient who presented 2 weeks after SWL, a large retroperitoneal hemorrhage was found with a rupture at the posterolateral aspect of the aneurysm neck. ³⁴ Interestingly, the stone to aneurysm distance in this patient was 10 cm, which should be significantly far from the F2 point for collateral energy from the shockwave to be dispersed, yet the authors conclude that the history was in keeping with SWL being the cause for AAA rupture. ³⁴

In contrast to other reported cases, one patient was asymptomatic after SWL until sudden onset of pain 14 days after SWL. ³⁵ At operation, a heavily calcified AAA was found with a large retroperitoneal hematoma, and a Dacron graft was used to repair the aorta in this patient. ³⁵ It is unusual that this patient was asymptomatic for 14 days, because rupture at the time of SWL should lead to pain or cardiovascular compromise indicative of disruption of the aorta. The authors concluded that SWL was the only precipitating factor for rupture of the 6 cm aneurysm, although we would argue that it is possible that rupture was coincidental and, in fact, SWL was not causative.

Plain radiography was mentioned as, or presumed to be, the only modality of stone localization in all of these reports of rupture. There has been no reported case of an AAA rupture when diagnosis has been made before SWL treatment. With CT becoming more accessible and requiring lower doses of radiation, patients will increasingly have undergone such imaging, and the presence of AAA should be identified before definitive management of calculi.

Aortic rupture in a nonaneurysmal calcified aorta has also been described in two patients. ^36,37 In the first case, left flank pain started post-SWL but the patient did not present until 3 months; a severely calcified aorta was found with an intimal dissection flap. ³⁶ At operation, a defect through a calcified plaque was found leading to the retroperitoneal hematoma; the patient had a successful aortic graft repair. The authors concluded that a pseudoaneurysm and psoas fistula occurred initially at 3 months before retroperitoneal rupture. In this case, there was no reported pre-SWL imaging by CT; neither was the stone to aneurysm distance given. In the second case where psuedoaneurysm after SWL was described, back pain started immediately after SWL. CT imaging showed a retroperitoneal hematoma, and at operation, the neck of the aneurysm was found at the lateral aspect of the aorta above the renal artery. ³⁷ Although the abdominal aorta was not described as aneurismal, the authors felt that pseudoaneurysm formation was from a severely calcified abdominal aorta.

Retroperitoneal hematomas that arise from the aorta were described in five of the cases. ^{32,34 –37} In the other case, there was no mention of where the abdominal aortic aneurysm ruptured or dissected. ³³ Although it is more common for rupture of the aorta to occur in a retroperitoneal manner, anterior rupture into the peritoneal cavity does occur, yet has never been described after SWL. Clinical symptoms in a ruptured normal caliber aorta would be similar to that of an AAA except for a palpable AAA; plain abdominal radiography should indicate calcification in the aorta. Unfortunately, the level of evidence to suggest that SWL is safe or unsafe is low. All these studies represent retrospective reports, and inferring that rupture was caused by SWL was based on clinical history. Only by prospectively collecting data on aneurysm patients who receive SWL and by measuring the distance from F2 to aneurysm will we be able to clarify if there is indeed any elevated risk.

SWL in the presence of renal artery aneurysm

Aneurysms of the renal artery are uncommon, with reported incidence in literature varying between 0.01% and 1%. ³⁸ Aneurysms of the renal artery are of particular interest because of the close proximity to the renal tract and exposure to shockwaves surrounding the F2 point. There have been two reports of successful SWL in three patients with renal artery aneurysm; in particular, one report was in a patient with a solitary kidney. ^28,39 In both of these reports, calcification was identified within the aneurysms. In two patients in whom the stone to aneurysm was measured, this distance was approximately 5 cm and similar to the SWL in AAA. ²⁸ There have been no reported cases of rupture, or any other vascular complication, of a renal artery aneurysm after SWL.

Arterial complications and pseudoaneurysms

Complications arising within the arterial tree but outwith the aorta are rare and are limited to several single case reports (Table 2). A pseudoaneurysm results from a defect in an arterial wall with communicating flow and subsequent hematoma in the surrounding tissue. Importantly, the communicating defect occurs through intima, media, and advential layer but may be encapsulated by some of the adventia layer of the vessel. Pseudoaneurysm formation within a kidney after SWL has been reported in a patient who presented with recurrent hematuria. ¹⁶ In this case, where the last SWL session was 4 years previous, CT imaging identified a pseudoaneurysm in relation to the space occupied by previous calculi. ¹⁶

Pseudoaneurysm of the superior mesenteric artery (SMA) has been described where periumbilical pain after SWL developed in a patient; 2 months before a second SWL session, persistent abdominal pain precipitated radiologic imaging. ⁴⁰ CT revealed a 5 cm mass in the mesentry, and selective angiography showed a saccular pseudoaneurysm of a distal jejunal branch of the SMA; subsequent arterial ligation with small bowel resection was successfully performed. ⁴⁰ No measurement of pseudoaneurysm to renal calculi distance was given, but noted by the authors to be sufficiently far from the right kidney on CT imaging to avoid injury. Although it was possible that SWL caused direct rupture of an atherosclerotic plaque in the SMA, the authors concluded that pseudoaneurysm formation was induced by SWL associated transient bacteremia, with subsequent seeding on a preexisting atheromatous plaque within the jejunal branch of the SMA.

There has been a solitary report of arterial stenosis after SWL. In this patient, an 80% stenosis of the right common, internal, and external iliac artery occurred 3 months after SWL; new symptoms consistent with intermittent claudication occurred progressively in the absence of any other vascular disease. ⁴¹ Histologic examination did not show any evidence of atherosclerosis, but subintimal collagen deposition with disruption of the internal elastic lamina was seen. The speculated pathophysiology was of arterial obstruction initiated by endothelial damage, leading to thrombosis obliteration of the lumen and recanalization.

Arteriovenous fistula formation has been attributed to SWL, occurring within the kidney. ¹⁵ This patient presented with recurrent hematuria 3 years after SWL, CT imaging and angiography revealed a pseudoaneurysm with arteriovenous fistulation, and selective embolization was performed in this patient. No mechanism for arteriovenous fistualation was proposed by the authors, but for SWL to be causative, it would require rupture of an arterial vessel into an adjacent vein. Arteriovenous fistula in the kidney is more commonly acquired from penetrating trauma, percutaneous biopsy, surgery, malignancy, or inflammation; presence of an accompanying pseudoaneurysm is also a common finding. ¹⁷

Venous complications

Thrombosis of the superficial femoral and external iliac vein has been described in a patient after SWL for renal calculi of the ipsilateral kidney. ¹⁸ This patient had no risk factors for venous thrombosis and had previously undergone nephrectomy of the right kidney for nephroblastoma. There was no measure of the distance from the F2 point to the thrombosis site, although traditional anatomy would suggest this to be greater than 5 cm. A second case of thrombosis of the common, deep, and superficial femoral veins has been described, although in this patient, factor V Leiden mutation was diagnosed, a mutation leading to resistance against activated protein C and a tendency to thrombosis. ⁴² In this patient, the calculus was located in the distal ureter, and the focus of SWL would be close to the venous system. The Virchow triad describes thrombosis to be dependent on three factors: Blood components, blood flow, and vessel or endothelial integrity. It can be speculated that in SWL, blood flow may become turbulent and that endothelial injury may occur, precipitating thrombosis.

Hepatic vein thrombosis has also been described that was preceded by a subcapsular hepatic hematoma. On enlarging, the hematoma caused compression and stasis within the intrahepatic vessels with thrombus extending into the inferior vena cava; operative management was necessary with evacuation of the subcapsular hematoma. ⁴³ Venous thrombosis of the portal vein has been reported in an obese patient who underwent SWL of gallbladder calculi; it was noted that this patient had a previous pulmonary embolism and thrombophlebitis of lower limb superficial veins. ¹⁹ There is currently no recommendation for venous thrombosis prophylactic therapy for patients who are undergoing SWL.

A solitary case of venous rupture has been reported in a patient with a preexisting connective tiisue disorder (Ehlers-Danos syndrome). ⁴⁴ The day after SWL for a ureteral calculus, abdominal pain developed, and the patient became hypovolemic; at laparotomy, bleeding from a ruptured superior mesenteric vein was found. ⁴⁴ The calculus was in the left ureter at the level of L4. The superior mesenteric vein lies close to this site, and it plausible that the vein was directly injured by SWL. Undoubtedly, connective tissue disorder greatly increased the risk of vascular rupture. In patients with connective tissue disorders, injury to any intra-abdominal organ or to the vasculature should be considered, and a period of observation in the hospital after SWL should be mandatory.

Coagulation and platelets

There are three groups of patients who should be considered regarding risk of hemorrhage: Those with intrinsic or acquired clotting factor disorder, such as hemophilia A or B, von Willebrand disease, or liver failure; those with intrinsic platelet disorder or thrombocytopenia; and those treated with anticoagulant or antiplatelet medication. Despite the prevalence of anticoagulant and antiplatelet medication in the general population, there is sparse evidence regarding its use in patients who are undergoing SWL; similarly, in the smaller population of pathologic coagulopathic states, data are limited to case studies and small series.

The first reported case of SWL in a patient with hemophila A was reported in 1987; this was successful, and no hemorrhagic complications occured. ⁴⁵ Since this initial report, there have been a total of 13 patients with hemophilia A who have safely undergone SWL; in all of these cases, correction of clotting was through administration of factor VIII to 80% to 100% of normal values before treatment. ^{46 –50} A total of four patients with hemophilia B, which is less common than hemophila A, have also been treated without complication after factor IX administration. ^49,51,52 Liver failure and cirrhosis lead to reduced synthesis of clotting factors, and SWL has been safely performed when coagulopathy is corrected by administration of vitamin K or by infusion of donor plasma products, such as fresh frozen plasma. ^47,50,53,54 In those reports that commented on International Normalized Ratio (INR) at treatment, 1.5 was the highest at which uncomplicated SWL was performed. ⁵⁰ Interestingly, recombinant factor VII has been used to achieve hemostasis in a continuing perirenal hematoma despite initial surgical evacuation and hemostasis; no reported coagulation or platelet defect was found in the patient. ⁵⁵

Thrombocytopenia is often associated with liver failure through splenomegaly or in disorders such as idiopathic thrombocytopenic purpura. Administration of donor platelets to normalize platelet count—or in idiopathic thrombocytopenic purpura, infusion of high dose gamma-globulin or previous splenectomy—has allowed treatment without hemorrhage in 23 patients in reported studies. ^{47,50,53,54,56} Four patients with von Willebrand disease, a congenital deficiency of von Willebrand factor crucial to platelet adhesion, have undergone SWL after previous treatment with cryoprecipitate; treatment was uneventful in three, while a small perinephric hematoma developed in one patient. ^53,57,58 There have been three patients reported who had thromboasthenia, a rare disorder in which platelets lack cell surface glycoprotein IIb/IIa, which binds to fibrinogen; they were treated with no adverse effects. ^47,48 In patients who have coagulopathy or a platelet disorder, discussion with a hematologic specialist is mandatory before embarking on SWL. Correction of coagulopathy has allowed safe SWL in several hematological disorders and should not be considered as a contraindication to SWL.

Currently, the only available evidence regarding antiplatelet or anticoagulant therapy and hemorrhage is based on retrospective case studies or small series of patients who present with hematoma after SWL, although there has only been a single prospective study. ⁵⁹ The most commonly used drugs are aspirin and clopidogrel that act to reduce clotting by reducing platelet activity, and warfarin, which inhibits clotting factor synthesis. The first reports of hematoma associated with aspirin therapy were in 1990; one patient was described as taking “two aspirins per day” before SWL and needed surgical evacuation, ⁶⁰ while the other stopped aspirin 10 days before treatment and was treated conservatively. ⁶¹ A further three series have reported on antiplatelet therapy; in a small series, two of nine patients with haematomas were receiving aspirin up to treatment; ⁶² in a series of 402 patients, 16 subcapsular hematomas were found with a significant correlation to antiplatelet therapy; ⁶³ and in the largest series of 31 hematomas, only one patient was receiving aspirin therapy. ⁵⁸

In these studies the patients reported presented with symptomatic hematoma and do not reflect the true incidence of all hematoma; therefore, it is difficult to surmise the true effect of antiplatelet therapy. More recently, clopidogrel, which is a potent inhibitor of platelet aggregation, has been implicated in perirenal haematoma formation in two case reports. ^64,65 Currently, only one prospective study has aimed to ascertain the safety of antiplatelet therapy. In this prospective study of 749 patients, 23 were receiving antiplatelet therapy, comprising aspirin, ticlopidine, or dipyridamole; these patients ceased their medication 8 days before SWL. In high-risk patients, unfractionated heparin was given in substitution; in both groups, there were no hemorrhagic complications. ⁵⁹

This study provides evidence that given sufficient time, the effects of aspirin can be reversed with no elevated risk of hemorrhage. The evidence that antiplatelet therapy increases the incidence of hemorrhage is weak and based on case reports and three small case series that did not convincingly conclude any increased risk. We would advise that in those patients who are high risk and need antiplatelet therapy for coronary artery stents or recurrent myocardial infarction, discussion with a cardiologist should be sought and potential SWL can be performed in the presence of this medication. In those cases where it is appropriate, aspirin therapy should be ceased 4 days before SWL because platelet function is restored in most patients by this time. ⁶⁶ Patients receiving clopidogrel should stop use 7 days before SWL; in healthy subjects, a once daily dose of 75 mg of clopidogrel can be reversed with recovery of platelet function in this time frame. ⁶⁷

Warfarin is a coumarin derivative and is the most commonly used anticoagulant for treatment of thromboembolic disorders and for patients with metallic heart valves. Its mode of action is through inhibition of vitamin K epoxide reductase and subsequent inhibition of factor VII and prothrombin synthesis. Reversal of warfarin is simply by cessation, with vitamin K supplementation if needed; similar to those with coagulopathy secondary to liver disease, INR can be closely monitored before SWL. Uncomplicated SWL after warfarin reversal has been reported in several case reports, with INR as high as 1.5. ^50,54,57 Of particular interest is a series of 14 elderly patients in whom conversion to 40 mg low molecular weight herparin was instituted, and SWL was not associated with any hemorrhagic complication. ³⁰ Similarly, in a study of 5739 patients where 8 patients receiving warfarin were converted to low molecular weight heparin, no perirenal hematomas were reported, but gross hematuria was found in 1 patient and a renal artery embolism necessitating eventual nephrectomy developed in another. ⁵⁶ In contrast, a large retrospective series of 31 hematomas reported an elevated risk despite cessation of medication; in this study group of 10,953 patients, 4 had previous been receiving a coumarin derivative with 3 converted to unfractionated intravenous heparin periprocedure and one with no further anticoagulation. ⁵⁸ Warfarin reversal is variable and measured by monitoring INR; in those with high thromboembolic risk, it is imperative unfractionated heparin is used in the periprocedure period, because adverse events associated with thromboemolism may outweigh the risk of hematoma or bleeding.

The difficulty with interpreting retrospective studies of patients in whom hemorrhage develops while they are receiving medication is that causality is presumed. To truly identify the risk of complication caused by antiplatelet or anticoagulant medication would need a randomized trial. Cessation of antiplatelet and anticoagulant medication may reduce the risk of hemorrhage to that of patients naïve to anticoagulants, but this inevitably carries the risk of precipitating pathologic thrombosis or embolus for which the medication was being administered. Correction of acquired or intrinsic coagulation disorders allows SWL to be performed, and there have been no reported cases of significant hemorrhage. It is also important to consider ureteroscopic methods, because they are a safe alternative to SWL and can be performed without reversal of anticoagulant agents. ^56,68