중환자실에입원한환자의장기부전및예후평가를위한 SOFA 점수체계의의의 한림대학교의과대학내과학교실, 강원대학교의과대학내과학교실 1 김수호, 이명구, 박상면, 박용범, 장승훈, 김철홍, 전만조, 신태림, 엄광석, 현인규, 정기석, 이승준 1 The SOFA Score to Evaluate Organ Failure and Prognosis in the Intensive Care Unit Patients Su Ho Kim, M.D., Myung Goo Lee, M.D., Sang Myeon Park, M.D., Young Bum Park, M.D., Seung Hun Jang, M.D., Cheol Hong Kim, M.D., Man Jo Jeon, M.D., Tae Rim Shin, M.D., Kwang Seok Eom, M.D., In-Gyu Hyun, M.D., Ki-Suck Jung, M.D., Seung-Joon Lee, M.D. 1 Department of Internal Medicine, College of Medicine, Hallym university, Chuncheon, Korea; Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Korea 1 Background : The Sequential Organ Failure Assessment (SOFA) score can help to assess organ failure over time and is useful to evaluate morbidity. The aim of this study is to evaluate the performance of SOFA score as a descriptor of multiple organ failure in critically ill patients in a local unit hospital, and to compare with APACHE Ⅲ scoring system. Methods : This study was carried out prospectively. A total of ninety one patients were included who admitted to the medical intensive care unit (ICU) in Chuncheon Sacred Heart Hospital from May 1 through June 30, 2000. We excluded patients with a length of stay in the ICU less than 2 days following scheduled procedure, admissions for ECG monitoring, other department and patients transferred to other hospital. The SOFA score and APACHE Ⅲ score were calculated on admission and then consecutively every 24 hours until ICU discharge. Results : The ICU mortality rate was 20%. The non-survivors had a higher SOFA score within 24 hours after admission. The number of organ failure was associated with increased mortality. The evaluation of a subgroup of 74 patients who stayed in the ICU for at least 48 hours showed that survivors and non-survivors followed a different course. In this subgroup, the total SOFA score increased in 81% of the non-survivors but in only 21% of the survivors. Conversely, the total SOFA score decreased in 48% of the survivors compared with 6% of the non-survivors. The non-survivors also had a higher APACHE Ⅲ score within 24 hours and there was a correlation between SOFA score and APACHE Ⅲ score. Conclusion : The SOFA score is a simple, but effective method to assess organ failure and to predict mortality in critically ill patients. Regular and repeated scoring enables patient's condition and clinical course to be monitored and better understood. The SOFA score well correlates with APACHE Ⅲ score. (Tuberc Respir Dis 2004; 57:329-335) Key words : APACHE Ⅲ, Intensive Care Unit, Multiple Organ failure, Sequential Organ Failure Assessment (SOFA) 서론 임상적연구에서예후판정지표 (prognostic scoring 본논문의요지는 2001 년제 93 차대한결핵및호흡기학회추계학술대회에서구연발표되었음. Address for correspondence : Myung Goo Lee, M.D. Department of Internal Medicine, Chuncheon Sacred Heart Hospital 153 Gyo-dong, Chuncheon-si, Gangwon-do, 200-704, Korea Phone : 82-33-252-9970 Fax : 82-33-256-4291 E-mail : mglee@hallym.or.kr Received : May. 31. 2004. Accepted : Aug. 17. 2004. system) 는중환자의중증도 (severity) 를평가하고병의경과를이해하는것을향상시키며, 새로운치료법에대한평가를가능하게한다. 과거에는병의중증도를평가하는수단으로 Acute Physiology And Chronic Health Evaluation (APACHE) Ⅱ & Ⅲ, Simplified Acute Physiology Score (SAPS) Ⅱ가많이사용되었다. 그러나이러한점수체계는이환율보다는사망률을예측하는것이기때문에중환자실의집중치료및치료효과를평가하는데에는적합하지가않다 1. 이런점때문에 1996년에 European Society of Intensive Care and Emergency Medicine (ESICEM) 329
SH Kim, et al.: The SOFA score to evaluate organ failure and prognosis in the intensive care unit patients Table 1. The sequential organ failure assessment (SOFA) score SOFA score variables 0 1 2 3 4 Respiration Coagulation Liver PaO 2/FIO 2 >400 400 300 200 * 100 * Platelets ( 10 9 /L) Bilirubin (μmol/l) Cardiovascular Hypotension Central Nervous System Renal Glasgow coma score >150 150 100 50 20 <20 20-32 33-101 102-204 >204 No hypotension MAP<70mmHg Dopamine 5 or dobutamine (any dose) Dopamine>5 or epi 0.1 or norepi 0.1 Dopamine>15 or epi>0.1 or norepi>0.1 15 13-14 10-12 6-9 <6 Creatinine (μmol/l) or urine output <110 110-170 171-299 300-440 or <500 ml/day >440 or <200 ml/day * With respiratory support. Mean arterial pressure. Adrenergic agents administered for at least 1 hour (dosages are in μg/kg/min). epinephrine. norepinephrine. 에서이환율을예측할수있는 Sequential Organ Failure Assessment (SOFA) 점수체계를발표하였고, Vincent 등 2 은다기관전향적연구를통하여 SOFA 점수체계가장기기능을평가하고경과를감시하는간편하고효과적인점수체계임을입증하였다. 이연구는춘천성심병원에서내과계중환자의장기부전을평가하는것에대해 SOFA 점수체계의유용성을조사하였고, 중환자실입원 24시간내 SOFA 점수와 APACHE Ⅲ 점수와의상관관계를알아보았다. 대상및방법 2000년 5월 1일부터 6월 30일까지춘천성심병원내과계중환자실에입원한 154명을대상으로전향적연구를시행하였다. 이중타과환자, 타병원으로전원된경우, ECG 관찰만을위하여입원한경우, 처치후관찰을위해 48시간이내만체류한환자 49명을제외한 105명을연구에포함시켰으며, 91명에서평가가가능하였다. SOFA 점수는입원시부터매일 24시간간격으로중환자실에서퇴실할때까지기록하였다 (Table 1). 처음 24시간이내에검사한 6개의생리적측정값중가장나쁜측정치를선택하여각각 0 4 점의점수를주고, 이들을합하여기록하였다. 또한측정값이 3점이상인경우장기부전으로정의하였다. Catecholamine 의투여는적절한수액공급후에도평균동맥압력 (mean arterial pressure) 이 70 mmhg 미만인경우에 dopamine 정맥투여를시작하였고, 최대용량까지증량한후평균동맥압력이유지되지않을경우 norepine phrine을투여하였으며, 심박출량을증가시키고자할때 dobutamine 을병용하였다. 또한평균동맥압력이 70 mmhg 이상유지되고저혈압에서회복되면 cate cholamine 투여를종료하였다. 연구의후반부터는 APACHE Ⅲ 점수를함께기록하였으며, 총 62명에서비교가가능하였다. 중환자실에서의체류기간과사망률은중환자실을퇴실할때까지의생존상태로하였다. 대상환자들의사망여부에따라서생존군과사망군으로분류하였다. SOFA 점수 330
Tuberculosis and Respiratory Diseases Vol. 57. No. 4, Oct, 2004 Table 2. Demographic data of study population Number of patients 91 Age (years) 61±15 Gender Male 70 Female 21 Source of admission (%) - emergency department - general ward - outpatient Median length of stay (days) 69 (76) 19 (21) 3 (3) 3 (1 44) MICU mortality (%) 18 (20) Medical intensive care unit Table 3. Comparison between SOFA score and APACHE Ⅲ score within 24 hours after admission (mean±sd). SOFA score APACHE Ⅲ score Survivors 3.85±3.24 ** 45.21±21.06 Non-survivors 8.17±4.05 ** 90.85±45.65 ** p < 0.01, p < 0.01 Figure 1. Mortality rate (%) and number of failing organs. 의변화는중환자실의입원시와치료기간중가장높게혹은가장낮게측정된 SOFA 점수와의차이로관찰하였다. 자료분석은 dbstat for Windows 통계프로그램을이용하였다. 사망군과생존군간의 SOFA 점수와 APACHE Ⅲ 점수의평균치의차이는 Student's t-test를이용하여분석하였고, 장기부전의수와사망률의경향분석은 Mantel-Haenzel trend test를이용하였다. 통계학적유의성은 p 값이 0.05 이하인경우로하였다. 결과대상환자는 91명으로남자가 70명, 여자가 21명이었고, 평균연령은 61세였다. 중환자실에입원한환자의원인질환을보면, 급성심근경색증 12명, 식도정맥류또는위궤양에의한상부위장관출혈 11명, 폐렴 8명, 울혈성심부전 7명, 패혈증 7명, 약물중독 6명으로나타났으며, 그외당뇨병성케톤산증, 만성폐쇄성폐질환의급성악화, 신부전, 간성혼수, 기흉, 악성종양등의질환이있었다. 사망률은 20% 였고, 중환자실체류기간의중앙값은 Figure 2. The number of organ failure was associated with increased mortality (p < 0.0001, Mantel-Haenzel trend test). 3일이었다 (Table 2). 사망군과생존군간의 24시간내 SOFA 점수는각각 8.17±4.05, 3.85±3.24로유의한차이가있었다 (Table 3). 사망률은입원시장기부전의수에따라서증가하였다. 장기부전이없는경우의사망률은 6.5%, 5개의다발성장기부전이있는경우사망률은 100% 였다. 장기부전의수가많을수록사망률이유의하게높았다 (Figure 1, 2). 임상경과에따른 SOFA 점수의변화를알아보기위해 48시간이상체류했던 74명을대상으로분석하였다. 최대 SOFA 점수의증가는사망군에서 81%, 생존군에서는 21% 로나타났으며, 최대 SOFA 점수의감소는사망군에서 6%, 생존군에서는 48% 로나타났다 (Table 4). 24시간내 APACHE Ⅲ 점수는사망군에서 90.85±45.65, 생존군에서 45.31±21.06으로유의한차이 331
SH Kim, et al.: The SOFA score to evaluate organ failure and prognosis in the intensive care unit patients Table 4. Total SOFA score changes according to clinical course. The evaluation of a subgroup of 74 patients who stayed in the ICU for at least 48 hours. Increase vs. others (%) Decrease vs. others (%) Survivors 12/46 (21) 28/30 (48) Non-survivors 13/3 (81) 1/15 (6) decrease or no change increase or no change p < 0.01, p < 0.01 가있었다. 또한 24시간내 SOFA 점수와 APACHE Ⅲ 점수와의관련성을평가한결과 r = 0.85 (p < 0.01) 로유의한상관관계를보였다 (Figure 3). 고찰 다발성장기부전은중환자실에서의사망률, 이환율의주요원인이므로치료시중환자의위험요인과질병의중증도를정확히평가하면 1) 집중적인치료로써환자예후가좋아질수있는환자선택이가능하며, 2) 치료시작과종료시기에관한객관적인기준설정이가능하며, 3) 정확하고객관적인예후평가로각중환자실간의임상성적에대한정보교환및질적인평가가가능해지며, 4) 새로운치료법의결과를기 존의치료법에의한결과와비교분석하여새로운치료법에대한확실한평가가가능하게된다 3. 중환자에대한중증도및예후판정에대한객관적인기술이나분류법의부재로인하여서로간의정보교환및예후판정을위한방법의개발이필요하였으며이에따라환자의질병의중증도를파악하는여러가지방법이연구되었다. 1970년초에 Cullen 등 4 은 Therapeutic Intervention Scoring System (TISS) 을소개하였고, 1981년에 Kanus 등 5 이 34가지의급성생리적점수 (Acute Physiologic Score) 를이용한 APACHE 점수체계를소개하였다. 이후 APACHE 점수체계를단순화한 Simplified Acute Physiologic Score (SAPS) 와 Mortality Prediction Model (MPM) 이발표되었다 6,7. APACHE 점수체계를발표하였던 Kanus 등 8,9 은생리적측정치를 12가지로줄이고나이에따른점수와만성병력에따른점수를추가또는개선하여새로운 APACHE Ⅱ 점수체계를발표하였으며, 이후 APACHE Ⅱ 점수체계의결점을보완하여 APACHE Ⅲ 점수체계를발표하였다. 다발성장기부전은사건 (event) 이라기보다는과정 (process) 이고, 장기의점진적인생리적기능부전에의해발생한다. 따라서장기부전을평가하는데있어 Figure 3. Correlation between SOFA score and APACHE Ⅲ score. 332
Tuberculosis and Respiratory Diseases Vol. 57. No. 4, Oct, 2004 서는다음의 3가지중요한원칙에근거해야한다. 첫째, 장기부전은 all-or-none phenomenon이아니라변화의연속으로보아야하고, 둘째, 장기부전은동적인진행과정이므로시간의흐름을염두에두어야하며, 셋째, 장기부전을기술하는데있어서는단순하면서도장기에특이적이고일상적으로검사가가능한변수를이용해야한다 2. 이러한원칙하에 European Society of Intensive Care and Emergency Medicine (ESICEM) 에서 Sequential Organ Failure Assessment (SOFA) 점수체계를제안하였으며 10, 다기관전향적연구를통하여 SOFA 점수체계가장기기능을평가하고경과를검사하는간편하고효과적인점수체계임을입증하였다 2. 현재유용한예후판정지표는사망률을예측하는데초점을두고있으며, 사망률을계산하기위해환자자료의단순분석에의존하고있어장기부전을기술하는데어려움이있다. 하지만새로운치료의효능과비용효과를평가하는데있어서는사망률만으로는부족하다고여겼으며, 이환율을분석하는것이중요하다는것을인식하게되었다 11. 또한반복측정에의한연속적인환자평가의중요성은여러연구에서보여주었다 12-15. APACHE Ⅱ와 APACHE Ⅲ 점수체계에서측정하는많은생리적측정치는혈관수축제의투여, 인공환기요법, 신대체요법 (renal replacement therapy) 등을포함한다양한치료법에의해쉽게영향을받는다. 그러므로이러한예후판정지표는환자가중환자실에입원할때의다발성장기부전의중증도를평가하는데에는적합하지만, 입원한이후의연속적인평가를하는데에는문제가있다. 이에비해서 SOFA 점수체계는개개의장기부전정도를간편하게연속적으로평가할수있으며, 생리적변수뿐만아니라인공환기요법의유무, catecholamine 의투여량, 소변량을변수로사용하여치료법에영향을받지않으면서각환자의장기부전정도를기술할수가있다 10. 따라서이환율에초점을두고있는 SOFA 점수체계는반복측정을통해장기부전을동적인진행과정으로분석하므로중환자실의치료효과를평가하는데유용할것으로생각된다. 본연구에서는사망군에서생존군에비해 SOFA 점수가증가한경우가더높게나타나서 SOFA 점수가증가할수록다발성장기부전이발생할가능성이높고따라서나쁜예후가나타날것으로예상할수있었다. 많은임상연구에서 SOFA 점수체계로장기부전을평가한정도가높은점수로나타난경우사망률이증가한다는상관관계가밝혀졌다 2,16-18. 본연구에서도장기부전이없는경우의사망률은 6.5%, 장기부전이 1개있는경우 20%, 2개있는경우 30%, 3개있는경우 67%, 5개의다발성장기부전이있는경우사망률은 100% 로나타나 SOFA 점수가사망률예측에유용한것으로나타났다. 48시간이상체류했던 74명을분석한결과에서는사망군에서최대 SOFA 점수가 81% 에서증가하고, 생존군에서 21% 에서증가하였으며, 반대로사망군에서는최대 SOFA 점수가 6% 에서감소하였고생존군에서는 48% 에서감소하였다. 따라서중환자실에입원하는기간중에나타나는장기부전변화도생존여부와상관관계를갖는다는것을알수있었다. 다른연구들에서는이것을 -SOFA로정의하여 -SOFA 점수가증가하였을때병원사망률이증가한다는것을보여주었고, 의사가매일환자를관찰하면서치료에대한반응을객관적으로평가할수있게한다고하였다 17-20. 또한 SOFA 점수체계가질병의경과를평가하며, 다발성장기부전이발생하는것을예측하는데유용하다는것을보여주었다 21-24. 본연구에서는중환자실입원 24시간내 SOFA 점수와 APACHE Ⅲ 점수와의상관분석을한결과유의한상관관계를보여서 SOFA 점수가입원 24시간내의소견으로예후를예측하는데에도 APACHE Ⅲ 점수체계못지않게유용함을알수있었다. 이번연구에서는 SOFA 점수와사망률간의관계를내과질환전체에대해서만계산하였으나질환별로는각환자수가통계적인의의를부여할만큼많지않았기때문에산출하지않았다. 이를위해서는대상병원수를늘리고보다충분한기간동안자료를축적하여야할것이다. 그리고각병원별로 SOFA 점수체계를사망률뿐만아니라다발성장기부전의발달및이환율예측에이용하게되면각중환자실간의임상성적에대한정보교환및질적인평가가가능해지며, 새로운치료법에대한평가를통해다발성장기부전 333
SH Kim, et al.: The SOFA score to evaluate organ failure and prognosis in the intensive care unit patients 환자에대한치료법의향상을가져올것으로기대한다. 이있는지표로서임상적으로많은도움이될것으로생각한다. 요약 참고문헌 연구배경 : 중환자의예후를예측할수있는지표로현재까지 APACHE Ⅱ, Ⅲ 점수체계와 SAPS 등이임상에응용되고있다. 1996년유럽에서 SOFA 점수체계가제안되었고 1998년다기관전향적연구를통하여장기부전을평가하고경과를감시하는간편하고효과적인점수체계임을입증하였다. 이연구는춘천성심병원에서내과계중환자만을대상으로 SOFA 점수체계의유용성을조사하였다. 방법 : 2000년 5월 1일부터 6월 30일까지춘천성심병원내과계중환자실에입원한 154명을대상으로하였고, 이중타과환자, 타병원으로전원된경우, ECG 관찰만을위하여입원한경우, 처치후관찰을위해 48시간이내만체류한환자를제외한 105명을연구에포함시켰으며, 91명에서평가가가능하였다. SOFA 점수와 APACHE Ⅲ 점수는입원시부터매일 24시간간격으로중환자실에서퇴실할때까지하였다. 결과 : 1) 사망률은 20% 였고중환자실체류기간의중앙값은 3일이었다. 2) 사망군과생존군간의 24시간내 SOFA 점수는각각 8.17±4.05, 3.85±3.24로유의한차이가있었다. 3) 장기부전이없는경우의사망률은 6.5%, 5개의다발성장기부전이있는경우사망률은 100% 였다. 4) 48시간이상체류했던 74명을분석한결과사망군에서는최대 SOFA 점수가 81% 에서증가하였고생존군에서는 21% 에서증가하여유의한차이를보였다. 5) 24시간내 SOFA 점수와 APACHE Ⅲ 점수와의관련성을평가한결과 r = 0.85 (p < 0.01) 로유의한상관관계가있었다. 결론 : SOFA 점수체계는다발성장기부전이있는환자에서장기부전을평가하고예후를예측하며임상경과를관찰하는데이용할수있는간편하고임상적효용성 1. Vincent JL, Ferreira FL. Evaluation of organ failure: we are making progress. Intensive Care Med 2000; 26:1023-4. 2. Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, pro spective study. Working group on sepsis-related problems of the European Society of Intensive Care Medicine. Crit Care Med 1998;26:1793-800. 3. Hall JB, Schmidt GA, Wood LD. Principle of critical care. 1st ed. New York: McGraw-Hill Inc; 1992. 4. Cullen DJ, Civetta JM, Briggs BA, Ferrara LC. Therapeutic intervention scoring system: a method for quantitative comparison of patient care. Crit Care Med 1974;2:57-60. 5. Knaus WA, Zimmerman JE, Wagner DP, Draper EA, Lawrence DE. APACHE-acute physiology and chronic health evaluation: a physiologically based classifi cation system. Crit Care Med 1981;9:591-7. 6. LE Gall JR, Loirat P, Alperovitch A, Glaser P, Gran thil C, Mathieu D, et al. A simplified acute physiology score for ICU patients. Crit Care Med 1984;12:975-7. 7. Lemeshow S, Klar J, Teres D, Avrunin JS, Gehlbach SH, Rapoport J, et al. Mortality probability models for patients in the intensive care unit for 48 or 72 hours: a prospective, multicenter study. Crit Care Med 1994;22:1351-8. 8. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE Ⅱ : a severity of disease classification sys tem. Crit Care Med 1985;13:818-29. 9. Knaus WA, Wagner DP, Draper EA, Zimmerman JE, Bergner M, Bastos PG, et al. The APACHE Ⅲ pro gnostic system. Risk prediction of hospital mortality for critically ill hospitalized adults. Chest 1991;100: 1619-36. 10. Vincent JL, Moreno R, Takala J, Willatts S, de Mendonca A, Bruining H, et al. The SOFA (Sepsisrelated Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996;22:707-10. 11. Suter PM, Armaganidis A, Beaufils F. Predicting outcome in ICU patients. 2nd European Concensus 334
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