Anaphylactic Reaction During Implantation of the Ovation Stent-Graft System in a Patient With Abdominal Aortic Aneurysm

Introduction

Endovascular aneurysm repair (EVAR) for the treatment of abdominal aortic aneurysms (AAAs) has steadily increased during the past decade, mainly due to studies reporting lower 30-day mortality compared to open surgical repair. ¹ Anatomic limitations, including excessive angulated, short, or tapered proximal necks, and narrow, tortuous, or angulated iliac arteries hinder adequate proximal fixation and sealing or iliac passage, respectively, rendering EVAR unfeasible. As a result, there is a continued interest in the development of newer stent-grafts that can cover a wider range of aortoiliac morphology and produce better results. Interestingly, although 6 US Food and Drug Administration–approved devices are currently in use, almost half of AAA patients are unsuitable for EVAR due to hostile neck or narrow iliac vessels. ²

To deal with this problem, the low-profile Ovation Prime Abdominal Stent Graft System (TriVascular, Santa Rosa, CA, USA) has recently received the Conformité Européenne Mark for use in patients with challenging proximal neck or small iliac vessels; initial results seem quite promising.^2–5 The device is a trimodular endoprosthesis with a main body and 2 limbs. The main body is delivered by the smallest commercially available, flexible, hydrophilic-coated 14-F catheter. In order to provide this ultralow profile, the Ovation endograft lacks the nitinol support that other endograft systems possess, competing with the endograft’s fabric for the same space in the delivery catheter. Instead, a network of compliant, inflatable rings is filled with a low-viscosity radiopaque polymer during stent-graft deployment. ⁶ The polymer is prepared separately and infused into the main body rings by an automated plunger, which exerts 1 atm of pressure. To date, there is no report of rupture of the endograft’s polymer-filled rings with consequent severe anaphylactic reaction.

Case Report

An 82-year-old man with a history of hypertension, diabetes mellitus, coronary artery disease, coronary angioplasty, and no known allergies presented with a 5.3-cm AAA. Laboratory studies documented a hemoglobin level of 14.7 g/dL, a white blood cell count of 7630/µL, a platelet count of 199×10³/µL, a prothrombin time of 10.1 seconds, an international normalized ratio of 0.94, a partial thromboplastin time of 47.9 seconds, and a serum glucose of 140 mg/dL; other findings were within normal reference values.

The patient underwent EVAR under epidural anesthesia. Owing to a tapered proximal neck and small-diameter iliac arteries, a TriVascular Ovation Prime Abdominal Stent Graft System was chosen. Arterial access was obtained through bilateral femoral cutdown, and 5000 units of heparin were given. Guidewires were placed in the aorta, and all implant procedure and deployment instructions were carefully followed according to the Instructions for Use ³ (IFU) and consultation with the local manufacturer’s representative. However, during polymer infusion of the inflatable rings under continuous angioscopy, the rings were incompletely filled, although the entire 11 mL of polymer was administered. Simultaneously, the patient reported a tingling sensation all over his body. He rapidly became unconsciousness, his systolic blood pressure dropped from 130 to 40 mm Hg, and he quickly suffered cardiopulmonary arrest. The patient was immediately intubated and cardiopulmonary resuscitation was initiated. Angiography revealed no signs of rupture. Angioscopy showed that the inflatable rings were completely empty of polymer. The episode was treated as an anaphylactic on-table cardiovascular collapse, and the patient was resuscitated. However, because of hemodynamic instability, the endovascular procedure was abandoned without trying to implant the limbs, and the patient was transferred intubated to the intensive care unit. He developed atrial fibrillation, which was successfully treated. He fully recovered after 3 days in the intensive care unit and was transferred to the main ward.

Postoperative computed tomographic angiography demonstrated no polymer in the inflatable rings of the endograft (Figure 1). The patient was fully informed about the episode, and he refused to be further treated in either an endovascular or open manner. He was discharged after 10 days. Laboratory investigations on discharge showed a hemoglobin of 11.2 g/dL, a white blood cell count of 5180/µL, a platelet count of 229×10³/µL, a prothrombin time of 9.9 seconds, an international normalized ratio of 0.86, a partial thromboplastin time of 29 seconds, serum glucose of 243 mg/dL, and a lactate dehydrogenase of 319 U/L; other findings were within normal reference values.

OPEN IN VIEWER

Figure 1.

Postoperative computed tomographic angiography showing that only the main body of the Ovation Abdominal Stent Graft System is deployed; the inflatable rings of the endograft do not contain any polymer.

After 4 months of follow-up, the patient is asymptomatic, and he still refuses any treatment. The adverse incident was fully reported to TriVascular immediately after the operation through its local representative. The manufacturing company has taken responsibility for investigating the incident and addressing the technical error in the production.

Discussion

The Ovation Abdominal Stent Graft System has demonstrated excellent 1-year safety and effectiveness in the treatment of AAA patients, particularly in patients with challenging anatomic characteristics, including short aortic necks and narrow iliac arteries. ² The results of a prospective, multicenter, single-arm trial conducted at 36 sites in the United States, Germany, and Chile recorded a 30-day major adverse event rate of 2.5%. At 1 year, AAA-related and all-cause mortality were 0.6% and 2.5%, respectively. The major and serious adverse event rates through 1 year were 6.2% and 38.5%, respectively. ² In another series of 37 patients with AAA treated with the Ovation endograft, 4 adjunctive procedures were required, including 2 distal extensions (type Ib endoleak and iliac limb disconnection resulting in type III endoleak) and 2 bypass surgeries (limb graft occlusion and gate cannulation failure). ⁷ However, despite its growing popularity and continuing use, no serious polymer-related allergic reactions have yet been reported in the literature.

According to the IFU from Trivascular, ³ the fill polymer is composed of 3 components that are mixed prior to injection. On mixing and injection into the graft, the components form a radiopaque polymer that fills the channels of the sealing rings in the wall of the aortic graft. In the contraindication section, it is underlined that the implant should be avoided in patients with known sensitivities or allergies to the device materials, including polyethylene glycol (PEG)–based polymers. ³ PEG is a polyether compound with many applications from industrial manufacturing to medicine. PEG is the most commonly used nonionic polymer in the field of polymer-based drug delivery. ⁸ Clinical experience with PEG has produced possible side effects and complications, such as hypersensitivity, unexpected changes in pharmacokinetic behavior, toxic side products, and an antagonism arising from the easy degradation of the polymer under mechanical stress as a result of its ether structure and its nonbiodegradability. ⁸ An association between PEG and blood clotting and clumping of cells was recognized in early studies in the 1950s.^8,9 Since then, it has been found that adverse reactions to PEG often occur through complement activation, which may lead to hypersensitivity reactions that can provoke anaphylactic shock.^10,11 Anaphylaxis as a result of hypersensitivity to PEG has also been observed with commercial PEG-containing contrast agents used for echocardiography. ¹² In our case, the diagnosis of anaphylactic reaction was based on clinical criteria. The patient experienced severe hemodynamic instability and loss of consciousness; no specific test was performed to confirm the diagnosis of the anaphylactic reaction.

Search of the Food and Drug Administration database from 2012 to 2015 was performed in January 28, 2015, using the term “Ovation.” All retrieved reports concerning the Ovation Abdominal Stent Graft were read. This search revealed 15 reported cases of leak of polymer fill into the vasculature. Interestingly, the majority of the events were observed in 29-mm aortic body stent-grafts. ¹³ In 2 of the 15 reviewed cases, the iliac limb stent-grafts were not deployed, and the exclusion of the aneurysm was not completed owing to hemodynamic instability. In another case, a patient needed chest compressions and a balloon placed in the suprarenal aorta to assist with stabilization of the blood pressure. None of the patients died. In the majority of cases, the cause was not identified and was attributed eventually to technical error of the polymer kit system. Other possible causes included difficulties in advancing the stent-graft, significant tension and manipulation of the delivery system, and significant tension before re-positioning the endograft, which may have compromised the delivery system connection to the graft fill polymer port, likely resulting in an intravascular leak of polymer. ¹³

Based on this event and an increase in complaints related to incomplete intraoperative polymer fill of the Ovation Prime 29-mm aortic body stent-graft, Trivascular initiated a field safety corrective action on September 20, 2014, to recall affected devices manufactured within the same time period as the devices for these events. This case report might alert vascular surgeons and interventionists to the potential risk of rupture of Ovation main body’s polymer-filled rings, which may lead to extremely severe anaphylactic reaction.