Adjuvant to Ropivacaine

This is to certify that this dissertation titled, “Comparison of Epidural Dexmedetomidine Vs Magnesium Sulphate used as Adjuvant to Ropivacaine for Analgesia in Post Thoracotomy patients” (A prospective, controlled, double blind randomized study) submitted by Dr. MILANJYOTI PATAR in partial fulfillment for the award of the degree of DOCTOR OF MEDICINE in Anaesthesiology, to The Tamilnadu Dr.M.G.R Medical University, Chennai is a bonafide record of work done by him in the INSTITUTE OF ANAESTHESIOLOGY & CRITICAL CARE, Rajiv Gandhi Govt General Hospital ,Madras Medical College, Chennai during the academic year 2015-2018.

The mechanism of dexmedetomidine acting perineurally has not been well studied. Like clonidine, dexmedetomidine can enhance the degree of hyperpolarization by blocking the Ih current (generated by low-grade stimulation and activa- tion of Na + /K + pump). 10 Animal studies have shown that the addition of dexmedetomidine to local anesthetic would increase the duration of sensory and motor blockade in a rat model of sciatic nerve blockade. 18 A study has been per- formed to compare two different doses of dexmedetomi- dine, 1 and 2 μ g/kg respectively, along with 0.25% bupivacaine used alone in FNB for postoperative analgesia after TKA. Consequently, they found that dexmedetomidine at 2 μ g/kg dose in FNB showed better analgesic effect than that at 1 μ g/kg after TKA. However, they only evaluated the effect of dexmedetomidine in providing analgesia, but failed to assess early ambulation. 19 Another study showed that the addition of dexmedetomidine 1 μ g/kg to 0.25% bupivacaine in thoracic paravertebral blocks (PVB) in patients under- going modi fi ed radical mastectomy improved the quality and the duration of analgesia, and also provided an analge- sic sparing effect without any serious side effects. 20 Thus, in our study, the dosage of 2 μ g/kg dexmedetomidine was selected as adjuvant to ropivacaine. Similar to previous studies, dexmedetomidine showed no adverse cardiovascu- lar responses.

The clonidine in the doses upto 150 μg being associated with minimal side effects. 10 As such, no single study has been done with 90 μg of clonidine as an adjuvant with ropivacaine in brachial plexus block. Which prompted us to use clonidine in the dose of 90 μg as an adjuvant to ropivacaine. In this study, statistically significant improved onset and duration of sensory and motor blockade in the group RC was observed as compared to group R. We also observed significant prolonged duration of analgesia of 799.00 ± 78.88 min in the study group as compared to the control group where it was 584.17 ± 36.0 min. El Saied A.H et al. 11 evaluated the effects of clonidine in the dose of 150 μ with 40 ml 0.75% ropivacaine in brachial plexus block and found that the duration of analgesia was significantly prolonged in the clonidine group (828 ± 35 min) as compared to control group (587 ± 40 min). Sidharth S Routray et al. 14 studied 150 μ clonidine with 35 ml 0.5% ropivacaine in supraclavicular brachial plexus block and

Adjuvant agents are pharmacological drugs that, when co-administered with local anaesthetic agents, may improve the speed of onset, the quality and / or duration of analgesia with desirable sedation. A wide range of drugs has been assessed for both neuraxial and peripheral nerve blocks. α-2 adrenergic agonists have both analgesic and sedative properties when used as an adjuvant in regional anaesthesia [5] . Dexmedetomidine is a highly selective α2 adrenergic agonist with an affinity of eight times greater than clonidine. There is no such study which has compared the dose equivalence of these drugs but the observations of various studies have stated that the dose of clonidine is 1.5−2 times higher than dexmedetomidine when used in epidural route [6] . The anaesthetic and the analgesic requirement get reduced to a huge extent by the use of these two agents. The aim of this study is to compare dexmedetomidine and clonidine as an adjuvant to ropivacaine for epidural anaesthesia in lower abdominal and lower limb surgeries.

Addition of epinephrine to ropivacaine has no limiting effect on the systemic absorption of ropivacaine. Systemic absorption can produce effects on the central nervous and cardiovascular systems. At blood concentration achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility and peripheral vascular resistance are minimal. However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias and to cardiac arrest. In addition, myocardial contractility is depressed and peripheral vasodilatation occurs, leading to decreased cardiac output and arterial blood pressure.

24. Vaghadia et al 47 (1999) in A multicentre trial of ropivacaine 7.5 mg/ml vs bupivacaine 5 mg/ml for supraclavicular brachial plexus anaesthesia, 104 ASA I-III adults participated in a randomized, double-blind, multi-center trial. They received 30 ml of either ropivacaine 7.5 mg/ml or bupivacaine 5.0 mg/ml for subclavian perivascular brachial plexus block prior to upper limb surgery. Onset and duration of sensory and motor block in the distribution of the axillary, median, musculo-cutaneous, radial and ulnar nerves were assessed. Finally it was concluded that 30 ml ropivacaine 7.5 mg/ml(225 mg) produced effective and well tolerated brachial plexus block of long duration by the subclavian perivascular route.

Administering dexmedetomidine as an adju- vant in brachial plexus blocks is an off-label use. Concerns are still left on the safety of dex- medetomidine’s off-label use. Although a cou- ple of studies [1, 6, 19, 21-24] have demon- strated the dexmedetomidine’s off-label use is safe and effective, adverse events are also noted in our study. MAP and HR levels were affected negatively using dexmeditomidine as an adjuvant in brachial plexus blocks, com- pared to the baseline. Fourteen patients in the Group RD suffered from bradycardia, although all of them were reversed by intravenously administering 0.5 mg of atropine. No significant hypotension, excessive sedation, or other ad- verse events were observed in this off-label use. Recently, Han and colleagues [25] found that rat axillary brachial plexus with a mildly curvilinear incision exposed to high-dose (40 μg/kg) dexmedetomidine did not show signifi- cant apoptosis and degeneration. Although fur- ther studies are still required to confirm the results, few current studies indicate that the safety of this off-label use of dexmedetomidine is in doubt.

Results: The mean dose of bolus epidural ropivacaine was significantly lower within the first 6 h after surgery in the dexmedeto- midine group, compared with the fentanyl group (0.029±0.030 mg/kg/h vs. 0.053±0.039 mg/kg/h, p=0.012). The median pain score at postoperative 6 h was also lower in the dexmedetomidine group, compared to the fentanyl group [0 (0–1.0) vs. 1.0 (0–3.0), p=0.039]. However, there was no difference in the need for rescue analgesia throughout the study period between groups. Conclusion: The use of dexmedetomidine as an epidural adjuvant had a significantly greater analgesic and local anesthetic-sparing effect, compared to fentanyl, in the early postoperative period in children undergoing major orthopedic lower extremity surgery.

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Background: Supraclavicular brachial plexus block is a frequently performed procedure to provide anesthesia and postoperative analgesia for upper limb surgeries. Bupivacaine is the most commonly used anesthetic, but ropivacaine has been successfully used as it is less cardiotoxic, less arrhythmogenic. Adjuvants to local anesthetics enhance the quality and duration of analgesia.

The results of this study show that 1 µg/kg DEX (as an adjuvant to ropivacaine) for SAPB is more effective than 0.5 µg/kg DEX. The analgesic effect of 1 µg/kg DEX signi fi cantly reduced both the consumption of sufentanil and pain intensity, while stable hemodynamics were main- tained. Additionally, the time to the fi rst dose of rescue analgesia, number of patients who required rescue analge- sia, total dose of rescue analgesia, and postoperative nau- sea were all reduced in the group involving 1 µg/kg DEX. VATS has been widely used as an alternative to thor- acotomy in the last 20 years due to lower postoperative pain, fewer complications, and improved quality of life. 18 However, 30 – 50% of patients undergoing VATS still have moderate-to-severe pain. 2 This may be due to local damage caused by the skin incision, retraction, dislocation of the costovertebral joints, injury of the intercostal nerves, irritation of the pleura by chest tubes, and visceral pain. 19 As a result, improved postoperative analgesia is a particularly important component in fast-track VATS applications, as mentioned in the latest guidelines of the European Society of Thoracic Surgeons (ESTS). 20 Opioids, nonsteroidal anti-in fl ammatory drugs (NSAIDs), Table 2 Intraoperative Variables Between the Two Groups

Birbal Baj, Vandana Tyagi et al., 18 (2013) on a comparative study of effects of clonidine added to ropivacaine versus plain ropivacaine during supra clavicular brachial plexus block in which total of 60 ASA Grade I to IV patient were taken and randomly allocated into 2 groups comprising 30 patients in each. Group I (control group) included patients which were given 30 ml of 0.75% ropivacaine (225 mg) and Group II (study group) included patients which were given 30 ml of 0.75% ropivacaine (225 mg) with 0.4 ml (60 μg) clonidine. They found that mean duration of Analgesia in Group II was 576.96 ± 81.45 min which was prolonged than Group I which was 442.14 ± 86.47 min, mean duration of sensory block in Group II was 551.07 ± 84.09 min compared to group I which was 422.50 ± 87.75 min and mean duration of Motor block in Group II was 533.75 ± 84.36 min compared to group I which was 403.39 ± 87.91 min. This was similar to our study. Asad Mohammad, Sangeeta Goel et al., 19 (2016) on Clonidine as an Adjuvant to Ropivacaine in Supraclavicular Brachial Plexus Block in which 60 adult ASA grade I and II patients scheduled for upper limb surgeries were randomized to receive either 30 ml of 0.5% Ropivacaine + 0.6 ml saline (Group R) or 30 ml 0.5% Ropivacaine and 0.6 ml (100 μg) of Clonidine (Group RC) in supra- clavicular block. They found that mean duration of analgesia in group RC was 912 ± 75.8 min which was prolonged than in group R which was 793 ± 75.4 min, mean duration of Sensory block in group RC was 885 ± 57.8 min compared to group R which was 676 ± 48.46 min and mean duration of Motor block in group RC was 770 ± 38.9 min compared to group R which was 470 ± 38.9 min. This was similar to our study.

dexmedetomidine but were able to manage easily. Incidence of bradycardia were comparable in both groups. Noepisode of respiratory depression was noted in both the study groups which are more common with opioids. Dexmedetomidine may be a better adjuvant to Ropivacaine intrathecally in the prolonging duration of analgesia with fewer side effects.

4. Sarabjit Kaur,et al (26) ( 2014) conducted a prospective study to compare analgesic effects of epidurally administered ropivacaine and dexmedetomidine when compared with plain ropivacaine in undergoing lower limb surgeries . They randomized 100 patients into two groups as group A and B . Group A (n = 50) patients received plain ropivacaine in the epidural and Group B (n = 50) patients received dexmedetomidine as adjuvant to epidural ropivacaine . They had compared the two groups with respect to time to onset of sensory level at T10, time to maximum sensory and motor block and time of rescue analgesia . They had observed that significant difference was seen in relation to the duration of sensory block prolonged in group group B (535.18 ± 19.85 min) than group A (375.20 ± 15.97 min ),p=0.000 and similarly duration of motor block prolonged in group B( 385.92 ± 17.71 min) than group A (259.80 ± 15.48) p=0.000 , prolonged duration of post-operative analgesia seen in group B (312.64 ± 16.21 min versus 496.56 ± 16.08 min in Group B ) and low doses of rescue analgesia needed in Group B as compared to Group A . Better sedation score was seen in Group B . Finally, they had concluded that epidural dexmedetomidine as a better adjuvant to Ropivacaine when compared to plain Ropivacaine.

Dexmedetomidine is a selective -2 agonist which provides sedation, anxiolysis, hypnosis, analgesia and sympatholysis. Dexmedetomidine has an eight-fold greater affinity for α2 adrenergic receptors than clonidine and much less α1 effects. A major advantage of dexmedetomidine is its higher selectivity compared with clonidine for α2Areceptors, responsible for the hypnotic and analgesic effects of such drugs. Therefore we performed a randomized, control prospective study to compare the effect of dexmedetomidine and fentanyl as adjuvant to ropivacaine 0.75% for epidural Anaesthesia in patient undergoing elective orthopaedic lower limb surgery and concluded that dexmedetomidine is a better adjuvant to ropivacaine than fentanyl for epidural analgesia with better quality of analgesia, prolonged duration of analgesia, higher sedation scores and no significant side effects

So we planned this study by using Dexmeditomidine as an adjuvant to ropivacaine in spinal anaesthesia and studied its effect on onset and duration of sensory and motor blockade, hemodynamic stability and incidence of side effects if any. In our study 27 males, 3 females and 24 (80%) patients of ASA I and 6 (20%) patients of ASA II respectively in Group R, while in group RD males, 5 females and 26 (56.55%) patients of ASA I and 4 (13.33%) patients of ASA II respectively, and found that this data was statistically comparable between two groups (P>0.05).

produced by ropivacaine hydrochloride increased by approximately 40 min. Sinatra R S et al(12) reported longest duration of pain relief in epidural bupivacaine fentanyl citrate than bupivacaine alone or bupivacaine lidocaine combination. Exact mechanism of prolonged analgesia in epidural fentanyl citrate group not known but may be due to lipophilic property of fentanyl citrate so the drug gets absorbed into the epidural vasculature and epidural pad of fat and slowly gets released and provides prolonged duration.

This study had several limitations: 1) There was no con- centration gradient, which was to reduce the number of groups and false-negative results from multiple comparisons. 2) We did not include a control group based on considering the needs of analgesia and the maximum patient bene fi t. 3) Clinical use of adjuvants may prolong the blocking effect of low- concentration ropivacaine, but that was not assessed in this study. 4) Plasma ropivacaine levels at different concentrations were not measured. Although previous studies have not reported any adverse reactions associated with SAP block, higher concentrations may carry a greater risk. 24 The results should be con fi rmed in a study with longer and more invasive follow-up and a larger study population.

and tourniquet in both the groups showed no difference statistically. There was no significant difference in variations in hemodynamics after tourniquet release. Four patients in group 1 perceived intraoperative tourniquet pain and this was nil in patients who received fentanyl along with ropivacaine. The incidence of nausea and vomiting was present in patients who received fentanyl along with ropivacaine. Duration of post op analgesia (VAS > 5) in group 1 was 120.76 ± 20.755 mins and in group 2 it was 137.52 ± 24.036 mins and this difference is statistically significant (p < 0.05). CONCLUSION: We conclude that ropivacaine 0.2% with fentanyl 50 mics in intravenous regional anaesthesia has good anaesthetic efficacy, lengthened post operative analgesia and less incidence of intra operative tourniquet pain with minimal alterations in hemodyanamics after tourniquet release when compared to ropivacaine 0.2% alone.

The present study was conducted to compare 0.5% ropivacaine and mixture of 0.5% ropivacaine with dexamethasone in ISB used for shoulder arthroscopic surgeries. Primary outcome measure was to evaluate the effect of mixing dexamethasone on duration of analgesia provided by ISB. Secondary outcomes measures were onset time of sensory and motor block, pain scores by visual analogue scale score (VAS), analgesic consumption in 24 h and interscalene brachial block-related complications.