Percutaneous sclerotherapy is well established as an effective treatment for low-flow vascular malformations, especially venous and lymphatic malformations.1 Compared with surgery, this procedure has the advantages of avoiding external scarring, nerve damage, massive bleeding, and/or deformity.2 Among the various sclerosing agents, ethanol is the most popular because it has a potent therapeutic effect with the lowest rate of recurrence of malformations.3,4
Although there are therapeutic advantages, ethanol sclerotherapy for vascular malformations can cause several complications. In most cases, ethanol sclerotherapy requires general anesthesia because of pain after injection.5 Acute complications that the anesthesiologist should be aware of include postanesthetic sedation enhanced by narcotics, hemolysis with subsequent hemoglobinuria,6,7 and potentially life-threatening cardiovascular effects such as circulatory collapse, pulmonary hypertension, and pulmonary embolus.5,8–10 Bronchospasm is an uncommon complication when ethanol is injected into vascular malformations. The following case report describes a patient who developed repetitive acute bronchospasm precipitated by a percutaneous ethanol injection into a craniofacial venous malformation.
The patient provided permission to publish his case.
A 36-year-old, 91 kg Japanese man with craniofacial venous malformations was admitted to the hospital. A magnetic resonance imaging and ultrasound examination revealed extensive venous malformations spreading from his left cheek to his pharynx, lower lip, and left cervical area, with several minute arteriovenous shunts. Because of enlargement of the cervical venous malformations and a complaint of dyspnea, the patient had undergone a tracheotomy at the age of 20 years. Apart from obesity (body mass index; 32.2) and a coagulopathy due to the giant venous malformation, the patient was otherwise well. He did not use tobacco or alcohol. He had no history of asthma or allergic reaction to contrast medium. He had undergone multiple uneventful procedures under general anesthesia for ethanol sclerotherapy of this lesion and a laparoscopic repair of an inguinal hernia.
The patient was brought into an operating room designed for image- and ultrasound-guided procedures. Routine patient monitoring included 3-lead electrocardiogram, noninvasive arterial blood pressure monitoring, measurement of oxyhemoglobin saturation (SpO2), and urine output. Anesthesia was induced with 200 mg propofol and 100 μg fentanyl. An 8.0-mm inner diameter cuffed flexible tube was inserted through the tracheotomy, and its position confirmed after auscultation of both sides, equal breath sounds, and positive end-tidal CO2. Muscle relaxation was then attained with 50 mg rocuronium. Anesthesia was maintained with oxygen, air, and sevoflurane (1.5%–2% end-tidal concentration) with continuous infusion of remifentanil (0.1–0.2 μg/kg/min). Mechanical ventilation by using a Draeger AV-2 ventilator (North American Draeger, Telford, PA) was adjusted to maintain end-tidal CO2 between 30 and 37 mm Hg, achieving tidal volumes of approximately 650 mL and peak airway pressures of 14 to 18 cm H2O. The patient was in a supine position. The patient’s hemodynamic and respiratory variables remained stable before intralesional injection of ethanol. The airway pressure of pressure-limited ventilation was adjusted to 14 cm H2O, and the SpO2 was 99% with end-tidal CO2 level of 33 to 37 mm Hg and a tidal volume of 550 to 600 mL. His heart rate and arterial blood pressure were stable in the range of 60 to 70 bpm and 95/55 mm Hg, respectively.
Sclerotherapy was scheduled to be performed in 2 distinct parts: the posterior pharyngeal region with image guidance and the left cervical area under ultrasound guidance. After the radiographic-guided identification of the treatment area with a contrast agent (iopamidol), a bolus of ethanol was initially injected into the posterior pharyngeal region. In this area, sclerotherapy was performed with a mixture of absolute ethanol and contrast medium (oypalomin) in a respective proportion of 90% to 10%. Within a minute after the initial ethanol injection (1.8 mL), acute ventilation difficulty and tachycardia developed. His tidal volume decreased from 550 to 300 mL at 14 cm H2O of airway pressure, and the SpO2 decreased from 99% to 96% on an FIO2 of 50%. His airway pressure increased to a peak of 30 cm H2O. At this time, mild bronchospasm or breath-holding was suspected, and the lungs were manually ventilated by using a lung recruitment maneuver. The SpO2 increased to 100%, and the peak inspiratory pressure returned to 15 cm H2O. His arterial blood pressure remained stable throughout the episode. Because the desaturation at this time was mild and transient, sclerotherapy was resumed. During the procedure, the patient gradually developed cutaneous flushing in his face and body.
Sclerotherapy proceeded to the cervical area under ultrasound guidance. When the total amount of absolute ethanol reached approximately 4 mL (in the cervical area), the patient again developed profound bronchospasm and tachycardia. His airway pressure increased to a peak of 50 cm H2O, and tidal volume decreased to 100 mL at this airway pressure. The SpO2 decreased from 99% to a low of 79%, heart rate increased from 62 to 80 bpm, and arterial blood pressure was stable at 80/55 mm Hg. Audible wheezing with greatly diminished respiratory excursions was observed. His lungs were manually ventilated and the FIO2 was increased from 40% to 100% oxygen and the inspired sevoflurane concentration was transiently increased to 5%. After this, 200 mg hydrocortisone was administered IV, and sevoflurane was immediately decreased to the baseline concentration. The bronchospasm gradually resolved, and peak airway pressure diminished within 5 minutes. The patient’s arterial blood pressure remained stable throughout the episode.
Further use of ethanol was abandoned because of our concern of another bronchospastic reaction to the ethanol. At this point, the total amount of absolute ethanol used was 28 mL Sclerotherapy with another agent, polidocasclerol, was resumed uneventfully. Recovery from anesthesia was uneventful, and the patient remained at his neurologic baseline without sequelae. After overnight observation in the intensive care unit, the patient was discharged without any further complications.
Although many complications during ethanol sclerotherapy have been documented in the literature, little is known about the temporal relationship between ethanol sclerotherapy for venous malformation and bronchospasm. The exact mechanism for ethanol-induced bronchospasm remains unknown. However, several theories have been proposed to explain bronchospasm precipitated by ethanol injection, including a direct toxic effect of ethanol on the bronchial smooth muscle and acetaldehyde-induced release of histamine.11
During sclerotherapy, ethanol can flow out from the target vessels.7 When the dose of ethanol is massive, a high concentration of ethanol can reach the pulmonary capillary bed immediately after the injection. This may induce pulmonary precapillary spasm, increasing pulmonary artery pressure, and subsequently decreasing right ventricular contractility.8 This sequence has been assumed to explain the pathophysiology underlying the life-threatening effect of ethanol, injected IV, such as circulatory collapse and pulmonary hypertension on cardiovascular systems. Smooth muscle spasm in the thoracic cavity can also interfere with the contractility of bronchiole vasculature,11 causing bronchoconstriction. In the present case, because severe bronchospasm occurred immediately after the bolus ethanol injection, we suspected that the anatomic course in the venous malformations (pharyngeal or cervical area) led to a nontarget bolus of ethanol provoking a toxic effect on the bronchiolar vasculature.
In addition to the direct toxic effect of ethanol, it is likely that the metabolite of ethanol, acetaldehyde, is also a factor in ethanol-induced bronchospasm. Although 2% to 10% of ingested ethanol is eliminated in exhaled air or in the urine, ethanol is metabolized primarily in the liver. In the liver, ethanol is degraded into acetaldehyde, which is degraded by aldehyde dehydrogenase (ALDH) into acetic acid and water. ALDH deficiency is seldom observed in Caucasians and Africans, while it is present in approximately 50% of the Japanese population.12 The lack of ALDH often causes an increased serum concentration of acetaldehyde and subsequent release of intrinsic histamine. It is important to note that histamine produces contractile effects on smooth muscles and capillary dilation. The time required for metabolism of alcohol is unclear; however, several reports have indicated that this alcohol-induced asthma can occur within 15 to 30 minutes of alcohol intake.13,14 This may indicate rapid alcohol metabolism and subsequent histamine release due to alcohol intake. Although the patient in this case had no history of asthma, obvious flushing of the face and body was observed during the procedures, suggesting alcohol and acetaldehyde intolerance. Therefore, we hypothesize that acetaldehyde and consequent release of histamine were the aggravating factors causing bronchospasm.
In this case, we were unable to measure the serum alcohol concentration. Several reports have shown a positive relationship between serum ethanol concentration and the amount of ethanol administered.7,15,16 Based on evidence obtained from the Asian population,15 the projected serum alcohol concentration after injection of 0.29 mL/kg ethanol in this patient was approximately 30 to 40 mg/dL,15 which may legally imply ethanol intoxication in Japan (maximum level, 30 mg/dL). In some Japanese patients, even a small amount of alcohol can cause acetaldehyde accumulation in the blood, leading to facial flushing and asthmatic attacks.13,17,18 Moreover, Bisdorff et al.19 demonstrated that an ethanol concentration >0.24 mL/kg can cause systemic toxic effects; therefore, they suggested limiting the dose of ethanol sclerotherapy used for venous malformation. In this regard, the ethanol dosage administered in this case could have been large enough to cause systemic complications, such as bronchospasm.
The reason for development of sudden bronchospasm in our patient is unclear, especially since he had undergone multiple previous ethanol sclerotherapies. For treatment of this extensive vascular malformation, the patient required multiple sclerotherapies with each treatment aimed at a different target area. We hypothesize that the target vessel selected for this case may have been one with high blood flow velocity, presumably near the jugular vein, causing rapid high ethanol concentration inflow into the pulmonary vessels. Since complex angioplasty for vascular malformation prevents prediction of the ethanol outflow pattern, anesthesiologists should be aware of the potentially serious ethanol-induced systemic complications throughout the procedure.
Although percutaneous ethanol sclerotherapy offers a minimally invasive treatment for venous malformations; it is associated with potential complications that are only now becoming apparent. Anesthesiologists should be aware that peripherally injected ethanol may produce a variety of cardiovascular and respiratory manifestations, including acute bronchospasm.
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