Sedative-hypnotic effects of midazolam in goats after intravenous and intramuscular administration

Objective To examine the effect of dose and route of administration on the sedative‐hypnotic effects of midazolam. Design Prospective randomized controlled study Animals Six indigenous, African bred goats. Methods Pilot studies indicated that the optimum dose of midazolam for producing sedation was 0.6 mg kg^?1 for intramuscular (IM) injection, while the optimum intravenous (IV) doses causing hypnosis without, and with loss of palpebral reflexes were 0.6 mg kg^?1 and 1.2 mg kg^?1, respectively. These doses and routes of administration were compared with a saline placebo in a randomized block design in the main experiment, and the sedative‐hypnotic effects evaluated according to pre‐determined scales. Results Intramuscular midazolam produced sedation with or without sternal recumbency in all animals with the peak effect occurring 20 minutes after administration. The scores for IM sedation with midazolam were significantly different (p < 0.05) from placebo. Intravenous midazolam at 0.6 mg kg^?1 resulted in hypnosis, and at 1.2 mg kg^?1 increased reflex suppression was observed. The maximum scores for hypnosis at both doses were obtained 5 minutes after IV injection. The mean (± SD) duration of lateral recumbency was 10.8 (± 3.8) minutes after IV midazolam (0.6 mg kg^?1) compared to 20 (± 5.2) minutes after midazolam at 1.2 mg kg^?1. Compared to baseline, the heart rate increased significantly (p < 0.05) after high dose IV midazolam. Conclusion Intramuscular midazolam (0.6 mg kg^?1) produced maximum sedation 20 minutes after injection. Intravenous injection produced maximum hypnosis within 5 minutes. Increasing the IV dose from 0.6 to 1.2 mg kg^?1 resulted in increased reflex suppression and duration of hypnosis. Clinical relevance For a profound effect with rapid onset midazolam should be given IV in doses between 0.6 and 1.2 mg kg^?1.     

Midazolam,as a co‐induction agent,has propofol sparing effects but also decreases systolic blood pressure in healthy dogs

ObjectiveTo evaluate the effects of the co-administration of midazolam on the dose requirement for propofol anesthesia induction, heart rate (HR), systolic arterial pressure (SAP) and the incidence of excitement.Study designProspective, randomized, controlled and blinded clinical study, with owner consent.AnimalsSeventeen healthy, client owned dogs weighing 28 ± 18 kg and aged 4.9 ± 3.9 years old.MethodsDogs were sedated with acepromazine 0.025 mg kg^?1 and morphine 0.25 mg kg^?1 intramuscularly (IM), 30 minutes prior to induction of anesthesia. Patients were randomly allocated to receive midazolam (MP; 0.2 mg kg^?1) or sterile normal saline (CP; 0.04 mL kg^?1) intravenously (IV) over 15 seconds. Propofol was administered IV immediately following test drug and delivered at 3 mg kg^?1 minute^?1 until intubation was possible. Scoring of pre-induction sedation, ease of intubation, quality of induction, and presence or absence of excitement following co-induction agent, was recorded. HR, SAP and respiratory rate (f_R) were obtained immediately prior to, immediately following, and 5 minutes following induction of anesthesia.ResultsThere were no significant differences between groups with regard to weight, age, gender, or sedation. Excitement occurred in 5/9 dogs following midazolam administration, with none noted in the control group. The dose of propofol administered to the midazolam group was significantly less than in the control group. Differences in HR were not significant between groups. SAP was significantly lower in the midazolam group compared with baseline values 5 minutes after its administration. However, values remained clinically acceptable.Conclusions and clinical relevanceThe co-administration of midazolam with propofol decreased the total dose of propofol needed for induction of anesthesia in sedated healthy dogs, caused some excitement and a clinically unimportant decrease in SAP.     

Effects of altering the sequence of midazolam and propofol during co‐induction of anaesthesia

ObjectiveTo assess the effects of varying the sequence of midazolam and propofol administration on the quality of induction, cardiorespiratory parameters and propofol requirements in dogs.Study designRandomized, controlled, clinical study.AnimalsThirty‐three client owned dogs (ASA I‐III, 0.5–10 years, 5–30 kg).MethodsDogs were premedicated with acepromazine (0.02 mg kg^?1) and morphine (0.4 mg kg^?1) intramuscularly. After 30 minutes, group midazolam‐propofol (MP) received midazolam (0.25 mg kg^?1) intravenously (IV) before propofol (1 mg kg^?1) IV, group propofol‐midazolam (PM) received propofol before midazolam IV at the same doses, and control group (CP) received saline IV, instead of midazolam, before propofol. Supplementary boluses of propofol (0.5 mg kg^?1) were administered to effect to all groups until orotracheal intubation was completed. Behaviour after midazolam administration, quality of sedation and induction, and ease of intubation were scored. Heart rate (HR), respiratory rate, and systolic arterial blood pressure were recorded before premedication, post‐premedication, after midazolam or saline administration, and at 0, 2, 5, and 10 minutes post‐intubation. End‐tidal CO₂ and arterial oxygen haemoglobin saturation were recorded at 2, 5 and 10 minutes post‐intubation.ResultsQuality of sedation and induction, and ease of intubation were similar in all groups. Incidence of excitement was higher in the MP compared to CP (p = 0.014) and PM (p = 0.026) groups. Propofol requirements were decreased in MP and PM groups with respect to CP (p < 0.001), and in PM compared to MP (p = 0.022). The HR decreased after premedication in all groups, and increased after midazolam and subsequent times in MP (p = 0.019) and PM (p = 0.001) groups. Incidence of apnoea and paddling was higher in CP (p = 0.005) and MP (p = 0.031) groups than in PM.Conclusions and clinical relevanceAdministration of midazolam before propofol reduced propofol requirements although caused mild excitement in some dogs. Administration of propofol before midazolam resulted in less excitatory phenomena and greater reduction of propofol requirements.     

The effects of diazepam or midazolam on the dose of propofol required to induce anaesthesia in cats

ObjectivesAssess effects of benzodiazepine administration on the propofol dose required to induce anaesthesia in healthy cats, investigate differences between midazolam and diazepam, and determine an optimal benzodiazepine dose for co-induction.Study designProspective, randomised, blinded, placebo-controlled clinical trial.AnimalsNinety client-owned cats (ASA I and II) with a median (interquartile range) body mass of 4.0 (3.4–4.9) kg.MethodsAll cats received 0.01 mg kg⁻¹ acepromazine and 0.2 mg kg⁻¹ methadone intravenously (IV). Fifteen minutes later, sedation was scored on a scale of 1–5, with 5 indicating greatest sedation. Propofol, 2 mg kg⁻¹, administered IV, was followed by either midazolam or diazepam at 0.2, 0.3, 0.4 or 0.5 mg kg⁻¹ or saline 0.1 mL kg⁻¹. Further propofol was administered until endotracheal intubation was possible. Patient signalment, sedation score, propofol dosage and adverse reactions were recorded.ResultsMidazolam and diazepam (all doses) significantly reduced the propofol dose required compared with saline (p < 0.001). There was no difference between midazolam and diazepam in propofol dose reduction (p = 0.488). All individual doses of midazolam reduced propofol requirement compared with saline (0.2 mg kg⁻¹, p = 0.028; 0.3 mg kg⁻¹, p = 0.006; 0.4 mg kg⁻¹, p < 0.001; 0.5 mg kg⁻¹, p = 0.009). Diazepam 0.2 mg kg⁻¹ did not reduce the propofol dose compared with saline (p = 0.087), but the remaining doses did (0.3 mg kg⁻¹, p = 0.001; 0.4 mg kg⁻¹, p = 0.032; 0.5 mg kg⁻¹, p = 0.041). Cats with sedation scores of 3 required less propofol than cats with scores of 2 (p = 0.008). There was no difference between groups in adverse events.Conclusions and clinical relevanceMidazolam (0.2–0.5 mg kg⁻¹) and diazepam (0.3–0.5 mg kg⁻¹) administered IV after 2 mg kg⁻¹ propofol significantly reduced the propofol dose required for tracheal intubation.     

Medetomidine/midazolam/ketamine anaesthesia in ferrets: effects on cardiorespiratory parameters and evaluation of plasma drug concentrations

ObjectiveTo evaluate the cardiorespiratory effects and plasma concentrations of medetomidine-midazolam-ketamine (MMK) combinations administered by intramuscular (IM) or subcutaneous (SC) injection in sable ferrets (Mustela putorius furo).Study designProspective randomized experimental study.AnimalsEighteen adult ferrets: weight median 1.19 (range 0.81–1.60) kg.MethodsAnimals were allocated to one of three groups: group IM07 received 20 μg kg^?1 medetomidine, 0.5 mg kg^?1 midazolam and 7 mg kg^?1 ketamine IM; group IM10 20 μg kg^?1 medetomidine, 0.5 mg kg^?1 midazolam and 10 mg kg^?1 ketamine IM; and group SC10 20 μg kg^?1 medetomidine, 0.5 mg kg^?1 midazolam and 10 mg kg^?1 ketamine SC. Following instrumentation, cardiorespiratory parameters and plasma drug concentrations were measured every 5 minutes (T5–T30) for 30 minutes Ferrets were then euthanased. Data were analysed using anova for repeated measures. p < 0.05 was considered significant.ResultsResults are mean ± SD. Induction of anaesthesia (minutes) in IM07 and IM10 [2 (1)] was significantly faster than in SC10 [5 (2)]. All groups demonstrated the following: results given as groups IM07, IM10 and SC10 respectively. Mean arterial blood pressures (mmHg) were initially high [186 (13); 174 (33) and 174 (9) at T5] but decreased steadily. Pulse rates were initially 202 (20), 213 (17) and 207 (33) beats minute^?1, decreasing with time. PaO₂ (mmHg) was low [54.0 (8), 47.7 (10) and 38.5 (1)] at T5, although in groups IM07 and IM10 it increased over time. Plasma concentrations of all drugs were highest at T5 (36, 794 and 8264 nmol L^?1 for medetomidine, midazolam and ketamine, respectively) and decreased thereafter: for both midazolam and ketamine, concentrations in IM07 and IM10 were higher than SC10.Conclusions and clinical relevanceMMK combinations containing either 7 or 10 mg kg^?1 ketamine and given IM are suitable combinations for anaesthetising ferrets, although the observed degree of hypoxaemia indicates that oxygen administration is vital.     

Total intravenous anaesthesia (TIVA) with propofol-fentanyl and propofol-midazolam combinations in spontaneously-breathing goats

ObjectiveTo compare the efficacy and cardiopulmonary effects of propofol and fentanyl, with propofol and midazolam for total intravenous anaesthesia.Study designProspective, randomized, crossover experimental study.AnimalsSix goats; three does and three wethers.MethodsGoats received either fentanyl 0.02 mg kg^?1 (treatment FP) or midazolam 0.3 mg kg^?1 (treatment MP) intravenously. One minute later anaesthesia was induced with propofol, then maintained by constant rate infusion of propofol 12.0 mg kg^?1 hour^?1 and fentanyl 0.02 mg kg^?1 hour^?1 (treatment FP) or propofol 12.0 mg kg^?1 hour^?1 and midazolam 0.3 mg kg^?1 hour^?1 (treatment MP) for 90 minutes. Response to noxious stimulus was tested every 10 minutes and propofol dose adjusted to prevent purposeful movement. Cardiopulmonary parameters were measured continuously, and arterial blood-gas analysis performed intermittently. Recovery was timed and quality scored. Results are presented as median (IQR).ResultsDifferences in the propofol induction dose [4.00 (3.96-4.01) and 3.97 (3.91-4.00) mg kg^?1 for treatments FP and MP, respectively] were not significant. Quality of induction in both groups was smooth. The median propofol dose for maintenance was less (p = 0.004) with treatment FP (12.0 mg kg^?1 hour^?1) than MP (18.0 mg kg^?1 hour^?1). Cardiopulmonary function was well maintained with both treatments. Recovery times in minutes from the end of anaesthetic infusion for treatments FP and MP respectively were; to extubation 3.0 (3.0-3.0) and 4.5 (3.3-5.0); to sternal position, 4.5 (3.3-5.0) and 5.0 (5.0-6.5) and to standing 13.0 (10.3-15.0) and 15.0 (11.3-17.3). Quality of recovery was acceptable in both groups, but abnormal behavioural signs were observed after treatment FP.Conclusions and clinical relevanceTotal intravenous anaesthesia with propofol and fentanyl or propofol and midazolam, at the doses studied, in spontaneously-breathing, oxygen-supplemented goats is practicable. Recovery from the fentanyl-propofol combination is not always smooth.     

Chemical immobilization of Weddell seals (Leptonychotes weddellii) by ketamine/midazolam combination

ObjectiveTo provide reliable, effective immobilization for Weddell seals under extreme field conditions using an injectable ketamine/midazolam combination.Study designObservational study.AnimalsThirty adult Weddell seals (12 male, 18 female) in Erebus Bay, Antarctica, body mass (mean ± SD) 412 ± 47 kg, aged 9–27 years.MethodsSeals were immobilized with a target dose of 2 mg kg^?1 ketamine hydrochloride and 0.1 mg kg^?1 midazolam hydrochloride (IM), based on visually estimated body mass. When required, maintenance doses were administered at a target of 0.5 mg kg^?1 ketamine hydrochloride and 0.025 mg kg^?1 midazolam hydrochloride (IV).ResultsComplete immobilization was achieved in 33 of 40 injections (14 of which were repeat events on the same individual). Time to immobilization averaged 12 ± 4 minutes, with a duration of initial immobility of 38 ± 19 minutes. Total immobilization time varied by handling protocol, including condition assessment and muscle biopsy (Protocol 1, 60 ± 13 minutes), condition assessment and instrument attachment (Protocol 2, 154 ± 13 minutes), and condition assessment, muscle biopsy and instrument retrieval (Protocol 3, 48 ± 8 minutes). Overall, a total immobilization time of 114 ± 60 minutes was accomplished with 4 ± 4 maintenance doses, and an average recovery time of 36 ± 17 minutes. Most effects of the anesthetic combination were unrelated to mass, age, sex or total body fat. However, leaner seals had longer duration of initial immobility (% and kg total body fat) and recovery times (kg fat). Apnea events were uncommon and treated effectively with doxapram. No animals died.Conclusions and clinical relevanceReliable and effective field immobilization of Weddell seals was accomplished with a low dose of ketamine hydrochloride and midazolam hydrochloride, utilizing IM injection initially and IV maintenance methods.     

Evaluation of butorphanol, medetomidine and midazolam as a reversible narcotic combination in free-ranging African lions (Panthera leo)

ObjectiveTo evaluate the effects of the combination butorphanol, medetomidine and midazolam (BMM) and its reversibility in lions.Study designProspective clinical trial.AnimalsThirty free-ranging lions, 10 male and 20 female, weighing 81-210 kg.MethodsLions were immobilised with butorphanol mean 0.31 ± SD 0.034 mg kg^?1, medetomidine 0.052 ± 0.006 mg kg^?1, midazolam 0.21 ± 0.024 mg kg^?1 and hyaluronidase 1250 IU administered intramuscularly with a dart gun. Upon recumbency, physiological parameters and anaesthetic depth were monitored 10-15 minutes after darting (T1) and repeated every 10 minutes for a further 30 minutes (T2, T3, T4). Arterial blood gas analyses were performed at T1 and T4. At the end of the procedure, 45-60 minutes after initial darting, immobilisation was reversed with naltrexone 0.68 ± 0.082 mg kg^?1, atipamezole 0.26 ± 0.031 mg kg^?1, and flumazenil 0.0032 ± 0.0007 mg kg^?1 administered intravenously and subcutaneously.ResultsThe BMM combination rapidly induced immobilisation and lateral recumbency was reached within 7.25 ± 2.3 minutes. Median induction score [scored 1 (excellent) to 4 (poor)] was 1.4 (range 1-2). Cardio-respiratory parameters were stable. Heart rate varied from 32 to 72 beats per minute, respiratory rate from 14 to 32 breaths minute^?1 and rectal temperature from 36.6 to 40.3 °C. No sudden arousals were observed. Arterial blood gas analyses revealed a mean pH of 7.33, PaCO₂ of 33 mmHg and PaO₂ of 87 mmHg. Mild to moderate hypoxemia was seen in four lions. Recovery was smooth and lions were walking within 4.4 ± 4.25 minutes. Median recovery score [scored 1 (excellent) to 4 (poor)] was 1.3 (range 1-2).Conclusion and clinical relevanceThe drug combination proved to be effective in immobilising free-ranging healthy lions of both sexes with minimal cardio-respiratory changes.     

Induction dose and recovery quality of propofol and alfaxalone with or without midazolam coinduction followed by total intravenous anesthesia in dogs

Objectives

To compare propofol and alfaxalone, with or without midazolam, for induction of anesthesia in fentanyl-sedated dogs, and to assess recovery from total intravenous anesthesia (TIVA).

Effects of opioids and anesthetic drugs on body temperature in cats

ObjectiveTo determine which class of opioid alone or in conjunction with other anesthetic drugs causes post-anesthetic hyperthermia in cats.Study designProspective, randomized, crossover study.AnimalsEight adult, healthy, cats (four spayed females and four castrated males weighing 3.8 ± 0.6 kg).MethodsEach 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 ～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).ResultsMean PBT for all unmedicated cats was 38.9 ± 0.6 °C (102.0 ± 1 °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 relevanceAll 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 °C (104.2 °F) and self limiting.     

Comparison of subcutaneous dexmedetomidine–midazolam versus alfaxalone–midazolam sedation in leopard geckos (Eublepharis macularius)

Objective

To compare dexmedetomidine–midazolam with alfaxalone–midazolam for sedation in leopard geckos (Eublepharis macularius).

A dose titration study into the effects of diazepam or midazolam on the propofol dose requirements for induction of general anaesthesia in client owned dogs,premedicated with methadone and acepromazine

ObjectiveTo assess the effect of a benzodiazepine co–induction on propofol dose requirement for induction of anaesthesia in healthy dogs, to describe any differences between midazolam and diazepam and to determine an optimal benzodiazepine dose for co–induction.Study designProspective, randomised, blinded placebo controlled clinical trial.AnimalsNinety client owned dogs (ASA I–III, median body mass 21.5kg (IQR 10–33)) presented for anaesthesia for a variety of procedures.MethodsDogs were randomised to receive saline 0.1 mL kg^?1, midazolam or diazepam at 0.2, 0.3, 0.4 or 0.5 mg kg^?1. All dogs received 0.01 mg kg^?1 acepromazine and 0.2 mg kg^?1 methadone intravenously (IV). Fifteen minutes later, sedation was assessed and scored prior to anaesthetic induction. Propofol, 1 mg kg^?1, was administered IV, followed by the treatment drug. Further propofol was administered until endotracheal intubation was possible. Recorded data included patient signalment, sedation score, propofol dosage and any adverse reactions.ResultsMidazolam (all groups combined) significantly reduced propofol dose requirement compared to saline (p < 0.001) and diazepam (p = 0.008). Midazolam (0.4 mg kg^?1) significantly reduced propofol dose requirement (p = 0.014) compared to saline, however other doses failed to reach statistical significance. Diazepam did not significantly reduce propofol dose requirement compared to saline (p = 0.089). Dogs weighing <5 kg, regardless of treatment group, required a greater propofol dose than those weighing 5–40 kg (p = 0.002) and those >40 kg (p = 0.008). Dogs which were profoundly sedated required less propofol than those which were mildly sedated (p < 0.001) and adequately sedated (p = 0.003).Conclusions and clinical relevanceMidazolam (0.4 mg kg^?1) given IV after 1 mg kg^?1 of propofol significantly reduced the further propofol dose required for intubation compared to saline. At the investigated doses, diazepam did not have significant propofol dose sparing effects.     

Sedative, cardiovascular, haematologic and biochemical effects of four different drug combinations administered intramuscularly in cats

ObjectiveTo compare effects of four drug combinations on sedation, echocardiographic, haematologic and biochemical variables and recovery in cats.Study designExperimental randomized ‘blinded’ cross-over study.AnimalsSix healthy cats.Materials and MethodsTreatments were administered intramuscularly: midazolam 0.4 mg kg^?1 and butorphanol 0.4 mg kg^?1 (MB); midazolam 0.4 mg kg^?1, butorphanol 0.4 mg kg^?1 and ketamine 3 mg kg^?1 (MBK); midazolam 0.4 mg kg^?1, butorphanol 0.4 mg kg^?1 and dexmedetomidine 5 μg kg^?1 (MBD); ketamine 3 mg kg^?1 and dexmedetomidine 5 μg kg^?1(KD). Sedation was evaluated at time-points over 10 minutes post injection. Echocardiography, systolic arterial blood pressure (SAP) measurement and blood sampling were performed at baseline and from 10 minutes after treatment. Quality of recovery was scored. Data were analysed by anova for repeated measures. p < 0.05 was considered significant.ResultsThe lowest sedation score was obtained by MB, (median 10.5 [7; 20]), highest by KD (36.5 [32; 38]). Quality of recovery was best with KD (0.5 [0; 2]), and worst with MB (7.5 [4; 11]). Relative to baseline measurements, treatments decreased SAP by 17%, 25%, 13%, 5% in MB, MBK, MBD and KD, respectively. Heart rate decreased (p < 0.05) after MBD (44%) and KD (34%). All treatments decreased stroke volume by 24%, 21%, 24%, 36%, and cardiac output by 23%, 34%, 54%, 53% in MB, MBK, MBD and KD, respectively. Packed cell volume was decreased (p < 0.05) by 20%, 31%, 29% in MBK, MBD and KD, respectively. Plasma glucose was increased after MBD (31%) and KD (52%) and lactate concentration was decreased (p < 0.05) after MBK (58%), MBD (72%) and KD (65%).Conclusions and clinical relevanceThe MB combination did not produce sedation in healthy cats. Treatment MBK led to acceptable sedation and minimal cardiovascular changes. Both treatments with dexmedetomidine produced excellent sedation and recovery but induced more cardiovascular depression and haematologic changes.     

Evaluation of alfaxalone and midazolam with or without flumazenil reversal in Egyptian fruit bats (Rousettus aegyptiacus)

ObjectivesTo evaluate alfaxalone–midazolam anesthesia in Egyptian fruit bats (Rousettus aegyptiacus) and the effect of flumazenil administration on recovery time and quality.Study designRandomized, blinded, crossover and controlled, experimental trial.AnimalsA total of 10 male Egyptian fruit bats.MethodsBats were anesthetized with alfaxalone (15 mg kg^?1) and midazolam (2 mg kg^?1) administered subcutaneously. During anesthesia, vital signs, muscle tone and reflexes were monitored every 10 minutes. Flumazenil (0.3 mg kg^?1) or saline at an equal volume was administered subcutaneously 60 minutes after anesthetic administration. Time to induction, time to first movement and recovery time (flying) were measured. Quality of induction, anesthesia and recovery were assessed on a 1–3 scale (1, poor; 2, good; 3, excellent).ResultsTime to induction was 4.2 ± 1.9 minutes (mean ± standard deviation), with median quality score of 2 (range, 1–3). Anesthesia quality score was 3 (1–3). During anesthesia, heart rate and respiratory frequency decreased significantly and penis relaxation, indicating muscle tone, increased significantly. Administration of flumazenil significantly reduced mean recovery time compared with saline (10 ± 5 versus 45 ± 17 minutes, respectively), and significantly improved the quality of recovery [2.5 (2–3) versus 1 (1–2), respectively].Conclusions and clinical relevanceAlfaxalone–midazolam anesthesia resulted in good induction, muscle relaxation and sufficient anesthesia to perform routine diagnostic and therapeutic procedures for approximately 40 minutes. Reversal of midazolam with flumazenil is recommended, resulting in quicker and better recovery.     

Comparison of azaperone–detomidine–butorphanol–ketamine and azaperone–tiletamine–zolazepam for anaesthesia in piglets

ObjectiveTo investigate a combination of azaperone, detomidine, butorphanol and ketamine (DBK) in pigs and to compare it with the combination of azaperone, tiletamine and zolazepam (TZ).Study designProspective, randomized, blinded, cross–over study.AnimalsTwelve clinically healthy crossbred pigs aged about 2 months and weighing 16–25 kg.MethodsPigs were pre–medicated with azaperone (4 mg kg^?1). Ten minutes later anaesthesia was induced with intramuscular DBK (detomidine 0.08 mg kg^?1, butorphanol 0.2 mg kg^?1, ketamine 10 mg kg^?1) or TZ (tiletamine and zolazepam 5 mg kg^?1). The pigs were positioned in dorsal recumbency. Heart and respiratory rates, posture, anaesthesia score, PaO₂, PaCO₂, pH and bicarbonate concentration were measured. t–test was used to compare the areas under time–anaesthesia index curve (AUC_anindex) between treatments. Data concerning heart and respiratory rates, PaO₂, PaCO₂ and anaesthesia score were analysed with anova for repeated measurements. Wilcoxon signed rank test was used for the data concerning the duration of sedation and anaesthesia.ResultsThe sedation, analgesia and anaesthesia lasted longer after DBK than TZ. The AUC_anscore were 863 ± 423 and 452 ± 274 for DBK and TZ, respectively (p = 0.002). The duration of surgical anaesthesia lasted a median of 35 minutes (0–105 minutes) after DBK and a median of 15 minutes (0–35 minutes) after TZ (p = 0.05). Four pigs after DBK and six after TZ did not achieve the plane of surgical anaesthesia. The heart rate was lower after DBK than after TZ. Both treatments had similar effects on the other parameters measured.ConclusionsAt the doses used DBK was more effective than TZ for anaesthesia in pigs under field conditions.Clinical relevanceThe combinations can be used for sedation and minor field surgery in pigs. The doses and drugs chosen were insufficient to produce a reliable surgical plane of anaesthesia in these young pigs.     

Acute noncardiogenic pulmonary edema in an anesthetized Nubian goat kid

ObservationsA 1-month-old Nubian goat presented for sialocyst resection. Physical examination and bloodwork were unremarkable. While pre-oxygenating, the goat was sedated with midazolam and morphine (0.1 mg kg^?1 each) intravenously (IV). General anesthesia was induced 5 minutes later with 1.7 mg kg^?1 propofol. Sevoflurane was administered in oxygen without assisted ventilation via a cuffed orotracheal tube. Throughout the first 85 minutes of anesthesia, the goat was well-oxygenated (SpO₂, ≥97%), ventilating adequately (Pe′CO₂, 36–48 mmHg), and had normal mean arterial blood pressure (MAP, 60–85 mmHg). Blood-gas values at 45 minutes were consistent with adequate ventilation on oxygen. At 75 minutes, the goat moved in response to surgical stimulation, requiring additional propofol (0.4 mg kg^?1). After 10 minutes, MAP dropped precipitously to 40 mmHg and frequent multiform premature ventricular contractions (PVCs) were observed. Crystalloids, hetastarch, and dopamine (5 μg kg^?1 minute^?1) were administered to correct the hypotension. Arterial blood-gas analysis revealed that the goat had become hypoxemic (PaO₂, 50 mmHg). Intermittent positive pressure ventilation (IPPV) was initiated. Subsequent blood-gas analysis did not show significant improvement in PaO₂ (53 and 56 mmHg, respectively). Occasional PVCs were observed thereafter. Surgery ended, and sevoflurane and IPPV were discontinued. The goat was extubated within 7 minutes and received 100% oxygen by mask. Diffuse crackles were ausculted over both hemithoraces. Suspecting pulmonary edema, furosemide (1 mg kg^?1) was administered IV. Radiographs taken immediately post-operatively revealed a severe, caudodorsal airspace (alveolar) pattern, confirming the diagnosis. Respiration improved considerably within an hour with nasal oxygen and two additional doses of furosemide.ConclusionsThe goat developed acute, drug-induced, noncardiogenic pulmonary edema in response to the second dose of propofol.     

Cardiovascular and autonomic nervous effects of edrophonium and atropine combinations during neuromuscular blockade antagonism in sheep

ObjectiveTo study heart rate (HR), arterial blood pressure (BP) and autonomic nervous (AN) effects of edrophonium–atropine combinations during neuromuscular blockade (NMB) antagonism in sheep.Experimental design Randomized, prospective and experimental study.AnimalsSeventy-eight Scottish blackface ewes; mean age: 4.5 years; mean body mass: 54 kg.MethodsAfter induction with IV etomidate (0.5 mg kg⁻¹) and midazolam (0.5 mg kg⁻¹), anaesthesia was maintained with halothane and NMB produced with atracurium or mivacurium. In the first study (n = 53), the electrocardiographic (ECG), HR, BP and AN effects of low (40 μg kg⁻¹) and high (80 μg kg⁻¹) atropine doses combined with either of two edrophonium doses (0.5 or 1.0 mg kg⁻¹) were investigated. These variables were also measured in a second study when edrophonium (1.0 mg kg⁻¹) was administered 5 minutes before atropine (80 μg kg⁻¹) and vice versa. Data were analysed using one-way within-subjects and repeated measures anova.ResultsIn the first study, all combinations reversed NMB but significantly (p < 0.001) increased HR and BP within 2 minutes without arrhythmias. In the second study, edrophonium (1.0 mg kg⁻¹) significantly increased HR and BP, saliva flow (n = 1) and lung sounds (n = 3) and caused ECG changes (n = 1). Cardiovascular changes were partially reversed by atropine (80 μg kg⁻¹) administered 5 minutes later. Administered first, atropine (80 μg kg⁻¹) significantly decreased HR and BP effects which were fully (HR) and partially (BP) reversed by edrophonium (1 mg kg⁻¹) administered 5 minutes later.Conclusion and clinical relevance The cardiovascular effects of edrophonium and atropine were opposite to those reported in humans and dogs. Edrophonium (0.5 mg kg⁻¹) and atropine (80 μg kg⁻¹) caused the mildest HR changes without ECG and noncardiac AN disturbances, and is recommended for the antagonism of NMB in sheep.     

Antagonistic effect of atipamezole, flumazenil and naloxone following anaesthesia with xylazine, tramadol and tiletamine/zolazepam combinations in pigs

ObjectiveTo evaluate the antagonistic effects of atipamezole (ATI), flumazenil (FLU) and naloxone (NAL) alone and in various combinations following administration of tiletamine–zolazepam–xylazine–tramadol.Study designProspective, experimental, randomized cross-over study.AnimalsEight Chinese miniature pigs (three females and five males) mean age 8 (range 7–10) months and bodyweight 57.5 (52.4–62.1) kg.MethodsAll animals were anaesthetized with tiletamine/zolazepam (3.0 mg kg^?1), xylazine (1.2 mg kg^?1) and tramadol (1.6 mg kg^?1) given intramuscularly (IM). Thirty minutes later, one of eight treatments was administered IM: saline control, ATI (0.12 mg kg^?1), FLU (0.1 mg kg^?1), NAL (0.03 mg kg^?1), ATI–FLU, FLU–NAL, ATI–NAL or ATI–FLU–NAL. After injection of antagonists the following times were recorded: to recovery of the palpebral, pedal and tail clamp reflexes, to head movement, sternal recumbency, standing and walking. Posture, sedation, analgesia, jaw relaxation and auditory response were scored at set times until 120 minutes after injection of antagonists. Heart rates, respiratory rates and rectal temperature were measured at those times. Data were analyzed by anova for repeated measures, followed by the Tukey’s test to compare differences between means, or by Kruskal–Wallis test as appropriate.ResultsFLU, NAL alone, or FLU–NAL did not effectively antagonize anaesthesia induced by tiletamine/zolazepam–xylazine–tramadol. ATI, ATI–FLU, ATI–NAL and ATI–FLU–NAL produced an immediate and effective recovery from anaesthesia. The combination of ATI–FLU–NAL was the most effective combination in antagonizing the anaesthetic effect. Adverse effects such as tachycardia, tachypnoea, excitement and muscle tremors were not observed during this study.Conclusion and clinical relevanceATI–FLU–NAL is the most effective combination for antagonizing tiletamine/zolazepam–xylazine–tramadol anaesthesia in pigs. However, ATI alone or in various combinations also provides effective antagonism.