Influence of fentanyl, medetomidine-fentanyl or acepromazine-fentanyl premedication on oesophageal and rectal temperature in dogs under anaesthesia.

OBJECTIVE: To compare changes in oesophageal (T-Oeso) and rectal (T-Rec) temperature in dogs during general anaesthesia and premedicated with fentanyl, medetomidine-fentanyl or acepromazine-fentanyl. STUDY DESIGN: Prospective, randomized, blind clinical study. ANIMALS: A total of 120 healthy dogs, aged 2-10 years and weighing 5-20 kg. METHODS: Dogs were randomly allocated to one of three groups. Animals of F group were premedicated with fentanyl (0.01 mg kg-1), MF group with medetomidine (0.005 mg kg-1) and fentanyl (0.01 mg kg-1) and AF group with acepromazine (0.01 mg kg-1) and fentanyl (0.01 mg kg-1). Anaesthesia was induced with propofol and maintained with isoflurane in oxygen-air mixture. Fentanyl was administered continuously (0.01 mg kg-1 hour-1). The T-Oeso, T-Rec and ambient temperatures were recorded after induction (T0) and subsequently at 10 minute intervals for 60 minutes (T10-T60). Data were analysed using anova or their non-parametric equivalents (p < 0.05). RESULTS: Median T-Oeso was significantly higher in MF group between T0-T20 compared with other groups. Median T-Oeso significantly decreased in F group from 38.0 °C (T0) to 37.4 °C (T30), 37.1 °C (T40), 36.9 °C (T50) and 36.6 °C (T60), in MF group from 38.3 °C (T0) to 37.7 °C (T30), 37.5 °C (T40), 37.2 °C (T50) and 37.1 °C (T60) and in AF group from 37.7 °C (T0) to 37.3 °C (T40), 37.2 °C (T50) and 37.1 °C (T60). The T-Rec significantly decreased in F group from 38.0 °C (T0) to 37.4 °C (T40), 37.2 °C (T50) and 36.9 °C (T60), in MF group from 38.3 °C (T0) to 37.5 °C (T50) and 37.4 °C (T60) and in AF group from 38.2 °C (T0) to 37.6 °C (T40), 37.5 °C (T50) and 37.4 °C (T60). CONCLUSIONS AND CLINICAL RELEVANCE: Premedication with fentanyl, medetomidine-fentanyl or acepromazine-fentanyl in the doses used decreased the T-Oeso and T-Rec. The T-Oeso at the beginning of anaesthesia was higher after premedication with medetomidine-fentanyl. However, this difference was not clinically significant.

Clonidine Versus Midazolam Premedication and Postoperative Negative Behavioral Changes in Younger Children: A Randomized Controlled Trial.

BACKGROUND: Postoperative negative behavioral changes (NBCs) are common among children, but risk for this is thought to be reduced with premedication. Midazolam has for many years been a standard premedication for children. More recently, the alpha-2 adrenergic agonist clonidine has also become popular as a preanesthetic sedative. We hypothesized that clonidine was superior to midazolam for limiting new NBCs in children as assessed using the Post Hospital Behavior Questionnaire (PHBQ). METHODS: This was a prospective, randomized, controlled, blinded study, including 115 participants aged 24 to 95 months and their parents. The participants underwent ear, nose, or throat outpatient surgery and were randomly allocated to premedication with oral midazolam 0.5 mg/kg or oral clonidine 4 µg/kg. Participants were anesthetized by protocol. At home, later, parents were asked to complete the PHBQ assessment instrument for postoperative NBCs for the participants 1 week, 1 month, and 6 months after the surgery. A secondary outcome, preinduction anxiety, was assessed using modified Yale Preoperative Anxiety Scale (mYPAS). RESULTS: The primary outcome, more than 3 NBCs in an individual case at 1 week, showed no difference in proportions between treatment in the clonidine group compared to the midazolam group, (12/59 or 20% vs 7/56 or 13%, respectively, odds ratio 1.39, 95% confidence interval [CI], 0.75-2.58; P = .32). A secondary result showed a higher preinduction anxiety level in the clonidine compared to the midazolam group (mYPAS >30, 43/59 or 71% vs 12/56 or 21%, respectively; P < .001). CONCLUSIONS: These results did not show a clinical or statistically significant difference, with respect to the primary outcome of behavior changes at 1 week, between the cohorts that received midazolam versus clonidine as a premedication.

Serum concentration of oral midazolam as pediatric preanesthetic medication and factors related to the sedation level.

BACKGROUND: Preanesthetic medication is important to eliminate surgical anxiety in pediatric patients and facilitate their smooth transfer to the operating room. Midazolam is the most commonly used preanesthetic medication. However, it has been reported that the sedative effect varies from patient to patient. In this study, the pharmacokinetics of midazolam were examined, and the aim was to assess the factors affecting the quality of sedation. METHODS: The participants were children ranging in age from 6 months to 8 years scheduled for surgery. Midazolam 0.5 mg/kg was administered orally 30 min before entering the operating room, and the sedation level was evaluated at the time of mask application. Blood was collected after slow induction, and the serum concentration of midazolam was measured using high-performance liquid chromatography. RESULTS: A total of 98 patients were registered. There was no difference in serum concentrations between the effective sedation group and the ineffective sedation group (48.0 vs. 49.1 ng/mL), regardless of the effect of midazolam. Percentages of ineffective sedation by age (0 to 7 years) were 66.6%, 60%, 33.3%, 11.1%, 0%, 0%, 12.5%, and 0%, respectively. On multivariate logistic regression analysis, siblings (OR = 3.9, CI: 1.1-14.0, p = .03) and age (OR = 3.2, CI:1.2-8.5, p = .02) were related to an insufficient sedative effect. CONCLUSION: The serum concentration of oral midazolam reached effective levels even in patients in whom the sedative effect was inadequate. It is important to manage the perioperative period with appropriate concurrent premedication taking into account patient age and social background characteristics. CLINICAL TRIAL REGISTRATION: Clinical trial registry: UMIN R000052504.

Modeling the Effect of Excitation on Depth of Anesthesia Monitoring in γ-Aminobutyric Acid Type A Receptor Agonist ABP-700.

BACKGROUND: γ-Aminobutyric acid type A (GABAA) receptor agonists are known to cause involuntary muscle movements. The mechanism of these movements is not known, and its relationship to depth of anesthesia monitoring is unclear. We have explored the effect of involuntary muscle movement on the pharmacokinetic-pharmacodynamic model for the GABAA receptor agonist ABP-700 and its effects on the Bispectral Index (BIS) as well as the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores. METHODS: Observations from 350 individuals (220 men, 130 women) were analyzed, comprising 6,312 ABP-700 concentrations, 5,658 ABP-700 metabolite (CPM-acid) concentrations, 25,745 filtered BIS values, and 6,249 MOAA/S scores, and a recirculatory model developed. Various subject covariates and pretreatment with an opioid or a benzodiazepine were explored as covariates. Relationships between BIS and MOAA/S models and involuntary muscle movements were examined. RESULTS: The final model shows that the pharmacokinetics of ABP-700 are characterized by small compartmental volumes and rapid clearance. The BIS model incorporates an effect-site for BIS suppression and a secondary excitatory/disinhibitory effect-site associated with a risk of involuntary muscle movements. The secondary effect-site has a threshold that decreases with age. The MOAA/S model did not show excitatory effects. CONCLUSIONS: The GABAA receptor agonist ABP-700 shows the expected suppressive effects for BIS and MOAA/S, but also disinhibitory effects for BIS associated with involuntary muscle movements and reduced by pretreatment. Our model provides information about involuntary muscle movements that may be useful to improve depth of anesthesia monitoring for GABAA receptor agonists.

Midazolam Premedication Immediately Before Surgery Is Not Associated With Early Postoperative Delirium.

BACKGROUND: Postoperative delirium is common among older surgical patients and may be associated with anesthetic management during the perioperative period. The aim of this study is to assess whether intravenous midazolam, a short-acting benzodiazepine used frequently as premedication, increased the incidence of postoperative delirium. METHODS: Analyses of existing data were conducted using a database created from 3 prospective studies in patients aged 65 years or older who underwent elective major noncardiac surgery. Postoperative delirium occurring on the first postoperative day was measured using the confusion assessment method. We assessed the association between the use or nonuse of premedication with midazolam and postoperative delirium using a χ2 test, using propensity scores to match up with 3 midazolam patients for each control patient who did not receive midazolam. RESULTS: A total of 1266 patients were included in this study. Intravenous midazolam was administered as premedication in 909 patients (72%), and 357 patients did not receive midazolam. Those who did and did not receive midazolam significantly differed in age, Charlson comorbidity scores, preoperative cognitive status, preoperative use of benzodiazepines, type of surgery, and year of surgery. Propensity score matching for these variables and American Society of Anesthesiology physical status scores resulted in propensity score-matched samples with 1-3 patients who used midazolam (N = 749) for each patient who did not receive midazolam (N = 357). After propensity score matching, all standardized differences in preoperative patient characteristics ranged from -0.07 to 0.06, indicating good balance on baseline variables between the 2 exposure groups. No association was found between premedication with midazolam and incident delirium on the morning of the first postoperative day in the matched dataset, with odds ratio (95% confidence interval) of 0.91 (0.65-1.29), P = .67. CONCLUSIONS: Premedication using midazolam was not associated with higher incidence of delirium on the first postoperative day in older patients undergoing major noncardiac surgery.

Preoperative anxiety in preschool children: A randomized clinical trial comparing midazolam, clonidine, and dexmedetomidine.

INTRODUCTION: Anxiety in pediatric patients may challenge perioperative anesthesiology management and worsen postoperative outcomes. Sedative drugs aimed to reducing anxiety are available with different pharmacologic profiles, and there is no consensus on their effect or the best option for preschool children. In this study, we aimed to compare the effect of three different premedications on anxiety before anesthesia induction in preschool children aged 2-6 years scheduled for elective surgery. The secondary outcomes comprised distress during peripheral catheter (PVC) insertion, compliance at anesthesia induction, and level of sedation. PATIENTS AND METHODS: In this double-blinded randomized clinical trial, we enrolled 90 participants aged 2-6 years, who were scheduled for elective ear-, nose-and-throat surgery. The participants were randomly assigned to three groups: those who were administered 0.5 mg/kg oral midazolam, 4 µg/kg oral clonidine, or 2 µg/kg intranasal dexmedetomidine. Anxiety, distress during PVC insertion, compliance with mask during preoxygenation, and sedation were measured using the modified Yale Preoperative Anxiety Scale, Behavioral Distress Scale, Induction Compliance Checklist, and Ramsay Sedation Scale, respectively. RESULTS: Six children who refused premedication were excluded, leaving 84 enrolled patients. At baseline, all groups had similar levels of preoperative anxiety and distress. During anesthesia preparation, anxiety was increased in the children who received clonidine and dexmedetomidine; however, it remained unaltered in the midazolam group. There were no differences in distress during PVC insertion or compliance at induction between the groups. The children in the clonidine and dexmedetomidine groups developed higher levels of sedation than those in the midazolam group. CONCLUSIONS: In preschool children, midazolam resulted in a more effective anxiolysis and less sedation compared to clonidine and dexmedetomidine.

Awake Sedation With Propofol Attenuates Intraoperative Stress of Carotid Endarterectomy in Regional Anesthesia.

BACKGROUND: Carotid endarterectomy in regional anesthesia is often associated with increased perioperative stress. We assumed that carotid endarterectomy performed under awake sedation with propofol is more beneficial to prevent such stress than alprazolam premedication only. METHODS: A total of 47 consecutive patients with significant carotid artery stenosis were enrolled into this investigation and followed up for 5 years to explore vascular complications. All operations were performed under regional anesthesia. As premedication, all patients took 0.5 mg of alprazolam 30 minutes before the procedure. After randomization, 22 patients had awake sedation with target controlled propofol infusion, and the other 25 had only premedication. Cortisol plasma levels were serially analyzed: before surgery (T1), before (T2) and after release of carotid clamp (T3), and at 2 (T4) and 24 postoperative hours (T5). Alprazolam levels were also measured before and after the surgery. RESULTS: The plasma concentration of cortisol was significantly lower in the propofol sedation group at T2 (P < 0.001), T3 (P = 0.001), and T4 (P < 0.001) than in the alprazolam-only group. Alprazolam levels did not correlate with cortisol levels at any time point. A significant positive correlation was found between the clamp time and plasma cortisol level at T3 (P = 0.018), similarly between the degree of contralateral carotid stenosis and plasma cortisol level at T3 (P = 0.03). Plasma cortisol concentration 2 hours after the operation (T4) proved to be an independent predictor of carotid restenosis during the 5-year follow-up (odds ratio: 1.67, 95% confidence interval: 1.02-2.73, P = 0.04). CONCLUSIONS: An additional intraoperative propofol sedation provides better stress relief than alprazolam-only premedication during awake carotid endarterectomy.

Promethazine and Oral Midazolam Preanesthetic Children Medication.

AIMS: Several kinds of drugs have been investigated in preschool children as a preanesthetic sedation after various routes of administration for surgeries. This study aims to compare the efficacy of promethazine and oral midazolam for premedication in children aged 3 to 9 years who were scheduled for surgeries. METHODS: This is a double-blind randomized controlled study conducted on 93 patients between the age of 3 and 9 years at Loresten University of Medical Sciences Teaching Hospital, Khoramabad, Iran. The subjects were grouped into P (promethazine), M (midazolam), and C (control). About 0.3 mg/kg of oral promethazine was administered to patients in group P, 0.5 mg/kg of oral midazolam was administered to patients in group M, and 3 mL of normal saline as placebo was administered to patients in group C. Patient satisfaction, sedation and emotional score, systolic blood pressure (SBP), diastolic blood pressure, respiratory rate (RR), and heart rate (HR) were recorded. RESULTS: There was no statistically significant difference among the 3 groups. However, the period after medication, it was observed that SBP, diastolic blood pressure, RR, and HR in group C were statistically significantly higher than those in groups M and P. These 2 groups are similar in terms of SBP, RR, and HR. The emotional scores were comparable for the 2 groups. It was between 3.97 ± 0.6 to 1.7 ± 0.5 in group M and from 3.45 ± 1.17 to 2.745 ± 0.997 in group P in a Kruskal-Wallis test. CONCLUSIONS: This study shows that both test groups reduce stress at the time of anesthetic induction and separation from their parents with similar effect. Both of the anesthetics are easily administered without the necessity of an additional equipment. A shorter period to maximal sedation for midazolam is an advantage, thus, making the drug helpful, mostly in the outpatient setting.

The effect of neuraxial morphine on postoperative pain in dogs after extrahepatic portosystemic shunt attenuation.

OBJECTIVE: To investigate the analgesic effect of epidural morphine after surgical extrahepatic portosystemic shunt (EHPSS) attenuation. STUDY DESIGN: Randomized clinical trial. ANIMALS: A total of 20 dogs with a congenital EHPSS. METHODS: Dogs were randomly allocated to be given either a single epidural dose of 0.2 mg kg-1 preservative-free morphine (group M) or not (group C) before surgery. All dogs were administered 0.3 mg kg-1 methadone intravenously (IV) as preanaesthetic medication. Pain scores were determined every 2 hours for the first 24 hours postoperatively using the short-form Glasgow Composite Measure Pain Scale (GCMPS-SF). Dogs with a GCMPS-SF pain score >4/20 or >5/24 received 0.1 mg kg-1 methadone IV as rescue analgesia and were reassessed 30 minutes later. If more than three doses of methadone were administered in a 2 hour period, alternative pain relief was provided and a treatment failure recorded. The GCMPS-SF pain scores and number of rescue analgesia injections were analysed over 24 hours. The last observation carried forward method was applied in case of treatment failure. Food consumption and time to first urination were recorded. Data were analysed using a Mann-Whitney U test and presented as median (minimum-maximum range), with significance set at p < 0.05. RESULTS: Group M showed lower GCMPS-SF pain scores [15 (11-41) versus 31 (11-86); p = 0.023] and lower postoperative methadone requirements [0 (0-0.2) versus 0.25 (0-0.5) mg kg-1; p = 0.029] than group C. There were three treatment failures in group C only. Food consumption and time to first urination did not differ between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Epidural morphine reduced the requirement for postoperative analgesia in this study population.

Pre-medication before dental procedures: A randomized controlled study comparing intranasal dexmedetomidine with oral midazolam.

BACKGROUND: This study aimed to determine if intranasal dexmedetomidine is a superior pre-medication to oral midazolam in older, difficult children. METHODS: This was conducted as a prospective, single-blind randomized control trial in a tertiary care center. Seventy-five children, age >5 years and weight >20 kg, who needed general anesthesia for dental procedures were randomly assigned to be pre-medicated with either oral midazolam at a dose of 0.5 mg/kg (max 15 mg) or intranasal dexmedetomidine at a dose of 2 mcg/kg (max 100 mcg). The primary outcome studied was the patients' level of sedation when separated from their parents, which was assessed using a 5-point University of Michigan Sedation Scale. Secondary outcome studied was the level of anxiolysis assessed by the acceptance of mask induction using a 4-point scale. All assessments were made by one research person blinded to the study drug. RESULTS: The two groups were similar in age, sex, weight, pre-anesthetic behavior, time from pre-medication to anesthesia induction, and surgical time. A significantly higher proportion of patients who received dexmedetomidine had satisfactory sedation at separation from parents (69.4% vs 40.5%, P = .03) compared to those who received midazolam. There were no significant differences in the rate of acceptance of mask induction (80.6% vs 78.4%, P = 1.00). Intranasal dexmedetomidine was tolerated well when administered using a mucosal atomizer and without any clinically significant effect on heart rate or systolic blood pressure. CONCLUSIONS: Intranasal dexmedetomidine provides higher success rate in sedation and parental separation compared to oral midazolam, in older, difficult children.

Influence of anxiolytic premedication on vasovagal reactions and home readiness following outpatient intrathecal anaesthesia-A retrospective analysis.

BACKGROUND: Vasovagal reactions during application of intrathecal anaesthesia (IA) are associated with high anxiety levels. A high percentage of patients undergoing outpatient surgery suffer from anxiety. Anxiolytic premedication in day-surgery is suspected to delay recovery and discharge and is, therefore, not routinely used. The aim of this retrospective analysis was to detect the influence of anxiolytic premedication on the incidence of vasovagal reactions and time until discharge home. METHODS: Anaesthesia records of all patients undergoing outpatient surgery under low-dose IA from January 2008 to June 2017 were analysed. Incidences of vasovagal reactions with a decrease in blood pressure and/or heart rate and need for cardiovascular activating medications were documented. Patients were categorised as having received an anxiolytic premedication or not. The time from intrathecal injection of the local anaesthetic until readiness for discharge was recorded. RESULTS: The records of 2747 patients were analysed. One thousand two hundred and ninety-one of them received an anxiolytic premedication of 1-2 mg midazolam intravenously. Three hundred and fourteen patients had vasovagal incidents during application of IA (no premedication n = 217 [15.0%], premedication n = 97 [7.5%], P < 0.0001). Premedication did not prolong time to achieve readiness for discharge (mepivacaine: P = 0.5886, chloroprocaine: P = 0.1555). However, in the prilocaine group, premedication led to a significantly earlier achievement of readiness for discharge (P = 0.0002). CONCLUSION: Anxiolytic premedication significantly reduces the incidence of vasovagal reactions during the application of IA and does not affect time until readiness for discharge.

Electroencephalographic (EEG) density spectral array monitoring in children during sevoflurane anaesthesia: a prospective observational study.

Electroencephalographic density spectral array monitoring has been developed to facilitate the interpretation of unprocessed electroencephalogram signals. The primary aim of this prospective observational study, performed in a tertiary children's hospital, was to identify the clinical applicability and validity of density spectral array monitoring in infants and children during sevoflurane anaesthesia. We included 104 children, aged < 6 years, undergoing elective surgery during sevoflurane anaesthesia. We investigated the correlation between non-steady state end-tidal sevoflurane and the expression of the four electroencephalogram frequency bands ß, α, θ and δ, representing density spectral array. Patients were divided into three age groups (< 6 months, 6-12 months, > 12 months). There was a significant correlation between end-tidal sevoflurane and density spectral array in the age groups 6-12 months (p < 0.05) and 1-6 years (p < 0.0001). In infants < 6 months of age, the relative percentages of density spectral array did not correlate with end-tidal sevoflurane. The main finding was that different end-tidal concentrations of sevoflurane produce age-dependent changes in the density spectral array power spectrum. In infants younger than 6 months-old, α and ß coherence are absent, whereas θ and δ oscillations have already emerged. In cases where anaesthesia was too deep, this presented as burst suppression on the electroencephalogram, θ disappeared, leaving the electroencephalographic activity in the δ range. Future research should address this issue, aiming to clarify whether the emergence of θ oscillations in infants helps to prevent sevoflurane overdosing.

The comparison of dexmedetomidine and midazolam premedication on postoperative anxiety in children for hernia repair surgery: A randomized controlled trial.

BACKGROUND: Perioperative anxiety is common in pediatric patients undergoing surgery. AIMS: The aim of this study was to determine whether an infusion of dexmedetomidine prior to hernia repair in children provides better postoperative anxiety outcomes that a preoperative infusion of midazolam. METHODS: Ninety 6-11-year-old children, who were scheduled to undergo elective hernia repair, were enrolled for this double-blind, randomized controlled trial. Group D (n = 45) received an intravenous infusion of dexmedetomidine (0.5 µg/kg) and Group M (n = 45) received an intravenous infusion of midazolam (0.08 mg/kg) in 20 mL of normal saline for 10 minutes before the induction of anesthesia. Pre- and postoperative scores on the modified Yale Preoperative Anxiety Scale were the main outcomes. Secondary outcomes included systolic blood pressure, diastolic blood pressure, heart rate, and postoperative pain measured on a visual analogue scale and patient satisfaction using a numerical rating scale. RESULTS: Postoperative anxiety in Group D was significantly lower than preoperative anxiety (2 hours postoperatively mean difference [95% CI]: 2.83 [0.87-4.79], P = 0.036, 4 hours postoperatively mean difference [95% CI]: 3.29 [1.39-5.20], P = 0.005). Preoperative and postoperative anxiety in Group M was similar. Anxiety scores in Group D were also significantly lower than anxiety in Group M 2 hours (mean difference [95% CI]: 1.89 [0.52-3.26], P = 0.01) and 4 hours (mean difference [95% CI]: 3.32 [1.98-4.66], P < 0.001) postoperatively. Systolic blood pressure, diastolic blood pressure and heart rate were lower in Group D than in Group M after administration of sedative drugs until children left PACU (SBP mean difference [95% CI]: 13.87 [10.30-17.43], P < 0.001, DBP mean difference [95% CI]: 5.96[3.80-8.11], P < 0.001, HR mean difference [95% CI]: 10.36 [7.58-13.13], P < 0.001). Pain was also significantly lower in Group D than in Group M at 2 hours (median difference [95% CI]: 1 [0.26-1.34], P = 0.004), 4 hours (median difference [95% CI]: 1 [0.31-1.02], P = 0.003), and 1 day (median difference [95% CI]: 0 [0.22-0.76], P = 0.003) postoperatively. Patient satisfaction scores were significantly higher in Group D than in Group M 1 day (median difference [95% CI]: 0 [-0.83 to -0.24], P = 0.006) and somewhat higher 1 week (median difference [95% CI]: 0 [-0.67 to -0.04], P = 0.06) postoperatively. CONCLUSION: Compared with midazolam, a single preoperative intravenous dose of dexmedetomidine appears to provide better postoperative anxiolytic effects for children undergoing same-day surgery.

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.

The Use of Alfaxalone in Quaker Parrots (Myiopsitta monachus).

Alfaxalone is a neurosteroid anesthetic that acts on gamma-aminobutyric acid alpha-receptors. The objective of this study was to evaluate the clinical safety and efficacy of alfaxalone (Alfaxan CD). Due to observed hyperexcitability in the subject animals when alfaxalone was the only drug used during the initial trials, premedication with midazolam was also evaluated during the final study. Ten adult Quaker parrots (Myiopsitta monachus) were assigned to 3 groups: 1) low-dose alfaxalone 10 mg/kg (LD), 2) high-dose alfaxalone 25 mg/kg (HD), and 3) alfaxalone 10 mg/ kg with midazolam 1 mg/kg premedication (AM), administered intramuscularly. Induction time, sedation quality, duration of action, and vital parameters, including heart rate, respiratory rate, and temperature, were recorded. All protocols achieved adequate sedation; however, muscle tremors and hyperexcitation were variable. The LD group had a significantly longer mean ± SD induction time (13.5 ± 4.5 minutes) as compared to the HD (6.0 ± 1.3 minutes, P = .002) and AM (6.5 ± 2.9 minutes, P = .006) groups, while recovery time was significantly longer in the HD group (86.2 ± 13.4 minutes) than the LD group (44.4 ± 10.8 minutes, P < .001). Midazolam premedication resulted in reduction of both muscle tremors and hyperexcitation associated with alfaxalone administration, but the recovery time was significantly longer (103.5 ± 15.1 minutes, P < .001) than for the LD group. Alfaxalone as a sole agent resulted in muscle tremors and hyperexcitation during induction, which was attenuated by premedication with midazolam. Further investigation is warranted to characterize the effects of alfaxalone and drugs used to premedicate Quaker parrots.

The effectiveness of transport in a toy car for reducing preoperative anxiety in preschool children: a randomised controlled prospective trial.

BACKGROUND: This study was designed to determine whether transport of a paediatric inpatient in a children's ride-on toy car has an effect on perioperative levels of anxiety compared with transport on a hospital gurney with or without oral midazolam premedication. METHODS: In this prospective study, 108 children aged 2-5 yr with congenital heart disease and undergoing first surgical correction were randomly allocated to one of three groups: Group C (transport in a children's ride-on car), Group G (transport on a gurney without premedication), or Group M (transport on a gurney and received premedication of oral midazolam 0.5 mg kg-1). The modified Yale Preoperative Anxiety Scale-Short Form and parent-recorded anxiety VAS were applied to evaluate anxiety in the following time points: pre-anaesthesia visit (the day before surgery), upon getting in the ride-on car or on the gurney in the ward, upon arriving in the preoperative holding area, at the moment of leaving from the holding area to the operating room (OR) (coincided with separation from parents), at the time after entering the OR, and at the time just before anaesthesia induction. RESULTS: Children in Group C exhibited significantly lower levels of anxiety from the time they got into the ride-on car until the time they entered the OR, compared with the other two groups (P<0.001). The subjects in Group C had similarly low anxiety levels to those in the Group M at the time before induction (P=0.914). CONCLUSIONS: Transport in a ride-on toy car can relieve preoperative anxiety in preschool children undergoing surgery to a comparable degree as midazolam. CLINICAL TRIAL REGISTRATION: ChiCTR-IOR-17012791.

Comparison of nebulised dexmedetomidine, ketamine, or midazolam for premedication in preschool children undergoing bone marrow biopsy.

BACKGROUND: The aim of our study was to compare the efficacy of dexmedetomidine, ketamine, and midazolam for sedative premedication administered by nebuliser 30 min before general anaesthesia in preschool children undergoing bone marrow biopsy and aspiration. METHODS: Ninety children aged 3-7 yr were randomly allocated into three equal groups to be premedicated with either nebulised ketamine 2 mg kg-1 (Group K), dexmedetomidine 2 µg kg-1 (Group D), or midazolam 0.2 mg kg-1 (Group M). The primary endpoint was a five-point sedation score on arrival in the operating room 30 min after end of study drug administration. Secondary outcomes included: parental separation anxiety scale; medication and mask acceptance scales; haemodynamic variables; recovery time; postoperative face, legs, activity, cry, and consolability scale; emergence agitation scale; and adverse effects. RESULTS: The median (range) sedation score on arrival in the operating room was 3.5 (1-4), 2.0 (2-3) and 2.0 (1-3) in Groups M, D, and K, respectively (P=0.000). Subjects in Group D showed higher medication (P<0.03) and mask acceptance scores (P<0.015) and more satisfactory parental separation anxiety scale (P<0.044). The median (range) recovery time was significantly shorter in Group D [5.5 (4-8) min] compared with Group K [10.0 (5-15) min, P=0.000] and M [8.0 (6-15) min, P=0.000]. The incidence of emergence agitation was lower in Group D (P<0.008). CONCLUSIONS: Preschool children premedicated with nebulised dexmedetomidine had more satisfactory sedation, shorter recovery time, and less postoperative agitation than those who received nebulised ketamine or midazolam. CLINICAL TRIAL REGISTRATION: NCT02935959.

The analgesic effects of buprenorphine (Vetergesic or Simbadol) in combination with carprofen in dogs undergoing ovariohysterectomy: a randomized, blinded, clinical trial.

BACKGROUND: Buprenorphine is a potent lipophilic opioid analgesic that is largely used in the multimodal treatment of acute pain. Simbadol (buprenorphine hydrochloride) is the first and only FDA-approved high-concentration formulation of buprenorphine for use in cats. The aim of this study was to evaluate the analgesic efficacy of carprofen in combination with one of two commercial formulations of buprenorphine (Simbadol and Vetergesic, 1.8 mg/mL and 0.3 mg/mL, respectively) in dogs undergoing ovariohysterectomy. Twenty-four dogs were included in a randomized, prospective, controlled, clinical trial. Patients were randomly divided into 2 groups as follows. Dogs were premedicated with acepromazine (0.02 mg/kg) and either 0.02 mg/kg of Vetergesic or Simbadol intramuscularly (Vetergesic group - VG; Simbadol group - SG, respectively; n = 12/group). General anesthesia was induced with propofol and maintained with isoflurane in 100% oxygen. Carprofen (4.4 mg/kg SC) was administered after induction of anesthesia. Heart rate, respiratory rate, blood pressure, pulse oximetry, pain scores using the Glasgow Composite Pain Scale Short Form (CMPS-SF), sedation scores using a dynamic interactive visual analogue scale and adverse events were evaluated before and after ovariohysterectomy by an observer who was unaware of treatment administration. If CMPS-SF scores were ≥ 5/20, dogs were administered rescue analgesia (morphine 0.5 mg/kg IM). Statistical analysis was performed using linear mixed models and Fisher's exact test (p < 0.05). RESULTS: Pain and sedation scores and physiological parameters were not significantly different between treatments. Three dogs in VG (25%) and none in SG (0%) required rescue analgesia (p = 0.109). Adverse effects (i.e. vomiting and melena) were observed in two dogs in SG and were thought to be related to stress and/or nonsteroidal anti-inflammatory drug toxicity. CONCLUSIONS: The administration of buprenorphine with carprofen preoperatively provided adequate postoperative analgesia for the majority of dogs undergoing OVH without serious adverse events. Prevalence of rescue analgesia was not significantly different between groups; however, it could be clinically relevant and explained by a type II error (i.e. small sample size). Future studies are necessary to determine if analgesic efficacy after Simbadol and Vetergesic is related to individual variability or pharmacokinetic differences.

Sedation of children undergoing dental treatment.

BACKGROUND: Children's fear about dental treatment may lead to behaviour management problems for the dentist, which can be a barrier to the successful dental treatment of children. Sedation can be used to relieve anxiety and manage behaviour in children undergoing dental treatment. There is a need to determine from published research which agents, dosages and regimens are effective. This is the second update of the Cochrane Review first published in 2005 and previously updated in 2012. OBJECTIVES: To evaluate the efficacy and relative efficacy of conscious sedation agents and dosages for behaviour management in paediatric dentistry. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 22 February 2018); the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1) in the Cochrane Library (searched 22 February 2018); MEDLINE Ovid (1946 to 22 February 2018); and Embase Ovid (1980 to 22 February 2018). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: Studies were selected if they met the following criteria: randomised controlled trials of conscious sedation comparing two or more drugs/techniques/placebo undertaken by the dentist or one of the dental team in children up to 16 years of age. We excluded cross-over trials. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted, in duplicate, information regarding methods, participants, interventions, outcome measures and results. Where information in trial reports was unclear or incomplete authors of trials were contacted. Trials were assessed for risk of bias. Cochrane statistical guidelines were followed. MAIN RESULTS: We included 50 studies with a total of 3704 participants. Forty studies (81%) were at high risk of bias, nine (18%) were at unclear risk of bias, with just one assessed as at low risk of bias. There were 34 different sedatives used with or without inhalational nitrous oxide. Dosages, mode of administration and time of administration varied widely. Studies were grouped into placebo-controlled, dosage and head-to-head comparisons. Meta-analysis of the available data for the primary outcome (behaviour) was possible for studies investigating oral midazolam versus placebo only. There is moderate-certainty evidence from six small clinically heterogeneous studies at high or unclear risk of bias, that the use of oral midazolam in doses between 0.25 mg/kg to 1 mg/kg is associated with more co-operative behaviour compared to placebo; standardized mean difference (SMD) favoured midazolam (SMD 1.96, 95% confidence interval (CI) 1.59 to 2.33, P < 0.0001, I2 = 90%; 6 studies; 202 participants). It was not possible to draw conclusions regarding the secondary outcomes due to inconsistent or inadequate reporting or both. AUTHORS' CONCLUSIONS: There is some moderate-certainty evidence that oral midazolam is an effective sedative agent for children undergoing dental treatment. There is a need for further well-designed and well-reported clinical trials to evaluate other potential sedation agents. Further recommendations for future research are described and it is suggested that future trials evaluate experimental regimens in comparison with oral midazolam or inhaled nitrous oxide.

A novel, palatable paediatric oral formulation of midazolam: pharmacokinetics, tolerability, efficacy and safety.

Midazolam is one of many bitter drugs where provision of a suitable oral paediatric formulation, particularly in the pre-anaesthetic setting, remains a challenge. To overcome this problem, a novel chocolate-based tablet formulation has been developed with positive pre-clinical results. To further investigate the potential of this formulation, 150 children aged 3-16 years who were prescribed midazolam as a premedication were randomly assigned to receive 0.5 mg.kg-1 either as the novel formulation or an intravenous solution given orally, which is the current standard at our institution. Tolerability was assessed by each child, parent and nurse using a 5-point facial hedonic scale and efficacy was determined as the time to onset of sedation. Blood samples for midazolam and 1-hydroxymidazolam levels were analysed using high-performance liquid chromatography. Population pharmacokinetics were evaluated using non-linear mixed effects modelling. The novel formulation had significantly improved tolerability scores from children, parents and nurses (all p < 0.001). Time to effect was not different between the groups (p = 0.140). The pharmacokinetics of midazolam and 1-hydroxymidazolam were able to be modelled simultaneously. The novel formulation was subject to a higher estimated first-pass metabolism compared with the intravenous solution (8.6% vs. 5.0%) and a significantly lower relative bioavailability of 82.1% (p = 0.013), with no other significant differences. Exposure relative to dose was in the range previously reported for midazolam syrup. We conclude that the novel chocolate-based formulation of midazolam provides improved tolerability while remaining efficacious with suitable pharmacokinetics when used as a premedicant for children.