Regula Bettschart-Wolfensberger

Resuscitation strategies from bupivacaine‐induced cardiac arrest

Objectives:  Local anesthetic (LA) intoxication with cardiovascular arrest is a potential fatal complication of regional anesthesia. Lipid resuscitation has been recommended for the treatment of LA‐induced cardiac arrest. Aim of the study was to compare four different rescue regimens using epinephrine and/or lipid emulsion and vasopressin to treat cardiac arrest caused by bupivacaine intoxication.

Development of a romifidine constant rate infusion with or without butorphanol for standing sedation of horses

OBJECTIVE To elaborate constant rate infusion (CRI) protocols for xylazine (X) and xylazine/butorphanol (XB) which will result in constant sedation and steady xylazine plasma concentrations. STUDY DESIGN Blinded randomized experimental study. ANIMALS Ten adult research horses. METHODS Part I: After normal height of head above ground (HHAG = 100%) was determined, a loading dose of xylazine (1 mg kg(-1) ) with butorphanol (XB: 18 μg kg(-1) ) or saline (X: equal volume) was given slowly intravenously (IV). Immediately afterwards, a CRI of butorphanol (XB: 25 μg kg(-1) hour(-1)) or saline (X) was administered for 2 hours. The HHAG was used as a marker of depth of sedation. Sedation was maintained for 2 hours by additional boluses of xylazine (0.3 mg kg(-1)) whenever HHAG >50%. The dose of xylazine (mg kg(-1) hour(-1)) required to maintain sedation was calculated for both groups. Part II: After the initial loading dose, the calculated xylazine infusion rates were administered in parallel to butorphanol (XB) or saline (X) and sedation evaluated. Xylazine plasma concentrations were measured by HPLC-MS-MS at time points 0, 5, 30, 45, 60, 90, and 120 minutes. Data were analyzed using paired t-test, Wilcoxon signed rank test and a 2-way anova for repeated measures (p < 0.05). RESULTS There was no significant difference in xylazine requirements (X: 0.69, XB: 0.65 mg kg(-1) hour(-1)) between groups. With treatment X, a CRI leading to prolonged sedation was developed. With XB, five horses (part I: two, part II: three) fell down and during part II four horses appeared insufficiently sedated. Xylazine plasma concentrations were constant after 45 minutes in both groups. CONCLUSION Xylazine bolus, followed by CRI, provided constant sedation. Additional butorphanol was ineffective in reducing xylazine requirements and increased ataxia and apparent early recovery from sedation in unstimulated horses. CLINICAL RELEVANCE Data were obtained on unstimulated healthy horses and extrapolation to clinical conditions requires caution.

Comparison of epinephrine vs lipid rescue to treat severe local anesthetic toxicity – an experimental study in piglets

Objectives:  Local anesthetic (LA) intoxication with severe hemodynamic compromise is a potential catastrophic event. Lipid resuscitation has been recommended for the treatment of LA‐induced cardiac arrest. However, there are no data about effectiveness of Intralipid® for the treatment of severe cardiovascular compromise prior to cardiac arrest. Aim of this study was to compare effectiveness of epinephrine and Intralipid® for the treatment of severe hemodynamic compromise owing to bupivacaine intoxication.

A study of cardiovascular function under controlled and spontaneous ventilation in isoflurane-medetomidine anaesthetized horses

OBJECTIVE To determine, in mildly hypercapnic horses under isoflurane-medetomidine balanced anaesthesia, whether there is a difference in cardiovascular function between spontaneous ventilation (SV) and intermittent positive pressure ventilation (IPPV). STUDY DESIGN Prospective randomized clinical study. ANIMALS Sixty horses, undergoing elective surgical procedures under general anaesthesia: ASA classification I or II. METHODS Horses were sedated with medetomidine and anaesthesia was induced with ketamine and diazepam. Anaesthesia was maintained with isoflurane and a constant rate infusion of medetomidine. Horses were assigned to either SV or IPPV for the duration of anaesthesia. Horses in group IPPV were maintained mildly hypercapnic (arterial partial pressure of carbon dioxide (PaCO(2)) 50-60 mmHg, 6.7-8 kPa). Mean arterial blood pressure (MAP) was maintained above 70 mmHg by an infusion of dobutamine administered to effect. Heart rate (HR), respiratory rate (f(R)), arterial blood pressure and inspiratory and expiratory gases were monitored continuously. A bolus of ketamine was administered when horses showed nystagmus. Cardiac output was measured using lithium dilution. Arterial blood-gas analysis was performed regularly. Recovery time was noted and recovery quality scored. RESULTS There were no differences between groups concerning age, weight, body position during anaesthesia and anaesthetic duration. Respiratory rate was significantly higher in group IPPV. Significantly more horses in group IPPV received supplemental ketamine. There were no other significant differences between groups. All horses recovered from anaesthesia without complications. CONCLUSIONS There was no difference in cardiovascular function in horses undergoing elective surgery during isoflurane-medetomidine anaesthesia with SV in comparison with IPPV, provided the horses are maintained slightly hypercapnic. CLINICAL RELEVANCE In horses with health status ASA I and II, cardiovascular function under general anaesthesia is equal with or without IPPV if the PaCO(2) is maintained at 50-60 mmHg.

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.

Effects on cardiopulmonary function and oxygen delivery of doses of romifidine and xylazine followed by constant rate infusions in standing horses.

The objective of this study was to compare the cardiopulmonary effects of a xylazine or romifidine loading-dose, followed by a constant rate infusion (CRI) of the same α(2)-agonist. Nine research horses were treated in a randomized, blinded, crossover design with xylazine or romifidine. After instrumentation, a loading dose of intravenous xylazine (1mg/kg) or romifidine (80μg/kg) was administered, immediately followed by a CRI of xylazine (0.69mg/kg/h) or romifidine (30μg/kg/h) for a duration of 2h. Cardiopulmonary variables were recorded before bolus administration, during CRI, and for 1h after discontinuing drug administration. A significant decrease in haemoglobin concentration (tHb), arterial oxygen content (CaO(2)), oxygen delivery (D˙O(2)), mixed venous partial pressure of oxygen, heart rate, and cardiac output (Q˙t) followed the loading dose with both treatments. Carotid arterial blood pressure (ABP), systemic vascular resistance, and right atrial pressure (RAP) increased significantly. The increased ABP was followed by a significant decrease compared to baseline. Mean pulmonary arterial pressure increased significantly with romifidine only. No significant changes in stroke volume, arterial partial pressure of oxygen, and oxygen consumption were observed. Changes in Q˙t and RAP were more pronounced with romifidine. During CRI, tHb, and CaO(2) were significantly higher with romifidine, whereas D˙O(2) did not differ between treatments. Overall, cardiopulmonary effects were more pronounced and lasted longer with romifidine compared to xylazine. However, during CRI, there was no difference in D˙O(2) between drugs. With both α(2)-agonists, cardiovascular effects were most pronounced after loading dose administration and tended to stabilize during CRI.

A clinical study on the effect in horses during medetomidine–isoflurane anaesthesia, of butorphanol constant rate infusion on isoflurane requirements, on cardiopulmonary function and on recovery characteristics

OBJECTIVE To test if the addition of butorphanol by constant rate infusion (CRI) to medetomidine-isoflurane anaesthesia reduced isoflurane requirements, and influenced cardiopulmonary function and/or recovery characteristics. STUDY DESIGN Prospective blinded randomised clinical trial. ANIMALS 61 horses undergoing elective surgery. METHODS Horses were sedated with intravenous (i.v.) medetomidine (7 μg kg(-1)); anaesthesia was induced with i.v. ketamine (2.2 mg kg(-1)) and diazepam (0.02 mg kg(-1)) and maintained with isoflurane and a CRI of medetomidine (3.5 μg kg(-1) hour(-1)). Group MB (n = 31) received butorphanol CRI (25 μg kg(-1) i.v. bolus then 25 μg kg(-1) hour(-1)); Group M (n = 30) an equal volume of saline. Artificial ventilation maintained end-tidal CO2 in the normal range. Horses received lactated Ringers solution 5 mL kg(-1) hour(-1), dobutamine <1.25 μg kg(-1) minute(-1) and colloids if required. Inspired and exhaled gases, heart rate and mean arterial blood pressure (MAP) were monitored continuously; pH and arterial blood gases were measured every 30 minutes. Recovery was timed and scored. Data were analyzed using two way repeated measures anova, independent t-tests or Mann-Whitney Rank Sum test (p < 0.05). RESULTS There was no difference between groups with respect to anaesthesia duration, end-tidal isoflurane (MB: mean 1.06 ± SD 0.11, M: 1.05 ± 0.1%), MAP (MB: 88 ± 9, M: 87 ± 7 mmHg), heart rate (MB: 33 ± 6, M: 35 ± 8 beats minute(-1)), pH, PaO2 (MB: 19.2 ± 6.6, M: 18.2 ± 6.6 kPa) or PaCO2. Recovery times and quality did not differ between groups, but the time to extubation was significantly longer in group MB (26.9 ± 10.9 minutes) than in group M (20.4 ± 9.4 minutes). CONCLUSION AND CLINICAL RELEVANCE Butorphanol CRI at the dose used does not decrease isoflurane requirements in horses anaesthetised with medetomidine-isoflurane and has no influence on cardiopulmonary function or recovery.

International online survey to assess current practice in equine anaesthesia.

REASONS FOR PERFORMING STUDY Multicentre Confidential Enquiries into Perioperative Equine Fatalities (CEPEF) have not been conducted since the initial CEPEF Phases 1-3, 20 years ago. OBJECTIVES To collect data on current practice in equine anaesthesia and to recruit participants for CEPEF-4. STUDY DESIGN Online questionnaire survey. METHODS An online questionnaire was prepared and the link distributed internationally to veterinarians possibly performing equine anaesthesia, using emails, posters, flyers and an editorial. The questionnaire included 52 closed, semiclosed and open questions divided into 8 subgroups: demographic data, anaesthetist, anaesthesia management (preoperative, technical equipment, monitoring, drugs, recovery), areas of improvements and risks and motivation for participation in CEPEF-4. Descriptive statistics and Chi-squared tests for comparison of categorical variables were performed. RESULTS A total of 199 questionnaires were completed by veterinarians from 14 different countries. Of the respondents, 43% worked in private hospitals, 36% in private practices and 21% in university teaching hospitals. In 40 institutions (23%) there was at least one diplomate of the European or American colleges of veterinary anaesthesia and analgesia on staff. Individual respondents reported routinely employ the following anaesthesia monitoring modalities: electrocardiography (80%), invasive arterial blood pressures (70%), pulse oximetry (60%), capnography (55%), arterial blood gases (47%), composition of inspired and expired gases (45%) and body temperature (35%). Drugs administered frequently or routinely as part of a standard protocol were: acepromazine (44%), xylazine (68%), butorphanol (59%), ketamine (96%), diazepam (83%), isoflurane (76%), dobutamine (46%), and, as a nonsteroidal anti-inflammatory drug, phenylbutazone (73%) or flunixin meglumine (66%). Recovery was routinely assisted by 40%. The main factors perceived by the respondents to affect outcome of equine anaesthesia were the preoperative health status of the animal and training of the anaesthetist. CONCLUSIONS Current practice in equine anaesthesia varies widely, and the study has highlighted important topics relevant for designing a future prospective multicentre cohort study (CEPEF-4). The Summary is available in Chinese - see Supporting information.

The effects of a loading dose followed by constant rate infusion of xylazine compared with romifidine on sedation, ataxia and response to stimuli in horses

OBJECTIVE To compare xylazine and romifidine constant rate infusion (CRI) protocols regarding degree of sedation, and effects on postural instability (PI), ataxia during motion (A) and reaction to different stimuli. STUDY DESIGN Blinded randomized experimental cross-over study. ANIMALS Ten adult horses. METHODS Degree of sedation was assessed by head height above ground (HHAG). Effects on PI, A and reaction to visual, tactile and acoustic stimulation were assessed by numerical rating scale (NRS) and by visual analogue scale (VAS). After baseline measurements, horses were sedated by intravenous loading doses of xylazine (1 mg kg(-1) ) or romifidine (80 μg kg(-1) ) administered over 3 minutes, immediately followed by a CRI of xylazine (0.69 mg kg(-1 ) hour(-1) ) or romifidine (30 μg kg(-1 ) hour(-1) ) which was administered for 120 minutes. Degree of sedation, PI, A and reaction to the different stimuli were measured at different time points before, during and for one hour after discontinuing drug administration. Data were analysed using two-way repeated measures anova, a Generalized Linear Model and a Wilcoxon Signed Rank Test (p < 0.05). RESULTS Significant changes over time were seen for all variables. With xylazine HHAG was significantly lower 10 minutes after the loading dose, and higher at 150 and 180 minutes (i.e. after CRI cessation) compared to romifidine. Reaction to acoustic stimulation was significantly more pronounced with xylazine. Reaction to visual stimulation was greater with xylazine at 145 and 175 minutes. PI was consistently but not significantly greater with xylazine during the first 30 minutes. Reaction to touch and A did not differ between treatments. Compared to romifidine, horses were more responsive to metallic noise with xylazine. CONCLUSIONS Time to maximal sedation and to recovery were longer with romifidine than with xylazine. CLINICAL RELEVANCE With romifidine sufficient time should be allowed for complete sedation before manipulation.

Microassay for ketamine and metabolites in plasma and serum based on enantioselective capillary electrophoresis with highly sulfated γ‐cyclodextrin and electrokinetic analyte injection

For the assessment of stereoselective aspects of the metabolism of ketamine, an enantioselective CE‐based microassay for determination of the stereoisomers of ketamine and three of its major metabolites in plasma and serum was developed. The assay is based on liquid/liquid extraction of the analytes of interest at alkaline pH from 0.05 mL plasma or serum followed by electrokinetic sample injection of the analytes from the extract across a buffer plug without chiral selector. Separation occurs cationically at normal polarity in a pH 3.0 phosphate buffer containing 0.66% of highly sulfated γ‐cyclodextrin (HS‐γ‐CD). Key parameters for optimization are identified as being the amount of HS‐γ‐CD in the BGE, the length of the buffer plug and its concentration, the duration of electrokinetic injection, and the extraction medium. Diluted buffer in the plug is employed to ascertain sufficient analyte stacking due to a combination of field amplification and complexation. The newly developed microassay is robust (intraday and interday RSD < 5% and <9%, respectively) and well suited to determine enantiomer levels of ketamine and its metabolites down to 10 ng/mL. It is more sensitive, uses less plasma or serum, organic solvent, and analysis time compared to previous CE‐based assays and was successfully applied to monitor ketamine, norketamine, 5,6‐dehydronorketamine (DHNK), and 6‐hydroxynorketamine (6HNK) stereoisomer levels in plasma of a Beagle dog that received a bolus of racemic ketamine or S‐ketamine after sevoflurane anesthesia. The data suggest that the formation of DHNK and 6HNK occur stereoselectively.