Endovascular treatment of arteriovenous malformation (AVM) with the Onyx Liquid Embolic System (Onyx; Micro Therapeutics, Inc., Irvine, California, USA) can achieve a high occlusion rate, enhance the safety of the operation and improve the clinical prognosis for the patients compared with other embolic agents [1,2]. The Onyx Liquid Embolic System is a newer embolic agent that was developed in the early 1990s . Onyx consists of ethylene vinyl alcohol dissolved in dimethyl sulphoxide (DMSO) and suspended micronized tantalum powder to provide contrast for visualization under fluoroscopy. In the present review, we report our experience with desaturation during embolization of AVMs.
Forty-six patients, 26 male and 20 female, 10–73 years of age (mean age 38.4 ± 16.75), who were treated for AVMs by an endovascular approach using Onyx over a period of 10 months (January–October 2008) were enrolled in this study. General anaesthesia was induced with propofol (2 mg kg−1), fentanyl (2 μg kg−1) and cicatracurium (0.15 mg kg−1) and was maintained with continuous intravenous remifentanil and sevoflurane (minimum alveolar concentration 0.5–0.8) in 50% O2–N2O. Ventilation was maintained to achieve a PaCO2 of 30–35 mmHg. Heart rate (HR), intraarterial blood pressure (IBP), oxygen saturation (SpO2) and end-tidal CO2 (EtCO2) values were continuously monitored. HR, IBP and SpO2 changes in response to DMSO and Onyx injection were recorded.
Seventeen of the patients developed desaturation during the infusion of DMSO; 11 of them demonstrated 3% desaturation from baseline, and six had severe desaturation (4–8% below baseline). None of these patients had any cardiological or pulmonary medical history. No significant changes in blood pressure (BP), HR or ECG were observed that could be attributable to DMSO infusion. The episodes of oxygen desaturation lasted a few minutes and the saturation returned to baseline, without any other clinical concerns during the procedure. Because of the fact that the desaturation was minimal, arterial blood gases were not taken. In only one case, in a patient with a giant AVM, we observed severe desaturation (SpO2 89%) after recovery from anaesthesia, accompanied by tachypnoea. The first arterial blood gases revealed hypoxaemia (pO2 61.8 mmHg). SpO2 gradually improved to 97%, pO2 returned to normal (pO2 92.3 mmHg) and the patient recovered fully 20 min later and was discharged from the postanaesthesia care unit. There were no other adverse events related to Onyx or anaesthesia. We saw no evidence of toxicity or any anaesthetic complications in our group of patients, our only clinical concern being a tendency to oxygen desaturation, lasting a few minutes with no clinical consequence.
The advantage of using Onyx is that it is a radio-opaque nonadhesive liquid embolic material easily injected through a microcatheter. It eliminates the risk of gluing the catheter to the vessel and therefore allows a longer injection time and a wider range of different injection rates. The disadvantage of Onyx is that it uses DMSO as a solvent. DMSO is a hydrogen-bound disrupter, a cell-differentiating agent and a hydroxyl radical scavenger and has been used as an anticancer and an analgesic agent . If given in too high a volume or concentration, or if it is injected too fast, DMSO is potentially toxic to blood vessels and may lead to acute vessel damage, vasospasm, endothelial necrosis and severe inflammatory response in the arterial wall . Dudeck et al. report that DMSO induced the most pronounced vasospasm with the longest recovery period of all solvents investigated. The systemic side effects of DMSO vary from bronchospasm and pulmonary oedema to vasospasm and cardiac arrest [3,5]. Systemic toxicity, resulting in cardiac complications, has therefore been a major concern [2,6].
Previous studies had focused on comparing the effects of different solvents on BP, HR and ECG without, however, commenting on Onyx injection and SpO2. Pamuk et al. demonstrated oxygen desaturation in the postoperative period for patients undergoing embolization of aneurysms using a combination of Onyx and stainless-steel stents. In the embolization of AVMs, not only is the percentage of DMSO higher than that used for aneurysms but also larger volumes are given with repeated injections of DMSO; this may result in a potentially higher risk of complications.
In our case series, desaturation was an event with more than one possible explanation. It can be attributed to a reduction in vital lung capacity after injection of DMSO. For instance, the patient with severe desaturation was unable to achieve maximal expiration and increase the inspiratory volume capacity over the tidal volume (resting) when she was prompted to do so. There was no evidence of atelectasia due to anaesthetic agents, so one can hypothesize that the vital capacity was affected by the injection of DMSO. Prospective studies on pulmonary function in these cases should help clarify the mechanism of hypoxaemia.
Although it is known that most of the DMSO metabolites are eliminated through the kidneys, some of the early elimination occurs via the skin and lungs. Dilution of oxygen in the lungs may cause a relative decrease in the partial pressure of oxygen in the alveoli. Desaturation cannot be attributed to the use of dyes such as methylene blue and indocyanine green as these agents are not routinely used during embolizations.
The patient with severe desaturation of SpO2 after extubation did not experience any respiratory distress or hypotension, and the PaO2–FiO2 was more than 200, so the possibility of pulmonary oedema and acute respiratory distress syndrome could not be established. Intraoperative embolism by air or Onyx is unlikely because patients did not present with tachycardia, systemic hypotension or cardiac arrhythmia in the intraoperative and postoperative period, and, also, the EtCO2 did not change in any of the patients.
Therefore, a larger prospective randomized study is needed to confirm our observation and explain its cause. Such a study should also include a longer follow-up period of oxygen monitoring.
1 Katsaridis V, Papagiannaki C, Aimar E. Curative embolization of cerebral arteriovenous malformations (AVMs) with Onyx in 101 patients. Neuroradiology 2008; 50:589–597.
2 Lv X, Jiang C, Zhang J, et al
. Complications related to percutaneous transarterial embolization of intracranial dural arteriovenous fistulas in 40 patients. AJNR Am J Neuroradiol 2009; 30:462–468.
3 Santos NC, Figueira-Coelho J, Martins-Silva J, Saldanha C. Multidisciplinary utilization of dimethyl sulfoxide: pharmacological, cellular, and molecular aspects. Biochem Pharmacol 2003; 65:1035–1041.
4 Dudeck O, Jordan O, Hoffmann KT, et al
. Organic solvents as vehicles for precipitating liquid embolics: a comparative angiotoxicity study with superselective injections of swine rete mirabile. AJNR Am J Neuroradiol 2006; 27:1900–1906.
5 Murugesan C, Saravanan S, Rajkumar J, et al
. Severe pulmonary oedema following therapeutic embolization with Onyx for cerebral arteriovenous malformation. Neuroradiology 2008; 50:439–442.
6 Laurent A, Mottu F, Chapot R, et al
. Cardiovascular effects of selected water-miscible solvents for pharmaceutical injections and embolization materials: a comparative hemodynamic study using a sheep model. PDA J Pharm Sci Technol 2007; 61:64–74.
7 Pamuk AG, Saatci I, Cekirge HS, Aypar U. A contribution to the controversy over dimethyl sulfoxide toxicity: anesthesia monitoring results in patients treated with Onyx embolization for intracranial aneurysms. Neuroradiology 2005; 47:380–386.