Comparison of Dexmedetomidine 50μg versus 100μg added to 0 Comparison of Dexmedetomidine 50μg versus 100μg added to 0.5% Levobupivacaine in Supraclavicular Brachial Plexus Block (BPB) for Arteriovenous Fistula (AVF) Surgery Chong SE, Mohd, Mohd Nikman A, Fakhzan H, Rhendra Hardy MZ, W Mohd Nazarudin WH Dept of Anaesthesia & Intensive Care, School of Medical Science, Universiti Sains Malaysia Good afternoon ladies & gentlemen, Respected Judges, and members of the floor. I am Dr Chong from USM, my presentation is on study:

Introduction AVF Surgery : a procedure to attach the vein to the artery & prepare a patient for hemodialysis. Normally done under LA Alternatively, it can be done under RA, with better analgesia coverage. Currently various drugs has been proven to be effective adjuncts to brachial plexus block: opioids, clonidine, neostigmine, and tramadol. (DB. Murphy, Anesth Analg 2000) This allows a portion of the high pressure blood in the artery to enter the low pressure and thin-walled vein. Over time, the vein gradually enlarges and has increased blood flow volume. Often this "development" of the fistula requires two months. imidazole compound active dextro-isomer of medetomidine S-enantiomer of medetomidine specific and selective α2-adrenoceptor agonist. produce more sedative eff & analgesia compare to clonidine. Dexmedetomidine compared to Clonidine is a much more selective alpha2-adrenoceptor agonist, which might permit its application in relatively high doses for sedation and analgesia without the unwanted vascular effects from activation of alpha1-receptors. In addition, Dexmedetomidine is shorter-acting drug than clonidine and has a reversal drug for its sedative effect, Atipamezole. These properties render Dexmedetomidine suitable for sedation and analgesia during the whole perioperative period: as premedication, as an anesthetic adjunct for general and regional anesthesia, and as postoperative sedative and analgesic4. the goal of which is to prolong analgesic effect without the disadvantage of systemic side effects or prolonged motor block. It may also allow for a reduction in the total dose of local anesthetic used. Novel adjuncts studied to date include opioids, clonidine, neostigmine, and tramadol

Introduction The search on a suitable LA + additive which is faster in onset, longer duration, stable haemodynamically, and better in safety profile is still in progress.

Introduction Dexmedetomidine (dex) is one of the latest α2-agonist. provides sedation without causing respiratory depression. Normally used as sedation in anaesthesia & ICU. Studies on the effect of dexmedetomidine as additive in brachial plexus block is still on-going. Dexmedetomidine isthe newest Alpha-2 agonist. active dextro-isomer of medetomidine S-enantiomer of medetomidine specific and selective α2-adrenoceptor agonist. produce more sedative eff & analgesia compare to clonidine. Dexmedetomidine compared to Clonidine is a much more selective alpha2-adrenoceptor agonist, which might permit its application in relatively high doses for sedation and analgesia without the unwanted vascular effects from activation of alpha1-receptors. In addition, Dexmedetomidine is shorter-acting drug than clonidine and has a reversal drug for its sedative effect, Atipamezole. These properties render Dexmedetomidine suitable for sedation and analgesia during the whole perioperative period: as premedication, as an anesthetic adjunct for general and regional anesthesia, and as postoperative sedative and analgesic4.

Dexmedetomidine High lipid solubility - rapidly absorbs and binds to the α2 receptor of the nerves for faster analgesic effect. 2. Central and peripheral enhancement of LA activity causing prolongation of nerve block. (Schnaider et al. 2005, Kanazi et al. 2006) Dexmedetomidine has a high lipid solubility which rapid absorbs into csf and binds to the α2 receptor of the spinal cord for faster analgesic effect. It also has Central and peripheral enhancement of LA activity causing prolongation of nerve block (Kanazi et al. 2006)

Objective To compare the effect of adding Dexmedetomidine 50μg versus 100μg to 0.5% Levobupivacaine in Supraclavicular BPB for AVF Surgery in terms of: Onset and Duration of block, Sedation effect and Haemodynamic parameters, Changes in Vascular diameters. Aim of this study is to compare different dose of dex + levo in BPB for AVF surgery & its effect on patients. Also able to provide A delicate balanced between patient comfort, adequate sedation and protected airway.

STUDY DESIGN Double blinded RCT, done in OT HUSM after ethical committee approval. Sample size calculated by using the difference of means from Esmaoglu’s study (2010) which compare: Dex 100μg versus placebo added to Levobupivacaine in Axillary Block. (ESRF patient were excluded) Alpha = 0.05 ( level of significance ) Power = 0.8 Mean onset time in placebo (1) 9.13 Difference in mean 10.46-9.13 = 1.33min (SD) Sample size is 23 patients for each arm. ESRF patient Sedative effect, ideal dose in terms of safety profile

Methodology Selection of patient N = 46 ESRF for AVF > 18 y/o, Well fasted Full GCS, consented Exclusion criterias Selection of patient N = 46 Dex 50 μg + 0.5ml NS + 20ml 0.5% Levo Dex 100 μg + 20ml 0.5% Levo Block randomization vital signs, VAS, Onset of block (sensory, motor), brachial. a. & basilic. v. diameters (by ultrasound) U/S guided supraclavicular block 46 adult patients with chronic renal failure who was scheduled for AVF surgery were studied in this study. Study design: prospective, randomized, single operator, double blinded Supraclavicular block was performed with ultrasound and nerve stimulator technique. Exclusion criteria: : Poor EF < 40%, severe brady (HR<50), perioperative hemodynamic instability, contraindication eg allergy to precedex or chirocaine Visual Analog Pain Score (VAS). vital signs, Ramsay Sedation Score, Duration of block, (sensory, motor) surgery

RESULT Demographic Data: No significant differences between the two groups in terms of age, gender, weight and height. Aim of this study is to compare different dose of dex + levo in BPB for AVF surgery & its effect on patients. Also able to provide A delicate balanced between patient comfort, adequate sedation and protected airway.

P value * 0.002** * Independent T-test ** Statistically significant For onset of sensory block, MEAN ONSET OF DEX 100 WAS 8.08 MIN WHICH IS SIG FASTER P value * 0.002** * Independent T-test ** Statistically significant

** Statistically significant P value * 0.024** * Independent T-test ** Statistically significant

P value * <0.001** * Independent T-test ** Statistically significant

** Statistically significant P value * 0.002** * Independent T-test ** Statistically significant

Ramsay Sedation score sedated *Chi-Square The degree of sedation for both group were not significance different, Majority of the pt had a ramsay score of 3, which is Patient responds to commands. This is better for patient in ESRF. Ramsay Sedation Score (RSS) [ 1= Patient anxious, agitated and restless; 2= Patient cooperative, orientated and tranquil; 3= Patient responds to commands;4= Asleep but with brisk response to light glabellar tap or loud auditory stimulus;5=Asleep, sluggish response to light glabellar tap or loud auditory stimulus and 6= Asleep, no response]. Ramsay sedation socre of 3 and above is considered significant in this study. *Chi-Square ** Statistically not significant

Mean arterial pressure comparison Repeated Measure ANOVA: Statistically not significant (p=0.581) No significance difference in terms of vital signs

Heart rate comparison Statistically not significant (p=0.078) Repeated Measure ANOVA: Statistically not significant (p=0.078)

vessel diameter DIFFERENCE pre & post block DEX 50 DEX 100 Mean (SD) t(44) p-value Brachial artery 0.020 (0.0067) 0.025 (0.0059) 2.55 0.014* Basilic Vein 0.022 (0.0074) 0.027 (0.0062) 2.60 0.013* For Vessel diameter difference pre & post block: vasodilatation for DEX 100 is significantly higher than DEX50 in both brachial artery & basilic vein Following the block with LA+dex, all cause significant brachial artery & basilic vein dilatation * Statistically significant

Discussion Result was similar to Esmaoglu’s 2010 study, where Dexmedetomidine 100μg versus placebo were added to 0.5% Levobupivacaine in Axillary Block. Dexmedetomidine 100 μg added to 0.5% Levobupivacaine in supraclavicular BPB has a faster onset & longer duration in terms of sensory & motor block. ESRF patient were excluded in their study.

Discussion The degree of sedation and vital signs does not significantly differ in both groups. However, Dexmedetomidine 100μg causes significant vasodilatation than 50μg group. This will ease the surgery & may result in an increased successful rate for AVF creation.

Conclusion The addition of dexmedetomidine as an adjuvant for BPB: fasten the onset and prolong the duration of analgesia. produce sedative effect with stable haemodynamic parameters. increase the artery and vein diameters to ease AVF surgery. Combination of dex with long acting LA for AVF creations is better not only for the pt (rapid onet, prolong duration, sedation effect, hemodynamics), but also for the surgeons.

Thank you

vessels diameter DIFFERENCE pre & post block Dex 100 Difference: 3.75-3.7 = +0.05mm 3.75mm 3.7mm Dex 50 Difference: 3.73-3.7= +0.03mm 3.73mm 3.7mm Brachial a. diameter difference in comparison of group: 0.02mm

Dermographic Data Group Dexmedetomidine 50 μg (n= 23) P- value* Mean SD Age (years) 57.59 12.44 60.67 9.02 0.12 Weight (kg) 61.7 8.94 58.59 8.91 0.24 Height (cm) 160.52 8.25 156.92 7.29 There is no significance in terms of age, weight & HT *Independent T-test

HOW U DO Sample Selection? Patients divided into: group A (dex 50μg) and group B (dex 100μg) using block randomization as below: 1. Six ballot cards will be put inside the envelope. Each of the cards stated 6 different sequences of grouping (AABB, BBAA, ABAB, BABA, ABBA, and BAAB).  2. A staffnurse was assign to pick One card be randomly - to decide the group for the first four patients. 3. This will be followed by other cards until all 6 sequences were completed. 4. The randomization will be continued again as above until the total samples of collection are completed

2. why do you say it is double blinded? patient & operator do not know 3. why do u compare 50 & 100? for ideal dose – prev study actually shows effect of severe bradycardia in dex100 group. 4. how do you prepare the drug? (1 ml of D100 vs 0.5ml of D50 + 0.5ml of NS) + 20ml of 0.5% Levobupivacaine 5. Why do u use ramsay score in stead of BIS postulation, more study is on going with BIS 6. how do you confirm sensory block? Onset of sensory block was defined by completion of the local anaesthetic infiltration to development of score 2, using a 3-point scale by pinprick test (0 = normal sensation; 1 = blunt sensation; 2 = nil sensation). Duration of the sensory block was defined as from the onset time until VAS more than 4.

7. how do you confirm motor block? Complete motor block = score 2 using modified Bromage three-point scale 0 = normal motor function with full flexion and extension of elbow, wrist and fingers; 1 = decreased motor strength, with the ability to move fingers only; 2 = complete motor block with in ability to move even the fingers. 8. how do you monitor duration of block? time interval between the end of LA administration and the recovery of complete motor function of the arm and forearm (score 0 ). Duration of the motor and sensory block been monitored by the ward SN and been confirm by the history taken by the investigator from the patient itself. Sensory and motor blocks were evaluated every 2 minutes until present of the block, every 10 min during the surgery, and 1 post surgery and subsequently 4 hourly. 9. Is it safe to use high dose of dex? No - Brumnet et al 2008 10. how do you measure the vessels? measuring vessels diametre is by measuaring image in ultrasound. landmark is at creast line of the upper limb which is blocked. largest brachial artery & basilic vein inner diameter will be taken pre and post block. the contra side is, it is only measured by single operater and is very operater dependent