Acute Life-Threatening Hemorrhage in Patients with Head and Neck Cancer Presenting with Carotid Blowout Syndrome: Follow-Up Results after Initial Hemostasis with Covered-Stent Placement

Discussion

CBS is a dreaded iatrogenic complication of HNC treatment. Since the syndrome was first described in 1962, several surgical and endovascular treatment options have been attempted.¹³ Before the advent of endovascular treatment modalities, CBS could be treated only with surgical ligation or surgical bypass of the carotid artery. However, open surgical techniques in the setting of HNC were associated with high mortality and major neurologic morbidity rates of 40% and 60%, respectively.⁴ Endovascular management of acute CBS by balloon occlusion of the carotid artery was first introduced in 1984.¹⁴ This treatment gained popularity because of the elegance and relative ease of the approach, especially in a hostile post-surgical or irradiated neck. Moreover, management with permanent balloon occlusion resulted in significantly lower morbidity and mortality rates than the surgical approach.^1,4,6 Despite this advancement, there is a rate of 0%–15% of cerebral ischemic complications with permanent balloon occlusion of the ICA or CCA.^1,4–8

The ischemic complications from vessel-deconstruction strategies subsequently led to the use of endovascular stents as a possible option. Many initial reports suggested that endovascular stents could not only reconstruct the arterial wall but also maintain vessel patency and decrease ischemic complications. Macdonald et al¹⁵ first reported a case of CBS managed successfully with CSP in an emergent presentation. Lesley et al¹¹ published a series of 16 CBS cases treated with endovascular stents, including 2 covered stents, resulting in no deaths, and 1 transient ischemic event. Kim et al¹² described a series of 4 CBS cases treated successfully with CSP without associated neurologic morbidity or mortality. In fact, these reports are similar to our findings because we noted no initial mortality or neurologic ischemic complications after CSP in our population. It follows that covered stents may represent an excellent treatment technique for the acute management of CBS, especially in patients who are at a high risk for stroke as a result of poor intracranial collaterals or an incomplete circle of Willis.

Early encouraging reports were mixed, with a series of complications associated with the use of covered stents. Warren et al⁹ reported 3 patients with CBS who were initially managed successfully with CSP, but on follow-up, 2 of these stents had extruded, leading to stent thrombosis in 1 patient and stroke in another. Simental et al¹⁰ similarly reported on delayed complications of stroke and stent thrombosis in 2 cases of CBS treated with CSP. Chang et al¹⁶ described a delayed case of brain abscess formation as a result of septic emboli from an infected self-expandable covered stent used for CBS. Chang et al¹⁷ also reported their experience in 24 patients with CBS who underwent endovascular therapy. Initial complications were encountered in 4 patients (36.4%) who underwent reconstructive management and in 1 patient (7.7%) who underwent deconstructive management (P = .142). Rebleeding occurred in 5 patients (45.5%) in the reconstructive management group and in 3 patients (23.1%) in the deconstructive management group (P = .659)

In our series, 3 patients (30%) had delayed complications of stent infections requiring stent extraction after endovascular carotid sacrifice or surgical bypass. In these cases, the stent may have become chronically infected after being deployed in an area of infective necrosis, serving as a nidus of infection and facilitating the formation of thrombi or septic emboli in the carotid artery. In fact, 1 patient developed multiple cerebral abscesses.¹⁸ Stent infection complications could not be entirely eliminated despite systematic prescription of postprocedural antibiotics.

We routinely initiate intravenous broad-spectrum antibiotics for 7–10 days postprocedure with adequate bacterial coverage native to the skin and oropharynx. Next, we place the patient on long-term antibiotic coverage with oral clindamycin, especially if there is the possibility of a chronically infected neck or dehiscent wound. Covered stents are prone to a high incidence of infection when deployed in an open environment, either communicating with the skin superficially or the deep aerodigestive tract. Most interesting, all 3 infected covered stents in our series exhibited communication with the aerodigestive tract and presented with recurrent hemorrhages. Pyun et al¹⁹ showed a recurrent bleeding rate in 6 of 7 patients treated with CSP within a short timeframe from 3 to 44 days. They postulated that the recurrent bleeding rate was most likely due to underlying infection or injury to the vasa vasorum after radiation therapy.

Recurrent hemorrhage is a feared complication of CSP and may be directly related to infection of the stent. Recurrence rates of 33%–86% have been quoted in prior studies.^11,17,19,20 In comparison, our rebleeding rate was (3/10) 30%. The recurrent hemorrhage rate in our series was slightly lower than that in other studies and may be due to our extended use of long-term antibiotics. All recurrences were managed successfully with either endovascular carotid sacrifice or surgical bypass followed by surgical debridement and stent extraction. Patients treated with endovascular covered stents must be cautioned on the possibility of rebleeding and followed closely for signs of recurrent CBS

We advocate CSP in the acute emergent setting of a patient with inadequate collateral circulation presenting with CBS. This is a straightforward procedure in experienced hands and can achieve immediate cessation of the hemorrhage with minimal risk of stroke. Primary vessel sacrifice in the acute emergent setting is still an excellent option in patients with good collateral circulation. It is possible to get control of the bleeding on the table with a temporary balloon before proceeding with permanent vessel sacrifice without the procedure being excessively time-consuming. Realistically, the number is too low in any of these series individually or in summation to form definitive conclusions about the risk of disabling neurologic events with 1 procedure versus the other, except in cases of inadequate collateral circulation, in which case CSP has an obvious advantage.

Once hemostasis is achieved, a balloon test occlusion followed by vessel sacrifice can be performed in a more controlled setting if infection develops in the region of the covered stent. The potential of infection in these patients is high due to associated open or dehiscent wounds and/or communication with the aerodigestive tract. Therefore, we suggest following these patients every 3–6 months with CT angiography of the neck or sonography to look for fluid or evidence of a pseudoaneurysm developing around the stent. In contrast, after permanent vessel sacrifice, there is very minimal risk of infection with recurrent delayed CBS.

To prevent thromboembolic complications related to stent placement, we routinely load patients with clopidogrel, 600 mg, and ASA, 325 mg, through a nasogastric tube just before the procedure. Furthermore, aggressive heparin anticoagulation is used during the procedure with repetitive ACT monitoring. Patients remain on clopidogrel, 75 mg, and ASA, 81 mg, daily postprocedure for at least 12 weeks. Following documentation of stent patency by Doppler sonography, the patient is placed on ASA, 81 mg daily, for life. It is possible that our relatively low rate of ischemic complications resulted from a strict adherence to the use of dual antiplatelet therapy. In our study, only 1 patient could not be administered the dual antiplatelet regimen, and a loading intravenous dose of a glycoprotein IIb/IIIa inhibitor was substituted during stent placement. Unfortunately, this patient had an asymptomatic 2-cm left temporal lobe intracranial hemorrhage, and antiplatelet agents (clopidogrel and ASA) were not initiated until 2 days postprocedure. The same patient had stent thrombosis and stroke at 8 months postprocedure, very likely coincidental. To prevent thromboembolic complications, we believe extended oral antiplatelet agents are mandatory, despite a possible increased risk of hemorrhagic complications. Parallel antiplatelet protocols have eloquently shown efficacy in the carotid and coronary stent literature.²¹

Several limitations of our study are readily apparent. The retrospective analysis invariably produces internal bias, and the relatively small number of patients makes generalization to a large cohort of similar patients very difficult. Unfortunately, the pathology is so rare that any single institution cannot recruit enough patients for the statistical power that multicenter registries or meta-analyses may provide. All patients were treated with the same manufactured covered stent (Bard Fluency); therefore, a comparison regarding the type of covered stent graft that may be advantageous for the treatment of CBS is impossible. Furthermore, the importance of postprocedure management with dual antiplatelet regimens is assumed from the non-covered stent literature. The time required for PTFE endothelialization, its thrombogenicity, and for antiplatelets to prevent thromboembolic complications is largely unknown.