Blood/gas partition coefficients of halothane, isoflurane and sevoflurane in horse blood

Background. Blood/gas partition coefficients (λb/g) for volatile agents in horse blood are reported for halothane but not for isoflurane and sevoflurane. We measured the λb/g of halothane, isoflurane and sevoflurane in the blood of fasted horses. The correlation with age, weight and some haematological and biochemical variables was studied. The temperature correction factor for isoflurane solubility was calculated. Methods. Twenty‐four horses were randomly allocated to halothane (n=8), isoflurane (n=8) or sevoflurane (n=8). Blood samples were taken after 10 h' fasting. Calculation of λb/g was based on the measurement of anaesthetic partial pressures in blood at 37 °C, which was achieved with tonometer equilibration and headspace gas chromatography. Results. Mean λb/g was 1.66 (sd 0.06) for halothane, 0.92 (0.04) for isoflurane, and 0.47 (0.03) for sevoflurane. The λb/g values were all significantly lower than in humans (P<0.001). No correlation was found between λb/g and weight, age, haematocrit, plasma triglycerides, cholesterol or total bilirubin. The change in isoflurane solubility per 1 °C temperature increase was -2.63 (0.13)%. Conclusion. The λb/g values of halothane, isoflurane and sevoflurane in fasted horses are significantly lower than those reported in humans. The λb/g for halothane in this study agrees with values reported in the literature but a positive correlation with plasma triglycerides could not be confirmed. Knowledge of λb/g can refine models of anaesthetic uptake. Br J Anaesth 2003; 91: 276-

Stereoselective pharmacokinetics of ketamine and norketamine after racemic ketamine or S-ketamine administration during isoflurane anaesthesia in Shetland ponies

Background The arterial pharmacokinetics of ketamine and norketamine enantiomers after racemic ketamine or S-ketamine i.v. administration were evaluated in seven gelding ponies in a crossover study (2-month interval). Methods Anaesthesia was induced with isoflurane in oxygen via a face-mask and then maintained at each pony's individual MAC. Racemic ketamine (2.2mgkg−1) or S-ketamine (1.1mgkg−1) was injected in the right jugular vein. Blood samples were collected from the right carotid artery before and at 1, 2, 4, 8, 16, 32, 64, and 128min after ketamine administration. Ketamine and norketamine enantiomer plasma concentrations were determined by capillary electrophoresis. Individual R-ketamine and S-ketamine concentration vs time curves were analysed by non-linear least square regression two-compartment model analysis using PCNonlin. Plasma disposition curves for R-norketamine and S-norketamine were described by estimating AUC, Cmax, and Tmax. Pulse rate (PR), respiratory rate (Rf), tidal volume (VT), minute volume ventilation (VE), end-tidal partial pressure of carbon dioxide (Pe′CO2), and mean arterial blood pressure (MAP) were also evaluated. Results The pharmacokinetic parameters of S- and R-ketamine administered in the racemic mixture or S-ketamine administered separately did not differ significantly. Statistically significant higher AUC and Cmax were found for S-norketamine compared with R-norketamine in the racemic group. Overall, Rf, VE, Pe′CO2, and MAP were significantly higher in the racemic group, whereas PR was higher in the S-ketamine group. Conclusions Norketamine enantiomers showed different pharmacokinetic profiles after single i.v. administration of racemic ketamine in ponies anaesthetised with isoflurane in oxygen (1 MAC). Cardiopulmonary variables require further investigatio

Stereoselective pharmacokinetics of ketamine and norketamine after racemic ketamine or S-ketamine administration during isoflurane anaesthesia in Shetland ponies

Background. The arterial pharmacokinetics of ketamine and norketamine enantiomers after racemic ketamine or S-ketamine i.v. administration were evaluated in seven gelding ponies in a crossover study (2-month interval). Methods. Anaesthesia was induced with isoflurane in oxygen via a face-mask and then maintained at each pony's individual MAC. Racemic ketamine (2.2 mg kg-1) or S-ketamine (1.1 mg kg-1) was injected in the right jugular vein. Blood samples were collected from the right carotid artery before and at 1, 2, 4, 8, 16, 32, 64, and 128 min after ketamine administration. Ketamine and norketamine enantiomer plasma concentrations were determined by capillary electrophoresis. Individual R-ketamine and S-ketamine concentration vs time curves were analysed by non-linear least square regression two-compartment model analysis using PCNonlin. Plasma disposition curves for R-norketamine and S-norketamine were described by estimating AUC, Cmax, and Tmax. Pulse rate (PR), respiratory rate (Rf), tidal volume (VT), minute volume ventilation (VE), end-tidal partial pressure of carbon dioxide (Pe′CO2), and mean arterial blood pressure (MAP) were also evaluated. Results. The pharmacokinetic parameters of S- and R-ketamine administered in the racemic mixture or S-ketamine administered separately did not differ significantly. Statistically significant higher AUC and Cmax were found for S-norketamine compared with R-norketamine in the racemic group. Overall, Rf, VE, Pe′CO2, and MAP were significantly higher in the racemic group, whereas PR was higher in the S-ketamine group. Conclusions. Norketamine enantiomers showed different pharmacokinetic profiles after single i.v. administration of racemic ketamine in ponies anaesthetised with isoflurane in oxygen (1 MAC). Cardiopulmonary variables require further investigation.Facultad de Ciencias Veterinaria

Stereoselective pharmacokinetics of ketamine and norketamine after racemic ketamine or S-ketamine administration during isoflurane anaesthesia in Shetland ponies

Background. The arterial pharmacokinetics of ketamine and norketamine enantiomers after racemic ketamine or S-ketamine i.v. administration were evaluated in seven gelding ponies in a crossover study (2-month interval). Methods. Anaesthesia was induced with isoflurane in oxygen via a face-mask and then maintained at each pony's individual MAC. Racemic ketamine (2.2 mg kg-1) or S-ketamine (1.1 mg kg-1) was injected in the right jugular vein. Blood samples were collected from the right carotid artery before and at 1, 2, 4, 8, 16, 32, 64, and 128 min after ketamine administration. Ketamine and norketamine enantiomer plasma concentrations were determined by capillary electrophoresis. Individual R-ketamine and S-ketamine concentration vs time curves were analysed by non-linear least square regression two-compartment model analysis using PCNonlin. Plasma disposition curves for R-norketamine and S-norketamine were described by estimating AUC, Cmax, and Tmax. Pulse rate (PR), respiratory rate (Rf), tidal volume (VT), minute volume ventilation (VE), end-tidal partial pressure of carbon dioxide (Pe′CO2), and mean arterial blood pressure (MAP) were also evaluated. Results. The pharmacokinetic parameters of S- and R-ketamine administered in the racemic mixture or S-ketamine administered separately did not differ significantly. Statistically significant higher AUC and Cmax were found for S-norketamine compared with R-norketamine in the racemic group. Overall, Rf, VE, Pe′CO2, and MAP were significantly higher in the racemic group, whereas PR was higher in the S-ketamine group. Conclusions. Norketamine enantiomers showed different pharmacokinetic profiles after single i.v. administration of racemic ketamine in ponies anaesthetised with isoflurane in oxygen (1 MAC). Cardiopulmonary variables require further investigation.Facultad de Ciencias Veterinaria

Use of pressure waves to confirm the correct placement of epidural needles in dogs

An epidural puncture was performed using the lumbosacral approach in 18 dogs, and the lack of resistance to an injection of saline was used to determine that the needle was positioned correctly. The dogs' arterial blood pressure and epidural pressure were recorded. They were randomly assigned to two groups: in one group an injection of a mixture of local anaesthetic agents was made slowly over 90 seconds and in the other it was made over 30 seconds. After 10 minutes contrast radiography was used to confirm the correct placement of the needle. The mean (sd) initial pressure in the epidural space was 0.1 (0.7) kPa. After the injection the mean maximum epidural pressure in the group injected slowly was 5.5 (2.1) kPa and in the group injected more quickly it was 6.0 (1.9) kPa. At the end of the period of measurement, the epidural pressure in the slow group was 0.8 (0.5) kPa and in the rapid group it was 0.7 (0.5) kPa. Waves synchronous with the arterial pulse wave were observed in 15 of the dogs before the epidural injection, and in all the dogs after the epidural injection

Comparison of the effects of the alpha-2 agonists detomidine, romifidine and xylazine on nociceptive withdrawal reflex and temporal summation in horses

OBJECTIVE: To evaluate and compare the antinociceptive effects of the three alpha-2 agonists, detomidine, romifidine and xylazine at doses considered equipotent for sedation, using the nociceptive withdrawal reflex (NWR) and temporal summation model in standing horses. STUDY DESIGN: Prospective, blinded, randomized cross-over study. ANIMALS: Ten healthy adult horses weighing 527-645 kg and aged 11-21 years old. METHODS: Electrical stimulation was applied to the digital nerves to evoke NWR and temporal summation in the left thoracic limb and pelvic limb of each horse. Electromyographic reflex activity was recorded from the common digital extensor and the cranial tibial muscles. After baseline measurements a single bolus dose of detomidine, 0.02 mg kg(-1), romifidine 0.08 mg kg(-1), or xylazine, 1 mg kg(-1), was administered intravenously (IV). Determinations of NWR and temporal summation thresholds were repeated at 10, 20, 30, 40, 60, 70, 90, 100, 120 and 130 minutes after test-drug administration alternating the thoracic limb and the pelvic limb. Depth of sedation was assessed before measurements at each time point. Behavioural reaction was observed and recorded following each stimulation. RESULTS: The administration of detomidine, romifidine and xylazine significantly increased the current intensities necessary to evoke NWR and temporal summation in thoracic limbs and pelvic limbs of all horses compared with baseline. Xylazine increased NWR thresholds over baseline values for 60 minutes, while detomidine and romifidine increased NWR thresholds over baseline for 100 and 120 minutes, respectively. Temporal summation thresholds were significantly increased for 40, 70 and 130 minutes after xylazine, detomidine and romifidine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Detomidine, romifidine and xylazine, administered IV at doses considered equipotent for sedation, significantly increased NWR and temporal summation thresholds, used as a measure of antinociceptive activity. The extent of maximal increase of NWR and temporal summation thresholds was comparable, while the duration of action was drug-specific