Development of a method for analysis of ketamine and norketamine enantiomers in equine brain and cerebrospinal fluid by capillary electrophoresis.

Ketamine and norketamine are being transported across the blood brain barrier and are also entering from blood into cerebrospinal fluid (CSF). Enantioselective distributions of these compounds in brain and CSF have never been determined. The enantioselective CE based assay previously developed for equine plasma was adapted to the analysis of these compounds in equine brain via use of an acidic pre-extraction of interferences prior to liquid/liquid extraction at alkaline pH. CSF can be treated as plasma. With 100 mg of brain tissue and 0.5 mL of CSF or plasma, assay conditions for up to 30 nmol/g and 6 µM, respectively, of each enantiomer with LOQs of 0.5 nmol/g and 0.1 µM, respectively, were established and the assays were applied to equine samples. CSF and plasma samples analyzed stemmed from anesthetized patient horses and brain, CSF and plasma were obtained from anesthetized horses that were euthanized with an overdose of pentobarbital. Data obtained indicate that ketamine and norketamine enantiomers are penetrating into brain and CSF with those of ketamine being more favorably transported than norketamine, whereas metabolites of norketamine are hindered. More work is required to properly investigate possible stereoselectivities of the ketamine metabolism and transport of metabolites from blood into brain tissue and CSF.

Prevalence and risk factors for canine post-anesthetic aspiration pneumonia (1999-2009): a multicenter study.

OBJECTIVE: To determine the incidence of canine post-anesthetic aspiration pneumonia (AP) and to identify anesthetic agents, procedures and management factors associated with the development of AP. STUDY DESIGN: Multicenter, randomized, case-controlled retrospective study. ANIMALS: Two hundred and forty dogs affected with AP and 488 unaffected control dogs. METHODS: Electronic medical record databases at six Veterinary colleges were searched for dogs, coded for anesthesia or sedation and pneumonia from January 1999 to December 2009. The resultant 2158 records were hand-searched to determine eligibility for inclusion. Diagnosis of AP was made radiographically. Two unaffected control dogs were randomly selected for each affected dog, from a list of dogs that underwent sedation or anesthesia in the same time period and did not develop aspiration pneumonia. Fifty-seven factors were then evaluated for association with aspiration pneumonia. Data analysis was performed using univariate Chi-square or student t-tests, then multivariate logistic regression. RESULTS: Incidence of post-anesthetic AP was 0.17%, from 140,711 cases anesthetized or sedated over the 10 year period. Two anesthesia-related events were significantly associated with development of AP: regurgitation and administration of hydromorphone at induction. Administration of anticholinergics was not associated with AP. Procedures associated with increased odds of aspiration pneumonia included laparotomy, upper airway surgery, neurosurgery, thoracotomy and endoscopy. Orthopedic surgery, ophthalmologic surgery, dental procedures, MRI, CT, bronchoscopy, cystoscopy, tracheoscopy and neutering were not associated with development of AP. Three patient factors were associated with the development of AP: megaesophagus, and a history of pre-existing respiratory or neurologic disease. Sixty-nine% of dogs with two or more of the above independent predictive variables developed AP. CONCLUSION AND CLINICAL RELEVANCE: Most anesthetic agents and procedures were not associated with the development of AP. We need to devise and evaluate strategies to protect at risk patients.

Suspected acute meperidine toxicity in a dog.

OBSERVATIONS: A 22-month-old male neutered Coton De Tulear dog was presented for upper gastrointestinal endoscopy under general anesthesia. The anesthetic plan included premedication with intramuscular meperidine (4 mg kg(-1)) but meperidine was inadvertently administered at ten-fold this dose. Within 5 minutes, the dog was unresponsive to external stimulation, and by 10 minutes post-injection developed generalized signs of central nervous system (CNS) excitement. Initial therapy included inspired oxygen supplementation, and single intravenous (IV) doses of diazepam (0.68 mg kg(-1)) and naloxone (0.03 mg kg(-1)) to no effect. A second dose of diazepam (0.46 mg kg(-1), IV) abolished most of the signs of CNS excitement. General anesthesia was induced and the endoscopy performed. Time to extubation was initially prolonged, but administering naloxone (final dose 0.1 mg kg(-1), IV) to effect enabled extubation. After naloxone, the dog became agitated, noise sensitive, and had leg and trunk muscle twitches. Diazepam (0.30 mg kg(-1), IV) abolished these signs and the dog became heavily sedated and laterally recumbent. Naloxone administration was continued as a constant rate infusion (0.02 mg kg(-1) hour(-1), IV) until approximately 280 minutes post-meperidine injection, at which time the dog suddenly sat up. Occasional twitches of the leg and trunk muscles were observed during the night. The dog was discharged the next day appearing clinically normal. CONCLUSIONS: Given that the CNS excitatory effects of normeperidine are not a mu opioid receptor effect, the use of naloxone should be considered carefully when normeperidine excitotoxicity is suspected. Benzodiazepines may be beneficial in ameliorating clinical signs of normeperidine excitotoxicity.

One-lung ventilation using a wire-guided endobronchial blocker for thoracoscopic pericardial fenestration in a dog.

Instead of a conventional double lumen tube, an Arndt wire-guided endobronchial blocker was used to achieve one-lung ventilation in a dog undergoing thoracoscopic pericardiectomy. Overall, lung separation was easy to perform and surgical conditions for the creation of a pericardial window were adequate. Special ventilation strategies were applied.

Stereoselective pharmacokinetics of ketamine and norketamine after constant rate infusion of a subanesthetic dose of racemic ketamine or S-ketamine in Shetland ponies.

OBJECTIVE: To evaluate pharmacokinetics of ketamine and norketamine enantiomers after constant rate infusion (CRI) of a subanesthetic dose of racemic ketamine or S-ketamine in ponies. ANIMALS: Five 6-year-old Shetland pony geldings that weighed between 101 and 152 kg. PROCEDURES: In a crossover study, each pony received a CRI of racemic ketamine (loading dose, 0.6 mg/kg; CRI, 0.02 mg/kg/min) and S-ketamine (loading dose, 0.3 mg/kg; CRI, 0.01 mg/kg/min), with a 1-month interval between treatments. Arterial blood samples were collected before and at 5, 15, 30, 45, and 60 minutes during drug administration and at 5, 10, 30, and 60 minutes after discontinuing the CRI. Plasma ketamine and norketamine enantiomers were quantified by use of capillary electrophoresis. Individual R-ketamine and S-ketamine concentration-versus-time curves were analyzed by use of a monocompartmental model. Plasma disposition curves for R-norketamine and S-norketamine were described by estimating the area under the concentration-versus-time curve (AUC), maximum concentration (Cmax), and time until Cmax. RESULTS: Plasma concentrations of S-ketamine decreased and biodegradation products increased more rapidly after S-ketamine CRI, compared with results after racemic ketamine CRI. The R-norketamine was eliminated faster than was the S-norketamine. Significant differences between treatments were found for the AUC of S-ketamine and within the racemic ketamine CRI for the AUC and Cmax of norketamine isomers. CONCLUSIONS AND CLINICAL RELEVANCE: CRI of S-ketamine may be preferable over CRI of racemic ketamine in standing equids because the S-enantiomer was eliminated faster when infused alone instead of as part of a racemic mixture.

Evaluation of anesthesia recovery quality after low-dose racemic or S-ketamine infusions during anesthesia with isoflurane in horses.

OBJECTIVE: To compare anesthesia recovery quality after racemic (R-/S-) or S-ketamine infusions during isoflurane anesthesia in horses. ANIMALS: 10 horses undergoing arthroscopy. PROCEDURES: After administration of xylazine for sedation, horses (n = 5/group) received R-/S-ketamine (2.2 mg/kg) or S-ketamine (1.1 mg/kg), IV, for anesthesia induction. Anesthesia was maintained with isoflurane in oxygen and R-/S-ketamine (1 mg/kg/h) or S-ketamine (0.5 mg/kg/h). Heart rate, invasive mean arterial pressure, and end-tidal isoflurane concentration were recorded before and during surgical stimulation. Arterial blood gases were evaluated every 30 minutes. Arterial ketamine and norketamine enantiomer plasma concentrations were quantified at 60 and 120 minutes. After surgery, horses were kept in a padded recovery box, sedated with xylazine, and video-recorded for evaluation of recovery quality by use of a visual analogue scale (VAS) and a numeric rating scale. RESULTS: Horses in the S-ketamine group had better numeric rating scale and VAS values than those in the R-/S-ketamine group. In the R-/S-ketamine group, duration of infusion was positively correlated with VAS value. Both groups had significant increases in heart rate and mean arterial pressure during surgical stimulation; values in the R-/S-ketamine group were significantly higher than those of the S-ketamine group. Horses in the R-/S-ketamine group required slightly higher end-tidal isoflurane concentration to maintain a surgical plane of anesthesia. Moderate respiratory acidosis and reduced oxygenation were evident. The R-norketamine concentrations were significantly lower than S-norketamine concentrations in the R-/S-ketamine group. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with R-/S-ketamine, anesthesia recovery was better with S-ketamine infusions in horses.

The extradural pressure profile in goats following extradural injection.

OBJECTIVE: To measure the extradural pressures in goats before and after extradural injection, and to investigate the occurrence of extradural pressure waves. STUDY DESIGN: Prospective experimental trial. ANIMALS: Nine healthy adult goats weighing 59.4 +/- 6.4 kg, scheduled for stifle arthroscopy. METHODS: The goats were pre-medicated with midazolam and anaesthesia was induced with propofol and maintained with sevoflurane. The goats were placed in lateral recumbency and extradural puncture was performed via the lumbosacral space. Correct placement of the needle was assessed by lack of resistance to the injection of saline. The needle was connected to an electronic pressure transducer to record extradural pressure. Measurements were taken before and after extradural injection of methadone (0.1 mg kg(-1), diluted to a total volume of 0.2 mL kg(-1)) and 10 minutes later. Contrast medium was injected and correct extradural needle placement confirmed by radiography. RESULTS: Lack of resistance to injection of saline occurred in all goats, but there were no pressure waves observed before injection in any animal. Radiography indicated incorrect needle placement in four animals and one had pressure waves synchronous with the arterial pulse after methadone injection. Correct needle placement was confirmed in the remaining five animals which exhibited pressure waves after extradural methadone injection. In the five goats with successful needle placement the baseline extradural pressure ranged from 0.4 to 2.5 kPa (3-19 mmHg), increasing to 4.4-39.9 kPa (33-300 mmHg) after injection. Ten minutes after injection, extradural pressure remained elevated and ranged from 2.5 to 17.3 kPa (19-130 mmHg). CONCLUSIONS AND CLINICAL RELEVANCE: Extradural pressure waves were not useful to confirm correct extradural needle placement in laterally recumbent goats. The presence of such waves after injection of 0.2 mL kg(-1) may be indicative of correct placement but even here we saw one of nine animals with extradural pressure waves where we failed to confirm correct needle placement. Extradural pressure increases after extradural injection.

Stereoselective pharmacokinetics of ketamine and norketamine after racemic ketamine or S-ketamine administration in Shetland ponies sedated with xylazine.

The pharmacokinetics of ketamine and norketamine enantiomers after administration of intravenous (IV) racemic ketamine (R-/S-ketamine; 2.2 mg/kg) or S-ketamine (1.1 mg/kg) to five ponies sedated with IV xylazine (1.1mg/kg) were compared. The time intervals to assume sternal and standing positions were recorded. Arterial blood samples were collected before and 1, 2, 4, 6, 8 and 13 min after ketamine administration. Arterial blood gases were evaluated 5 min after ketamine injection. Plasma concentrations of ketamine and norketamine enantiomers were determined by capillary electrophoresis and were evaluated by non-linear least square regression analysis applying a monocompartmental model. The first-order elimination rate constant was significantly higher and elimination half-life and mean residence time were lower for S-ketamine after S-ketamine compared to R-/S-ketamine administration. The maximum concentration of S-norketamine was higher after S-ketamine administration. Time to standing position was significantly diminished after S-ketamine compared to R-/S-ketamine. Blood gases showed low-degree hypoxaemia and hypercarbia.

Comparison of the cardiopulmonary effects of anesthesia maintained by continuous infusion of ketamine and propofol with anesthesia maintained by inhalation of sevoflurane in goats undergoing magnetic resonance imaging.

OBJECTIVE: To compare the cardiopulmonary effects of anesthesia maintained by continuous infusion of ketamine and propofol with anesthesia maintained by inhalation of sevoflurane in goats undergoing magnetic resonance imaging. ANIMALS: 8 Saanen goats. PROCEDURES: Goats were anesthetized twice (1-month interval) following sedation with midazolam (0.4 mg/kg, IV). Anesthesia was induced via IV administration of ketamine (3 mg/kg) and propofol (1 mg/kg) and maintained with an IV infusion of ketamine (0.03 mg/kg/min) and propofol (0.3 mg/kg/min) and 100% inspired oxygen (K-P treatment) or induced via IV administration of propofol (4 mg/kg) and maintained via inhalation of sevoflurane in oxygen (end-expired concentration, 2.3%; 1X minimum alveolar concentration; SEVO treatment). Cardiopulmonary and blood gas variables were assessed at intervals after induction of anesthesia. RESULTS: Mean +/- SD end-expired sevoflurane was 2.24 +/- 0.2%; ketamine and propofol were infused at rates of 0.03 +/- 0.002 mg/kg/min and 0.29 +/- 0.02 mg/kg/min, respectively. Overall, administration of ketamine and propofol for total IV anesthesia was associated with a degree of immobility and effects on cardiopulmonary parameters that were comparable to those associated with anesthesia maintained by inhalation of sevoflurane. Compared with the K-P treatment group, mean and diastolic blood pressure values in the SEVO treatment group were significantly lower at most or all time points after induction of anesthesia. After both treatments, recovery from anesthesia was good or excellent. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that ketamine-propofol total IV anesthesia in goats breathing 100% oxygen is practical and safe for performance of magnetic resonance imaging procedures.

Intraoperative antinociception and postoperative analgesia following epidural anesthesia versus femoral and sciatic nerve blockade in dogs undergoing stifle joint surgery.

OBJECTIVE: To compare analgesic efficacy of preoperative epidural anesthesia with efficacy of femoral and sciatic nerve blockade in dogs undergoing hind limb orthopedic surgery. DESIGN: Prospective randomized blinded clinical study. ANIMALS: 22 dogs requiring stifle joint surgery. PROCEDURES: Dogs were premedicated with acepromazine and morphine, and anesthesia was induced with diazepam and propofol and maintained with sevoflurane in oxygen. Prior to surgery, a combination of 1.0% lidocaine solution with 0.25% bupivacaine solution was administered either into the lumbosacral epidural space (11 dogs) or perineurally along the femoral and sciatic nerves (11). Intraoperative nociception was assumed if heart rate or systolic blood pressure increased by > 10% from baseline, in which case fentanyl (2 µg/kg [0.9 µg/lb], IV) was administered as rescue analgesia. Following recovery from anesthesia, signs of postoperative pain were assessed every 30 minutes for 360 minutes from the time of local anesthetic administration via the modified Glasgow pain scale. Patients with scores > 5 (scale, 0 to 20) received hydromorphone (0.1 mg/kg [0.05 mg/lb], IV) as rescue analgesia and were then withdrawn from further pain scoring. RESULTS: Treatment groups did not differ significantly in the number fentanyl boluses administered for intraoperative rescue analgesia. Time to administration of first postoperative rescue analgesia was comparable between groups. Furthermore, there was no significant difference between groups in baseline pain scores, nor were there significant differences at any other point during the postoperative period. CONCLUSIONS AND CLINICAL RELEVANCE: Femoral and sciatic nerve blocks provided intraoperative antinociception and postoperative analgesia similar to epidural anesthesia in dogs undergoing stifle joint surgery.

Use of the oxygen content-based index, Fshunt, as an indicator of pulmonary venous admixture at various inspired oxygen fractions in anesthetized sheep.

OBJECTIVE: To evaluate the use of the oxygen content-based index, Fshunt, as an indicator of venous admixture (Qs/Qt) at various fractions of inspired oxygen (FIO(2)s) in anesthetized sheep undergoing Flung or 2-lung ventilation. Animals-6 healthy adult female sheep. PROCEDURES: Sheep were anesthetized and administered 5 different FIO(2)s (0.21, 0.40, 0.60, 0.80, and 1.00) in random order during 2-lung mechanical ventilation. Arterial and mixed venous blood samples were obtained at each FIO(2) after a 15-minute stabilization period. Vital capacity alveolar recruitment maneuvers were performed after blood collection. The previously used FIO(2) sequence was reversed for sample collection during Flung ventilation. Blood samples were analyzed for arterial, pulmonary end-capillary, and mixed venous oxygen content and partial pressure and for hemoglobin concentration. Oxygen hemoglobin saturation, Qs/Qt, Fshunt, and oxygen tension-based indices (OTIs; including PAO(2):FIO(2), alveolar-arterial difference in partial pressure of oxygen [PAO(2) - PAO(2)], [PAO(2) - Pao(2)]:FIO(2), [PAO(2) - PAO(2)]:PAO(2), and PAO(2):PAO(2)) were calculated at each FIO(2); associations were evaluated with linear regression analysis, concordance, and correlation tests. Intermethod agreement between Qs/Qt and Fshunt was tested via Bland-Altman analysis. RESULTS: Strong and significant associations and substantial agreement were detected between Fshunt and Qs/Qt. Relationships between OTIs and Qs/Qt varied, but overall correlations were weak. Conclusions and Clinical Relevance-Whereas OTIs were generally poor indicators of Qs/Qt, Fshunt was a good indicator of Qs/Qt at various FIO(2)s, regardless of the magnitude of Qs/Qt, and could be potentially used as a surrogate for Qs/Qt measurements in healthy sheep.

A technique for ultrasound-guided paravertebral brachial plexus injections in dogs.

Using cadaveric dogs, we established the ultrasonographic landmarks for performing paravertebral injections around the brachial plexus nerve roots in the dog, and assessed the accuracy and regional spread of the aliquots. A mixture of methylene blue dye and an iodinated contrast medium was used as the injectate. A 0.3 ml volume was used to assess accuracy and a 3.0 ml volume was used to assess regional spread. Accuracy and regional spread were assessed from computed tomography (CT) images acquired after injection by measuring the distance from each foramen to the nearest edge of contrast medium, and the dimensions of spread of contrast medium in each anatomic plane, respectively. The mean distance of small volume injections from each foramen was 0.9 cm (standard deviation [SD] 0.56 cm). The mean spread of contrast medium for the small volume injections measured 1.7 cm (SD 0.6 cm) cranial-to-caudal, 1.2 cm (SD 0.4 cm) dorsal-to-ventral and 7.4 cm (SD 0.4 cm) medial-to-lateral. The mean spread of contrast medium for the combined three large volume injections measured 7.4 cm (SD 1.7 cm) cranial-to-caudal, 3.1 cm (SD 0.8 cm) medial-to-lateral, and 2.8 cm (SD 0.5 cm) dorsal-to-ventral. After the CT studies, staining of each nerve root and any other regional structure was assessed grossly. Based on our results, ultrasound can be used to guide injections around the nerve roots of the brachial plexus in dogs.