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.

Continuous infusion of propofol in calves: bispectral index and hemodynamic effects.

OBJECTIVE: To assess the bispectral index (BIS) and the hemodynamic effects of propofol administered by continuous infusion at different rates in calves. STUDY DESIGN: Experimental crossover study. ANIMALS: Eight intact male Dutch calves, aged 6-12 months and weighing 84-124 kg. METHODS: The calves were anesthetized with propofol (5 mg kg(-1) ) intravenously (IV), and after endotracheal intubation, positioned in right lateral recumbency and allowed to breathe ambient air. Anesthesia was maintained by continuous infusion of propofol, administered IV with an infusion pump at 0.6 mg kg(-1)  minute(-1) (treatment G6) or 0.8 mg kg(-1)  minute(-1) IV (treatment G8), for 60 minutes. The eight animals were anesthetized twice, 1 week apart. The following hemodynamic variables and BIS were assessed before the induction of anesthesia (baseline) and 15, 30, 45, and 60 minutes after beginning the infusion of propofol: heart rate, systolic, diastolic and mean arterial pressures, cardiac output, mean pulmonary artery pressure, cardiac index, stroke index, pulmonary vascular resistance index, and systemic vascular resistance index, BIS, electromyography, and signal quality index. RESULTS: The continuous infusions of propofol at different rates did not alter BIS variables during the infusion time between dose rates, and no clinically significant hemodynamic changes were observed. CONCLUSIONS AND CLINICAL RELEVANCE: A continuous infusion of propofol at 0.6 or 0.8 mg kg(-1)  minute(-1) caused minimal hemodynamic changes without clinical relevance in calves. BIS could not be reliably used to discriminate the anesthetic depth during the two propofol infusion rates.

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.

Cardiovascular and respiratory effects, and quality of anesthesia produced by alfaxalone administered intramuscularly to cats sedated with dexmedetomidine and hydromorphone.

The cardiovascular and respiratory effects, and the quality of anesthesia of alfaxalone administered intramuscularly (IM) to cats sedated with dexmedetomidine and hydromorphone were evaluated. Twelve healthy adult cats were anesthetized, with six cats receiving dexmedetomidine (0.01 mg/kg IM) followed by alfaxalone (5 mg/kg IM; group DA) and six receiving dexmedetomidine (0.01 mg/kg IM) plus hydromorphone (0.1 mg/kg IM) followed by alfaxalone (5 mg/kg IM; group DHA). Cardiorespiratory (pulse rate, blood pressure, respiratory rate, saturation of oxygen with hemoglobin, end tidal carbon dioxide partial pressure) and bispectral index (BIS) data were collected every 10 mins for 90 mins starting immediately after intubation. The quality of anesthesia was scored by a blinded researcher at induction and at 5 and 60 mins after extubation. Recovery scores ranged from 1 (prolonged struggling) to 4 (no struggling). There were no clinically significant (P >0.05) differences in any data between groups or over time. Physiologic parameters were within normal limits for cats at all times. BIS values were consistent with light anesthesia in both groups. However, recovery was prolonged and marked with excitement, ataxia and hyper-reactivity in all cats. Thus, although cardiovascular and respiratory parameters are stable following IM injection of alfaxalone to cats sedated with dexmedetomidine and hydromorphone, recovery is extremely poor and this route of administration is not recommended for anesthesia in cats.

Electroencephalogram-based anaesthetic depth monitoring in laboratory animals.

Objective measurements of physiological parameters controlled by the autonomic nervous system such as blood pressure, heart rate and respiration are easily obtained nowadays during anaesthesia by the use of monitors: oscillometers, pulseoximeters, electrocardiograms and capnographs are available for laboratory animals. However, the effect-site of hypnotic drugs that cause general anaesthesia is the central nervous system (the brain). In the present, the adjustment of hypnotic drugs in veterinary anaesthesia is performed according to subjective evaluation of clinical signs which are not direct reflexes of anaesthetic effects on the brain, making depth of anaesthesia (DoA) assessment a complicated task. The difficulties in assessing the real anaesthetic state of a laboratory animal may not only result in welfare-threatening situations, such as awareness and pain sensation during surgery, but also in a lack of standardization of experimental conditions, as it is not easy to keep all animals from an experiment in the same DoA without a measure of anaesthetic effect. A direct measure of this dose-effect relationship, although highly necessary, is still missing in the veterinary market. Meanwhile, research has been intense in this subject and methods based on the brain electrical activity (electroencephalogram) have been explored in laboratory animal species. The objective of this review is to explain the achievements made in this topic and clarify how far we are from an objective measure of DoA for animals.

The effects of atracurium on bispectral index (BIS) values in dogs anaesthetized with isoflurane.

Balanced anaesthesia techniques employ specific drugs in addition to general anaesthetics. The potential effect of some of these drugs on the bispectral index (BIS) remains unclear. BIS seems to be unaffected by the administration of neuromuscular blockers while opioids may block nociceptive-induced BIS increases in anaesthetized humans. In this study, the effect of a single dose of atracurium on BIS values was assessed in dogs premedicated with morphine and anaesthetized with isoflurane (1 MAC). Fifteen female dogs undergoing elective ovariohysterectomy were employed. BIS values were recorded before and after the administration of atracurium. These values were then recorded again once the animals were surgically stimulated. The end tidal isoflurane concentration, cardiovascular and respiratory parameters were recorded through the study. Results show that the mean (±SD) BIS values decreased slightly, but significantly (P=0.033) from 67±8.42 to 65±5.84 after the administration of atracurium. Despite significant increase in heart rate and arterial pressure during the surgical phase, the mean BIS values were not modified by ovariohysterectomy. Atracurium appeared to have minimal clinical effect on the BIS in anaesthetized dogs.

Correlation between clinical signs of depth of anaesthesia and cerebral state index responses in dogs with different target-controlled infusions of propofol.

OBJECTIVE: To evaluate if the cerebral state index (CSI), measured by a Cerebral State Monitor (CSM), can predict depth of anaesthesia as assessed clinically or by estimated propofol plasma concentrations. STUDY DESIGN: Prospective clinical study. ANIMALS: Fourteen mixed breed dogs, weighing 24.5 ± 4.7 kg, scheduled to undergo neutering procedures. METHODS: Dogs were premedicated with 0.05 mg kg(-1) acepromazine intramuscularly. The CSM and cardiovascular monitoring equipment were attached. Anaesthesia was induced with propofol using a target controlled infusion (TCI) to varying plasma propofol targets (PropCp). Following endotracheal intubation the dogs were ventilated with oxygen. Anaesthetic maintenance was with propofol by TCI. A PropCp of 3 µg dL(-1) was set initially, then PropCps were increased in 1 µg dL(-1) steps to 7, 9 and then 11 µg dL(-1). Each PropCp was held constant for a 5 minute period, at the end of which depth of anaesthesia was classified using a previously evaluated scale of 'planes' based on palpebral and corneal reflexes and eye position. Cerebral state index (CSI), burst suppression (BSR) and electromyogram were measured at these time points. The prediction probability (PK) of these variables, or of the PropCp in predicting depth of anaesthesia was calculated. RESULTS: The PKs for predicting anaesthetic planes were 0.74, 0.91, 0.76 and 0.78 for CSI, BSR, EMG and PropCp, respectively. The PKs for PropCp to predict CSI, BSR and EMG were 0.65, 0.71 and 0.65 respectively. CONCLUSION AND CLINICAL RELEVANCE: The Cerebral State Monitor was able to detect very deep planes of anaesthesia when BSR occurs, but was not able to distinguish between the intermediate anaesthetic planes likely to be used in clinical anaesthesia.

Bispectral index and the clinically evaluated anaesthetic depth in dogs.

OBJECTIVE: This study investigated whether the bispectral index (BIS monitor) corresponded with the clinical assessment of anaesthetic depth in dogs. STUDY DESIGN: Prospective clinical study. ANIMALS: Sixty-five dogs undergoing anaesthesia for surgery. METHODS: Dogs were assigned to one of three different anaesthetic techniques. A three point scale was devised to determine the clinical depth of anaesthesia (CDA); CDA 1 represented light, CDA 2 surgical and CDA 3 excessive depth of anaesthesia. BIS values were recorded and CDA assessed at specific times and points throughout surgery. Data were statistically analysed using mixed model regression. RESULTS: Clinical depth of anaesthesia was assessed as CDA 1 on 68, 2 on 748 and 3 on four occasions. The BIS recorded for CDA 1 differed significantly from that for CDA 2 (p<0.001). However, individual BIS values measured at light and surgical levels of anaesthesia overlapped considerably. The sensitivities and specificities calculated for BIS to diagnose CDA 1 compared to CDA 2 in the three anaesthetic protocols were 28-86% and 55-85%. The accompanying positive predictive value was 0.08-0.29 and the negative predictive value was 0.95-0.97. End-tidal isoflurane concentrations (anaesthetic techniques 1 and 3) and propofol infusion (technique 2) at CDA 1 was significantly lower than those at CDA 2 (p=0.001). CONCLUSIONS: Although BIS values overall distinguished between CDA scores, the calculated specificities, sensitivities and predictive values were low, and there were anomalous results in individual cases. CLINICAL RELEVANCE: The use of the BIS as the sole method to determine anaesthetic depth in dogs is imprudent.

Effects of different doses of L-659'066 on the bispectral index and clinical sedation in dogs treated with dexmedetomidine.

OBJECTIVE: To evaluate the effects of three doses of L-659'066 (MK-467) on the bispectral index (BIS) and clinical sedation in dexmedetomidine-sedated Beagles. STUDY DESIGN: Randomized, experimental cross over study. ANIMALS: Eight purpose-bred healthy laboratory Beagles. METHODS: Dexmedetomidine (10 µg kg(-1) IV [DEX]) was administered alone or in combination with three doses of L-659'066 (250 µg kg(-1) [DL250]; 500 µg kg(-1) [DL500] and 750 µg kg(-1) [DL750] IV) in the same syringe in a randomized crossover manner. The bispectral index (BIS), electromyography (EMG) and sedation score were recorded at baseline and 5, 10, 20, 30, 45 and 60 minutes after treatment. RESULTS: When compared to DEX, BIS and EMG were significantly higher and the sedation score significantly lower with DL500 and DL750. With DEX, BIS was significantly decreased at times 20, 30 and 60 minutes whereas the sedation scores were significantly increased at all time points after drug administration in all groups. Bioequivalence for clinical sedation was detected between DEX and all doses of L-659'066, reaching European Medicines Agency (EMA) standards. CONCLUSIONS AND CLINICAL RELEVANCE: Although L-659'066 interfered with dexmedetomidine induced sedation, the degree of the reduction was not clinically relevant. Despite performing better when dexmedetomidine was used alone, BIS did not reflect the clinical sedative status when the antagonist was added.

Bispectral monitoring in dogs subjected to ovariohysterectomy and anesthetized with halothane, isoflurane or sevoflurane.

OBJECTIVE: To assess the effect of halothane (H), isoflurane (I) or sevoflurane (S) on the bispectral index (BIS), and the effect of the addition of meperidine in dogs subjected to ovariohysterectomy. STUDY DESIGN: Prospective, randomized, blinded, clinical trial. ANIMALS: Forty-eight female mixed-breed dogs, with weights varying from 10 to 25 kg. METHODS: All dogs were premedicated with acepromazine (A) (0.1 mg kg(-1) IM) or A and meperidine (M) (3 mg kg(-1) IM) and they were divided into six groups of eight animals (AH, AMH, AI, AMI, AS, and AMS). Fifteen minutes after premedication they were anesthetized with propofol (5 mg kg(-1) IV) and then orotracheally intubated. Anesthesia was maintained with halothane, isoflurane or sevoflurane, respectively. The BIS, variables were recorded at 15 minutes after administering pre-anesthetic medication (T0); 10 minutes of anesthesia maintenance (T1); right ovarian pedicle ligation (T2); muscle suturing (T3); skin suture (T4) and 10 minutes after terminating the inhalant anesthetic (T5), respectively. RESULTS: BIS values were decreased at all times when compared to the baseline values in all groups (p<0.05). In the comparative assessment between groups, the values obtained at T0 and T1 were similar for all groups. At T2, the values in AMH were lower than those obtained in AI, AMI and AS (p<0.05). At the same time significantly higher values were found for AI when compared to AMS (p<0.01). There was a correlation between the bispectral index and the expired anesthetic fraction in all groups. CONCLUSIONS AND CLINICAL RELEVANCE: Within groups given the same inhalant anesthetic the bispectral index was a good indicator for the degree of hypnosis in dogs, indicating a good correlation with the amount of anesthetic and the nociceptive stimulation. BIS was a less reliable indicator of relative anesthetic depth when comparing equipotent end-tidal concentrations between the three inhalants.

The bispectral index during recovery from halothane and sevoflurane anaesthesia in horses.

OBJECTIVE: To record the bispectral index (BIS) when horses moved during either halothane or sevoflurane anaesthesia and when they made volitional movements during recovery from these anaesthetics. STUDY DESIGN: Randomized prospective clinical study. ANIMALS: Twenty-five client-owned horses undergoing surgery aged 8.8 (+/- 5.3; 1-19) years (mean +/- SD; range). METHODS: Baseline BIS values were recorded before pre-anaesthetic medication (BIS(B)) and during anaesthesia (BIS(A)) maintained with halothane (group H; n = 12) or sevoflurane (group S; n =13) at approximately 0.8-0.9 x minimum alveolar concentrations (MAC). Bispectral indices were recorded during the surgery when unexpected movement occurred (BIS(MA)), during recovery when the first movement convincingly associated with consciousness was observed (BIS(M1)) and once sternal recumbency was achieved (BIS(ST)). RESULTS: No significant difference in BIS(M1) was found between halothane- (85 +/- 7; 75-93) and sevoflurane- (87 +/- 10; 70-98) anaesthetized horses although BIS(A) was significantly (p = 0.0002) lower in group S (62 +/- 7; 53-72) than group H (74 +/- 7; 60-84). Differences between BIS(M1) and BIS(A) were significant in sevoflurane (p = 0.00001) and halothane recipients (p = 0.002) but were greater in group S (25 +/- 9; 4-38) compared with group H (12 +/- 10; -9-25). In six of eight horses, BIS(MA) values ranged between those recorded during anaesthesia and at first movement. CONCLUSIONS AND CLINICAL RELEVANCE: Bispectral indices appear to approximate levels of unconsciousness, suggesting that monitoring the BIS may assist equine anaesthesia. However, it does not predict intra-operative movement.

Evaluation of bispectral index (BIS) as an indicator of central nervous system depression in horses anesthetized with propofol.

The bispectral index (BIS) was evaluated as an indicator of central nervous system (CNS) depression in horses anesthetized with propofol. Five non-premedicated horses were anesthetized with 7 mg/kg, IV propofol and the minimum infusion rate (MIR) of propofol required to maintain anesthesia was determined during intermittent positive pressure ventilation in each horse. The BIS was determined 20 min later and after stabilization at 2.0 MIR, 1.5 MIR, and 1.0 MIR. The BIS was also recorded after the cessation of propofol infusion when the horses regained spontaneous breathing and swallowing reflex. The MIR and plasma concentration (Cp) of propofol were 0.20 +/- 0.03 mg/kg/min and 17.5 +/- 4.0 microg/ml, respectively. The BIS value and Cp were 59 +/- 13 and 26.7 +/- 8.6 microg/ml at 2.0 MIR, 63 +/- 9 and 22.9 +/- 9.7 microg/ml at 1.5 MIR, 64 +/- 13 and 20.1 +/- 5.9 microg/ml at 1.0 MIR, 64 +/- 24 and 13.0 +/- 2.8 microg/ml at return of spontaneous breathing, and 91 +/- 4 and 11.0 +/- 3.4 microg/ml when the swallowing reflex returned, respectively. The BIS value was significantly less in anesthetized horses compared to horses once swallowing returned (p=0.025). The BIS value was significantly correlated with the propofol Cp (r=-0.625, p=0.001). There was not a significant difference in the BIS values during the MIR multiples of propofol. The BIS was a useful indicator of awakening but did not indicate the degree of CNS depression during propofol-anesthesia in horses.