Á¾¼³

J Korean Soc Coloproctol: Vol. 26, No. 2, 87-92, 2010 DOI: 10.3393/jksc.2010.26.2.87 REVIEW 직결장수술에서의 Fast-Track 이인규 가톨릭대학교의과대학외과학교실 Fast-Track Colorectal Surgery In Kyu Lee Department of Surgery, The Catholic University of Korea College of Medicine, Seoul, Korea Conventional treatment after intra-abdominal surgery has emphasized prolonged rest of the gastrointestinal tract. The postoperative patient suffers a certain amount of functional or nutritional decline. However, using the fast-track protocol through a multidisciplinary team approach, the patient can overcome post-surgical troubles. Decrease of stress, return to normal functions, and avoidance of after effects can be achieved. The main elements of the fast track are epidural anesthesia, sublating the routine use of nasogastric tubes, enforced postoperative mobilization, and oral feeding. These prove to be effective in improving the patients status, in reducing the overall hospital stay, and in reducing postoperative complications. The ultimate aim of enhanced recovery after surgery should not be based on practical reasons such as early patient discharge, but should be founded on evidence-based medicine focusing on improving quality of life through standardized treatment. Keywords: Enhanced recovery programs; Fast-track protocols; Colorectal surgery 중심단어 : 수술후조기회복프로그램 ; Fast-track 프로토콜 ; 직결장수술 서 최근들어의료비의증가및포괄수가제 (diagnois related group, DRG) 도입등으로인하여조기퇴원에대한관심이증가되고있다. 또한, 대장수술에있어서도복강경수술이도입됨에따라재원기간이줄어들고있다. 하지만아직까지직결장수술후합병증의비율이 15-40% 로보고되고있으며, 1,2 개복수술에있어서재원기간은 6-13일까지다양하게보고되고있어 fast-track이일반화되어있지는않다. 1,3,4 Fast-track이라고부르는개념은 1999년 Kehlet에의해다학제적재활프로그램을통한구불결장절제술후재원기간을줄이고자하는노력에서시작되었다. 5 재원기간을줄이고 론 Received: January 21, 2010 Accepted: March 22, 2010 Correspondence to: In Kyu Lee, M.D. Department of Surgery, Yeouido St. Mary s Hospital, The Catholic University of Korea College of Medicine, 62 Yeouido-dong, Yeongdeungpo-gu, Seoul 150-713, Korea Tel: +82-2-3779-2235, Fax: +82-2-786-0802 E-mail: cmcgslee@catholic.ac.kr The Korean Society of Coloproctology 자하는목적으로초기에는조기경구섭취라는개념에서시작되었고, 우리나라에서는 fast-track이라는이름으로처음받아들여졌기때문에 fast-track을단지조기경구섭취, 조기퇴원이라는개념으로만받아들이는오류를범하기가쉽다. 하지만이러한목적및방법외에도수술적스트레스반응의감소, 회복속도의상승, 합병증의감소, 환자의안전성에문제가없는상태에서의비용의감소등다양한목적과많은요소를포함하고있는개념으로, 수술후조기회복프로그램 (enhanced recovery after surgery, ERAS) 으로부르는것이보다정확한개념을이해하는데도움이될것으로생각된다. 6 본문에서는이러한 ERAS의전체적인개념과주요구성요소에관하여논하고실제적인프로토콜에대해알아보고자한다. 본론일반적인수술후치료방법으로환자와위장관계의오랜휴식을강조해왔고, 수술후어느정도의영양상태감소나피로 87

88 In Kyu Lee : Fast-Track Colorectal Surgery 등이있는것으로생각되어왔다. 그러나다학제적인팀접근방식인 ERAS 프로토콜을통해스트레스의감소, 정상기능으로의빠른복귀, 수술후유증의회피등을이룰수있다는개념으로바뀌고있다. 1,6 이러한프로토콜의주요구성요소는 Table 1과같으며이중이제까지일반적이지않았으나증거의학을바탕으로입증되었으며 ERAS의중요한요소로생각되는구성요소에대해논하도록하겠다. 7 Major principles of the enhanced recovery after surgery protocol Preoperative fasting 이제까지수술전금식은마취과적인이유와대장의수술을위한장처치때문에시행해왔다. 하지만, 최근들어수술전장처치가많은연구결과에있어직결장수술에도움이되지않으며오히려문합부누출의위험성을증가시킨다는연구결과가발표되고있다. 8,9 그러므로모든환자에있어서장처치가필요하지않으므로수술전에금식을해야하는이유는마취중발생할수있는음식물의폐흡입을막기위해서다. 위배출시간 (gastric emptying time) 을연구한결과에서음료수 (clear liquid) 의경우에는 1시간내에위내부체적의 10% 이내로남았으며고형식의경우 3시간이경과한후비슷한결과를보였다. 이러한결과등을바탕으로여러국가의마취과학회에서는음료수는마취전 2-3시간전까지, 고형식은 6-8시간전까지허용하고있다. 마취의이유외에도환자의회복에있어서도음식의섭취는중요하다는보고가있다. 여러동물실험에있어서도음식물을섭취한동물에있어 Table 1. Main elements of the enhanced recovery after surgery protocol Preadmission information and counseling No preoperative bowel preparation Fluid and CHO-loading/no fasting Anti-thrombotic prophylaxis Anti-microbial prophylaxis Mid-thoracic epidural anaesthesia/analgesia Short-acting anaesthetic agent No nasogastric intubation Warm air body heating in theatre Avoidance of sodium/fluid overload Short incisions and no drain Early removal of urinary drainage Prevention of nausea and vomiting Ileus prophylaxis and promotion of gastrointestinal motility Non-opiate oral analgesics/non-steroidal anti-inflammatory drugs analgesia Perioperative oral nutrition Early mobilization 서외상에대한반응으로스트레스에대한내분비반응이적었고, 당대사작용이보다더동화 (anabolic) 방식으로반응하였다. 10,11 또한, 이러한사건후근육의높은강도를보였으며세균의 translocation이적음을보였다. 10,11 사람에있어서도수술전 30% 의당을주거나탄수화물이다량포함된 (12.6%) 음료수를준경우에있어서수술후인슐린저항성이감소한연구결과가있고수술후갈증, 배고픔, 불안까지감소시킨다는보고가있으므로마취에위험을주지않을정도로수술전에음식을섭취하는것이수술후회복에중요한역할을함을알수가있다. 12,13 일반적으로수술전 2시간전까지음료수의섭취, 6시간전까지고형물의섭취를가능하게하고환자가경구로탄수화물을포함한음료수의섭취를할수있도록하는것이중요하다. Epidural anesthesia and analgesia effects 수술로인한스트레스반응은여러가지메커니즘에의하여그반응이변형된다. 관련된메커니즘으로는신경내분비계반응, 염증반응등일반적인반응뿐아니라감염, 출혈, 금식, 저체온, 불안, 고정 (immobilization) 등이있으며이로인하여그반응이증가된다. 14,15 이러한반응들이과도하게일어날경우합병증이나기능이상등이나타나게된다. 하지만 epidural blockade나 analgesia를통해 afferent neural stimuli를막거나감소시킴으로써수술후이화작용 (catabolism) 을야기하는 cortisol, glucagon, catecholamine의분비를감소시키고스트레스로인한효과를감소시켜빨리동화상태 (anabolic state) 로의전환을촉진시킨다. 14 사용하는약제에있어서는뒤에서다시언급하겠지만장기간작용을하는 opioid (morphine, fentanyl) 는수술후장마비를유발하므로피해야하며, 직결장수술시에는 T7/8 레벨의 midthoracic epidural anesthesia를수술전에시행하는것이수술로인한스트레스반응을줄이는동시에교감신경차단을통해장마비를예방할수있다. 6,16 Perioperative fluid management 전통적인외과적치료에있어서수술당일에는 3.5-5 L 가량의수액을주며수술후 3-4일까지하루에 2 L 가량의수액을주는것이일반적이었다. 하지만최근들어체액평형을유지할정도이상의수액을주지않도록수액을제한하는것이수술후합병증을줄이고수술후재원기간을감소시킨다는연구결과들이발표되고있다. 6,17,18 Lobo 등 17 은수분과나트륨을 2 L와 77 mmol 이하로제한한환자가일반적으로치료

이인규 : 직결장수술에서의 Fast-Track 89 한군에비하여체중 ( 감소 ) 과혈장알부민 ( 증가 ) 에있어유의한차이가있었으며고형식과유동식의위의배출시간이유의하게빨리배출되었다고보고하였다. 또한경과관찰중가스및대변배출, 고형식의시작, 재원기간, 합병증병발에있어서도유의한차이가있었다. Brandstrup 등 18 도수술전후수액을제한하고체중이 1 kg 증가시 furosemide를준군이제한을하지않은군에비하여두군간에몸무게가수술후 6일까지유의한차이가있었으며, 합병증에있어서도유의한차이가있었다고보고하였다. 이러한합병증의빈도는투여된수액과몸무게가증가될수록증가한다고발표하였다. 그러므로수술후에는체액평형을유지할정도의수액을주는것이수술후합병증을줄이게한다. 또한, 과도한식염수의투여는정상위장관기능회복의지체를가져오므로적절한경구섭취가가능하면정맥수액투여는중단하도록하는것이권장된다. Ileus prophylaxis and promotion of gastrointestinal motility 주요복부수술을받은환자에있어서수술후특별한처치를하지않는다면수술후장마비는 4-5일간지속된다. 16 이러한수술후장마비의주원인은자율신경계의기능이상으로생겨난다. 교감신경의경우장운동의억제작용을담당하는데반하여부교감신경은장운동의자극제로작용한다. 그외에 calcitonin gene-related peptide, nitric oxide, vasoactive intestinal peptide, substance P와같은장신경전달물질 (enteric neurotransmitter) 이장운동억제작용을하는것으로알려져있다. 16 Prostaglandin을통한염증반응도장마비와관련이있으며, 19 앞에서언급했듯이 narcotics의경우도장신경계 (enteric nervous system) 을통해위장관평활근 (gastrointestinal smooth muscle) 에영향을주어장운동을감소시키는것으로알려져있다. 20 그외에도 vasopressin과 corticotropin releasing factor와같은위장관호르몬도장마비를유발하는것으로되어있으며, 16 마취의경우도 nitrous oxide나 opioid와같은약제를통해장마비를유발한다. 21 장마비의전통적치료방법으로는경비관배액술, 정맥내수액투여, 전해질불균형교정및관찰등을해왔지만현재에는이러한경비관의경우복부수술후에는도움이안되며오히려장마비의기간을증가시킨다는보고까지있다. 22 현재에는 sympatholytics, parasympathetic drugs (neostigmine, metoclopramide, cisapride 등 ), non-steroidal antiinflammatory drugs 등이사용되고있으며 ceruletide, erythromycin과같은위장관호르몬과관련된약제등이장마 비를감소시키는것으로알려져있다. 그외에도 magnesium salt laxative, 수용성방사능조영제, 껌, 조기경구투여, 조기보행등도도움이된다는보고가있다. 16 최근에는 cyclo-oxygenase 2 inhibitor, motilin agonist 등이임상적실험을시행하고있으며 19,23 Alvimopan과같은 peripherally restricted μopioid receptor antagonist가 3상실험을통해위장관기능의회복을빠르게하며특별한합병증이없이사용될수있다는연구결과가발표되고있다. 24 Postoperative nutritional care 조기경구섭취는수술후영양관리의중요한요소중에하나이며, 위장관수술후조기경구섭취한군과전혀음식을먹지않은군과의중재분석 (meta-analysis) 에서조기경구섭취는문합부누출과창상감염, 폐렴, 복강내농양형성등의모든종류의감염과수술후사망등에있어서이점이있는것으로분석되었으나단지구토는증가되는것으로보고하고있다. 25 하지만, 이러한조기경구섭취를위해서는앞에서언급한다양한방법의장마비예방을위한조치가필요하며, 이러한처치를시행하지않았을경우조기경구섭취군에서환자의활동이나폐기능이떨어지는결과를보였고장마비로인한복부팽만을야기하였다. 26 그러므로적절한장마비예방조치와함께수술후 4시간후경구섭취를권유하며수술당일 800 ml 이상의경구수분섭취를목표하여점진적으로정상경구섭취상태를이루도록권장하고있다. 6 Discharge criteria ERAS 프로토콜을통해환자가충분이회복되어퇴원을하게되는기준은경구진통제로통증조절이되며, 고형식을먹으며정맥수액보충이필요없고, 입원전상태의독립적인활동이가능하며, 환자가집에가고자하는의지가있는경우로이러한모든요건을충족할경우퇴원을하는것이권고되고있다. 6 Protocol for the enhanced recovery after surgery ERAS protocol을실제적으로적용하는데있어서 Table 1 의요소를모두적용하는데는어려움이있다. 2009년도까지 15그룹에서시행한 ERAS를비교하였을때 10 개 group 이상에서동시에시행한요소를보면 preoperative counseling, epidural anesthesia, no routine use of nasogastric (NG) tube, enforced postoperative mobilization, enforced postoperative oral feeding이었다 (Table 2). 1,3,7

90 In Kyu Lee : Fast-Track Colorectal Surgery Table 2. Fast-track elements included per study Study Design Preoperative counseling Preoperative feeding No bowel preparation No premedication Fluid restriction Active prevention of hypothermia Epidural analgesia Minimal invasive/transverse incisions No routine use of NG tubes No use of drains Enforced postoperative mobilization Enforced postoperative feeding No systemic morphine use Standard laxatives Early removal of bladder catheter Gatt RCT King RCT Anderson RCT Delaney RCT Khoo RCT Kariv CCT Stephen CCT Bradshaw CCT Raue CCT Wichmann CCT Basse CCT Polle CCT MacKay CCT Junghans CCT Lee CCT RCT=randomized controlled trial; CCT=controlled clinical trial; NG=nasogastric. 2005년도부터 2007년까지 24개기관, 2,047명을대상으로독일에서시행한 Fast-track Colon II (FTCII) 연구에서는수술전장처치를시행하지않으며수술 2시간전까지탄수화물을포함한음료수를먹였으며수술전 thoracic epidural anesthesia를시행하였다. 또한수술후수액을제한하였으며조기경구섭취와함께 magnesium oxide를섭취하였고조기활동을권유하였다. 27 독일의경우한국과비슷한의료환경으로 DRG 등으로인하여짧은입원기간의경우삭감을하는경우가있어빠른퇴원보다는합병증을줄이는데더관심이많아이러한 fast-track 에대한관심이늘어가고있다. 저자나대한민국의 ERAS를시행하는그룹에있어서아직까지이러한모든중요프로토콜을시행하고있지않으며그중에서도수술전 epidural anesthesia는여러여건상대부분병원에서시행하지않고있다. 또한, 장세척이나장마비예방처치에대한인식이적게되어있는것을알수있었다. 본저자의경우에는우측대장절제술부터전방위절제술환자에있어서 ERAS를시행하고있으며프로토콜로는장세척은시행하지만수술전까지수액의경구섭취를시행하며수 술후즉각적인 NG tube를제거한다. 수술후 1일째부터경구섭취를시행하며정맥을통한수액의보충을제한하고체중검사를통해체중증가시 furosemide를투여하고있다. 또한 magnesium oxide와장운동증강제를수술당일부터경구투여하고있다. 아직까지는 RCT를통한연구는시행하고있지못하지만단순비교를통해재원기간이짧아졌으며통계적으로는의의가없었지만환자의합병증에있어서감소하는경향을보였다. 결론대장절제술에있어서 ERAS를통한환자의관리는환자의재원기간의감소뿐만아니라환자의전반적인상태에향상을가져온다. 또한, 조기경구투여로인한문합부누출등의증가를가져오지않으며여러종류의감염의감소등많은이점이있다. 하지만아직까지이를시행하는데는조기경구투여의개념외에도많은중요한요소가있고외과, 마취과뿐만아니라병원전체의시스템적인뒷받침이있어야한다. 우선은외과의사가 ERAS에대한정확한이해와관심을

이인규 : 직결장수술에서의 Fast-Track 91 가지고이러한프로토콜의임상적적용을통해진정한의미의 ERAS를이루는것이중요하다생각된다. 마지막으로, ERAS의목적을조기퇴원이라는현실적인이유보다환자치료에있어서증거중심의의학을바탕으로한표준화된치료를통해합병증발생률을감소시키고조기회복을통한삶의질의향상에목표를두어야겠다. REFERENCES 1. Gouvas N, Tan E, Windsor A, Xynos E, Tekkis PP. Fast-track vs standard care in colorectal surgery: a meta-analysis update. Int J Colorectal Dis 2009;24:1119-31. 2. Lang M, Niskanen M, Miettinen P, Alhava E, Takala J. Outcome and resource utilization in gastroenterological surgery. Br J Surg 2001;88: 1006-14. 3. Vlug MS, Wind J, van der Zaag E, Ubbink DT, Cense HA, Bemelman WA. Systematic review of laparoscopic vs open colonic surgery within an enhanced recovery programme. Colorectal Dis 2009;11:335-43. 4. Lee IK, Lee SM, Kim SS, Lee YS, Koh WL, Kim HK, et al. Critical pathway for colorectal and gastric cancer. J Korean Soc Coloproctol 2007;23:80-6. 5. Kehlet H, Mogensen T. Hospital stay of 2 days after open sigmoidectomy with a multimodal rehabilitation programme. Br J Surg 1999;86: 227-30. 6. Fearon KC, Ljungqvist O, Von Meyenfeldt M, Revhaug A, Dejong CH, Lassen K, et al. Enhanced recovery after surgery: a consensus review of clinical care for patients undergoing colonic resection. Clin Nutr 2005; 24:466-77. 7. Lee IK, editor. Fast-track pathway protocol for colorectal surgery. The 15th Seoul coloproctology course 2009. Seoul: Medrang; 2009. p. 79-83. 8. Wille-Jorgensen P, Guenaga KF, Castro AA, Matos D. Clinical value of preoperative mechanical bowel cleansing in elective colorectal surgery: a systematic review. Dis Colon Rectum 2003;46:1013-20. 9. Platell C, Hall J. What is the role of mechanical bowel preparation in patients undergoing colorectal surgery? Dis Colon Rectum 1998;41: 875-82. 10. Ljungqvist O, Soreide E. Preoperative fasting. Br J Surg 2003;90:400-6. 11. Ljungqvist O, Nygren J, Hausel J, Thorell A. Preoperative nutrition therapy-novel developments. Scan J Nutr 2000;44:3-7. 12. Nygren JO, Thorell A, Soop M, Efendic S, Brismar K, Karpe F, et al. Perioperative insulin and glucose infusion maintains normal insulin sensitivity after surgery. Am J Physiol 1998;275:140-8. 13. Hausel J, Nygren J, Lagerkranser M, Hellstrom PM, Hammarqvist F, Almstrom C, et al. A carbohydrate-rich drink reduces preoperative discomfort in elective surgery patients. Anesth Analg 2001;93:1344-50. 14. Holte K, Kehlet H. Epidural anaesthesia and analgesia-effects on surgical stress responses and implications for postoperative nutrition. Clin Nutr 2002;21:199-206. 15. Kehlet H. Modification of responses to surgery by neural blockade: clincal implications. In: Clousins MJ, Bridenbaugh PO, editors. Neural blockade in clinical anesthesia and management of pain. 3rd ed. Philadelphia: Lippincott-Raven; 1998. 16. Miedema BW, Johnson JO. Methods for decreasing postoperative gut dysmotility. Lancet Oncol 2003;4:365-72. 17. Lobo DN, Bostock KA, Neal KR, Perkins AC, Rowlands BJ, Allison SP. Effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection: a randomised controlled trial. Lancet 2002;359:1812-8. 18. Brandstrup B, Tonnesen H, Beier-Holgersen R, Hjortso E, Ording H, Lindorff-Larsen K, et al. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Ann Surg 2003;238:641-8. 19. Schwarz NT, Kalff JC, Turler A, Engel BM, Watkins SC, Billiar TR, et al. Prostanoid production via COX-2 as a causative mechanism of rodent postoperative ileus. Gastroenterology 2001;121:1354-71. 20. Bardon T, Ruckebusch Y. Comparative effects of opiate agonists on proximal and distal colonic motility in dogs. Eur J Pharmacol 1985; 110:329-34. 21. Condon RE, Cowles V, Ekbom GA, Schulte WJ, Hess G. Effects of halothane, enflurane, and nitrous oxide on colon motility. Surgery 1987; 101:81-5. 22. Cheatham ML, Chapman WC, Key SP, Sawyers JL. A meta-analysis of selective versus routine nasogastric decompression after elective laparotomy. Ann Surg 1995;221:469-78. 23. Trudel L, Tomasetto C, Rio MC, Bouin M, Plourde V, Eberling P, et al. Ghrelin/motilin-related peptide is a potent prokinetic to reverse gastric postoperative ileus in rat. Am J Physiol Gastrointest Liver Physiol 2002;282:948-52. 24. Delaney CP, Wolff BG, Viscusi ER, Senagore AJ, Fort JG, Du W, et al. Alvimopan, for postoperative ileus following bowel resection: a pooled analysis of phase III studies. Ann Surg 2007;245:355-63.

92 In Kyu Lee : Fast-Track Colorectal Surgery 25. Lewis SJ, Egger M, Sylvester PA, Thomas S. Early enteral feeding versus nil by mouth after gastrointestinal surgery: systematic review and meta-analysis of controlled trials. BMJ 2001;323:773-6. 26. Watters JM, Kirkpatrick SM, Norris SB, Shamji FM, Wells GA. Immediate postoperative enteral feeding results in impaired respiratory mechanics and decreased mobility. Ann Surg 1997;226:369-80. 27. Braumann C, Guenther N, Wendling P, Engemann R, Germer CT, Probst W, et al. Multimodal perioperative rehabilitation in elective conventional resection of colonic cancer: results from the German Multicenter Quality Assurance Program Fast-Track Colon II. Dig Surg 2009;26:123-9.