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1 대한마취과학회지 2007; 52: 663~8 Korean J Anesthesiol Vol. 52, No. 6, June, 2007 임상연구 간엽절제술시중심정맥압이출혈량에미치는영향 연세대학교의과대학 1 마취통증의학교실및 2 마취통증의학연구소, 3 외과학교실 최승호 1,2 반소영 1,2 전나형 1 전동병 1 남순호 1,2 길혜금 1,2 김경식 3 Central Venous Pressure and Its Effect on Blood Loss during Hepatic Lobectomy Seung Ho Choi, M.D. 1,2, So Young Ban, M.D. 1,2, Na Hyung Jun, M.D. 1, Dong Byeong Jun, M.D. 1, Soon Ho Nam, M.D. 1,2, Hae Keum Kil, M.D. 1,2, Kyung Sik Kim, M.D. 3 1 Department of Anesthesiology and Pain Medicine, 2 Anesthesia and Pain Research Institute, 3 Department of General Surgery, Yonsei University College of Medicine, Seoul, Korea Background: Some studies reported that lowering central venous pressure (LCVP) during liver resection could significantly reduce the intra-operative blood loss, however it is still controversial concerning LCVP induced renal dysfunction, hypovolemia, hemodynamic instability. This study evaluated the association of low central venous pressure with blood loss during liver resection comparing the control group. Methods: A total 62 patients aged 20 to 70 underwent hepatectomy by the same group of surgeon were randomized into group L (CVP < 10 mmhg, n = 30) and control group C (CVP > 10 mmhg, n = 32) during dissection and lobectomy period. Data such as age, sex, concurrent disease, liver resection site (right or left), pre-, intra- and postoperative day 3 hemoglobin, blood urea nitrogen, creatinine, bleeding time, prothrombin time, activated partitial thromboplastin time, intraoperative blood loss, urine output, transfusion volume, length of hospital stay were collected and compared between the two groups and t-test was used for comparison of results. Results: The difference of total blood loss between two groups was ± ml (group L; ± ml, group C; ± ml), however statistically insignificant (P value = ). Additionally, there were no significant differences in other data including the length of hospital stay. Conclusions: Our results suggest maintaining CVP under 10 mmhg is not effective in reducing blood loss during liver resection. (Korean J Anesthesiol 2007; 52: 663~8) Key Words: blood loss, central venuos pressure, hepatic lobectomy. 서 간절제술의마취관리는대량출혈에 1,2) 따른수혈및간혈류보존이가장중요하여사망률과유병률도출혈및수혈량에영향을받는다. 3,4) 출혈을줄이기위한방법으로 hepatic vascular exclusion의방법등이 5,6) 개발되었으나그과정이복잡하고혈관결찰기간동안간혈류가감소되므로황달이나간경화가있는경우에는수술후광범위간괴사상 론 논문접수일 :2007 년 3 월 27 일책임저자 : 남순호, 서울시서대문구신촌동 134 연세대신촌세브란스병원마취통증의학과우편번호 : Tel: , Fax: nsh66@yumc.yonsei.ac.kr 석사학위논문임. 태에이르는경우도있다. 6,7) 또한 Greenway와 Stark가 8) 제시한이론에근거하여중심정맥압을낮게유지하는방법도있다. 9,10) Hepatic vascular exclusion 방법은집도의들이시도해볼수있는방법이지만, 중심정맥압을낮게유지하는방법은마취통증의학과의사들이주도하는방법이라할수있다. 많은문헌에서중심정맥압을낮추는기준점으로 5 mmhg를추천하였지만, 저자들은중심정맥압을너무낮추는경우저혈압, 핍뇨, 공기색전증등이염려되어간절제술의마취관리에서중심정맥압 10 mmhg를기준으로하여출혈량이상관관계가있는지알아보기위하여본연구를시작하였다. 대상및방법 2004년 3월부터 2005년 12월까지연구의오차를없애기 663

2 대한마취과학회지 : 제 52 권제 6 호 2007 Table 1. Demographic Data Group L (n = 30) C (n = 32) Sex (M/F) 20/10 24/8 Age (yr) 54.9 ± ± 9.7 Anesthetic duration (min) ± ± 43.4 Operation duration (min) ± ± 35.1 Hospital stay 12.8 ± ± 4.2 Pathologic diagnosis cholangitis 1 0 HCC IHD stone 5 7 Cholangiocellular carcinoma 2 2 Hemangioma 2 0 Mass 0 1 Metastatic mass 3 4 Distribution of operations performed Right lobectomy Left lobectomy 10 9 All values except sex ratio are expressed as mean ± SD. Hospital stay: hospital day after operation, HCC: hepatocellular carcinoma, IHD: intrahepatic duct, CVP: central venous pressure. group L: CVP < 10 mmhg, group C: control group, CVP > 10 mmhg. 위해본원외과의동일한집도의에게서계획된대량간절제술 ( 제한혹은구역간절제술제외 ) 을시행받는 20세이상 70세미만의환자들중사전동의를얻은 62명을대상으로무작위로실험군 (L군, 간절제술후지혈완료때까지수액제한으로중심정맥압을 10 mmhg 이하로유지한군, n = 30) 및대조군 (C군, 전기간동안수액제한없이정상혈량을유지한군, n = 32) 으로나누었다. 양군간의남녀성비, 마취및수술시간, 간절제술후퇴원까지의기간, 진단명, 간절제의좌, 우여부등은 Table 1에기록하였다. 연구에서제외하는경우는미국마취과학회신체등급 3 이상, 혈액응고가심하게나쁜경우, 수축기혈압이 90 mmhg 미만인환자, 복부수술의과거력이있는경우, 생체간이식공여자등으로하였다. 마취전처지로 midazolam mg, glycopyrrolate 0.2 mg을근육주사하였으며환자가수술실에입실하면비침습적인혈압계, 심전도, 맥박산소측정기를부착하고, 술후진통을위해경막외카테터를거치하였다. 마취전산소를투여하고, fentanyl 100μg, propofol mg, rocuronium bromide mg을정주한후기관내삽관을하였다. 침습적동맥압감시를위해요골동맥, 중심정맥압감시를위해오른쪽내경정맥을천자한후압력변환기 (transducer) 는수술대에부착하여술중자세의변화에영향을받지않게하였으며요골동맥압은 5분단위로, 중심정맥압은 15분단위로기록하였다 (Dräger Infinity Delta, Dräger Inc., USA). 의인 성혈액량감소상태를보상하고사구체여과율을증가시켜신장을보호하며, 술중발생할수있는공기색전증을방지하기위하여환자체위를 10 정도낮추는 Trendelenberg 자세를유지하였다 ) 마취는 oxygen, air, isoflurane으로유지하고, 일회호흡량은 10 ml/kg로, 호흡횟수는호기말이산화탄소분압이 35 mmhg 정도로유지되게조절하였으며, 근육이완은 rocuronium bromide 5-10μg/kg/min을지속주입하였다. L군은 Greenway와 Stark가 8) 제시한이론에근거하여수액을제한하여중심정맥압 10 mmhg 미만으로유지하다가, 간절제술및지혈완료후에는수액을충분히주어정상혈량으로회복시켰으며, C군은수술전기간동안중심정맥압 10 mmhg 이상의정상혈량을유지하게끔수액공급을하였다. 수액제한의정도는 Hwang 등의 14) 경우와같이간절제수술중특별한처치를하지않을경우일반적으로중심정맥압이 10 mmhg 이상으로유지되는것에착안하여중심정맥압 10 mmhg를기준으로하였다. 소변량이시간당 25 ml 이하이면 furosemide 5-10 mg을, 수축기혈압이 90 mmhg 이하이면, 소량의승압제 (ephedrine) 나수액을투여하였다. 간절제술이완료되고지혈을마친후에중심정맥압이낮은환자의경우에는교질액혹은농축적혈구로보충하였다. 심장질환이있거나혈역학이불안정한환자는혈색소 10 g/dl 이하의경우에, 그외의경우는 8 g/dl 이하의경우에만농축적혈구를수혈하였다. 간동맥과문맥을간헐적으로결찰하는프링글기법은 6) 사용하지않았으며, 간실질절제는주로초음파분쇄흡인기 (CUSA R, Cavitron Ultrasonic Surgical Aspirator, Valley lab, Colorado, USA) 를사용하였고부분적으로지혈감자를이용한수지분쇄법을사용하였다. 환자의기본자료, 간엽절제부위 ( 좌측혹은우측 ), 수술전, 수술직후, 술후 3일째 (POD3) 의혈색소, 신장기능 (BUN, creatinine), 혈액응고기능 (bleeding time, PT, aptt), 수술중출혈량 ( 초음파분쇄흡인기회수통, suction 흡인통에모인용액중세척용액을제외한혈액량및피에적셔진가제및테이프의무게에서마른가아제및테이프의무게를제외한양의합 ), 소변량, 수혈량, 수술후입원기간등을비교하였다. 각자료들은 SAS system을이용하여두군간은 t-test를, 술전, 후의비교는 paired t-test를시행하여 P값이 0.05 미만이거나, serum creatinine은 Melendez 등의 9) 경우처럼 0.5 mg/dl 이상증가한경우를의의있는결과로간주하였다. 결과수술중각군의최고중심정맥압은 L군에서 8.8 ± 1.2 mmhg, C군에서 14.3 ± 2.8 mmhg, 최저중심정맥압은 L군 5.1 ± 1.7 mmhg, C군 8.6 ± 2.7 mmhg으로, 두군간유의한차이를보였다 (P < 0.05)(Table 2). 중심정맥압은처음 664

3 최승호외 6 인 : 간절제시중심정맥압의영향 Table 2. Perioperative Data Group L (n = 30) C (n = 32) P value Lowest CVP (mmhg) 5.1 ± ± 2.7 <0.05 Highest CVP (mmhg) 8.8 ± ± 2.8 <0.05 Bleeding (ml) ± ± Transfusion (ml) 81.0 ± ± Fluid intake (ml) 3,027.5 ± 1, ,290.4 ± 1, Urine output (ml) ± ± Furosemide (mg) 0.4 ± ± Ephedrine (mg) 4.0 ± ± All values are expressed as mean ± SD. CVP: central venous pressure, group L: CVP < 10 mmhg, group C: control group, CVP > 10 mmhg. 2,500 2,000 Blood loss (ml) 1,500 1, Central venous pressure (mmhg) Fig. 1. Changes of central venous pressure (CVP) during study period. CVP in control group at initial and op. end show no difference between low CVP group, but CVP at op. start, dissection and lobectomy show significantly high than low CVP group. Values are mean ± SD. Initial: just after CVP monitoring, Op. start: operation start, Dissection: dissection for liver lobectomy, Lobectomy: just after liver lobectomy, Op. end: operation finish. *: P < 0.05 compared with low CVP group. 과수술종료시점에는양군간차이가없었으나, 간절제기간동안은 L군에서 C군보다의의있게낮았다 (Fig. 1). L군에서는간절제술및지혈기간동안혈관확장제를사용하지않고수액제한만으로중심정맥압이 10 mmhg 미만으로유지되었다. 출혈량은 L군에서 ± ml, C군에서 ± ml로통계적으로유의하지는않았다 (Table 2). 모든환자에서간절제술및지혈기간동안가장높게측정된중심정맥압과출혈량은 Y = X. regression = 0.282로상관관계가없었다 (Fig. 2). 수혈량역시 L 군 81.0 ± ml, C 군 ± ml Fig. 2. Linear regression analysis represent no significant relation between amount of blood loss and most high central venous pressure during liver dissection period. Y = X. Regression (r = 0.282). 로유의한차이는없었다. 수술중투여된수액의양은 L군 3,027.5 ± 1,098.2 ml, C군 3,290.4 ± 1,125.3 ml였고, 소변량은 L군 495 ± ml, C군 ± ml으로역시통계적차이는없었다. 소변량이적을때사용한 furosemide 및수축기혈압이떨어졌을때사용한약물인 ephedrine 사용량및또한두군간차이가없었다 (Table 2). 수술전, 수술직후, 수술후 1일과 3일의혈색소치및헤마토크리트의변화도두군간에통계적으로의미있는차이를보이지않았으며 (Table 3), 수술전및직후혈액응고, 간기능검사, 신장기능검사등의진단검사의학검사상두군간의통계적인차이도없었다 (Table 4). 고 일반적으로대량출혈의가능성이있는수술의마취관리 찰 665

4 대한마취과학회지 : 제 52 권제 6 호 2007 Table 3. Changes in the Level of Hemoglobin (g/dl) and Hematocrit (%) Group L (n = 30) C (n = 32) P value PreOp Hemoglobin 13.7 ± ± Hematocrit 40.4 ± ± POD#0 Hemoglobin 12.2 ± ± Hematocrit 36.0 ± ± POD#1 Hemoglobin 11.8 ± ± Hematocrit 34.3 ± ± POD#3 Hemoglobin 11.7 ± ± Hematocrit 42.9 ± ± All values are expressed as mean ± SD. PreOP: preoperation data, POD: post operative day, CVP: central venous pressure. group L: CVP < 10 mmhg, group C: control group, CVP > 10 mmhg. Table 4. Pre and Immediate Postoperative Laboratory Data Group L (n = 30) C (n = 32) P value PT (sec) Pre 11.9 ± ± Post 15.3 ± ± aptt Pre 34.5 ± ± (sec) Post 41.8 ± ± INR Pre 1.0 ± ± Post 1.4 ± ± AST Pre 34.2 ± ± (U/L) Post ± ± ALT Pre 42.4 ± ± (U/L) Post ± ± BUN Pre 13.3 ± ± (mg/dl) Post 10.8 ± ± Creatinine Pre 1.0 ± ± (mg/dl) Post 0.8 ± ± All values are expressed as mean ± SD. PT: prothrombin time, aptt: activated partial thromboplastin time, INR: internatinal normalized ratio, AST: aminotransferases aspartate, ALT: aminotransferases alanine, BUN: blood urea nitrogen, Pre: preoperation, Post: postoperation, CVP: central venous pressure. group L: CVP < 10 mmhg, group C: control group, CVP > 10 mmhg. 는출혈및이로인한혈역학적불안정의위험때문에수액을여유있게주어적정혈량혹은과혈량상태를유지하여예상되는출혈에대비하는것이일반적이다. 예전에는이러한개념이간절제술의경우에도해당되었다. 이러한경우중심정맥압이증가되며, 중심정맥도확장된다. 그결과로간정맥에서출혈이있을경우조절하기가쉽지않으며, 특히, 대정맥과유착된큰종양을절제할때는더욱지혈이힘든상황을초래한다. 또한절제기간동안출혈은조절할수있지만겸자를풀어혈류가정상으로돌아오면 간의절제면에서절제기간동안인식되지않은출혈이뒤따르게되어이로인한대량수혈및그로인한합병증 9) 등은피할수없는과정으로생각되어왔다. 간절제의범위가점점확대되어대량출혈이빈발해지자출혈을줄이기위한수술방법과마취관리의새로운개념이나방법들이도입되었다. 수술적인방법중간으로유입되는문맥혈과동맥혈류를차단하면서간정맥도동시에차단하는전간혈류차단법, 간문맥혈과간동맥혈류를차단하는프링글기법과복강경을이용한수술법등이있다. 2,5) 마취관리에대한개념은 1970년대초 Greenway 등의 8) 이론이후새로운지평을열게되었다. 즉 Greenway 등은 8) 중심정맥압이높은경우간에미치는영향에대하여다음과같은이론을제시하였다. 첫째, 간동모양혈관 (sinusoid) 을통해간정맥에서후방압력이생겨간동맥과문맥의혈류가감소된다. 둘째, 간동모양혈관에서압력이증가하여간동맥과문맥계의세동맥및세정맥에서반사성혈관수축이생기며증가된간동맥및문맥계의혈관저항은간의산소화를더욱감소시킨다. 셋째, 증가된간동모양혈관에서의압력으로인해수액의혈관외누출로부종이생겨문맥, 정맥및간동맥계의혈관저항을증가시켜혈전증및부종의빈도를높인다. 즉 Greenway와 Stark가 8) 제시한낮은중심정맥압을유지하는것이효과적이라는주장은낮은중심정맥압이간정맥과간동모양혈관의압력을낮게하여간절제동안출혈을줄인다는것에근거를둔다. 14,15) 대부분수술중의출혈은동맥혈출혈로중심정맥압과관련성이적지만간절제술시발생되는출혈은정맥혈출혈로중심정맥압과밀접한연관성이있어서적절한중심정맥압의관리가요구되어왔다. 중심정맥압을감소시키면대정맥확장이예방되어간정맥출혈이감소됨과동시에간의동원 (mobilization) 및주요간정맥절개를용이하게할수있다고한다. 3,5) 666

5 최승호외 6 인 : 간절제시중심정맥압의영향 Table 5. Comparison of Perioperative Blood Loss between Various Low Central Venous Pressure Anesthesia First author Technique Total patients Blood loss (ml) Cunningham, LCVP Melendez, LCVP Hwang, LCVP You, LCVP Lee, LCVP Presents series LCVP LCVP: low central venous pressure. 이러한이론은당시에는의학계의주목을받지못하였지만, 그후절제할간의범위가점점넓어지면서출혈이문제가되자, 1990년대후반부터여러연구자들이간절제술의경우수액관리를제한하여중심정맥압을낮추는방법및그효과를보고한논문들을살펴보면다음과같다. Johnson 등은 3) 간절제술동안하대정맥압과출혈과의상관관계를연구한바하대정맥압이 5 mmhg 이하로유지된경우는출혈량이 500 ml 이하였지만, 하대정맥압이 14 mmhg 이상으로유지된경우는출혈량이 2,000 ml 이상임을보고하였으며, 하대정맥압이 7 mmhg 미만으로유지된경우는수술후합병증이없었으나, 하대정맥압이 7 mmhg 이상으로유지된경우는합병증이생겼음을보고하였다. 또한 Jones 등은 10) 중심정맥압이 5 mmhg 이하로유지된경우는 200 ml의출혈량을, 5 mmhg 이상으로유지된경우는 1,000 ml의출혈량을보고하였다. 또한 Melendez 등, 9) Chen 등도 15) 중심정맥압을낮게유지하는방법을사용한결과각각 849 ml, 725 ml의출혈량을보고하였다. 출혈량을줄이기위한또다른노력으로기계호흡시일회호흡량을줄이면흡기말중심정맥상승을줄여 Greenway와 Stark의 8) 이론에의거하여출혈량을줄일수있다는보고도있으나, 별이득이없다는연구결과도있다. 17) 본연구에서중심정맥압과출혈량의차이가통계적인의의가없는이유로는첫째, 대부분의논문에서중심정맥압을 5 mmhg 이하로유지하였으나, 본실험에서는중심정맥압을 10 mmhg을기준점으로삼았으며, 둘째, 타논문에서는환자를 Trendelenburg 체위로 15 낮추었으나본연구에서는집도의의요구때문에 10 밖에낮추지못한점, 셋째, 지혈및수술기법의발달로중심정맥압에관계없이출혈량자체가타논문보다적었던점등을들수있겠다 (Table 5). 양군에서수액투여량의차이가없는이유는 L군에서는간절제및지혈전까지는 C군에비해수액을제한하였으나, 그이후는수액투여량을 C군에비해증가한결과로결국수술중투여한총수액투여량이비슷했다고생각된다. 667 이러한간절제완료전후의수액량투여비교가없는점은본연구뿐만아니라다른논문에서도마찬가지인데, 이는연구자들이간절제완료의시점을정확히기록하지못한결과라고생각되며이는본연구뿐만아니라다른연구에서도큰제한점이라하겠다. 간절제동안출혈을줄이기위해중심정맥압을낮게유지할때우려되는점은저혈압과핍뇨등합병증을유발할수있고, CUSA R 를이용한간절제중공기색전증의위험성이증가할가능성도있으며, 13) 간절제중대량출혈시혈역학적불안정이생길위험또한매우높다. 또한드물지않게신부전이발생할수있는데, 이는치명적인술후합병증중하나이며출혈량이증가할경우신부전발생가능성이증가하게된다. 4) 본연구에서도이러한합병증이염려되어실험군에서수액제한의기준점을타논문들의 5 mmhg보다높은 10 mmhg 이하로정하였으며, 기준점이 10 mmhg이므로실험군에서중심정맥압을낮추기위해혈관확장제를사용한경우는없었다. 이러한이유로혈관확장제까지사용하여중심정맥압을 5 mmhg 미만으로유지한연구들의결과와 6,9,10) 다른결과를초래한것으로생각되며차후기회가되면수액제한의기준점을중심정맥압을 5 mmhg 미만으로삼고연구해볼만한가치가있다고하겠다. 결론적으로간절제술중단순히중심정맥압을 10 mmhg 이하로유지하는것은그렇지않은경우와비교하여술중출혈량, 수혈량간유의한상관관계는없었으며, 술후간기능및유병률에도별영향을주지않았다. 그러므로간절제술시중심정맥압이외의다른많은인자들이출혈량에관여하므로출혈량및수혈량을줄이기위해서는중심정맥압을낮게유지하는노력외에도, 술전환자의상태나수술위치, 수술진행에따른세심한마취관리가필요하다고생각된다. 참고문헌 1. Nagorney DM, van Heerden JA, Ilstrup DM, Adson MA: Primary hepatic malignancy: surgical management and determinants of survival. Surgery 1989; 106: Farid H, O'Connell T: Hepatic resections: changing mortality and morbidity. Am Surg 1994; 60: Johnson M, Mannar R, Wu AV: Correlation between blood loss and inferior vena caval pressure during liver resection. Br J Surg 1998; 85: Yanaga K, Kanematsu T, Takenaka K, Matsumata T, Yoshida Y, Sugimachi K: Hepatic resection for hepatocellular carcinoma in elderly patients. Am J Surg 1988; 155: Cunningham JD, Fong Y, Shriver C, Melendez J, Marx WL, Blumgart LH: One hundred consecutive hepatic resections. Blood loss, transfusion, and operative technique. Arch Surg 1994; 129:

6 대한마취과학회지 : 제 52 권제 6 호 Lee SY, Kang KJ, Kim YH, Lim TJ, Hwang JS, Kwon JH, et al: Outcomes of hepatic resection using intermittent hepatic vascular inflow occlusion with low central venous pressure. Korean J Hepatobiliary Pancreat Surg 2004; 8: Thomas PG, Baer HU, Marthews JB: Postoperative hepatic necrosis due to reduction in hepatic arterial blood flow during surgery for chronic biliary obstruction. Dia Surg 1990; 7: Greenway CV, Stark RD: Hepatic vascular bed. Physiol Rev 1971; 51: Melendez JA, Arslan V, Fischer ME, Wuest D, Jarnagin WR, Fong Y, et al: Perioperative outcomes of major hepatic resections under low central venous pressure anesthesia: blood loss, blood transfusion, and the risk of postoperative renal dysfunction. J Am Coll Surg 1998; 187: Jones RM, Moulton CE, Hardy KJ: Central venous pressure and its effect on blood loss during liver resection. Br J Surg 1998; 85: Terai C, Anada H, Matsushima S, Shimizu S, Okada Y: Effects of mild Trendelenburg on central hemodynamics and internal jugular vein velocity, cross-sectional area, and flow. Am J Emerg Med 1995; 13: Hughson RL, Maillet A, Gauquelin G, Arbeille P, Yamamoto Y, Gharib C: Investigation of hormonal effects during 10-h head- down tilt on heart rate and blood pressure variability. J Appl Physiol 1995; 78: Koo BN, Kil HK, Choi JS, Kim JY, Chun DH, Hong YW: Hepatic resection by the Cavitron Ultrasonic Surgical Aspirator increases the incidence and severity of venous air embolism. Anesth Analg 2005; 101: Hwang SH, Kim KH, Chang YG, Hong SW, Paik IW, Lee HS: Effectiveness of continuing low central venous pressure during major hepatic resection. Korean J HBP Surg 2002; 6: Chen H, Merchant NB, Didolkar MS: Hepatic resection using intermittent vascular inflow occlusion and low central venous pressure anesthesia improves morbidity and mortality. J Gastrointest Surg 2000; 4: McCombs GB, Ott CE, Jackson BA: Effects of thoracic volume expansion on cardiorenal function in the conscious rat. Aviat Space Environ Med 1996; 67: Hasegawa K, Takayama T, Orii R, Sano K, Sugawara Y, Imamura H, et al: Effect of hypoventilation on bleeding during hepatic resection: a randomized controlled trial. Arch Surg 2002; 137: Yoo JG, Jang YH, Kim JM, Kim AR, Kang KJ: Changes in renal function by low dose dopamine in patients undergoing hepatectomy with low central venous pressure maintenance. Korean J Anesthesiol 2004; 47:

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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