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

Upton, Richard N.; Ludbrook, Guy L.

doi:10.1093/bja/82.6.890

Cited by 37 publications

(31 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also our assumption of the fractional blood flow to FT is in accordance with that of q F ϭ 0.17 in rats (Ebling et al, 1994). Furthermore, a fractional blood flow to fat of 9.7% has been reported for the dog (Brown et al, 1997), a value of 11% has been estimated for perfusion of the slowly equilibrating compartment (Avram et al, 2002), and a value of 25% has been assumed for the tissue pool with the higher distribution volume in a circulatory compartment model of thiopental kinetics in sheep (Upton and Ludbrook, 1999). The diffusional equilibration time in nonfat tissues, d NF ϭ 11.7 min, is shorter than that in fat, d F ϭ 131.4 min.…”

Section: Discussionsupporting

confidence: 64%

A Minimal Physiological Model of Thiopental Distribution Kinetics Based on a Multiple Indicator Approach

Weiß

Krejcie²,

Avram³

2007

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:Currently available models of thiopental disposition kinetics using only plasma concentration-time data neglect the influence of intratissue diffusion and provide no direct information on tissue partitioning in individual subjects. Our approach was based on a lumped-organ recirculatory model that has recently been applied to unbound compounds. The goal was to find the simplest model that accounts for the heterogeneity in tissue partition coefficients and accurately describes initial distribution kinetics of thiopental in dogs. To ensure identifiability of the underlying axially distributed capillary-tissue exchange model, simultaneously measured disposition data of the vascular indicator, indocyanine green, and the marker of whole body water, antipyrine, were analyzed together with those of thiopental. A model obtained by grouping the systemic organs in two subsystems containing fat and nonfat tissues, successfully described all data and allowed an accurate estimation of model parameters. The estimated tissue partition coefficients were in accordance with those measured in rats. Because of the effect of tissue binding, the diffusional equilibration time characterizing intratissue distribution of thiopental is longer than that of antipyrine. The approach could potentially be used in clinical pharmacokinetics and could increase our understanding of the effect of obesity on the disposition kinetics of lipid-soluble drugs.

show abstract

Section: Discussionsupporting

confidence: 64%

A Minimal Physiological Model of Thiopental Distribution Kinetics Based on a Multiple Indicator Approach

Weiß

Krejcie²,

Avram³

2007

Drug Metab Dispos

View full text Add to dashboard Cite

show abstract

“…This increase in high-amplitude, low-frequency activity was also characterised by an increased PTot and decreased F95. The increase in PTot and decrease in F95 represent a loss of functional cerebrocortical activity when amplitudes of EEG waves increase due to synchronised firing of neurons, as described previously (Sleigh and Donovan, 1999;Upton and Ludbrook 1999). Similar results have been found during anaesthesia in a range of species and during slaughter (Johnson et al, 1994;McKeegan et al, 2013a), but there is a lack of studies that assess EEG activity and behavioural indicators simultaneously.…”

Section: Experiments 1: Propofol Anaesthesiasupporting

confidence: 76%

Assessing unconsciousness in livestock at slaughter

Verhoeven¹

View full text Add to dashboard Cite

Verhoeven, M.T.W. (2016). Assessing unconsciousness in livestock at slaughter. PhD thesis, Wageningen University, The Netherlands Assessing unconsciousness in livestock at different stages of the slaughter process is a legal requirement according to EU legislation. The assessment can be based on absence of readily observable indicators (behavioural indicators, physical signs and reflexes) or, under experimental conditions, by recording and subsequent assessment of brain activity as presented in an electroencephalogram (EEG). There is no consensus, however, to what extent different behavioural indicators, physical signs and reflexes accurately reflect unconsciousness. The aim of this thesis was to study the relationships between these readily observable indicators and EEG activity to provide information on 1. the exact point in time at which animals lose consciousness when subjected to different stunning and slaughter methods and 2. the validity of behavioural indicators, physical signs and reflexes used to assess unconsciousness at slaughter under commercial conditions. The results showed a large variation in time to loss of consciousness, based on EEG activity, both between stunning and slaughter procedures and amongst animals. Captive bolt stunned calves lost consciousness instantly following the stun. Loss of consciousness in pigs during CO 2 stunning varied from 21 to 61 s after start of the exposure. An increased CO 2 concentration decreased the time to loss of consciousness. Times to loss of consciousness in sheep slaughtered without stunning varied from 6 to 24 s. In cattle slaughtered without stunning, times to loss of consciousness varied from 14 s up to over two minutes. Following captive bolt stunning in calves, absence of reflexes indicated unconsciousness. When consciousness was lost gradually (e.g. CO 2 stunning and nonstunned slaughter) none of the readily observable indicators could identify the exact point in time at which animals lost consciousness. Absence of rhythmic breathing, corneal reflex-and eyelid reflex were valid indicators of unconsciousness following CO 2 stunning and non-stunned slaughter, but these indicators were quite conservative as they were initially absent long after EEG activity indicated unconsciousness. When presence of these indicators would require (re)stunning, many animals will have to be (re)stunned. The results also showed that under full commercial conditions, stunning effectiveness must be closely monitored by slaughter plant employees, since risks for stun failures are higher under commercial conditions compared to experimental conditions. CONTENTS

show abstract

“…5 Although the prediction of the optimal infusion rate for inducing anaesthesia depends on the blood:brain equilibrium half-life of the anaesthetic agent, general pharmacological principles demonstrated using propofol will likely apply to alfaxalone. 9 The lack of evidence for cardiovascular advantages in the present study using a slower infusion rate is probably owing to the nature of the study (pilot study), the inadequate cardiovascular monitoring (non-invasive blood pressure), the small size of the groups and the good cardiovascular functional reserve of the population (young and healthy animals). The durations of apnoea were, unfortunately, not recorded; however, they were not clinically significant as none of the cats required positive pressure ventilation.…”

Section: Discussionmentioning

confidence: 81%

Influence of two administration rates of alfaxalone at induction on its relative potency in cats: a pilot study

Bauquier

Warne

Carter

et al. 2016

Journal of Feline Medicine and Surgery

View full text Add to dashboard Cite

Objectives The aim of the study was to evaluate, in a controlled, randomised, masked clinical trial, the influence of administration rate of alfaxalone at induction on its relative potency in cats and to report the incidence of cardiorespiratory adverse effects. Methods Twelve healthy female domestic cats admitted for ovariohysterectomy were premedicated with buprenorphine 20 µg/kg intramuscularly and alfaxalone 3.0 mg/kg subcutaneously. Sedation scores were established (using a published scale ranging from 1 [no sedation] to 5 [profound sedation]) prior to anaesthesia induction with alfaxalone intravenously at 2 mg/kg/min (group A2; n = 6) or 0.5 mg/kg/min (group A0.5; n = 6) to effect until orotracheal intubation was achieved. Sedation scores and alfaxalone induction doses were compared between the groups, using a Mann-Whitney exact test. Results are reported as median and range. Presence of apnoea (no breathing for more than 30 s) or hypotension (mean arterial blood pressure <60 mmHg) within 5 mins postintubation was also reported. Results Although sedation scores (1.5 [range 1.0-3.0] and 2.5 [range 1.0-3.0] for A2 and A0.5, respectively) were not significantly different ( P = 0.32), cats in group A2 required significantly more alfaxalone (4.3 mg/kg [range 3.4-7.0 mg/kg]) than group A0.5 (2.1 mg/kg [range 1.5-2.5 mg/kg]) ( P = 0.002). Two cats in each group presented postinduction apnoea, and two cats in group A2 and three cats in group A0.5 presented postinduction hypotension. Conclusions and relevance The use of a slower induction infusion rate resulted in an increase in the alfaxalone relative potency without obvious cardiorespiratory benefit.

show abstract

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

Cited by 37 publications

References 25 publications

A Minimal Physiological Model of Thiopental Distribution Kinetics Based on a Multiple Indicator Approach

A Minimal Physiological Model of Thiopental Distribution Kinetics Based on a Multiple Indicator Approach

Assessing unconsciousness in livestock at slaughter

Influence of two administration rates of alfaxalone at induction on its relative potency in cats: a pilot study

Contact Info

Product

Resources

About