Treatment Options for AVMs
Treatment options for AVMs have improved dramatically in the past decade. The goal of treating an AVM is to completely close off the abnormal vessels, thereby curing the patient. This can be achieved in a variety of ways and requires a team of highly experienced specialists to provide the safest methods available posing minimal risks for individuals with AVMs.
Types of Treatments Available for AVMs
In many cases, surgery may be recommended to completely remove the AVM. This is appropriate when the AVM is small and located on the surface of the brain or spinal cord. When the AVM is deep in the brain, other minimally invasive techniques are used to prevent damage to surrounding tissue.
The history behind absolute ethanol as an intravascular embolic agent, its mechanism of action, and applications of its use.
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.
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.
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 email@example.com.
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THREE YEAR OUTCOME OF BLEOMYCIN SCLEROTHERAPY TREATMENT OF VASCULAR ANOMALIES: CLEVELAND VASCULAR MALFORMATION GROUP RESULTS
1 Plastic and Reconstructive Surgery Department, James Cook University Hospital, Middlesbrough, North Yorkshire, UK
2 Paediatric Department, James Cook University Hospital, Middlesbrough, North Yorkshire, UK
3 Medical Department, James Cook University Hospital, Middlesbrough, North Yorkshire, UK
4 Anaesthetic Department, James Cook University Hospital, Middlesbrough, North Yorkshire, UK
5 Psychology Department, James Cook University Hospital, Middlesbrough, North Yorkshire, UK
Introduction and aims: Intralesional bleomycin sclerotherapy has been offered to 63 of 238 patients presenting with haemangiomas and vascular malformations in our centre over the last three years.
Methods: Clinical response, administered dose, amount of sessions and complications were recorded. 42 of the 66 patients have completed their treatment thus far. Respiratory surveillance is provided by an adult and paediatric pulomonologist utilising the locally agreed Cleveland malformation surveillance protocol.
Results: Thirteen children and 29 adults completed treatment with a mean of 3.4 sclerotherapy sessions. 17% of children treated were under the age of 1. Treatment lasted for an average of 88 days. 43% of patients received prior treatment other than bleomycin. The following pathologies were treated: haemangioma 10, venous malformation 26, lymphatic malformation 4, capillary malformation 1, AVM 1. Complete resolution occurred in 66%, with an overall response rate of 98%. Skin ulceration occurred in 1 patient, minor blistering in 5, infection 1, swelling 1, headache 1, bruising, skin rash 1 and skin pigmentation occurred in 3 patients. The maximum administered dose was 3 mg/kg.
Conclusion: Predictable results were obtained with a high success rate. No systemic or pulmonary complications occurred. Secondary treatment, apart from bleomycin sclerotherapy was only needed in two patients with partially resoluted hemangiomas.