Objective—To evaluate whether guaifenesin can prevent adverse anesthetic induction events caused by propofol and whether a guaifenesin-propofol induction combination has brief cardiovascular effects commensurate with rapid drug washout.
Animals—8 healthy adult horses.
Procedures—Guaifenesin was administered IV for 3 minutes followed by IV injection of a bolus of propofol (2 mg/kg). Additional propofol was administered if purposeful movement was detected. Anesthesia was maintained for 2 hours with isoflurane or sevoflurane at 1.2 times the minimum alveolar concentration with controlled normocapnic ventilation. Normotension was maintained via a dobutamine infusion. Plasma concentrations of propofol and guaifenesin were measured every 30 minutes.
Results—Mean ± SD guaifenesin and propofol doses inducing anesthesia in half of the horses were 73 ± 18 mg/kg and 2.2 ± 0.3 mg/kg, respectively. No adverse anesthetic induction events were observed. By 70 minutes, there was no significant temporal change in the dobutamine infusion rate required to maintain normotension for horses anesthetized with isoflurane or sevoflurane. Mean plasma guaifenesin concentrations were 122 ± 30μM, 101 ± 33μM, 93 ± 28μM, and 80 ± 24μM at 30, 60, 90, and 120 minutes after anesthetic induction, respectively. All plasma propofol concentrations were below the limit of quantitation.
Conclusions and Clinical Relevance—Guaifenesin prevented adverse anesthetic induction events caused by propofol. Guaifenesin (90 mg/kg) followed by propofol (3 mg/kg) should be sufficient to immobilize > 99% of calm healthy adult horses. Anesthetic drug washout was rapid, and there was no change in inotrope requirements after anesthesia for 70 minutes.
Objective—To determine the pharmacokinetics of dexmedetomidine administered as a short-duration IV infusion in isoflurane-anesthetized cats.
Animals—6 healthy adult domestic female cats.
Procedures—Dexmedetomidine hydrochloride was injected IV (10 μg/kg over 5 minutes [rate, 2 μg/kg/min]) in isoflurane-anesthetized cats. Blood samples were obtained immediately prior to and at 1, 2, 5, 6, 7, 10, 15, 30, 60, 90, 120, 240, and 480 minutes following the start of the IV infusion. Collected blood samples were transferred to tubes containing EDTA, immediately placed on ice, and then centrifuged at 3,901 × g for 10 minutes at 4°C. The plasma was harvested and stored at −20°C until analyzed. Plasma dexmedetomidine concentrations were determined by means of liquid chromatography–mass spectrometry. Dexmedetomidine plasma concentration-time data were fitted to compartmental models.
Results—A 2-compartment model with input in and elimination from the central compartment best described the disposition of dexmedetomidine administered via short-duration IV infusion in isoflurane-anesthetized cats. Weighted mean ± SEM apparent volume of distribution of the central compartment and apparent volume of distribution at steady-state were 402 ± 47 mL/kg and 1,701 ± 200 mL/kg, respectively; clearance and terminal half-life (harmonic mean ± jackknife pseudo-SD) were 6.3 ± 2.8 mL/min/kg and 198 ± 75 minutes, respectively. The area under the plasma concentration curve and maximal plasma concentration were 1,061 ± 292 min•ng/mL and 17.6 ± 1.8 ng/mL, respectively.
Conclusions and Clinical Relevance—Disposition of dexmedetomidine administered via short-duration IV infusion in isoflurane-anesthetized cats was characterized by a moderate clearance and a long terminal half-life.
To determine the minimum alveolar concentration (MAC) of isoflurane in donkeys and characterize recovery from anesthesia.
7 healthy castrated male adult donkeys.
Anesthesia was induced with propofol and maintained under mechanical ventilation with 1.3% isoflurane end-tidal concentration (ETiso). The MAC of isoflurane was determined after a 60-minute propofol washout period using the bracketing method. A continuous noxious electrical stimulation was applied to the oral mucosa for 1 minute or until the donkey moved. The ETiso was increased or decreased by 10% depending on the response, and MAC was defined as the average of 2 ETiso values allowing and preventing movement in response to stimulation. Arterial blood gases were measured during anesthesia and the recovery period. Unassisted recovery was timed, and a quality score was assigned from 1 (very poor) to 5 (excellent).
The mean dose of propofol required for induction was 3.0 ± 0.6 mg/kg. The MAC of isoflurane was 1.44 ± 0.13%. One donkey was excluded from the study because it was still responsive when stimulated at ETiso of 2.8%. Immediately after extubation, the median (range) partial pressure of oxygen in the arterial blood was 63 (minimum to maximum, 46 to 72) mm Hg and 3 donkeys were hypoxemic (partial pressure of arterial oxygen < 60 mm Hg). The median time to standing was 13 (7 to 38) minutes, while the recovery score was 3 (2 to 5).
The MAC of isoflurane in donkeys is similar to that reported in other species. Oxygen support should be provided to donkeys during recovery from isoflurane anesthesia to prevent hypoxemia.
Procedures—Each bird was anesthetized with sevoflurane, and a standard bracketing method was used to measure the MAC in response to a noxious electrical stimulus. Subsequently, conditions were adjusted so that each bird was anesthetized with sevoflurane at a fraction of its respective MAC (eg, 0.7 times the MAC for that bird). Butorphanol tartrate (2 mg/kg, IV) was administered, and a noxious stimulus was applied every 15 minutes until the bird moved in response. The reduction in MAC was estimated with logistic regression by use of a standard quantal method. After an interval of ≥ 1 week, the MAC reduction experiment was repeated with an increased butorphanol dosage (4 mg/kg).
Results—Individual mean ± SE MAC for sevoflurane was 2.9 ± 0.1%. At 15 minutes after administration of 2 mg of butorphanol/kg, estimated reduction in the MAC for sevoflurane was 9 ± 3%. At 15 and 30 minutes after administration of 4 mg of butorphanol/kg, estimated reduction in the MAC for sevoflurane was 21 ± 4% and 11 ± 8%, respectively.
Conclusions and Clinical Relevance—In guineafowl, the MAC for sevoflurane was similar to values reported for other species. Increasing the butorphanol dosage decreased the MAC for sevoflurane, but the effect was small and of short duration for dosages up to 4 mg/kg.
To determine the pharmacokinetics and pharmacodynamics of methadone after IV or IM administration to isoflurane-anesthetized chickens.
6 healthy adult Hy-Line hens.
In a randomized crossover-design study, methadone (6 mg/kg) was administered IV and IM to isoflurane-anesthetized chickens with a 1-week washout period between experiments. Blood samples were collected immediately before and at predetermined time points up to 480 minutes after methadone administration. Plasma concentrations were determined by liquid chromatography–mass spectrometry, and appropriate compartmental models were fit to the plasma concentration-versus-time data. Cardiorespiratory variables were compared between treatments and over time with mixed-effect repeated-measures analysis.
A 3-compartment model best described the changes in plasma methadone concentration after IV or IM administration. Estimated typical values for volumes of distribution were 692 mL/kg for the central compartment and 2,439 and 2,293 mL/kg for the first and second peripheral compartments, respectively, with metabolic clearance of 23.3 mL/kg/min and first and second distributional clearances of 556.4 and 51.8 mL/kg/min, respectively. Typical bioavailability after IM administration was 79%. Elimination half-life was 177 minutes, and maximum plasma concentration after IM administration was 950 ng/mL. Heart rate was mildly decreased at most time points beginning 5 minutes after IV or IM drug administration.
CONCLUSIONS AND CLINICAL RELEVANCE
Disposition of methadone in isoflurane-anesthetized chickens was characterized by a large volume of distribution and moderate clearance, with high bioavailability after IM administration. Additional studies are warranted to assess pharmacokinetics and pharmacodynamics of methadone in awake chickens.