JVSV LD Regarding “Retrograde administration o
JVSV LD Regarding “Retrograde administration o
REFERENCES
Bounds MC, Endean ED. Treatment of postoperative high-volume lymphatic complications using isosulfan blue. J Vasc Surg Venous Lymphat Disord 2018;6:737-40.
Akhan O, Karcaaltincaba M, Ozmen MN, Akinci D, Karcaaltincaba D, Ayhan A. Percutaneous transcatheter ethanol sclerotherapy and catheter drainage of postoperative pelvic lymphoceles. Cardiovasc Intervent Radiol 2007;30:237-40.
Johnson OW, Chick FJ, Chauhan NR, Fairchild AH, Fan CM, Stecker MS, et al. The thoracic duct: clinical importance, anatomic variation, imaging, and embolization. Eur Radiol 2016;26:2482-93.
Hill H, Srinivasa RN, Gemmete JJ, Hage A, Bundy J, Chick JF. Lymphangiography and cyanoacrylate glue embolization for the treatment of postoperative lymphatic leak after robot- assisted laparoscopic pelvic resection. J Endourol Case Rep 2018;4:66-71.
https://doi.org/10.1016/j.jvsv.2018.11.001
Regarding “Retrograde administration of ultrasound-guided endovenous microfoam chemical ablation for the treatment of superficial venous insufficiency”
We read with interest Dr Deak’s case series1 of 250 patients treated with U.S. Food and Drug Administra-
tion (FDA)-approved polidocanol microfoam 1% con- sisting of 65% oxygen and 35% carbon dioxide (O2CO2FS) containing <0.8% nitrogen. The absence of neurologic or cardiac adverse events (NCAEs) in Dr Deak’s community practice case series is consistent with the absence of clinically important neurologic events in the Efficacy and Safety Study of Polidocanol Injectable Foam for the Treatment of Saphenofemoral Junction Incompetence (VANISH-1) and Polidocanol Endovenous Microfoam Versus Vehicle for the Treatment of Saphenofemoral Junction Incompetence (VANISH-2).2,3 We recently reviewed leg vein sclerosant-associated NCAEs to see whether foamed preparation contributed to postmarketing reports of NCAEs. We searched the FDA Adverse Event Report- ing System database and MEDLINE for NCAEs using any formulation of polidocanol or sodium tetradecyl sulfate (STS) for leg vein sclerotherapy. Search dates were from March 30, 2010, for all polidocanol products (U.S. approved date for Asclera) and from January 1, 1968, for STS (introduction of the FDA Adverse Event Reporting System database) through September 19, 2017, for these products. We included only NCAEs with onset within 24 hours of the sclerotherapy pro- cedure so as to exclude secondary or cascade events not directly attributable to sclerotherapy.
NCAEs attributable to pulmonary embolus, deep venous thrombosis, and anaphylaxis were excluded, as these have previously been labeled in the polidoca- nol and STS package inserts. Cases reported as vaso- vagal reactions were also excluded.
We retrieved 83 reports of polidocanol and 57 reports of STS. After applying the inclusion and exclusion criteria, we identified 23 leg vein sclerotherapy NCAE cases (Table). Patent foramen ovale or right to left shunt was documented in 11 cases, including all but one STS neuro- logic case. Physician-compounded foamed sclerosant, generally with room air, was documented in 10 patients. Twelve cases did not report the presence or absence of foam. One case documented liquid formula- tion associated with lumbar ischemia and spinal vein oc- clusion without brain involvement. NCAE onset occurred within 30 minutes after the sclerosant injection in 18 cases. Of the 13 patients with brain ischemia, 9 patients had complete clinical recovery within 3 days, and 6 pa- tients had documentation of intracranial intra-arterial air. Coronary artery imaging showed no hemodynamically significant coronary artery disease in any of our cardiac cases. One cardiac arrest case reporting death before hospital arrival did not provide coronary artery information.
Our case series, which excluded pulmonary embolus and deep venous thrombosis, found no NCAEs for O2CO2FS (Varithena; BTG International Ltd, London, UK), although global market authorizations and approval date differences likely contributed to less O2CO2FS use. Polidocanol is available as Varithena O2CO2FS to treat incompetent great saphenous veins, accessory saphenous veins, and visible varicosities of the great saphenous vein system above and below the knee.4 The liquid formulation of polidocanol is available as Asclera to treat uncomplicated spider veins and uncomplicated reticular veins.5
Mitigation potential exists for NCAEs associated with leg vein sclerotherapy paradoxical embolism of room air. The safety and efficacy of polidocanol or STS foamed with room air has not been established and its use should be avoided. This statement was recently included in the Asclera5 and Sotradecol6 product labels under the heading Arterial Embolism.
The authors would like to thank Mary Ross Southworth, PharmD (Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Md), for her thoughtful suggestions in preparing this manuscript.
Table. Case series clinical characteristics
| Neurologic cases (n ¼ 14) | Cardiac cases (n ¼ 9) | ||||||
| Polidocanol (n ¼ 9) | STS (n ¼ 5) | Polidocanol (n ¼ 7) | STS (n ¼ 2) | ||||
| Events | Stroke/TIA (13) | 8 | 5 | Events | Cardiac arrest (2) | 2a | 0 |
| Spinal ischemia (1) | 1 | 0 | NSTEMI, STEMI (3) | 2 | 1 | ||
| SC/TTS per reporter (4) | 3 | 1 | |||||
| Formulation | PCFS (6) | 3 | 3 | Formulation | PCFS (4) | 3 | 1 |
| Un-foamed liquid (1) | 1 | 0 | Un-foamed liquid (0) | 0 | 0 | ||
| NR (7) | 5 | 2 | NR (5) | 4 | 1 | ||
| Air embolism | ICA on imaging (6) | 1 | 5 | Coronaries | Normalb (8) | 6 | 2 |
| NR (8) | 8 | 0 | NR (1) | 1 | 0 | ||
| PFO/RLS | Found (9) | 5 | 4 | PFO/RLS | Found (2) | 1 | 1 |
| Not found (3) | 2 | 1 | Not found (1) | 1 | 0 | ||
| NR (2) | 2 | 0 | NR (6) | 5 | 1 | ||
| Time to onset | Within 30 minutes (11) | 6 | 5 | Time to onset | Within 30 minutes (7) | 6 | 1 |
| 30 minutes to 3 hours (1) | 1 | 0 | 30 minutes to 3 hours (1) | 1 | 0 | ||
| NR but <24 hours (2) | 2 | 0 | NR but <24 hours (1) | 0 | 1 | ||
| LVEF at time of acute presentation | Range | 24%-50% | 45% to normal EF | ||||
| Mean | 38% | – | |||||
| NR | – | ||||||
| Time to complete neurologic recovery | 3 days or less (9) | 5 | 4 | Time to normalization of LV wall motion | 9 days or less (4) | 2 | 2 |
| 4-14 days (2) | 2 | 0 | <3 months (2) | 2 | 0 | ||
| <3 months (2) | 1 | 1d | Died within 48 hours (2) | 2a | |||
| Not recovered (1) | 1e | 0 | NR (1) | 1 |
Daniel Woronow, MD
Thao Tran, PharmD
Amy Chen, PharmD
Monica Muñoz, PharmD,MS
Cindy Kortepeter, PharmD
Division of Pharmacovigilance
Office of Surveillance and Epidemiology Center for Drug Evaluation and Research
U.S. Food and Drug Administration Silver Spring, Md
The views expressed are those of the authors and not neces- sarily those of the U.S. Food and Drug Administration.
REFERENCES
- Deak ST. Retrograde administration of ultrasound-guided endovenous microfoam chemical ablation for the treatment of superficial venous insufficiency. J Vasc Surg Venous Lymphat Disord 2018;6:477-84.
- King JT, O’Byrne M; VANISH-1 Investigator Group. Treatment of truncal incompetence and varicose veins with a single administration of a new polidocanol endovenous microfoam preparation improves symptoms and appearance. Eur J Vasc Endovasc Surg 2015;50:784-93.
- Todd KL 3rd, Wright DI; VANISH-2 Investigator Group. Durability of treatment effect with polidocanol endovenous microfoam on varicose vein symptoms and appearance (VANISH-2). J Vasc Surg Venous Lymphat Disord 2015;3: 258-64.e1.
- U.S. Food and Drug Administration. Varithena. Full prescribing information. U.S. Department of Health and Human Services. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205098s026lbl.pdf. Accessed July , 2018.
- U.S. Food and Drug Administration. Asclera. Full prescribing information. U.S. Department of Health and Human Services. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021201s002lbl.pdf. Accessed July , 2018.
- U.S. Food and Drug Administration. Sotradecol. Full prescribing information. U.S. Department of Health and Human Services. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm setid¼f1756c28-dcd2-4b49-be62-07ca20682018.
Accessed July , 2018.
https://doi.org/10.1016/j.jvsv.2018.09.014
Reply
Reply
I thank Dr Woronow and colleagues for their letter to the Editor recognizing the absence of neurologic and cardiac adverse events (NCAEs) in my recently published case series regarding outcomes from 250 patients treated with Food and Drug Administration-approved
polidocanol microfoam 1%.1 The safety profile demon-
strated in phase 3 clinical trials was the rationale for incorporating this treatment in my practice in place of physician-compounded foam (PCF). The analysis in Dr Woronow’s letter revealed 23 leg vein sclerotherapy
NCAE cases with use of PCF. NCAE cases are likely the
result of gas emboli that occur in using foams made with room air that have a high nitrogen content. Polido- canol microfoam 1% has a low nitrogen content (<0.8%) to reduce the risk of neurologic complications.
Before adopting polidocanol microfoam 1% in my prac- tice, I refrained from using PCF because of the published reports of patients who suffered significant neurologic
events after treatment, including stroke, seizure, and
transient ischemic attack.2-7 I also noted that the exis- tence of a patent foramen ovale (PFO) may contribute to the increased risk of NCAE. In the analysis performed by Dr Woronow, more than half of the patients with NCAEs had a PFO. This incidence was similar to an anal- ysis of 82 patients undergoing polidocanol microfoam 1% ablation of the great saphenous vein.8 In that study,
61% of the patients were PFO positive. In another study, middle cerebral artery bubbles were detected during polidocanol microfoam 1% ablation in 89% of the PFO- positive patients and 29% of PFO-negative patients. No patients displayed evidence of cerebral or cardiac micro- infarction 30 days after treatment, nor did they display any adverse neurologic signs or elevated cardiac troponin I.9 Therefore, if arterial bubble emboli are unavoidable during the injection of sclerosant foam, it is critical to select a Food and Drug Administration- approved formulation that minimizes risk to the patient. I have since treated 420 patients with polidocanol
microfoam 1%. My patients continue to benefit from treatment, with no NCAEs reported.
Steven Deak, MD, PhD
Deak Vein NJ Clinic Somerset, NJ
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Hill DA. Neurological and chest symptoms following sclero- therapy: a single centre experience. Phlebology 2014;29: 619-27.
Parsi K. Paradoxical embolism, stroke and sclerotherapy. Phlebology 2012;27:147-67.
Engelberger RP, Ney B, Clair M, Dabiri A, Alatri A, Mazzolai L, et al. Myocardial infarction after ultrasound-guided foam sclerother- apy for varicose veinsda case report and review of the literature of a rare but serious adverse event. Vasa 2016;45:255-8.
Malvehy MA, Asbjornsen C. Transient neurologic event following administration of foam sclerotherapy. Phlebology 2017;32:66-8.
Wright DD, Gibson KD, Barclay J, Razumovsky A, Rush J, McCollum CN. High prevalence of right-to-left shunt in pa- tients with symptomatic great saphenous incompetence and varicose veins. J Vasc Surg 2010;51:104-7.
Regan JD, Gibson KD, Rush JE, Shortell CK, Hirsch SA, Wright DD. Clinical significance of cerebrovascular gas emboli during polidocanol endovenous ultra-low nitrogen micro- foam ablation and correlation with magnetic resonance im-
aging in patients with right-to-left shunt. J Vasc Surg 2011;53: 131-7.
