Abstract
Purpose
To characterize the pharmacodynamic relationships between plasma pentobarbitone and thiopentone concentrations and nocifensive reflexes during emergence from anaesthesia.
Methods
Forty-nine rats were studied. Plasma barbiturate concentrations were measured with high performance liquid chromatography. Noofensive reflexes were assessed with the hindlimb withdrawal latency (WL) to heat and the somatic motor response threshold (SMRT) to tail pressure. In Protocol I, SMRT. WL. sedation, and the presence of paw-licking and the righting reflex were assessed in unrestrained rats before and every 10 min for two hours after an intrapentoneal injection of pentobarbitone (30 mg · kg−1). Plasma pentobarbitone kinetics were determined in a separate group of rats. In Protocol II. SMRT and drug concentrators were measured concurrently in partially restrained animals before and for 35 min after a computer-controlled iv bolus of thiopentone. In Protocol III the SMRT-plasma thiopentone relationship was determined during increasing and decreasing plasma thiopentone concentrations.
Results
Enhancement of both nocifensive reflexes was observed in the unrestrained animals. Enhancement of SMRT was maximal [175% (153–197) of control values] at a mean plasma thiopentone concentration of 11 (9–13) μg · ml−1. The SMRT-plasma thiopentone curve showed a mean efflux-influx difference in plasma thiopentone concentration of 4 (2.3–5.7) μg · ml−1.
Conclusion
Barbiturate-associated nocifensive reflex enhancement occurs in unrestrained animals with both thermal and pressure stimuli. The SMRT-plasma thiopentone concentraton relatonship during emergence from anaesthesia was similar to that observed previously during induction. The thiopentone plasma concentration-SMRT plot showed an equilibration delay similar to that previously described by others for thiopentone at an etectroencephalographic effect site.
Résumé
Objectif
Préciser les relations pharmacodynamiques entre les concentrations de pentobarbitone et de thiopentone et les réflexes nocifs de défense pendant le réveil anesthésique.
Méthodes
Quarante-neuf rats ont été étudiés. Les concentrations plasmatiques de barbituriques ont été mesurées par Chromatographie liquide à haute performance. Les réflexes nocifs de défense ont été évalués par la latence du retrait (LR) du membre postérieur provoqué par la chaleur et par te seuil de réponse motrice somatique (SRMS) au serrement de la queue. Dans te protocote I. le SRMS, la LR. le degré de sédation et l’existence du léchage de la patte et du réflexe de redressement ont été recherchés sur des rats sans contention avant et aux dix min pendant deux heures après une injecton intrapéntoméale de pentobarbitone (30 mg · kg−1). La Cinétique plasmatique du pentobarbitone a été déterminée chez un groupe séparé de rats. Dans te protocole II. le SRMS et les concentrations de thiopentone ont été mesurés simultanément chez des rats sous contention partielle avant et 35 min après l’administration contrôlée par ordinateur d’un bolus de thiopentone. Dans te protocole III. la relation entre le SRMS et la concentration de thiopentone a été déterminée au moment de la croissance et la décroissance plasmatique du thiopentone
Résultats
On a observé une facilitation des deux réflexes nocifs de défense chez les rats sans contenton. La facilitation du SRMS était maximale [ 175% (153 –197) des valeurs initiales] à la concentration plasmatique moyenne de thiopentone de II (9–13) μ · ml−1. La courbe SRMS/thiopentone a révélé une différence efflux-influx de la concentration plasmatique de thiopentone de 4 (2.3–5.7) g · ml−1.
Conclusion
Une facilitation du réflexe nocif de défense associée aux barbituriques suivent chez des rats sans con tenton stimulés par la chaleur ou la compresson. La relaton entre te SRMS et la concentraton plasmatique du thiopentone pendant te réveil anesthésique est identique à celte qui a déjà été observée à l’induction. Le graphique concentraton-SRMS montre un délai d’équilibraton identique a celui déjà décnt par d’autres pour te thiopentone au niveau d’un site effecteur électroencéphalographique.
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Archer, D.P., Samanani, N. & Roth, S.H. Nocifensive reflex thresholds in rats: measures of central nervous system effects of barbiturates. Can J Anaesth 44, 765–774 (1997). https://doi.org/10.1007/BF03013393
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DOI: https://doi.org/10.1007/BF03013393