대한응급의학회지제 18 권제 3 호 Volume 18, Number 3, June, 2007 원 저 중증익수환자의초기사망원인에대한분석 가톨릭대학교의과대학응급의학교실 위정희ㆍ이미진ㆍ최승필ㆍ박규남 Clinical Analysis of Early Death in Severe Drowning Patients Jung Hee Wee, M.D., Mi Jin Lee, M.D., Seung Pill Choi, M.D., Kyu Nam Park, M.D. Purpose: Historically, acute respiratory failure is the most common cause of death in drowning patients. However, there are an increasing number of severe drowning cases where patients die of circulatory failure or cardiovascular collapse. The aim of this study was to analyze the causes of death in severe drowning patients and evaluate the data in terms of survival curves in order to propose a treatment plan for severe drowning patients in the future. Methods: The subjects were 58 patients that visited St. Mary s Hospital from January 2000 to September 2006 who had drowned and required CPR and mechanical ventilation. Univariate analysis was performed to evaluate factors known to be predictive of severity. Survival analysis was done to determine the degrees of correlation with acute respiratory distress syndrome (ARDS) and refractory shock. Results: Thirty-nine out of 58 severely drowning patients expired in all, with most deaths occurring in the early stages - 45% expired on the first day, 55% on the second day, and 60% on the third day. Cause of death analysis yielded the following results: the correlation coefficient for the existence of ARDS was 2.96 (p=0.086), which did not achieve statistical significance, but, the coefficient for refractory shock was 9.23 (p=0.002) and was statistically significant. Conclusion: Most severe drowning patients expired in the first three days after drowning, and refractory shock was a more significant contributor to patients death than ARDS. This result underscores the need for treatment protocols that includes active management of hemodynamic instability combined with mechanical ventilatory management in the initial stages of treatment. Key Words: Drowning, Acute respiratory distress syndrome, Shock, Mortality Department of Emergency Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea 서 익수에의한연간사망률은줄어들고있는추세이지만, 익수사고는여전히비의도적사고사의가장흔한원인중의하나이다 1). 지금까지중증익수환자인경우폐로흡인된물에의해폐포의직접손상이나표면활성제의비정상적인기능부전을유발함에따라발생하는급성폐손상이나급성호흡부전증후군이주사망원인으로알려져왔다 2). 하지만, 현재발달된기계호흡장치와중환자치료로중증익수환자의호흡기능을유지하는데진보된방법을제시하고는있지만, 실제초기의많은중증익수환자들이순환부전이나심혈관계허탈을해결하는데아직도어려움이많고, 초기사망률은줄지않고있다. 이에본저자들은응급의료센터에서기계환기와중환자치료가필요한중증익수환자를대상으로생존곡선을이용하여사망시기와원인을분석하고, 이를토대로중증익수환자의사망률을감소시키기위한중환자치료의방향을제안하고자이연구를계획하였다. 론 책임저자 : 이미진서울특별시영등포구여의도동 62번지가톨릭대학교의과대학성모병원응급의학과 Tel: 02) 3779-1778, Fax: 02) 761-8440 E-mail: emmam@catholic.ac.kr 접수일 : 2006년 12월 18일, 1차교정일 : 2006년 12월 27일게재승인일 : 2007년 5월 15일 250 대상과방법 2000년 1월 1일부터 2006년 9월 30 일까지성모병원응급의료센터에내원한침수환자 279 명중전문심폐소생술이나기계환기의중환자치료를필요로한경우를중증익
위정희외 : 중증익수환자의초기사망원인에대한분석 / 251 Table 1. Clinical characteristics of 58 severe drowning patients Patient data Sex (female:male) 27:31 Age (years) 40.18 (8~86) Performed CPR* ratio 54/58 (93%) CPR* duration (min) 22.10 (0~158) Initial rectal temperature ( ) 31.0 (19.0~36.4) Survival : death 19:39 Initial rhythm Asystole / PEA 51 Ventricular fibrillation 2 Others 5 *CPR: cardiopulmonary resuscitation PEA: pulseless electrical activity 수환자로정의하였고, 이중심폐소생술을시행한경우에는 20 분이상의자발순환회복이없었던환자는본연구에서제외하였다 3). 성별, 연령등의인구학적인특성과전문심폐소생술시간, 생존시간, 사망유무와함께 24 시간이내수축기와이완기의최저혈압, 직장체온, 중심정맥압, 동맥혈가스분석소견, 혈당, 혈액요소질소, 크레아틴, 혈청전해질, 전문의판독에의한방사선학적소견등의임상경과특성을의무기록을토대로조사하였다. 이때혈압상승제에반응하지않는쇼크 (refractory shock) 는도파민이나노르에피네프린, 바소프레신을투여함에도불구하고평균동맥압 (MAP; mean arterial pressure) 이 60 mmhg 미만인경우로, 급성호흡부전증후군 (ARDS; acute respiratory distress syndrome) 은기존방사선학적소견과함께 PaO 2/FiO 2 가 200 미만인경우로정의하였다 4). 연구는생존군과사망군으로나누어인구학적인특성과 Table 2. The results of clinical data for survival versus death group in severe drowning patients Survival (n=19) Death (n=39) p-value Sex (male:female) 11:8 20:19 0.64 Age (years) 33.77±16.02 43.24±16.26 0.04* CPR duration (min) 12.67±14.38 27.74±29.29 0.04* Initial rectal temperature ( ) 30.36±4.960 31.45±3.710 0.41 Central venous pressure (cmh 2O) 8.55±3.74 10.18±3.840 0.32 Worst MAP in 24 hr 57.46±14.65 49.97±15.97 0.28 Ratio of worst MAP<60 mmhg 11/18(61.1%) 32/39(82.1%) 0.09 Initial ph 6.91±0.26 6.91±0.22 0.89 Initial base excess -19.97±8.980- -18.33±8.740-0.56 Worst ph in 24hr 7.26±0.15 7.10±0.22 0.01* Worst base excess -13.58±5.640- -17.44±6.550-0.09 Worst PaO 2/FiO 2 195.88±142.83 89.12±82.26 0.01* Ratio of PaO 2/FiO 2 <200 12/19 (63.2%) 33/37 (89.2%) 0.03* CPR performed 15/19 (78.9%) 39/39 (100%) 0.01* Aspiration pneumonia 13/19 (68.4%) 17/38 (44.7%) 0.09 Acute respiratory distress syndrome 11/19 (57.9%) 27/37 (73.0%) 0.25 Refractory shock 9/19 (47.4%) 35/39 (89.7%) 0.00* White blood cell (10 9 /L) 13.43±5.660 10.16±4.300 0.02* International normalized ratio 1.20±0.20 1.70±1.19 0.23 Activated partial thromboplastin time (sec) 36.73±10.79 47.00±23.92 0.14 Glucose (mg/dl) 175.26±72.690 274.65±75.510 0.00* Blood urea nitrogen (mg/dl) 12.42±4.710 17.56±22.53 0.33 Creatinine (mg/dl) 1.01±0.32 1.42±1.02 0.09 Sodium (Na, meq/l) 139.16±7.2200 138.15±6.2100 0.59 Potassium (K, meq/l) 3.80±1.34 3.94±1.33 0.71 Aspartate transaminase (IU/L) 131.21±117.12 175.03±171.98 0.33 Alanine transaminase (IU/L) 47.84±27.11 125.76±167.13 0.01* * p-value <0.05 CPR: cardiopulmonary resuscitation MAP: mean arterial pressure These analysis were carried out except for missing data due to the incomplete recorders during the chart review
252 / 대한응급의학회지 : 제 18 권제 3 호 2007 임상경과특성의차이를분석하여사망연관인자를알아보고, 사망시기나원인분석을위해이들대상환자군의생존곡선을이용하여분석을시행하였다. 통계는 SPSS 13.0 프로그램을이용하였으며, 연속형변수인경우에는 Student s t-test를, 빈도분석은 Chisquare test와 Fisher s exact test를, 생존분석은 Kaplan-Meier 생존곡선분석을이용하였고, p값이 0.05 미만인경우를통계학적인유의성이있는것으로하였다. 결과연구기간중본원응급의료센터에내원한침수환자는총 279 명이었고, 전문심폐소생술을시행한환자 83 명중 20 분이상자발순환이회복된환자 54 명과심폐소생술은시행하지않았으나기계환기와중환자치료가필요했던환자 4명을포함한 58 명의환자를본연구의대상으로하였다 (Fig. 1). 대상환자의나이는평균 40.2세 (8~86세) 였고, 남자가 31명 (53.4%), 여자가 27명 (46.6%) 이었고, 전문심폐소생술시간은평균 22.1분 (0~158분), 초기직장 체온은평균 31.0 (19.0~36.4 ), 초기심전도는무수축이대부분이었다 (Table 1). 이들 58 명의중증익수환자중최종 39 명 (67%) 이사망하였는데, 45% 가내원 24시간이내에, 2일째는 55%, 2.73일째 60%, 4일째 62%, 15일째 67% 의사망률을보여 1~3 일내의초기사망률이높고그이후에는다소감소되는양상을보였다 (Fig. 2). 대상환자중심폐소생술을시행한군에서는 54 명중 39 명 (72%) 이사망한반면, 비시행군 4명은사망이없었다. 방사선과전문의판독이시행된 57 명에서흉부방사선소견상흡인폐렴이확인된 30 명중에서는 17 명이사망 (57%) 하였으나, 흡인폐렴이보이지않은 27명에서오히려 21명 (78%) 이사망하였고 (p=0.091), PaO 2/FiO 2 비율의확인이어려운 2명의환자를제외한 56 명의환자중급성호흡부전증후군이있는 38 명중에서는 27 명 (71%) 이사망, 급성호흡부전증후군이없는 18 명의환자에서도 10 명 (56%) 이사망하였다 (p=0.253). 또한, 심혈관계순환부전이없었던 14 명중에서는 4명 (29%) 이사망, 심혈관계순환부전이있는 44명의환자중에서는 35명 (80%) 이사망하여 (p=0.001), 중증익수환자에서급성폐병변보다는혈역 + + Fig. 1. Flow sheet in submersion patients. Fig. 1. *CPR: Cardiopulmonary resuscitation Fig. 1. ROSC: Return of spontaneous circulation Fig. 1. DOA: Death on arrival Fig. 1. DAMA: Discharge against medical advice
위정희외 : 중증익수환자의초기사망원인에대한분석 / 253 학적불안정성이사망원인으로더유의한인자로나타났다 (Table 2). 사망과연관된인자분석시심폐소생술을받은시간이길고, 저산소증이악화될수록, 순환부전이심하여혈압상승제에반응하지않는경우, 대사성산증이나감염, 간기능저하등의다발성장기부전이진행하는경우에더높은사망결과를보였으나, 내원초기저체온여부와흡인성폐렴동반여부, 급성호흡부전증후군유무는통계학적인유의한차이를보이지않았다 (Table 2). 이들중기존초기사망의주요인자로알려진급성호흡부전증후군과본연구에서통계학적유의성이가장높은심혈관계순환부전에대해 Log-rank 분석을시행한결과급성호흡부전증후군유무를기준으로분석했을경우에는통계학적인차이를보이지않았지만 (Fig. 3), 심혈관계순환부전의유무를기준으로 분석했을때는생존기간의통계학적인유의한차이를보였다 (Fig. 4). 고찰연간전세계적으로 400,000명의환자가익수로인해사망하고있고 5), 익수에의한사망은미국에서 1~4 세의비의도적사고사의 27% 에해당하며, 다양한예방및방지프로그램을시행함에도불구하고어린이사망의주요원인으로작용하고있다 6). 본연구에서중증익수환자의사망률은 67% 였고, 전체환자의 45% 에서내원 24 시간이내사망하였으며, 2.73일째 60% 의사망률을보여중증익수환자의경우초기사망률이높음을알수있었다. 이런결과는 Park 등 7) 이연구한심폐소생술후혼수환자의생존곡선에서대부분의사망이 1주이내에일정비율로발생하던것과는달리중증익수환자의경우에서는처음 1~3 일내에거의모든사망이일어나중증익수환자의치료에있어서초기사망을막는것이환자생존및예후에관건이될수있음을알수있었다. 침수와연관된여러가지손상들이있지만, 호흡부전과허혈성신경손상이생명을위협한다고알려져왔다. 초기의저산소혈증은폐포에물이차서가스교환이안되어일어나고, 폐포에서표면활성제의손실이되며, 무기폐, 환기-관류불균형, 폐포모세혈관의파괴를일으킨다 8). 폐부종은침수손상을입은환자의초기소생후직면하는가장 Fig. 2. The Kaplan-Meier survival curve in severe drowning patients required mechanical ventilation and intensive care management Fig. 3. Log-rank test between severe drowning patients with and without acute respiratory distress syndrome (ARDS) Fig. 4. Log-rank test between severe drowning patients with and without refractory shock
254 / 대한응급의학회지 : 제 18 권제 3 호 2007 흔한문제로, 비심인성폐부종은직접적폐손상, 표면활성제소실, 염증성오염물, 뇌저산소증등에기인한다. 일부환자들은응급실도착당시폐손상이없는것처럼보이고, 또한흉부방사선에서도정상인소견을보이나, 12시간정도가지난익수환자에서심각한폐부종이나타나기도한다 9). 또한, 익수환자들은과도한양의물의삼킴, 위내용물의구토, 흡인에따른흡인성폐렴도동반되게된다 6). 따라서이전연구보고는대부분사망원인의주요인으로호흡부전에대한경각심을강조하고, 호흡부전치료를가장중요한관점으로내세워, 몇몇실험에서는민물때문에발생한호흡부전시에표면활성제를사용한예도보고하고있다 10). 그러나본연구결과에서는급성호흡부전증후군유무를초기사망인자로생존분석했을경우에는연관계수 2.96 (p=0.086) 으로통계학적인차이를보이지않았고, 이는 Woo 등 11) 의연구에서중증폐병변동반유무가익수환자의나쁜신경학적예후, 사망과의연관성이없었다는결과와도유사하였다. 기존연구에서익수환자들의경우저체온증에노출이잘되고, 극심한저체온증발생시심박수저하, 심박출량감소, 혈압하강, 심실세동을포함하는중증부정맥을일으켜궁극에는심정지에까지도달하게하여환자의생존및예후에영향을미치게된다고알려져왔다 12). 따라서저체온을해결하기위하여적극적인재가온법을시행하거나체외막형산소섭취 (extracorporeal membrane oxygenation, ECMO) 의사용예도보고되고있다 13). 그러나본중증익수환자의사망연관분석시저체온동반유무는생존 / 사망군간의차이가없었는데, 이또한 Woo 등 11) 의이전익수환자에있어서예후평가연구와도유사한결과를보였다. 본연구에서도보듯대다수의중증익수환자는응급센터에심정지상태로내원하여전문심폐소생술후자발순환이회복되는상태에있는데, 이들환자는혈역학적불안정성을보이는경우가흔하고, 다발성장기부전에의한초기사망은소생후 24시간동안의지속적으로낮은심계수 (cardiac index) 와연관이있다 14). 그러나앞에서도언급했던 Park 등 7) 이연구한심폐소생술후혼수환자의생존곡선과는달리중증익수환자의경우에서는초기사망률이현저하였고, 그원인으로심혈관계순환부전의유무를기준으로생존분석했을때연관계수 9.23 (p=0.002) 으로통계학적인유의성을보여주어, 이런심혈관계순환부전이중증익수환자의초기사망의주요원인이고이의해결이급성호흡부전증후군 (p=0.086) 보다중요함을보여주었다. 기존치료나약물에반응하지않는심혈관계순환부전의치료로최근대동맥내풍선펌프 (intra-aortic balloon pump, IABP) 뿐아니라경피적체외순환 (percutaneous cardiopulmonary bypass) 의사용이심정지, 심인성쇼크로부터의순환부전, 혈역학적불안정성의해결의대안으 로제시되고있고 8,15), 우리나라응급센터에서도이의사용으로심기능을회복시키거나소생을유지한보고가점차많아지고있어 16,17), 이에대한적극적인임상적용도고려되어져야할것이다. 즉, 중증익수환자의초기사망에서는기존의주요인자였던급성호흡부전증후군, 저체온증, 흡인성폐렴뿐만아니라심혈관계불안정성이중요하므로, 중환자치료의목표로진보된기계환기치료와더불어 IABP, 경피적응급체외순환사용을고려하는등의적극적인치료프로토콜의마련도필요할것으로생각된다. 본논문의제한점으로는첫째, 단일기관에서연구가시행되어대상환자수가적고다양한관점에서의분석이제한적이며, 결과분석에대한편향이있다는점이다. 둘째로, 기존의익수환자에대한연구는생존후 6시간또는 24 시간이상의환자를대상으로예후평가가이루어진반면, 본연구는초기사망원인분석을위해 20 분이상생존한환자를대상으로하였기때문에기존연구에서보다사망률이높게분석되었다는것과본기관이한강변에위치하여내원한환자들의익수가민물에서발생한경우가대부분을차지하여타연구와직접적인비교에제약이있다는점이다. 결 중증익수환자에있어대부분의사망은초기 1~3 일째발생하고, 이와같은초기사망을유발하는원인으로는기존에주요사망원인으로알려진호흡부전보다는심혈관계순환부전이더통계적으로유의한중요한사망원인으로나타났다. 이에따라초기익수환자치료시기계환기치료와병행하여혈역학적인순환부전을위해체외순환등을이용한적극적인중환자치료프로토콜이필요하겠다. 론 참고문헌 11. Marx JA, Hockberger RS, Walls RM. Rosen s Emergency Medicine. Concepts and clinical practice. 6th ed. Philadelphia: Mosby; 2006. p.2311-6. 12. Ibsen LM, Koch T. Submersion and asphyxia injury. Crit Care Med 2002;30:S402-8. 13. Jacobs I, Nadkarni V, Bahr J, Berg RA, Billi JE, Bossaert L, et al. Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the Utstein templates for resuscitation registries. A statement for healthcare professionals from a task force of the international liaison committee on resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, Inter
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