Cardiac Output Assessments in Anesthetized Children: Dynamic Capnography Versus Esophageal Doppler.

BACKGROUND: The objective of this study was to compare esophageal Doppler cardiac output (COEDM) against the reference method effective pulmonary blood flow cardiac output (COEPBF), for agreement of absolute values and ability to detect change in cardiac output (CO) in pediatric surgical patients. Furthermore, the relationship between these 2 methods and noninvasive blood pressure (NIBP) parameters was evaluated. METHODS: Fifteen children American Society of Anesthesiology (ASA) I and II (median age, 8 months; median weight, 9 kg) scheduled for surgery were investigated in this prospective observational cohort study. Baseline COEPBF/COEDM/NIBP measurements were made at positive end-expiratory pressure (PEEP) 3 cm H2O. PEEP was increased to 10 cm H2O and COEPBF/COEDM/NIBP was recorded after 1 and 3 minutes. PEEP was then lowered to 3 cm H2O, and all measurements were repeated after 3 minutes. Finally, 20-µg kg-1 intravenous atropine was given with the intent to increase CO, and all measurements were recorded again after 5 minutes. Paired recordings of COEDM and COEPBF were examined for agreement and trending ability, and all parameters were analyzed for their responses to the hemodynamic challenges. RESULTS: Bias between COEDM and COEPBF (COEDM - COEPBF) was -17 mL kg-1 min-1 (limits of agreement, -67 to +33 mL kg-1 min-1) with a mean percentage error of 32% (95% confidence interval [CI], 25-37) and a concordance rate of 71% (95% CI, 63-80). The hemodynamic interventions caused by PEEP manipulations resulted in significant decrease in COEPBF absolute numbers (155 mL kg-1 min-1 [95% CI, 151-159] to 127 mL kg-1 min-1 [95% CI, 113-141]) and a corresponding relative decrease of 18% (95% CI, 14-22) 3 minutes after application of PEEP 10. No corresponding decreases were detected by COEDM. Mean arterial pressure showed a relative decrease with 5 (95% CI, 2-8) and 6% (95% CI, 2-10) 1 and 3 minutes after the application of PEEP 10, respectively. Systolic arterial pressure showed a relative decrease of 5% (95% CI, 2-10) 3 minutes after application of PEEP 10. None of the recorded parameters responded to atropine administration except for heart rate that showed a 4% relative increase (95% CI, 1-7, P = .02) 5 minutes after atropine. CONCLUSIONS: COEDM was unable to detect the reduction of CO cause by increased PEEP, whereas COEPBF and to a minimal extent NIBP detected these changes in CO. The ability of COEPBF to react to minor reductions in CO, before noticeable changes in NIBP are seen, suggests that COEPBF may be a potentially useful tool for hemodynamic monitoring in mechanically ventilated children.

Effects of the Sufentanil and Dexmedetomidine Combination on Spinal Anesthesia in Patients Undergoing Lower Abdominal or Lower Extremity Surgery: A Double-Blind Randomized Controlled Trial.

Background: Intrathecal additive drugs are becoming increasingly common in anesthesia practice. We aimed to evaluate the additive effects of dexmedetomidine on spinal anesthesia with sufentanil in patients undergoing lower abdominal or lower limb surgery. Methods: This double-blind randomized controlled trial was performed in Mashhad, Iran, between 2017 and 2018. Sixty patients undergoing lower abdominal or lower limb surgery were randomly divided to receive 15 mg of bupivacaine and 3 µg of sufentanil (control group; n=30) or 15 mg of bupivacaine, 3 µg of sufentanil, and 10 µg of dexmedetomidine (intervention group; n=30). Outcomes, comprised of the onset and regression of sensory and motor blocks, the duration of analgesia, analgesic use, hemodynamic parameters, and side effects, were assessed. The data were analyzed in the SPSS software (version 22), using different statistical tests. A P value of less than 0.05 was considered significant. Results: The times of sensory and motor blocks reaching T10 and Bromage 3, respectively, were significantly shorter, while the times of sensory and motor regressions to S1 and Bromage 0, correspondingly, were significantly longer in the intervention group than in the control group (P<0.001). Both the frequency (P=0.006) and the dose (P<0.001) of postoperative analgesic use were significantly lower, and the duration of analgesia was significantly longer in the intervention group (P<0.001). The frequency of side effects and changes in hemodynamic parameters had no significant differences between the groups. Conclusion: The sufentanil and dexmedetomidine combination in spinal anesthesia caused the earlier onset and later regression of sensory and motor blocks, longer postoperative analgesia, and lower analgesic use without significant side effects or hemodynamic changes, which appears to be due to the combined effects of sufentanil and dexmedetomidine. Trial Registration Number: IRCT2017082833680N3.

Comparison of the effects of perineural or intravenous dexamethasone on low volume interscalene brachial plexus block: a randomised equivalence trial.

BACKGROUND: Efforts to prolong interscalene block (ISB) analgesia include the use of local anaesthetic adjuvants such as dexamethasone. Previous work showing prolonged block duration suggests that both perineural and intravenous (i.v.) routes can both prolong analgesia. The superiority of either route is controversial given the design of previous studies. As perineural dexamethasone is an off-label use, anaesthesiologists should be fully informed of the clinical differences, if any, on block duration. This study was designed to test whether perineural vs i.v. dexamethasone administration are equivalent. METHODS: We randomised 182 eligible patients scheduled for arthroscopic shoulder surgery to receive low-dose ISB (0.5% ropivacaine 5 ml) with perineural or i.v. dexamethasone 4 mg. Subjects, anaesthesiologists, and research personnel were blinded. All subjects also received a standardised general anaesthetic and multimodal analgesia. The primary outcome was duration of analgesia analysed as an equivalence outcome (2 h equivalency margin) using the two one-sided test (TOST) method. RESULTS: For the primary outcome, duration of analgesia, and perineural and i.v. administration of dexamethasone were not equivalent. The upper and lower bounds of the 90% confidence interval were 1 h (P=0.12) and -2.5 h (P=0.01), respectively. The observed difference in mean block duration was not clinically relevant (0.75 h longer for i.v. dexamethasone). There were no other clinically significant differences between groups. CONCLUSION: In the context of low-volume ISB with ropivacaine, perineural and i.v. dexamethasone were not equivalent in terms of their effects on block duration. However, there were no clinically significant differences in outcomes, and there is no advantage of perineural over intravenous dexamethasone. WWW.CLINICALTRIALS. GOV REGISTRATION: NCT02322242.

Minimum anesthetic concentration of isoflurane and sparing effect of midazolam in Quaker parrots (Myiopsitta monachus).

OBJECTIVE: To determine the effects of midazolam on the minimum anesthetic concentration (MAC) reduction of end-tidal isoflurane concentration (Fe'Iso) measured using an electrical stimulus in Quaker parrots (Myiopsitta monachus). STUDY DESIGN: Randomized crossover experimental study. ANIMALS: A group of six adult Quaker parrots, weighing 98-124 g. METHODS: Birds were anesthetized with isoflurane in oxygen delivered by mask, then tracheally intubated and mechanically ventilated. Three treatments were applied with a 4 day interval between anesthetic events. Each anesthetized bird was administered midazolam (1 mg kg-1; treatment MID1), midazolam (2 mg kg-1; treatment MID2) or electrolyte solution (control) intramuscularly. The treatments were administered using a replicated Latin square design and the observers were blinded. Based on a pilot bird, the starting Fe'Iso was 1.8%. After equilibration for 10 minutes, a supramaximal stimulus was delivered using an electrical current (20 V and 50 Hz for 10 ms) and birds were observed for non-reflex movement. The Fe'Iso was titrated by 0.1% until a crossover event was observed. The MAC was estimated using logistic regression. RESULTS: The MAC of isoflurane (MACISO) was estimated at 2.52% [95% confidence interval (CI), 2.19-2.85] with a range of 1.85-2.65%. MACISO in MID1 was 2.04% (95% CI, 1.71-2.37) and in MID2 was 1.81% (95% CI, 1.48-2.14); reductions in MACISO from control of 19% (p = 0.001) and 28% (p < 0.001), respectively. Heart rate, temperature, sex and anesthetic time were not different among treatments. CONCLUSIONS: Midazolam (1-2 mg kg-1) intramuscularly resulted in a significant isoflurane-sparing effect in response to a noxious stimulus in Quaker parrots without observable adverse effects. CLINICAL RELEVANCE: Midazolam can be used as part of a balanced anesthetic approach using isoflurane in Quaker parrots, and potentially in other psittacine species.

Evaluation of a Safety Protocol for the Management of Thirst in the Postoperative Period.

PURPOSE: To associate medications, anesthetic techniques, and clinical conditions that interfere in the time of patient approval in the safety protocol for thirst management. DESIGN: A quantitative, analytical, and longitudinal study conducted in Southern Brazil. METHODS: A nonprobabilistic sample, of 203 adult patients in the immediate postoperative period, evaluated every 15 minutes for 1 hour. FINDINGS: A general prevalence of thirst of 67.7%, and mean intensity of 6.38. Fentanyl, morphine, rocuronium, and sevoflurane increased lack of approval in the protocol within 30 minutes (P < .05). General anesthesia (P < .0001) and level of consciousness (95.4%) presented the highest nonapproval rates. CONCLUSIONS: Anesthetics and general anesthesia delayed protocol approval; however, after 30 minutes, 75.4% of patients had been approved. Level of consciousness was the main criterion of disapproval. The protocol identified crucial clinical conditions that made it impossible for the patient to receive thirst relief strategies and demonstrated that thirst can be satiated precociously with safety.

The effect of two doses of fentanyl on chest wall rigidity at equipotent doses of isoflurane in dogs.

OBJECTIVE: To evaluate the effect of two doses of fentanyl upon chest wall rigidity of dogs anesthetized at equipotent doses of isoflurane [1.3 minimum alveolar concentration (MACISO) of each dose of fentanyl]. STUDY DESIGN: Prospective crossover randomized study. ANIMALS: A group of eight male Beagle dogs, approximately 1 year old and weighing 12.1 ± 1.6 kg (mean ± standard deviation). METHODS: The dogs were anesthetized with isoflurane and instrumented for the measurement of esophageal pressure (PESO), flow (V˙) and volume (V). Chest wall elastance (ECW) was estimated by multiple linear regression of the model. PESO(t) = V˙(t) × RCW + V(t) × ECW + EEPESO where t is time, RCW is chest wall resistance and EEPESO is end-expiratory PESO. Chest wall compliance (CCW) was calculated as 1/ECW and normalized to the body weight of each dog (mL cmH2O-1 kg-1). Anesthesia was maintained at 1.3 MACISO for at least 15 minutes and CCW recorded (CCW-ISO). The dogs were randomly assigned to the lower fentanyl dose [loading dose (33 µg kg-1) and infusion (0.2 µg kg-1 minute-1)] or the higher fentanyl dose [loading dose (102 µg kg-1) and infusion (0.8 µg kg-1 minute-1)]. After 60 minutes of fentanyl infusion, CCW was recorded for each dose (CCW-FENT). During fentanyl infusion, the dogs were maintained at equipotent doses of isoflurane (1.3 MACISO for each fentanyl dose). A two-way analysis of variance followed by a Bonferroni test was used to compare CCW-ISO and CCW-FENT in both treatments and CCW-FENT between treatments. A p value <0.05 was considered significant. RESULTS: Neither of the fentanyl doses decreased CCW and there was no difference in CCW-FENT between doses. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl at the studied doses did not result in chest wall rigidity in dogs anesthetized with equipotent doses of isoflurane (1.3 MACISO).

Evaluation of two different radiotherapy anaesthetic protocols for dogs: a randomized clinical crossover trial.

OBJECTIVES: To describe alfentanil-propofol admixture for induction of anaesthesia for canine radiotherapy and compare it to alfentanil-atropine followed by propofol induction in terms of heart rate (HR), mean arterial pressure (MAP), recovery duration and quality. STUDY DESIGN: Prospective, masked, randomized clinical crossover trial. ANIMALS: A group of 40 client-owned dogs anaesthetized from October 2017 to June 2018. METHODS: Dogs were randomly assigned to be administered one of two protocols. For both protocols, IV preanaesthetic medication was given 30 seconds before rapid IV administration of a set volume of induction agent, with further induction agent administered as needed to permit intubation. For protocol ADMIX, the preanaesthetic medication was 0.04 mL kg-1 0.9% sodium chloride and the induction agent was 0.2 mL kg-1 propofol-alfentanil admixture. For protocol ATRO, the preanaesthetic medication was 10 µg kg-1 alfentanil with 12 µg kg-1 atropine (0.04 mL kg-1 total volume) and the induction agent was 0.2 mL kg-1 propofol. Anaesthesia was maintained with sevoflurane. Cardiorespiratory variables, agitation, hypotension, or inadequate depth of anaesthesia requiring supplemental boluses of propofol or increased vaporizer settings were recorded. Time to extubation, sternal recumbency and walking was noted. Videos were recorded for recovery quality scoring. Owner questionnaires gave feedback about recoveries at home. The other protocol was administered for the next radiotherapy session. RESULTS: The only significantly different variable between protocols was mean HR during anaesthesia, which was lower in ADMIX (p < 0.001). Hypotension was recorded in seven (17.5%) dogs in ATRO and three (7.5%) in ADMIX, with an association (p < 0.005) between ATRO and hypotension. Owners reported animals recovered 'normal' behaviour and appetite by the next morning. CONCLUSIONS AND CLINICAL RELEVANCE: Both protocols were acceptable for dogs undergoing radiotherapy, with minimal differences in anaesthetic quality, recovery duration and quality. Although MAP did not differ overall, the incidence of hypotension was higher in ATRO.

Criteria for gauging response to sodium oxybate for narcolepsy.

Our objective was to define responder criteria using an anchor-based approach for frequency of cataplexy attacks and excessive daytime sleepiness in patients with narcolepsy undergoing sodium oxybate treatment. We used pooled data from two randomized, placebo-controlled, double-blind, multicentre 4- and 8-week trials of sodium oxybate for narcolepsy with cataplexy and analysed using receiver operator characteristics analysis. The percentage change in frequency of weekly cataplexy attacks and the Epworth Sleepiness Scale outcomes were compared with Clinical Global Impression of Change ratings, used as the anchor to define true response. Participants (n = 336) were 39% male, 89% white, with a mean age of 41.5 (15.3) years, reporting a median of 20.5 cataplexy attacks per week and a mean Epworth Sleepiness score of 17.5 at baseline. A majority (51%) were Much Improved or Very Much Improved based on Clinical Global Impression of Change ratings, considered a true response to treatment. Area under the curve values for % reduction in cataplexy attacks (77%) and % change in sleepiness score (78%) supported response definition thresholds of 46% and 12%, respectively. Classification using either response definition agreed with the anchor for approximately 71% of participants. Cataplexy response definition was more sensitive (cataplexy = 0.77, Epworth Sleepiness Scale = 0.69), while sleepiness was more specific (cataplexy = 0.66, Epworth Sleepiness Scale = 0.75). Both responder definitions showed a dose-response relationship with sodium oxybate, demonstrating their validity using an external criterion. Weekly cataplexy attacks and Epworth Sleepiness Scale can be used to help document clinical response to narcolepsy treatment using criteria of 46% and 12% reductions, respectively.

Potential learning and memory disruptors and enhancers in a simple, 1-day operant task in mice.

The objective of this study was to develop a rapid, 1-day learning and memory assay in mice that is sensitive to the effects of compounds that could impair or enhance acquisition and retrieval. Swiss-Webster, male mice were placed in experimental chambers for a 1-h acquisition session with an intermittent, audible tone. If a nose-poke response occurred during the tone, an Ensure water solution was presented. After 1 h, the mice returned to the chambers for 2 h. Drugs were injected before or after sessions to determine the effects on acquisition and/or retrieval. Mice injected with saline learned a nose-poke response as measured by decreased latencies to earn 10 reinforcers, increased reinforced response rates, and decreased nonreinforced response rates. Scopolamine and acetazolamide impaired retrieval of the nose-poke response, whereas ketamine only modestly impaired retrieval. Doses of 8-OH-DPAT or the novel carbonic anhydrase activator, MAI27, either had no effect or impaired some measures of responding. Neither 8-OH-DPAT nor MAI27 were able to prevent the modest impairments produced by ketamine. The simple, 1-day operant task is a rapid assay that can be used as an initial screen to test the effects of learning and memory disruptors and potentially enhancers.

Ketamine versus ketamine pluses atropine for pediatric sedation: A meta-analysis.

OBJECTIVES: The application of atropine for pediatric sedation in the emergency department remains controversial. Our objective was to perform a comprehensive review of the literature and assess the clinical indexes in groups with and without atropine use. METHODS: PubMed, EMBASE, and the Cochrane Library were searched for randomized and non-randomized studies that compared ketamine and ketamine plus atropine for pediatric sedation. The risk ratio with 95% confidence interval was calculated using either a fixed- or random-effects model according to the value of I2. RESULTS: One retrospective study and four randomized controlled trials were identified to compare the clinical indexes. For the clinical indexes, the ketamine plus atropine group had better outcomes than the ketamine group in hypersalivation (P<0.05), but indexes of rash and tachycardia were worse. The two methods of sedation were comparable for nausea, vomiting, desaturation, agitation and laryngospasm (P>0.05). CONCLUSIONS: Based on the current evidence, the group receiving atropine had reduced hypersalivation and increased rash and tachycardia; no differences were observed in nausea, vomiting, desaturation, agitation and laryngospasm between the two groups. Given that some of the studies were of low quality, additional high-quality randomized controlled trials should be conducted to further verify these findings.

Effect of Atropine With Propofol vs Atropine With Atracurium and Sufentanil on Oxygen Desaturation in Neonates Requiring Nonemergency Intubation: A Randomized Clinical Trial.

Importance: Propofol or a combination of a synthetic opioid and muscle relaxant are both recommended for premedication before neonatal intubation but have yet to be compared. Objective: To compare prolonged desaturation during neonatal nasotracheal intubation after premedication with atropine-propofol vs atropine-atracurium-sufentanil treatment. Design, Setting, and Participants: Multicenter, double-blind, randomized clinical trial (2012-2016) in 6 NICUs in France that included 173 neonates requiring nonemergency intubation. The study was interrupted due to expired study kits and lack of funding. Interventions: Eighty-nine participants were randomly assigned to the atropine-propofol group and 82 to the atropine-atracurium-sufentanil group before nasotracheal intubation. Main Outcomes and Measures: The primary outcome was prolonged desaturation (Spo2 <80% lasting > 60 seconds), using intention-to-treat analysis using mixed models. Secondary outcomes assessed the characteristics of the procedure and its tolerance. Results: Of 173 neonates randomized (mean gestational age, 30.6 weeks; mean birth weight, 1502 g; 71 girls), 171 (99%) completed the trial. Of 89 infants, 53 (59.6%) in the atropine-propofol group vs 54 of 82 (65.9%) in the atropine-atracurium-sufentanil group achieved the primary outcome (adjusted RD, -6.4; 95% CI, -21.0 to 8.1; P = .38). The atropine-propofol group had a longer mean procedure duration than did the atropine-atracurium-sufentanil group (adjusted RD, 1.7 minutes; 95% CI, 0.1-3.3 minutes; P = .04); a less frequent excellent quality of sedation rate, 51.7% (45 of 87) vs 92.6% (75 of 81; P < .001); a shorter median time to respiratory recovery, 14 minutes (IQR, 8-34 minutes) vs 33 minutes (IQR, 15-56 minutes; P = .002), and shorter median time to limb movement recovery, 18 minutes (IQR, 10-43 minutes) vs 36 minutes (IQR, 19-65 minutes; P = .003). In the 60 minutes after inclusion, Spo2 was preserved significantly better in the atropine-propofol group (time × treatment interaction P = .02). Of the atropine-propofol group 20.6% had head ultrasound scans that showed worsening intracranial hemorrhaging (any or increased intraventricular hemorrhage) in the 7 days after randomization vs 17.6% in the atropine-atracurium-sufentanil group (adjusted RD, 1.2; 95% CI, -13.1 to 15.5, P = .87). Severe adverse events occurred in 11% of the atropine-propofol group and in 20% of the atropine-atracurium-sufentanil group. Conclusions and Relevance: Among neonates undergoing nonemergency nasotracheal intubation, the frequency of prolonged desaturation did not differ significantly between atropine used with propofol or atropine used with atracurium and sufentanil. However, the study may have been underpowered to detect a clinically important difference, and further research may be warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT01490580, EudraCT number: 2009-014885-25.

Effect of benzodiazepines on the dose of alfaxalone needed for endotracheal intubation in healthy dogs.

OBJECTIVE: To evaluate the dose-sparing effect of midazolam or diazepam on the dose of alfaxalone required to achieve endotracheal intubation in premedicated dogs. STUDY DESIGN: Prospective, randomized, 'blinded', controlled clinical trial. ANIMALS: Ninety healthy dogs anaesthetized for elective surgery or diagnostic procedures. METHODS: Saline (0.1 mL kg-1), or midazolam or diazepam (0.2, 0.3, 0.4 or 0.5 mg kg-1) intravenously (IV) was randomly assigned; investigators were unaware of group designation. After premedication with IV acepromazine 0.01 mg kg-1 and methadone 0.2 mg kg-1, the degree of sedation was assessed. Alfaxalone (0.5 mg kg-1) was administered IV, followed by the assigned treatment. Further alfaxalone was administered until endotracheal intubation could be performed. Ease of endotracheal intubation, pulse rate and arterial blood pressure were assessed. General linear models were used to examine the effect of treatment drug and dose on induction dose of alfaxalone with Tukey's post hoc tests. Incidence of adverse reactions was assessed with chi-square tests. RESULTS: There were no significant differences between groups with regard to demographic data or sedation. Median (range) induction dose of alfaxalone in the saline group was 0.74 (0.43-1.26) mg kg-1 compared with 0.5 (0.46-0.75) mg kg-1 and 0.5 (0.42-1.2) mg kg-1 for the midazolam and diazepam groups, respectively. Midazolam 0.3 and 0.5 mg kg-1 (p = 0.005 and 0.044, respectively) and diazepam 0.4 mg kg-1 (p = 0.032) reduced the alfaxalone dose compared with saline. Adverse effects were not significantly different between groups. Midazolam 0.2, 0.3, 0.4 and 0.5 mg kg-1 (p < 0.044, p = 0.001, p = 0.007, p = 0.044, respectively) and diazepam 0.2 and 0.5 mg kg-1 (p = 0.025 and p = 0.025) improved intubation score compared with saline. CONCLUSION AND CLINICAL RELEVANCE: Midazolam 0.3 and 0.5 mg kg-1 and diazepam 0.4 mg kg-1 coadministered at anaesthetic induction allow alfaxalone dose reduction in healthy dogs. Use of benzodiazepines improved the ease of endotracheal intubation.

Fentanyl Suppresses the Survival of CD4+ T Cells Isolated from Human Umbilical Cord Blood through Inhibition of IKKs-mediated NF-κB Activation.

The aim of this study was to investigate the effects and the underlying mechanisms of fentanyl anaesthetic on T lymphocytes isolated from human umbilical cord blood in vitro. The percentages of CD4+ , CD8+ and regulatory T (Treg) cells in human umbilical cord blood mononuclear cells (UBMC) treated with fentanyl in vitro were analysed by flow cytometry. The levels of cytokines IFN-γ, IL-2, IL-4 and IL-17 secreted by activated CD4+ T cells were measured by ELISA assays. Expressions of MAPK and NF-κB signalling pathway proteins were determined by Western blotting. Effects of fentanyl on IKK and p65 expression promoter activities were analysed by luciferase assay. Fentanyl decreased the percentages and amounts of CD4+ , CD8+ and Foxp3+ Treg T lymphocyte subsets in UBMCs in a dose-dependent manner. Fentanyl inhibited the proliferation and induced apoptosis of activated CD4+ T cells dose dependently. Fentanyl could not reverse the increase of cell proliferation in activated groups to be equivalent with those in inactivated group. Secretions of IFN-γ, IL-2 and IL-4 cytokines were significantly decreased by moderate to high dose of fentanyl compared with controls. No significant differences were observed in protein expressions of MAPK pathway. In addition, fentanyl suppressed the IKKs-mediated activation of NF-κB. This study demonstrates that fentanyl exerts immunosuppressive effects on T lymphocytes obtained from UBMCs. Thus, the clinical application of fentanyl would not only relieve pain caused by surgery but regulate immune responses post-operation possibly through inhibition of IKKs-mediated NF-κB activation.

A combination of alfaxalone, medetomidine and midazolam for the chemical immobilization of Rhesus macaque (Macaca mulatta): Preliminary results.

BACKGROUND: Chemical immobilization of non-human primates can be required to perform scientific or veterinary procedure with different invasiveness degrees. This preliminary study was undertaken to assess the clinical effects of a combination of alfaxalone, medetomidine and midazolam (AMM). METHODS: Seven rhesus macaques were chemically immobilized, for invasive veterinary procedures, with alfaxan 2 mg kg-1 , medetomidine 20 µg kg-1 and midazolam 0.3 mg kg-1 injected subcutaneously. RESULTS: The alfaxalone combination induced surgical anaesthesia, with a complete absence of response to noxious stimuli, for at least 20 minutes. The total duration of anaesthesia was 56 ± 7 minutes, and the administration of atipamezole, to partially reverse the combination effects, did not appear to alter the depth of anaesthesia. CONCLUSION: In conclusion, the AMM combination produced rapid onset general anaesthesia, following subcutaneous administration of a relatively low volume (0.28 mL/kg) of injectate.

ALFAXALONE ANESTHESIA IN THE BENGALESE FINCH ( LONCHURA DOMESTICA).

The objective of this study was to evaluate the use of alfaxalone in a small passerine species. A dose-response trial was conducted whereby 10, 30, and 50 mg/kg alfaxalone was administered subcutaneously (SC) to 10 Bengalese finches ( Lonchura domestica) in a randomized complete crossover study design. Subsequently, a similar protocol was used to compare 30 mg/kg alfaxalone alone or combined with either 0.7 mg/kg midazolam or 1 mg/kg butorphanol SC. Induction and recovery times were recorded and depth of anesthesia monitored at 5-min intervals throughout each procedure. Functional oxygen saturation and pulse rates were measured with a pulse oximeter at 15 min after administration of the anesthetic agent(s). Dose-dependent decreases in induction time and prolongation of anesthetic duration were seen with increasing alfaxalone dosage. Alfaxalone combined with midazolam resulted in faster inductions, and the addition of both midazolam and butorphanol resulted in longer durations of anesthesia than alfaxalone alone. The addition of midazolam significantly decreased the pulse rate at 15 min compared with alfaxalone alone. Alfaxalone was found to be an effective agent for inducing anesthesia when administered subcutaneously, and no complications were observed. Increasing the dose, and combining with a benzodiazepine or opioid increased the duration of anesthesia with minimal or no effects on respiratory or pulse rates, within the dose range investigated.

ANESTHETIC MANAGEMENT OF AN INDO-PACIFIC BOTTLENOSE DOLPHIN (TURSIOPS ADUNCUS) REQUIRING SURGICAL DEBRIDEMENT OF A TAIL ABSCESS.

This report describes the anesthetic management of a 14-yr-old, 160-kg, female Indo-Pacific bottlenose dolphin ( Tursiops aduncus ) that underwent surgical debridement for a refractory subcutaneous abscess twice within a 6-mo interval. The animal was otherwise in good physical condition at each anesthetic procedure. Following premedication with intramuscular midazolam and butorphanol, anesthesia was induced with propofol and maintained with sevoflurane by intubation. During surgery ventilation was controlled. Blood pressure was indirectly estimated using either oscillometric or pulse oximetry. Presumed hypotension was managed by adjusting the sevoflurane concentration and infusion of dopamine. During recovery, the dolphin regained adequate spontaneous respiration following intravenous administration of flumazenil and doxapram. The dolphin was extubated at 85 min and 53 min after the first and second surgeries, respectively. Successful weaning from the ventilator and initiation of spontaneous respiration was the most important complication encountered. Establishment of a reliable blood pressure measurement technique is critical to success for anesthesia in this species.

The Role of 5-HT3 Receptors in Signaling from Taste Buds to Nerves.

Activation of taste buds triggers the release of several neurotransmitters, including ATP and serotonin (5-hydroxytryptamine; 5-HT). Type III taste cells release 5-HT directly in response to acidic (sour) stimuli and indirectly in response to bitter and sweet tasting stimuli. Although ATP is necessary for activation of nerve fibers for all taste stimuli, the role of 5-HT is unclear. We investigated whether gustatory afferents express functional 5-HT3 receptors and, if so, whether these receptors play a role in transmission of taste information from taste buds to nerves. In mice expressing GFP under the control of the 5-HT(3A) promoter, a subset of cells in the geniculate ganglion and nerve fibers in taste buds are GFP-positive. RT-PCR and in situ hybridization confirmed the presence of 5-HT(3A) mRNA in the geniculate ganglion. Functional studies show that only those geniculate ganglion cells expressing 5-HT3A-driven GFP respond to 10 µM 5-HT and this response is blocked by 1 µM ondansetron, a 5-HT3 antagonist, and mimicked by application of 10 µM m-chlorophenylbiguanide, a 5-HT3 agonist. Pharmacological blockade of 5-HT3 receptors in vivo or genetic deletion of the 5-HT3 receptors reduces taste nerve responses to acids and other taste stimuli compared with controls, but only when urethane was used as the anesthetic. We find that anesthetic levels of pentobarbital reduce taste nerve responses apparently by blocking the 5-HT3 receptors. Our results suggest that 5-HT released from type III cells activates gustatory nerve fibers via 5-HT3 receptors, accounting for a significant proportion of the neural taste response.

Safety and efficiency of dexmedetomidine as adjuvant to local anesthetics.

PURPOSE OF REVIEW: To review the current knowledge of dexmedetomidine as an additive drug to local anesthetics in peripheral and neuraxial regional anesthesia. RECENT FINDINGS: Recent studies show a perineural mode of action of dexmedetomidine. Pharmacodynamic characteristics of peripheral and neuraxial regional anesthetic techniques are optimized by the addition of dexmedetomidine to long-acting local anesthetics. Bradycardia and sedation are the main systemic side-effects of dexmedetomidine for regional anesthesia purposes. A dose of approximately 100 µg dexmedetomidine for peripheral techniques may represent the optimal balance between optimization of block characteristics and side-effects. Doses between 3 and 10 µg are described to be sufficient for spinal administration. SUMMARY: Dexmedetomidine has a potency to ameliorate pharmacodynamic characteristics of peripheral and neuraxial regional anesthetic techniques and is therefore currently the most promising additive drug in regional anesthesia. Future scientific efforts should focus on dose finding studies for particular regional anesthetic techniques. Approval of dexmedetomidine for regional anesthetic indications should be the final target.

[Impact of dexmedetomidine-sevoflurane anesthesia on intraoperative wake-up test in children patients undergoing scoliosis surgery].

OBJECTIVE: To observe the effects of 0.4 µg/(kg×h) dose of dexmedetomidine on intra-operative wake-up test in children patients undergoing scoliosis surgery. METHODS: Sixty patients for posterior scoliosis correction (ASA I-II, aged 5-16 years) from March 2013 to April 2015 were enrolled in this prospective, double-blinded, randomized, placebo-controlled study, The patients were randomly classified into two groups to receive dexmedetomidine (group RD, n=30) or saline solution (group R, n=30). In group RD, dexmedetomidine [0.4 µg/(kg×h)] was administered after tracheal intubation, while the equal volume saline solution was given instead in group R. Anesthesia was induced with midazolam, propofol, sufentanyl and cisatracurium, and anesthesia was maintained with sevoflurane inhalation and a continuous intravenous infusion of remifentanil in the both groups.BIS (bispectral index, BIS) value was maintained at 40-60,and mean arterial pressure (MAP) was maintained at ≥ 60 mmHg before the wake-up test.When the wake-up test was performed, immediately the dexmedetomidine and remifentanil infusion were stopped, and the end-tidal concentration of sevoflurane was adjusted to 0. Mean arterial pressure, and heart rate (HR) were recorded before anesthesia and at 5-minute intervals during the wake-up test. The wake-up test time, arousal quality and sedation scores were recorded also.In addition, the data were also gathered on the dosage of ephedrine and atropine were used, as well as the intraoperative awareness in the patients who were followed up on the first day after the operation. RESULTS: There were no differences between group RD and group R with regard to HR and MAP at getting into the operation room (t=-1.460, P=0.150;t =-1.015, P=0.315). In group RD, no evidence was found for a difference in HR and MAP at awakening up versus at getting into the operation room (t=0.974, P=0.340; t=-1.449, P=0.161), while in group R, an increase in HR and MAP occurred at awakening versus at getting into the operation room (t=-2.106, P=0.044; t=-2.352, P=0.026). There were no significant differences in sedation scores and wake-up test time between the two groups (t=1.986, P=0.052; t=0.392, P=0.697). The wake-up test quality was significantly better in group RD than in group R (t=-2.098,P=0.041). HR in group RD was significantly lower than that in group R at any time point during the wake-up test (P<0.05). Four patients had awareness occurrence during the operation in group R, and no awareness occurrence in group RD. CONCLUSION: Dexmedetomidine, when administered at a rate of 0.4 µg/(kg×h) as an adjuvant of sevoflurane inhalational anesthesia, could improve the wake-up test quality, and maintain hemodynamic stability during scoliosis surgery.

The Influence of a Combined Butorphanol and Midazolam Premedication on Anesthesia in Psittacid Species.

Premedication is considered routine for domestic animal and human anesthesia but is rarely applied to avian patients, and few controlled studies exist to document effects of premedication in avian species. To determine the effects of a butorphanol and midazolam premedication on general anesthesia and quality of induction and recovery phases in psittacid species, 17 clinically healthy birds undergoing anesthesia were randomly allocated into either a premedicated or control group. Anesthetic parameters were subsequently compared. Induction time and isoflurane concentration required for anesthetic maintenance were reduced in the premedicated group. Induction quality scores were improved in the premedicated group and no adverse effects on anesthesia and cardiovascular stability were observed. Use of a combined butorphanol and midazolam premedication in clinically healthy psittacine birds appears safe and effective. Premedication provides a beneficial effect at induction and enables maintenance levels of anesthetic gas to be reduced.