Effect of fentanyl on the induction dose and minimum infusion rate of propofol preventing movement in dogs.

OBJECTIVE: To determine the effect of fentanyl on the induction dose of propofol and minimum infusion rate required to prevent movement in response to noxious stimulation (MIRNM) in dogs. STUDY DESIGN: Crossover experimental design. ANIMALS: Six healthy, adult intact male Beagle dogs, mean±standard deviation 12.6±0.4 kg. METHODS: Dogs were administered 0.9% saline (treatment P), fentanyl (5 µg kg-1) (treatment PLDF) or fentanyl (10 µg kg-1) (treatment PHDF) intravenously over 5 minutes. Five minutes later, anesthesia was induced with propofol (2 mg kg-1, followed by 1 mg kg-1 every 15 seconds to achieve intubation) and maintained for 90 minutes by constant rate infusions (CRIs) of propofol alone or with fentanyl: P, propofol (0.5 mg kg-1 minute-1); PLDF, propofol (0.35 mg kg-1 minute-1) and fentanyl (0.1 µg kg-1 minute-1); PHDF, propofol (0.3 mg kg-1 minute-1) and fentanyl (0.2 µg kg-1 minute-1). Propofol CRI was increased or decreased based on the response to stimulation (50 V, 50 Hz, 10 mA), with 20 minutes between adjustments. Data were analyzed using a mixed-model anova and presented as mean±standard error. RESULTS: ropofol induction doses were 6.16±0.31, 3.67±0.21 and 3.33±0.42 mg kg-1 for P, PLDF and PHDF, respectively. Doses for PLDF and PHDF were significantly decreased from P (p<0.05) but not different between treatments. Propofol MIRNM was 0.60±0.04, 0.29±0.02 and 0.22±0.02 mg kg-1 minute-1 for P, PLDF and PHDF, respectively. MIRNM in PLDF and PHDF was significantly decreased from P. MIRNM in PLDF and PHDF were not different, but their respective percent decreases of 51±3 and 63±2% differed (p=0.035). CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl, at the doses studied, caused statistically significant and clinically important decreases in the propofol induction dose and MIRNM.

Effect of fentanyl and lidocaine on the end-tidal sevoflurane concentration preventing motor movement in dogs.

OBJECTIVE To determine effects of fentanyl, lidocaine, and a fentanyl-lidocaine combination on the minimum alveolar concentration of sevoflurane preventing motor movement (MACNM) in dogs. ANIMALS 6 adult Beagles. PROCEDURES Dogs were anesthetized with sevoflurane in oxygen 3 times (1-week intervals). Baseline MACNM (MACNM-B) was determined starting 45 minutes after induction of anesthesia. Dogs then received 1 of 3 treatments IV: fentanyl (loading dose, 15 µg/kg; constant rate infusion [CRI], 6 µg/kg/h), lidocaine (loading dose, 2 mg/kg; CRI, 6 mg/kg/h), and the fentanyl-lidocaine combination at the same doses. Determination of treatment MACNM (MACNM-T) was initiated 90 minutes after start of the CRI. Venous blood samples were collected at the time of each treatment MACNM measurement for determination of plasma concentrations of fentanyl and lidocaine. RESULTS Mean ± SEM overall MACNM-B for the 3 treatments was 2.70 ± 0.27 vol%. The MACNM decreased from MACNM-B to MACNM-T by 39%, 21%, and 55% for fentanyl, lidocaine, and the fentanyl-lidocaine combination, respectively. This decrease differed significantly among treatments. Plasma fentanyl concentration was 3.25 and 2.94 ng/mL for fentanyl and the fentanyl-lidocaine combination, respectively. Plasma lidocaine concentration was 2,570 and 2,417 ng/mL for lidocaine and the fentanyl-lidocaine combination, respectively. Plasma fentanyl and lidocaine concentrations did not differ significantly between fentanyl and the fentanyl-lidocaine combination or between lidocaine and the fentanyl-lidocaine combination. CONCLUSIONS AND CLINICAL RELEVANCE CRIs of fentanyl, lidocaine, and the fentanyl-lidocaine combination at the doses used were associated with clinically important and significant decreases in the MACNM of sevoflurane in dogs.

Effects of magnesium sulfate and propofol on the minimum alveolar concentration preventing motor movement in sevoflurane-anesthetized dogs.

OBJECTIVE To evaluate the effect of MgSO4, alone and in combination with propofol, on the minimum alveolar concentration preventing motor movement (MACNM) in sevoflurane-anesthetized dogs. ANIMALS 6 healthy purpose-bred adult male Beagles (least squares mean ± SEM body weight, 12.0 ± 1.1 kg). PROCEDURES Dogs were anesthetized 3 times at weekly intervals. The MACNM was measured 45 minutes after induction of anesthesia (baseline; MACNM-B) and was determined each time by use of a noxious electrical stimulus. Treatments were administered as a loading dose and constant rate infusion (CRI) as follows: treatment 1, MgSO4 loading dose of 45 mg/kg and CRI of 15 mg/kg/h; treatment 2, propofol loading dose of 4 mg/kg and CRI of 9 mg/kg/h; and treatment 3, MgSO4 and propofol combination (same doses used previously for each drug). A mixed-model ANOVA and Tukey-Kramer tests were used to determine effects of each treatment on the percentage decrease from MACNM-B. Data were reported as least squares mean ± SEM values. RESULTS Decrease from MACNM-B was 3.4 ± 3.1%, 48.3 ± 3.1%, and 50.3 ± 3.1%, for treatments 1, 2, and 3, respectively. The decrease for treatments 2 and 3 was significantly different from that for treatment 1; however, no significant difference existed between results for treatments 2 and 3. CONCLUSIONS AND CLINICAL RELEVANCE MgSO4 did not affect MACNM, nor did it potentiate the effects of propofol on MACNM. Administration of MgSO4 in this study appeared to provide no clinical advantage as an anesthetic adjuvant.

Effect of ketamine on the minimum infusion rate of propofol needed to prevent motor movement in dogs.

OBJECTIVE: To determine the minimum infusion rate (MIR) of propofol required to prevent movement in response to a noxious stimulus in dogs anesthetized with propofol alone or propofol in combination with a constant rate infusion (CRI) of ketamine. ANIMALS: 6 male Beagles. PROCEDURES: Dogs were anesthetized on 3 occasions, at weekly intervals, with propofol alone (loading dose, 6 mg/kg; initial CRI, 0.45 mg/kg/min), propofol (loading dose, 5 mg/kg; initial CRI, 0.35 mg/kg/min) and a low dose of ketamine (loading dose, 2 mg/kg; CRI, 0.025 mg/kg/min), or propofol (loading dose, 4 mg/kg; initial CRI, 0.3 mg/kg/min) and a high dose of ketamine (loading dose, 3 mg/kg; CRI, 0.05 mg/kg/min). After 60 minutes, the propofol MIR required to prevent movement in response to a noxious electrical stimulus was determined in duplicate. RESULTS: Least squares mean ± SEM propofol MIRs required to prevent movement in response to the noxious stimulus were 0.76 ± 0.1 mg/kg/min, 0.60 ± 0.1 mg/kg/min, and 0.41 ± 0.1 mg/kg/min when dogs were anesthetized with propofol alone, propofol and low-dose ketamine, and propofol and high-dose ketamine, respectively. There were significant decreases in the propofol MIR required to prevent movement in response to the noxious stimulus when dogs were anesthetized with propofol and low-dose ketamine (27 ± 10%) or with propofol and high-dose ketamine (30 ± 10%). CONCLUSIONS AND CLINICAL RELEVANCE: Ketamine, at the doses studied, significantly decreased the propofol MIR required to prevent movement in response to a noxious stimulus in dogs.

The anesthetic interaction of propofol and sevoflurane on the minimum alveolar concentration preventing motor movement (MACNM) in dogs.

The objective of this study was to determine the effects of propofol on the minimum alveolar concentration of sevoflurane needed to prevent motor movement (MAC(NM)) in dogs subjected to a noxious stimulus using randomized crossover design. Six, healthy, adult beagles (9.2 ± 1.3 kg) were used. Dogs were anesthetized with sevoflurane on 3 occasions, at weekly intervals, and baseline MAC(NM) (MAC(NM-B)) was determined on each occasion. Propofol treatments were administered as loading dose (LD) and constant rate infusion (CRI) as follows: Treatment 1 (T1) was 2 mg/kg body weight (BW) and 4.5 mg/kg BW per hour; T2 was 4 mg/kg BW and 9 mg/kg BW per hour; T3 was 8 mg/kg BW and 18 mg/kg BW per hour, respectively. Treatment MAC(NM) (MAC(NM-T)) determination was initiated 60 min after the start of the CRI. Two venous blood samples were collected and combined at each MAC(NM-T) determination for measurement of blood propofol concentration using high-performance liquid chromatography method (HPLC). Data were analyzed using a mixed-model ANOVA and are presented as least square means (LSM) ± standard error of means (SEM). Propofol infusions in the range of 4.5 to 18 mg/kg BW per hour resulted in mean blood concentrations between 1.3 and 4.4 µg/mL, and decreased (P < 0.05) sevoflurane MAC(NM) in a concentration-dependent manner. The percentage decrease in MAC(NM) was 20.5%, 43.0%, and 68.3%, with corresponding blood propofol concentrations of 1.3 ± 0.3 µg/mL, 2.5 ± 0.3 µg/mL, and 4.4 ± 0.3 µg/mL, for T1, T2, and T3, respectively. Venous blood propofol concentrations were strongly correlated (r = 0.855, P < 0.0001) with the decrease in MAC(NM). In dogs, propofol decreased the sevoflurane MAC(NM) in a concentration-dependent manner.

L'objectif de la présente étude était de déterminer les effets du propofol sur la concentration alvéolaire minimale de sevoflurane requise pour empêcher les mouvements moteurs (MACNM) chez des chiens soumis à un stimulus délétère en utilisant un modèle expérimental croisé aléatoire. Six chiens Beagle adultes et en santé (9,2 ± 1,3 kg) ont été utilisés. Les chiens étaient anesthésiés avec du sevoflurane à trois occasions, à une semaine d'intervalle, et la valeur de base de MACNM (MACNM-B) déterminée à chaque occasion. Les traitements de propofol furent administrés à une dose d'attaque (LD) et un taux d'infusion constant (CRI) comme suit: Traitement 1 (T1) était de 2 mg/kg de poids corporel (BW) et 4,5 mg/kg BW par heure; T2 était de 4 mg/kg BW et 9 mg/kg BW par heure; T3 était de 8 mg/kg BW et 18 mg/kg BW par heure, respectivement. La détermination de la MACNM du traitement (MACNM-T) fut initiée 60 min après le début du CRI. Deux échantillons de sang veineux furent prélevés et combinés à chaque mesure de MACNM-T pour mesurer la concentration sanguine de propofol par une méthode de chromatographie à haute performance en phase liquide (HPLC). Les données furent analysées par un modèle mixte d'ANOVA et sont présentées sous forme du moindre carré (LSM) ± écart-type (SEM).Les infusions de propofol variant entre 4,5 à 18 mg/kg BW par heure ont résulté en des concentrations sanguines moyennes entre 1,3 et 4,4 µg/mL, et diminuèrent (P < 0,05) la MACNM de sevoflurane d'une manière dépendante de la concentration. Le pourcentage de diminution de MACNM était de 20,5 %, 43,0 % et 68,3 %, avec des concentrations sanguines de propofol correspondantes de 1,3 ± 0,3 µg/mL, 2,5 ± 0,3 µg/mL, et 4,4 ± 0,3 µg/mL, pour T1, T2 et T3, respectivement. Les concentrations veineuses en propofol étaient fortement corrélées (r = 0,855, P < 0,0001) avec la diminution de MACNM. Chez les chiens, le propofol a diminué la MACNM du sevoflurane de manière dépendante de la concentration.(Traduit par Docteur Serge Messier).

The interaction of nitrous oxide and fentanyl on the minimum alveolar concentration of sevoflurane blocking motor movement (MACNM) in dogs.

The study objective was to determine the effects of 70% nitrous oxide (N2O) and fentanyl on the end-tidal concentration of sevoflurane necessary to prevent movement (MACNM) in response to noxious stimulation in dogs. Six healthy, adult, intact male, mixed-breed dogs were used on 3 occasions in a randomized crossover design. After induction of anesthesia with sevoflurane, each of the following treatments was randomly administered: fentanyl loading dose (Ld) of 15 µg/kg and infusion of 6 µg/kg per hour [treatment 1 (T1)], 70% N2O (T2), or fentanyl (Ld of 15 µg/kg and infusion of 6 µg/kg per hour) combined with 70% N2O (T3). Each dog received each of the 3 treatments once during the 3-week period. Determination of MACNM was initiated 90 min after the start of each treatment. The values were compared using the baseline MACNM, which had been determined in a previous study on the same group of dogs. Data were analyzed using a mixed-model analysis of variance (ANOVA) and Tukey-Kramer tests, and expressed as least squares mean ± SEM. The baseline MACNM decreased by 36.6 ± 4.0%, 15.0 ± 4.0%, and 46.0 ± 4.0% for T1, T2, and T3, respectively (P < 0.05), and differed (P < 0.05) among treatments. Mean fentanyl plasma concentrations did not differ (P ≥ 0.05) between T1 (3.70 ± 0.56 ng/mL) and T3 (3.50 ± 0.56 ng/mL). The combination of fentanyl and N2O resulted in a greater sevoflurane MACNM sparing effect than either treatment alone.

L'objectif de la présente étude était de déterminer les effets de l'oxyde nitreux (N2O) à 70 % et du fentanyl sur la concentration de sevoflurane en fin d'expiration nécessaire pour empêcher le mouvement (MACNM) en réponse à une stimulation désagréable chez des chiens. Six chiens mâles intacts adultes en santé de race croisée furent utilisés en 3 occasions dans des études croisées aléatoires. Après induction de l'anesthésie avec du sevoflurane, chacun des traitements suivants fut administré de manière aléatoire : dose d'induction de fentanyl (Ld) de 15 µg/kg et infusion de 6 µg/kg par heure [traitement 1 (T1)], 70 % N2O (T2), ou fentalyl (Ld de 15 µg/kg et infusion de 6 µg/kg par heure) combiné avec 70 % N2O (T3). Chaque chien a reçu chacun des trois traitements une fois durant la période d'essai de 3 semaines. La détermination du MACNM fut débutée 90 min après le début de chaque traitement. Les valeurs furent comparées en utilisant la valeur de base de MACNM, qui avait été déterminée dans une étude antérieure avec le même groupe de chiens. Les données furent analysées en utilisant un modèle mixte d'analyse de variance (ANOVA) et un test de Tukey-Kramer, et présentées comme la moyenne des moindres carrés ± écart-type. La valeur de base de MACNM diminua de 36,6 ± 4,0 %, 15,0 ± 4,0 %, et 46,0 ± 4,0 % respectivement pour T1, T2 et T3 (P < 0,05), et différait (P < 0,05) entre les traitements. Les concentrations plasmatiques moyennes ne différaient pas (P ≥ 0,05) entre T1 (3,70 ± 0,56 ng/mL) et T3 (3,50 ± 0,56 ng/mL). La combinaison de fentanyl et de N2O a produit un plus grand effet réducteur sur le MACNM de sevoflurane que chaque traitement individuel.(Traduit par Docteur Serge Messier).

Antinociceptive and selected physiological effects of morphine and xylazine on tiletamine-zolazepam anesthesia in llamas.

OBJECTIVE: Evaluate antinociception, anesthesia, and recovery in llamas given tiletamine-zolazepam (TZ) with either morphine, xylazine, morphine and xylazine, or saline. STUDY DESIGN: Randomized crossover experimental study. ANIMALS: Six healthy, adult intact male llamas. METHODS: Llamas were given each of four treatments intramuscularly with a 1-week washout: TZ (2 mg kg(-1) ) combined with either morphine (0.5 mg kg(-1) ; M), xylazine (0.15 mg kg(-1) ; X), morphine (0.5 mg kg(-1) ) and xylazine (0.15mg kg(-1) ) (MX), or saline (C). Llamas breathed room air during the experiment. Characteristics of anesthesia, recovery, and selected cardiopulmonary variables were recorded. Antinociception was assessed by clamping a claw at 5-minute intervals. Data were analyzed using a mixed-model anova and Tukey-Kramer test, and are expressed as least squares mean ± SEM. Significance was set at p < 0.05. RESULTS: No llama in the control group demonstrated antinociception. Antinociception was longest with treatment MX, followed by treatments X and M, respectively. Heart rates in llamas given treatments X and MX were significantly lower than with other treatments. The respiratory rate in llamas given treatment C was greater (p < 0.05) than for all other treatments, however, the respiratory rate was not significantly different among treatments X, M and MX. The PaO2 for llamas given MX remained <60 mmHg throughout the 20 minute period of blood gas analysis. Mean arterial blood pressure in llamas in treatment MX was less than for treatments M or C. CONCLUSION AND CLINICAL RELEVANCE: The combination of morphine (0.5 mg kg(-1) ) and xylazine (0.15 mg kg(-1) ) increased the duration of antinociception compared with xylazine alone, in TZ-anesthetized llamas. Treatments X, M and MX were associated with hypoxemia (PaO2 < 60 mmHg).

The effect of nitrous oxide on the minimum alveolar concentration (MAC) and MAC derivatives of isoflurane in dogs.

This study investigated the effects of 70% nitrous oxide (N2O) on the minimum alveolar concentration (MAC) of isoflurane (ISO) that prevents purposeful movement, the MAC of ISO at which there is no motor movement (MACNM), and the MAC of ISO at which autonomic responses are blocked (MACBAR) in dogs. Six adult, healthy, mixed-breed, intact male dogs were anesthetized with ISO delivered via mask. Baseline MAC, MACNM, and MACBAR of ISO were determined for each dog using a supra-maximal electrical stimulus (50 V, 50 Hz, 10 ms). Nitrous oxide (70%) was then administered and MAC and its derivatives (N2O-MAC, N2O-MACNM, and N2O-MACBAR) were determined using the same methodology. The values for baseline MAC, MACNM, and MACBAR were 1.39 ± 0.14, 1.59 ± 0.10, and 1.72 ± 0.16, respectively. The addition of 70% N2O decreased MAC, MACNM, and MACBAR by 32%, 15%, and 25%, respectively.

Cette étude avait comme objectif d'évaluer chez des chiens les effets de 70 % d'oxyde nitreux (N2O) sur la concentration alvéolaire minimum (MAC) d'isoflurane (ISO) qui empêche les mouvements volontaires, la MAC d'ISO à laquelle il n'y a pas de mouvement moteur (MACNM), et la MAC d'ISO à laquelle les réponses autonomes sont bloquées (MACBAR).Six chiens mâles intacts adultes de race mélangée ont été anesthésiés avec de l'ISO administré via un masque. Les valeurs de base de MAC, MACNM et de MACBAR d'ISO ont été déterminées pour chaque chien à l'aide d'un stimulus électrique supra-maximal (50 V, 50 Hz, 10 ms). De l'oxyde nitreux (70 %) fut ensuite administré et la MAC et ses dérivées (N2O-MAC, N2O-MACNM et N2O-MACBAR) déterminées à l'aide de la même méthodologie. Les valeurs des données de base de MAC, MACNM et MACBAR étaient respectivement 1,39 ± 0,14, 1,59 ± 0,10 et 1,72 ± 0,16. L'ajout de 70 % de N2O a entrainé des diminutions de MAC, MACNM et MACBAR de 32 %, 15 % et 25 %, respectivement.(Traduit par Docteur Serge Messier).

Repeated administration of tribromoethanol in C57BL/6NHsd mice.

We evaluated the effect of repeated intraperitoneal administration of tribromoethanol on various parameters in C57BL/6NHsd mice. Mice (n = 68) were randomly assigned to 1 of 7 groups to receive tribromoethanol (500 mg/kg IP) on day 0 or days 0 and 8; vehicle (tert-amyl alcohol in sterile water) only on day 0 or days 0 and 8; sterile water injection on day 0 or days 0 and 8; or no treatment. A single dose of tribromoethanol failed to produce loss of pedal reflex and had no effect on median food and water consumption but altered median body weight on days 1 through 4 when compared with that in mice that received vehicle only or no treatment. Median body weight did not differ between mice that received a single dose of tribromoethanol and those that received an injection of water. Among mice given 2 doses of tribromoethanol, induction time, anesthetic duration, and recovery time varied widely. Repeated administration of tribromoethanol had no effect on median food and water consumption or body weight compared with those in controls. Median liver weight was significantly greater in mice that received 2 doses compared with a single dose of tribromoethanol. Median liver weight did not differ between untreated mice and those that received tribromoethanol. No significant organ or tissue pathology was observed in any study animal. Although tribromoethanol did not produce morbidity, mortality, or pathologic changes in treated animals, we urge caution in use of tribromoethanol in C57BL/6NHsd mice due to its variable anesthetic effectiveness.

Physiologic and antinociceptive effects following intramuscular administration of xylazine hydrochloride in combination with tiletamine-zolazepam in llamas.

OBJECTIVE: To evaluate antinociceptive and selected effects associated with IM administration of xylazine hydrochloride in combination with tiletamine-zolazepam in llamas. ANIMALS: 8 adult male llamas. Procedures-Each llama received tiletamine-zolazepam (2 mg/kg) combined with either xylazine (0.1, 0.2, or 0.4 mg/kg) or saline (0.9% NaCl) solution IM (treatments designated as TZ-Xy0.1, TZ-Xy0.2, TZ-Xy0.4, and TZ-Sal, respectively) at 1-week intervals. Selected cardiorespiratory variables were assessed during lateral recumbency and anesthesia, and recovery characteristics were recorded. Duration of antinociception was evaluated by clamping a claw every 5 minutes. RESULTS: Interval between treatment administration and lateral recumbency for TZ-Xy0.4 was shorter than that for TZ-Xy0.1 or TZ-Sal. Mean ± SEM duration of antinociception was longer for TZ-Xy0.4 (51.3 ± 7. 0 minutes), compared with findings for TZ-Xy0.2 (31.9 ± 6.0 minutes), TZ-Xy0.1 (8.1 ± 4.0 minutes), and TZ-Sal (0.6 ± 0.6 minutes). Interval between treatment administration and standing was longer for TZ-Xy0.4 (112 ± 9 minutes) than it was for TZ-Xy0.2 (77 ± 9 minutes) or TZ-Sal (68 ± 9 minutes). Mean heart and respiratory rates during the first 30 minutes for TZ-Sal exceeded values for the other treatments. Administration of TZ-Xy0.2 and TZ-Xy0.4 resulted in Pao2 < 60 mm Hg at 5 minutes after llamas attained lateral recumbency, and values differed from TZ-Sal findings at 5, 10, and 15 minutes; Paco2 was greater for TZ-Xy0.2 and TZ-Xy0.4 than for TZ-Sal at 5, 10, 15, and 20 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: Xylazine (0.2 and 0.4 mg/kg) increased the duration of antinociception in llamas anesthetized with tiletamine-zolazepam.

The effect of fentanyl on the end-tidal sevoflurane concentration needed to prevent motor movement in dogs.

OBJECTIVE: The objectives of this study were to determine the effects of fentanyl on the end-tidal concentration of sevoflurane needed to prevent motor movement (MACNM ) in response to noxious stimulation, and to evaluate if acute tolerance develops. STUDY DESIGN: Randomized cross-over experimental study. ANIMALS: Six healthy, adult (2-3 years old), intact male, mixed-breed dogs weighing 16.2 ± 1.1 kg. METHODS: Six dogs were randomly assigned to receive one of three separate treatments over a 3 week period. After baseline sevoflurane MACNM (MACNM-B) determination, fentanyl treatments (T) were administered as a loading dose (Ld) and constant rate infusion (CRI) as follows: T1-Ld of 7.5 µg kg(-1) and CRI at 3 µg kg(-1) hour(-1); T2-Ld of 15 µg kg(-1) and CRI at 6.0 µg kg (-1) hour(-1); T3-Ld of 30 µg kg(-1) and CRI at 12 µg kg(-1) hour(-1). The MACNM was defined as the minimum end-tidal sevoflurane concentration preventing motor movement. The first post-treatment MACNM (MACNM-I) determination was initiated 90 minutes after the start of the CRI, and a second MACNM (MACNM - II) determination was initiated 3 hours after MACNM-I was established. RESULTS: The overall least square mean MACNM-B for all groups was 2.66%. All treatments decreased (p < 0.05) MACNM, and the decrease from baseline was 22%, 35% and 41% for T1, T2 and T3, respectively. Percentage change in T1 differed (p < 0.05) from T2 and T3; however, T2 did not differ from T3. MACNM-I was not significantly different from MACNM-II within treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl doses in the range of 3-12 µg kg(-1) hour(-1) significantly decreased the sevoflurane MACNM. Clinically significant tolerance to fentanyl did not occur under the study conditions.

Effect of nitrous oxide on the minimum alveolar concentration for sevoflurane and the minimum alveolar concentration derivatives that prevent motor movement and autonomic responses in dogs.

OBJECTIVE: To investigate the effects of the concurrent administration of 70% N(2)O on the minimum alveolar concentration (MAC) for sevoflurane in dogs, the MAC derivative that blocks motor movement (MAC(NM)), and the MAC derivative that blocks autonomic responses (MAC(BAR)). ANIMALS: 7 adult sexually intact male mixed-breed dogs. PROCEDURES: For each dog, anesthesia was induced with sevoflurane delivered via a face mask. Initially, the baseline MAC, MAC(NM), and MAC(BAR) for sevoflurane were determined by use of a noxious stimulus (50 V, 50 Hz, and 10 milliseconds) applied subcutaneously over a midulnar region. Nitrous oxide (70%) was added to the breathing circuit, and MAC, MAC(NM), and MAC(BAR) were determined again. Percentage changes from the respective baseline concentrations for MAC, MAC(NM)' and MAC(BAR) were calculated after the administration of N(2)O. RESULTS: Baseline median values for the MAC, MAC(NM), and MAC(BAR) for sevoflurane were 1.75%, 2.00%, and 2.50%, respectively. Addition of 70% N(2)O significantly decreased MAC, MAC(NM), and MAC(BAR) by 24.4%, 25.0%, and 35.2%, respectively, and these values did not differ significantly from each other. CONCLUSIONS AND CLINICAL RELEVANCE: Supplementation with 70% N(2)O caused a clinically important and significant decrease in the MAC, MAC(NM)' and MAC(BAR) for sevoflurane in dogs.

The effect of midazolam on the end-tidal concentration of isoflurane necessary to prevent movement in dogs.

OBJECTIVE: To determine the possible additive effect of midazolam, a GABA(A) agonist, on the end-tidal concentration of isoflurane that prevents movement (MAC(NM) ) in response to noxious stimulation. STUDY DESIGN: Randomized cross-over experimental study. ANIMALS: Six healthy, adult intact male, mixed-breed dogs. METHODS: After baseline isoflurane MAC(NM) (MAC(NM-B) ) determination, midazolam was administered as a low (LDS), medium (MDS) or high (HDS) dose series of midazolam. Each series consisted of two dose levels, low and high. The LDS was a loading dose (Ld) of 0.2 mg kg(-1) and constant rate infusion (CRI) (2.5 µg kg(-1) minute(-1)) (LDL), followed by an Ld (0.4 mg kg(-1)) and CRI (5 µg kg(-1) minute(-1)) (LDH). The MDS was an Ld (0.8 mg kg(-1)) and CRI (10 µg kg(-1) minute(-1)) (MDL) followed by an Ld (1.6 mg kg(-1)) and CRI (20 µg kg(-1) minute(-1)) (MDH). The HDS was an Ld (3.2 mg kg(-1)) and CRI (40 µg kg(-1) minute(-1)) (HDL) followed by an Ld (6.4 mg kg(-1)) and CRI (80 µg kg(-1) minute(-1)) (HDH). MAC(NM) was re-determined after each dose in each series (MAC(NM-T)). RESULTS: The median MAC(NM-B) was 1.42. MAC(NM-B) did not differ among groups (p > 0.05). Percentage reduction in MAC(NM) was significantly less in the LDS (11 ± 5%) compared with MDS (30 ± 5%) and HDS (32 ± 5%). There was a weak correlation between the plasma midazolam concentration and percentage MAC(NM) reduction (r = 0.36). CONCLUSION AND CLINICAL RELEVANCE: Midazolam doses in the range of 10-80 µg kg(-1) minute(-1) significantly reduced the isoflurane MAC(NM) . However, doses greater than 10 µg kg(-1) minute(-1) did not further decrease MAC(NM) indicating a ceiling effect.

Effect of intravenous administration of tramadol hydrochloride on the minimum alveolar concentration of isoflurane in rabbits.

OBJECTIVE: To evaluate the effect of IV administration of tramadol hydrochloride on the minimum alveolar concentration of isoflurane (ISOMAC) that prevented purposeful movement of rabbits in response to a noxious stimulus. ANIMALS: Six 6- to 12-month-old female New Zealand White rabbits. PROCEDURES: Anesthesia was induced and maintained with isoflurane in oxygen. A baseline ISOMAC was determined by clamping a pedal digit with sponge forceps until gross purposeful movement was detected or a period of 60 seconds elapsed. Subsequently, tramadol (4.4 mg/kg) was administered IV and the posttreatment ISOMAC (ISOMAC(T)) was measured. RESULTS: Mean +/- SD ISOMAC and ISOMAC(T) values were 2.33 +/- 0.13% and 2.12 +/- 0.17%, respectively. The ISOMAC value decreased by 9 +/- 4% after tramadol was administered. Plasma tramadol and its major metabolite (M1) concentrations at the time of ISOMAC(T) determination varied widely (ranges, 181 to 636 ng/mL and 32 to 61 ng/mL, respectively). Intervals to determination of ISOMAC(T) and plasma tramadol and M1 concentrations were not correlated with percentage change in the ISOMAC. Heart rate decreased significantly immediately after tramadol administration but by 10 minutes afterward was not different from the pretreatment value. Systolic arterial blood pressure decreased to approximately 60 mm Hg for approximately 5 minutes in 3 rabbits after tramadol administration. No adverse effects were detected. CONCLUSIONS AND CLINICAL RELEVANCE: As administered, tramadol had a significant but clinically unimportant effect on the ISOMAC in rabbits. Higher doses of tramadol may provide clinically important reductions but may result in a greater degree of cardiovascular depression.

Prognostic indicators for dogs and cats with cardiopulmonary arrest treated by cardiopulmonary cerebral resuscitation at a university teaching hospital.

OBJECTIVE: To determine the association among signalment, health status, other clinical variables, and treatments and events during cardiopulmonary cerebral resuscitation (CPCR) with the return of spontaneous circulation (ROSC) for animals with cardiopulmonary arrest (CPA) in a veterinary teaching hospital. DESIGN: Cross-sectional study. ANIMALS: 161 dogs and 43 cats with CPA. PROCEDURES: Data were gathered during a 60-month period on animals that had CPA and underwent CPCR. Logistic regression was used to evaluate effects of multiple predictors for ROSC. RESULTS: 56 (35%) dogs and 19 (44%) cats had successful CPCR. Twelve (6%) animals (9 dogs and 3 cats) were discharged from the hospital. Successfully resuscitated dogs were significantly more likely to have been treated with mannitol, lidocaine, fluids, dopamine, corticosteroids, or vasopressin; had CPA while anesthetized; received chest compressions while positioned in lateral recumbency; and had a suspected cause of CPA other than hemorrhage or anemia, shock, hypoxemia, multiple organ dysfunction syndrome, cerebral trauma, malignant arrhythmia, or an anaphylactoid reaction and were less likely to have been treated with multiple doses of epinephrine, had a longer duration of CPA, or had multiple disease conditions, compared with findings in dogs that were not successfully resuscitated. Successfully resuscitated cats were significantly more likely to have had more people participate in CPCR and less likely to have had shock as the suspected cause of CPA, compared with findings in cats that were not successfully resuscitated. CONCLUSIONS AND CLINICAL RELEVANCE: The prognosis was grave for animals with CPA, except for those that had CPA while anesthetized.

Effects of tramadol on the minimum alveolar concentration of sevoflurane in dogs.

OBJECTIVE: To evaluate the effect of tramadol on sevoflurane minimum alveolar concentration (MAC(SEVO)) in dogs. It was hypothesized that tramadol would dose-dependently decrease MAC(SEVO). STUDY DESIGN: Randomized crossover experimental study. ANIMALS: Six healthy, adult female mixed-breed dogs (24.2 +/- 2.6 kg). METHODS: Each dog was studied on two occasions with a 7-day washout period. Anesthesia was induced using sevoflurane delivered via a mask. Baseline MAC (MAC(B)) was determined starting 45 minutes after tracheal intubation. A noxious stimulus (50 V, 50 Hz, 10 ms) was applied subcutaneously over the mid-humeral area. If purposeful movement occurred, the end-tidal sevoflurane was increased by 0.1%; otherwise, it was decreased by 0.1%, and the stimulus was re-applied after a 20-minute equilibration. After MAC(B) determination, dogs randomly received a tramadol loading dose of either 1.5 mg kg(-1) followed by a continuous rate infusion (CRI) of 1.3 mg kg(-1 )hour(-1) (T1) or 3 mg kg(-1) followed by a 2.6 mg kg(-1 )hour(-1) CRI (T2). Post-treatment MAC determination (MAC(T)) began 45 minutes after starting the CRI. Data were analyzed using a mixed model anova to determine the effect of treatment on percentage change in baseline MAC(SEVO) (p < 0.05). RESULTS: The MAC(B) values were 1.80 +/- 0.3 and 1.75 +/- 0.2 for T1 and T2, respectively, and did not differ significantly. MAC(T) decreased by 26 +/- 8% for T1 and 36 +/- 12% for T2. However, there was no statistically significant difference in the decrease between the two treatments. CONCLUSION AND CLINICAL RELEVANCE: Tramadol significantly reduced MAC(SEVO) but this was not dose dependent at the doses studied.

Effects of intravenous lidocaine, ketamine, and the combination on the minimum alveolar concentration of sevoflurane in dogs.

OBJECTIVE: To evaluate the effects of intravenous lidocaine (L) and ketamine (K) alone and their combination (LK) on the minimum alveolar concentration (MAC) of sevoflurane (SEVO) in dogs. STUDY DESIGN: Prospective randomized, Latin-square experimental study. ANIMALS: Six, healthy, adult Beagles, 2 males, 4 females, weighing 7.8 - 12.8 kg. METHODS: Anesthesia was induced with SEVO in oxygen delivered by face mask. The tracheas were intubated and the lungs ventilated to maintain normocapnia. Baseline minimum alveolar concentration of SEVO (MAC(B)) was determined in duplicate for each dog using an electrical stimulus and then the treatment was initiated. Each dog received each of the following treatments, intravenously as a loading dose (LD) followed by a constant rate infusion (CRI): lidocaine (LD 2 mg kg(-1), CRI 50 microg kg(-1)minute(-1)), lidocaine (LD 2 mg kg(-1), CRI 100 microg kg(-1) minute(-1)), lidocaine (LD 2 mg kg(-1), CRI 200 microg kg(-1) minute(-1)), ketamine (LD 3 mg kg(-1), CRI 50 microg kg(-1) minute(-1)), ketamine (LD 3 mgkg(-1), CRI 100 microg kg(-1) minute(-1)), or lidocaine (LD 2 mg kg(-1), CRI 100 microg kg(-1) minute(-1)) + ketamine (LD 3 mg kg(-1), CRI 100 microg kg(-1) minute(-1)) in combination. Post-treatment MAC (MAC(T)) determination started 30 minutes after initiation of treatment. RESULTS: Least squares mean +/- SEM MAC(B) of all groups was 1.9 +/- 0.2%. Lidocaine infusions of 50, 100, and 200 microg kg(-1) minute(-1) significantly reduced MAC(B) by 22.6%, 29.0%, and 39.6%, respectively. Ketamine infusions of 50 and 100 microg kg(-1) minute(-1) significantly reduced MAC(B) by 40.0% and 44.7%, respectively. The combination of K and L significantly reduced MAC(B) by 62.8%. CONCLUSIONS AND CLINICAL RELEVANCE: Lidocaine and K, alone and in combination, decrease SEVO MAC in dogs. Their use, at the doses studied, provides a clinically important reduction in the concentration of SEVO during anesthesia in dogs.

Efficacy and cost-effectiveness of transdermal fentanyl patches for the relief of post-operative pain in dogs after anterior cruciate ligament and pelvic limb repair.

OBJECTIVES: To determine whether transdermal fentanyl patches provided cost-effective post-operative analgesia in dogs with pelvic limb injuries. STUDY DESIGN: Prospective, randomized, blinded clinical trial. ANIMALS: Twenty-four dogs undergoing repair of ruptured cranial cruciate ligaments or pelvic limb fractures. METHODS: Dogs were randomly assigned to one of two groups: those receiving transdermal fentanyl patches (group F) and those receiving injectable morphine for control of post-operative pain (group M). Patients in both treatment groups were monitored for adequacy of analgesia and alterations in physiological variables. Plasma fentanyl concentrations were measured in Group F. Rescue morphine was given if a dog was deemed uncomfortable. The time of first rescue morphine, the total amount, and number of doses of morphine administered over 72 hours was quantified and compared for each group. RESULTS: There was no significant treatment effect on any of the parameters, except for serum cortisol concentration, which was significantly lower overall in group F (p = 0.01). Pain scores peaked at 6 hours post-extubation and were higher than baseline from 2 to 20 hours post-extubation. Cortisol concentrations were the highest at time 0 (extubation) and were significantly higher than baseline until 2 hours post-extubation. Pain scores correlated with fentanyl plasma concentrations (p = 0.0001 and p = 0.01, respectively), but the correlation was low (r = 0.26 and r = 0.16, respectively). No correlation was found between serum cortisol concentrations and pain scores in either group. Fentanyl cost and total cost for pain management were considerably higher for group F. CONCLUSIONS: Fentanyl patches did not provide better analgesia or a reduced requirement for rescue opioid compared with intramuscular morphine. CLINICAL RELEVANCE: When considering overall costs to the client for comparable analgesic intervention, fentanyl patches increased rather than decreased cost during the first 24 hours post-operatively.

Comparison of oral and subcutaneous administration of buprenorphine and meloxicam for preemptive analgesia in cats undergoing ovariohysterectomy.

OBJECTIVE: To compare the effectiveness of preoperative PO and SC administration of buprenorphine and meloxicam for prevention of postoperative pain-associated behaviors in cats undergoing ovariohysterectomy. DESIGN: Randomized controlled study. ANIMALS: 51 female cats (4 to 60 months old; weight range, 1.41 to 4.73 kg [3.1 to 10.4 lb]). PROCEDURE: Cats received 1 of 5 treatments at the time of anesthetic induction: buprenorphine PO (0.01 mg/kg [0.0045 mg/lb]; n = 10), buprenorphine SC (0.01 mg/kg; 10), meloxicam SC (0.3 mg/kg 10.14 mg/lb]; 10), meloxicam PO (0.3 mg/kg; 10), or 0.3 mL of sterile saline (0.9% NaCI) solution SC (control group; 11). Sedation scores and visual analog scale and interactive visual analog scale (IVAS) pain-associated behavior scores were assigned to each cat 2 hours before and at intervals until 20 hours after surgery. RESULTS: Cats receiving meloxicam PO or SC had significantly lower IVAS scores (2.91 and 2.02, respectively), compared with IVAS scores for cats receiving buprenorphine PO (755). Pain-associated behavior scores for cats administered buprenorphine or meloxicam PO or SC preoperatively did not differ significantly from control group scores. Rescue analgesia was not required by any of the cats receiving meloxicam, whereas 3 of 10 cats receiving buprenorphine PO, 2 of 10 cats receiving buprenorphine SC, and 1 of 11 cats receiving the control treatment required rescue analgesia. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of pain-associated behavior scores, cats receiving meloxicam PO or SC before ovariohysterectomy appeared to have less pain after surgery than those receiving buprenorphine PO preoperatively.