Concentration of carprofen in the milk of lactating bitches after cesarean section and during inflammatory conditions.

Pain treatment of lactating bitches is a clinically relevant, but complicated issue. Published scientific studies regarding the excretion of drugs in canine milk are scarce. When considering the risk of side effects in their offspring, lactating bitches have traditionally received very restricted analgesic and anti-inflammatory therapy. Our aim was to quantify the concentrations of carprofen in milk from lactating bitches and relate those to potential risks for the puppies. A second aim was to evaluate the impact mastitis may have on the concentration of carprofen in milk. A population of 100 bitches was enrolled in the study, among which 88 were bitches treated with carprofen after cesarean section (Group CS), eight were bitches with painful inflammatory conditions (Group I) and four were bitches with mastitis (Group M). The patients enrolled in the study received carprofen 4 mg/kg sc at day 1 followed by 2 mg/kg po every 12 h for the following 2-5 days. Owners were instructed to collect milk once a day for five days. The concentration of carprofen in the milk was quantified with ultra-performance liquid chromatography-tandem mass spectrometry. The data obtained were statistically analyzed as repeated-measures data with a mixed-model approach. Data were used to calculate the theoretical maximum total daily intake of carprofen by the puppies in order to perform a computerized simulation of the plasma concentration of carprofen in the puppies. Follow-up telephone interviews to check the status of the enrolled bitches and their litters occurred at one week and three-six months after treatment with carprofen. The major finding of the study was that the concentration of carprofen in the milk was <700 ng/mL from bitches undergoing CS or suffering painful conditions other than mastitis. In comparison, administration of 2 mg/kg of carprofen sc or po to adult dogs, results in mean maximal plasma concentrations of 19480 ± 5420 ng/mL (mean ± SD). Moreover, data suggests that inflammation of the mammary gland results in a higher concentration of carprofen in milk (up to 1300 ng/mL). In the computerized simulation, the plasma concentrations of carprofen in puppies in group CS and in group I are one tenth of the concentration in adult dogs receiving carprofen at standard doses. Considering the low excretion into milk, carprofen provides an analgesic alternative to lactating bitches without mastitis.

STANDING SEDATION WITH XYLAZINE AND REVERSAL WITH YOHIMBINE IN JUVENILE ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

Evaluation and improvement of immobilization methods are important for wildlife welfare and biodiversity conservation. The sedative and physiological effects of xylazine (50-110 mg per elephant; 0.09-0.15 mg/kg IM) were evaluated in 15 juvenile Asian elephants (Elephas maximus) in Sri Lanka. The time from xylazine injection until first sign of sedation, handling, and reversal with yohimbine (0.009-0.03 mg/kg IV) were recorded. Behavioral signs, level of sedation (no effect, light, moderate, or deep) and response to handling were assessed. Rectal temperature, pulse, and respiratory rates were recorded and arterial blood samples were analyzed 30 and 45 min after xylazine injection. The first sign of sedation occurred within 5-18 min. Standing sedation was induced in all elephants, but the level of sedation varied differently over time for each elephant. Twelve elephants remained standing throughout the sedation period, while 3 elephants became laterally recumbent. Sedative effects included lowered head and trunk, droopy ears, snoring, and penis protrusion. Pulse rate, respiratory rate, and rectal temperature ranged between 30-45 beats/min, 4-12 breaths/min, and 35.6-37.2°C, respectively, at 30 min after xylazine injection, and there were no changes over time. Pulmonary function and acid-base balance were adequate (range partial pressures of arterial oxygen 73-123 mmHg and carbon dioxide 33-52 mmHg, arterial hemoglobin oxygen saturation 96-99%, pH 7.34-7.54, lactate 0.9-2.5 mmol/L). Yohimbine was administered 46-110 min after the injection of xylazine, and the first sign of recovery occurred within 1-4 min. Resedation after reversal with yohimbine was observed in two elephants. In conclusion, xylazine at the doses used induced light to deep sedation with stable physiology and most elephants remained standing.

Hematologic, prostaglandin F2α -metabolite, serum amyloid A, and serum iron changes in horses with experimentally induced endotoxemia.

BACKGROUND: Endotoxemia is a common and severe disease of horses. Most previous studies have monitored changes caused by a bolus dose of endotoxin over short time periods. OBJECTIVES: We aimed to describe inflammatory responses to endotoxin with inflammatory and hematologic markers monitored over a longer time than has been performed in the past using more prolonged endotoxin exposures. METHODS: Escherichia coli O55:B5 endotoxin was administered as a 6-hour continuous intravenous infusion of lipopolysaccharide (LPS) to eight horses. Blood cell counts, and prostaglandin F2α -metabolite (PGM), serum amyloid A (SAA), and serum total iron concentrations were monitored for up to 3 or 6 days. RESULTS: An immediate and severe decrease in neutrophils and monocytes occurred in all horses, which subsequently changed to a moderate to strong neutrophilia and monocytosis that persisted for more than 78 hours postinfusion (PI) of LPS. Lymphocyte and eosinophil numbers decreased gradually and then normalized after 66- and 78-hours PI, respectively. Mild to moderate, biphasic thrombocytopenia occurred. A pronounced, transient increase in PGM occurred between 1 and 7 hours, peaking at 2 hours. Serum amyloid A began to increase after 6 hours PI and remained elevated after 72 hours PI. Serum iron was decreased between 6 and 48 hours. The clinical signs were most prominent during the first 24 hours PI and subsided within 48 hours PI. CONCLUSIONS: Neutrophilia, monocytoses, and high SAA concentrations were present in horses even after the clinical signs had subsided. Serum iron normalized before SAA. Knowledge of these findings is imperative when interpreting laboratory results in horses with possible endotoxin exposure.

Effect of non-steroidal anti-inflammatory drugs on postoperative respiratory and heart rate in cats subjected to ovariohysterectomy.

Objectives The use of physiological parameters such as respiratory rate and heart rate to assess pain has long been discussed. The aim of the study was to compare postoperative respiratory rate and heart rate in cats subjected to flank ovariohysterectomy treated with a preoperative non-steroidal anti-inflammatory drug (NSAID) or no NSAID, and determine whether these parameters are suitable for postoperative pain assessment in cats. We hypothesised that cats without an NSAID would experience more postoperative pain, which may increase heart rate and respiratory rate. Methods A total of 168 female privately owned cats were studied. All cats were premedicated with medetomidine (0.08 mg/kg) and butorphanol (0.4 mg/kg) subcutaneously and anaesthesia was induced with intramuscular ketamine (5 mg/kg). Cats were divided into subgroups; controls (no NSAID) or cats given an NSAID, carprofen (4 mg/kg) or meloxicam (0.3 mg/kg), at premedication or induction of anaesthesia. Cats were subjected to flank ovariohysterectomy by the same surgeon. Atipamezole was administered 2.5 h after induction of anaesthesia. Respiratory rate and heart rate were measured 3.5 h after the induction of anaesthesia. Data were analysed using one-way ANOVA with mixed procedure and Tukey's adjustment method for multiplicity. Results The postoperative respiratory rate and heart rate per minute for all cats were 34.0 ± 8.6 and 167.5 ± 27.4, respectively. Neither respiratory rate nor heart rate differed significantly between the control group and the NSAID groups or between different time points of administration of NSAIDs. Conclusion and relevance Assuming there was less postoperative pain in the group administered NSAIDs, the results of the study presented no support for use of respiratory rate and heart rate as parameters for postoperative pain assessment in individual cats. Study limitations included a lack of pain scoring and baseline data for respiratory rate and heart rate.

Time-related changes in equine neutrophils after experimental endotoxemia: myeloperoxidase staining, size, and numbers.

BACKGROUND: Neutrophil myeloperoxidase content is determined by the Advia 2120 hematology system by staining characteristics. Changes in myeloperoxidase staining are shown by location of neutrophils on Advia peroxidase dot plots and as myeloperoxidase index (MPXI). Significant changes in MPXI have been reported during severe inflammation in horses, dogs, and people but conclusions were inconsistent. OBJECTIVES: Infusion of endotoxin was used to initiate an inflammatory stimulus under controlled conditions and over a longer time period than in previous studies to document kinetics of changes in neutrophil numbers, morphology, and myeloperoxidase staining. Identification of consistent time-related changes may allow better interpretation of changes in neutrophil characteristics during inflammation. MATERIALS: Five Standardbred trotting horses received an intravenous infusion over a 6-hour period with Escherichia coli endotoxin. Neutrophil count, MPXI, neutrophil characteristics in Advia 2120 Perox dot plots and neutrophil morphology in blood smears were monitored with repeated sampling for up to 10 days. RESULTS: Endotoxin infusion immediately caused severe neutropenia which converted to neutrophilia 14 hours after start of endotoxin infusion. Neutrophilia was still present 78 hours after start of infusion. Large "giant" neutrophils first appeared in blood smears and Advia Perox dot plots after 36-48 hours. A marked and consistent decrease in MPXI was seen in all horses 6 days (150 hours) after endotoxin exposure. CONCLUSIONS: Endotoxemia caused prominent, time-related changes in equine neutrophil characteristics including emergence of giant neutrophils and markedly decreased MPXI several days after endotoxin infusion.

Pulmonary gas exchange and acid-base status during immobilisation of black rhinoceroses (Diceros bicornis) in Zimbabwe.

When immobilising wildlife, adverse side effects can include hypoxaemia, acidosis and hypertension. Pulmonary gas exchange and acid-base status were evaluated during immobilisation of 25 free-ranging and one boma-held black rhinoceros (Diceros bicornis) in Zimbabwe. The effect of different body positions on arterial oxygenation was evaluated. A combination of the following drugs was used: an opioid (etorphine or thiafentanil), azaperone and an a2 -adrenoceptor agonist (detomidine or xylazine). Respiratory and heart rates, rectal temperature and pulse oximetry-derived haemoglobin oxygen saturation were recorded. Serial arterial blood samples were analysed immediately in the field. Marked hypoxaemia and hypercapnia were recorded in immobilised free-ranging black rhinoceroses. Arterial oxygenation was higher during sternal compared to lateral recumbency. Most rhinoceroses developed acidaemia of respiratory and metabolic origin. Initially high lactate concentrations in free-ranging rhinoceroses decreased during immobilisation. Pulse oximetry was unreliable in the detection of hypoxaemia. Positioning in sternal recumbency and routine use of oxygen supplementation are recommended in the management of immobilised rhinoceroses as measures to improve arterial oxygenation.

Lumbo-sacral epidural anaesthesia as a complement to dissociative anaesthesia during scrotal herniorrhaphy of livestock pigs in the field.

BACKGROUND: In Sweden, scrotal or inguinal herniorrhaphy of livestock pigs in the field has traditionally been an important part of the surgical skills training of veterinary students. Few substances meet the legal requirements for field anaesthesia of production animals in the European Union but a protocol based on azaperone-detomidine-butorphanol-ketamine does. Unfortunately the anaesthesia is characterised by unpredictable duration and depth and of abrupt awakenings which is not acceptable from an animal welfare perspective and impedes surgical training. Lumbo-sacral epidural analgesia is proven to provide sufficient analgesia to allow abdominal surgery, but there are few reports on the field use of this loco-regional technique. The study aim was to evaluate whether lumbo-sacral anaesthesia can be safely and successfully used in the field by a veterinary student and whether the combination of dissociative and lumbo-sacral epidural anaesthesia improves analgesia and anaesthesia to guarantee animal welfare during herniorrhaphy in livestock pigs, enabling surgical skills training. RESULTS: Pigs in the control-group (placebo) responded significantly stronger to surgery, with five out of 11 requiring additional doses of detomidine and ketamine. There were no significant differences between groups in respiratory rate, heart rate, blood pressure, SpO2 or blood gases. SpO2 levels <94 % were recorded in several pigs in both groups. No post-injection complications were reported at follow-up. CONCLUSIONS: The results from this study showed that lumbo-sacral epidural anaesthesia with lidocaine could successfully be administered during dissociative anaesthesia of livestock pigs by a veterinary student and without reported post-injection complications. It improved analgesia and anaesthesia during herniorrhaphy of sufficient duration to enable surgical skills training. The risks and consequences of hypoxaemia and hypoventilation should be considered.

Intravenous sufentanil-midazolam versus sevoflurane anaesthesia in medetomidine pre-medicated Himalayan rabbits undergoing ovariohysterectomy.

OBJECTIVE: To compare physiological effects of sufentanil-midazolam with sevoflurane for surgical anaesthesia in medetomidine premedicated rabbits. STUDY DESIGN: Prospective, randomized controlled experimental study. ANIMALS: Eighteen female Himalayan rabbits, weight 2.1 ± 0.1 kg. METHODS: Premedication with 0.1 mg kg(-1) medetomidine and 5 mg kg(-1) carprofen subcutaneously, was followed by intravenous anaesthetic induction with sufentanil (2.3 µg mL(-1)) and midazolam (0.45 mg mL(-1)). After endotracheal intubation, anaesthesia was maintained with sufentanil-midazolam (n = 9) or sevoflurane (n = 9). Ovariohysterectomy was performed. Intermittent positive pressure ventilation was performed as required. Physiological variables were studied perioperatively. Group means of physiologic data were generated for different anaesthetic periods. Data were compared for changes from sedation, and between groups by anova. Post-operatively, 0.05 mg kg(-1) buprenorphine was administered once and 5 mg kg(-1) carprofen once daily for 2-3 days. Rabbits were examined and weighed daily until one week after surgery. RESULTS: Smooth induction of anaesthesia was achieved within 5 minutes. Sufentanil and midazolam doses were 0.5 µg kg(-1) and 0.1 mg kg(-1), during induction and 3.9 µg kg(-1) hour(-1) and 0.8 mg kg(-1) hour(-1) during surgery, respectively. End-tidal sevoflurane concentration was 2.1% during surgery. Assisted ventilation was required in nine rabbits receiving sufentanil-midazolam and four receiving sevoflurane. There were no differences between groups in physiologic data other than arterial carbon dioxide. In rabbits receiving sevoflurane, mean arterial pressure decreased pre-surgical intervention, heart rate increased 25% during and after surgery and body weight decreased 4% post-operatively. Post-operative problems sometimes resulted from catheterization of the ear artery. CONCLUSION: Sevoflurane and sufentanil-midazolam provided surgical anaesthesia of similar quality. Arterial blood pressure was sustained during sufentanil-midazolam anaesthesia and rabbits receiving sevoflurane lost body weight following ovariohysterectomy. Mechanical ventilation was required with both anaesthetic regimens. CLINICAL RELEVANCE: Anaesthesia with sufentanil-midazolam in medetomidine premedicated healthy rabbits is useful in the clinical and the research setting, as an alternative to sevoflurane.

Effects of pulse-delivered inhaled nitric oxide administration on pulmonary perfusion and arterial oxygenation in dorsally recumbent isoflurane-anesthetized horses.

OBJECTIVE: To image the spatial distribution of pulmonary blood flow by means of scintigraphy, evaluate ventilation-perfusion (VA/Q) matching and pulmonary blood shunting (Qs/Qt) by means of the multiple inert gas elimination technique (MIGET), and measure arterial oxygenation and plasma endothelin-1 concentrations before, during, and after pulse-delivered inhaled nitric oxide (PiNO) administration to isoflurane-anesthetized horses in dorsal recumbency. ANIMALS: 3 healthy adult Standardbreds. PROCEDURES: Nitric oxide was pulsed into the inspired gases in dorsally recumbent isoflurane-anesthetized horses. Assessment of VA/Q matching, Qs/Qt, and Pao2 content was performed by use of the MIGET, and spatial distribution of pulmonary blood flow was measured by perfusion scintigraphy following IV injection of technetium Tc 99m-labeled macroaggregated human albumin before, during, and 30 minutes after cessation of PiNO administration. RESULTS: During PiNO administration, significant redistribution of blood flow from the dependent regions to the nondependent regions of the lungs was found and was reflected by improvements in VA/Q matching, decreases in Qs/Qt, and increases in Pao2 content, all of which reverted to baseline values at 30 minutes after PiNO administration. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of PiNO in anesthetized dorsally recumbent horses resulted in redistribution of pulmonary blood flow from dependent atelectatic lung regions to nondependent aerated lung regions. Because hypoxemia is commonly the result of atelectasis in anesthetized dorsally recumbent horses, the addition of nitric oxide to inhaled gases could be used clinically to alleviate hypoxemia in horses during anesthesia.

Anaesthesia in medetomidine premedicated New Zealand White rabbits: a comparison between intravenous sufentanil-midazolam and isoflurane anaesthesia for orthopaedic surgery.

Eighteen female New Zealand White rabbits (3.9 ± 0.4 kg) were anaesthetized with sufentanil-midazolam by intravenous infusion (SUF-MID, n = 9) or isoflurane (ISO, n = 9) for bilateral creation of an osteochondral defect in the medial femur condyle. Subcutaneous premedication with 0.1 mg/kg medetomidine and anaesthesia induction by intravenous infusion of 1.1 µg/kg sufentanil and 0.2 mg/kg midazolam were identical in both groups. During surgery (60 min), the effects on respiratory and circulatory variables serum lactate, total protein and blood glucose were examined. Intermittent positive pressure ventilation (IPPV) was initiated if apnoea lasted>30 s or if end-tidal CO2 ≥8 kPa. The righting reflex was lost in 3 min. IPPV was necessary during most of the anaesthesia for most of the rabbits. Maintenance doses during surgery were 2.0 µg/kg/h sufentanil and 0.4 mg/kg/h midazolam, and 1.4% isoflurane, respectively. Mean arterial blood pressure (MAP) was higher in group SUF-MID than group ISO during surgery (63 ± 12 vs 50 ± 8 mmHg). In group ISO the heart rate was higher during surgery than before anaesthesia (197 ± 26 vs 158 ± 40 bpm) as was blood glucose (9 ± 2 vs 12 ± 3 mmol/L). Serum lactate levels remained unchanged whereas total protein decreased in both groups. Time to recover from anaesthesia did not differ between groups (20 min). Intravenous sufentanil-midazolam infusion provided surgical anaesthesia with a higher MAP than isoflurane anaesthesia. The protocol can be useful in situations in which gas anaesthesia cannot be used or in animals with limited cardiovascular reserves. However, IPPV is necessary.

The effects of pulse-delivered inhaled nitric oxide on arterial oxygenation, ventilation-perfusion distribution and plasma endothelin-1 concentration in laterally recumbent isoflurane-anaesthetized horses.

OBJECTIVES: Anaesthetized horses commonly become hypoxaemic due to ventilation/perfusion (V·A/Q·) mismatch and increased pulmonary shunt fraction (Qs·/Qt·). Pulse-delivered inhaled nitric oxide may improve oxygenation but may increase plasma concentration of the potent vasoconstrictor, endothelin-1 (ET-1). Objectives: Study 1) compare arterial oxygen concentration (PaO2) and saturation (SaO2), calculated Qs·/Qt· and ET-1 concentration; and Study 2) assess V·A/Q· matching and measured Qs·/Qt· in isoflurane-anaesthetized horses in left lateral recumbency receiving pulse-delivered inhaled nitric oxide (PiNO group) or inhalant gas only (C group). STUDY DESIGN: Prospective research trial. ANIMALS: Ten Healthy adult Standardbred horses. Two horses were anaesthestized in both groups in a random cross-over design with >4 weeks between studies. METHODS: Study 1) Cardiopulmonary data including PaO2, SaO2, Qs·/Qt· and ET-1 concentration were measured or calculated prior to and at various points during PiNO administration in 6PiNO and 6C horses. Two-way repeated measures anova with Bonferroni significant difference test was used for data analysis with p < 0.05 considered significant. Study 2) V·A/Q· matching and Qs·/Qt· were determined using the multiple inert gas elimination technique in 3 horses. Data were collected after 60 minutes of anaesthesia without PiNO (baseline) and 15 minutes after PiNO was pulsed during the first 30%, and then the first 60%, of inspiration. Data were descriptive only. RESULTS: Study 1) PaO2 and SaO2 were higher and calculated Qs·/Qt· was lower in the PiNO group than the C group at most time points. ET-1 was not different over time or between groups. Study 2) V·A/Q· matching and measured Qs·/Qt· were improved from baseline in all horses but PiNO60% provided no improvement when compared to PiNO30%. CONCLUSIONS AND CLINICAL RELEVANCE: PiNO delivered in the initial portion of the inspiration effectively relieves hypoxaemia in anaesthetized horses by improving V·A/Q· matching and decreasing Qs·/Qt· without affecting ET-1.

Continuous intravenous anaesthesia with sufentanil and midazolam in medetomidine premedicated New Zealand White rabbits.

BACKGROUND: Anaesthesia in rabbits is associated with a high mortality rate, compared to that in cats and dogs. Total intravenous anaesthesia (TIVA) with drugs that provide cardiovascular stability and are rapidly metabolised could be of benefit for use in rabbits. The aim was to evaluate cardiorespiratory effects of TIVA with sufentanil-midazolam in eight New Zealand White rabbits. Subcutaneous premedication with medetomidine (0.1 mg/kg BW) was followed by IV administration of a mixture of 2.5 µg/mL sufentanil and 0.45 mg/mL midazolam at a rate of 0.3 mL/kg BW/h for anaesthetic induction. Additionally, intravenous boluses of 0.1 mL of the mixture were administered every 20 s until the righting reflex was lost. Following endotracheal intubation, anaesthesia was maintained for 60 min with an infusion rate adjusted to supress the pedal withdrawal reflex. Air and oxygen (1:2) were delivered at 3 L/min. Physiological variables were recorded before induction and at predefined time points during and after anaesthesia. RESULTS: Righting and pedal withdrawal reflexes were lost within 3 and 5 min, respectively. Doses of sufentanil and midazolam were 0.48 µg/kg BW and 0.09 mg/kg BW for induction, and 0.72 µg/kg BW/h and 0.13 mg/kg BW/h for maintenance. Apnoea occurred in two rabbits. Induction of anaesthesia caused a significant increase in heart rate, cardiac output and arterial CO2 partial pressure and a decrease in mean arterial pressure, respiratory rate and pH. Mean time from stopping the infusion to endotracheal extubation was 5 min, and to return of the righting reflex 7 min. Anaesthesia was characterized by induction and recovery without excitation, with muscle relaxation, and absence of the pedal withdrawal reflex. CONCLUSIONS: TIVA with sufentanil-midazolam provided smooth induction and recovery of anaesthesia in rabbits but with marked hypotension and respiratory depression, requiring mechanical ventilation. Further evaluation is needed to establish if the protocol is useful for rabbits undergoing surgery.

Oxygenation and plasma endothelin-1 concentrations in healthy horses recovering from isoflurane anaesthesia administered with or without pulse-delivered inhaled nitric oxide.

OBJECTIVE: To assess oxygenation, ventilation-perfusion (V/Q) matching and plasma endothelin (ET-1) concentrations in healthy horses recovering from isoflurane anaesthesia administered with or without pulse-delivered inhaled nitric oxide (iNO). STUDY DESIGN: Prospective experimental trial. ANIMALS: Healthy adult Standardbred horses. METHODS: Horses were anaesthetized with isoflurane in oxygen and placed in lateral recumbency. Six control (C group) horses were anaesthetized without iNO delivery and six horses received pulse-delivered iNO (NO group). After 2.5 hours of anaesthesia isoflurane and iNO were abruptly discontinued, inhaled oxygen was reduced from 100% to approximately 30%, and the horses were moved to the recovery stall. At intervals during a 30-minute period following the discontinuation of anaesthesia, arterial and mixed venous blood gas values, shunt fraction (Qs/Qt), plasma ET-1 concentration, pulse rate and respiratory rate were measured or calculated. Repeated measures anova and a Bonferroni post hoc test was used to analyze data with significance set at p < 0.05. RESULTS: At all time points in the recovery period, NO horses maintained better arterial oxygenation (oxygen partial pressure: NO 13.2 ± 2.7-11.1 ± 2.7 versus C 6.7 ± 1.1-7.1 ± 1.1 kPa) and better V/Q matching (Qs/Qt NO 0.23 ± 0.05-0.14 ± 0.06 versus C 0.48 ± 0.03-0.32 ± 0.08%) than C horses. Mixed venous oxygenation was higher in NO for 25 minutes following the discontinuation of anaesthesia (NO 6.3 ± 0.2-4.5 ± 0.07 versus C 4.7 ± 0.6-3.7 ± 0.3 kPa). In both groups of horses arterial oxygenation remained fairly stable; venous oxygenation declined over this time period in the NO group but still remained higher than venous oxygen in the C group. ET-1 concentrations were higher at most time points in C than NO. Changes in other parameters were either minor or absent. CONCLUSIONS AND CLINICAL RELEVANCE: Delivery of iNO to healthy horses during anaesthesia results in better arterial and venous oxygenation and V/Q matching (as determined by lower Qs/Qt) and lower ET-1 concentrations throughout a 30-minute anaesthetic recovery period.

Pulsed delivery of inhaled nitric oxide counteracts hypoxaemia during 2.5 hours of inhalation anaesthesia in dorsally recumbent horses.

OBJECTIVE: The study aimed to investigate the effect of varying pulse lengths of inhaled nitric oxide (iNO), and 2.5 hours of continuous pulse-delivered iNO on pulmonary gas exchange in anaesthetized horses. STUDY DESIGN: Experimental study. ANIMALS: Six Standardbred horses. METHODS: Horses received acepromazine, detomidine, guaifenesin, thiopentone and isoflurane in oxygen, were positioned in dorsal recumbency and were breathing spontaneously. iNO was on average pulsed during the first 20, 30, 43 or 73% of the inspiration in 15 minute steps. The pulse length that corresponded to the highest (peak) partial pressure of arterial oxygen (PaO(2) ) in the individual horses was determined and delivered for a further 1.5 hours. Data measured or calculated included arterial and mixed venous partial pressures of O(2) and CO(2) , heart rate, respiratory rate, expired minute ventilation, pulmonary and systemic arterial mean pressures, cardiac output and venous admixture. Data (mean ± SD) was analysed using anova with p < 0.05 considered significant. RESULTS: Although the pulse length of iNO that corresponded to peak PaO(2) varied between horses, administration of all pulse lengths of iNO increased PaO(2) compared to baseline. The shortest pulse lengths that resulted in the peak PaO(2) were 30 and 43% of the inspiration. Administration of iNO increased PaO(2) (12.6 ± 4.1 kPa [95 ± 31 mmHg] at baseline to a range of 23.0 ± 8.4 to 25.3 ± 9.0 kPa [173 to 190 mmHg]) and PaCO(2) (8.5 ± 1.2 kPa [64 ± 9 mmHg] to 9.8 ± 1.5 kPa [73 ± 11 mmHg]) and decreased venous admixture from 32 ± 6% to 25 ± 6%. The increase in PaO(2) and decrease in venous admixture was sustained for the entire 2.5 hours of iNO delivery. CONCLUSIONS: The improvement in arterial oxygenation during pulsed delivery of iNO was significant and sustained throughout 2.5 hours of anaesthesia. CLINICAL RELEVANCE: Pulsed iNO potentially could be used clinically to counteract hypoxemia in anaesthetized horses.

Cardiac troponin I and the occurrence of cardiac arrhythmias in horses with experimentally induced endotoxaemia.

The aim of this study was to determine whether experimentally-induced endotoxaemia induced elevations in plasma cardiac troponin I (cTnI) concentrations in horses and how this might affect the incidence of cardiac arrhythmias. Eight Standardbred horses received an intravenous continuous rate infusion of endotoxin (total dose 500 ng/kg) for 6 h while being monitored using electrocardiography (ECG). Blood samples were collected before the start of the endotoxin infusion, every 60 min during the infusion, then 1, 2, 3, 8, 10 and 24 h post-infusion, and analysed for cTnI concentrations. One horse was excluded from the study owing to a high initial cTnI concentration. Endotoxin infusion induced an increase in cTnI concentrations in all horses, reaching mean peak concentration of 0.135±0.094 µg/L by 1 h post-infusion. The cTnI concentrations then decreased and were no longer significantly different from pre-infusion concentrations at 6, 10 and 24 h post-infusion. The number of ventricular events was generally low during the infusion period, but increased during the first 3 h post-infusion in 6/7 horses. In conclusion, elevated cTnI concentrations could be detected early after an endotoxaemic insult using an ultrasensitive cTnI assay, with peak cTnI concentrations preceding the occurrence of ventricular events on ECG.

Effect of sedation with detomidine and butorphanol on pulmonary gas exchange in the horse.

BACKGROUND: Sedation with alpha2-agonists in the horse is reported to be accompanied by impairment of arterial oxygenation. The present study was undertaken to investigate pulmonary gas exchange using the Multiple Inert Gas Elimination Technique (MIGET), during sedation with the alpha2-agonist detomidine alone and in combination with the opioid butorphanol. METHODS: Seven Standardbred trotter horses aged 3-7 years and weighing 380-520 kg, were studied. The protocol consisted of three consecutive measurements; in the unsedated horse, after intravenous administration of detomidine (0.02 mg/kg) and after subsequent butorphanol administration (0.025 mg/kg). Pulmonary function and haemodynamic effects were investigated. The distribution of ventilation-perfusion ratios (VA/Q) was estimated with MIGET. RESULTS: During detomidine sedation, arterial oxygen tension (PaO2) decreased (12.8 +/- 0.7 to 10.8 +/- 1.2 kPa) and arterial carbon dioxide tension (PaCO2) increased (5.9 +/- 0.3 to 6.1 +/- 0.2 kPa) compared to measurements in the unsedated horse. Mismatch between ventilation and perfusion in the lungs was evident, but no increase in intrapulmonary shunt could be detected. Respiratory rate and minute ventilation did not change. Heart rate and cardiac output decreased, while pulmonary and systemic blood pressure and vascular resistance increased. Addition of butorphanol resulted in a significant decrease in ventilation and increase in PaCO2. Alveolar-arterial oxygen content difference P(A-a)O2 remained impaired after butorphanol administration, the VA/Q distribution improved as the decreased ventilation and persistent low blood flow was well matched. Also after subsequent butorphanol no increase in intrapulmonary shunt was evident. CONCLUSION: The results of the present study suggest that both pulmonary and cardiovascular factors contribute to the impaired pulmonary gas exchange during detomidine and butorphanol sedation in the horse.

Metabolism during anaesthesia and recovery in colic and healthy horses: a microdialysis study.

BACKGROUND: Muscle metabolism in horses has been studied mainly by analysis of substances in blood or plasma and muscle biopsy specimens. By using microdialysis, real-time monitoring of the metabolic events in local tissue with a minimum of trauma is possible. There is limited information about muscle metabolism in the early recovery period after anaesthesia in horses and especially in the colic horse. The aims were to evaluate the microdialysis technique as a complement to plasma analysis and to study the concentration changes in lactate, pyruvate, glucose, glycerol, and urea during anaesthesia and in the recovery period in colic horses undergoing abdominal surgery and in healthy horses not subjected to surgery. METHODS: Ten healthy university-owned horses given anaesthesia alone and ten client-owned colic horses subjected to emergency abdominal surgery were anaesthetised for a mean (range) of 230 min (193-273) and 208 min (145-300) respectively. Venous blood samples were taken before anaesthesia. Venous blood sampling and microdialysis in the gluteal muscle were performed during anaesthesia and until 24 h after anaesthesia. Temporal changes and differences between groups were analysed with an ANOVA for repeated measures followed by Tukey Post Hoc test or Planned Comparisons. RESULTS: Lactate, glucose and urea, in both dialysate and plasma, were higher in the colic horses than in the healthy horses for several hours after recovery to standing. In the colic horses, lactate, glucose, and urea in dialysate, and lactate in plasma increased during the attempts to stand. The lactate-to-pyruvate ratio was initially high in sampled colic horses but decreased over time. In the colic horses, dialysate glycerol concentrations varied considerably whereas in the healthy horses, dialysate glycerol was elevated during anaesthesia but decreased after standing. In both groups, lactate concentration was higher in dialysate than in plasma. The correspondence between dialysate and plasma concentrations of glucose, urea and glycerol varied. CONCLUSION: Microdialysis proved to be suitable in the clinical setting for monitoring of the metabolic events during anaesthesia and recovery. It was possible with this technique to show greater muscle metabolic alterations in the colic horses compared to the healthy horses in response to regaining the standing position.

Physiologic responses and plasma endothelin-1 concentrations associated with abrupt cessation of nitric oxide inhalation in isoflurane-anesthetized horses.

OBJECTIVE: To assess physiologic responses and plasma endothelin (ET)-1 concentrations associated with abrupt cessation of nitric oxide (NO) inhalation in isoflurane-anesthetized horses. ANIMALS: 6 healthy adult Standardbreds. PROCEDURES: Horses were anesthetized with isoflurane in oxygen and placed in dorsal recumbency. Nitric oxide was pulsed into the respiratory tract for 2.5 hours, and then administration was abruptly discontinued. Just prior to commencement and at cessation of NO administration, and at intervals during a 30-minute period following cessation of NO inhalation, several variables including PaO(2), mean pulmonary artery pressure, venous admixture or pulmonary shunt fraction (Qs/Qt), and plasma ET-1 concentration were recorded or calculated. RESULTS: After cessation of NO inhalation, PaO(2) decreased slowly but significantly (172.7 +/- 29.8 mm Hg to 84.6 +/- 10.9 mm Hg) and Qs/Qt increased slowly but significantly (25 +/- 2% to 40 +/- 3%) over a 30-minute period. Mean pulmonary artery pressure increased slightly (14.0 +/- 1.3 mm Hg to 16.8 +/- 1 mm Hg) over the same time period. No change in serum ET-1 concentration was detected, and other variables did not change or underwent minor changes. CONCLUSIONS AND CLINICAL RELEVANCE: The improvement in arterial oxygenation during pulsed inhalation of NO to healthy isoflurane-anesthetized horses decreased only gradually during a 30-minute period following cessation of NO inhalation, and serum ET-1 concentration was not affected. Because a rapid rebound response did not develop, inhalation of NO might be clinically useful in the treatment of hypoxemia in healthy isoflurane-anesthetized horses.

Metabolism before, during and after anaesthesia in colic and healthy horses.

BACKGROUND: Many colic horses are compromised due to the disease state and from hours of starvation and sometimes long trailer rides. This could influence their muscle energy reserves and affect the horses' ability to recover. The principal aim was to follow metabolic parameter before, during, and up to 7 days after anaesthesia in healthy horses and in horses undergoing abdominal surgery due to colic. METHODS: 20 healthy horses given anaesthesia alone and 20 colic horses subjected to emergency abdominal surgery were anaesthetised for a mean of 228 minutes and 183 minutes respectively. Blood for analysis of haematology, electrolytes, cortisol, creatine kinase (CK), free fatty acids (FFA), glycerol, glucose and lactate was sampled before, during, and up to 7 days after anaesthesia. Arterial and venous blood gases were obtained before, during and up to 8 hours after recovery. Gluteal muscle biopsy specimens for biochemical analysis of muscle metabolites were obtained at start and end of anaesthesia and 1 h and 1 day after recovery. RESULTS: Plasma cortisol, FFA, glycerol, glucose, lactate and CK were elevated and serum phosphate and potassium were lower in colic horses before anaesthesia. Muscle adenosine triphosphate (ATP) content was low in several colic horses. Anaesthesia and surgery resulted in a decrease in plasma FFA and glycerol in colic horses whereas levels increased in healthy horses. During anaesthesia muscle and plasma lactate and plasma phosphate increased in both groups. In the colic horses plasma lactate increased further after recovery. Plasma FFA and glycerol increased 8 h after standing in the colic horses. In both groups, plasma concentrations of CK increased and serum phosphate decreased post-anaesthesia. On Day 7 most parameters were not different between groups. Colic horses lost on average 8% of their initial weight. Eleven colic horses completed the study. CONCLUSION: Colic horses entered anaesthesia with altered metabolism and in a negative oxygen balance. Muscle oxygenation was insufficient during anaesthesia in both groups, although to a lesser extent in the healthy horses. The post-anaesthetic period was associated with increased lipolysis and weight loss in the colic horses, indicating a negative energy balance during the first week post-operatively.

The effects of spontaneous and mechanical ventilation on central cardiovascular function and peripheral perfusion during isoflurane anaesthesia in horses.

OBJECTIVE: To compare the effects of spontaneous breathing and mechanical ventilation on haemodynamic variables, including muscle and skin perfusion measured with laser Doppler flowmetery, in horses anaesthetized with isoflurane. STUDY DESIGN: Prospective controlled study. ANIMALS: Ten warm-blood trotter horses (five males, five females). Mean mass was 492 kg (range 420-584 kg) and mean age was 5 years (range 4-8 years). MATERIALS AND METHODS: After pre-anaesthetic medication with detomidine (10 microg kg(-1)) anaesthesia was induced with intravenous (IV) guaifenesin and thiopental (4-5 mg kg(-1) IV) and maintained using isoflurane in oxygen. The horses were positioned in dorsal recumbency. In five animals breathing was initially spontaneous (SB) while the lungs of the other five were ventilated mechanically using intermittent positive pressure ventilation (IPPV). Total anaesthesia time was 4 hours with the ventilatory mode changed after 2 hours. During anaesthesia, heart rate (HR) cardiac output (Qt) stroke volume (SV) systemic arterial blood pressures (sAP), and pulmonary arterial pressure (pAP) were recorded. Peripheral perfusion was measured in the semimembranosus and gluteal muscles and on the tail skin using laser Doppler flowmetry. Arterial (a) and mixed venous (v) blood gases, pH, haemoglobin concentration [Hb], haematocrit (Hct), plasma lactate concentration and muscle temperature were measured. Oxygen content, venous admixture (s/Qt) oxygen delivery (DO(2)) and oxygen consumption (VO(2)) were calculated. RESULTS: During mechanical ventilation, HR, sAP, pAP, Qt, SV, Qs/Qt and PaCO(2) were lower and PaO(2) was higher compared with spontaneous breathing. There were no differences between the modes of ventilation in the level of perfusion, DO(2), VO(2), [Hb], (Hct), or plasma lactate concentration. After the change from IPPV to SB, left semimembranosus muscle and skin perfusion improved, while muscle perfusion tended to decrease when SB was changed to IPPV. Low-frequency flow motion was seen twice as frequently during IPPV compared with SB. CONCLUSIONS: Mechanical ventilation impaired cardiovascular function compared with SB in horses during isoflurane anaesthesia. Muscle and skin perfusion changes occurred with ventilation, although further studies are needed to elucidate the underlying mechanisms.