Arteriovenous malformations (AVMs) are congenital or acquired high-flow vascular lesions that present with pain due to tissue ischemia secondary to arteriovenous shunting. While a few AVMs may be suitable for surgical excision, most lesions are managed by endovascular techniques due to their size, location, or infiltrative nature. In addition, interventional radiology (IR) could perform preoperative embolization to reduce blood loss during subsequent surgical excision. The approach, techniques, and agents used for embolization have evolved over the years.1 The most common agents used are ethanol, N-butyl cyanoacrylate, ethylene vinyl alcohol copolymer (Onyx; Medtronic, Minneapolis, MN), and coils. Any agent injected within the arterial feeders of an AVM has the risk of migration into the venous system through arteriovenous shunts and may cause systemic side effects such as allergic reactions, arrhythmias, pulmonary embolism, and pulmonary hypertension. Commonly referred to as glue, N-butyl cyanoacrylate is a liquid monomer that polymerizes upon contact with ionic media such as blood and saline and is Food and Drug Administration approved for treatment of AVMs.2 It is mixed with an oily contrast agent lipiodol to make the mixture radiopaque and to control the polymerization time of glue. The ratio of glue and lipiodol is adjusted such that it solidifies within the nidus (site of communication between arteries and veins) of the AVM without extension into the normal venous system. Pulmonary embolism developing either intra- or postprocedure is a well-characterized complication of glue–lipiodol injection for embolization of vascular malformations.3–6 The systemic effects of these agents are also well described when used by gastroenterologists for injection of gastroesophageal varices under endoscopic visualization.7–9 Written consent and Health Insurance Portability and Accountability Act authorization have been obtained from the patient’s mother because he is a minor.
Arrhythmia as a clinical manifestation of systemic migration of glue–lipiodol is uncommon. Our patient experienced accelerated idioventricular rhythm (AIVR), a wide complex rhythm with a rate that is within 20% of the patient’s resting heart rate as an unusual side effect of systemic migration of glue–lipiodol during AVM embolization.
A 16-year-old boy with pain secondary to right calf intramuscular AVM (Figure 1) was undergoing staged embolization at a tertiary care pediatric hospital. He was diagnosed with Bannayan-Riley-Ruvalcaba syndrome based on a constellation of findings such as developmental delay, benign follicular thyroid nodules, intramuscular hamartoma, and penile freckles.10 In the past, he had pharmacoresistant epilepsy treated with magnetic resonance imaging–guided stereotactic laser ablation of focal cortical dysplasia with resolution of seizures and was on a weaning schedule of his anticonvulsant regimen. He underwent 2 sessions of transarterial embolization using absolute ethanol with 50% reduction of the AVM and now presented for the third treatment session. Antiepileptic medications taken on the day of surgery included zonisamide, rufinamide, and oxcarbazepine.
General anesthesia was administered with intravenous induction and succinylcholine to facilitate endotracheal intubation. Due to postoperative nausea after previous procedures, total intravenous anesthesia was chosen using propofol, dexmedetomidine, and hydromorphone. The IR procedure was initiated by gaining antegrade arterial access into the right common femoral artery and placement of a vascular sheath, the side arm of which was continuously perfused with pressurized saline to prevent arterial thrombosis. This was followed by right popliteal angiography (Figure 1A), selective angiography of multiple feeding arteries to the AVM, and injection of transarterial absolute ethanol. Although this was successful in flow reduction through the AVM, there were multiple residual arteriovenous shunts draining into large ectatic venous lakes that subsequently drained into the popliteal vein. To gain further reduction of arteriovenous shunting, it was decided to access these venous lakes percutaneously under ultrasound guidance and occlude them using glue–lipiodol mixture. This was successfully performed at 3 different sites (Figure 1B) with satisfactory polymerization of a 1:1 glue (Histoacryl; B.Braun Surgical, S.A., Rubi, Spain) and lipiodol (Lipiodol; Guerbet LLC, Bloomington, IN) mixture within the venous lakes without extension into the popliteal vein. Throughout this period, the patient was stable in sinus rhythm just above 60 beats per minute and ventilated with a fraction of inspired oxygen (Fio2) of 30%. During injection of glue–lipiodol into the fourth site, a small amount of the mixture was observed to extend into the popliteal vein on fluoroscopy before its polymerization within the venous lake. This coincided with development of a wide complex rhythm at 89 beats per minute (Figure 2). The oxygen saturation, mean arterial pressure, and respiratory rate, however, remained unchanged. Pulmonary embolism was suspected based on the popliteal vein fluoroscopy, but chest fluoroscopy did not demonstrate any radiopacity to suggest lipiodol emboli. Venography performed through posterior tibial venous access demonstrated patency of the popliteal, femoral and iliac veins, and the inferior vena cava. Electrolytes and arterial blood gas results were normal. Two-dimensional echocardiography in the IR suite was also normal. In particular, there was no evidence of right heart strain. A 12-lead electrocardiogram (ECG) showed reduced frequency of the ectopic beats (Figure 3) and an AIVR. Provocative testing with changing Fio2 revealed suppression of the ectopic beats with increase in Fio2. This was interpreted as suggestive of elevation in right ventricular pressure. Management included temporary hyperoxia with Fio2 of 100%, intravenous lidocaine, and empirical intravenous magnesium. After complete emergence from general anesthesia, the patient was extubated and observed in the intensive care unit. He was maintained on supplemental oxygen by nasal cannula overnight as a precaution for possibly dynamic physiology and late effects of the glue–lipiodol combination on the pulmonary vasculature. During the intensive care unit stay, there was a 6 beat run of ventricular tachycardia at 163 beats per minute 3 hours after the initial episode and intermittent ventricular ectopy continued for a total of 5 hours after the procedure. Chest radiograph did not reveal any radiopacity suggestive of glue–lipiodol mixture, and 24-hour Holter monitoring on the following day did not reveal any abnormality.
Systemic complications of migration of embolic agents into the venous system have been reported during embolization of AVMs3–6 and endoscopic injection of gastroesophageal varices.7–9,11,12 The reported acute presentation of pulmonary embolism includes hypoxia, tachypnea, and hypotension and rarely disseminated intravascular coagulopathy8 and death,11 whereas delayed presentation includes febrile illness, hypoxia, and septicemia.8 There are a few reports of ventricular tachycardia managed with amiodarone and high-flow oxygen as part of the clinical manifestation of pulmonary embolism due to glue–lipiodol migration.9,12
To the best of our knowledge, arrhythmia without demonstrable pulmonary embolic burden after glue–lipiodol injection has not been reported. Several electrophysiological aspects of this case are worthy of discussion. Preoperatively, there was no history of cardiac arrhythmia, but the patient was on rufinamide, an antiepileptic known to shorten the QT interval.13 Before initiation of rufinamide, ECG revealed sinus bradycardia at a rate of 58 with QT/QTc of 376/372. ECG after initiation of rufinamide but before the IR procedure was not available. After glue–lipiodol injection, ECG was notable for QT/QTc of 362/401 at a rate of 72 beats per minute. In this case, rufinamide appeared to shorten the corrected QT interval by 29 milliseconds; however, this was within 1 SD of previously reported mean impact on corrected QT interval duration. This degree of QT interval shortening has not been associated with symptomatic cardiac events.
Intraoperatively, dexmedetomidine was used as an adjunct to the anesthetic at a dose of 0.25 µg/kg/h after a 0.3 µg/kg bolus. Dexmedetomidine is a negative chronotrope known to depress sinus and atrioventricular node dromotropy and cause transient decrease in QT/QTc.14,15 It is possible that the patient’s ventricular ectopy was slower than in previously reported cases due in part to dexmedetomidine. However, the episode of nonsustained ventricular tachycardia was approximately 7 hours after the last administration of dexmedetomidine. By that time, the clinical effect of dexmedetomidine and depression of chronotropy would be expected to have resolved.
Decreased burden of ventricular ectopy was noted after increasing Fio2. Mass effect from embolization of glue–lipiodol mixture as a cause of symptomatic pulmonary embolus was essentially ruled out based on the lack of lipiodol emboli on chest fluoroscopy and radiograph. However, there was transient fluoroscopic visualization of glue–lipiodol mixture in the popliteal vein followed by AIVR, so pharmacological irritation of the pulmonary vessels and increased pulmonary vascular resistance are likely. Decreasing ectopy burden with increased Fio2 suggests some relief of irritable pulmonary vasculature because oxygen is a potent pulmonary vasodilator.
Full recovery and normal Holter results suggest that the transient AIVR was related to some combination of glue–lipiodol injection and anesthetic agents.
AIVR is an uncommon rhythm. It often occurs after failure of the sinus and atrioventricular nodes. The causes are multiple with the most common being reperfusion after acute myocardial infarction, then β-agonists, digoxin toxicity, electrolyte abnormalities, cardiomyopathy, myocarditis, return of spontaneous circulation after cardiac arrest, and the athletic heart. The natural history of AIVR is a benign one that does not require treatment. Despite multiple confounding factors contributing to the electrophysiological milieu of this patient, arrhythmia after glue–lipiodol injection was prominent. Familiarity with this systemic response to glue–lipiodol and confidence in its diagnosis are uncommon among anesthesiologists, hence the importance of this case to the literature.
Name: Jamie W. Sinton, MD.
Contribution: This author helped prepare the manuscript.
Name: Ionela Iacobas, MD.
Contribution: This author helped provide information regarding rufinamide and QT shortening.
Name: Heather Cleveland, BSRS.
Contribution: This author helpled explain the details of the interventional radiology procedure portion of the manuscript.
Name: Sheena Pimpalwar, MD.
Contribution: This author helped perform the interventional radiology procedure and provide information regarding procedural details and manufacturer information for the materials used in the case.
This manuscript was handled by: Richard C. Prielipp, MD.
1. Gilbert P, Dubois J, Giroux MF, Soulez G. New treatment approaches to arteriovenous malformations. Semin Intervent Radiol. 2017;34:258–271.
2. Pollak JS, White RI Jr. The use of cyanoacrylate adhesives in peripheral embolization. J Vasc Interv Radiol. 2001;12:907–913.
3. Carapiet DA, Stevens JE. Pulmonary embolism following embolization of an arteriovenous malformation. Paediatr Anaesth. 1996;6:491–494.
4. Pelz DM, Lownie SP, Fox AJ, Hutton LC. Symptomatic pulmonary complications from liquid acrylate embolization of brain arteriovenous malformations. AJNR Am J Neuroradiol. 1995;16:19–26.
5. Haller I, Kofler A, Lederer W, Chemelli A, Wiedermann FJ. Acute pulmonary artery embolism during transcatheter embolization: successful resuscitation with veno-arterial extracorporeal membrane oxygenation. Anesth Analg. 2008;107:945–947.
6. Kjellin IB, Boechat MI, Vinuela F, Westra SJ, Duckwiler GR. Pulmonary emboli following therapeutic embolization of cerebral arteriovenous malformations in children. Pediatr Radiol. 2000;30:279–283.
7. Al-Hillawi L, Wong T, Tritto G, Berry PA. Pitfalls in Histoacryl glue injection therapy for oesophageal, gastric and ectopic varices: a review. World J Gastrointest Surg. 2016;8:729–734.
8. Kazi S, Spanger M, Lubel J. Gastrointestinal: pulmonary embolism of cyanoacrylate glue following endoscopic injection of gastric varices. J Gastroenterol Hepatol. 2012;27:1874–1874.
9. Papiamonis NE, Matrella E, Blevrakis EG, Kouroumalis EA. Acute pulmonary embolism following N-butyl-cyanoacrylate endoscopic injection sclerotherapy. Ann Gastroenterol. 2012;25:261.
10. Litzendorf M, Hoang K, Vaccaro P. Recurrent and extensive vascular malformations in a patient with Bannayan–Riley–Ruvalcaba syndrome. Ann Vasc Surg. 2011;25:1138.e15–1138.e19.
11. Burke MP, O’Donnell C, Baber Y. Death from pulmonary embolism of cyanoacrylate glue following gastric varix endoscopic injection. Forensic Sci Med Pathol. 2017;13:82–85.
12. Berry PA, Cross TJ, Orr DW. Clinical challenges and images in GI. Gastroenterology. 2007;133:1413–1748.
13. Schimpf R, Veltmann C, Papavassiliu T. NIH public access. Heart Rhythm. 2012;9:776–781.
14. Tirotta CF, Nguyen T, Fishberger S, et al. Dexmedetomidine use in patients undergoing electrophysiological study for supraventricular tachyarrhythmias. Paediatr Anaesth. 2017;27:45–51.
15. Görges M, Whyte SD, Sanatani S, Dawes J, Montgomery CJ, Ansermino JM. Changes in QTc associated with a rapid bolus dose of dexmedetomidine in patients receiving TIVA: a retrospective study. Paediatr Anaesth. 2015;25:1287–1293.