Effect of fentanyl on thermal and mechanical nociceptive thresholds in horses and estimation of anti-nociceptive plasma concentration.

There are few investigations relating anti-nociception to plasma concentrations of fentanyl in horses. The study objective was to evaluate analgesic efficacy and duration in horses and determine the minimum anti-nociceptive plasma concentrations. Eight horses were treated with saline (P) and fentanyl (F2.5=2.5µg/kg; F5=5µg/kg; F10=10µg/kg) given IV over 5min, with a wash-out period of 10 days. To evaluate thermal (°C) and mechanical (N) nociceptive threshold single stimulations were applied prior to (baseline) and 10, 30, 60, 90, 120, 180, 240, 300, 360, 420, 540min and 22.5h after treatment. Plasma fentanyl concentrations were measured at specific time points. Locomotor activity, heart rate, respiratory rate and gastrointestinal sounds were recorded. Two-way repeated measures ANOVA and pairwise comparisons were used for data analysis (P<0.05). With treatment F10, there was a significant increase in thermal threshold above baseline (47.2ö4.1°C) at t10 (53.7ö4.2°C) and t30 (52.1ö5.6°C), whereas mechanical threshold increased considerably above baseline (3.7ö1.3N) only at t10 (6.6ö3.6N). Estimated mean minimum anti-nociceptive plasma concentration determined by thermal stimulation was 6.1-6.8ng/mL. Dose-dependent increased locomotion occurred, but no significant changes in heart rate, respiratory rate and gastrointestinal sounds were observed. Fentanyl IV at 10µg/kg produced anti-nociception for 10-30min and fentanyl plasma concentrations of ≥6.1-6.8ng/mL appear necessary to induce thermal anti-nociception. Dose-dependent increased locomotion was the main side effect observed.

Development and clinical evaluation of a new sensor design for buccal pulse oximetry in horses.

BACKGROUND: The use of pulse oximetry in horses is limited due to inadequate readings with conventional transmission sensor probes. OBJECTIVES: The objectives of this study were to 1) develop an improved sensor design for horses to be used at an appropriate anatomical site, and 2) evaluate this design in an experimental study. STUDY DESIGN: In vivo experiment. METHODS: A new sensor design for reflectance pulse oximetry at the buccal mucosa was developed. A conventional Nonin 2000SL sensor for transmission pulse oximetry was included into this design. Three different prototypes (N1, N2a, N2b) were constructed and used with the Nonin 2500A Vet pulse oximetry monitor. Thirteen anaesthetised warmblood horses were included into a desaturation protocol (100-70% SaO2 ). SpO2 and pulse frequency values were recorded, using SaO2 calculated from blood gas analysis and invasive pulse frequency measurements as reference methods. Bias and precision were evaluated by calculations of the root mean square deviation (Arms ). The agreement of the methods was tested with Bland-Altman analysis. RESULTS: The quality of the pulse frequency readings determined the quality of the SpO2 -readings. Good pulse signal strength resulted in a SpO2 -accuracy comparable to that of the original sensor (Nonin 2000SL: Arms = 3%; N1: Arms = 3.60%; N2b: Arms = 3.46%). Especially at heart rates ≤30 bpm, pulse rate readings that were about twice as high as the reference value occurred. Their exclusion from the dataset resulted in a pulse rate accuracy similar to that of the original sensor. Bland-Altman plots showed limits of agreement typical of pulse oximeters. MAIN LIMITATIONS: The pulse frequency accuracy requires further improvement. The usability in clinical cases needs to be tested. CONCLUSIONS: The new sensor design has been shown to be suitable for buccal pulse oximetry in horses.

Effects of dobutamine, dopamine, phenylephrine and noradrenaline on systemic haemodynamics and intestinal perfusion in isoflurane anaesthetised horses.

BACKGROUND: In the horse, effects of cardiovascular-active drugs on local perfusion of the gastrointestinal tract are poorly understood. OBJECTIVES: To determine the effect of drugs commonly used to support blood pressure, on local intestinal blood flow and tissue oxygenation under isoflurane anaesthesia. STUDY DESIGN: In vivo randomised crossover experiment. METHODS: Ten horses were anaesthetised with isoflurane. After 90 min of equilibration three doses (µg/kg bwt/min) of dobutamine (DOB 0.5/1/3), dopamine (DA 1/2/5), noradrenaline (NA 0.1/0.2/0.5) and phenylephrine (PHE 0.5/1/3) were infused for 15 min, in a randomised order, with a 45 min washout-period. Blood flow and tissue oxygenation (sO2 ) of jejunum, colon and stomach were measured using white light remission spectrophotometry and laser doppler flowmetry; heart rate (HR), mean arterial blood pressure (MAP), cardiac output (CO) were measured and systemic vascular resistance (SVR) calculated. RESULTS: Compared to baseline high dose dobutamine significantly increased CO, HR, MAP (P<0.001) and blood flow to the jejunum (+47 ± 26%, P = 0.001) and colon (+29 ± 15%, P<0.001) (mean ± s.d.). Dopamine (DA5) increased CO but decreased colonic blood flow (-39 ± 21% from baseline, P<0.001), as well as SVR and MAP compared to baseline (P<0.001). Noradrenaline had no significant influence on intestinal perfusion, but increased MAP and SVR from baseline (P<0.001). Phenylephrine (PHE3) caused a significant decrease in blood flow and sO2 , most profoundly at the colon compared to baseline (flow -44 ± 21%; sO2 -16 ± 3%, P<0.001), while MAP and SVR increased and CO and HR decreased (P<0.001). MAIN LIMITATIONS: The measurement technique only allows for flow measurements in arbitrary units, which can limit comparability to other techniques. CONCLUSION: At the investigated doses dobutamine improved systemic and peripheral haemodynamics, while dopamine decreased MAP and peripheral perfusion. Noradrenaline increased MAP and SVR while peripheral blood flow was maintained, phenylephrine increased MAP, but reduced both local and systemic perfusion.

Evaluation of intravenous regional anaesthesia and four-point nerve block efficacy in the distal hind limb of dairy cows.

BACKGROUND: Intravenous regional anaesthesia (IVRA) and hindfoot four-point nerve block anaesthesia (NBA) are recommended for local anaesthesia (LA) in the distal limb of dairy cows. Two studies were conducted to compare the efficacy, time until onset and stress responses to IVRA and NBA in dairy cows. In the first cross-over designed study, eight healthy unsedated German Holstein cows, restrained in lateral recumbency (LR) on a surgical tipping table, were treated with IVRA and NBA using procaine 2% as a local anaesthetic. Distal limb desensitization was tested by electrical (e-), mechanical (m-) and thermal (t-) nociceptive stimulation 10 min before and 15 and 30 min after LA. Hormonal-metabolic (blood concentrations of cortisol, lactate, non-esterified fatty acids, and glucose) and cardio-respiratory (heart and respiratory rate, mean arterial blood pressure) stress responses to treatment were assessed at predetermined intervals. In the second study, six healthy, unsedated German Holstein cows in LR were treated (crossover design) with IVRA and NBA. Short-interval e-stimulation was measured by the time until complete distal limb desensitization. RESULTS: In the first study, four of eight cows responded to e-stimulation 15 min after IVRA, while none of the cows treated with NBA responded until the safety cut-off level was reached. E-stimulation revealed complete desensitization of the distal limb 30 min after LA in all cows. Half of the cows did not respond to m- and t-stimulation before LA, so no further evaluation was performed. Stress reactions to IVRA and NBA treatment were similar, but differences may have been masked by stress response to LR restraint. In the second study, complete desensitization was achieved 12.5 min after NBA, while one of the six cows still responded to e-stimulation 20 min after IVRA. CONCLUSION: Hindfoot nerve block anaesthesia and intravenous regional anaesthesia induced complete desensitization of the distal hind limb in dairy cows. However, the anaesthesia onset after NBA was significantly faster than that of IVRA, which may be clinically relevant in the field, particularly when distal limb anaesthesia is required for major claw surgeries under time constraints.

Effects of positive end-expiratory pressure titration on intestinal oxygenation and perfusion in isoflurane anaesthetised horses.

REASONS FOR PERFORMING STUDY: High airway pressures, necessary to keep equine lungs open, can have a detrimental impact on central and peripheral perfusion. OBJECTIVE: The aim of this study was to assess the effects of stepwise increasing airway pressure recruitment on central and intestinal perfusion and oxygenation during isoflurane anaesthesia in horses. STUDY DESIGN: In vivo experimental study. METHODS: Ten anaesthetised horses were ventilated using intermittent positive pressure ventilation immediately after induction. After 90 min, end-expiratory pressure (PEEP) was increased by steps of 5 cmH2 O every 10 min up to a PEEP of 30 cmH2 O and decreased back to zero maintaining a constant airway pressure difference of 20 cmH2 O. Mean arterial blood pressure (MAP), heart rate, central venous pressure, pulmonary artery pressure, expiratory isoflurane concentration and cardiac output (thermodilution method) were measured. Cardiac index (CI) was calculated. Arterial blood gases were taken to measure arterial partial oxygen pressure (PaO2 ) and calculate arterial oxygen saturation (SaO2 ). Intestinal microperfusion and oxygenation were measured by laser Doppler flowmetry and white-light spectrophotometry. After ventral median laparotomy, a probe was placed on the stomach, jejunum and pelvic flexion of the colon. An ANOVA for repeated measurements and Tukey's post hoc test were used for statistical analysis (α = 5%). RESULTS: Recruitment of the lungs resulted in a significant increase in PaO2 from 201 ± 58 mmHg (baseline) to a maximum of 495 ± 75 mmHg. The CI and MAP decreased continuously with increasing airway pressures. When CI and MAP were 37 ± 9 ml/kg/min and 52 ± 8 mmHg (at PEEP of 25 cmH2 O), respectively, a sudden decrease in intestinal perfusion followed by a delayed decrease in oxygenation occurred. CONCLUSIONS: There was linear correlation between airway pressures and CI and MAP but not between central and gastrointestinal perfusion. Despite improvement of arterial oxygenation the decrease in CI and, therefore, in oxygen delivery PEEP resulted in a decrease in gastrointestinal oxygenation.

Histopathological changes and mRNA expression in lungs of horses after inhalation anaesthesia with different ventilation strategies.

Inappropriate mechanical ventilation can lead to ventilator-induced lung injury (VILI). Aim of this study was to evaluate the effects of inhalation anaesthesia and ventilation with and without recruitment (RM) and PEEP titration on alveolar integrity in horses. Twenty-three horses were divided into 4 groups (group OLC ventilated with OLC, group IPPV ventilated with intermittent positive pressure ventilation, group NV non-ventilated, and group C non-anaesthetized control group). After sedation with xylazine and induction with diazepam and ketamine anaesthetized horses were under isoflurane anaesthesia for 5.5h. The horses were euthanized and tissue samples of the dependent and non-dependent lung areas were collected. Histopathological examinations of the lung tissue as well as relative quantification of mRNA of IL-1ß, IL-6, iNOS, MMP1 and MMP9 by PCR were performed. Horses of group OLC had significantly less alveolar congestion and atelectasis but greater alveolar overdistension compared to groups NV and IPPV. In groups OLC and group IPPV an increase in IL-1ß/6 and MMP1/9 was detected compared to groups NV and C. In conclusion, in breathing spontaneously or IPPV-ventilated horses a higher degree of atelectasis was detected, whereas in OLC-ventilated horses a higher degree of overdistention was present. Elevated levels in IL and MMP might be early signs of VILI in ventilated horses.

Temporal and concentration effects of isoflurane anaesthesia on intestinal tissue oxygenation and perfusion in horses.

The aim of this study was to assess the effect of duration of anaesthesia and concentration of isoflurane on global perfusion as well as intestinal microperfusion and oxygenation. Nine Warmblood horses were premedicated with xylazine; anaesthesia was induced with midazolam and ketamine, and maintained with isoflurane. Horses were ventilated to normocapnia. During 7 h of anaesthesia, mean arterial blood pressures (MAP), heart rate, central venous pressure, pulmonary artery pressure, expiratory isoflurane concentration (ETIso) and cardiac output using lithium dilution were measured; cardiac index (CI) was calculated. Intestinal microperfusion and oxygenation were measured using laser Doppler flowmetry and white-light spectrophotometry. Surface probes were placed via median laparotomy on the serosal and mucosal site of the jejunum and the pelvic flexion of the colon. After 3 h of constant ETIso (1.4%), ETIso was increased in 0.2% increments up to 2.4%, followed by a decrease to 1.2% and an increase to 1.4%. The CI and MAP decreased continuously with increasing ETIso to 40 ± 5 mL/kg/min and 52 ± 8 mmHg, respectively. Microperfusion and oxygenation remained unchanged until an ETIso of 2.0% resulted in CI and MAP of 48 ± 5 mL/kg/min and 62 ± 6 mmHg, respectively, and then decreased rapidly. When ETIso decreased back to baseline, CI, MAP, microperfusion and oxygenation recovered to baseline. Isoflurane concentration but not duration of isoflurane anaesthesia influenced central and intestinal oxygenation and perfusion in healthy horses. Under isoflurane, intestinal perfusion appeared to be preserved until a threshold MAP or blood flow was reached.

[Influence of atracurium on cardiovascular parameters in horses undergoing vitrectomy during general anaesthesia, and on recovery duration and quality]. / Einsatz von Atracurium bei der Vitrektomie des Pferdes. Einfluss auf Operationsbedingungen, Allgemeinanästhesie und Aufstehphase.

OBJECTIVE: In most ocular procedures, a central position of the eye is necessary. This can be achieved using a deep plane of anaesthesia, locoregional blocks or with neuromuscular blocking agents. The aim of this study was to evaluate the influence of atracurium on cardiovascular parameters, and on recovery quality and duration in horses. MATERIAL AND METHODS: Thirty-four warmblood horses undergoing in total 50 vitrectomies were divided into two groups. Premedication, induction and maintenance were identical in all patients. After 20 minutes, horses of group A received atracurium (0.1 mg/kg) while in the control group (group K) the depth of anaesthesia was adapted to keep the bulbus in a central position. Dobutamine and fluids were administered to maintain the mean arterial blood pressure (MAP) above 70 mmHg. Cardiac output (CO), heart rate (HR), MAP, respiratory rate, end-expiratory isoflurane concentration (ETIso) and dobutamine requirements were determined. Position and movement of the globe during the surgical procedure were scored. Time and quality of the recovery period was scored. RESULTS: Horses of group K required significantly higher concentrations of isoflurane (group A: 1.08 ± 0.1%; group K: 1.34 ± 0.2%) and had an overall lower MAP (group A: 88.4 ± 10.3 mmHg; group K: 76.6 ± 11.6 mmHg) and CO (group A: 36.9 ± 11.7 l/min; group K: 28.5 ± 7.2 l/min) but needed significantly more dobutamine (group A: 0.37 ± 0.17 µg/kg/min; group K: 0.99 ± 0.46 µg/kg/min) compared to group A. Complete relaxation occurred 9.5 ± 2.5 minutes after atracurium bolus and lasted for 25 ± 7.1 minutes. The score of the bulbus position and movement was significantly lower in group A, resulting in a better quality for the surgical procedure. In group A, the recovery time to standing was significantly shorter (group A: 18.1 ± 5.4 min; group K: 31.5 ± 7.1 min), with no difference in quality. CONCLUSION AND CLINICAL RELEVANCE: The use of atracurium resulted in a better cardiovascular condition, probably because of the isoflurane-sparing effect. The recovery time was shorter in these horses without negative effects on recovery quality. No signs of residual atracurium effects were detected.

Effects of a constant-rate infusion of dexmedetomidine on the minimal alveolar concentration of sevoflurane in ponies.

REASONS FOR PERFORMING STUDY: Dexmedetomidine has been administered in the equine as a constant-rate infusion (CRI) during inhalation anaesthesia, preserving optimal cardiopulmonary function with calm and coordinated recoveries. Inhalant anaesthetic sparing effects have been demonstrated in other species, but not in horses. OBJECTIVES: To determine the effects of a CRI of dexmedetomidine on the minimal alveolar concentration (MAC) of sevoflurane in ponies. METHODS: Six healthy adult ponies were involved in this prospective, randomised, crossover, blinded, experimental study. Each pony was anaesthetised twice (3 weeks washout period). After induction with sevoflurane in oxygen (via nasotracheal tube), the ponies were positioned on a surgical table (T0), and anaesthesia was maintained with sevoflurane (expired sevoflurane fraction 2.5%) in 55% oxygen. The ponies were randomly allocated to treatment D (dexmedetomidine 3.5 µg/kg bwt i.v. [T10-T15] followed by a CRI of dexmedetomidine at 1.75 µg/kg bwt/h) or treatment S (bolus and CRI of saline at the same volume and rate as treatment D). After T60, MAC determination, using a classic bracketing technique, was initiated. Stimuli consisted of constant-current electrical stimuli at the skin of the lateral pastern region. Triplicate MAC estimations were obtained and averaged in each pony. Monitoring included pulse oximetry, electrocardiography, anaesthetic gas monitoring, arterial blood pressure measurement and arterial blood gases. Normocapnia was maintained by mechanical ventilation. Analysis of variance (treatment and period as fixed factors) was used to detect differences between treatments (α= 0.05). RESULTS: An intravenous (i.v.) dexmedetomidine CRI decreased mean ± s.d. sevoflurane MAC from 2.42 ± 0.55 to 1.07 ± 0.21% (mean MAC reduction 53 ± 15%). CONCLUSIONS AND POTENTIAL RELEVANCE: A dexmedetomidine CRI at the reported dose significantly reduces the MAC of sevoflurane.

Influence of mechanical manipulations on the local inflammatory reaction in the equine colon.

REASONS FOR PERFORMING STUDY: Large intestinal diseases in horses are characterised by inflammation, which could arise from the disease process with some contribution from intestinal manipulation. The effects of the latter are unknown but important to surgeons and could contribute to post operative complications. OBJECTIVES: To characterise type and degree of intestinal inflammation induced by various mechanical stimuli in the equine ascending colon. METHODS: Laparotomy was performed in 12 horses, the left dorsal colon exteriorised and 3 segments randomly exposed to different mechanical manipulations: 1) enterotomy, 2) enterotomy and mucosal irritation and 3) serosal irritation. Intestinal biopsies were harvested before, immediately after and 30 min after each manipulation for histological evaluation. Eosinophils were detected with Luna's stain and neutrophils identified by immunohistochemical staining for calprotectin. Additionally, left dorsal colon samples from 14 horses from a jejunal ischaemia-reperfusion study were collected immediately after laparotomy (7 horses) and at the end of the experiment without previous manipulation of the colon (7 horses). Horses were subjected to euthanasia at the end of both studies. RESULTS: Redistribution of mucosal neutrophils and eosinophils towards the luminal surface and increased neutrophilic infiltration of the submucosa were demonstrated after serosal and mucosal irritation. All manipulations resulted in serosal infiltration with neutrophils. Laparotomy and small intestinal manipulation increased mucosal eosinophilic infiltration. CONCLUSIONS AND POTENTIAL RELEVANCE: Mechanical intestinal manipulation caused a rapid local inflammatory reaction in the mucosa, submucosa and serosa including a mucosal eosinophilic response. These changes could exacerbate existing inflammation in horses with large colon disease. Colic surgery can lead to intestinal inflammation in nonmanipulated intestine and this could contribute to a higher morbidity rate in horses after prolonged colic surgery. An intestinal biopsy should be collected at the beginning of surgery to avoid false interpretations.

Influence of modified open lung concept ventilation on the cardiovascular and pulmonary function of horses during total intravenous anaesthesia.

The influence of a modified open lung concept (mOLC) on pulmonary and cardiovascular function during total intravenous anaesthesia (TIVA) in horses was evaluated. Forty-two warmblood horses (American Society of Anesthesiologists class 1 to 2), scheduled for elective surgery (mean [sd] weight 526 [65] kg, age 6.4 [5.4] years) were randomly divided into three groups: ventilation with mOLC, intermittent positive-pressure ventilation (IPPV), and spontaneous breathing. Premedication (0.8 mg/kg xylazine), induction (2.2 mg/kg ketamine and 0.05 mg/kg diazepam) and maintenance of anaesthesia with TIVA (1.4 mg/kg/hour xylazine, 5.6 mg/kg/hour ketamine and 131.1 mg/kg/hour guaifenesin), with inhalation of 35 per cent oxygen in air, were identical in all horses. Heart rate, respiratory rate, mean arterial blood pressure (MAP), pH, and arterial partial pressure of oxygen (p(a)O(2)) and carbon dioxide (p(a)CO(2)) were evaluated. Data were collected every 10 minutes from 20 to 90 minutes anaesthesia time. Factorial analysis of variance and Tukey's post hoc test were used for statistical analysis (a=5 per cent). Horses in the mOLC-ventilated group had an overall significantly higher p(a)O(2) (16.9 [1.0] v 11.7 [1.34] v 10.5 [0.57] kPa) and lower MAP (93.1 [5.47] v 107.1 [6.99] v 101.2 [5.45] mmHg) than the IPPV and spontaneously breathing groups, respectively.