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Methyl tert-butyl ether dissolves cholesterol gallbladder stones when infused through a percutaneous transhepatic catheter. All gallstones, however, contain noncholesterol components that are insoluble in lipid solvents and may be too large to be aspirated through a small catheter or flushed from the gallbladder. To identify which patients have gallstones that are most likely to completely dissolve, we evaluated the ability of methyl tert-butyl ether to dissolve gallstones in vitro based on their radiodensity and size. Radiodensity influenced completeness of dissolution (p less than 0.01), but size did not (p greater than 0.5). Twenty-six of 32 radiolucent stones (81%) dissolved completely, leaving residual debris less than 2 mm in diameter. Only 2 of 32 radiopaque stones (6%) dissolved completely. Insoluble radiolucent and radiopaque stones less than 0.5 cm in diameter were black pigment stones. Four radiolucent and 19 of 22 radiopaque stones (86%) greater than 0.5 cm in diameter underwent partial dissolution leaving residual debris 2 mm or larger. By infrared spectroscopy, calcium bilirubinate and calcium carbonate were identified as the principal components of this methyl tert-butyl ether-insoluble debris. Until methods for dissolving or fragmenting noncholesterol components of gallstones are available, only patients with radiolucent gallstones should be treated with methyl tert-butyl ether.

Methyl tert-butyl ether rapidly dissolves cholesterol gallstones, although insoluble debris may remain. Total gallstone dissolution could be achieved if safe solvents for these noncholesterol components can be developed. We evaluated the in vitro ability of ethylenediaminetetraacetic acid, citrate, dimethyl sulfoxide, and ionic or nonionic detergents to dissolve the predominantly calcium bilirubinate and calcium carbonate debris remaining after methyl tert-butyl ether gallstone dissolution. Ethylenediaminetetraacetic acid 1% or 2% at pH 9.5 was the most effective of the solvents studied for dissolving calcium and bile pigment. The addition of cholate (25-200 mM) or polysorbate (1%-10%) to ethylenediaminetetraacetic acid 1% at pH 9.5 enhanced pigment dissolution compared to ethylenediaminetetraacetic acid alone. Dissolution of pellets prepared from human gallstones and composed predominantly of either calcium bilirubinate or calcium carbonate was 80% and 85% at 4 h using ethylenediaminetetraacetic acid 1% plus polysorbate-20 1% at pH 9.5. We conclude that ethylenediaminetetraacetic acid, either alone or with a detergent, is an effective solvent for methyl tert-butyl ether-insoluble gallstone debris and deserves assessment in vivo.