Original Article J Korean Soc Transplant 2015;29:194-199 http://dx.doi.org/10.4285/jkstn.2015.29.4.194 신이식환자에서생리식염수와하트만용액이전해질과산염기및신기능에미치는영향 울산대학교간호학과 1, 계명대학교동산의료원이식혈관외과 2 김민영 1 ㆍ전나연 2 ㆍ현슬기 2 ㆍ김형태 2 ㆍ조원현 2 ㆍ박의준 2 The Effects of Normal Saline Solution versus Hartmann s Solution on the Acid-base and Electrolytes Status and Renal Function after Kidney Transplantation Min Young Kim, Ph.D. 1, Na Yeon Jeon, R.N. 2, Seul Ki Hyun, M.D. 2, Hyoung Tae Kim, M.D. 2, Won Hyun Cho, M.D. 2 and Ui Jun Park, M.D. 2 Department of Nursing, Ulsan University College of Medicine 1, Ulsan, Division of Transplant and Vascular Surgery, Department of Surgery, Keimyung University Dongsan Medical Center, Keimyung University School of Medicine 2, Daegu, Korea Background: The purpose of this study was to elucidate the effects of fluid on the acid base and electrolytes status and renal function after kidney transplantation (KT). Methods: We retrospectively analyzed 103 patients who underwent KT. Analyses were performed separately according to the donor type (living, 52; deceased, 51). In the living donor KT group, 28 patients received normal saline solution (NS) and 24 patients received Hartmann s solution (HS). In the deceased donor KT group, 27 patients received NS, and 24 received HS. The acid base and electrolyte status, urine volume, and renal function between patients receiving NS and patients receiving HS were compared in each group. Results: Regardless of donor type, there were no differences in potassium, ph, base excess, PCO 2 and HCO 3 between HS and NS on immediate postoperative and postoperative day 1. However, changes to neutral acid-base balance in terms of ph, HCO 3, and base excess were significantly higher in HS than in NS. In living donor KT, NS increased serum potassium and chloride significantly during fluid therapy. On postoperative day 7, renal function showed no difference between two groups but urine volume was significantly larger in NS than in HS. Conclusions: HS does not increase the incidence of hyperkalemia after KT. The use of HS resulted in less metabolic acidosis than the use of NS. Renal function was similar but polyuria was more severe in patients who received NS than in those who received HS. Key Words: Kidney transplantation, Fluid therapy, Electrolytes, Acid-base, Hartman s solution, Normal saline solution 중심단어 : 신장이식, 수액, 전해질, 산염기, 하트만용액, 생리식염수 Received May 19, 2015, Revised October 13, 2015, Accepted October 28, 2015 Corresponding author: Ui Jun Park Division of Transplant and Vascular Surgery, Department of Surgery, Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, 56 Dalseong-ro, Jung-gu, Daegu 41931, Korea Tel: 82-53-250-7315, Fax: 82-53-250-7322 E-mail: parkuijun@gmail.com Copyright c the Korean Society for Transplantation, 2015
Min Young Kim, et al: Fluid Therapy in Kidney Transplantation 서론 수액은병원에입원환환자에게가장많이주입되는약제이지만그중요성은간과되기쉽다. 신이식후환자는소변량이적을수도있으며반대로하루수천에서 10,000 ml 이상의소변을배설할수도있어, 신이식후수액을적절하게조절하는것은중요하다. 어떤종류의수액을어느정도공급하는것이적절한지에대한연구는많지않다. 만성신부전환자의경우대사성산증을주로보이며, 신이식직후에도대사성산증이지속되는경우가흔하다. 산염기의균형을조절하기위해서폐와신장이중요한완충기능을하는것은잘알려진사실이다. 이식초기에는신장의완충기능이완전히회복되지않아산염기불균형에대한즉각적인보상이어려울수있으며, 이에따른산염기불균형이지속되거나전해질장애가발생하여, 이식환자의임상경과에부정적인영향을미칠수있다 (1). 이식환자에게사용되는수액의종류에대한연구는많지않으며, 대부분의연구는수술중사용한수액에대한연구이다 (2,3). 수액에대한연구에서대량의생리식염수의주입은대사성산증의요인중하나로알려져있으며, 신장이식환자의경우, 기존의대사성산증을더악화시킬수있는요인이된다. 수술직후소변량이확보되지않은상태에서고칼륨혈증에대한부담으로국내의이식센터에서는생리식염수또는 1/2 생리식염수를신이식후수액으로사용하는경향이있으며, 경우에따라서는콜로이드용액도병행하고있다. 생리식염수의경우일반적으로수술환자에서다량으로사용할경우신장기능의감소, 감염및출혈의증가등의부작용이보고되며, 신이식환자에서는자유수분으로인한소변량의증가로수액의주입을증가시키게되고, 다시소변량의증가와수액주입의증가로반복될수있다 (3-9). 하트만용액은생리식염수에비해전해질조성과삼투질농도가혈장의구성과유사하며, 수술환자에서대사성산증의발생이적은것으로보고되고있다 (2,10). 본연구는신이식후하트만용액과생리식염수를사용한환자들의수술초기전해질, 산염기, 그리고소변량및초기신기능의차이를비교하고자한다. 대상및방법 2012년 11월부터 2014년 12월까지계명대학교동산의료원에서신이식후정맥주입용액으로하트만용액을사용한환자와생리식염수용액을사용한환자를대상으로 수술직후와 1일째의산염기상태및전해질상태를비교하였고, 7일째신기능과소변량을비교하였다. 환자는 18 세에서 70세의환자를대상으로하였고, 수술후이식신기능지연으로투석을시행한환자는산염기및전해질상태의변화가투석에의해영향을받기때문에연구에서제외하였다. 1. 마취및면역억제제모든환자에서요골동맥을통한동맥관및경정맥을통한중심정맥관을삽입후전신마취를시행하였다. 전신마취유도는 propofol (1.5 2 mg/kg) 과 sufentanil citrate (0.8 g/kg) 를사용하였고, 근이완제로는 cisatracurium besilate (0.15 ml/kg) 를사용하였다. 수술중마취의유지는 desflurane을사용하였다. 수술중수액은생리식염수를사용하였고, 수술중수액은시간당약 400 500 ml/hr 를주입하면서목표중심정맥압을 7 12 mmhg로유지하였다. 모든환자에서수술중 5% 알부민 250 ml를정주하였고, 혈관문합이끝나고나면 furosemide 20 mg과 mannitol 300 ml를정주하였다. 유도면역억제제로는 basiliximab 또는 thymoglobulin을사용하였고, 유지면역억제제로는 tacrolimus, mycophenolate mofetil과 prednisolone을사용하였다. 수술중혈관문합을시작할때 methylprednisolone (500 mg) 을투여하였다. 생체신이식의경우기증자신장은복강경수술을통하여적출하였다. 2. 신이식후수액요법 2012년 11월부터 2013년 12월까지신이식을받은환자에서는정맥주입용액으로생리식염수를사용하였고, 2014 년 1월부터 2014년 12월까지는하트만용액을사용하였다. 뇌사기증자부터신이식을받은경우생체기증자신이식에비해요량이적고고용량의이뇨제를사용하는경우가더많기때문에기증자유형에따라두군으로나누어연구를시행하였다. 신이식후정맥주입량은수술직후부터매시간배출되는소변량에따라 100 ml/hr 이하에서는 100 ml/hr, 100 300 ml/hr 인경우는소변량의 100%, 300 500 ml/hr인경우는소변량의 90%, 500 ml/hr 이상에서는소변량의 80% 를정맥주입하였다. 신이식후모든환자는외과중환자실의이식병상에서 2일간치료를받은후이식병동으로전실하였다. 중환자실에입실해있는동안노모그람에따라시간당수액보충을하고, 이식병동으로전실후 1 2일간은 4시간마다, 그이후는 8시간마다환자의소변량과체액상태를고려하여수액보충을하였다. 195
J Korean Soc Transplant ㆍ December 2015 ㆍ Volume 29 ㆍ Issue 4 3. 검사및통계전해질분석및동맥혈분석은수술직후 (T0) 와수술후 1일째 (T1) 의나트륨, 칼륨, 염소와 ph, PCO 2, HCO - 3, base excess (BE) 를평가하였다. 이식신의신기능은 7일째혈청크레아티닌으로 Modification of Diet in Renal Disease (MDRD) 공식 [estimated GFR MDRD=186 serum creatinine (mg/dl) 1.154 Age 0.203 (0.742 if female)] 을이용하여계산하였다. 통계분석은 IBM SPSS ver. 20.0 (IBM Co., Armonk, NY, USA) 을이용하였고, 범주형변수는 chi-square test, 연속형변수는 independent t-test를이용하여비교하였다. 생리식염수군과하트만용액군간 T0와 T1 시점에서각변수의변화의비교는 repeated measure analysis of variance test를이용하여분석하였다. 본연구는계명대학교동산병원의학연구윤리심의위원회의심의를통과하였다 (IRB 2015-03-54). 결과 전체환자는 103명이었고, 평균연령은 45.8세 ( 범위 ; 18 70), 남자가 59명 (57.3%) 이었다. 생체기증자로부터신이식을받은환자는 52명이었고, 뇌사기증자로부터신이식을받은환자는 51명이었다. 1. 생체신이식생체신이식환자중생리식염수를사용한환자는 28명이었고, 하트만용액을사용한환자는 24명이었다. 생리식염수군과하트만용액군에서연령, 성별, 원인신질환의 차이는없었다 (Table 1). T0와 T1시점에서칼륨은생리식염수군에서평균 0.3 mmol/l, 하트만용액군에서평균 0.1 mmol/l 증가하여생리식염수에서유의하게증가량이많았고 (P=0.029), 염소도생리식염수군에서평균 6.8 mmol/l, 하트만용액군에서평균 1.3 mmol/l 증가하여생리식염수군에서증가량이많았다 (P<0.001). 산염기변화량은, 생리식염수군에서 ph는평균 0.02, 하트만용액군에서 ph는평균 0.05 로하트만용액군에서 ph의증가량이컸다 (P=0.030). HCO 3 는생리식염수군에서평균 3.4 mmol/l, 하트만용액군에서평균 1.2 mmol/l 였고 (P=0.009), BE는각각평균 0.1 mmol/l 와 2.4 mmol/l (P=0.005) 로하트만용액군에서중성화경향이높았다. T0와 T1의나트륨과 PCO 2 의변화량은유의한차이를보이지않았다 (Table 2). 이식후 7일째평균요량은생리식염수군에서 10,896 ml/day, 하트만용액군에서 8,811 ml/day로생리식염수군에서평균요량이많았고 (P=0.049), 7일째신기능은생리식염수군에서 89.2 ml/min/1.73 m 2, 하트만용액군에서 81.8 ml/min/1.73 m 2 으로두용액군간차이를보이지않았다 (P=0.307) (Table 3). 2. 뇌사신이식뇌사신이식환자중생리식염수를사용한환자는 27명이었고, 하트만용액을사용한환자는 24명이었다. 생리식염수군과하트만용액군에서연령, 성별, 원인신질환의차이는없었다 (Table 1). 뇌사신이식에서 T0와 T1의산염기변화량은, 생리식염 Table 1. Patients demographics Variable Living donor KT Deceased donor KT P-value P-value Age (yr) Male sex Height (cm) Weight (kg) BMI (kg/m 2 ) Cause of ESRD Diabetes mellitus Hypertension Glomerulonephritis Others 41.9±11.9 15 (53.6) 165.3±9.9 62.7±14.0 22.7±2.9 3 (10.7) 1 (3.6) 17 (60.7) 7 (25.0) 44.9±11.5 13 (54.2) 164.7±9.4 64.3±14.6 23.6±4.4 9 (37.5) 0 10 (41.7) 5 (20.8) 0.334 0.966 0.832 0.688 0.386 0.118 45.2±11.4 15 (55.6) 162.2±8.3 58.6±8.7 22.2±2.0 6 (22.2) 3 (11.1) 14 (51.9) 4 (14.8) 48.9±9.4 16 (66.7) 163.9±7.8 60.9±7.6 22.6±2.2 2 (8.3) 1 (4.2) 15 (62.5) 6 (25.0) 0.300 0.417 0.460 0.335 0.428 0.352 Data are presented as mean±sd or number (%). Abbreviations: KT, kidney transplantation; NS, normal saline solution; HS, Hartmann s solution; BMI, body mass index; ESRD, end-stage renal disease. 196
Min Young Kim, et al: Fluid Therapy in Kidney Transplantation Table 2. Blood electrolytes and acid-base in normal saline group and Hartmann s solution in living donor kidney transplantation Variable Group Immediate postoperative (T0) Postoperative day 1 (T1) Difference P-value Serum electolyte Sodium (mmol/l) Potassium (mmol/l) Chloride (mmol/l) Acid-base analysis ph PCO 2 (mmhg) HCO 3 (mmol/l) BE (mmol/l) 132.8±3.9 134.3±2.8 4.0±0.5 4.1±0.6 98.5±4.8 102.2±4.3 7.35±0.44 7.33±0.58 37.3±3.7 38.9±4.3 24.0±5.7 20.5±4.0 4.2±3.1 4.6±4.4 136.3±3.5 135.9±2.1 4.3±0.4 4.2±0.5 105.3±4.5 103.5±3.5 7.37±0.36 7.38±0.38 35.5±3.3 37.7±3.2 20.8±3.9 22.1±2.9 4.1±2.5 2.2±3.10 3.6±4.6 1.6±3.1 0.3±0.4 0.1±0.5 6.8±4.8 1.3±3.6 0.02±0.04 0.05±0.05 1.8±3.8 1.2±3.2 3.4±5.8 1.7±2.6 0.1±2.5 2.4±2.9 0.087 0.029 <0.001 0.030 0.531 0.009 0.005 Data are presented as mean±sd. Abbreviations: NS, normal saline solution; HS, Hartmann s solution; BE, base excess. Table 3. Allograft renal function and urine volume on postoperative day 7 Variable NS HS P-value Living donor KT egfr (ml/min/1.73 m 2 ) Urine volume (ml/day) Deceased donor KT egfr (ml/min/1.73 m 2 ) Urine volume (ml/day) 89.2±28.8 10,896.4±3,889.6 59.7±34.1 6,871.1±3,579.3 81.8±21.6 8,811.3±3,485.2 61.3±30.8 4,996.6±2,361.1 0.307 0.049 0.860 0.031 Data are presented as mean±sd. Abbreviations: NS, normal saline solution; HS, Hartmann s solution; KT, kidney transplantation; egfr, epidermal growth factor receptor. 수군에서 ph는평균 0.01, 하트만용액군에서 ph는평균 0.05로하트만용액군에서 ph의증가량이컸다 (P=0.006). HCO 3 는생리식염수군에서평균 0.1 mmol/l, 하트만용액군에서평균 3.9 mmol/l였고 (P=0.002), BE 는각각평균 0.1 mmol/l와 3.6 mmol/l (P=0.009) 로하트만용액군에서중성화경향이높았다. T0와 T1의나트륨, 칼륨, 염소그리고 PCO 2 의변화량은유의한차이를보이지않았다 (Table 4). 이식후 7일째평균요량은생리식염수군에서 6,871 ml/ day, 하트만용액군에서 4,997mL/day 많았고 (P=0.031), 7 일째신기능은생리식염수군에서 59.7 ml/min/1.73 m 2, 하트만용액군에서 61.3 ml/min/1.73 m 2 으로두용액군간차이를보이지않았다 (P=0.860) (Table 3). 고찰 다량의생리식염수를정주하면혈중염소가증가하며중탄산염이감소하여대사성산증이유발되는것은잘알려진현상이다 (1,2,11-14). 신이식환자에서는수술후다뇨와함께다량의수액공급이요구되는환자가많으며, 정주하는수액의종류가환자의전해질및산염기의상태에영향을줄수있다. 신이식후정주하는수액의종류에대한연구는많지않으며, 지금까지의연구들은수술중사용하는수액의종류에대한연구들이대부분이다 (2,13). 본연구는신이식후초기투여한생리식염수와평형염액인하트만용액을사용한환자에서전해질및산염기상태를비교하였다. 신이식환자에서이식직후정주용액으로생리식염수와하트만용액을주입받은환자모두기증신 197
J Korean Soc Transplant ㆍ December 2015 ㆍ Volume 29 ㆍ Issue 4 Table 4. Blood electrolytes and acid-base in normal saline group and Hartmann s solution in deceased donor kidney transplantation Variable Group Immediate postoperative (T0) Postoperative day 1 (T1) Difference P-value Serum electolyte Sodium (mmol/l) Potassium (mmol/l) Chloride (mmol/l) Acid-base analysis ph PCO 2 (mmhg) HCO 3 (mmol/l) BE (mmol/l) 134.8±3.8 132.9±2.6 4.7±0.6 4.5±0.2 98.8±3.8 99.9±2.7 7.37±0.52 7.33±0.44 38.1±5.4 37.8±5.4 21.9±2.7 19.3±2.4 1.7±4.7 5.2±2.8 135.7±4.1 134.7±2.6 4.5±0.7 4.6±0.9 100.1±4.7 99.0±2.6 7.36±0.04 7.38±0.05 38.7±3.7 39.3±4.3 21.9±2.7 23.2±4.4 1.9±5.6 1.6±4.7 0.9±5.5 1.8±2.6 0.2±0.7 0.1±0.7 1.3±6.0 0.3±3.7 0.01±0.07 0.05±0.07 1.1±5.1 1.5±5.8 0.1±3.0 3.9±4.7 0.1±7.5 3.6±5.8 0.081 0.121 0.243 0.006 0.807 0.002 0.009 Data are presented as mean±sd. Abbreviations: NS, normal saline solution; HS, Hartmann s solution; BE, base excess. 장의유형과관계없이산증의유발또는전해질의장애없이안전하게사용할수있었다. 이식후 1주일에평가한신기능은투여한정주용액의종류간차이를보이지않았다. 본연구에서두용액군간유의한 ph의감소는없었으나, 산염기의상태를분석해보면생리식염수군에서 HCO 3 의감소및 BE의감소를보이는것은대사성산증이유발되는것으로이해할수있으며, PCO 2 의감소가동반되는것은유발된대사성산증에대한호흡보상이이루어지는것으로해석할수있다. 생리식염수는완충액을포함하지않기때문에많은양을정주하게되면체내의중탄산염을희석시켜대사성산증을유발할수있으며, 생리식염수에포함된다량의염소가대사성산증을유발하게된다 (15,16). 신이식을받는말기신부전환자에서흔히산염기의불균형이동반되어있고, 이식과정에서허혈재관류손상으로인한대사성산증이동반될수있기때문에, 다량의생리식염수를정주하는것은산증을악화시키게되거나산염기검사결과의해석을복잡하게만들수있다. 말기신부전환자는투석을시행하고있어도전해질불균형이발생하는경우가흔히있다. 신이식환자의수술후치료에있어서과칼륨혈증의발생을줄이는것이중요하기때문에, 칼륨이포함된하트만용액의사용을주의하게된다. 그러나, 본연구에서는수술후하트만용액을사용한환자에서치료나투석을필요로하는과칼륨혈증을보이는환자는없었고, 5.5 mmol/l 이상의과칼륨혈증을보이는환자는하트만용액군에서 4명, 생리식염수군에 서 3명으로두군간유의한차이를나타내지않았다. 본연구의결과만으로칼륨이포함된다량의하트만용액을정주하는것이과칼륨혈증의유발없이안전하다는결론을내리는것은무리가있다. 그러나, 이론적으로는생리식염수를투여하여발생하는고염소성대사성산증이혈액내의증가된수소이온과세포내칼륨의교환을일으켜과칼륨혈증을유발하게된다 (4,5,7). 생리식염수정주에따른혈중과염소증이신동맥의수축과신혈류의감소에따른신기능을저하시킬수있다 (9). 신이식환자에서정주용액의종류가신기능에영향을미칠수있다는것에대해서는논란의여지가있다 (17,18). 그러나, 이전의결정질용액을비교한연구에서는정주액의종류가이식신기능에영향을미치지않는것으로보고하였다 (2,3,13). 본연구에서는두용액군의소변량을비교해볼때생리식염수군에서하트만용액군에비해소변량이많았다. 본연구의결과만으로생리식염수군에서소변량이더많은이유를설명하는것에는한계가있으며, 추가적인연구가필요할것으로사료된다. 기증신장의유형에관계없이생리식염수와하트만용액두군간에초기신기능은차이를보이지않았다. 본연구는후향적연구이며, 환자의수가적고, 짧은기간의검사결과및임상정보를바탕으로시행한한계를가지고있다. 198
Min Young Kim, et al: Fluid Therapy in Kidney Transplantation 결론 본연구결과신이식후정주액으로생리식염수와하트만용액모두안전하게사용될수있다. 이식후정주액으로하트만용액은과칼륨혈증의증가가없었고, 생리식염수에비해산염기불균형이적었다. REFERENCES 1) McFarlane C, Lee A. A comparison of plasmalyte 148 and 0.9% saline for intra-operative fluid replacement. Anaesthesia 1994;49:779-81. 2) O'Malley CM, Frumento RJ, Hardy MA, Benvenisty AI, Brentjens TE, Mercer JS, et al. A randomized, double-blind comparison of lactated Ringer's solution and 0.9% NaCl during renal transplantation. Anesth Analg 2005;100: 1518-24. 3) Hadimioglu N, Saadawy I, Saglam T, Ertug Z, Dinckan A. The effect of different crystalloid solutions on acid-base balance and early kidney function after kidney transplantation. Anesth Analg 2008;107:264-9. 4) Adrogue HJ, Madias NE. Changes in plasma potassium concentration during acute acid-base disturbances. Am J Med 1981;71:456-67. 5) Halperin ML, Kamel KS. Potassium. Lancet 1998;352: 135-40. 6) Waters JH, Gottlieb A, Schoenwald P, Popovich MJ, Sprung J, Nelson DR. Normal saline versus lactated Ringer's solution for intraoperative fluid management in patients undergoing abdominal aortic aneurysm repair: an outcome study. Anesth Analg 2001;93:817-22. 7) Magder S. Balanced versus unbalanced salt solutions: what difference does it make? Best Pract Res Clin Anaesthesiol 2014;28:235-47. 8) Wu BU, Hwang JQ, Gardner TH, Repas K, Delee R, Yu S, et al. Lactated Ringer s solution reduces systemic inflammation compared with saline in patients with acute pancreatitis. Clin Gastroenterol Hepatol 2011;9:710-7. 9) Wilcox CS. Regulation of renal blood flow by plasma chloride. J Clin Invest 1983;71:726-35. 10) Takil A, Eti Z, Irmak P, Yilmaz Gogus F. Early postoperative respiratory acidosis after large intravascular volume infusion of lactated ringer s solution during major spine surgery. Anesth Analg 2002;95:294-8. 11) Tellan G, Antonucci A, Marandola M, Naclerio M, Fiengo L, Molinari S, et al. Postoperative metabolic acidosis: use of three different fluid therapy models. Chir Ital 2008; 60:33-40. 12) Scheingraber S, Rehm M, Sehmisch C, Finsterer U. Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery. Anesthesiology 1999;90:1265-70. 13) Khajavi MR, Etezadi F, Moharari RS, Imani F, Meysamie AP, Khashayar P, et al. Effects of normal saline vs. lactated ringer s during renal transplantation. Ren Fail 2008;30: 535-9. 14) Wilkes NJ, Woolf R, Mutch M, Mallett SV, Peachey T, Stephens R, et al. The effects of balanced versus salinebased hetastarch and crystalloid solutions on acid-base and electrolyte status and gastric mucosal perfusion in elderly surgical patients. Anesth Analg 2001;93:811-6. 15) Prough DS, White RT. Acidosis associated with perioperative saline administration: dilution or delusion? Anesthesiology 2000;93:1167-9. 16) Kellum JA. Determinants of blood ph in health and disease. Crit Care 2000;4:6-14. 17) Cittanova ML, Leblanc I, Legendre C, Mouquet C, Riou B, Coriat P. Effect of hydroxyethylstarch in brain-dead kidney donors on renal function in kidney-transplant recipients. Lancet 1996;348:1620-2. 18) Abdallah E, El-Shishtawy S, Mosbah O, Zeidan M. Comparison between the effects of intraoperative human albumin and normal saline on early graft function in renal transplantation. Int Urol Nephrol 2014;46:2221-6. 199