HEPATOCELLULAR carcinoma accounts for 4.1% of all cancers, with an estimated 315,000 new cases reported per year. The time of diagnosis determines the type of treatment offered. Current therapeutic modalities include surgical resection, liver transplantation, local ablative techniques, and radiation and systemic therapy. 1
Local percutaneous intratumoral ablative therapy with ethyl alcohol was first described by Livraghi et al. 2in 1986. Percutaneous ethanol injection has traditionally been performed for hepatocellular carcinomas smaller than 5 cm, although in 1998, larger tumors were reported to have been treated during a single session under general anesthesia. 3Acute complications seen after percutaneous ethanol injection include bleeding, hemoglobinuria, fever, and inebriation (particularly in non-drinkers). In addition, there have been reports of sudden hypotension immediately after percutaneous ethanol injection therapy. 4,5Overall mortality associated with percutaneous ethanol injection is 0.6%, primarily as a result of the underlying illness. 4We report a case of a patient who experienced sudden cardiovascular instability during intraoperative percutaneous ethanol injection and was successfully resuscitated.
Case Report
A 67-yr-old man presented with a 15 × 23 × 24-cm hepatocellular carcinoma involving the right lobe of the liver and a smaller mass in the distal right lobe. Further workup revealed no invasion of the inferior vena cava or portal and suprahepatic veins. Preoperative embolization of the right intrahepatic portal vein was performed to induce hypertrophy of the left hepatic lobe, in anticipation of possible resection of the tumor.
In addition to standard monitors, radial arterial and internal jugular central venous catheters were placed percutaneously. General anesthesia was induced with sodium thiopental, vecuronium, and fentanyl and was maintained with isoflurane in oxygen–air delivered via mechanical ventilation.
Laparoscopy was performed to determine the resectability of the tumor. The large size of the tumor and the presence of extensive intraabdominal metastasis made the tumor nonresectable. Ultrasound evaluation of the tumor showed multiple intrahepatic arteriovenous shunts. A suitable nonvascular area in the tumor was identified, and percutaneous ethanol injection was performed. Twenty grams absolute alcohol (20 ml ethanol, 100%) was injected over 20 s under ultrasound guidance. Immediately after the injection, the patient’s blood pressure decreased precipitously from 120/80 mmHg to 60/40 mmHg. The electrocardiogram initially showed sinus tachycardia followed by profound sinus bradycardia at a rate of 30–40 beats/min. Twenty-five milligrams ephedrine, 1 mg atropine, and 200 μg phenylephrine were administered.
During cardiopulmonary resuscitation, end-tidal carbon dioxide (ETCO2) was noted to be 12 mmHg. After approximately 1 min, the patient’s blood pressure improved to 130/80 mmHg, and cardiopulmonary resuscitation was terminated. Blood gas analysis showed a mixed respiratory–metabolic acidosis (pH, 7.11; partial pressure of carbon dioxide [PCO2], 68 mmHg; and base excess, −9.4 mEq/l). His blood alcohol level was 50 mg/dl (0.05 mg/%). Sodium bicarbonate was administered to correct the underlying metabolic acidosis, and minute ventilation was adjusted to compensate for the respiratory acidosis.
A repeat blood gas analysis performed 30 min later showed a normalized acid–base status. When hemodynamic stability was achieved, transesophageal echocardiography was performed, which revealed adequate biventricular function, and no wall motion abnormalities or echogenic masses were seen in the pulmonary artery. The patient remained hemodynamically stable and was successfully extubated at the end of surgery. He was then transferred to the surgical intensive care unit for further monitoring. No neurologic deficits were found, and his postoperative period was uneventful.
Discussion
The mechanism of ethanol-induced tumor lysis is due to dehydration of cytoplasmic proteins with subsequent cellular destruction, followed by endothelial cell necrosis and platelet aggregation in small blood vessels, eventually leading to ischemia of the neoplastic tissue. 1
Routine blood sampling after intrahepatic injection reveals low concentrations of ethanol, suggesting at least partial absorption into the bloodstream. This increase is usually transient and devoid of significant hemodynamic abnormalities. Alternatively, the sudden entry of moderate to large doses of ethanol through the venous circulation may be associated with pulmonary vasoconstriction and increased right ventricular strain. In animal models, the acute intravenous administration of 0.5–1.5 g/kg absolute ethanol increased pulmonary vascular resistance and decreased right ventricular systolic function. 5,6
A study in healthy physician volunteers showed a significant increase in pulmonary vascular resistance 30 min after the oral ingestion of 0.5 g/kg ethanol diluted to 15%, with return to normal values after 60 min. 5Although the mechanism of ethanol-induced pulmonary vasoconstriction is not fully understood, there is some evidence that ethanol potentiates hypoxic pulmonary vasoconstriction. 7,8Pulmonary vascular resistance can remain increased for up to 2 h after the ingestion of ethanol, 5whereas the cardiovascular effects of ethanol seem to be dose dependent. Sarin et al. 9reported a minimal change in pulmonary hemodynamics when using doses of 8 –12 ml absolute alcohol for intravariceal sclerotherapy. However, in both animal and human models, doses of 0.5 g/kg or higher are associated with altered pulmonary and systemic hemodyamics. 5,10The combined effect of an acute increase in pulmonary vascular resistance and negative inotropism can precipitate acute cor pulmonale in susceptible individuals. Patients with primary and secondary pulmonary hypertension may be especially sensitive to the pulmonary vasoconstrictive effects of large doses of intravenous ethanol.
In the absence of other plausible explanations and the temporal correlation with the intrahepatic injection of ethanol, we concluded that our patient’s cardiovascular instability most likely was related to ethanol-induced pulmonary vasoconstriction and transient right ventricular dysfunction. Rapid institution of cardiopulmonary resuscitation, use of an indirect sympathomimetic to improve contractility, volume loading to improve ventricular end-diastolic volume, and the use of 100% fraction of inspired oxygen (Fio2) during resuscitation helped to ameliorate the detrimental effects of ethanol in this patient.
Oxygen supplementation has been shown to attenuate ethanol-induced pulmonary vasoconstriction in an animal model. 7Hypercarbia, acidosis, and hypothermia should be aggressively treated because of their propensity to increase pulmonary vasoconstriction. Phenylephrine, however, should be used cautiously in this setting because it may exacerbate the existing pulmonary hypertension. 11In the presence of systemic hypotension, restoration of coronary perfusion pressure with the use of an α1-adrenoreceptor agonist may offset any effects on the pulmonary circulation and thus improve right ventricular function. 12,13
In summary, acute pulmonary vasoconstriction should be strongly suspected in the presence of hemodynamic instability shortly after intrahepatic ethanol injection. Clinicians must institute measures to decrease pulmonary vascular resistance and improve right ventricular function immediately to minimize the possibility of cardiovascular collapse. In patients with preexisting pulmonary hypertension, caution should be exercised when using ethanol. Access to pulmonary vasodilators, pulmonary artery catheterization, or transesophageal echocardiography may also be helpful.
