Embolotherapy is a burgeoning field developed by the subspecialties of interventional radiology and interventional neuroradiology and is rapidly being embraced by neurosurgeons, neurologists, vascular surgeons, and cardiologists who began performing minimally invasive catheter-directed procedures in recent years. The vast array of embolic agents that can be superselectively delivered with multiple catheter systems and direct puncture needles has blossomed due to the innovative ideas of numerous investigators and has led to improved quality and lower costs of care, quicker patient recuperation times, and the better outcomes that our patients deserve. This article describes the current uses of absolute ethanol as an embolic agent.

HISTORY

Particulate agents, coils, and detachable balloons dominated the early years of embolotherapy. Prof. Plinio Rossi was the first to develop selective catheter arteriography of the brachiocephalic arteries. In the late 1960s, Prof. Rossi had a scientific exhibit at Karolinska University Hospital in Stockholm, Sweden (P. Rossi, oral communication, September 1994; later collaborated by T. H. Newton, oral communication, October 1997) where he described his pioneering selective catheter technique to Prof. Hans Newton. Previously, only a technique using direct carotid injections with 18-gauge needles was employed. This method of selective catheterization along the carotid artery distribution gave rise to the concept of selective catheter delivery of contrast and embolic agents in other arterial anatomies as well.

In the late 1960s, Prof. Fedor A. Serbinenko pioneered catheter systems to navigate the internal carotid artery to the level of the cavernous carotid artery to deliver his hand-made detachable balloons to treat carotid-cavernous fistulas, either resulting from trauma or aneurysm rupture.1 By the early 1970s, Prof. Charles Kerber began working with isobutyl cyanoacrylate (IBCA).2 When he finished his neuroradiology fellowship under Prof. Newton, he then became a staff neuroradiologist at the University of Oregon Health Sciences Center in Portland, Oregon (as an aside, Prof. Kerber performed the first carotid angioplasty). 3

Prof. Kerber took the next step and developed microcatheter systems to navigate the cerebral vasculature (a calibrated-leak balloon catheter system) and many other pioneering developments.4 Because the lumen size of the calibrated-leak balloon system was small (no wire system was developed for it yet), only liquid agents were able to be injected through this catheter system. Prof. Kerber then integrated his work with IBCA, making embolization of cerebral arteriovenous malformations (AVMs) possible. Prof. Charles Dotter broke into Prof. Kerber's desk to use the IBCA to close pelvic vasculature trauma while Prof. Kerber was on vacation (C. Kerber, oral communication, July 1998).

Because the concept of selective catheterization in arterial systems was firmly in place, investigators aggressively pursued transcatheter delivery of many embolic agents. Dr. Brian Elman first developed preoperative transcatheter embolization of renal cell carcinomas with absolute ethanol.5 Absolute ethanol proved to be a superior embolic agent to particle and coil renal artery embolization due to the absence of any postembolization infarction syndrome. Other indications for the use of absolute ethanol soon came to light (see the Current Indications for the Use of Ethanol as an Embolic Agent sidebar).6

CARDIOPULMONARY COLLAPSE ISSUES

Before the etiology of postethanol injection-cardiopulmonary (CP) collapse was elucidated, it was a rare but dire complication. A bolus of ethanol reaches the pulmonary vascular bed, and pulmonary artery spasm can then occur. If the spasm becomes severe enough, it can lead to pulmonary hypertension and right heart failure, which causes decreased left heart filling and resultant systemic hypotension. Severe systemic hypotension causes decreased coronary artery perfusion. If severe enough, this can lead to cardiac arrhythmias such as electromechanical dissociation and asytole.

Prof. Young Soo Do and coinvestigators7 published an AVM treatment series showing that if the operator does not exceed 0.14 mL of ethanol/kg of body weight during a 10-minute period, CP collapse will not occur. I did a prospective in-house study of > 200 consecutive procedures in conjunction with my anesthesiologists. When treating high-flow lesions (AVMs/arteriovenous fistulas [congenital and acquired]), as well as low-flow lesions (venous malformations, lymphatic malformations, mixed lesions), with endovascular ethanol in doses of 0.1 mL/kg ideal body weight every 10 minutes, pulmonary pressures never increased to any significant degree, and CP collapse was obviated. Therefore, if one stays within these parameters for any intravascular ethanol procedure, CP collapse should not occur.

If a patient has pulmonary hypertension (whatever the etiology), they should have an arterial line placed and Swan-Ganz catheter monitoring of pulmonary pressures during the ethanol procedure. Small ethanol amounts can worsen their pulmonary hypertension and cause CP collapse.

MECHANISM OF ACTION

Absolute ethanol is a liquid embolic agent that penetrates to the capillary bed levels. Because of the distal penetration to the capillary bed level, tissues are totally devitalized, and infarcted collateral flow cannot occur. Therefore, great care and vigilance must be maintained to prevent unwarranted, nontarget embolization of vascular territories with ethanol. When injected into any vascular space (arterial, venous, lymphatic), ethanol denudes the endothelial cell from the vascular wall and precipitates its protoplasm. The denuded vascular wall is then fractured to the level of the internal elastic lamina. Platelet aggregation then occurs on the fractured and denuded vascular wall. Thus, thrombosis occurs beginning at the vascular wall with more and more accumulation until it thromboses centrally in the vascular lumen.

In vascular malformations, the endothelial cell is the reason recurrences are so common with embolic agents other than ethanol. The acute thrombosis that occurs with any embolic agent (polyvinyl alcohol, coils, glues, etc.) produces an ischemic state that is sensed by the intact endothelial cell lining of all vascular surfaces. Reacting to the acute ischemic state caused by the thrombosis, the endothelial cell releases chemotactic cellular factor and angiogenesis factor. Chemotactic cellular factor causes the migration of macrophages that carries off the intravascular debris formed during the embolization procedure. After there is significant debris removal, the endothelial cell then re-endothelializes the “new” lumen, which recanalizes the vascular malformation, leading to recurrences. The angiogenesis factor secreted by the endothelial cell stimulates new vascularity to the thrombosed ischemic area of the vascular malformation. This is called the “neovascular stimulation phenomenon” or “neovascular recruitment phenomenon.”

By using ethanol as an embolic agent, you can destroy the endothelial cell, and these two phenomena of recanalization and neovascular recruitment are noticeably absent. Thus, there is a permanence of treatment, and cures are now possible.

SUMMARY

Absolute ethanol as an intravascular embolic agent must be respected. Inadvertent nontarget ethanol embolization must be completely obviated or devitalization of tissues with resultant necrosis will invariably occur. Unopacified ethanol as an embolic agent can be challenging to use successfully when one is only used to visualizing embolic agents fluoroscopically. Adhering to an ethanol injection protocol that does not exceed 0.1 mL/kg ideal body weight every 10 minutes will obviate the need for Swan-Ganz catheter monitoring of pulmonary artery pressure and arterial line monitoring of systemic arterial pressures unless the patient suffers from chronic pulmonary artery hypertension. Absolute ethanol has many indications for the treatment of the previously listed pathologic conditions, and investigators will invariably develop more indications for its use in the future.

Wayne F. Yakes, MD, FSIR, FCIRSE, is the Founder and Director of the Vascular Malformation Center in Englewood, Colorado. He has disclosed that he has no financial interests related to this article. Dr. Yakes may be reached at wayne.yakes@vascularmalformationcenter.com.

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