Accelerated ethanol elimination via the lungs

Abstract

Ethanol poisoning is endemic the world over. Morbidity and mortality depend on blood ethanol levels which in turn depend on the balance between its rates of absorption and clearance. Clearance of ethanol is mostly at a constant rate via enzymatic metabolism. We hypothesized that isocapnic hyperpnea (IH), previously shown to be effective in acceleration of clearance of vapour anesthetics and carbon monoxide, would also accelerate the clearance of ethanol. In this proof-of-concept pilot study, five healthy male subjects were brought to a mildly elevated blood ethanol concentration (~ 0.1%) and ethanol clearance monitored during normal ventilation and IH on different days. IH increased elimination rate of ethanol in proportion to blood levels, increasing the elimination rate more than three-fold. Increased veno-arterial ethanol concentration differences during IH verified the efficacy of ethanol clearance via the lung. These data indicate that IH is a nonpharmacologic means to accelerate the elimination of ethanol by superimposing first order elimination kinetics on underlying zero order liver metabolism. Such kinetics may prove useful in treating acute severe ethanol intoxication.

Figure 1

Effect of isocapnic hyperpnea (IH) on ethanol elimination based on breathalyzer blood ethanol concentration measurements. (A) Schematic of the ClearMate^TM passive non- rebreathing, hyperoxic, IH circuit. (From Ref., Copyright (2011) John Wiley and Sons, Inc. Reprinted with permission from John Wiley and Sons, Inc.) (B) Breathalyzer measurements in subject 1 without and with IH started at the 70 min mark after alcohol ingestion. Linear, zero order elimination kinetics are demonstrated without IH (blue dashed line) while exponential first order elimination kinetics are demonstrated with IH (red line). (C) Normalized breathalyzer measures versus time for 5 male subjects demonstrating consistent zero order elimination kinetics without IH (dashed blue line) compared with first order elimination kinetics with IH (red line).

Figure 2

“Rebound” effect with intermittent IH. Breathalyzer measurements of subject 1 with two periods of intermittent IH demonstrate first order ethanol elimination kinetics while IH is performed, with a “rebound” increase in blood ethanol concentration when IH is ceased, followed by return to zero order elimination kinetics (red lines). However, the “rebound” occurs to a level below that expected if no IH had been performed, as demonstrated by offsets in the linear elimination kinetics after the first (*) and second (**) IH period; the offset increasing with the total duration of IH (black double arrows).

Figure 3

Effect of IH on blood ethanol concentration. (A) Arterial and venous blood ethanol concentration measurements in subject 1 with two intermittent periods of IH performed. Clear establishment of a veno-arterial gradient that increases in magnitude with duration of IH is demonstrated. Similar results were observed in subject 2 (B).

Figure 4

Blood alcohol concentration after ingestion in a test subject with and without administration of CO₂. “The solid line representing the blood alcohol concentration on the first day when no carbon dioxide was given, and the broken line the concentration on the second day when carbon dioxide was administered. The shaded area at the bottom of the chart shows the time during which carbon dioxide was given on this day.” (From Ref., Copyright (1924) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.).