Lysa P. Posner

Effects of opioids and anesthetic drugs on body temperature in cats.

OBJECTIVE To determine which class of opioid alone or in conjunction with other anesthetic drugs causes post-anesthetic hyperthermia in cats. STUDY DESIGN Prospective, randomized, crossover study. ANIMALS Eight adult, healthy, cats (four spayed females and four castrated males weighing 3.8 +/- 0.6 kg). METHODS Each cat was instrumented with a wireless thermistor in the abdominal cavity. Temperature in all phases was recorded every 5 minutes for 5 hours. Population body temperature (PBT) was recorded for approximately 8 days. Baseline body temperature is the final 24 hours of the PBT. All injectable drugs were given intramuscularly. The cats were administered drugs in four phases: 1) hydromorphone (H) 0.05, 0.1, or 0.2 mg kg(-1); 2) morphine (M) (0.5 mg kg(-1)), buprenorphine (BUP) (0.02 mg kg(-1)), or butorphanol (BUT) (0.2 mg kg(-1)); 3) ketamine (K) (5 mg kg(-1)) or ketamine (5 mg kg(-1)) plus hydromorphone (0.1 mg kg(-1)) (KH); 4) isoflurane in oxygen for 1 hour. Fifteen minutes prior to inhalant anesthetic, cats received either no premed (I), hydromorphone (0.1 mg kg(-1)) (IH), or hydromorphone (0.1 mg kg(-1)) plus ketamine (5 mg kg(-1)) (IHK). RESULTS Mean PBT for all unmedicated cats was 38.9 +/- 0.6 degrees C (102.0 +/- 1 degrees F). The temperature of cats administered all doses of hydromorphone increased from baseline (p < 0.03) All four opioids (H, M, BUP and BUT) studied increased body temperature compared with baseline (p < 0.005). A significant difference was observed between baseline temperature values and those in treatment KH (p < 0.03). Following recovery from anesthesia, temperature in treatments IH and IHK was different from baseline (p < 0.002). CONCLUSIONS AND CLINICAL RELEVANCE All of the opioids tested, alone or in combination with ketamine or isoflurane, caused an increase in body temperature. The increase seen was mild to moderate (<40.1 degrees C (104.2 degrees F) and self limiting.

Intravenous and sublingual buprenorphine in horses: pharmacokinetics and influence of sampling site

OBJECTIVE To describe the pharmacokinetics and adverse effects of intravenous (IV) and sublingual (SL) buprenorphine in horses, and to determine the effect of sampling site on plasma concentrations after SL administration. STUDY DESIGN Randomized crossover experiment; prospective study. ANIMALS Eleven healthy adult horses between 6 and 20 years of age and weighing 487-592 kg. METHODS In the first phase; buprenorphine was administered as a single IV or SL dose (0.006 mg kg(-1)) and pharmacokinetic parameters were determined for each route of administration using a noncompartmental model. In the second phase; the jugular and lateral thoracic veins were catheterized for simultaneous venous blood sampling, following a dose of 0.006 mg kg(-1) SL buprenorphine. For both phases, plasma buprenorphine concentrations were measured using ultra-performance liquid chromatography with mass spectrometry. At each sampling period, horses were assessed for behavioral excitement and gastrointestinal motility. RESULTS Following IV administration, buprenorphine mean ± SD half-life was 5.79 ± 1.09 hours. Systemic clearance (Cl) following IV administration was 6.13 ± 0.86 mL kg(-1) minute(-1) and volume of distribution at steady-state was 3.16 ± 0.65 L kg(-1). Following IV administration, horses showed signs of excitement. Gastrointestinal sounds were decreased following both routes of administration; however, none of the horses exhibited signs of colic. There was a significant discrepancy between plasma buprenorphine concentrations measured in the jugular vein versus the lateral thoracic vein following phase 2, thus pharmacokinetic parameters following SL buprenorphine are not reported. CONCLUSIONS AND CLINICAL RELEVANCE Buprenorphine has a long plasma half-life and results in plasma concentrations that are consistent with analgesia in other species for up to 4 hours following IV administration of this dose in horses. While buprenorphine is absorbed into the circulation following SL administration, jugular venous sampling gave a false measurement of the quantity absorbed and should not be used to study the uptake from SL administration.

The hemodynamic effects of medetomidine continuous rate infusions in the dog

OBJECTIVE To characterize the hemodynamic effects of continuous rate infusions (CRI) of medetomidine administered at doses ranging from 0 to 3 microg kg(-1) hour(-1). STUDY DESIGN Prospective, blinded, randomized experimental trial. ANIMALS Six adult purpose-bred mongrel dogs. METHODS Anesthesia was induced with sevoflurane for placement of arterial and venous catheters. Dogs recovered from anesthesia after which baseline hemodynamic measurements were obtained via lithium dilution cardiac output (CO) determination, with subsequent measurements via pulse power analysis to provide continuous CO determinations. Medetomidine, 1, 2, or 3 microg kg(-1) hour(-1) or a volume equivalent placebo, was administered via CRI for 60 minutes. Systolic, mean, and diastolic arterial pressure, heart rate (HR), CO and stroke volume were measured and stroke index (SI), cardiac index (CI), total peripheral resistance (TPR), and total peripheral resistance index (TPRI) were calculated at 3, 7, 10, 20, 30, 45, 60, 90, and 120 minutes from the start of the infusion. RESULTS Increase in dose decreased SI by 25%, 19%, and 30%, HR by 33%, 57%, and 60%, CI by 50%, 65%, 70% and increased TPRI by 109%, 235%, and 222% from baseline to the 60-minute measurement for the 1, 2, and 3 microg kg(-1) hour(-1) doses, respectively. HR, TPRI, and CI all showed significant differences over the duration of the study from the placebo treatment. CONCLUSIONS Medetomidine CRI produces clinically relevant changes in CO, TPR, and HR. The demonstrated decrease in CO is largely because of bradycardia and the degree of cardiovascular depression appears to be dose-dependent. These findings are consistent with previously described hemodynamic changes with single bolus administration of medetomidine. CLINICAL RELEVANCE Low-dose medetomidine CRIs produce clinically relevant hemodynamic depression at doses as low as 1 microg kg(-1) hour(-1) and should be used cautiously in dogs.

Pharmacokinetics of intravenous and intramuscular buprenorphine in the horse.

The purpose of this study was to determine the pharmacokinetics of buprenorphine following intravenous (i.v.) and intramuscular (i.m.) administration in horses. Six horses received i.v. or i.m. buprenorphine (0.005 mg/kg) in a randomized, crossover design. Plasma samples were collected at predetermined times and horses were monitored for adverse reactions. Buprenorphine concentrations were measured using ultra-performance liquid chromatography with electrospray ionization mass spectrometry. Following i.v. administration, clearance was 7.97±5.16 mL/kg/min, and half-life (T(1/2)) was 3.58 h (harmonic mean). Volume of distribution was 3.01±1.69 L/kg. Following i.m. administration, maximum concentration (C(max)) was 1.74±0.09 ng/mL, which was significantly lower than the highest measured concentration (4.34±1.22 ng/mL) after i.v. administration (P<0.001). Time to C(max) was 0.9±0.69 h and T(1/2) was 4.24 h. Bioavailability was variable (51-88%). Several horses showed signs of excitement. Gut sounds were decreased 10±2.19 and 8.67±1.63 h in the i.v. and i.m. group, respectively. Buprenorphine has a moderate T(1/2) in the horse and was detected at concentrations expected to be therapeutic in other species after i.v. and i.m. administration of 0.005 mg/kg. Signs of excitement and gastrointestinal stasis may be noted.

Recovery of horses from general anesthesia in a darkened or illuminated recovery stall

OBJECTIVE To assess whether recovery from general anesthesia, in an illuminated or a darkened stall, has an effect on time to first movement, time to standing, and recovery score. STUDY DESIGN Prospective randomized clinical study. ANIMALS Twenty-nine healthy, 2- to 5-year-old horses undergoing surgical correction of dorsal displacement of the soft palate. METHODS Each horse was assigned randomly to recover in either an illuminated (n = 15) or a darkened stall (n = 14). For pre-anesthetic medication, all horses received intravenous (IV) xylazine (0.4 mg kg(-1)) and butorphanol (0.02 mg kg(-1)). Anesthesia was induced with midazolam (0.1 mg kg(-1)) and ketamine (2.2 mg kg(-1)) IV and maintained on isoflurane in oxygen. Vital parameters, end-tidal CO(2) and isoflurane were recorded at 5-minute intervals. At the conclusion of anesthesia, horses were placed in either an illuminated or a darkened stall and xylazine (0.2 mg kg(-1)) IV was administered at extubation. Video cameras were used to record the horses while they were allowed to recover undisturbed. Video recordings were later viewed and recoveries were evaluated on a 100-point scale by three graders. RESULTS Horses in illuminated and darkened recovery stalls were evaluated on total anesthesia time, minimum alveolar concentration hours of isoflurane, time to first movement, time to standing, and total recovery score. There were no significant differences between the two groups in any of the measured parameters. CONCLUSION Recovering horses in a darkened versus an illuminated recovery stall may provide no benefit. CLINICAL RELEVANCE Darkening the recovery stalls for horses recovering from general anesthesia may be unnecessary.

Use of propofol for anesthesia in cats with primary hepatic lipidosis: 44 cases (1995–2004)

OBJECTIVE-To determine morbidity and fatalities in cats with hepatic lipidosis that received propofol to facilitate placement of a feeding tube. STUDY DESIGN-Retrospective case series. ANIMALS-44 Cats with presumed primary hepatic lipidosis anesthetized for placement of a feeding tube. PROCEDURES-Medical records from January 1995 through December 2004 were reviewed to identify cats that matched the inclusion criteria (histologic confirmation of hepatic lipidosis, anesthetized for placement of feeding tube, complete intensive care unit [ICU] records, and recorded outcome). Data extracted included age, body weight, sex, anesthetic drugs, drug dosages, type of feeding tube, duration of anesthesia, number of hours in ICU, administration of blood products, and survival until discharge from ICU. RESULTS-44 Cats (21 females and 23 males) were included in the analysis. Age range was 3 to 15 years (median, 8 years), and body weight ranged from 1.8 to 9.0 kg (4.0 to 19.8 lb), with a median of 4.8 kg (10.6 lb). Twenty-seven cats were administered propofol. There was no significant association between the use of propofol or the dosage of propofol and any risk factor, need for blood products, number of hours in the ICU, or survival. There was no significant difference between cats that received propofol and cats that did not receive propofol with regard to interval until discharge from the ICU. CONCLUSIONS AND CLINICAL RELEVANCE-The use of propofol did not increase morbidity or fatalities in cats with primary hepatic lipidosis. Thus, propofol can be used in these cats for placement of a feeding tube.

DEVELOPMENT OF A MINIMUM-ANESTHETIC-CONCENTRATION DEPRESSION MODEL TO STUDY THE EFFECTS OF VARIOUS ANALGESICS IN GOLDFISH (CARASSIUS AURATUS)

Abstract:  Teleost fish demonstrate the neurophysiologic capacity to experience pain and analgesia. A common model for assessing analgesic effect is the reduction of minimum anesthetic concentration (MAC). The present study adapted the model of MAC depression to evaluate the analgesic effects of morphine, butorphanol, medetomidine, and ketoprofen in goldfish (Carassius auratus). MAC was determined by an up–down method of sequential population sampling, anesthetizing fish with tricaine methanesulfonate (MS-222) in concentration increments of 10 parts per million (ppm), and using intramuscular needle insertion as a supramaximal noxious stimulus. Baseline MAC was determined in triplicate at the beginning (MACi) and conclusion (MACf) of the experiment (approximately 60 days). For drug trials, MAC was redetermined 1 hr after administration of morphine (10, 20, 40 mg/kg i.m.), butorphanol (0.1, 0.2, 0.4 mg/kg i.m.), medetomidine (0.01, 0.015, 0.025 mg/kg i.m.), ketoprofen (0.5, 1.0, 2.0 mg/kg i.m.), or saline control. Each drug/dose was tested in random order with a >6-day washout period. MACi and MACf were 163 and 182 ppm, respectively, and were significantly different from each other (P = 0.02). All doses of morphine and ketoprofen decreased MAC below MACi. The highest dose of medetomidine decreased MAC below MACi. The lowest dose of butorphanol decreased MAC below MACi, but higher doses increased MAC above MACf. The authors conclude that MAC determination in fish using MS-222 was feasible and reproducible in the short term. The fact that MAC increased over time and/or exposure may limit the usefulness of MS-222 in MAC depression studies. Morphine and ketoprofen decrease anesthetic needs in goldfish and may provide analgesia.

The efficacy of alfaxalone for immersion anesthesia in koi carp (Cyprinus carpio)

OBJECTIVE To characterize the physiologic and behavioral effects of a single induction dose and two maintenance doses of alfaxalone delivered by water immersion in the anesthesia of koi (Cyprinus carpio). STUDY DESIGN Prospective, within-subject complete crossover design. ANIMALS Six adult koi (Cyprinus carpio) with a median body weight of 344.5 g (range 292.0-405.0 g). METHODS Koi were immersed in water containing 10 mg L(-1) alfaxalone until immobile and then maintained with alfaxalone at either 1 or 2.5 mg L(-1) via a recirculating water system. Times for anesthetic induction and recovery periods were recorded. Physiologic and blood gas parameters were evaluated before, during and after the anesthetic trial. Response to noxious stimuli was also assessed. RESULTS Median anesthesia induction time for all fish was 5.4 minutes. Median recovery time was 11.8 and 26.4 minutes in the 1.0 and 2.5 mg L(-1) doses, respectively, which were significantly different (p = 0.04). Cessation of opercular movement occurred in 0/6 and 4/6 fish exposed to 1.0 and 2.5 mg L(-1) dose respectively. No difference was observed in median heart rate over the duration of the anesthetic events. Response to noxious stimulation was 4/6 and 0/6 in the 1.0 and 2.5 mg L(-1) doses respectively. Oxygenation and ventilation did not change during the experiment, but there was a significant decrease in blood pH along with an increase in blood lactate concentration. CONCLUSION AND CLINICAL RELEVANCE Administration of alfaxalone, via water immersion, as an induction and maintenance anesthesia agent provided rapid and reliable anesthesia of koi with no mortality. The maintenance dose of 2.5 mg L(-1) was sufficient to prevent response to noxious stimuli but was associated with a clinically relevant depression in opercular rate.

Fetal oxygen content is restored after maternal hemorrhage and fluid replacement with polymerized bovine hemoglobin, but not with hetastarch, in pregnant sheep.

We investigated the ability of hemoglobin-based oxygen carrying solutions (HBOCs) to alleviate fetal hypoxemia from maternal hemorrhage. Fifteen pregnant ewes (132-day gestational age) were hemorrhaged 20 mL/kg over 1 h; they were randomized to receive 20 mL/kg IV of HBOC, hetastarch (HTS), or autologous blood (BLD) (n = 5 each) over 30 min and were monitored for 2 h. Hemorrhage significantly (P ≤ 0.05) decreased maternal mean blood pressure (from 98 to 48 mm Hg, median), arterial oxygen content (from 12.2 to 11.1 mL/dL), and fetal arterial oxygen content (from 8.1 to 3.9 mL/dL). Fluid replacement restored maternal blood pressure in all groups, although maternal oxygen content immediately returned to baseline only after BLD or HBOC. Maternal oxygen saturation decreased after HBOC (from 98% to 88%). Fetal oxygen content rapidly returned to baseline with either BLD (7.1 mL/dL) or HBOC (8.0 mL/dL) but was never restored with HTS (4.7 mL/dL), and, 60 min after fluid replacement, it was higher with HBOC (8.3 mL/dL) than with HTS (4.7 mL/dL). Fetal plasma-free hemoglobin did not change after HBOC. In conclusion, maternal fluid replacement with HBOC or BLD effectively restored fetal oxygenation, primarily by restoring maternal oxygen content, whereas HTS did not.

Physiologic and biochemical assessments of koi (Cyprinus carpio) following immersion in propofol.

OBJECTIVE To determine efficacy of propofol as an immersion agent to induce general anesthesia in koi (Cyprinus carpio). DESIGN Prospective, crossover study. ANIMALS 10 adult koi (mean ± SD weight, 325 ± 81 g). PROCEDURES Koi were exposed to each of 4 concentrations of propofol (1, 2.5, 5, and 10 mg/L) with a 1-week washout period between trials. In a subsequent trial, koi were anesthetized with propofol (5 mg/L) and anesthesia was maintained with propofol (3 mg/L) for 20 minutes. Response to a noxious stimulus was assessed by means of needle insertion into an epaxial muscle. RESULTS At a propofol concentration of 1 mg/L, koi were sedated but never anesthetized. At propofol concentrations of 2.5, 5, and 10 mg/L, mean ± SD anesthetic induction times were 13.4 ± 3.3, 3.8 ± 1.1, and 2.3 ± 0.9 minutes, respectively; mean recovery times were 12.9 ± 8.3, 11.0 ± 6.3, and 18.1 ± 13.0 minutes; mean heart rates were 57 ± 25, 30 ± 14, and 22 ± 14 beats/min; mean opercular rates were 58 ± 18, 68 ± 15, and 48 ± 22 beats/min; and 1 of 10, 2 of 10, and 0 of 10 fish responded to needle insertion. All fish recovered satisfactorily. Following 20 minutes of anesthesia, 2 fish had recovery times > 4 hours and 1 fish died. CONCLUSIONS AND CLINICAL RELEVANCE Immersion in propofol at concentrations ≥ 2.5 mg/L induced general anesthesia in koi. Maintenance of anesthesia with propofol for 20 minutes was associated with prolonged recovery times in 2 of 9 and death in 1 of 9 koi.