Objective—To determine the effect of dexmedetomidine, morphine-lidocaine-ketamine (MLK), and dexmedetomidine-morphine-lidocaine-ketamine (DMLK) constant rate infusions on the minimum alveolar concentration (MAC) of isoflurane and bispectral index (BIS) in dogs.
Animals—6 healthy adult dogs.
Procedures—Each dog was anesthetized 4 times with a 7-day washout period between anesthetic episodes. During the first anesthetic episode, the MAC of isoflurane (baseline) was established. During the 3 subsequent anesthetic episodes, the MAC of isoflurane was determined following constant rate infusion of dexmedetomidine (0.5 μg/kg/h), MLK (morphine, 0.2 mg/kg/h; lidocaine, 3 mg/kg/h; and ketamine, 0.6 mg/kg/h), or DMLK (dexmedetomidine, 0.5 μg/kg/h; morphine, 0.2 mg/kg/h; lidocaine, 3 mg/kg/h; and ketamine 0.6 mg/kg/h). Among treatments, MAC of isoflurane was compared by means of a Friedman test with Conover posttest comparisons, and heart rate, direct arterial pressures, cardiac output, body temperature, inspired and expired gas concentrations, arterial blood gas values, and BIS were compared with repeated-measures ANOVA and a Dunn test for multiple comparisons.
Results—Infusion of dexmedetomidine, MLK, and DMLK decreased the MAC of isoflurane from baseline by 30%, 55%, and 90%, respectively. Mean heart rates during dexmedetomidine and DMLK treatments was lower than that during MLK treatment. Compared with baseline values, mean heart rate decreased for all treatments, arterial pressure increased for the DMLK treatment, cardiac output decreased for the dexmedetomidine treatment, and BIS increased for the MLK and DMLK treatments. Time to extubation and sternal recumbency did not differ among treatments.
Conclusions and Clinical Relevance—Infusion of dexmedetomidine, MLK, or DMLK reduced the MAC of isoflurane in dogs. (Am J Vet Res 2013;74:963–970)
Objective—To evaluate the use of midazolam, ketamine, and xylazine for total IV anesthesia (TIVA) in horses.
Animals—6 healthy Thoroughbred mares.
Procedures—Horses were sedated with xylazine (1.0 mg/kg, IV). Anesthesia was induced with midazolam (0.1 mg/kg, IV) followed by ketamine (2.2 mg/kg, IV) and was maintained with an IV infusion of midazolam (0.002 mg/kg/min), ketamine (0.03 mg/kg/min), and xylazine (0.016 mg/kg/min). Horses underwent surgical manipulation and injection of the palmar digital nerves; duration of the infusion was 60 minutes. Additional ketamine (0.2 to 0.4 mg/kg, IV) was administered if a horse moved its head or limbs during procedures. Cardiopulmonary and arterial blood variables were measured prior to anesthesia; at 10, 20, 30, 45, and 60 minutes during infusion; and 10 minutes after horses stood during recovery. Recovery quality was assessed by use of a numeric (1 to 10) scale with 1 as an optimal score.
Results—Anesthesia was produced for 70 minutes after induction; supplemental ketamine administration was required in 4 horses. Heart rate, respiratory rate, arterial blood pressures, and cardiac output remained similar to preanesthetic values throughout TIVA. Arterial partial pressure of oxygen and oxygen saturation of arterial hemoglobin were significantly decreased from preanesthetic values throughout anesthesia; oxygen delivery was significantly decreased at 10- to 30-minute time points. Each horse stood on its first attempt, and median recovery score was 2.
Conclusions and Clinical Relevance—Midazolam, ketamine, and xylazine in combination produced TIVA in horses. Further studies to investigate various dosages for midazolam and ketamine or the substitution of other α2-adrenoceptor for xylazine are warranted.
Objective—To compare systemic bioavailability and
duration for therapeutic plasma concentrations and
cardiovascular, respiratory, and analgesic effects of
morphine administered per rectum, compared with IV
and IM administration in dogs.
Animals—6 healthy Beagles.
Procedure—In a randomized study, each dog
received the following: morphine IV (0.5 mg/kg of
body weight), morphine per rectum (1, 2, and 5 mg/kg
as a suppository and 2 mg/kg as a solution), and a control
treatment. Intramuscular administration of morphine
(1 mg/kg) was evaluated separately. Heart and
respiratory rates, systolic, diastolic, and mean blood
pressures, adverse effects, and plasma morphine concentrations
were measured. Analgesia was defined as
an increase in response threshold, compared with
baseline values, to applications of noxious mechanical
(pressure) and thermal (heat) stimuli. Data were evaluated,
using Friedman repeated-measures ANOVA on
ranks and Student-Newman-Keuls post-hoc t-tests.
Results—Significant differences were not found in
cardiovascular, respiratory, or analgesia values
between control and morphine groups. Overall systemic
bioavailability of morphine administered per rectum
was 19.6%. Plasma morphine concentration after
administration of the highest dose (5 mg/kg) as a suppository
was significantly higher than concentrations
60 and 360 minutes after IV and IM administration,
respectively. A single route of administration did not
consistently fulfill our criteria for providing analgesia.
Conclusions and Clinical Relevance—Rectal administration
of morphine did not increase bioavailability
above that reported for oral administration of morphine
in dogs. Low bioavailability and plasma concentrations
limit the clinical usefulness of morphine
administered per rectum in dogs. (Am J Vet Res
Animals—48 client-owned dogs that underwent stifle joint surgery.
Procedures—Dogs undergoing tibial plateau leveling osteotomy were randomly assigned to receive a constant rate infusion of a combination of morphine, lidocaine, and ketamine; a lumbosacral epidural with morphine and ropivacaine; both treatments (ie, constant rate infusion and lumbosacral epidural); or only IM premedication with morphine. Indices of cardiorespiratory function and isoflurane requirement were recorded at 5-minute intervals during anesthesia. A validated sedation scoring system and the modified Glasgow composite measure pain score were used to assess comfort and sedation after surgery and anesthesia once the swallowing reflex returned and a body temperature of ≥ 36.7°C (98.1°F) was attained. Pain and sedation scores were acquired at 60-minute intervals for 4 hours, then at 4-hour intervals for 24 hours. Dogs with a postoperative pain score > 5 of 24 were given morphine as rescue analgesia.
Results—No differences in heart rate, respiratory rate, systolic arterial blood pressure, end-tidal Pco2, end-tidal isoflurane concentration, and vaporizer setting were detected among groups. No differences in pain score, sedation score, rescue analgesia requirement, or time to first rescue analgesia after surgery were detected.
Conclusions and Clinical Relevance—Pain scores were similar among groups, and all 4 groups had similar rescue analgesia requirements and similar times to first administration of rescue analgesia. All 4 analgesic protocols provided acceptable analgesia for 24 hours after stifle joint surgery.
Objective—To determine the effect of IV administration of crystalloid (lactated Ringer's solution [LRS]) or colloid (hetastarch) fluid on isoflurane-induced hypotension in dogs.
Animals—6 healthy Beagles.
Procedures—On 3 occasions, each dog was anesthetized with propofol and isoflurane and instrumented with a thermodilution catheter (pulmonary artery). Following baseline assessments of hemodynamic variables, end-tidal isoflurane concentration was increased to achieve systolic arterial blood pressure (SABP) of 80 mm Hg. At that time (0 minutes), 1 of 3 IV treatments (no fluid, LRS [80 mL/kg/h], or hetastarch [80 mL/kg/h]) was initiated. Fluid administration continued until SABP was within 10% of baseline or to a maximum volume of 80 mL/kg (LRS) or 40 mL/kg (hetastarch). Hemodynamic variables were measured at intervals (0 through 120 minutes and additionally at 150 and 180 minutes in LRS- or hetastarch-treated dogs). Several clinicopathologic variables including total protein concentration, PCV, colloid osmotic pressure, and viscosity of blood were assessed at baseline and intervals thereafter (0 through 120 minutes).
Results—Administration of 80 mL of LRS/kg did not increase SABP in any dog, whereas administration of ≤ 40 mL of hetastarch/kg increased SABP in 4 of 6 dogs. Fluid administration increased cardiac index and decreased systemic vascular resistance. Compared with hetastarch treatment, administration of LRS decreased blood viscosity. Treatment with LRS decreased PCV and total protein concentration, whereas treatment with hetastarch increased colloid osmotic pressure.
Conclusions and Clinical Relevance—Results indicated that IV administration of hetastarch rather than LRS is recommended for the treatment of isoflurane-induced hypotension in dogs.
OBJECTIVE To determine pharmacokinetics and pharmacodynamics of buprenorphine after IV and SC administration and of sustained-release (SR) buprenorphine after SC administration to adult alpacas.
ANIMALS 6 alpacas.
PROCEDURES Buprenorphine (0.02 mg/kg, IV and SC) and SR buprenorphine (0.12 mg/kg, SC) were administered to each alpaca, with a 14-day washout period between administrations. Twenty-one venous blood samples were collected over 96 hours and used to determine plasma concentrations of buprenorphine. Pharmacokinetic parameters were calculated by use of noncompartmental analysis. Pharmacodynamic parameters were assessed via sedation, heart and respiratory rates, and thermal and mechanical antinociception indices.
RESULTS Mean ± SD maximum concentration after IV and SC administration of buprenorphine were 11.60 ± 4.50 ng/mL and 1.95 ± 0.80 ng/mL, respectively. Mean clearance was 3.00 ± 0.33 L/h/kg, and steady-state volume of distribution after IV administration was 3.8 ± l.0 L/kg. Terminal elimination half-life was 1.0 ± 0.2 hours and 2.7 ± 2.8 hours after IV and SC administration, respectively. Mean residence time was 1.3 ± 0.3 hours and 3.6 ± 3.7 hours after IV and SC administration, respectively. Bioavailability was 64 ± 28%. Plasma concentrations after SC administration of SR buprenorphine were below the LLOQ in samples from 4 alpacas. There were no significant changes in pharmacodynamic parameters after buprenorphine administration. Alpacas exhibited mild behavioral changes after all treatments.
CONCLUSIONS AND CLINICAL RELEVANCE Buprenorphine administration to healthy alpacas resulted in moderate bioavailability, rapid clearance, and a short half-life. Plasma concentrations were detectable in only 2 alpacas after SC administration of SR buprenorphine.
To evaluate the pharmacokinetics and pharmacodynamics of naloxone hydrochloride in dogs following intranasal (IN) and IV administration.
6 healthy adult mixed-breed dogs.
In a blinded crossover design involving 2 experimental periods separated by a washout period (minimum of 7 days), dogs were randomly assigned to receive naloxone IN (4 mg via a commercially available fixed-dose naloxone atomizer; mean ± SD dose, 0.17 ± 0.02 mg/kg) or IV (0.04 mg/kg) in the first period and then the opposite treatment in the second period. Plasma naloxone concentrations, dog behavior, heart rate, and respiratory rate were evaluated for 24 hours/period.
Naloxone administered IN was well absorbed after a short lag time (mean ± SD, 2.3 ± 1.4 minutes). Mean maximum plasma concentration following IN and IV administration was 9.3 ± 2.5 ng/mL and 18.8 ± 3.9 ng/mL, respectively. Mean time to maximum concentration following IN administration was 22.5 ± 8.2 minutes. Mean terminal half-life after IN and IV administration was 47.4 ± 6.7 minutes and 37.0 ± 6.7 minutes, respectively. Mean bioavailability of naloxone administered IN was 32 ± 13%. There were no notable changes in dog behavior, heart rate, or respiratory rate following naloxone administration by either route.
CONCLUSIONS AND CLINICAL RELEVANCE
Use of a naloxone atomizer for IN naloxone administration in dogs may represent an effective alternative to IV administration in emergency situations involving opioid exposure. Future studies are needed to evaluate the efficacy of IN naloxone administration in dogs with opioid intoxication, including a determination of effective doses.
Objective—To determine pharmacokinetic and pharmacodynamic properties of midazolam after IV and IM administration in alpacas.
Animals—6 healthy alpacas.
Procedures—Midazolam (0.5 mg/kg) was administered IV or IM in a randomized crossover design. Twelve hours prior to administration, catheters were placed in 1 (IM trial) or both (IV trial) jugular veins for drug administration and blood sample collection for determination of serum midazolam concentrations. Blood samples were obtained at intervals up to 24 hours after IM and IV administration. Midazolam concentrations were determined by use of tandem liquid chromatography–mass spectrometry.
Results—Maximum concentrations after IV administration (median, 1,394 ng/mL [range, 1,150 to 1,503 ng/mL]) and IM administration (411 ng/mL [217 to 675 ng/mL]) were measured at 3 minutes and at 5 to 30 minutes, respectively. Distribution half-life was 18.7 minutes (13 to 47 minutes) after IV administration and 41 minutes (30 to 80 minutes) after IM administration. Elimination half-life was 98 minutes (67 to 373 minutes) and 234 minutes (103 to 320 minutes) after IV and IM administration, respectively. Total clearance after IV administration was 11.3 mL/min/kg (6.7 to 13.9 mL/min/kg), and steady-state volume of distribution was 525 mL/kg (446 to 798 mL/kg). Bioavailability of midazolam after IM administration was 92%. Peak onset of sedation occurred at 0.4 minutes (IV) and 15 minutes (IM). Sedation was significantly greater after IV administration.
Conclusions and Clinical Relevance—Midazolam was well absorbed after IM administration, had a short duration of action, and induced moderate levels of sedation in alpacas.