Addition of Dexmedetomidine to Propofol Anesthesia for Middle-Ear Surgeries: A Prospective Randomized Double-Blind Study.

Background Middle-ear surgery commonly performed under a microscope requires a bloodless field provided by hypotensive anesthesia. Our objective was to study the effects of dexmedetomidine on propofol consumption and intraoperative hemodynamic stability. Methods One hundred adults undergoing elective middle-ear surgery were randomized into two groups. The propofol+dexmedetomidine group (Group PD) received a loading dose of dexmedetomidine 1µg/kg in 10ml normal saline over 10min followed by infusion of the same at 0.5µg/kg/h. Propofol-only group (Group P) received 10ml normal saline over 10min followed by an infusion of the same. General anesthesia was induced with intravenous morphine, propofol, and vecuronium, and maintained with propofol, oxygen, and N2O. During microscope use, we aimed to maintain mean arterial pressure (MAP) within 60-69mmHg. Results There was no significant difference in the mean (SD) consumption of propofol [Group P 8.6 (2.1)mg/kg/h vs Group PD 8.1 (1.5)mg/kg/h, P=0.172]. The induction dose of propofol was significantly less in Group PD [1.8 (0.3) vs 2 (0.4)mg/kg, P<0.001]. Except for the baseline value, the heart rate was significantly lower in Group PD, P<0.001. The time duration during which MAP was within 60-69mmHg was higher in Group P [37.5 (36.8) vs 30.9 (38.3)min] though the difference was not statistically significant. The recovery was delayed in Group PD [25.4 (8.6) vs 17.6 (4.9)min, P<0.001]. Group PD had a significantly better operative field, P=0.0003. Conclusion The addition of dexmedetomidine did not reduce propofol consumption but reduced the induction dose of propofol. Propofol and dexmedetomidine combination provided comparable mean arterial pressure and better operative field but caused delayed recovery.

Pharmacokinetics of dexmedetomidine in anaesthetized horses following repeated subcutaneous administration and intravenous constant rate infusion.

BACKGROUND: The inclusion of dexmedetomidine (DEX) within a balanced general anaesthesia protocol is effective in improving the clinical outcome and recovery quality of anaesthesia in horses. This study aimed to determine the pharmacokinetic profile of DEX following repeated subcutaneous (SC) administration at 2 µg/kg every 60 min till the end of the procedure in comparison to intravenous constant rate infusion (CRI) at 1 µg/kg/h in anaesthetized horses undergoing diagnostic procedures up to the end of the diagnostic procedure. RESULTS: In the CRI and SC groups DEX maximum concentrations (Cmax) were 0.83 ± 0.27 ng/mL and 1.14 ± 0.71 ng/mL, respectively, reached at a time (Tmax) of 57.0 ± 13.4 min and 105.5 ± 29.9 min. Mean residence time to the last measurable concentration (MRTlast) was 11.7 ± 6.2 and 55.8 ± 19.7 min for the CRI group and SC groups, respectively. The apparent elimination half-life was 18.0 ± 10.0 min in the CRI group and 94.8 ± 69.8 min for the SC group, whereas the area under the curve (AUC0-last) resulted 67.7 ± 29.3 and 83.2 ± 60.5 min*ng/mL for CRI and SC group, respectively. Clearance was 16.26 ± 8.07 mL/min/kg for the CRI group. No signs of adverse effects were recorded in both groups. CONCLUSIONS: The pharmacokinetic profile of DEX following repeated SC administration in anaesthetized horses was comparable to intravenous CRI administration during the intranaesthetic period and beneficial during the recovery phase from general anaesthesia. The SC route could be considered as an alternative to CRI for improving the recovery quality of equine patients undergoing general anaesthesia.

Use of dexmedetomidine repeated subcutaneous administration for balanced anaesthesia in horses.

BACKGROUND: A balanced anaesthetic protocol is a common concept in modern veterinary anaesthesia and aims to maintain good intraoperative cardiopulmonary function. In horses, alpha-2-agonists produce sedation and analgesia and have been shown to reduce inhalational anaesthetic requirements when administered intravenously. Furthermore, these drugs can improve recovery quality. Preliminary investigations of subcutaneous dexmedetomidine administration in humans demonstrated a reduced haemodynamic impact if compared with the intravenous route suggesting that dexmedetomidine is adequately absorbed with both administration routes. The aim of the study was to compare two different dexmedetomidine (DEX) administration routes: intravenous constant rate infusion (CRI) versus repeated subcutaneous (SC) injections on cardiopulmonary function and recovery in anaesthetized horses. RESULTS: No significant differences between groups in heart rate and systolic arterial pressure were detected. A significantly higher mean and diastolic arterial pressure were detected in the SC group at T25 (p = 0.04; p = 0.02), T75 (p = 0.02; p = 0.009), and T85 (p = 0.001; p = 0.005). In SC group there was a significantly lower dobutamine infusion rate (p = 0.03) and a significantly higher urinary output (p = 0.02). Moreover, recovery quality was higher (p = 0.01). CONCLUSIONS: Cardiopulmonary effects in both groups were comparable and within clinical ranges with less dobutamine requirement in the subcutaneous group. Recovery was of better quality with fewer attempts in horses receiving subcutaneous dexmedetomidine. The present study suggests that intravenous constant rate infusion and subcutaneous repeated administration of dexmedetomidine at indicated dosage can be useful in balanced anaesthesia without any systemic or local adverse effects; moreover, in healthy horses undergoing general anaesthesia, repeated subcutaneous dexmedetomidine administration may be a suitable alternative if constant rate infusion is not feasible.

Total Intravenous Anaesthesia with Ketamine, Medetomidine and Midazolam as Part of a Balanced Anaesthesia Technique in Horses Undergoing Castration.

To evaluate the use of ketamine-medetomidine-midazolam total intravenous infusion as part of a balanced anaesthetic technique for surgical castration in horses. Five healthy Standardbred cross colts were premedicated with IV acepromazine (0.01-0.02 mg/kg), medetomidine (7 µg/kg) and methadone (0.1 mg/kg) and anaesthesia induced with IV ketamine (2.2 mg/kg) and midazolam (0.06 mg/kg). Horses were anaesthetised for 40 min with an IV infusion of ketamine (3 mg/kg/h), medetomidine (5 µg/kg/h) and midazolam (0.1 mg/kg/h) while routine surgical castration was performed. Cardiorespiratory variables, arterial blood gases, and anaesthetic depth were assessed at 5 to 10 min intervals. Post-anaesthesia recovery times were recorded, and the quality of the recovery period was assessed. The anaesthetic period and surgical conditions were acceptable with good muscle relaxation and no additional anaesthetic required. The median (range) time from cessation of the infusion to endotracheal tube extubation, head lift and sternal recumbency were 17.2 (7-35) min, 25 (18.9-53) min and 28.1 (23-54) min, respectively. The quality of anaesthetic recovery was good, with horses standing 31.9 (28-61) min after the infusion was ceased. During anaesthesia, physiological variables, presented as a range of median values for each time point were: heart rate 37-44 beats/min, mean arterial pressure 107-119 mmHg, respiratory rate 6-13 breaths/min, arterial partial pressure of oxygen 88-126 mmHg, arterial partial pressure of carbon dioxide 52-57 mmHg and pH 7.36-7.39. In conclusion, the co-administration of midazolam, ketamine and medetomidine as in IV infusion, when used as part of a balanced anaesthetic technique, was suitable for short term anaesthesia in horses undergoing castration.

Pharmacokinetics and pharmacodynamics of l-methadone in isoflurane-anaesthetized and mechanically ventilated ponies.

OBJECTIVE: To evaluate the pharmacokinetics and selected pharmacodynamic effects of a commercially available l-methadone/fenpipramide combination administered to isoflurane anaesthetized ponies. STUDY DESIGN: Prospective single-group interventional study. ANIMALS: A group of six healthy adult research ponies (four mares, two geldings). METHODS: Ponies were sedated with intravenous (IV) detomidine (0.02 mg kg-1) and butorphanol (0.01 mg kg-1) for an unrelated study. Additional IV detomidine (0.004 mg kg-1) was administered 85 minutes later, followed by induction of anaesthesia using IV diazepam (0.05 mg kg-1) and ketamine (2.2 mg kg-1). Anaesthesia was maintained with isoflurane in oxygen. Baseline readings were taken after 15 minutes of stable isoflurane anaesthesia. l-Methadone (0.25 mg kg-1) with fenpipramide (0.0125 mg kg-1) was then administered IV. Selected cardiorespiratory variables were recorded every 10 minutes and compared to baseline using the Wilcoxon signed-rank test. Adverse events were recorded. Arterial plasma samples for analysis of plasma concentrations and pharmacokinetics of l-methadone were collected throughout anaesthesia at predetermined time points. Data are shown as mean ± standard deviation or median and interquartile range (p < 0.05). RESULTS: Plasma concentrations of l-methadone showed a rapid initial distribution phase followed by a slower elimination phase which is best described with a two-compartment model. The terminal half-life was 44.3 ± 18.0 minutes, volume of distribution 0.43 ± 0.12 L kg-1 and plasma clearance 7.77 ± 1.98 mL minute-1 kg-1. Mean arterial blood pressure increased from 85 (±16) at baseline to 100 (±26) 10 minutes after l-methadone/fenpipramide administration (p = 0.031). Heart rate remained constant. In two ponies fasciculations occurred at different time points after l-methadone administration. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of a l-methadone/fenpipramide combination to isoflurane anaesthetized ponies led to a transient increase in blood pressure without concurrent increases in heart rate. Pharmacokinetics of l-methadone were similar to those reported for conscious horses administered racemic methadone.

Effects of fentanyl-lidocaine-ketamine versus sufentanil-lidocaine-ketamine on the isoflurane requirements in dogs undergoing total ear canal ablation and lateral bulla osteotomy.

OBJECTIVE: To compare the isoflurane-sparing effects of sufentanil-lidocaine-ketamine (SLK) and fentanyl-lidocaine-ketamine (FLK) infusions in dogs undergoing total ear canal ablation and lateral bulla osteotomy (TECA-LBO). STUDY DESIGN: Randomized blinded clinical study. ANIMALS: A group of 20 client-owned dogs undergoing TECA-LBO. METHODS: Intravenous (IV) administration of lidocaine (3 mg kg-1) and ketamine (0.6 mg kg-1) with fentanyl (5.4 µg kg-1; n = 10; FLK group) or sufentanil (0.72 µg kg-1; n = 10; SLK group) was immediately followed by the corresponding constant rate infusion (CRI) (lidocaine 3 mg kg-1 hour-1; ketamine 0.6 mg kg-1 hour-1; either fentanyl 5.4 µg kg-1 hour-1 or sufentanil 0.72 µg kg-1 hour-1). Anaesthesia was induced with propofol 3-5 mg kg-1 IV and was maintained with isoflurane. End-tidal isoflurane concentration (Fe'Iso) was decreased in 0.2% steps every 15 minutes until spontaneous movements were observed (treated with propofol 1 mg kg-1 IV) or an increase of > 30% in heart rate or mean arterial pressure from baseline occurred (treated with rescue fentanyl or sufentanil). Quality of recovery and pain were assessed at extubation using the short-form Glasgow Composite Pain Scale (SF-GCPS), Colorado State University Canine Acute Pain scale (CSU-CAP), and visual analogue scale (VAS). Data were analysed with analysis of variance, t tests, Fisher test and Spearman coefficient (p < 0.05). RESULTS: Fe'Iso decreased significantly in SLK group (45%; p = 0.0006) but not in FLK (15%; p = 0.1135) (p = 0.0136). SLK group had lower scores for recovery quality (p = 0.0204), SF-GCPS (p = 0.0071) and CSU-CAP (p = 0.0273) than FLK at extubation. Intraoperative rescue analgesia and VAS were not significantly different between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with FLK infusion, CRI of SLK at these doses decreased isoflurane requirements, decreased pain scores and improved recovery quality at extubation in dogs undergoing TECA-LBO.

Intravenous clonidine as a part of balanced anaesthesia for controlled hypotension in functional endoscopic sinus surgery: A randomised controled trial.

BACKGROUND AND AIMS: Controlled hypotension with balanced anaesthesia minimises blood loss. This study was done to evaluate the effectiveness of intravenous clonidine as a single bolus dose to establish controlled hypotension during functional endoscopic sinus surgery (FESS). METHODS: This randomised, double-blind, placebo-controlled study was done in a tertiary hospital in India. Sixty American Society of Anesthesiologists physical status I and II patients (18-65 years) undergoing FESS were randomly allocated to one of the two groups. Placebo group (group A, n = 30) received sterile water whereas the clonidine group (group B, n = 30) received 3µg/kg of clonidine intravenously, 30 min prior to induction of anaesthesia. The primary outcome was to achieve a target mean arterial blood pressure (MAP) of 55-65 mmHg intraoperatively. The secondary outcomes measured were requirement of additional fentanyl and metoprolol, intra-operative blood loss, surgeon's opinion on the surgical field, pain, sedation score and complications requiring treatment. RESULTS: Target MAP was easily achieved in clonidine group as against the placebo group (P < 0.001). Significant reduction in intra-operative blood loss (P = 0.0449), a better surgical site scoring (P = 0.02), less requirement of additional hypotensive drugs and good analgesia (P = 0.01) were seen in clonidine group. The complication rates were similar in both the groups. CONCLUSION: Clonidine is effective in achieving controlled hypotension in patients undergoing FESS. It reduces intra-operative blood loss, requirement of additional hypotensive drugs, improves the surgical field and offers good analgesia without significant side effects.

Influence of ketamine or xylazine supplementation on isoflurane anaesthetized horses--a controlled clinical trial.

OBJECTIVES: To determine the influence of ketamine or xylazine constant rate infusions on isoflurane requirements, cardiovascular parameters and quality of anaesthesia in horses undergoing elective surgery. STUDY DESIGN: Prospective, matched paired clinical trial. ANIMALS: Fifty four adult Warmblood horses. METHODS: After premedication with acepromazine, xylazine and butorphanol, anaesthesia was induced with ketamine-midazolam and maintained with isoflurane alone (I), isoflurane with either 1 mg kg(-1)  hour(-1) ketamine (IK) or same dose of xylazine (IX). End tidal concentration of isoflurane (Fe'Iso) was adjusted by the same anaesthetist in all horses according to a scoring system. Dobutamine was infused to maintain mean arterial pressure (MAP) ≥70 mmHg. Arterial blood gases, heart rate (HR), respiratory rate, MAP and cardiac output (lithium dilution) were measured. Groups I and IK received xylazine before recovery. Recovery quality was scored. RESULTS: Mean ± SD averaged Fe'Iso (volume%) was significantly lower in IX (0.95 ± 0.07) and IK (0.97 ± 0.08) than in I (1.16 ± 0.13). In group IX, HR was significantly lower and averaged MAP (90 ± 13 mmHg) significantly higher than in groups I (71 ± 7 mmHg) and IK (76 ± 7 mm Hg). Differences in other cardiopulmonary variables did not reach statistical significance. All horses recovered well with best score in group IX. CONCLUSIONS: Both CRIs of xylazine and of ketamine resulted in pronounced reduction of isoflurane requirements and blood pressure support based on routinely monitored parameters. Cardiac output appeared well maintained in all three protocols, but lithium dilution induced errors mean the results are untrustworthy. The work requires repetition with another mode of measurement of cardiac output. CLINICAL RELEVANCE: All three protocols provided good clinical anaesthesia with clinically acceptable cardiovascular effects.

Short-term Parameters of Heart Rate Variability During Balanced Anaesthesia with Administration of Two Different Inhalation Anaesthetics.

INTRODUCTION: Heart rate variability which denotes variations of the length of consecutive heart cycles has been suggested to reflect the modulation of heart rate by autonomic nervous system. METHODS: Sixty four patients of ASA I and ASA II status scheduled for elective abdominal surgical procedures were randomly allocated to group 1 and group 2. Premedication and induction of anaesthesia were performed with same agents. After orotracheal intubation maintenance of balanced anaesthesia was based on administration of same induction agents,opioids and muscle relaxant while delivery of gaseous mixture with sevoflurane in the group 1 (n=32) and isoflurane in the group 2(n=32). Haemodynamic parameters were monitored in perioperative and electrocardiogram was recorded by holter ECG recorder, while the analysis of the parameters were performed by corresponding softwares . Data were presented as mean values of logarithmic (natural logarithm) values of the power of the total spectrum of heart rate variability(TP), mean values of the logarithmic values of low frequency band (LF), mean values of the logarithmic values of high frequency range(HF), and mean values of SD1 and SD2 parameters. RESULTS: Analysis of the values of hemodynamic parameters has shown changes of haemodynamic parameters during perioperative period without significant statistical differences between the groups. Analysis of the logarhitmic values of parameters of heart rate variability of frequency domain has shown changes of the total spectrum power and LF and HF spestra with variations of the values of total power spectrum and individual components of the spectrum of heart rate variability during the balanced anaesthesia with administration of two different inhalation anaesthetics, without statistically significant differences between the groups. CONCLUSION: The results have shown that during balanced anaesthesia with two different inhalation anaesthetics there are variations of haemodynamic variables and parameters of heart rate variability without statistically significance that could show the difference between the groups and different agents administered.

Comparison of sodium diclofenac, ketamine and propofol with fentanyl and midazolam in balanced anaesthesia.

CONTEXT: Analgesia is based on balanced anaesthesia, which is usually maintained by administration of narcotic agents. In some patients, it is not possible to use narcotics. We compared hemodynamic changes, anaesthesia depth, emetic sequelae and post-operative pain between sodium Diclofenac, Ketamine-Propofol (DKP) and Fentanyl-Midazolam (FM). AIMS: The effectiveness of an anaesthetic technique employing sodium was compared against in patients undergoing elective surgery. SETTINGS AND DESIGN: In a clinical trial study, 82 patients who attended for an elective surgery were randomly divided into two groups. MATERIALS AND METHODS: In DKP group pre-medication included Sodium Diclofenac 1 mg/kg and Midazolam 0.02 mg/kg, whereas, in FM group they were Fentanyl 2 µg/kg and Midazolam 0.02 mg/ kg. Anaesthesia induction in both groups was the same. Anaesthesia was conserved in DKP group by using Propofol plus Ketamine infusion plus N2O 50% and in FM group with Fentanyl plus Midazolam plus N2O 50%. Hemodynamic changes, depth of anaesthesia, nausea and vomiting, post operative analgesic effects were recorded. RESULTS: Hemodynamic changes and depth of anaesthesia were similar throughout the maintenance phase in two groups. In FM group, significant increase in heart rate was recorded in recovery room. Pain score according to visual analogue scale (VAS) and need for analgesics, was significantly more in FM group compared to DKP group (P = 0.000). No patient suffered from nausea, vomiting or hallucinations. CONCLUSIONS: This study revealed that intravenous administration of Sodium Diclofenac along with Ketamine and Propofolplus N2O 50% for general anaesthesia provides a balanced anaesthesia as well as hemodynamic stability, and adequate depth of anaesthesia. It also reduces the postoperative pain and need for narcotics. We recommended DKP plus N2O 50% method for patients prohibited from opioid administration. It will be an acceptable method in sensitive patients.