A comparison of two ketamine doses for field anaesthesia in horses undergoing castration.

BACKGROUND: Ketamine at 2.2 mg/kg given i.v. is often used to induce anaesthesia for surgical procedures in horses under field conditions. Commonly, additional doses are needed to complete the surgery. We hypothesised that surgical conditions would be improved when 5 mg/kg of ketamine was used to induce anaesthesia, while induction and recovery qualities would not differ from those when 2.2 mg/kg ketamine was used. OBJECTIVE: To compare the anaesthetic effects of two ketamine doses (5 and 2.2 mg/kg) during field anaesthesia for castration of horses. STUDY DESIGN: Prospective, randomised, blinded, clinical study. METHOD: Seventy-seven client-owned Icelandic horses presented for castration under field conditions were studied. Pre-anaesthetic medication was xylazine (0.7 mg/kg) butorphanol (25 µg/kg) and acepromazine (50 µg/kg) injected i.v. Anaesthesia was induced with either 2.2 mg/kg (K2.2) or 5 mg/kg (K5) i.v. of ketamine mixed with diazepam (30 µg/kg). The quality of induction, surgical conditions and recovery were compared using subjective and objective measures, and the number of additional ketamine doses recorded. RESULTS: Ketamine 5 mg/kg provided better surgical conditions and a more rapid induction. Recovery quality was subjectively better in K2.2. Five horses in K2.2 and two in K5 required additional ketamine doses. MAIN LIMITATIONS: While the pre-anaesthetic sedation and benzodiazepine doses were consistent among horses, the level of sedation and muscle relaxation achieved differed. CONCLUSION: A ketamine dose of 5 mg/kg can be used to improve the quality of field anaesthesia for castration in Icelandic horses. Although recovery quality is subjectively better when using 2.2 mg/kg, no adverse events were observed during recovery with either dose The Summary is available in Portuguese - see Supporting Information.

A review of factors affecting analgesic selection in large animals undergoing translational research.

The widespread physiological effects of pain in experimental animals are likely to reduce the validity of data except when pain itself is studied. Appropriately prescribed analgesics will limit pain and improve the welfare of animals undergoing noxious experimental procedures. However, their injudicious use may also introduce variability in data and limit study reproducibility. Optimizing both animal welfare and the value of scientific data from experimental studies requires the ability to identify, quantify and treat animal pain by applying a knowledge of analgesic pharmacology that is sympathetic to study objectives. This review first examines the reasons for promoting analgesic use in translational animal research and, in focussing on pigs and small ruminants, then identifies factors that should be considered when devising analgesic plans.

Are neuromuscular blocking agents being misused in laboratory pigs?

The literature (2012-4) describing experimental pig surgery was reviewed to estimate the extent to which neuromuscular block (NMB) is used, to examine methods for ensuring unconsciousness, and to identify the rationale for use of NMB and establish the anaesthetist's training. In the first stage of a two-stage review, NMB use was estimated using Web of Knowledge to identify articles describing NMB during pig surgeries. In the second stage, PubMed and Google Scholar were used to increase the number of articles for determining measures taken to prevent accidental awareness during general anaesthesia (AAGA). The corresponding authors of screened articles were emailed four times to establish the reason for using NMB and the anaesthetists' backgrounds (medical, veterinary, or technical). The first search revealed NMB use in 80 of 411 (20%) studies. Of the 153 articles analysed in the second stage, two described strategies to reduce AAGA. Some (6%) papers did not provide information on anaesthetic doses; citations supporting anaesthetic efficacy were found in only 13. Five of 69 papers using inhalation agents measured end-tidal anaesthetic concentrations based on human, not porcine, minimal alveolar concentrations. The methods in 13% of articles reporting anaesthetic depth assessment were incomplete or questionable, or both; four described using somatic motor reflexes. Corresponding authors of 121 articles reported that the principal reason for NMB was improved 'surgical visualization' (26%). Medical or veterinary anaesthetists supervised anaesthesia in 70% of studies; non-anaesthetists provided NMB, unsupervised, in 23. Nine respondents prioritized experimental expediency over pig welfare. In laboratory pig studies, AAGA may be prevalent; reported details of its attempted prevention are woefully inadequate.

Pain management in pigs undergoing experimental surgery; a literature review (2012-4).

Failure to provide effective analgesia to animals in noxious studies contravenes the obligation to refine animal experimentation and, by increasing 'noise' in physiological data sets, may decrease the scientific validity of results. Pig models of surgical conditions are becoming increasingly important and used for translational work. This review aimed to determine the extent to which the recent biomedical literature describes pain assessment and alleviation in pigs recovering from experimental surgery. Three databases (Medline, Web of Knowledge, and Google Scholar) were searched to find relevant studies published from January 2012 to March 2014. Information on pain assessment and peri- and postoperative analgesia was extracted. The review identified 233 papers meeting selection criteria. Most articles (193/233, 83%) described use of drugs with analgesic properties, but only 87/233 (37%) described postoperative analgesia. No article provided justification for the analgesic chosen, despite the lack of guidelines for analgesia in porcine surgical models and the lack of formal studies on this subject. Postoperative pain assessment was reported in only 23/233 (10%) articles. It was found that the reporting of postoperative pain management in the studies was remarkably low, reflecting either under-reporting or under-use. Analgesic description, when given, was frequently too limited to enable reproducibility. Development of a pain-scoring system in pigs, together with the mandatory description of pain management in submitted articles, would contribute to improved laboratory pig welfare.

Prophylactic use of antimicrobials in surgical pig models; a literature review (2012-2014).

There are no guidelines for antimicrobial use in experimental animals even though appropriate selection is required to reduce risk of surgical site infection (SSI) and resistance development. Pigs are used extensively as experimental surgical models for people. This review compares reported antimicrobial prescription in recently published pig surgical studies (retrieved by PubMed, Web of Knowledge and Google Scholar) with human guidelines for prophylactic antimicrobial use (National Institute of Clinical Excellence and the American Society of Health-System Pharmacists). A five-point appropriate antimicrobial use index (AAUI), based on aforementioned guidelines, was used to grade 233 studies. Use of World Health Organization-designated critically important antimicrobials (CIA) was recorded. Antimicrobial use was described in 111 of 233 (48 per cent) papers. AAUI scores of 5 (maximal compliance) and 0 (no compliance) were awarded to 34 (15 per cent) and 101 (43 per cent) articles. Where reported, prophylactic antimicrobials were mostly administered after surgery (62/95, 65 per cent) and intramuscularly (36/72, 50 per cent). CIAs were described in 21 of 111 (19 per cent) papers and SSIs in 21 of 233 (9 per cent). Reported antimicrobial prophylaxis in experimental pig surgery deviates from human clinical guidelines. This has implications for antimicrobial resistance, study quality and animal welfare. Until species-specific guidelines are formulated, experimental surgical studies involving animals would probably benefit from adherence to human guidelines.

Influence of age and body mass on the response of adolescent male pigs to anaesthesia.

Age and body mass affect a human's response to drugs, including anaesthetics. In pigs, such effects, if they occur, are likely to be pronounced: commercial breeds have been selected for rapid growth, meaning rapid body composition and mass change with age. Thirty-six male pigs were anaesthetised for CT scanning on three occasions (S1-3) when aged 105, 137 and 166 days and when mean (±sd) masses were 57.2±4.4, 88.4±6.2 and 114.7±7.6 kg, respectively. Medetomidine (5 µg/kg), azaperone (1 mg/kg), ketamine (5 mg/kg) and midazolam (0.25 mg/kg) were combined and injected intramuscularly. The times when pigs became recumbent (R1) and remained so (RP) were recorded. If venous cannulation was not possible five minutes after recumbency, 2-3 per cent isoflurane in a 1:2 O2/N2O mixture was delivered by mask until cannulation was possible and then discontinued. If anaesthetic depth was inadequate for CT scanning, a full dose (midazolam 0.25 mg/kg, ketamine 2 mg/kg) or half dose of induction agents was administered intravenously. During recovery from anaesthesia, the times at first movement (M1), first standing attempt (S1) and successful sustained standing (SP) were recorded. The relationship between mass and time (minutes) from injection to each end point was assessed using regression analysis and linear mixed-effect models (LMEM); LMEM were used to assess isoflurane and intravenous anaesthetic effects. Analysis using LMEM showed no significant relationships between mass and the times from injection to the five end points. Isoflurane reduced the time to M1, S1 and SP (P<0.037); intravenous agents had no effect on S1 or SP (P>0.585) but increased the time from injection to M1 (P<0.001). In conclusion, age and mass do not influence the response of commercially bred pigs to the intravenous anaesthetic combination described.

Spontaneous electroencephalographic changes in a castration model as an indicator of nociception: a comparison between donkeys and ponies.

REASONS FOR PERFORMING STUDY: Donkeys are believed to be less demonstrative of pain than ponies. Research into comparative sensory processing between these species is required to elucidate these behavioural differences. OBJECTIVES: To compare changes in the electroencephalogram (EEG) recorded during castration between donkeys and ponies. STUDY DESIGN: Prospective clinical study. METHODS: Six ponies and 6 donkeys were castrated under halothane anaesthesia after acepromazine premedication and thiopental anaesthetic induction. Markers were inserted into the EEG recording at the time of skin incision (skin) and emasculation (emasc) for both testicles (T1 and T2) during a closed castration. Raw EEG data were analysed and the EEG variables median frequency (F50 ), total power (Ptot ) and spectral edge frequency (F95 ) derived using standard techniques. Baseline values of F50 , Ptot and F95 for each animal were used to calculate the percentage change from baseline at T1skin, T2skin, T1emasc and T2emasc. RESULTS: Decreased F50 values relative to baseline were observed in 4 ponies and 2 donkeys across all castration time points. In the remaining animals, the F50 value increased compared with baseline. Both donkey and pony groups showed an overall decrease in Ptot values compared with baseline at T1skin, but the magnitude of the decrease was significantly less (P = 0.004) in ponies than in donkeys. Donkeys demonstrated an overall greater increase (P = 0.05) in F95 values at T1skin relative to baseline compared with ponies. CONCLUSIONS: Electroencephalographic responses to the noxious stimulus of castration were noted in both donkeys and ponies. Donkeys demonstrated a greater change in Ptot in response to castration than ponies; thus, donkeys appear to demonstrate a cerebral cortical response to a noxious stimulus that is similar to or greater than that in ponies, suggesting that their subtle behavioural expression of pain is not due to a difference in cortical processing of noxious sensory stimuli.

A model describing the use of a bronchial blocking device and a sheathed bronchoscope for pulmonary aspiration studies in the Gottingen minipig.

The administration of test substances into a single lung, or lung lobe, allows the remaining untreated lung to act as an experimental control and effectively halves the number of animals required in a given experiment. It reduces the likelihood of early fatal pulmonary failure when noxious substances are studied which may lessen the need for replacement animals. However, the ease of substance administration and the subsequent analysis of its effects, for example by bronchoalveolar lavage or bronchoscopy, depend critically on the size of the animal model. The advantages of using minipigs; ease of handling, reduced housing requirements, genetic homogeneity, etc. are reduced if their diminutive size makes lung studies difficult. This article describes the use of a bronchial blocking device and a sheathed bronchoscope which enabled sterile endobronchial substance administration in Göttingen minipigs, and allowed pulmonary aspiration studies to be conducted with each animal acting as its own control.

Factors affecting the perception of recovery quality in horses after anaesthesia.

REASONS FOR PERFORMING STUDY: A significant effect of gender, experience and background, i.e. an evaluator's relationship with horses as equine anaesthetists, orthopaedic surgeons, practitioners or owners, on perceptions of recovery quality after anaesthesia would reduce the validity of recovery quality scoring systems. OBJECTIVES: To determine the effects of evaluator background, experience and gender on their perceptions of recovery quality; and questionnaire response rate as a function of background. STUDY DESIGN: Cross-sectional survey. METHODS: A total of 440 potential evaluators were invited to evaluate the video-recorded recoveries of 24 horses using a visual analogue scale (VAS) in which 0 = worst, 100 = best possible recovery. A mean score was generated for each of the 1-24 recoveries within each background group. These were compared using Spearman's rank correlation. The effect of gender and experience on VAS scores were analysed using an ordinal logistic regression after scores were categorised into 'intermediate, 'worst' and 'best' recovery categories based on median, 25th and 75th percentile VAS scores, respectively. RESULTS: The overall response rate was 35%. The greatest was from the anaesthetists (78%) followed by surgeons (43%). The response rate among owners and practitioners was 26%. Correlation among VAS scores across all background groups was high (Spearman rank > 0.90; P < 0.001). Among the combined veterinarians, there was no significant gender (P = 0.551) or experience (P = 0.103) effect. Among horse owners, the effect of experience was not significant (P = 0.116) although gender was (P = 0.027). Male horse owners awarded significantly greater scores than females. CONCLUSIONS: When VAS are used to grade recovery quality, neither the background nor the gender of veterinary evaluators affects quality perception. Male owners awarded greater scores than female owners, implying that they are less critical of recovery quality and a gender effect among horse owners must be considered when VAS are used to score recovery quality.

Translational toxicological research: investigating and preventing acute lung injury in organophosphorus insecticide poisoning.

Poisoning through ingestion of organophosphorus (OP) insecticide is a leading cause of suicide globally. Severe poisoning with OP compounds creates an unconscious, paralysed patient with respiratory failure. These symptoms make pulmonary aspiration of stomach contents highly likely, potentially causing an acute lung injury. To explore this hypothesis, we created a Gottingen minipig pulmonary aspiration model (n=26) to investigate the mechanism and severity of lung injury created through pulmonary instillation of 0.5 mL/kg mixtures of porcine gastric juice (GJ), OP and/or its solvent. Early results show that aspiration of OP and GJ causes pulmonary neutrophil sequestration, alveolar haemorrhage and interstitial oedema, with disruption of the alveolar-capillary membrane. Further measurements will include quantitative CT imaging, histopathology scoring, acute lung injury biomarkers and respiratory function. In order to test the validity of the minipig model, a pilot study in Sri Lanka has been devised to observe signs of lung injury in human patients who have ingested OP insecticide with or without clinical evidence of pulmonary aspiration. Lung injury will be assessed with PaO2/FIO2 ratios and physiological dead space measurement. Blood, bronchoalveolar lavage and urine will be taken at 24 and 48 h after poisoning and at 3-4 h in surgical control patients to measure acute lung injury biomarkers. An unpublished toxicology study from Sri Lanka, 2011-2012, showed that over 40% of unconscious poisoned patients with a GCS <9 were not intubated for ambulance transfer between rural and district hospitals. Delay in intubation leads to aspiration pneumonitis and pneumonia in 38%-45% of unconscious poisoned patients. We hypothesise that non-drug assisted placement of supraglottic airways may be a good tool for use in unconscious poisoned patients requiring transfer from small rural hospitals in Asia. They could confer better airway protection than no airway intervention and reduce both morbidity and mortality.

A comparison of two morphine doses on the quality of recovery from general anaesthesia in horses.

Previous studies indicated that perioperative morphine improves recovery quality after general anaesthesia in horses. This clinical trial investigated whether this effect was dose-dependant. Twenty-six horses anaesthetised for surgery were block-randomised to receive one of two intraoperative morphine treatments: Treatment M1 consisted of a constant rate infusion (CRI) of morphine at 0.1mg/kg/h, begun after a loading dose (LD) of 0.15 mg/kg. Treatment M2 was a CRI of 0.2mg/kg/h preceded by an LD of 0.3mg/kg. During recovery, times at the first attempt and at achieving sternal recumbency and standing, and the total recovery duration were not different between groups. Total recovery quality score was not significantly different between groups. Scores for the "sternal phase" were higher (of poorer quality) for M2 but scores in both groups were low. Morphine doses of M2, which are greater than those described previously, do not appear to alter or improve the quality or duration of recovery in horses after surgical anaesthesia.

Reducing the oxygen concentration of gases delivered from anaesthetic machines unadapted for medical air.

High fractional concentrations of inspired oxygen (FiO(2)) delivered over prolonged periods produce characteristic histological changes in the lungs and airway of exposed animals. Modern medical anaesthetic machines are adapted to deliver medical air (FiO(2)=0.21) for the purpose of reducing FiO(2); anaesthetic machines designed for the veterinary market have not been so adapted. Two inexpensive modifications that allow medical air to be added to the gas flow from veterinary anaesthetic machines are described. The advantages and disadvantages of each modification are discussed.

Vertical dimensions of suspended horses.

REASONS FOR STUDY: The dimensions of anaesthetised hobbled horses during suspension and transfer onto the operating table are unknown. These data are required for the cost-effective construction of equine surgical facilities. OBJECTIVES: To measure the distance from the toe to dependent back margin (Bsusp) and poll (Psusp) of anaesthetised suspended horses and correlate them with readily obtained measures from standing animals. METHODS: Digital photographs of suspended horses were taken in the anaesthesia induction box at a fixed position that allowed trigonometric determination of Bsusp and Psusp. These values were linked with body mass, height at the withers (Wstand), the length of the crest from the poll to the withers (crest) and of the back (back) from the withers to the crop, by deriving an equine morphological index (EMI) using principal component analysis. The EMI and other linear variables were then subjected to single variable regression analysis. RESULTS: EMI was 0.531mass((kg)) + 0.528Wstand((cm)) + 0.469crest((cm)) + 0.468back((cm)) . Bsusp was most accurately estimated using the expression Bsusp= 118.71 + 0.128EMI while Psusp was most strongly associated with Wstand, i.e. Psusp= 46.9 + 1.01Wstand((cm)) . CONCLUSIONS: The height of suspended horses at the most ventral margin of the back and the poll can be estimated from measures taken from the standing animal. POTENTIAL RELEVANCE: The data will allow the more informed planning and construction of equine surgical facilities in which mechanical hoists are used.

A comparison of four systems for scoring recovery quality after general anaesthesia in horses.

REASON FOR PERFORMING STUDY: The recovery quality scoring systems (RQSSs) in current use have not been critically reviewed for reliability. OBJECTIVE: To examine reliability (reproducibility) of 4 RQSSs when applied to a ranked series. METHODS: A DVD incorporating the recordings of 9 horses recovering from general anaesthesia was evaluated by final year students over 5 days. On Day 1, each evaluator ranked recoveries from 1-9 (1 = best). Over the following 4 days, each evaluator scored the same recoveries using 4 different RQSSs (3 of them in common usage and previously published) applied in random order. The scores from each RQSS were ranked and plotted against the Day 1 ranking of each evaluator to establish the extent of agreement using generalisability theory. The same 9 recoveries were also ranked by 12 experienced equine anaesthetists and the Spearman Rank Correlation coefficient calculated to determine the agreement between experienced and inexperienced evaluators. RESULTS: The recoveries were evaluated by 117 students. All 4 RQSSs were equally reliable with low (<4%) interobserver variability. The main (80%) source of total variation arose from differences between horses. The overall ranking within each RQSS was strongly correlated with Day 1 ranking. There was strong correlation (r = 0.983) between the students' ranking and that established by experienced anaesthetists. Interobserver reliability was similar with all 4 RQSSs. CONCLUSION: All 4 RQSSs studied were similarly reliable. POTENTIAL RELEVANCE: The selection of a universally acceptable RQSS from amongst the 4 examined can be based on criteria other than reliability, e.g. ease of use. This will facilitate wider scale multi-centre studies in recovery quality after anaesthesia in horses.

Effect of muscle injection site on preanaesthetic sedation in dogs.

The demeanour of 122 dogs was assessed, and a mixture of 0.025 mg/kg acepromazine and 0.3 mg/kg morphine was injected intramuscularly into one of four randomly assigned muscle sites (cervical epaxial, triceps brachii, middle gluteal and quadriceps femoris) and the dogs' reactions to the injections were assessed. The development of sedation and the occurrence of side effects were assessed after 10, 20 and 30 minutes, and each dog's reaction to venous catheterisation was scored. All the dogs became similarly sedated after 30 minutes. The degree of sedation and the incidence of side effects were independent of the injection site, but the dogs receiving intragluteal injections had lower sedation scores after 10 minutes. The dogs' demeanour had no effect on their response to venous catheterisation. The dogs receiving an injection into the postural quadriceps and triceps muscles showed more marked reactions than those injected into the non-postural cervical epaxial and gluteal muscles.

A comparison of microbial growth in alfaxalone, propofol and thiopental.

OBJECTIVES: To compare the growth of Staphylococcus aureus and Escherichia coli in alfaxalone with that in propofol and thiopental and to evaluate contaminant microbial growth in these agents under two different conditions of storage and handling. METHODS: Known quanta of S aureus and E coli were inoculated into separate 5 ml samples of propofol, thiopental and alfaxalone. Quantitative bacterial analysis was performed at intervals over a 14 day period. Commercial preparations of propofol, thiopental and alfaxalone were stored and handled using "dirty" or "clean" techniques. Microbial quantification and identification was performed over a 14 day period. RESULTS: S aureus and E coli grew rapidly in propofol after six hours. Both bacteria were killed by thiopental. S aureus numbers slowly declined in alfaxalone; E coli growth was rapid after 24 hours. In "dirty" and "clean" groups of intravenous anaesthetics, 9.3 and 7.4 per cent of samples, respectively, were positive for microbial growth; none were considered to represent colonisation of bottles. CLINICAL SIGNIFICANCE: Alfaxalone supports growth of some microorganisms but less readily than propofol. Bacterial colonisation of intravenous anaesthetic bottles is uncommon, but contamination as syringes are prepared for injection occurs regardless of storage and handling technique.

Post anaesthetic colic in horses: a preventable complication?

REASONS FOR PERFORMING STUDY: There is little information on the prevalence of, and risk factors associated with, post anaesthetic colic (PAC) in horses undergoing nonabdominal operations. OBJECTIVES: To undertake the first prospective study of prevalence of PAC and identify risk factors in its development in nonabdominal procedures. METHODS: A multicentre prospective case-control study was conducted, on every horse undergoing anaesthesia for a nonabdominal procedure between April 2004 and June 2005. Colic cases were defined as any horse with recognised signs of abdominal pain within 72 h of general anaesthesia that could not be attributed to any concurrent disease. Five control horses per case were selected randomly from the study population at all hospitals. Multivariable logistic regression analysis was used to examine the relationship between predictor variables and the risk of developing PAC. RESULTS: The estimated mean prevalence of PAC in the study population was 5.2% (95% CI, 2.8, 8.0). However, the prevalence of colic varied between each centre. The most commonly diagnosed cause of colic was impaction. Multivariable analyses showed that the centre involved and the type of surgery performed were associated with an increased risk of PAC. Preoperative food deprivation and the use of opioid drugs were confounding factors. CONCLUSIONS: Prevalence of PAC varied significantly between the 4 hospitals studied; there may be hospital-related covariates that account for this. The type of surgery performed influenced the risk of PAC. POTENTIAL RELEVANCE: Identifying the risk factors for PAC is a prerequisite for its prevention. This study indicates horses at increased risk of PAC that might benefit from a more critical evaluation of post anaesthetic gastrointestinal function and/or the provision of preventative measures. Further investigation is required to explain the variation in prevalence of PAC between centres.