QUANTITATION OF DEPTH OF THIOPENTAL ANESTHESIA IN THE RAT

Background: In contrast to that of inhalational anesthetics, quantitat ion of anesthetic depth for,intravenous agents has not been well defin ed. In this study, using rodents, the relationship between the constan t plasma thioperital concentrations arid the clinical response to mult iple nociceptive stimuli were investigated characterizing the anesthet ic state from light sedation to deep anesthesia and correlated to the degree of electroencephalogram (EEG) drug effect. Methods: Thirty rats were instrumented with chronically implanted EEG electrodes, arterial and venous catheters. A computer-driven infusion pump was used to rap idly attain and then maintain constant, target plasma thiopental conce ntrations ranging from 7 io 100 mu g/ml. Three different target plasma thiopental concentrations were achieved in each rat. Electroencephalo graphic effects were monitored with aperiodic waveform analysis. The f ollowing nociceptive stimuli were applied: (1) unprovoked righting ref lex, (2) provoked lighting reflex, (3) noise stimulus, (4) tail clampi ng with an alligator clip, (5) constant tail pressure with an analgesi a-meter, (6) corneal reflex, and (7) tracheal intubation. For, tail cl amping, tail pressure, and intubation, either purposeful extremity mov ement or abdominal muscle contraction response was noted to be present or absent. The clinical responses (present dr absent) were modeled us ing logistic regression to estimate the CP50, the plasma thiopental co ncentration with a 50% probability of no response. Results:The followi ng mean Cp(50), values (95% confidence interval) were obtained: unprov oked righting reflex, 15.9 (15.1-16.6) mu g/ml; provoked righting refl ex, 21.4 (20.2-22.7)mu g/ml; noise stimuli, 31.3 (29.7-33.0) mu g/ml; tail clamp and limb movement, 38.3 (36.1-40.4) mu g/ml, tail pressure and limb movement, 39.2 (37.1-41.3) mu g/ml; tail pressure and abdomin al muscle contraction, 52.5 (50.0-55) mu g/ml; tail clamping and abdom inal muscle contraction, 56.1 (50.0-56.2) mu g/ml; corneal reflex, 60. 0 (56.6-63.4) mu g/ml; and limb movement or muscle abdominal contracti on response to intubation, 67.7 (59.2-76.1) mu g/ml. At an EEG-effect of 9.1 and 2.2 waves/s, there was a 50% chance of limb movement respon se to tan clamping add tracheal intubation, respectively. There was a poor relationship between the plasma thiopental concentration and the percent increase of either heart rite or mean arterial blood pressure after applying either tail pressure or tail clamp stimuli. Conclusions : A range of nociceptive stimuli and their observed clinical responses can be used to quantitate thiopental anesthetic depth, ranging from l ight sedation to deep anesthesia (isoelectric EEG and unresponsive to intubation) in the rodent. Clinical response can be mapped to surrogat e EEG measures.