Effects of isoflurane and sevoflurane alone and in combination with butorphanol or medetomidine on the bispectral index in chickens.

BACKGROUND: The bispectral index (BIS) is an anaesthesia monitoring technique able to assess the level of central nervous system depression in humans and various animal species. In birds, it has been validated in chickens undergoing isoflurane anaesthesia. The aim of this study was to evaluate in an avian species the influence of isoflurane and sevoflurane on BIS, each at different minimum anaesthetic concentrations (MAC) multiples, alone or combined with butorphanol or medetomidine. Ten chickens (5 males and 5 females) underwent general anaesthesia with isoflurane or sevoflurane alone, and combined with either intramuscular administration of butorphanol (1 mg/kg) or medetomidine (0.1 mg/kg), in a prospective and cross-over study (i.e., 6 treatments per animal). BIS measurements were compared to heart rate (HR), non-invasive blood pressure (NIBP) and to a visual analogue scale (VAS) of anaesthesia depth. RESULTS: HR was significantly increased, and both NIBP and VAS were significantly reduced, with higher gas concentrations. NIBP (but not HR or VAS) was additionally affected by the type of gas, being lower at higher concentrations of sevoflurane. Butorphanol had no additional effect, but medetomidine led to differences in HR, NIBP, and in particular a reduction in VAS. With respect to deeper level of hypnosis at higher concentrations and the absence of difference between gases, BIS measurements correlated with all other measures (except with HR, where no significant relationship was found) The difference in BIS before (BISpre) and after stimulation (BISpost) did not remain constant, but increased with increasing MAC multiples, indicating that the BISpost is not suppressed proportionately to the suppression of the BISpre values due to gas concentration. Furthermore, neither butorphanol nor medetomidine affected the BIS. CONCLUSIONS: The difference of degree of central nervous system depression monitored by BIS compared with neuromuscular reflexes monitored by VAS, indicate that BIS records a level of anaesthetic depth different from the one deducted from VAS monitoring alone. BIS provided complementary information such as that medetomidine suppressed spinal reflexes without deepening the hypnotic state. As a consequence, it is concluded that BIS improves the assessment of the level of hypnosis in chickens, improving anaesthesia monitoring and anaesthesia quality in this species.

Further development of the MRONJ minipig large animal model.

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious and potentially severe side effect of antiresorptive therapy with bisphosphonates or denosumab. Recently, a large animal minipig MRONJ model was introduced which led to early necrotic lesions in the majority of extraction sites after bisphosphonate administration. The aim of this project was to modify the preoperative cumulative bisphosphonate dose (zoledronate) and hereby firstly to demonstrate the reliability and reproducibility of the established model. Secondly, the MRONJ lesions should be carefully investigated using clinical and µCT as well as detailed histological analyses. Twelve 1.5-year-old Göttingen minipigs were divided into three groups. In group 1 (n = 3) minipigs received weekly doses of zoledronate intravenously (0.05 mg/kg bodyweight) for 20 weeks. No interventions were performed. In group 2 (n = 6) animals received the identical zoledronate dosage as animals in group 1 and tooth extractions of two premolars (PM 2 and 4) in each jaw (maxilla and mandible) were performed after 12 weeks. Group 3 (n = 3) served as tooth extraction only control (no zoledronate administrations). The jaw-bones were subjected to detailed macroscopic, radiological and histological investigations. All extraction sites (24/24) in animals of group 2 showed clinical, radiological and histological signs of MRONJ (mainly stage II), whereas no bone necrosis was found in group 3. Animals of group 1 and group 2 showed further MRONJ lesions in areas where infections (periodontitis) were present. This is the first large animal model to show a 100% incidence of MRONJ at all extraction sites in bisphosphonate pretreated animals (group 2). In addition, in this preclinical model for MRONJ it is shown that tooth extractions are not mandatory for a MRONJ manifestation. MRONJ also developed in areas of gingival or periodontal infections.

Comparison of isoflurane and alfaxalone (Alfaxan) for the induction of anesthesia in flamingos (Phoenicopterus roseus) undergoing orthopedic surgery.

Used since the 1970s as an avian anesthetic, the neurosteroid alfaxalone has been reformulated to avoid side effects from its castor oil excipient. This case report describes the clinical use of a new alfaxalone formulation (Alfaxan) as an intravenous anesthetic induction agent in wild isoflurane-anesthetized rose flamingos (Phoenicopterus roseus). Twenty-five male and female rose flamingos underwent orthopedic surgery using isoflurane anesthesia. The animals were induced following one of two protocols: inhaled isoflurane by facemask (ISO; n = 9) or intravenous alfaxalone (2 mg/kg; ALF; n = 16). The time and quality of anesthetic induction (until first signs of muscle relaxation) and the time and quality of recovery (sternal recumbency) were recorded using a scoring system. Mild sedation was first observed at 18.4 +/- 3.8 min and 1.7 +/- 0.3 min, following isoflurane and alfaxalone administration, respectively (P < 0.001). Alfaxalone induction time was significantly shorter and induction quality was considered smoother than in the ISO group. Flamingos given alfaxalone induction required lower isoflurane concentrations for maintenance anesthesia than did flamingos induced with mask isoflurane (1.5-2 % vol vs. 4-5 % vol for ALF vs. ISO, respectively). Alfaxalone produced moderate cardiorespiratory effects not seen in the isoflurane induction group. Recovery times were similar with both protocols without significant differences in quality and length. The new alfaxalone formulation produces a safe and effective anesthetic induction in rose flamingos and has significant isoflurane-sparing effects during anesthesia.

Bispectral index analysis during cardiac arrest and cardiopulmonary resuscitation in a propofol-anesthetized calf.

OBJECTIVE: To describe bispectral index (BIS) findings and compare them with cardiovascular and respiratory trends during cardiac arrest and successful CPR in a propofol-anesthetized calf. CASE SUMMARY: A 3-month-old calf was anesthetized as part of a research project. A thromboxane analog drug (U46619) was administered IV to induce pulmonary hypertension. Within 10 minutes following U46619 administration, cardiac activity deteriorated, leading to asystole. At this point, BIS and suppression rate were 0 and 100, respectively. Anesthetic drug delivery was discontinued and external chest compressions were initiated. During CPR, end-tidal CO2 concentration decreased and BIS increased, but no spontaneous cardiac activity was noted, thus IV epinephrine was administered. Return of spontaneous circulation was achieved and systemic arterial hypertension developed, while BIS briefly decreased and then increased during the following 2 minutes. The calf's cardiopulmonary variables returned to physiological ranges within 10 minutes after the return of spontaneous circulation and remained stable. UNIQUE INFORMATION PROVIDED: This is the first report in which BIS is documented together with standard monitoring techniques during cardiopulmonary arrest and resuscitation in a calf. BIS varied with cardiovascular performance, and may be indicative of cerebral blood flow in this context. Further research may be warranted to define the role of BIS for monitoring cerebral activity during CPR.

Comparison of fluid types for resuscitation in acute hemorrhagic shock and evaluation of gastric luminal and transcutaneous Pco2 in Leghorn chickens.

The objective of this study was to compare the effects of 3 different fluid types for resuscitation after experimentally induced hemorrhagic shock in anesthetized chickens and to evaluate partial pressures of carbon dioxide measured in arterial blood (Paco2), with a transcutaneous monitor (TcPco2), with a gastric intraluminal monitor (GiPco2), and by end tidal measurements (Etco2) under stable conditions and after induced hemorrhagic shock. Hemorrhagic shock was induced in 40 white leghorn chickens by removing 50% of blood volume by phlebotomy under general anesthesia. Birds were divided into 4 groups: untreated (control group) and treated with intravenous hetastarch (haes group), with a hemoglobin-based oxygen carrier (hemospan group), or by autotransfusion (blood group). Respiratory rates, heart rates, and systolic arterial blood pressure (SAP) were compared at 8 time points (baseline [T0]; at the loss of 10% [T10%], 20% [T20%], 30% [T30%], 40% [T40%], and 50% [T50%] of blood volume; at the end of resuscitation [RES]; and at the end of anesthesia [END]). Packed cell volume (PCV) and blood hemoglobin content were compared at 6 time points (T0, T50%, RES, and 1, 3, and 7 days after induced hemorrhagic shock). Measurements of Paco2, TcPco2, GiPco2, and Etco2 were evaluated at 2 time points (T0 and T50%), and venous lactic acid concentrations were evaluated at 3 time points (T0, T50%, and END). No significant differences were found in mortality, respiratory rate, heart rate, PCV, or hemoglobin values among the 4 groups. Birds given fluid resuscitation had significantly higher SAPs after fluid administration than did birds in the control group. In all groups, PCV and hemoglobin concentrations began to rise by day 3 after phlebotomy, and baseline values were reached 7 days after blood removal. At T0, TcPco2 did not differ significantly from Paco2, but GiPco2 and Etco2 differed significantly from Paco2. After hemorrhagic shock, GiPco2 and TcPco2 differed significantly from Paco2. The TcPco2 or GiPco2 values did not differ significantly at any time point in birds that survived or died in any of the groups and across all groups. These results showed no difference in mortality in leghorn chickens treated with fluid resuscitation after hemorrhagic shock and that the PCV and hemoglobin concentrations increased by 3 days after acute hemorrhage with or without treatment. The different CO2 measurements document changes in CO2-values consistent with poor perfusion and may prove useful for serial evaluation of responses to shock and shock treatment.

Evaluation of two devices for point-of-care testing of haemoglobin in neonatal pigs.

In veterinary medicine, point-of-care testing (POCT) techniques have become popular, since they provide immediate results and only small amounts of blood are needed. However, their accuracy is controversial. Pigs are often used for research purposes and accurate measurement of haemoglobin (Hb) is important during invasive procedures. The aim of this study was to evaluate two different Hb POCT devices in neonatal pigs. A prospective study with 57 pigs of 3-6 weeks of age, weighing 4.1-6.2 kg (median 5.1 kg) was performed. Fifty-seven blood samples were analysed for Hb using a conductivity-based and a photometrical POCT device and compared with a photometrical reference method. Statistical analysis was performed with Bland-Altman analysis, Spearman correlation and Passing-Bablok regression analysis. Hb values ranged from 32 to 108 g/L (median 80 g/L) using the reference method. The bias of the photometrical method (HemoCue(®)) to the reference method was -1 g/L, with limits of agreement (LOA) of -7 to 6 g/L. The conductivity-based method (i-STAT(®)) had a bias of -15 g/L with LOA from -24 to -6 g/L. There was a significant association between protein values and the bias of i-STAT versus CellDyn (r(2) = 0.27, P < 0.05) but not with the bias of HemoCue versus CellDyn (r(2) = 0.001, P = 0.79). The lower the protein values were, the lower the Hb values were measured by the i-STAT. The conductivity-based measurement of Hb constantly underestimated Hb values, whereas the photometrical method demonstrated a better accuracy and is therefore more reliable for on-site measurement of Hb in pigs.

Bispectral index reveals death-feigning behavior in a red kite (Milvus milvus).

Red kites (Milvus milvus) are birds of prey known to feign death in the presence of humans. An adult wild red kite was anesthetized with isoflurane for coelioscopy. During surgery, heart rate and respiratory rate ranged from 240 to 260 beats per minute and from 16 to 28 breaths rates per minute, respectively. Pupil and corneal reflexes remained present, and body temperature was maintained at 40.4 degrees C (104.7 degrees F). Suppression ratio was 0 during the anesthetic episode. The bispectral index was 44 immediately after intubation, ranged from 44 to 57 during maintenance of anesthesia, and was 59 at the moment of extubation. The index increased to 85 while the kite remained immobile, which was suggestive of feigning death in sternal recumbency. Once the bird was perched upright, it immediately kept the upright position, which confirmed the correspondence of the bispectral index value (85) with a fully conscious patient. Although behavioral or cardiorespiratory variables remained unchanged, the degree of hypnosis was indicated by the bispectral index, which anticipated a possible sudden awakening episode of this bird.

Comparison of the effects of racemic ketamine and S-ketamine for anesthesia in Rheem gazelles (Gazella subgutturosa marica) and Subgutturosa gazelles (Gazella subgutturosa subgutturosa).

OBJECTIVE: To evaluate effects of racemic ketamine and S-ketamine in gazelles. ANIMALS: 21 male gazelles (10 Rheem gazelles [Gazella subgutturosa marica] and 11 Subgutturosa gazelles [Gazella subgutturosa subgutturosa]), 6 to 67 months old and weighing (mean±SD) 19 ± 3 kg. PROCEDURES: In a randomized, blinded crossover study, a combination of medetomidine (80 µg/kg) with racemic ketamine (5 mg/kg) or S-ketamine (3 mg/kg) was administered i.m.. Heart rate, blood pressure, respiratory rate, rectal temperature, and oxygen saturation (determined by means of pulse oximetry) were measured. An evaluator timed and scored induction of, maintenance of, and recovery from anesthesia. Medetomidine was reversed with atipamezole. The alternate combination was used after a 4-day interval. Comparisons between groups were performed with Wilcoxon signed rank and paired t tests. RESULTS: Anesthesia induction was poor in 2 gazelles receiving S-ketamine, but other phases of anesthesia were uneventful. A dominant male required an additional dose of S-ketamine (0.75 mg/kg, i.m.). After administration of atipamezole, gazelles were uncoordinated for a significantly shorter period with S-ketamine than with racemic ketamine. Recovery quality was poor in 3 gazelles with racemic ketamine. No significant differences between treatments were found for any other variables. Time from drug administration to antagonism was similar between racemic ketamine (44.5 to 53.0 minutes) and S-ketamine (44.0 to 50.0 minutes). CONCLUSIONS AND CLINICAL RELEVANCE: Administration of S-ketamine at a dose 60% that of racemic ketamine resulted in poorer induction of anesthesia, an analogous degree of sedation, and better recovery from anesthesia in gazelles with unremarkable alterations in physiologic variables, compared with racemic ketamine.

Influence of bupivacaine injection dose rate on cardiovascular depression, subsequent hemodynamic course, and related bupivacaine plasma levels in piglets.

PURPOSE: Systemic local anesthetic (LA) toxicity resulting from inadvertent intravascular injection of LA is a rare but potentially fatal event. Early recognition of intravascular injection and approaches to improve therapeutic safety are required. This study investigated the influence of intravascular injection dose rate of bupivacaine on bupivacaine plasma levels and timing of LA-induced cardiovascular compromise. METHODS: Forty-five piglets, anesthetized with sevoflurane, were randomized into three groups. Bupivacaine was intravenously infused at a rate of 1, 4, or 16 mg/kg/min (groups A, B, and C, respectively) until mean arterial pressure (MAP) dropped to 50% of initial value. Thereafter, bupivacaine infusion was stopped and spontaneous hemodynamic course was observed. Time to MAP 50%, amount of bupivacaine infused, bupivacaine plasma level at infusion stop, spontaneous survivors, or time from bupivacaine stop to circulatory arrest were recorded. RESULTS: Median time to MAP 50% was 297, 119, and 65 s, respectively, in groups A, B, and C (P < 0.001). Median corresponding total amounts of bupivacaine infused were 5.0, 7.8, and 17.0 mg/kg (P < 0.01), and median bupivacaine plasma levels were 53.8, 180.0, and 439.8 µmol/l (P < 0.001). Five of 15 piglets in group A recovered spontaneously; in groups B and C, all animals died within 120 and 21 s, respectively. CONCLUSION: Higher dose rates of bupivacaine showed much higher plasma bupivacaine levels related to absolute infused dose at MAP 50% and were associated with an increased mortality. Slow administration of LA is recommended to allow timely detection and stopping of inadvertent intravascular administration.

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. METHODS: Piglets were anesthetized with sevoflurane, intubated, and ventilated. Bupivacaine was infused with a syringe driver via a central venous catheter at a rate of 1 mg·kg(-1) ·min(-1) until invasively measured mean arterial pressure (MAP) dropped to 50% of the initial value. Bupivacaine infusion was then stopped, and epinephrine 3 µg·kg(-1) (group 1), Intralipid(®) 20% 2 ml·kg(-1) (group 2), or Intralipid 20% 4 ml·kg(-1) (group 3) was immediately administered. Survival, hemodynamic course, and ET(CO2) were recorded. RESULTS: Twenty-one piglets (3 × 7), with median age of 26 days (19-43) and weighing 4.9 kg (4.3-5.8), were investigated. All animals in group 1 (100%) but only four of seven (57%) piglets in group 2 and group 3, respectively, survived. Normalization of hemodynamic parameters (HR, MAP) and ET(CO2) was fastest in group 1 with all piglets achieving HR and MAP values at or above baseline within 1 min. CONCLUSION: For the treatment of severe hemodynamic compromise owing to bupivacaine intoxication in piglets, first-line rescue with epinephrine was more effective than Intralipid with regard to survival as well as normalization of hemodynamic parameters and ET(CO2) .

Impact of propofol on electrocardiographic alterations during intravascular application of bupivacaine--a study in piglets.

BACKGROUND: Intravascular application of a small dose of local anesthetics (LA) with epinephrine as well as larger doses of LA under sevoflurane anesthesia results in increase in T-wave amplitude in the electrocardiogram (ECG). The aim of this study was to elucidate whether propofol anesthesia affects these ECG alterations or not. METHODS: Thirty neonatal pigs were randomized into two groups. Group 1 was anesthetized with sevoflurane, group 2 with sevoflurane plus continuous propofol infusion (10 mg·kg(-1)·h(-1)). A test dose of 0.2 ml·kg(-1) bupivacaine 0.125% + epinephrine 1 : 200,000 was injected intravenously. Arterial pressure was monitored. ECG was analyzed for changes in T-wave amplitude (positive if ≥25% baseline) and heart rate. In another setting, bupivacaine 0.125% was intravenous infused at a rate of 4 mg·kg(-1)·min(-1). ECG was analyzed for alteration in T-wave amplitude and heart rate at 1.25, 2.5, and 5 mg·kg(-1) bupivacaine infused. RESULTS: T-wave elevation after the administration of an epinephrine containing LA test dose was similar between the two groups. Increase in heart rate caused by the test dose were significantly higher in group 2 (P = 0.008). During continuous bupivacaine administration, T-wave elevation occurred in 40% and 71% (group 1 and 2) at 1.25 mg·kg(-1), in 80% and 100% at 2.5 mg·kg(-1), and in 93% and 86% at 5 mg·kg(-1) bupivacaine infused. CONCLUSION: Continuous propofol infusion does not suppress the ECG signs of a systemically administered epinephrine containing LA test dose nor does it suppress the ECG signs caused by high doses of intravenous applied bupivacaine.

Effect of inhalation of isoflurane at end-tidal concentrations greater than, equal to, and less than the minimum anesthetic concentration on bispectral index in chickens.

OBJECTIVE: To determine the effect of inhalation of isoflurane at end-tidal concentrations greater than, equal to, and less than the minimum anesthetic concentration (MAC) on bispectral index (BIS) in chickens. Animals-10 chickens. PROCEDURES: For each chicken, the individual MAC of isoflurane was determined by use of the toe-pinch method. After a 1-week interval, chickens were anesthetized with isoflurane at concentrations 1.75, 1.50, 1.25, 1.00, and 0.75 times their individual MAC (administered from higher to lower concentrations). At each MAC multiple, a toe pinch was performed and BIS was assessed and correlated with heart rate, blood pressure, and an awareness score (derived by use of a visual analogue scale). RESULTS: Among the chickens, mean +/- SD MAC of isoflurane was 1.15 +/- 0.20%. Burst suppression was detected at every MAC multiple. The BIS and awareness score were correlated directly with each other and changed inversely with increasing isoflurane concentration. Median (range) BIS values during anesthesia at 1.75, 1.50, 1.25, 1.00, and 0.75 MAC of isoflurane were 25 (15 to 35), 35 (25 to 45), 35 (20 to 50), 40 (25 to 55), and 50 (35 to 65), respectively. Median BIS value at extubation was 70 +/- 9. Values of BIS correlated with blood pressure, but not with heart rate. Blood pressure changed with end-tidal isoflurane concentrations, whereas heart rate did not. CONCLUSIONS AND CLINICAL RELEVANCE: Assessment of BIS can be used to monitor the electrical activity of the brain and the degree of unconsciousness in chickens during isoflurane anesthesia.