Central nervous system effects of alcohol at a pseudo-steady-state concentration using alcohol clamping in healthy volunteers.
OBJECTIVE
In determining the acute effects of alcohol, it is helpful if alcohol concentrations are maintained at stable levels, to facilitate the interpretation of the results. Recently, an alcohol clamping method was developed that resulted in stable alcohol concentrations for hours. The aim of this study was to test a range of central nervous system (CNS) effects under pseudo-steady-state conditions.


METHODS
To achieve a pseudo-steady state of 0.6 g l(-1), breath alcohol concentrations (BrAC) were frequently measured and fed back into a spreadsheet-based program to guide intravenous dosing. CNS effects were frequently measured throughout the clamp.


RESULTS
The clamping paradigm resulted in a pseudo-steady-state BrAC of 0.61 g l(-1) (coefficient of variation 6.2%). A plateau was maintained from 25 to 300 min and caused significant effects on smooth pursuit eye movements [-9.7%, 95% confidence interval (CI) -12.4, -7.1], adaptive tracking (-3.4%, 95% CI -4.5, -2.2), visual analogue scale (VAS) alertness (-13 mm, 95% CI -20, -6), VAS alcohol effects (16 mm, 95% CI 7, 25) and body sway (21.3%, 95% CI 1.8, 45). Some effects (like smooth pursuit eye movements) closely followed the relatively stable alcohol concentrations, whereas others (such as body sway and VAS alcohol effects) fluctuated during the plateau phase.


CONCLUSIONS
Most CNS effects of alcohol showed a trend to change over time, despite stable concentrations. Other variables remained stable under pseudo-steady-state conditions. The intravenous clamping method provides precise control over BrAC levels and allows frequent repetition of different CNS measurements. These features make this technique eminently suitable to study the complex pharmacodynamic effects of acute alcohol administration.
Centre for Human Drug Research, Central Laboratory for Clinical Chemistry, Leiden University Medical Centre, 2333 CL Leiden, the Netherlands. rzoethout@chdr.nl
Remco W M
RW
Zoethout
Rik C
RC
Schoemaker
Lineke
L
Zuurman
Hans
H
van Pelt
Albert
A
Dahan
Adam F
AF
Cohen
Joop M A
JM
van Gerven
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001944:Breath Tests / Q000379:methods; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000009:adverse effects*; D003250:Constriction; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D055815:Young Adult
D002492:Central Nervous System Depressants; D000431:Ethanol