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1 원저 ISSN 일산병원학술지 2019;18(1):39-44 깊은근이완이복강경하담낭절제술후발생하는어깨통증에주는영향 국민건강보험일산병원마취통증의학과 최관웅, 이해연, 배재찬, 강상화 Effect of Deep Neuromuscular Block on the Shoulder Pain after Laparoscopic Cholecystectomy Kwan Woong Choi, Haeyeon Lee, Jae Chan Bae, Sang Hwa Kang Department of Anesthesiology and Pain Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea Background: Patients commonly experience postoperative shoulder pain after laparoscopic surgery. Previous studies have reported that a deep neuromuscular block can provide good working conditions for surgeons and reduce postoperative pain in patients by lowering intra-abdominal pressure. The objective of this study was to evaluate the effect of a deep neuromuscular block on shoulder pain after laparoscopic cholecystectomy. Methods: Eighty-two patients who were scheduled for laparoscopic cholecystectomy were randomly assigned to the control (group C) or deep neuromuscular block (group D) groups. The patients received 0.6 mg/kg (group C) or 1.2 mg/kg (group D) of rocuronium during anesthesia induction. The deep neuromuscular block state in group D was maintained by continuous infusion of rocuronium (10 16 mcg/kg/min) by monitoring of post-tetanic count (PTC). Both postoperative shoulder and incisional site pain were assessed in the recovery room and ward for 24 hours. Results: There were no clinically significant differences in postoperative shoulder pain or incisional pain between the two groups at each time point. Conclusion: Deep neuromuscular block in laparoscopic cholecystectomy could not reduce postoperative shoulder pain. The limitation of this study was the lack of agreement on the optimal pressure during laparoscopic cholecystectomy. Key Words: Deep neuromuscular block, Laparoscopic surgery, Postoperative shoulder pain 서론 복강경을이용한수술은개복수술과비교할때수술후통 증이적고회복이빠르며흉터가적게발생하는미용적효과 등의장점이있다. 1 하지만, 복강경수술은개복수술에비해서 수술자의시야가제한되는단점을극복하기위해이산화탄소 책임저자 : 강상화 경기도고양시일산동구일산로 100 국민건강보험일산병원마취통증의학과전화: (031) , 팩스: moong73@nhimc.or.kr * 본연구는국민건강보험일산병원의연구비지원으로이루어졌음 (NHIMC 2017CR057). (CO 2 ) 를환자의복강내에주입하여기복 (pneumoperiton- eum) 을만들어수술에필요한시야와공간을확보하는과정 이필요하다. 하지만이산화탄소를통한기복은환자의복압 (intra-abdominal pressure) 의상승을유발하며이는체내이 산화탄소의흡수를일으켜심혈관계, 호흡계및내장혈류순환 (splanchnic perfusion) 의병태생리의변화를일으킨다. 2 복강경하담낭절제술을받는환자에있어서어깨통증 (post- laparoscopic shoulder pain) 은수술부위통증(incisional site pain) 과함께흔히호소하는증상이다. 수술후어깨통증 이발생하는기전은아직까지명확하게알려져있지않지만, 최 근연구에따르면 CO 2 를통한기복의생성이어깨통증의발생 과연관된것으로보고되고있다. 3-6 기존연구에의하면깊은수준의근이완은수술시야의확보 Volume 18 Number 1 June

2 KW Choi et al. Effect of Deep Neuromuscular Block on Postoperative Shoulder Pain 를도우며, 낮은압력의기복을이용한복강경수술에서수술 후어깨통증이줄어들었다는보고가있다 최근개발된 sugammadex(bridion, Merck Sharp and Dohme-MSD, Oss, the Netherlands) 는비탈분극성근이완 제인 rocuronium 에매우강한친화력을가지며, 선택적으로 결합하여근이완을역전시킨다. Rocuronium 을이용한매우 깊은정도의근이완에서도 sugammadex 는근이완의빠른역 전이가능하기에, 최근그사용빈도가점차증가하고있다. 11 이에본연구에서는 rocuronium 의지속주입을통한깊은 근이완이복강경하담낭절제술을받는환자에게서수술후어 깨통증에미치는영향을알아보며, 이러한깊은근이완의역 전은 sugammadex 를이용하도록한다. 부가적으로수술중 복압의정도, 수술후통증, 진통제의사용량의정도, 부작용의 발생및환자퇴원일수에미치는영향에대해서알아보고자한 다. 또한본연구결과에따라복강경하담낭절제술환자에서 수술중깊은근이완을유지해야하는근거를마련할수있을 것이다. 대상및방법 본연구는국민건강보험일산병원의임상연구윤리위원회의 승인을받았다. 2017년 11월부터 2018년 9월까지복강경하담낭절제술이 예정된만 19세이상 70세미만의미국마취과의사협회신체 등급(ASA class) 1~3에해당하는총 82명의대상자를모집하 였다. 심각한심장, 호흡기, 간, 신장및뇌신경계질환이있는 환자나 rocuronium 또는 sugammadex 에과민반응이있는 환자, 임산부, 본연구에대해이해를하지못하거나의사소통 이불가능한환자는대상자에서제외되었다. 본연구는전향적무작위조절연구 (prospective random- ized controlled study) 로진행하였으며, 모든대상자들은 에서제공된배정표에따라 대조군과대상군으로무작위배정하였다. 연구참여동의획득 및술전후평가는한명의연구자(S.H.K) 가시행하였고, 이연 구자는수술중마취및연구약제투여에관여하지않았으며, 대상자개개인의배정군을알수없었다. 수술후통증점수의 평가는 numeric rating scale(nrs; 0~10) 를이용하여연구 담당자(K.W.C) 가수행하였다. 대상자가수술실에도착하면표준마취감시장치인심전도 와맥박산소계측기를부착하고혈압을측정하였다. 마취유도 를위해 propofol 1.5~2mg/kg, remifentanil 1µg/kg를정 주하였으며대조군(group C) 과대상군(group D) 모두 rocuronium 으로근이완을유발한후기관내삽관을시행하였다. 마취의유지는 50% 산소와흡입마취제인 desflurane 으로하 였으며수술중통증의조절은 절한마취깊이를유지하기위해 시하여그값을 remifentanil 을이용하였다. 적 bispectral index(bis) 를감 40~60 정도로유지할수있도록 desflurane 의투여농도를조절하였으며, remifentanil 의투여율은피 험자의기저혈압및맥박수의 20% 범위에서유지될수있도 록농도를조절하였다. 두군모두수술예상종료시점 30분 전에수술후통증조절을위한진통제로 과항구토제인 1µg/kg의 fentanyl ramosetron 0.3mg 을정주하였다. 수술이 끝나면 desflurane과 remifentanil의투여를종료하고배 정된군에따라미리준비된근이완역전제 (group C, glycopyrrolate 0.2mg과 neostigmine 1mg; group D, sugam- madex 4mg/kg) 를투여한후, 피험자의의식이돌아오고자 발호흡의회복이확인된후발관하고회복실로이동하였다. Sugammadex 를이용한근이완의역전시에는신경근감시장 치(nerve stimulator) 에서 Post-tetanic count(ptc) 가 1~2 회나타나는것을확인한뒤에 4mg/kg 을정맥투여하였다. 신경근감시장치는수술중근이완의상태를보기 15초간 격으로 train-of-four(tof) 및 5분간격으로 PTC를측정 하였으며, group C( 대조군) 의경우마취유도시에만 rocuro- nium 0.6mg/kg 을투여하였고 group D( 대상군) 의경우 rocuronium 1.2mg/kg 을마취유도시투여한이후감시하에 10~16mcg/kg/min 으로지속주입하였으며, 투여량이최대 16mcg/kg/min 를넘지않도록하였다. 본연구에서보고자하는주요관찰항목인수술후어깨통 증뿐아니라부가적으로알아보고자했던수술부위통증을 다음과같은시점에 NRS 를통해서측정하였다. NRS는 0~10 점까지측정하였으며통증이하나도없는경우를 0, 상상할수 있는최악의통증이 10으로대상자에게설명을한뒤그점수 를말하도록하였다. 통증점수의측정은회복실과병실에서이 루어졌으며, 회복실에서는입실직후, 입실 10 분후, 퇴실직전 까지총 3 번에걸쳐서어깨통증과수술부위통증, 명치의통증 을측정하였다. 병실에서는수술종료후 4, 8, 12 및 24시간에 서동일한항목에대해서측정하였다. 또한두군모두에서회 복실및병실에서사용한총진통제의양도측정하였다. 부가적 으로수술중복강내압을알아보기위해복강경이들어간직 후, 15분그리고 30분총 3 차례에걸쳐서복강내압력(mmHg) 을측정하였으며, 환자의수술후회복의지표가될수있는가 스배출시간및입원기간도함께알아보았다. 40 Korean Journal of National Health Insurance Service Ilsan Hospital

3 최관웅외. 깊은근이완이수술후어깨통증에주는영향 기존연구에서복강경하수술에서복강내압력이 12mmHg 보다낮은경우에어깨통증발생율의 relative risk가 47% 감 소한다고하였으며, 이에따라서본연구에서깊은근이완이 어깨통증의발생율을 1/3 으로감소시킨다고가정했을때, al- pha 0.05, power 90% 에서군당 37 명의대상자가필요하며, 중도탈락을고려하여각군당 41명으로총 82명의대상자를 연구에참여시켰다. 통계자료의표시는정규분포를따르는연 속형자료의결과는평균 ± 표준편차로, 정규분포를따르지않 는연속형자료는중위수( 사분위범위) 로표시하였다. 또한두 군에서시간의변화에따른측정지표의변화도확인하기위해 선형복합모델 (linear mixed model) 을적용하였다. 통계분석 은 PASW statistics 18(SPSS Inc. USA) 를사용하였으며자료 의특성에따라 independent t-test( 혹은 Mann-Whitney rank sum test), Chi-square( 또는 Fisher s exact test) 또는 repeated measures ANOVA with the Bonferroni correc- tion 를사용하였다. 통계의결과는 p 값이 0.05 미만일때통계 적으로유의한것으로간주하였다. 결과 대조군(group C) 과대상군(group D) 에서두군간의성별, 나이, 키와체중, ASA class 및수술중투여된수액의양은유 의한차이를보이지않았다(Table 1). 본연구에서주로관찰 하고자했던수술후어깨통증은각각의시간대에회복실및 병실에서측정한값이두군간에임상적으로의미있는차이 가없었으며, 수술부위통증과상복부통증또한의미있는차 이를보이지않았다(Table 2, Figs. 1-3). 또한두군간의수술 중복강내압력도차이는없었다(Table 2, Fig 4). 부가적으로 알아보았던수술중및수술후진통제의총투여량과환자의 수술후가스배출시간및입원기간역시의미있는차이를보 이지않았으나, 수술중투여한 remifentanil 의총투여량이 깊은근이완을유지한 group D에서대조군에비해임상적으 로유의한차이를보였다 (group D ± vs group C ±133.59; p = ; Table 3). 고찰 수술후통증은수술이후에불가피하게따르는중요한부작 용이다. 이는각종합병증의위험을높이며수술후환자의회 복을지연시킬뿐아니라환자의삶의질에도영향을미치게된 다. 12 복강경을이용한수술의경우수술적절개부위가적어수 술후통증이감소되어환자의회복이빠르고추가적으로흉터 가적게남는미용적인효과도있어서최근복부수술이나흉부 수술의대부분은복강경을이용해서이루어지고있다. 1 또한담 낭절제술의경우복강경을도입하면서수술적인합병증의감 소와수술후회복의촉진을통한재원기간의감소의장점이뚜 렷하여최근에는기존의개복수술을거의대체하고있다. 13 하지만수술중시야와공간확보를위해이산화탄소를이용 한기복(pneumoperitoneum) 을만드는과정에서발생하는 복강내압력의상승은체내의이산화탄소의흡수를일으켜내 장혈류순환및병태생리의변화를일으킨다. 2 또한복강경하 수술을시행받은환자에서수술부위통증뿐만아니라횡경 막하통증과어깨의통증도흔하게호소하는것을볼수있는 데, 아직까지이기전에대해서는명확하게알려져있지는않 으나기복의생성이복강내횡경신경말단 (phrenic nerve ending) 을자극이어깨통증의발생의중요한원인이라고최 Table 1. Demographic data Total (N=82) Group D (N=41) Group C (N=41) p-value Sex Male 24 (29.27%) 9 (21.95%) 15 (36.59%) Female 58 (70.73%) 32 (78.05%) 26 (63.41%) Age 44.65± ± ± Height (cm) ± ± ± Weight (kg) 67.82± ± ± ASA class (71.95%) 32 (78.05%) 27 (65.85%) 2 20 (24.39%) 7 (17.07%) 13 (31.71%) 3 3 (3.66%) 2 (4.88%) 1 (2.44%) Fluid intake (ml) ± ± ± Group D: deep neuromuscular block group; Group C: control group Volume 18 Number 1 June

4 KW Choi et al. Effect of Deep Neuromuscular Block on Postoperative Shoulder Pain Table 2. Comparison of intra-abdominal pressure (mmhg) and pain score (Numeric rating scale) Total (N=82) Group D (N=41) Group C (N=41) p-value p-value (adjusted) IAP (mmhg) T ± ± ± T ± ± ± T ± ± ± Incision site pain P1 4.72± ± ± >.9999 P2 5.25±1.89 5± ± >.9999 P3 4± ± ± >.9999 W1 3.76± ± ± >.9999 W2 2.9± ± ± >.9999 W3 2.45± ± ± >.9999 W4 2.15±1.81 2± ± >.9999 Epigastric pain P1 1.86± ± ± >.9999 P2 2.06± ± ± >.9999 P3 1.69± ± ± W1 2.51± ± ± >.9999 W2 1.78± ±2 1.85± >.9999 W3 1.39± ± ± >.9999 W4 1.09± ± ± Shoulder pain P1 0.65± ± ± >.9999 P2 0.49± ± ± >.9999 P3 0.41± ± ± >.9999 W1 0.71± ± ± >.9999 W2 0.73± ± ± W3 0.64± ± ± >.9999 W4 0.69± ± ± >.9999 IAP: Intra-abdominal pressure; T1: scope entry time; T2 and T3: 15min and 30min after scope enter; P1: PACU admission; P2: 10 minutes after PACU admission; P3: discharge from PACU; W1: 4hrs after surgery; W2: 8hrs after surgery; W3: 12hrs after surgery; W4: 24hrs after surgery Fig. 1. Comparison of postoperative shoulder pain. Bridion is deep neuromuscular block group. (PA: PACU admission; P10: 10 minutes after PACU admission; PD: discharge from PACU; W4: 4 hours after surgery; W8: 8 hours after surgery; W12: 12 hours after surgery; W24: 24 hours after surgery) Fig. 2. Comparison of postoperative incision site pain. Bridion is deep neuromuscular block group. (PA: PACU admission; P10: 10 minutes after PACU admission; PD: discharge from PACU; W4: 4 hours after surgery; W8: 8 hours after surgery; W12: 12 hours after surgery; W24: 24 hours after surgery) 42 Korean Journal of National Health Insurance Service Ilsan Hospital

5 최관웅외. 깊은근이완이수술후어깨통증에주는영향 Table 3. Comparison of intraoperative and postoperative analgesics, gas pass time and hospital stay Total (N=82) Group D (N=41) Group C (N=41) p-value Remifentanil (mcg) ± ± ± Fentanyl (mcg, at PACU) 54.69± ± ± Tridol (mg, at Ward) 80.32± ± ± Gas pass time (hour) 27.05± ± ± Hospital stay time (day) 4.23± ± ± Fig. 3. Comparison of postoperative epigastric pain. Bridion is deep neuromuscular block group. (PA: PACU admission; P10: 10 minutes after PACU admission; PD: discharge from PACU; W4: 4 hours after surgery; W8: 8 hours after surgery; W12: 12 hours after surgery; W24: 24 hours after surgery) Fig. 4. Comparison of intra-abdominal pressure (mmhg). Bridion is deep neuromuscular block group. (TI: scope entry time; 15min: 15 minutes after scope enter; 30min: 30 minutes after scope enter) 근연구에서보고되었다. 3-6 기존연구에따르면일반적으로사용하는압력 (11~12mmHg) 보다낮은압력(8~9mmHg) 으로복강경하담낭절제술을시 행하였을때수술후어깨통증이줄어들었으며, 14,15 산부인과 수술에서깊은수준의근이완이이루어질경우수술시야확 보를도와주고이와동시에복강내압력을줄여복강경수술 후어깨통증이줄어들었다고보고하였다 이에본연구자 들은마취중깊은근이완의유지가복강경하담낭절제술에서 수술후어깨통증의감소에도움이될것이라고가정하고이 연구를진행하였다. 하지만, 본연구의결과에서는깊은근이완을유지한군에 서대조군과비교하여어깨통증정도의차이는없었으며, 절개 부위통증및횡경막하의통증의정도또한차이가없었다. 추 가적으로회복실및병동에서수술후통증을조절하기위해 투여된진통제의양과환자의수술후회복의지표중하나인 가스배출시간및입원기간도임상적으로의미있는차이를보 이지않았다. 본연구에서두군사이에서수술후어깨및수술부위통 증의차이가발생하지않았던이유는다음과같이해석할수 있을것같다. 본연구에서연구자들은깊은수준의근이완이 유지가되고있는경우라면, 동일한압력이복강내횡경신경말 단에작용한다고하더라도일반적인수준의근이완의상태보 다는이에미치는영향이적을것이라고가정하였다. 하지만, 결과에서알수있듯이본연구에서는 10~13mmHg의복강 내압력이유지되고있었으며(Table 2), 이는깊은근이완을 유발하지않고진행한기존연구에서어깨통증의발생을줄 이기위해유지한압력인 8~9mmHg보다는높은일반적인수 준의기복을만들기위한압력이다. 14,15 따라서깊은수준의근 이완을유지하는것보다는절대적인복강내압력을줄여주는 것이수술후어깨통증의발생은줄이는데매우중요한요소 라고해석할수있을것같다. 하지만최근발표된메타분석결 과에의하면연구자에따라어깨통증및복부의통증의차이가 없는것으로도보고되기도하였다. 16 본연구에서주로관찰하고자하는지표는아니었으나, 깊은 근이완을유지한군에서수술중통증조절을위해서투여된 remifentanil 의양이대조군에비해임상적으로의미있는차 이를보였다(Table 3). 이결과를나타낸원인에대해서는더 연구를해봐야확인할수있겠지만, 마취중깊은근이완의유 Volume 18 Number 1 June

6 KW Choi et al. Effect of Deep Neuromuscular Block on Postoperative Shoulder Pain 지가수술중혹은수술후의통증의발생기전에어느정도연 관이있을것으로사료된다. 결론적으로본연구를통해서알수있는사실은복강경을 이용한담낭절제술에서수술후어깨통증을줄이기위해서 는깊은근이완을유지함과동시에외과의사의수술시야를 방해하지않는조건하에서최대한낮은복강내압력을유지 하는것이필요하다는것이다. 하지만기존의다른연구들에서 도본연구와같이수술후통증에차이가없는결과가보고되 었던것을고려하여볼때, 17,18 복강경수술에서발생하는어 깨통증을줄이기위해서는이를유발하는병태생리에대한깊 은연구가더필요할것으로생각한다. REFERENCES 1. Neudecker J, Sauerland S, Neugebauer E, et al. The European Association for Endoscopic Surgery clinical practice guideline on the pneumoperitoneum for laparoscopic surgery. Surg Endosc. 2002;16: Nguyen NT, Anderson JT, Budd M, et al. Effects of pneumoperitoneum on intraoperative pulmonary mechanics and gas exchange during laparoscopic gastric bypass. Surg Endosc. 2004;18: Coventry DM. Anaesthesia for laparoscopic surgery. J R Coll Surg Edinb. 1995;40: Yu TC, Hamill JK, Liley A, Hill AG. Warm, humidified carbon dioxide gas insufflation for laparoscopic appendicectomy in children: a double-blinded randomized controlled trial. Ann Surg. 2013;257: Aitola P, Airo I, Kaukinen S, Ylitalo P. Comparison of N2O and CO2 pneumoperitoneums during laparoscopic cholecystectomy with special reference to postoperative pain. Surg Laparosc Endosc. 1998;8: Corsale I, Fantini C, Gentili C, Sapere P, Garruto O, Conte R. Peritoneal innervation and post-laparoscopic course. Role of CO2. Minerva Chir. 2000;55: Madsen MV, Gatke MR, Springborg HH, et al. Optimising abdominal space with deep neuromuscular blockade in gynaecologic laparoscopy-a randomised, blinded crossover study. Acta Anaesthesiol Scand. 2015;59: Dubois PE, Putz L, Jamart J, et al. Deep neuromuscular block improves surgical conditions during laparoscopic hysterectomy: a randomised controlled trial. Eur J Anaesthesiol. 2014;31: Martini CH, Boon M, Bevers RF, et al. Evaluation of surgical conditions during laparoscopic surgery in patients with moderate vs deep neuromuscular block. Br J Anaesth. 2014;112: Madsen MV, Istre O, Staehr-Rye AK, et al. Postoperative shoulder pain after laparoscopic hysterectomy with deep neuromuscular blockade and low-pressure pneumoperitoneum: A randomised controlled trial. Eur J Anaesthesiol. 2016;33: Welliver M, McDonough J, Kalynych N, et al. Discovery development and clinical application of sugammadex sodium, a selective relaxant binding agent. Drug Des Devel Ther. 2009;2: Wu CL, Raja SN. Treatment of acute postoperative pain. The Lancet. 2011;377: Lujan JA, Parrilla P, Robles R, et al. Laparoscopic cholecystectomy vs open cholecystectomy in the treatment of acute cholecystitis: a prospective study. Arch Surg. 1998;133: Yasir M, Mehta KS, Banday VH, et al. Evaluation of postoperative shoulder tip pain in low pressure versus standard pressure pneumoperitoneum during laparoscopic cholecystectomy. Surgeon. 2012;10: Sarli L, Costi R, Sansebastiano G, Trivelli M, Roncoroni L. Prospective randomized trial of low-pressure pneumoperitoneum for reduction of shoulder-tip pain following laparoscopy. Br J Surg. 2000;87: Bruintjes MH, van Helden EV, Braat AE, et al. Deep neuromuscular block to optimize surgical space conditions during laparoscopic surgery: a systematic review and metaanalysis. Br J Anaesth. 2017;118: Staehr-Rye AK, Rasmussen LS, Rosenberg J, et al. Surgical space conditions during low-pressure laparoscopic cholecystectomy with deep versus moderate neuromuscular blockade: a randomized clinical study. Anesth Analg. 2014; 119: Blobner M, Frick CG, Stäuble RB, et al. Neuromuscular blockade improves surgical conditions (NISCO). Surg Endosc. 2015;29: Korean Journal of National Health Insurance Service Ilsan Hospital

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012임수진 Received : 2012. 11. 27 Reviewed : 2012. 12. 10 Accepted : 2012. 12. 12 A Clinical Study on Effect of Electro-acupuncture Treatment for Low Back Pain and Radicular Pain in Patients Diagnosed with Lumbar