The Effects of Short Intravenous Infusions of Thiopentone on Myocardial Function, Blood Flow and Oxygen Consumption in Sheep

Huang, Yi; Upton, Richard N.; Gray, Elke C.; Grant, Cliff; Zheng, D.; Ludbrook, Guy L.

doi:10.1177/0310057x9702500605

Cited by 8 publications

(6 citation statements)

References 23 publications

(40 reference statements)

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“…Although rac ‐thiopentone has a long history of successful clinical use it also has some recognized drawbacks. It causes myocardial and respiratory depression, and its repeated use leads to prolonged time to awakening (Crankshaw, 1987; Hirshman et al ., 1975; Huang et al ., 1997; Upton et al ., 1997). We believe that there is now sufficient evidence to suggest that substitution of enantiopure R‐thiopentone for the clinically used rac ‐thiopentone may have merit.…”

Section: Discussionsupporting

confidence: 94%

Electroencephalographic effects of thiopentone and its enantiomers in the rat: correlation with drug tissue distribution

Mather

Edwards

Duke

1999

British J Pharmacology

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1 To better understand the pharmacology of the thiopentone enantiomers, we studied their quantitative electroencephalographic e ects and their distribution into vital tissues. 2 Adult Wistar rats were infused with rac-, R-or S-thiopentone at 4 mg kg 71 min 71 until death ensued. The EEG signal was acquired continuously; serial arterial plasma and terminal tissue thiopentone concentrations were measured enantiospeci®cally. Relevant drug tissue : plasma distribution coe cients and plasma concentration-EEG e ect relationships were determined. 3 Doses (mg kg 71 ) (mean+s.e.mean) for anaesthesia (toe pinch) and lethality (respiratory failure), respectively, decreased in the order R-thiopentone (55.8+2.4 and 176.2+11.2)4 rac-thiopentone (39.3+2.1 and 97.5+3.9)4 S-thiopentone (35.6+1.9 and 74.2+5.2); plasma drug concentrations (mg ml 71 ) decreased in the order R-thiopentone (66.3+4.5 and 89.8+5.2)4 rac-thiopentone (56.7+2.0 and 77.8+2.8)4 S-thiopentone (55.0+1.9 and 64.1+2.8). 4 Initial EEG activation was similar for all thiopentone forms. Plasma drug concentrations for the same extent of EEG deactivation re¯ected the potency order. 5 After infusion of rac-thiopentone, tissue : plasma distribution coe cients were higher for R-than for S-thiopentone in brain and visceral regions, but not in fat or muscle. After infusion of the separate enantiomers, the relative heart : brain distribution ratio was for S-thiopentone was double that for R-thiopentone. 6 The therapeutic index of R-thiopentone (3.16+0.14) was more advantageous than either racthiopentone (2.52+0.13) or S-thiopentone (2.10+0.14), possibly due to the relatively greater distribution into CNS tissues than heart. The data suggest that R-thiopentone could make a satisfactory single enantiomer substitute for rac-thiopentone. Keywords: Thiopentone; enantiomers; potency; tissue equilibration; blood-brain barrier Abbreviations: C max , plasma thiopentone concentrations corresponding to E max ; CNS, central nervous system; CSP, chiral stationary phase; EEG, electroencephalogram; E max , maximum activation e ect; GABA, gamma-aminobutyric acid; HPLC, high performance liquid chromatography; IC, integrated circuit; IC 0 , plasma thiopentone concentrations corresponding to crossing the baseline EEG value; IC 50 , plasma thiopentone concentrations corresponding to 50% E max ; i.m., intramuscular; i.v., intravenous; m, nonlinear regression slope of line of best ®t from E max through the remaining data on plasma thiopentone concentration;

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Section: Discussionsupporting

confidence: 94%

Electroencephalographic effects of thiopentone and its enantiomers in the rat: correlation with drug tissue distribution

Mather

Edwards

Duke

1999

British J Pharmacology

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“…18 Previous work has shown that thiopental 750 mg over 2 min transiently reduced cardiac output for approximately 6 min to a minimum of 75% of baseline. 19 Given the fundamental role of cardiac output in this type of model, 11 it was felt the model should account for this observation. Hybrid effect compartment analysis with linear, Emax and sigmoid Emax dynamic models were used to compare the time course of changes in cardiac output with the time course of arterial concentrations of thiopental.…”

Section: Thiopental Effects On Cardiac Outputmentioning

confidence: 99%

A model of the kinetics and dynamics of induction of anaesthesia in sheep: variable estimation for thiopental and comparison with propofol

Upton

Ludbrook

1999

British Journal of Anaesthesia

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We describe a six-compartment kinetic and dynamic physiological model of induction of anaesthesia with thiopental. The model included an accurate account of initial drug distribution by representing the inter-relationships between initial vascular mixing, lung kinetics and cardiac output, and the use of the brain as the target organ for anaesthesia (two-compartment sub-model with slight membrane limitation). It also accounted for thiopental-induced reductions in cerebral blood flow and cardiac output. Parameters for the model were estimated using hybrid modelling from an extensive in vivo data set collected in sheep. Simulations were used to compare the properties of the thiopental model with an analogous previously published model of propofol. Differences in the blood:brain equilibrium half-lives of thiopental (1.22 min) and propofol (4.32 min) contributed to significant differences in the predicted optimal rate of bolus injection of each agent for inducing anaesthesia in sheep.

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“…This finding agrees with the work done by Pundits (2008) who discovered the occurrence of respiratory depression and apnoea after thiopental administration. Similarly, earlier studies have shown that thiopentone injection caused pulmonary depression (Gaudy et al, 1983;Huang et al, 1997;Gargiulo et al, 2012).…”

Section: Discussionmentioning

confidence: 62%

Comparative Evaluation of Thiopental Sodium and Ketamine Hydrochloride ‎in the Maintenance of General Anaesthesia during Exploratory Laparotomy ‎in Nigerian Indigenous Dogs

Sani

Khan

et al. 2022

SJVS

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This study was conducted to evaluate the effects of thiopental sodium and ketamine hydrochloride on rectal temperature, pulse and respiratory rates, anaesthetic duration/recovery time indogs during the maintenance of general anaesthesia post-induction with thiopental sodium. Ten apparently healthy male and female dogs, aged 12-30 months, weighing 7-14 kg were divided into two groups of 5dogs each. Atropine (0.02 mg/kg) and chlorpromazine (4 mg/kg) were used for premedication. Thiopental sodium (20 mg/kg) was used for induction and maintenance in group A while dogs in group B were given thiopental sodium (20 mg/kg) for induction and ketamine hydrochloride (20 mg/kg) for maintenance. Duration of anaesthesia to recovery time, and vital parameters were monitored and recorded accordingly. Results revealed group A had significantly (p<0.001) prolonged duration of anaesthesia to recovery time (400 minutes) when compared to group B (200 minutes). Significant decrease was however observed in rectal temperature of group A at 50 minutes (p< 0.05), 60-90 minutes (p<0.01) and100-110 minutes (p<0.001) when compared to group B. Similarly, the respiratory rates of dogs in group A showed significant decrease at 50 minutes (p< 0.01), 60-110 minutes (p< 0.001) when compared to group B. There was no significant (p> 0.05) effect in the pulse rates of either group. It was concluded that a relative shorter recovery time, stability in rectal temperature, pulse and respiratory rates in the group maintained with ketamine hydrochloride were observed when compared to the group induced and maintained with thiopental sodium.

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The Effects of Short Intravenous Infusions of Thiopentone on Myocardial Function, Blood Flow and Oxygen Consumption in Sheep

Cited by 8 publications

References 23 publications

Electroencephalographic effects of thiopentone and its enantiomers in the rat: correlation with drug tissue distribution

Electroencephalographic effects of thiopentone and its enantiomers in the rat: correlation with drug tissue distribution

A model of the kinetics and dynamics of induction of anaesthesia in sheep: variable estimation for thiopental and comparison with propofol

Comparative Evaluation of Thiopental Sodium and Ketamine Hydrochloride ‎in the Maintenance of General Anaesthesia during Exploratory Laparotomy ‎in Nigerian Indigenous Dogs

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