Use of medetomidine-zolazepam-tiletamine with and without atipamezole reversal to immobilize captive California sea lions

From June 1998 to August 1999, 39 California sea lions (Zalophus californianus) were immobilized at a rehabilitation center in northern California (USA) using medetomidine plus zolazepam and tiletamine (MZT), alone and in combination with isoflurane, with atipamezole reversal. Animals were given 70 microg/kg medetomidine with 1 mg/kg of a 1:1 solution of tiletamine and zolazepam intramuscularly. Mean (+/-SD) time to maximal effect was 5+/-3 min. At the end of the procedure, animals were given 200 microg/kg atipamezole intramuscularly. Immobilization and recovery times were, respectively, 28+/-18 and 9+/-7 min for 15 animals maintained with MZT alone and 56+/-47 and 9+/-6 min for 18 animals intubated and maintained with isoflurane. One mortality occurred during anesthesia. Other disadvantages of the MZT combination included some prolonged ataxia, weakness and disorientation during recovery. However, the use of MZT resulted in faster induction and a more reliable plane of anesthesia that was reversible with atipamezole and safer than other previously used intramuscular agents. Physiological parameters including heart rate, respiratory rate, temperature, pulse oximeter saturation, and end-tidal carbon dioxide were monitored.     

Effects of epidural morphine and transdermal fentanyl analgesia on physiology and behaviour after abdominal surgery in pigs

The objective of this work was to evaluate the physiological and behavioural effects of opioid analgesic treatment in pigs subjected to abdominal surgery. Ten Swedish Landrace x Yorkshire pigs (20 +/- 4 kg b.w.) were submitted for intestinal cannulation. The pigs were allocated into two groups during one preoperative, one surgical and two postoperative days. All pigs were anaesthetized with medetomidine, tiletamine and zolazepam. One group was treated with epidural morphine (0.1 mg/kg) preoperatively, and transdermal fentanyl patches (50 microg/kg/h) were applied behind the ear immediately after surgery. The other group received epidural saline (equivalent volume) and placebo patches. All pigs were regularly weighed and clinically examined and repeated blood samples were analysed for serum concentrations of cortisol, beta-endorphin and fentanyl. Pre- and postoperative behaviours were evaluated by a swine specialist blinded to the treatment, three times a day, and were also videotape recorded for a total of 84 h per pig. No differences in behaviour were noted by the observer. During the first postoperative 12 h, treated pigs did not differ in activity compared with preoperative recordings, while untreated pigs were found to be less active. The treated group started to show interest in eating immediately after anaesthesia recovery, whereas the placebo group did not. During the 12-60 h postoperative period, the treated group had lower activity levels compared with the preoperative levels, which were similar to those in the placebo group. Treated pigs gained 0.5 +/- 0.2 kg during the subsequent two postoperative days, whereas the untreated pigs lost weight throughout the experiment. Cortisol concentration differed immediately after the surgery: Group P had 325 +/- 120 nmol/L and Group M 159 +/- 49 nmol/L. beta-endorphin concentration did not differ between groups. The highest serum fentanyl concentration (0.37 +/- 0.3 ng/mL) was measured 24 h postoperatively. Preoperative epidural morphine in combination with postoperative transdermal fentanyl resulted in earlier return to normal activity levels and an immediate weight gain after surgery.     

Reduction of isoflurane MAC with buprenorphine and morphine in rats

Preoperative analgesics are being increasingly used to provide analgesia in the intraoperative and postoperative period. Opioids reduce anaesthetic requirements, although the effect varies with the different drug and species. The aim of this work was to determine whether buprenorphine reduces the minimum alveolar concentration (MAC) of isoflurane in a dose-related fashion, and whether this effect is similar to morphine when clinical doses of both drugs are used in the rat. Thirty-six male Wistar rats were anaesthetized with isoflurane, and MAC was determined before and after the administration of either buprenorphine or morphine. MAC of isoflurane was determined from alveolar gas samples when a standard noxious stimulus, in the form of a tail clamp, was applied. The duration and degree of reduction of the MAC of isoflurane were recorded. Basic cardiovascular and respiratory measurements were also recorded. Buprenorphine (10, 30 and 100 microg/kg) and morphine (1, 3 and 10 mg/kg) reduced in a dose-dependent fashion the MAC of isoflurane by 15%, 30% and 50%, respectively. Buprenorphine resulted in less cardiovascular and respiratory depression and had a longer-lasting action than morphine. In conclusion, buprenorphine has a dose-related isoflurane sparing effect in the rat similar to that caused by morphine at clinical doses of both drugs.     

Pharmacokinetics and tissue residues of Telazol in free-ranging polar bears

A pharmacokinetic and tissue residue study was conducted to assess the risks associated with human consumption of polar bears in arctic Canada that have been exposed to the immobilizing drug Telazol, a mixture of tiletamine hydrochloride and zolazepam hydrochloride. Twenty-two bears were remotely injected with about 10 mg/kg of Telazol. Following immobilization, serum samples were collected serially at regular intervals until the bears awakened. Sixteen of the bears were relocated and killed under permit by local hunters at various times from 0.5 to 11 days after dosing. Serum, kidney, muscle and adipose tissue samples were collected immediately after death. All samples were stored at -70 C until analysis by HPLC. The concentration-time data of tiletamine and zolazepam in serum during the immobilization period were fitted to curves by computer and the pharmacokinetic parameters assessed. In addition, the serum and tissue samples collected at the time of death were analyzed for both parent drugs, for one metabolite of tiletamine (CI-398), and for three metabolites of zolazepam (metabolites 1, 2 and 4). A one-compartment model with first-order absorption and elimination best fit the time-series data for the drugs in serum during the immobilization period. This model gave half-lives (mean +/- SE) for tiletamine and zolazepam of 1.8+/-0.2 h and 1.2+/-0.08 h, respectively, clearance values of 2.1+/-0.3 l x h(-1) x kg(-1) and 1.1+/-0.1 l x h(-1) x kg(-1), and volumes of distribution of 5.2+/-0.6 l/kg and 1.8+/-0.2 l/kg. The concentrations of both drugs and their metabolites declined rapidly to trace levels by 24 h post-dosing, although extremely low concentrations of some metabolites were encountered sporadically over the entire sampling period. In particular, zolazepam metabolite 2, remained detectable in fat and muscle tissue at the end of the study, 11 days after dosing. It was concluded that during immobilization, both tiletamine and zolazepam levels decline rapidly in a monoexponential fashion, and their pharmacokinetic parameters in polar bears are similar to those observed in other species. Tissue levels of the drugs and their metabolites declined sufficiently rapidly that individuals eating meat from exposed bears would be unlikely to experience pharmacological effects from the drugs. Nevertheless, slight exposure to the drugs and/or their metabolites might be possible for an indeterminate time after dosing.     

Determination of constituents of Telazol--tiletamine and zolazepam by a gas chromatography/mass spectrometry-based method

Tiletamine and zolazepam injection (Telazol) is used in veterinary surgical practice to induce short-term anesthesia and also to immobilize wild animals. The present work describes a sensitive method to measure tiletamine and zolazepam concentrations in plasma by means of GC/EI-MS on a 5% phenyl/95% methylpolysiloxane column. A simple liquid extraction procedure with ethyl acetate was used to isolate the two compounds and the same were separated and analyzed by GC/MS without derivatization. A formal validation of the assay demonstrated good accuracy and precision for both tiletamine (98-100.8%; C.V.total < 6.7%) and zolazepam (98.3-103.4; C.V.total < 13.2%). With 500 microl of plasma, the limits of quantification for both tiletamine and zolazepam were found to be 10 ng/ml. Both compounds were stable after three freeze-thaw cycles. The assay was used to analyze plasma samples collected from a pig after intramuscular administration of 10 mg/kg of Telazol. The plasma concentration-time profile of tiletamine and zolazepam from this representative pig is also provided.     

Nephrotoxicity of tiletamine in New Zealand white rabbits.

Tiletamine and zolazepam, the two constituents of Telazol, were evaluated independently to determine which agent was responsible for the nephrotoxicity caused by Telazol in New Zealand White rabbits. Five rabbits were injected i.m. with 32 mg/kg of tiletamine, four animals received 7.5 mg/kg of tiletamine, and five rabbits received 32 mg/kg of zolazepam. Urinalysis was performed and blood urea nitrogen and serum creatinine were monitored for 7 days postinjection. In all five rabbits injected with the high dose of tiletamine, blood urea nitrogen and creatinine rose by 3 days postinjection and increased steadily throughout the week. By 4 days postinjection, urine protein and glucose were elevated and cellular and protein casts were present. No serum chemistry or urine abnormalities were detected in rabbits receiving low doses of tiletamine, zolazepam, or in the four control rabbits. All animals were euthanized and necropsied at 7 days postinjection. Histopathology showed severe renal tubular necrosis in all five rabbits injected with 32 mg/kg tiletamine. Mild nephrosis was present in three of four rabbits injected with 7.5 mg/kg of tiletamine. No lesions were present in the zolazepam-injected or control rabbits. The results of this study show that tiletamine is the constituent responsible for the nephrotoxicity of Telazol in rabbits. They further demonstrate that doses commonly used for anesthetic induction or restraint can produce renal lesions in rabbits.     

The influence of pre-anaesthetic administration of buprenorphine on the anaesthetic effects of ketamine/medetomidine and pentobarbitone in rats and the consequences of repeated anaesthesia

Rats received pentobarbitone (60, 48 and 36 mg/kg i.p.) or ketamine/medetomidine (75/100, 60/80 and 45/60 mg/microg/kg i.p.) alone, or one hour following buprenorphine (0.5 mg/kg s.c.). Animals were anaesthetized once per week for 6 weeks with one of three anaesthetic doses according to a randomized block design. In the pentobarbitone group, animals which received buprenorphine had longer sleep times (236 +/- 22 cf. 204 +/- 21 min) and longer durations of surgical anaesthesia (83 +/- 14 cf. 27 +/- 8 min) (P<0.01), these effects being potentiated with increasing anaesthetic doses (P<0.01). A greater degree of respiratory depression was found in animals that received buprenorphine (P<0.01) although this was judged clinically acceptable in all cases. Unexpectedly high mortality and a high incidence of anaesthetic complications (nine of 16 animals) in the ketamine/medetomidine group made statistical analysis of these data impossible. We conclude that for pentobarbitone, pre-anaesthetic administration of buprenorphine reduces the dose of anaesthetic required to produce surgical anaesthesia, in addition to the presumed benefits of pre-emptive analgesia. In view of the high mortality encountered, we advise caution when considering pre-anaesthetic use of opioids in combination with ketamine/medetomidine in rats.     

Effect of Acetaminophen Alone and in Combination with Morphine and Tramadol on the Minimum Alveolar Concentration of Isoflurane in Rats

Background

It has been observed that acetaminophen potentiates the analgesic effect of morphine and tramadol in postoperative pain management. Its capacity as an analgesic drug or in combinations thereof to reduce the minimum alveolar concentration (MAC) of inhalational anesthetics represents an objective measure of this effect during general anesthesia. In this study, the effect of acetaminophen with and without morphine or tramadol was evaluated on the isoflurane MAC.

Methods

Forty-eight male Wistar rats were anesthetized with isoflurane in oxygen. MAC_ISO was determined from alveolar gas samples at the time of tail clamping without the drug, after administering acetaminophen (300 mg/kg), morphine (3 mg/kg), tramadol (10 mg/kg), acetaminophen (300 mg/kg) + morphine (3 mg/kg), and acetaminophen (300 mg/kg) + tramadol (10 mg/kg).

Results

The control and acetaminophen groups did not present statistically significant differences (p = 0.98). The values determined for MAC_ISO after treatment with acetaminophen + morphine, acetaminophen + tramadol, morphine, and tramadol were 0.98% ± 0.04%, 0.99% ± 0.009%, 0.97% ± 0.02%, and 0.99% ± 0.01%, respectively.

Conclusions

The administration of acetaminophen did not reduce the MAC of isoflurane and did not potentiate the reduction in MAC_ISO by morphine and tramadol in rats, and therefore does not present a sparing effect of morphine or tramadol in rats anesthetized with isoflurane.     

Comparative immobilization of wild felids in Thailand

We immobilized individuals of four free-ranging felid species, leopard cat (Prionailurus bengalensis), clouded leopard (Neofelis nebulosa), Asiatic golden cat (Catopuma temminckii), and marbled cat (Pardofelis marmorata) with ketamine hydrochloride and xylazine hydrochloride (KH-XH) and with tiletamine hydrochloride and zolazepam hydrochloride (TH-ZH) between March 1998 and July 2002. Mean (+/-SD) dose of KH and XH was 26.51+/-5.71 mg/kg and 1.89+/-0.43 mg/kg, respectively (n=25), and mean dose of TH-ZH was 11.61+/-3.39 mg/kg (n=28). Dose was significantly correlated with induction time (P<0.001) and duration of anesthesia (P<0.05), but not with recovery time. There were significant differences between the drug combinations in time to induction (P<0.03) and time to anesthesia (P<0.01); recovery times were not significantly different. We conclude that immobilization of these felids with TH-ZH and KH-XH is effective and safe, but TH-ZH is preferred because of the smaller volume of drug necessary for sedation, faster time to induction, and absence of prolonged muscle rigidity during anesthesia.     

Effects of repeated anaesthesia with ketamine/medetomidine and of pre-anaesthetic administration of buprenorphine in rats

Two groups of rats were anaesthetized at weekly intervals for 6 weeks with either ketamine/medetomidine alone (60 mg/0.4 mg/kg i.p.) or ketamine/medetomidine (45 mg/0.3 mg/kg i.p.) one hour following buprenorphine (0.05 mg/kg s.c.). Animals that received buprenorphine had longer periods of surgical anaesthesia (P = 0.04) and a greater depression of both mean pedal withdrawal score (P < 0.01) and mean respiratory rate (P = 0.014). Mean total duration of anaesthesia was also greater in the buprenorphine group on day 1. Sleep times reduced with successive doses of anaesthetic in the buprenorphine group (P = 0.024). Two animals in the buprenorphine group died. Repeated anaesthesia with ketamine/medetomidine alone was not associated with anaesthetic mortality. These results indicate that although buprenorphine has a clear anaesthetic-sparing effect, its use with ketamine/medetomidine may be associated with an increased risk of anaesthetic-related mortality.     

Immobilization of California sea lions using medetomidine plus ketamine with and without isoflurane and reversal with atipamezole

The use of medetomidine and ketamine, alone and in combination with isoflurane, with atipamezole reversal was evaluated for immobilizing 51 California sea lions (Zalophus californianus) for a variety of medical procedures at a rehabilitation center in northern California (USA) between May 1997 and August 1998. Animals were given 140 microg/kg medetomidine with 2.5 mg/kg ketamine intramuscularly. Mean (+/-SD) time to maximal effect was 8+/-5 min. At the end of the procedure, animals were given 200 microg/kg atipamezole intramuscularly. Immobilization and recovery times were, respectively, 25+/-12 and 9+/-7 min for 35 animals maintained with medetomidine and ketamine alone and 58+/-30 and 9+/-9 min for 16 animals intubated and maintained with isoflurane. No mortalities occurred as a result of the immobilizations. Disadvantages of the medetomidine and ketamine combination included a moderate variation in time to maximal effect and plane of sedation, a large injection volume and high cost. However, this combination offers safe and reversible immobilization that can be easily administered by the intramuscular route and that produces a plane of anesthesia that is sufficient to carry out most routine diagnostic procedures.     

Effect of isoflurane, atracurium, fentanyl, and noxious stimulation on bispectral index in pigs

The study reported here was done to determine the relationship between anesthesia depth and bispectral index (BIS) in stimulated pigs. Isoflurane minimal alveolar concentration (MAC) was determined using the tail-clamp method in 16 Yorkshire/Landrace-cross pigs with mean+/-SEM weight of 27.7+/-1.76 kg. One week later, BIS, ECG, heart rate, arterial blood pressure, esophageal temperature, end-tidal CO2 tension and isoflurane concentration, arterial pH, PaO2, PaCO2, plasma bicarbonate concentration, and base excess were determined at each of five isoflurane MAC-multiples: 0.8, 1.0, 1.3, 1.6, and 2.0. Six treatments were studied: isoflurane; isoflurane and atracurium; isoflurane, atracurium, and fentanyl; isoflurane with noxious stimulation; isoflurane and atracurium with noxious stimulation; and isoflurane, atracurium, and fentanyl with noxious stimulation. The noxious stimulus during BIS measurement was the same as that for MAC determination. Each pig was studied three times (n = 8), and order of MAC-multiples and treatments was randomized. Data were evaluated by use of general linear model analysis of variance and linear regression analysis, with statistical significance set at P < 0.05. Significant differences in BIS values were identified between MAC-multiples within each treatment and between treatment 3 compared with treatments 2 and 4. Significant differences also were observed within and between treatments for heart rate, arterial blood pressure, and PaO2. Use of BIS appears reliable for identification of light versus deep anesthesia, but is of limited use for discrimination between isoflurane MAC-multiples of 1 and 1.6. We conclude that, compared with other treatments, atracurium and noxious stimulation had no significant effect on BIS.     

Field immobilization of raccoons (Procyon lotor) with Telazol and xylazine

The effectiveness of tiletamine plus zolazepam (Telazol) and xylazine was evaluated as an immobilizing combination for raccoons (Procyon lotor). Fifteen raccoons were injected intramuscularly with a 3:2 mixture of Telazol (3.2+/-0.6 mg/kg [mean+/-SD]) and xylazine (2.1+/-0.4 mg/kg) at Pictured Rocks National Lakeshore, Michigan, USA, during May-October, 2001-03. Mean induction time was 4.8+/-3.8 min; mean recovery time was 128.5+/-48.4 min. No linear relationships were found between the amount (mg/kg) of Telazol-xylazine injected and induction (r2 = 0.06, P = 0.40) or recovery times (r2 = 0.01, P = 0.78). Mean heart rate, respiratory rate, and body temperature declined through 20 min after induction (P< 0.05). No mortality occurred and no short-term adverse effects were observed in recaptured individuals. I conclude that a 3:2 mixture of Telazol-xylazine is a safe and effective immobilizing agent for raccoons when conducting nonsurgical field procedures. Immobilizing raccoons with Telazol at 3 mg/kg and xylazine at 2 mg/kg should provide up to 60 min of handling time and usually allow full recovery in about 120 min.     

Estimation of minimum alveolar concentration (MAC) for halothane, enflurane and isoflurane in spontaneously breathing guinea pigs

MAC for halothane, enflurane and isoflurane was determined in guinea pigs (Cavia porcellus) exposed to constant anesthetic concentrations (2.5 hours each) in a flow-through glass chamber. The following values were obtained (N = 8 for each anesthetic): 1.01 +/- 0.03 vol% for halothane, 2.17 +/- 0.04 vol% for enflurane, and 1.15 +/- 0.05 vol% for isoflurane. In guinea pigs, MAC for halothane and enflurane are similar to those reported for other rodents, while MAC for isoflurane is lower. The data indicate that guinea pigs possibly are more susceptible to isoflurane's anesthetic actions than other rodents.     

Immobilization of free-ranging nine-banded and great long-nosed armadillos with three anesthetic combinations

Nine-banded (n = 47) and great (n = 31) long-nosed armadillos (Dasypus novemcinctus and Dasypus kappleri) were immobilized for clinical examination and collection of biological samples as part of a wildlife rescue during the filling of a hydroelectric dam (Petit Saut, French Guiana) from May 1994 to April 1995. Three intramuscular (i.m.) anesthetic combinations were evaluated: (1) tiletamine/zolazepam (T/Z) at a dose of 8.5 mg/kg in 12 nine-banded long-nosed armadillos (NBA) and 10 great long-nosed armadillos (GLA), (2) ketamine at 40 mg/kg combined with xylazine at 1.0 mg/kg (K/X) in 18 NBA and nine GLA, and (3) ketamine at 7.5 mg/kg combined with medetomidine at 75 microng/kg (K/M) in 17 NBA and 12 GLA, antagonized by 375 microg/kg atipamezole. Induction was smooth, ranged from mean +/- SD = 2.8+/-0.6 to 4.3+/-1.8 min, and did not differ significantly between protocols, species, or sex. In NBA, immobilization time ranged from 43.8+/-27.8 to 66.5+/-40.0 min and did not differ between protocols or sex. Muscle relaxation was judged to be better with K/X and K/M versus T/Z. In GLA, the response to the anesthetic protocols was more variable and immobilization time ranged from 30.4+/-6.2 to 98.4+/-33.7 min. The main difference was observed in GLA females receiving the T/Z combination, in which immobilization time was significantly longer versus males, but also versus GLA K/M group, and versus NBA T/Z group. Effects on body temperature, heart rate and respiratory rate were limited. Thirty six to 50% of the individuals showed hypoxemia (SpO2 < 85%) throughout anesthesia and values <80% also were recorded but the hypoxemia was not associated with clinical signs. With T/Z and K/X, recovery was irregular and prolonged up to 2 to 3 hr in some individuals. In K/M groups, first standing was observed 1.0 to 16.4 min after i.m. atipamezole injection without adverse effects. Finally, the three anesthetic combinations used in this study were effective and safe agents for 30 to 40 min immobilizations including minor surgery procedures. The ability to antagonize the medetomidine-induced sedation with atipamezole significantly reduces the recovery time, making the K/M combination preferable, especially in field conditions.     

Tiletamine-zolazepam-xylazine immobilization of fishers (Martes pennanti)

The effectiveness of tiletamine plus zolazepam (Telazol) and xylazine as an immobilizing combination for fishers (Martes pennanti) was evaluated. Ten fishers were intramuscularly injected using a 5:3 mixture of Telazol (2.9+/-0.6 mg/kg [mean+/-SD]) and xylazine (2.1+/-0.4 mg/kg) at Pictured Rocks National Lakeshore, Michigan (USA) during May to October, 2001-05. Mean induction time was 4.7+/-4.4 min; mean recovery time was 94.6+/-46.0 min. There was no relationship between the amount (mg/kg) of Telazol-xylazine injected and time to first effect of immobilants, dosage and time to induction, or between dosage and time to recovery. Mean heart rate remained constant through 20 min postinduction. Respiratory rate and body temperature declined through 10 and 20 min postinduction, respectively. No mortality occurred and no adverse effects were observed in individuals up to 19 mo later. It was concluded that a 5:3 mixture of Telazol-xylazine is a safe and effective immobilizing agent for fishers when conducting nonsurgical field procedures. Immobilizing fishers with 6-7 mg/kg of the combination (3.8-4.4 mg/kg Telazol and 2.3-2.6 mg/kg xylazine) should provide > or =30 min of handling time and allow full recovery in < 90 min.     

Evaluation of a combination of tiletamine and zolazepam as an anesthetic for laboratory rodents

A combination of equal parts of tiletamine hydrochloride and zolazepam hydrochloride was evaluated as an injectable anesthetic for rats, mice, and hamsters. The drug produced satisfactory anesthesia and analgesia in rats when given either intraperitoneally or intramuscularly at concentrations of 20 or 40 mg/kg body weight. The length of anesthesia was dose dependent and was somewhat longer in females as compared to males, and inbreds compared to outbreds. Incisions through the peritoneum of anesthetized rats evoked little or no response, whereas cervical skin incisions evoked a slight response in many rats. Anesthesia without analgesia occurred in mice at dosages of 80 mg/kg body weight and higher, however, many animals developed respiratory distress and died at dosages of 100 to 160 mg/kg body weight. In hamsters, anesthesia but not analgesia occurred at drug concentrations of 50 to 80 mg/kg body weight. It was concluded that a tiletamine and zolazepam combination was an effective anesthetic for rats, but not for mice or hamsters.     

Effect of morphine on breathing and behavior in fetal sheep

To define the dose response of apnea and breathing to morphine we studied 12 fetuses at 116-141 days of gestation using our window technique. We instrumented the fetus to record electrocortical activity (ECoG), eye movements (EOG), diaphragmatic activity (integral of EMGdi), heart rate, carotid blood pressure, and amniotic pressure. Saline and morphine in doses of 0.03, 0.1, 0.5, 1, and 3 mg/kg were injected in random order in the jugular vein of the fetus during low-voltage ECoG. Fetuses were videotaped for evaluation of fetal behavior. We found 1) that saline did not elicit a response; 2) apnea, associated with a change from low- to high-voltage ECoG, increased from 2.2 +/- 1.5 (SE) min in two fetuses at a dose of 0.03 mg to 20 +/- 6.3 min in seven fetuses at 3 mg/kg (P less than 0.005); 3) the length of the breathing responses, associated with a change from high- to low-voltage ECoG, were 15 +/- 1.8 and 135.9 +/- 18.1 min (P less than 0.0005); 4) integral of EMGdi X frequency, an index equivalent to minute ventilation, increased from 1,763 +/- 317 arbitrary units to 10,658 +/- 1,843 at 1.0 mg/kg and then decreased to 7,997 +/- 1,335 at 3.0 mg/kg. These changes were related to a steady increase in integral of EMGdi, whereas frequency decreased at 3 mg/kg. There was an increase in breathing response to morphine plasma concentrations or morphine doses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Potency of isoflurane and nitrous oxide in conventional swine

The minimum alveolar concentration (MAC) of isoflurane in oxygen (O2) was determined to be 1.55 +/- 0.08 (SEM) volumes % in twelve pigs (Sus scrofa). Values for isoflurane MAC in the presence of 50% (I-50%N2O) and 66% (I-66%N2O) nitrous oxide were determined in nine and six of these same animals, respectively, and equalled 1.03 +/- 0.05 vol % for I-50%N2O and 0.95 +/- 0.07 vol % for I-66%N2O. Animals respired spontaneously and arterial blood pressure (AP), heart rate (HR), rectal body temperature, and arterial blood gases (PO2, PCO2, and pH) were recorded throughout the study period. These parameters were within normal limits near MAC for all three gas combinations. The MAC for isoflurane in swine was similar to that for other animals and, man and the use of this agent was associated with rapid and uneventful anesthetic induction and recovery. The addition of 50% and 66% nitrous oxide (N2O) reduced the isoflurane MAC by 30% and 42%, respectively.     

Cardiorespiratory and minimum alveolar concentration sparing effects of a continuous intravenous infusion of dexmedetomidine in halothane or isoflurane-anaesthetized rats

Dexmedetomidine (DEX) is a highly selective alpha(2)-adrenoceptor agonist in both the central and peripheral nervous systems. Its cardiorespiratory effects have been described; however, these effects have not been reported when it is used in combination with volatile anaesthetics in rats. The cardiovascular and respiratory actions of a continuous intravenous infusion of 0.25 microg/kg/min of DEX administered to rats anaesthetized at 1 minimum alveolar concentration (MAC) of either halothane (HAL) or isoflurane (ISO) were studied. Twenty-eight rats were grouped into four treatment groups: HAL alone, ISO alone, DEX + HAL and DEX + ISO. The MAC(HAL) or MAC(ISO) was determined in each rat from alveolar gas samples at the time of tail clamping. Control MAC values, expressed as mean +/- standard deviation, were 1.31 +/- 0.1% for HAL and 1.46 +/- 0.05% for ISO. DEX reduced HAL MAC from 1.31 +/- 0.1% to 0.36 +/- 0.22% (72 +/- 17% MAC reduction) and ISO MAC from 1.46 +/- 0.05% to 0.83 +/- 0.2% (43 +/- 14% MAC reduction). Heart rate (HR) was decreased in both DEX groups at 1 MAC, with no differences between HAL and ISO. The mean arterial pressure was significantly depressed in the DEX + ISO group compared with the ISO only group. This difference in mean arterial blood pressure (MABP) was not seen between the DEX + HAL and HAL only groups. Respiratory depression was minor at 1 MAC with both inhalant anaesthetics. DEX reduced the MAC of HAL to a degree greater than it decreased the MAC of ISO. The effects of DEX on HR and ventilation were similar in rats anaesthetized with HAL or ISO at 1 MAC; however, hypotension was more pronounced when DEX was combined with ISO at 1 MAC.