DISSERTATION SUBMITTED IN FULFILMENT OF THE

Tekspenuh

(1)A PROSPECTIVE STUDY OF ANA LG SIA EFFIC PLASMA ROPIV ACAIN. ON ENTRA Tl N. CY AND. FT R PECS II. al ay a. BLOCK IN PATI "'NT UNDER. of M. DR. KHA W SOON KEONG. rs i. ty. PERPUSTAKAA.N PERUBATAN TJ. DANARAJ UNIVERSJTI MALAYA. ve. DISSERTATION SUBMITTED IN FULFILMENT OF THE. ANAESTHESIOLOGY. U. ni. REQUIREMENTS FOR THE DEGREE OF MASTERS IN. D PARTM NT OF ANA STH SIOLOGY UNIV RSITY OF MALAY A KUALA LUMPUR. 2017. ~il ~i. 1111~11 fm11if1i1A617122758 iilil~~if~i~l11. II" ~ 1111.

(2) UNIVERSITY OF MALA YA ORIGINAL LITERARY \YORK DE L\RATlON Name of Candidate: KHAW. N I'E. N. I. l.C Number. :. Matric Number. : M. Name of. : Mast 'rs in Ann isth 'Si 1 g. Title of Thesis. ()Q_ 1. : A prosp cti stud f 1111]0 si efficacy and plasma Ropivacain on ntration aft r PECS II block in patients undergoing ma t t m. Field of Study. nae th iology. a. cgrcc. ~I. al. I am the sole author/writer of this Work; This Work is original; Any use of any work in which copyright exists was done by way of fair dealing and for permitted purposes and any excerpt or extract from, or reference to or reproduction of any copyright work has been di clo d expressly and sufficiently and the title of the Work and its authorship ha e been acknowledged in this Work; I do not have any actual knowledge nor do I ought reasonably to kn w th t the making of this work constitutes an infringement of any copyright work; I hereby assign all and every rights in the copyright to thi Work to th University of Malaya ("UM'), who henceforth shall be ov ncr of the copyright in this Work and that any reproduction or use in any form orb an means whatsoever is prohibited without the written consent of UM ha ing been first had and obtained; I am fully aware that if in the course of making this W rk I ha c infringed any copyright whether intentionally or otherwise, I may be subject to legal action or any other action a may be determined by UM.. U. ni. (6). ity. (5). ve rs. (4). of. M. (I) (2) (3). ay. I do solemnly and sincerely declare that:. andidates. ignature. ate: '2. 'ljlM~//2-0fl DR~OON KEONG. :. No. Pendaftaran Ptnuh MPM 48194. Subscribed and olemnly declared beforePegawal f'erubatan Sarjane. :J1batan Anesteslologt i-usat Perubatan Unlverslti Malaya. Witness's. ignatur. ate: 2i./) / ·2-01r-. Name:. Designation:. DI MOH ~j0, ,,, rjnltar.m P. 11,111. Ml'M 25'311. Pfln•.y,1 .h l<'.unun 1. l.il.J1.11 n /\n io;l i .•tolo!Jl flu 1 ~. ,,,,. t. n Jn111 1• \ti M lny.1. l1.

(3) ABSTRA. T. Background and Objective: The introduction. has changed the choice for providin. 1. of novel ultrusoun I guid d Pees block. inn .sth .si. mi or malu .sia to th' upper part of. 1. the anterior chest wall. This tcchniquc v as l 1t 'r id ipt .d P. ll block) to provide. better coverage for more ext nsivc procedures, 'SP" i llv involving the axilla. We would like to conduct a prospc 'ti c d _ riptiv. stud 't. m asure the safety level of. Method:. After obtaining. approval. ya. Ropivacaine and the analgesic efficacy for PECS II block using 30ml Ropivacaine 0.5%.. from the UMMC. Medical. Research. Ethics. al a. Committee (20165-2443) and written informed general anaesthesia (GA) and regional block consent, adult female patients undergoing unilateral mastectomy. and chronological. of. of anaesthesia,. M. enrolled. PECS II block was performed with ultras und. clearance were prospectively guidance before induction. with axillary. pecifically. ample pla. '. r. d in th. ity. obtained by a piration from a large bore venous cannula. blood. antecubital fossa. All participants received a total dose of R pivacaine not more than. rs. 3mg/kg, which is diluted with 0.9% saline to constitute 30ml of Ropi a aine 0.5%. ni ve. solution concentration. Venous blood was sampled from the blood taking canulla at I 0, 20, 30, 45, 60, 90, and. wa. minute. after Ropivacaine. administration.. mea ured with liquid chr matography-. U. Ropivacaine concentration. 120. spectrometry method at the Pharmacology. department. Pia ma. tandem ma. Medical Faculty,. ni er it. Malaya. Results: There were 6 patient. wh. succe. fully c mplet d thi. were aged between 52 and 71 (mean 63) years old. The weight of th betw .cn 54 and 70kg (rn .an 6 kg). Total Ropivacainc u eel for , at l 50mg. In our study, th 're w ire no iigns or. durin. 1. th· stud. p 'riml. 'I h ·. pg/ml ( I 0. I, n111. I\. 111 •1111. V. or. peak v .nou» plasma. N. t. i it. r pati mt \ a fix 'd en in th patient. .onc mtrati in (. 1.80-2.(1 I). 'I Ii. 111 .diun time point. or ma. irnum. 111.". wa -· '-. ' n icntrati n 111.

(4) (Tmax) of Ropivacaine occurred at 37.Smin (range 20-60 min). Th high. t individual. venous plasma concentration ( max) was 2.61 p r/ml oc .urred at 45 min.. Conclusion: This study dcmonstrnt unilateral. P. II block in adult. 'S. fcmnl. thnt the use. )r. is s rte withou:. 'S. or. 'X'. toxicity.. al a M of ity rs ni ve U. 111. the. .eding the toxic level.. ya. There were no patients report 'd to h l 'signs. I 50ml?. Ropivacaine.

(5) ABSTRAK ulunsoun i novel l 'll undu P 'cs blok telah. Latar Bclakang dan Objcktif: Pcngcnal.m bcrubah pilihan. untuk mcnycdiakan. :111 'St 'Si 1. it iu un II~ 'sin untuk bahagian ata. d in. dinding dada. Tcknik ini kcmudiann u discsu iiknn. P .cs 11 l lok) untuk menyediakan. liputan yang lcbih baik untuk pros xiur. m~ I .bih luas, t .rutamanya yang melibatkan. bahagian. kuji n dcskriptif bakal untuk mengukur tahap. Ropivacainc. 30ml Ropivaeainc. Kaedah:. dan kcbcrkc anan analg. ik untuk Pees II blok menggunakan. 0.5%.. Selepa. mendapat. kelulusan. Perubatan PPUM (20165-2443). Jawatankuasa. Etika. dan kebenaran bertulis dimaklumkan. pesakit dewasa wanita menjalani. mastektomi. M. dan blok stempat,. daripada. ya. keselamatan. Kami ingin m cnjalunkan. al a. kctiak.. Penyelidikan. bius umum (GA). satu belah dengan. of. pelepasan axillary telah didaftar seeara aktif. Pees II blok dilakukan dengan bimbingan ultrasound. scbelum induksi ane te ia, dan sampel darah kronologi. ity. aspira i dari kanula bore vena besar diletakkan. dipcrol 'hi dcngan. ccara khusus dalarn lckuk nnt .cubitnl.. dengan 0.9% masin untuk membcntuk. ni ve. dicairkan. rs. Semua peserta menerima sejumlah dos Ropivaeaine tidak lcbih daripada. U. diukur dengan Farmakologi,. Kcputusan: adalah. diberi Ropivacaine.. ciring chromatography-. Fakulti Pcrubatan,. (min (>.kg).. dit 'l<1pka11 pudu 150111 ntou k ·toksiknn. 1•. _o, . 0,. ji im cccair di Jabatan. ni crsiti Malaya.. Tcrdapat 6 pcsakit yang bcrja a rncnarnatkan. 1. darah pada I 0,. Kcpckatan pla ma Ropivacainc. kacdah .pcktromctri. bcrusia antara 5_ dun 71 (min 63) tahun.. clan 70 k. ang. 30ml Ropi acaine 0.5% kcpckatan. larutan. Darah vena telah di ampel daripada canulla pengarnbilan 45, 60, 90, dan 120 minit selepa. mg I kg,. protokol kajian ini; mer ika. rat daripada. pcsakit adalah antara 54. Jumluh Ropi ucain • di runukun untuk Dulam kujiun kami, liclak ada tanda-tanda. s sl 'Ill smur dilihnt. s tiap. r \ akit. I !ah. s st 111 kardiova ular. dulu111 p ·snkit s ·pnnjnng t ·mpoh kajinn.. Pun ·ak. v.

(6) kepekatan plasma vena (Cmax ) adalah 2.12 pg/ml (SD 0.-t I, julut I .1.'0-_.6 \ ). Titik ma a median kepekatan. maksimum. 20-60 min). Kcpekatan. (Tmax) daripudn Ropi,. :1. .nine h .rlaku. ii _ 7.5min (julat. individu plasmu (<.'nH\:\) :1 blah _,( l p~ I ml b .rlaku pada 45. 111111.. Kesimpulan:. I ajian ini rn .nunjukkun b ihnw 1 pcnggunnan l SOmg Ropivacaine dalam. Pees II blok pada wanita dcwasa adalah pcsakit. dilaporkan. mcmpunyai. s ilnmat. tanda-tanda. tanpa melebihi tahap toksik. Tiada. k tok ikan. sistem. saraf. and. U. ni ve. rs i. ty. of. M. al. ay. a. kardiovascular.. sistem.

(7) ACKNOWLEDGEMENT. J would first like to thank my thesis advisor Ass 1 .iute Prof. Shahnaz Bin Hasan Medical. of the D .pnrtm ·nt of Ann .sth. enter. The door to A/Prof.. 'Sil. logy,. 'S ·or. Dr Mohd. niv rsity of Malaya. hahn iz office w ~ always open whenever 1 ran. into a trouble spot or had a question ab ut m. r sear h or writing. He consistently. allowed this paper to be my own work, but. te r d me in the right the direction. whenever he thought I ne ded it.. ay. a. I would also like to thank th experts who were involved in the validation survey. for this research project: Dr Azrin Mohd Azidin (Consultant Anaesthesiologist, Hospital Hospital. al. Kuala Lumpur), Dr. Beh Zhi Yuen (Anaesthesiologist,. Kuala Lumpur).. M. Without their passionate participation and input, the validation survey could not have. of. been successfully conducted.. ty. I would also like to acknowledge Professor Gracie Ong. Univerversity. rs i. Department of Anaesthsiology,. Malaya. Medical. iok Yan (Pr fcs or in enter) wh. pro ided. ni ve. insight and expertise that greatly assisted the research.. Finally, I must express my very profound gratitude to my par nt and t. U. spouse, for providing me with unfailing support. and continuou. m. enc uragement. throughout my years of study and through the process of re earching and. riting thi. thesis. This accomplishment would not have been possible without them. Thank you.. Dr l haw. oon I .ong. II.

(8) TABLE OF. ONTENT ll. Abstract. ll1. Acknowledgments. Yll. List of Tables. lX. List of Symbols and Abbreviations. lX. List of Appendices. lX. Chapter 1: Introduction. 1. ay. a. Original Literary Work Declaration Form. Chapter 2: Literature Review. M. 3.1 Blood processing. al. Chapter 3: Material and Methodology. of. 3.2 LCMSMS procedure. rs i. Chapter 5: Discussion. 4 6 6 8. ty. Chapter 4: Results. 2. 12. 5.2: Further study. 12. Chapter 6: Conclusion and Recommendation. 14. References. 15. U. ni ve. 5.1 Limitations. 17. Appendix. 111.

(9) LIST OF TABLES Table 4.1: Patient characteristic, Table 5.1:. average dose. Summary of previous studi. 'S. or Ropiv. 1. .uinc.. and its r 'Sult on. LIST OF YMBOL. m. ix. mt· and Trnax and Trna ·. AND ABBR YI TlONS. BMI - Body Mas Index Cmax - maximum venous pla ma cone ntration HKL - Hospital Kuala Lumpur y tcmic Toxicity. a. LAST - Local Anaesthetic. al. PECS Block- Pectoral nerve block. ay. LCMS - tandem mass liquid chromatography. M. QLB - Quadratus Lumborum Block. of. RSB - Rectus Sheath Block TAP - Transversus Abdominis Plane Block. ty. Tmax - time point of maximum concentration. of Ropivacaine occurred. rs i. TPVB - Thoracic paravertebral block. U. ni ve. UMMC - university Malaya Medical Center. LIST OF APPENDI. APPENDIX A: Data collection Sheet APPENDIX B: Flow APPENDIX. :. hart of Methology. on ent form f r. APP "'NDIX D: Patient Information. linical Re carch heel. ES.

(10) CHAPTER 1: INTRODUCTION. Regional. anaesthesia. techniques. arc common. tu Ialitics. u sed to provide. analgesia following both upper and lower .xtr 'mity suru .ri .s. lt is al 'O often u ed for r '111ivdy n 'W trun '11 block, fir t de cribed. truncal procedures for the same purpos '. in 2012 by Blanco, called the p .ctoralis. n crvc blo 'k P. used successfully. . pit. for breast surg r .. it. l and ll block) has been. d s ription and success in clinical. practice, the extent of y tcmic ab orption of lo al anaesth tics from this truncal plane block has not been described to date. data on chronological. a. there has been no published. ay. To our knowledge,. ropivacaine concentration after PECS II block. Therefore, we would like to conduct a tudy to measure the safety level of Ropivacaine. and th. efficacy for PECS II block using 30ml Ropivacaine 0.5%, a well a t. M. analgesic. descriptive. al. prospective. of. determine the maximum venous plasma concentration (Cmax) and time point of that. ty. maximum after the start of injection (Tmax).. rs i. Primary outcome:. To measure the chronological. changes in venous concentration. ni ve. PECS II block, in which the calculation for the time point Ropivacaine occurred (Tmax) and maximum. venou. of Ropi acam. f maximum cone ntration. pla ma concentration. U. mandatory. Thi would determine whether the peak pla ma Ropi acain level is within the safety level allowed. The venou. aft r. threshold valu. f. ( max) ar. con entrati n. of y temic t. icit. is 2.2 µg/ml. The re ult of thi study might change future rec mmended do ing regimen for P CS 11 block practice using R pivacaine. econdary. utcome. To de .cribc the quality or cnsory blockade in t .rms of dermal logical duration. or th'. anulg .sic effect.. xtent and bl. k.

(11) CHAPTER 2: LITERATURE. ln the past, thoracic epidural. analg 'sin\1). REYIE". was th' aold. .tundard. regional. technique for breast surgery while thorn cic p irav 'rt .brnl th 'ks (TPVB -)l2l were the approach.. complications, inadvertent. However,. though rare intrava cular. uch. both. t cchni 1u .s " ire. !L. pu 'Um thorax, total. punctur . TP B i. anesthesia for surgery, and not all anesth Paravertebral. block alway. gen rall. 1. 'L. sociated. with. serious. pinal anaesthesia. and. performed before general. iologists feel comfortable doing the block.. ha the risk of iatrogenic pneumothorax and nerve injury.. ay. Additionally, it cannot be performed in the supine position.. a. alternative. al. The introduction of novel ultrasound guided Pees block has changed the choice. This block is easy to perform and avoids complications. associated with neura rial. of. 4). M. for providing anaesthesia and/or analgesia to the upper part of the anterior chest wall. (3•. techniques or TPVBs. Pees block has recently been given Grade A recommendation. after US-guided Pees block has been rcported.i'" first described by Blanco. ni ve. Pees Block wa. in 2011. Y1. This ultra ound-guid 'd. inter-fascia! plane block involved placing local anae thetic (LA) in the plan. U. the pectoralis. thoracoacromial 0.25%.. major and minor mu cles, adjacent artery ("Pees" or "PE. This block is particularly. to the pectoral. I" block) with 0.4 ml/kg I. u eful for patient. during reconstructive breast cancer urgery. betx e n f th. branch. bupi acain. who have brea t e pander placed. r ub pect ral prosthe e .. This technique wa later adapted (PE. II bl ck) l4l to pro ide bctt 'r o. for more e ten sivc proc xlurcs, 'specially involving PE. f. lb to Ill studies.i" To date, no r port. rs i. complication. of level of evidences. ty. with the support. the a ilia. The fir t inj. rage. ti n i a. I block with I 0 ml or LA. The second injection of A is perform cd more lateral!. in the plan' b .tw · ·11 the p · ·toralis minor and scrratus ant .rior mu. I'. at th' Jc, I of th· third nud fourth ribs with .. Oml L/\. I nshundy. and Abba. re entl. r 'P rt id that.

(12) PECS II block was able to reduce intraopcrativc pain, postoperative. morphine consumption,. vomiting (PONY) in patients undcrgoin. l. fcntanyl. requirem nt, po t perative. as well as l ostop .rutivc nau ea and (7). B. Dr Blanco had used Lcvobupi n .uinc is th' lo '11 m 1 isth 'ti' in his studies.' · 41 I lowcvcr, Ropi a mine is th' prcfcrrc with its better safety profile. lR\. a o on tri tiv. block. Several studies have evaluated. ) of choice. L s in regional anaesthesia. ffect and preferential more sensory. the m a urement the maximum time to peak. (Tmax) and the ma imum concentration. 1,. l9. (Cmax) after. transverse abdominis plane block no,. 1,. 11. ay. regional blocks such as intercostal blocks. of Ropivacaine. a. concentration. (L. quadratus lumborum block <12\ and scalp block <13l. The above blocks were evaluated,. al. with intercostals block and scalp block found to have the shortest time to reach Tmax, at. M. l l minutes<9l and 15 minutes' 131respecti vel y.. system ( NS) symptoms. the maximum tolerated. rs i. changes as compared to bupivacaine; plasma concentration. cardio as ular. and less pronounced. ty. for central nervous. of. Knudsen and colleagues had shown that ropivacaine has a higher tolerated d. of ropivacaine is 2.2µg/ml.(8l Having. pla ma 'Om' ntrntion aid that,. e eral. tudi. ni ve. revealed that despite having higher plasma ropivacaine mea ured of more than 2.2µg/ml, the subject does not experience significant. NS and. V. ymptom .. l9-i. U. In this study, we will use venous plasma ropivacaine. measurement significant. as this method is less invasive.. difference. for mea uring. arterial. 1.. 13l. level for ampling and. In a study by Behnke and central. ropivacaine concentration after 5 minutes time cour e.(91. mi. d. th re i. no. pla ma.

(13) CHAPTER 3: MATERIAL. AND M THODOLOGY lul lY \ lcdi .al. After obtaining ethics committee approval ( ni crsit · of and written inform 'i. Lumpur, Malaysia). adult female patients undergoing. ''11. .rnl inn .sth 'sin (. enter, Kuala. ) and block consent,. uni Int crnl m istc 't vmy with . xillary clearance were. prospectively enrolled. [nclusion criteria: ASA I, 2 and 3 (without. ignificant Ii r or r nal impairment). ay. a. Age above 18 year old Able to give consent. M. al. Body weight > 50kg. Patient'. of. Exclusion Criteria:. r fusal and inability to give consent or cooperation during procedure. rs i. BM1>35. ty. Allergy or sensitivity to local anaesthetics. ni ve. All patients recruited received 30ml Ropivacaine. Every patient was provided with Oral Paracetamol. I g and. ral Celebre. k.. n. T. Upon arrival in the induction room, an 1 - or 20-gaug. intravenous catheter wa placed in the upper limb contralateral to the urgical site for peripheral intravenous access was chosen if required. Premedication if required during block procedure at the juri diction of th mg intravenously. 11 bl. 200mg. U. call for multimodal analgesia.. 0.5% during P ~. and/or Fentanyl 25 - 100 ug intravenou ly).. given ii' the I aticnt r .cci id sedation. (nasal cannulas at. monitoring (non-inva sive blood pres ure electrocardiogram,. appli ·cl throu ihout th· pro· .dur ·.. ite.. ther. wa offered. pcrator (Midaz lam I upplem ntal o · gen '· a /min) and and pul e. tandard im tr ). \J. a.

(14) After induction of anaesthesia, blood samples ' er' obtained by a piration from a large bore venous cannula spcci Iically. pluc .d in the ant' .ubital. fo ssa on the. contralateral side to the cannula used for ndruinist niu ' Ilui is and m 'di .ation . The infraclavicular. and axillur. nr 'n of the n1 .rntivc sit' w 're cleaned with. solution. P. 11 block \ as pcrf rm db' a study investigator (or by a. senior trainee experienced. in the tc hniqu ', un er the dir ct supervision of a study. chlorhcxidinc. investigator).. Images were obtained u ing a. (Sonosite lnc., Bothwell. ono ite M-Turbo® ultrasound' machine. WA, U A) with an L38x l 0-5 MHz 38 mm broadband linear. ay. a. array probe. Blocks were performed with a 150 mm Stimuplex® needle (B-Braun Medical, Bethlehem, PA, USA) using an in-plane approach. The skin point of puncture were identified with. al. was infiltrated with 2% lidocaine and once the structures. London, UK) was inject d. between the pectoral muscles and 20 ml under Pectoralis. minor above the s rratu. as described. by Blanco".. Overall,. participants. received. a total d. f. ty. muscle. of. M. ultrasound, l 0 ml of Ropivacaine (Naropin 'Iv' AstraZeneca,. rs i. Ropivacaine not more than 3mg/kg, which was diluted with 0.9% saline to c nstitut 30ml of Ropivacaine 0.5% solution concentration.. ni ve. The duration from the end of the block to start. f the. urgical in i ion wa. recorded. Venous blood was sampled from the blood taking canulla at 10, 20, 30, 45, 60, ign. and. ympt m. f. U. 90, and 120 minutes aft r Ropivacaine admini tration. toxicity were also recorded if present.. General anesthesia was induced with fentanyl 1-2 mcg/kg, prop fl l 2and supraglotic. airway wa. u cd for ventilation.. scvofluranc or desfluranc with MA. Anae the ia wa. maintained. mg/kg ' ith. 0.8 - 1.0. lV Morphine total O. l mg/kg v a gi en. intraopcrat ivcly, Aller rccov .ry from anesthesia,. unit (PA. patient. were tran fcrr d t p t-ane th ti care. U) tor th' first - hours. Pui11 int .nsity was measured usinu. (I I 0 at r st.

(15) and during abduction of the ipsilatcral. upper limb.. duration of the block and the extent or dcrmutom. 'S. ccondurv end point. \osine,. 1. w re th. s .nsution of pain and cold. due to the block. The duration or th' blo 'k w 1s cv ilu it 'i bv m .asuring the amount of time that clap cd between comp! 't ion or th' hi) .k mi th' first ad mini tration of postoperative. rescue analgesia.. R 'Seu' 1111\ 1'Si1 was sub utaneou Morphine 0.1 mg/kg,. administered upon patient request. Sensory blocks wer. d 30 minutes after the blocks as. unable. patients had to undergo general anacthe ia once the blocks were performed.. ay. a. Plasma Ropivacaine concentration was measured with liquid chromatographytandem mass spectrometry method at the Pharmacology department, Medical Faculty,. 3.1 Blood processing. before drug administration. and at van u. of. Blood samples were collected. M. al. University Malaya.. amples were centrifuged at 4500 rpm fl r I 0. ty. intervals post-drug administration. The. rs i. min to obtain plasma. The plasma samples were transferred into cparatc cryo-vial tub' frozen and stored at -20 °. was extracted. ni ve. Ropivacaine. for further analysis. from plasma. ample. u mg a. impl. pr t. 111. precipitation method. I OOuL of plasma sample was taken and in ertcd into clean mi ro-. U. centrifuge tube. Then, 400uL acetonitrile (I 00%) wa added to precipitate the protein. The sample was vortexed for 20 seconds and centrifuged at 14,800 rpm for 15 minute to separate the supernatant. Then, 400uL of the upematant wa tran ferrcd to a n \ chromatography. glass vial. Total. I OuL of the c tractcd. ample wa. inje tcd into. L M M for analysis. 3.2 L 'MSM. procedure. The L /M /M syst 80. 0 trip! i-qundrupol. 111. consisted or two L -20A. and c up! d t an. XR pump. · tund nn nrnss spcctrornct -r ( hirnadzu,. ot. Japan). with a.

(16) turbo ion spray interface. The chromatographic analytical column Phenomcnex,. length).. 18 ( 150 mm l '111.!th. cmini-N). particle size 5µm) and Phcnorncnc ,. 1. separation was d tect d u mg an. nnini-Nx. x _, l. mm l.D,. I,' iu ir i .olumu (4mm lO x 2.0mm. Mobile phase A was I SmM ummonium form itc in w it 'r with 0.0 I% formic. acid, and mobile pha c. gr fo nc itonitrile. The initial gradient. consist cd of L. started from I 0% of mobile phase. from 0.01 mi nut. minute and hold for 7 minut . At 7.01 rninut. and then went up to 95% to 5. mobile phase B was set to 10% again. and hold for another I 0 minute . The flow rat \ a 0.3 mL/min. The retention times for of mlz 275.00-d26.10. a. with mass transitions. and m/z. ay. ropivacainc is 2.87 minute. U. ni ve. rs i. ty. of. M. al. 275.00-+84.0.. 7.

(17) CHAPTER. 4: RESULT. There were 6 patients who successful!. .ompl 'led this stu iy r rotocol; they were. aged between 52 and 71 (mean 63) years old. Thew 'i!..!.ht )f th' p iticnts i between 54 and 70kg (mean 63kg). Total Ropivn 'nine us id Ior -v .rv T iti nt wa the dose according to weight rang d b 't\. ''11 _. \ 4--.7. fixed at l 50mg,. mg cg, with the average of. 2.4mg/kg Ropivacaine. In our study, there were no sign. of C. or CNS toxicity seen in the patients. during the study period. Only one patient r quired post operative rescue SC Morphine analgesia. ay. a. for severe pain at 8 hours po t op when she initially refused the prescribed. given by nurses. All patients underwent the surgery successfully with standard dose of. al. analgesia prescribed.. 1.80-2.61 ). The median time point of maximum. concentration. (Tmnx ). of. range. M. The mean peak venous plasma concentration (Crnax) was 2.12 µg/ml (SD 0.41,. (Cmax) was 2.61 µg/ml occurred at 45 min.. ni ve. rs i. plasma concentration. ty. Ropivacaine occurred at 37.5min (range 20-60 min). The highest individual v n u. Table 4.1: Patients' characteristics, average dose of Ropivacaine, Cmax and Truax Age (year ). Weight (kg). Height (cm). BMI. 1 2 3 4 5 6. 63 64 71 69 52 57. 63 63 65 54 63 70. 153 148 158 154 149 157. 26.9 28.8 26.0 22.8 28.4 28.4. U. Patient number. Average Dose (mg/kg) 2.38 2.38 2.3 l 2.78 2.38 2.14. Cma (µg/ml). Tmax (min). 2.57 2.61 2.23 l.80 l.84 1.66. 20 45 30 30 60 60. urg r tim (min) 70 55 60 45 85 120. f.

(18) CHAPTER 5: DISCUSSION The mean peak venous plasma concentration. ( m.1,) for the. 'UlT. nt tudy was. 2. 12 µg/ml. This was lower than previous I published by Knu Iscn and coll 'ague (8) a study of volunteers receiving titru! 'cl intra\ revealed. the onset. concentration. or ncurologi cal. 'H. ms (i.x . infusions. s mptoms. it. 1. mean. of ropivacainc. total plasma. 111. the. venou~. of 2.2µg/n I. The dose of lo cnl anc c thetic in the current study was. standardi ed at l 50mg of Ropi acaine d pit weight differ nces; thus Cmax may have differed if different dosage. of local anae th tics were used, as demonstrated. in a study. ay. a. by Behnke (9) for interco tals block with different concentrations.. All patients in the current study did not show signs of toxicity, despite having an. al. individual highest level of 2.61 µg/ml at 45 minutes after injection. However, Knudsen·. M. paper represented a diff rent clinical scenario, where i.v. local anaesthetic. infu ion. of. were titrated in volunteers, without supplemental anaesthetic agents which may r due ymptoms. Knudsen'. study measured the onset or minor. ty. the likelihood of neurotoxic. rs i. neurotoxic symptom , rather than potentially life-threatening toxicity. In Behnke's study. plasma ropivacaine. level after interco tals blo k. ni ve. Ropivacaine 1 % resulted in Central (mixed)venous. plasma concentration. higher compared with arterial concentration at 2 min after completion. U. ith. that v r. f the block.. the other hand, no significant differences were found in further time cour e. current study, the fir t sample after injection was I 0 minute. \l. <9l. n. In th". after injection wa. ompleted. In addition. to absolute plasma. levels, the rate. f increa c in pla ma local. anaesthetic concentration was implicated in resulting to icity. Jn our tud , P has a Tma 1141,. or 37.5 mi nut is, which. Bl ck. was comparable to llioinguinul block at 45 minute·. Infra .lu iclur brachia! pie us block at 25minutcs 115>, TAP block at 30minut. R · ·t\1s sh ·nth bin .k al •. 111i11ut ·s l101, and. \ltil. L block at. Sminuics (Pl. In · mtrast, alter.

(19) Intercostal block (9\ scalp block (131 and supracla Tmax at I Ominutes, I Sminutcs,. 13.4minut. 'S. icular hlo .k. \tSl. showed a horter. r .spcctivcl ,'. 8) kuowina the Tmax of. each block, it served as a caution to nun isth 'lists µ,i\ iru; th' t lo .k to observe for local anaesthetic systemic toxicity (L/\ T) s st nu while p .rfonuinu r 'SP' .tive block . In our becau e most patients. study, we were unable to ch 'ck for iutcnous bl ck and 7 minutes.. Different anatomical. locations di pla. differ nt pharmacokinetic characteristics. influencing toxicity. Do age rccomm ndation. to the brachia! plexus result in significantly. a. example, different approaches. supraclavicular. approach 3.3 and 2.55µg/ml. approach has higher Cmax than. respectively;. Tmax of 13.4 min, and. Having said that Cmax was higher; the mean do age u ed in compared to other regional. of. this study was among the highest (3.75mg/kg). (Table 2) TAP block and plasma ropivcaine. level. ty. conducted.. (It). Tmax value but differences. and l.8µg/ml. (JOJ. blo k. were condu 'led b in. ma. rs i. different authors with comparable 2.54µg/ml. different. M. 25.0min respectively.i'". For. al. Cmax and Tmax of local anaesthetic; infraclavicular. hould also be technique-specific.. ay. underwent surgery before. uluc of. f Ropi acain .. despite having the same average dose. ni ve. This difference is important as one value is higher than the toxicity level, and the rca on for the difference may be due to the methodology.. Griffith. that wa. gave a. U. diluted to 40ml , wherea. Ropivacaine 0.5%. Thi. Murouchi. the risk to ome extent, becau c it reduce max and extends Tmax. ( 17, 18). max.. abs rption. tandard f L. may uggest that the total volume. max value; a higher volume may result in a higher. decrease. u ed Ropi acainc do e of. gt en ma. pincphrine. f injected. mg/kg Om\. affect the. might redu. I cal ane th tic ,.

(20) Table 5.1: Summary of previous studies and its result on Yr. Type of Block. Author. Menn close (mu/kt?). max and Tmax. Cmnx (~1g/ml) (range). 2001 2002. Wulf (14) Behnke (9). llioinuuinnl lntcrcostal block. -. 2004 2007. Costello ( l 3) Rettig(\ 5). Scalp block Supraclavicular block lnfraclavicular block TAP block Rectus Sheath block TAP block QL block PECS Block. 2.15-4.38 3.75. l .O (0.3-2.3) 0 - 1.8 (0.5-4.5) *0.75%-2.2 (1.5-5.1) * 1.0% - 2.3 ( 1.6-5.6) *#1.0%-2.2 (1.5-3.6) 1.5 (0.7-2.5) 3.30#. 3.75. 2.55#. 3 2.66. 2.54 1.79#. 1.83# 1.0# 2.12 ( 1.66-2.61). 25. -30 53 35 35 37.5. U. ni. ve. rs. ity. *Ropivacaine concentration #Arterial sample. 3 2.8 2.14-2.78. 15 (15-45) 13.4. ya. Murouchi (10) Murouchi ( 12) Current Study. al a. 2015 2016. M. Griffiths (11) Murouchi (10). 45 (30-60) 10 (5-15) 7 .5 (5-20) 10 (5-20) 10 (5-45). of. 2010 2015. \ .5 (0.7-_.6). * .2° o * . co. Truax (min). ll.

(21) 5.1 Limitations. PECS block is a truncal block which utilis. 'S. th' spre \ 1 of volume to the de ired. dermatorne. However, the dosage that th' .urr int inv ·stiL?. uors us .d wa a fixed do age and not based on patient',. weight.. mnx nnd sign )f tox! 'it ' .ould vary if a higher. dosage was used. One limitation of our tudy i that th inve tigator. did not have enough time to. assess the quality of the block before the induction of anesthesia. In the current study, the peak ropivacaine level occurr d at 37.5 min where most patients were already under. ya. anaesthesia.. al a. Another limitation of the study is the small sample size. During the course of the study, several breast cancer registries as well as other studies conducted by the primary in. M. team involved blood sampling. Not surprisingly, patients were reluctant to participat. of. the current study due to the need for multiple blood taking. This subsequently made th recruitment of participants challenging.. However, if more patients could be r ruit d for. ity. this study, then the Cmax and Tmax could have been more precised. in this study were healthy adult female patients.. rs. Lastly, the participants. ve. possible that the measured concentrations. would be different in male , childr n or the in which plasma concentrati n. ma. be. ni. elderly, or in pregnancy. Other condition. It i. U. unexpectedly increased could include renal or cardiac failure. 5.2: Further study If weight-based. Ropivacaine. is u ed in a 30 ml. concentration may be used which may affect the profile of Ropivacainc,. f LA. max and Tma . In. iew. max which is lower that the toxic le el, Tma. the truncal plane block, bilateral PE. block could al o be considered. differ nt L f the afet re embl. th. in future tudic .. A rec .ntly published case report of intruopcrative catheter placem nt fl r P. block .ath 'l 'r infusion \191, post op »uti c pain relieve and infusion cl sc iould be an.

(22) area to explore.. Ultrasound-guided. parastcrnul. Pee- block:. a n '". and useful. U. ni. ve. rs. ity. of. M. al a. ya. supplement for current Pectoral nerve blocks.('01.

(23) CHAPTER 6: CONCLUSION. In conclusion, unilateral p. cs. AND RE Ol\ll\lENDATION. this study demonstrates. II block in adult fcmnl. that the use if L Ouu; Ropivacuinc is snfc without. 'S. Further study could look into th' safct. 'X 'C. )t' I rst '1\ imtiv. 'ding the toxic I vel.. Ropivacainc. infusion in. ni. ve. rs. ity. of. M. al a. ya. patient undergoing mastectomy.. U. in the.

(24) REFERENCES 1. Lynch EP, Welch KJ, arabucna JM, Eberlein TJ. Anaesthesia Improves Outcomes Aller Breast urgcry. A 1995;222(5):663-9.. Thoracic F. Epidural URGERY.. 2. Coveney ~,Weltz R, rccngrass , l ilehnrt J , l .ieht . tecle M, et al. Use of paravcrtcbral block ancsth 'Sia in th' surgjc il m m1g '111 int of brca t cancer: experience in 156 cases. Annals of surg 'r [Intern 'I]. I l : --7(4):(496 p.]. Available from: http://www.ncbi.nlm.nih.gov/pm '/nrti 'l 's/P 1\ 11 \.JO.;/. 3. Blanco R. The 'pee block': a no cl tc hnique for providing analgesia after breast surgery. Anaesthesia [Internet]. _Q 11; 66(9):(847-8 pp.]. Available from: http://onlinelibrary.wiley.com/doi/l 0.1111/j. l 65-_044.2011.06838.x/full.. al a. ya. 4. Blanco R, Fajardo M, Parra Maldonado T. Ultrasound description of Pees II (modified Pees I): a novel approach to breast surgery. Revista espanola de anestesiologia y reanimacion [Internet]. 2012 Nov; 59(9):(470-5 pp.]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22939099.. M. 5. Abrahams M, Derby R, Hom JL. Update on Ultrasound for Truncal Blocks: A Review of the Evidence. Regional anesthesia and pain medicine [Internet]. 2016 MarApr; 41 (2):[275-88 pp.]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26866299. 'Wahba SS, Kamal SM. Thoracic paravertebral block versus pectoral nerve bl k for analgesia after breast surgery. Egyptian Journal of Anaesthesia. 2014;30(2): 129- 5. 7. Bashandy GM, Abbas ON. Pectoral nerves 1 and II blocks in multimodal analgesia for breast cancer surgery: a randomized clinical trial. Reg Anesth Pain M d. 2015;40( l ):68-74.. rs. ity. of. 6.. ve. 8. Knudsen K, Suurki..ila MB, Blomberg S, Sjovall J, Edvard on N. Central nervous and cardiovascular effects of iv infusions of ropivacaine, bupivacaine and placebo in volunteers. British journal of anaesthesia. I 997;78(5):507-14.. U. ni. 9. Behnke H, Worthmann F, Cornelissen J, Kahl M, Wulf H. Pla ma concentration of ropivacaine after intercostal blocks for video-assisted thoracic urger . Briti h journal of anaesthesia [Internet]. 2002; 89(2):(251-3 pp.]. A ailablc fr m: http://bja.oxfordjournals.org/content/89/2/25 I. hort. 10. Murouchi T, Iwasaki S, Yamakage M. hronological hange in Ropi acam Concentration and Analgesic Effects Between Tran ver us Abdomini Plane Bl k and Rectus Sheath Block. Regional Anesthesia & Pain Medicine ptemb r/October [Internet]. 2015· 40(5):(568-71 pp.]. A ail able fr m: http://ovidsp.ovid.com/ovidweb.cgi?T=J & =Y &N W =N&PA =fulltext&D= vftg&AN=OO 115550-201509000-00017. 11. riffiths J , Barron l•A, rant , jorkstcn AR, 11 ebbard P, R F. Pla ma ropivacainc concentrations after ultra sound-guided tran ver u abdomini plan bl k. Br J Ana isth [Internet]. 2010 Dec; 105(6):[85 -6 pp.]. Availabl fr rn: 1 ov/ hll ://www.n·bi.nl111.nih. >uhm ·d/208(> I 094.. IS.

(25) Murouchi T, [wasaki S, Yamakage M. Quadratus Lumborurn Block: Analge ic 12. Effects and Chronological Ropivacainc onccntrations tter Loparo scopic urgery. Reg Anesth Pain Med [Internet]. 2016 Mar-Apr; 41(-):[146-50 pp.]. vailable from: http://www.ncbi.nlm.nih.gov/pubmcd/267. 5154. 13. Costello TG, Cormack JR, lloy , W .ss \, l runiff \. -lartin KRN, et al. Plasma Ropivacainc Levels Followin 1 calp Block for Awake rnniotorny. Journal of Ncurosurgical Anesthesiology [Int irn it]. _004; I _):[ 147- 0 pp.]. Available from: http://ovidsp.ovid.com/ovidwcb.cgi?T .I Y c' ~ \\ - &P GE=fulltext&D=o vft:g&A N=00008506-200404000-00007. 14. Wulf H, Behnke H, Vogel I, hr d r J. linical u efulnes , safety, and plasma concentration of ropivacaine 0.5% for inguinal h mia repair in regional anesthesia. Reg Anesth Pain Med. 200 I ;26(4):348-5 l.. ya. 15. Rettig HC, Lcrou JGC, Gielen MJM, Boersma E, Burm AGL. The pharmacokinetics of ropivacaine after four different techniques of brachia! plexus blockade. Anaesthesia. 2007;62( 10): 1008-14.. M. al a. 16. Griffiths JD, Barron FA, Grant S, Bjorksten AR, Hebbard P, Royse CF. Plasma ropivacaine concentrations after ultrasound-guided transversus abdominis plane block. Br J Anaesth. 20lO;105(6):853-6.. of. 17. Schoenmakers KPW, Vree TB, Jack NTM, van den Bemt B, van Limbeek J, Stienstra R. Pharmacokinetics of 450 mg ropivacaine with and without epinephrin f r combined femoral and sciatic nerve block in lower extremity surgery. pilot tud . British Journal of Clinical Pharmacology. 20l3;75(5):1321-7.. ve. rs. ity. 18. Corvetto MAMO, Echevarria GCMDM, De La Fuente NMD, Mo qu ira LMD, Solari SMD, Altermatt FRMDM. Comparison of Plasma onccntration f Levobupivacaine With and Without Epinephrine for Transvcrsus Abdomini Plan Block. Regional Anesthesia & Pain Medicine November/December. 2012;3 7( 6):6 - 7.. U. ni. 19. Hinchcliff KMMD, Hylton JRMD, Orbay HMDP, Wong MSMD. lntraoperati c Placement of Pectoral Nerve Block Catheters: Description of a Novel Technique and Review of the Literature. Annals of Plastic Surgery. 2017;78(5) Supplemcnt(4): l 9S93. 20. Hansen CK, Dam M, Poulson T, Lonnqvi t P-A Bend t n T, B rglum J. Ultrasound-guided parasternal Pees block: a new and useful supplement to Pee I and serratus anterior plane blocks. A nae thesia ase . 2016:2016-0007.. 16.

(26) APPENDIX A tud 1 numb .r: -------. Data collection Sheet A Date: Name RN Age. Malay I Chin e I Indian I Others:. Race. ya. Weight (kg). BMl (kg/rn'') I I II /Ill. M. ASA. al a. Height (cm). of. Diagnosis. rs. Time of block completed. ity. Operation. Start :. start and end). End:. ve. Duration of surgery (stating time. ni. Duration of Anaesthesia. (stating. End:. U. time start and end of anaesthesia). Start :. 17.

(27) Data Collection Sheet B. Time. from. block. completed. is. Ropivacainc concentration (pr ml). OMin lOmin 20 min 30 min 45 min. a. 60 min. ay. 90 min. M. al. 120 min. Time point of maximum concentration ofRopivacaine occurred (Tmax):. ity. of. Maximum venous plasma concentration (Cmax) :. µg/ml. U. ni ve rs. Date and Time for rescue analgesia (SC Morphine 0.1 mg/kg):. mm.

(28) Loss of sensation to pin prick:. ay. a. (Map the area of block). al. Loss of sensation to cold ice pack:. U. ni ve rs. ity. of. M. (Map the area if block). Ic.

(29) APPENDIX. B. A prospective study of analgesic efficacy and plasma Ropivacalne concentration after PECS 11 block in patients undergoing mustcctomy Patients for clccti c Mast "tom. I. with ixillnrv .l .arauce. Exclusion (without significant renal impairment) AJJ. abo 1 ears old Ab\ to gi' consent Body v eight > 50kg. Patient's refusal and inability to give consent Allergy or hypersensitivity local anaesthetics BMI>35. liver or. ay. a. Enrollment and Consent. T. Paracetamol lg on OT call 2. T. Celebrex 200mg on OT call. 1.. Intra-operative :. M. al. Pre-operative :. Procedues:. of. 18G canulla inserted on cubital fossa, contralateral. side with. surgery site.. ity. May provide IV Midazolam 1-3mg, ±IV Fentanyl 25-lOOmcg per Anaesthetist.. ni ve rs. Injection site clean and drap, LA Lignocaine given. PECS II block is performed with Ropivacaine 0.5%, total 30mls.. Venous blood taken from canulla at 10, 20, 30, 45, 60, 90, 120 min after administration. of Rpivacaine.. Area of sensory blockade is done with cold and pin-prick. U. after 30 min.. Induction and Maintenance. of Anaesthesia. General Anaesthesia with supraglottic airway, IV Fentanyl 1-2 mcg/kg, IV Propofol 2-3mg/kg, Sevoflurane/Desflurane at 0.8-1.0. MAC, IV Morphine O.lmg/kg.. Routine post Anaesthetic observation in OT Recovery. Post-. pcrativc :. Post op oral analgesia:. T Paracetamol lg qid, T. Celebrex. 200mg bd. lssu ·s pertaining lo postoperutiv · p 1i11 ruuuu • ·111 ·nt 11111. ·011111. ·t I )r Khnw S. 0 I .-HOH I (1()9.. nt. If pain score >4, or when patient requested for more. I R. I :. cu Analgesla Is SC Morphine O.lmg/kg stat, and. r cord time: ~~~ and date: ~~~.

(30) APPENDIX CONSENT BY PATIENT FOR CLINICAL. RESE/\RCI. C. I. Version No.: 1 Version Date: 6 May 20 I (5 Id ntit r ard No. 1,. .. (Name of Patient). of. .. (Addre. s). hereby agree to take part in the clinical study/drug trial) specified below:. research ( .linical study/questionnaire. prospective study of analgesic efficacy and plasma Ropivacaine concentration after PECS II block in patients undergoing mastectomy. a. ······························································································································ the nature and purpose of which has been explained to me by Dr. ... ay. (Name & Designation of Doctor). and interpreted by. to the best of his/her ability in. language/dialect. M. .............................................. al. (Name & Designation of Interpreter). ity. of. I have been told about the nature of the clinical research in terms of methodology, possible adverse effects and complications (as per patient information sheet). ft r knowing and understanding all the possible advantages and disadvantages of this clirucal research, I voluntarily consent of my own free will to participat ' in th' clinical research specified above.. ate:. ni ve rs. I understand that I can withdraw from this clinical r .scarch at any time v ithout assigning any reason whatsoever and in such a situation shall not he denied the enefits of usual treatment by the attending doctors. Signature or Thumbprint. . (Patient). IN THE PRESENCE OF. U. Name. ·········································. Identity Card No Designation. Signatur '. . (Witness for Signature of Patient). ··········································. I confirm that I have explained to the pat icnr the nature and purpos , oft h abov 'mentioned clinical research.. Date. .. BY P TIENT FOR J\L RE 'EAR 11. Signature. ONSENT. R.N.. CLINI. S. . ( llending Do tor). Name 'X. g· Unit BK·MIS·lll. 7-E02. _1.

(31) KEIZINAN OLEH PESAKIT UNTUK PENYEUOIKAN. 1'.l.IN\k.\l. Nombor Vcrsi: l Tarikh Vcrsi: 6 May 20 I G Saya,. No. 1'.ntl Pcnaennlan. .. (Nama Pesakit). b .ralamat. . (Al 1111 it). dcngan 1111 b 'rs .tuju mcny m ai dalam pen) clidikan klinikal klinikal/pcngajian soal-s .lidik/pcrcubaan ubat-ubatan) disebut berikut: A prospective study of analgesic. (pengajian. efficacy and plasma Ropivacaine concentration after mastectomy. ay. a. PECS II block in patients undergoing. yang mana sifat dan tujuannya telah diterangkan. kepada saya oleh Dr. ... (Nama & [awatan Doktor). al. rnengikut tcrjemahan. yang telah menterjemahkan. (Nama & [awatan Penterjemah). kemampuan. di dalam. Bahasa /. .. of. loghat. dan kebolehannya. M. kepada saya dengan sepenuh. ity. Saya rclah diberitahu bahawa dasar pcnyclidikan klinikal dalam k .adaan mcthodologt, risiko dan komplikasi (rncngikut kcrras maklumat pcsakit). S .lcpas rncng nahui dan memahami scmua kcmungkinan kebaikan dan kcburukan p my lidikan kltnikal ini, saya merelakan/mengizinkan sendiri menycrtai pcnyclidtkan klinikal I 'rs .but di alas.. Tarikh:. ni ve rs. Saya faham bahawa saya belch mcnarik diri dari pcnyclidil an klinikal ini pada bila-bila masa tanpa memberi sebarang alasan dalam situasi ini dan tidak akan dikccualikan dari kcrnudahan rawatan dari doktor yang rncrawat. ... Tandatangan. ... (Pesa kit). DIHADAPAN. ... U. Nama. No. K/P. Tandatangan. .. (Saksi. Jawatan. untuk Tandatanqan. Pesakit). .. Saya sahkan bahawa saya rclah rncncrangkan pcnyelidikan klinikal tcrscbut di alas.. Tarikh:. ... k .pada. pcsakit. sifat. dan. Tandatangan. tujuan. .. (Doktor. any merawal). No. Pend. KEIZINAN. OLLI I PES NTK. KIT. Nam a junilna lJ n I I. BK-MIS-1117-E02. .. 2.

(32) APPENDIX. D. strtnc IL ETll/C 'CO.~l/11/TTEE { ·"' rus: n ll IL Ir I \IEDIC4L CENTRE PATIENT. INFORM \TlON. H ET. Version No.: 1 Version Date: 6 May 2016. Please read the following. information. carefully,. do not hesitate to discuss any. Study Title:. ay. 1.. a. questions you may have with your Doctor/Investigator. M. PECS II block in patients undergoing mastectomy. al. A prospective study of analgesic efficacy and plasma Ropivacaine concentration after. Introduction (Scientific basis of the study). In the past, pain relieve. of. 2.. for breast surgery. is done. by providing. local. ity. anaesthetics (pain relieve medication} around the spinal cord (eg. thoracic epidural. ni ve rs. analgesia or paravertebrae block}. However, both techniques were associated serious complications, such as trauma to the lung (pneumothorax}, accidental. with blood. vessel injection.. The introduction of using ultrasound guided chest wall block (PECS II block) has. U. changed the choice for providing analgesia to the upper part of the chest wall. Ropivacaine is a type of local anaesthetic with an established safety profile. We. would like to conduct a study to measure the blood safety level of Ropivacaine and the duration of this pain reliever with a specific dose.. 3.. What is the purpose of this study?. To measure the blood concentration of this pain reliever II block. This would determine. whether the peak plasma. level is within the safety lev I allowed. medication. ov r th ch. W. (Ropivacaine) after PECS. Ropivacaine concentration. also want to know the spread of this. t wall providing numbn ss..

(33) What are the procedures to be carried out?. 4.. Injection of local anaesthetic over the chest wall guided using an ultrasound machine to ensure precise injection. Several Blood taking (approximat. ly 20 ml in tot I}. inserted on an upper limb prior to th. ur. ry,. The cannula is similar to a cannula in. rt d for. nd. pirated from a cannula nd for analysis in a lab.. iving intravenous drugs and. intravenous drips. After the block is performed, we will use 'pin prick' and 'cold pack' technique over the numbness area. General Anaesthesia will be provided just before surgery until surgery is. ay. a. completed.. al. 5. How long will I be involved in this study?. M. 24-48 hours. Who should not enter the study (exclusion criteria)?. of. 6.. Patient refusal for blood taking. ity. Patient with a body mass index above 35. 7.. ni ve rs. Patient with history of allergy to local anaesthetics. How many patients/research subjects will be recruited into this study?. 28 patients. U. 8. Who will have access to the subjects medical records or research data? Investigators and co-investigator for this study. 9.. Will the records/data be kept confidential? Yes. 10. What will be the benefits of the study to the subject? Patient will exp ri nc. numbness ov r the location for PECS II block. Indirectly we will. also reduce the us of oth r pain reli ve medication such as Morphine which has its own ompll. tlon. uch. n us. , vomltln , nd llergy..

(34) 11.. What are the possible drawbacks (side effects, etc.)?. There is no report of complications after ultr sound- uld d PECS II block has been reported.. 12. Is the investigatory product derived from a source that may be cultural sensitive, eg: bovine or porcine? (If applicable) No. 13. What payments or reimbursement will research subjects receive? No. 14. Can I refuse to take part in the study?. ay. Who should I contact if I have additional questions during the course of the. al. 15.. a. Yes. Dr Khaw Soon Keong (012-8081609). of. Dr Mohd Shahnaz Hasan (019-2627277). M. study?. Dr Azrin Mohd Azidin (019-3657215). U. ni ve rs. ity. Dr Beh Zhi Yuen (016-2333083).

(35)