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1 REVIEW ARTICLE 외과중환자에서급성호흡부전증후군 연세대학교의과대학외과학교실, 중환자관리및외상외과 이재길 Acute Respiratory Distress Syndrome in Critically Ill Surgical Patients Jae Gil Lee, M.D., Ph.D. Division of Surgical Critical Care & Trauma, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea 책임저자 : 이재길서울시서대문구연세로 50, , 연세대학교의과대학외과학교실, 중환자관리및외상외과 Tel: Fax: jakii@yuhs.ac Acute respiratory distress syndrome (ARDS) is one of the causes of death in critically ill surgical patients. ARDS is a rapidly progressive pulmonary disorder that manifests respiratory failure. It is associated with postoperative infection, sepsis, and severe trauma, etc. The management of ARDS is complicate and targeting the underlying causes. In addition, many supportive managements such as nutritional support, prevention of stress ulcer and thromboembolism, with lung- protective ventilation strategies are necessary. (J Surg Crit Care 2012;2:53-57) Key Words: Respiratory failure, Mechanical ventilation, Critically ill 서론 급성호흡부전증후군 (ARDS) 은호흡곤란과빈호흡을동반한심각한저산소증및폐부전증을유발하는폐질환으로빠른경과를보인다 (Fig. 1). 급성호흡부전증은 35 55% 의높은사망률을보이는치명적인질환으로, 대부분의환자가인공호흡기치료를필요로하며, 호흡부전증과연관된다발성장기부전증으로사망하게된다. 1-3 급성호흡부전증은치료후에도많은후유증을유발할수있어서조기진단과적절한치료가시행되어야한다. 본론 1. 정의 ARDS는명확하게정의하기가쉽지않다. Cute onset.rative infection andherapy) Open wound icated wound whom such a trauma patients has. 여러진단기준이마련되어사용되고있으나 일반적으로 1994년미국-유럽컨센서스기준 (Amerian European Consensus Criteria, AECC) 이가장많이사용되고있다. 4 AECC 에서는급성폐손상의기준으로 1) 급성발현, 2) 흉부방사선에서양측폐의미만성침윤, 3) PaO 2/FiO mmhg ( 급성폐손상 ) 또는 PaO 2/FiO mm Hg ( 급성호흡부전증 ) 을보이는심한저산소증, 4) 폐침윤의원인이심부전증이나수액과다증에의한것이아니고, 폐동맥쇄기압이 18 mmhg 이하인경우로정의하였다. 그러나급성발현의의미를정확하게표현하기는쉽지않고, 일반적으로원인이발생한후 72시간이내에발현되는것으로정의한다. 또한 AECC 진단기준은민감도는높지만특이도가높지않아 Murray 의폐손상점수 (lung injury score, LIS) 나 Delphi 컨센서스기준이사용되기도한다. 5 이와같이진단기준이뚜렷하지않아기준을명확히한새로운진단기준이 2012년미국중환자의학회와흉부학회에서제시되였으나 (Table 1), 6 현재일반화되어사용되고있지는않으며주로는 ARCC기준에따라급성호흡부전증을진단하고있다. Journal of Surgical Critical Care Vol. 2 No. 2, October

J Surg Crit Care Vol. 2, No. 2, Oct. 2012 2. 원인급성호흡부전증은폐렴이나흡인성폐렴, 폐좌상과같의폐의직접적인손상에의해발생하지만, 패혈증이나화상, 수혈등과관련되어폐의직접적인손상이없어도발생할수있다. 외과환자에서는수술후무기폐나위내용물또는음식물의흡인, 대량수혈및다발성외상에의해발생할수있다 (Table 2). 2,4,7 3.

2 J Surg Crit Care Vol. 2, No. 2, Oct 원인급성호흡부전증은폐렴이나흡인성폐렴, 폐좌상과같의폐의직접적인손상에의해발생하지만, 패혈증이나화상, 수혈등과관련되어폐의직접적인손상이없어도발생할수있다. 외과환자에서는수술후무기폐나위내용물또는음식물의흡인, 대량수혈및다발성외상에의해발생할수있다 (Table 2). 2,4,7 3. 발생빈도전세계적으로인구 100,000 명당 13 58명에서발생하는것으로보고되고있으며, 미국에서는연간사망환자수를 59,000명정도로보고하였다. ARDS 환자의사망률은약 36 44% 정도로높으며, 회복되어퇴원을하더라도정신적으로나육체적인장애 를동반하는경우가많다. 4,7,8 4. 발생기전급성호흡부전증의발생기전은아직까지명확히규명되어있지는않다. Gattinoni 등 9 은급성폐손상시에염증의반응시기에따라변화가일어남을보고하였다. 급성기에는호산구의침윤과더불어폐포가미만성으로손상되고, 폐포출혈및유리막이형성된다. 이후섬유화및신생혈관생성등이일어나는반응이뒤따르게된다. 급성폐손상은폐의급격한염증반응에의해폐포와혈관의내피세포가손상되면서나타나게된다. 기저막이노출되면서유리막 (hyaline membrane) 이형성되고, 호산구가손상된혈관내피세포에결합하여간질내로유입되어단백분해효소를분비하게된다. 또한폐포내대식구에서사이토카인을분비하여염증반응을악화시키게된다. 또한폐포내호산구에서도산화물과혈소판 Table 2. Causes of the acute respiratory distress syndrome Fig. 1. Chest X-ray of acute respiratory distress syndrome. It shows bilateral infiltration with acute onset. Direct lung injury Indirect lung injury Common causes Common causes Pneumonia Sepsis Aspiration of gastric content Shock Multiple trauma requiring massive transfusion Other causes Lung contusion Pulmonary hemorrhage Other causes Pulmonary thrombo-embolism Pulmonary bypass Inhalation burn Drug intoxication Pulmonary edema Acute pancreatitis Transfusion Table 1. The Berlin definition of acutre respiratory distress syndorme Acute respiratory distress syndrome Timing Within 1 week of a known clinical insult or new or worsening respiratory symptoms Chest imaging* Bilateral opacities - not fully explained by effusions, lobar/lung collapse, or nodules Origin of edema Respiratory failure not fully explained by cardiac failure or fluid overload Need objective assessment (eg, echocardiography) to exclude hydrostatic edema if no risk factor present Oxygenation Mild 200 mmhg<pao 2/FiO mmhg with PEEP or CPAP 5 cmh 2O Moderate 100 mmhg<pao 2/FiO mmhg with PEEP 5 cmh 2O Severe PaO 2/FiO mmhg with PEEP 5 cmh 2O CPAP: continuous positive airway pressure, FiO 2: fraction of inspired oxygen, PaO 2: partial pressure of arterial oxygen, PEEP: positive end expiratory pressure. *Chest radiograph or computed tomography scan, If altitude is higher than 1,000 m, the correction factor should be calculated as follows: [PaO 2/FiO 2 (barometric pressure/760)], This may be delivered noninvasively in the mild acute respiratory distress syndrome group. 54

3 이재길 : 급성호흡부전증후군 Table 3. Treatment modality of the acute respiratory distress syndrome Method Indications Effects Lung protective strategies All patients with acute lung injury or Reduce the mortality acute respiratory distress syndrome 1) Low tidal volume ( 6 ml/kg, PBW) Reduce the inflammatory cytokines 2) PEEP according to the ARDS net 3) Plateau pressure<30 cmh 2O Prone position Severe hypoxemia Improve oxygenation May increase the survival in severe ARDS patients High frequency oscillatory ventilation Severe hypoxemia Improve oxygenation Restrictive fluid therapy All ARDS/ALI patients Improve lung function Reduce the duration of mechanical ventilation Low dose steroid Early ARDS Improve oxygenation Severe hypoxemia Reduce the mortality ECMO Severe ARDS Reduce the mortality Contraindicated in patients more than 7 days of high pressure ventilator 활성인자등을분비하여폐포손상을악화시키게된다. 폐손상을일으키는데가장중요한역할을하는것은호산구로사이토카인, 단백분해효소, 활성산소등을분비하여폐손상을악화시키게된다 임상양상급성호흡부전증의증상의비특이적인호흡기증상이주로나타난다. 호흡곤란이나빈호흡, 열, 기침가래등을동반할수있으며, 패혈증이나장기부전증으로나타나기도한다. 또한다른호흡기질환들의증상과비슷할수있다. 특히심부전증이나수액과다에의해나타나는호흡기증상도영상검사에서는미만성침윤을보일수있어이에대한감별도필요하다. 7,8,11 6. 진단우선흉부방사선 (CXR), 흉부전산화단층촬영등의영상검사가도움이된다. 실제로흉부전산화단층촬영에서중력부의폐는허탈되어있으나, 비중력부의폐포는보존되어있는것을발견한이후로치료에많은변화를가져오게되었다. 12,13 즉, 중력부의허탈된폐는 cyclic atelectasis ( 폐포의과도한확장과수축 ) 을반복함으로써폐포의손상과해로운사이토카인의분비를촉진한다는개념이다. 이것을바탕으로 2000년 ARDS net에서는 low tidal ventilation과 PEEP을 ARDS 치료의권고사항으로정하고있다. 항생제를적절하게사용하기위해서는기관지폐포세척술과세균배양검사를시행하여, 항균범위에맞는항생제를선택하여 야한다. 혈역학적감시나평가도진단에중요하다. 하지만, 폐동맥관삽입은환자의치료결과에영향을주지못하는것으로알려지면서최근에는일반적으로사용되지않고있으며, 이를대체할수있는덜침습적인방법들 (PiCCO나 LiDCO) 이사용되고있다. 또한염증반응을반영하는표지자나내피세포에서분비되는물질들을포함하는생체표지자들이진단적도구로써유용한지활발히연구되고있다. 14,15 7. 치료급성호흡부전증의치료는기저질환에대한치료, 항생제, 조기경장영양, 스트레스성궤양의예방과심부정맥혈전증의예방을포함하는지지요법과더불어인공호흡기치료가주를이루게된다. 7,8,16 특별한치료제는없으며기저질환에대한치료가가장우선적으로시행되어야하며, 폐부전증에대한보조치료를시행해야한다 (Table 3). 급성호흡부전증에서폐보호환기전략은매우중요하다. 인공호흡기를유치하는것자체가폐의손상 ( 압력손상및용적손상 ) 을유발하여회복후폐기능의장애를일으킬수있어이에대한예방방법으로폐보호환기전략이시행되고있다. 폐보호환기전략에대한여러차례의무작위조절임상시험을시행되었으며, 이를바탕으로급성호흡부전증인공호흡기치료에서폐보호전략은중요한치료방법으로확립되었다 (Table 4) 이런폐보호환기전략을통해급서호흡부전증환자의사망률을 30% 대로낮추게되었다. 55

4 J Surg Crit Care Vol. 2, No. 2, Oct Table 4. Lung protective strategies for acute respiratory distress syndrome 1. Low tidal volume : 6 ml/kg PBW 2. Plateau pressure<30 cmh 2O 3. Permissive hypercapnea 4. Adjustable PEEP by the ARDSNet protocol FiO PEEP Semirecumbent position 6. Target of oxygenation ph : Oxygen saturation (SaO 2) : 88 95% Arterial oxygen (PaO 2) : mmhg 이러한인공호흡기의폐보호전략과더불어엎드린자세를유지하거나, 고빈도진동호흡기 (high frequency oscillatory ventilation), surfactant, 저용량의스테로이드등을이용한치료등이도움을주고있다. 또한환자의상태가심각한경우에는체외순환 (extracorporeal membrane oxygenator, ECMO) 등이도움을주기도한다. 이와더불어인공호흡기이탈도환자의예후에매우중요한요소중의하나이다. 인공호흡기치료중에자발적인호흡을촉진하는자발자각검사 (spontaneous awakening test, SAT) 와자발호흡검사 (spontaneous breathing test, SBT) 를통한호흡기이탈을시도하는것이인공호흡기기간및중환자실기간을줄일수있는것으로알려져있다. 그러나이러한폐보호전략이나인공호흡기치료외에도보조적인치료가뒷받침되어야한다. 보조적인치료로는 1) 조기경장영양공급과면역증강제제의사용, 2) 스트레스성궤양의예방및치료, 3) 정맥혈전증의예방, 4) 과도한수액공급을제한하고, 5) 적절한항생제치료를병행하여야한다. 결론 급성호흡부전증후군은심한저산소증을유발하는폐부전증으로높은사망률을보인다. 그러나실제로외과환자에서급성호흡부전증은폐자체의손상에의한것도있지만복강내감염이나패혈증, 다발성외상등여러가지원인에의해발생하므로, 폐부전증에대한치료뿐만아니라기저질환에대한적극적인치료가중요하다. 이와더불어폐보호환기가필수적으로시행되어야하며, 영양공급과기타합병증을예방할수있는보조치료가동반되어야한다. 참고문헌 1. Bersten AD, Edibam C, Hunt T, Moran J; Australian and New Zealand Intensive Care Society Clinical Trials Group. Incidence and mortality of acute lung injury and the acute respiratory distress syndrome in three Australian States. Am J Respir Crit Care Med 2002;165: Brun-Buisson C, Minelli C, Bertolini G, Brazzi L, Pimentel J, Lewandowski K, et al; ALIVE Study Group. Epidemiology and outcome of acute lung injury in European intensive care units. Results from the ALIVE study. Intensive Care Med 2004;30: Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, et al. Incidence and outcomes of acute lung injury. N Engl J Med 2005;353: Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994;149: Raghavendran K, Napolitano LM. Definition of ALI/ARDS. Crit Care Clin 2011;27: ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA 2012;307: Johnson ER, Matthay MA. Acute lung injury: epidemiology, pathogenesis, and treatment. J Aerosol Med Pulm Drug Deliv 2010;23: Saguil A, Fargo M. Acute respiratory distress syndrome: diagnosis and management. Am Fam Physician 2012;85: Gattinoni L, Bombino M, Pelosi P, Lissoni A, Pesenti A, Fumagalli R, et al. Lung structure and function in different stages of severe adult respiratory distress syndrome. JAMA 1994;271: Perl M, Lomas-Neira J, Venet F, Chung CS, Ayala A. Pathogenesis of indirect (secondary) acute lung injury. Expert Rev Respir Med 2011;5: Dushianthan A, Grocott MP, Postle AD, Cusack R. Acute respiratory distress syndrome and acute lung injury. Postgrad Med J 2011;87: Caironi P, Langer T, Gattinoni L. Acute lung injury/acute respiratory distress syndrome pathophysiology: what we have learned from computed tomography scanning. Curr Opin Crit Care 2008;14: Gattinoni L, Caironi P, Valenza F, Carlesso E. The role of CT-scan studies for the diagnosis and therapy of acute respiratory distress syndrome. Clin Chest Med 2006;27: Bhargava M, Wendt CH. Biomarkers in acute lung injury. Transl Res 2012;159: Cross LJ, Matthay MA. Biomarkers in acute lung injury: insights into the pathogenesis of acute lung injury. Crit Care Clin 2011;27: Cortés I, Peñuelas O, Esteban A. Acute respiratory distress syndrome: evaluation and management. Minerva Anestesiol 56

5 이재길 : 급성호흡부전증후군 2012;78: Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998;338: Brochard L, Roudot-Thoraval F, Roupie E, Delclaux C, Chastre J, Fernandez-Mondéjar E, et al. Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume reduction in ARDS. Am J Respir Crit Care Med 1998;158: Villar J, Kacmarek RM, Pérez-Méndez L, Aguirre-Jaime A. A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial. Crit Care Med 2006;34: Eichacker PQ, Gerstenberger EP, Banks SM, Cui X, Natanson C. Meta-analysis of acute lung injury and acute respiratory distress syndrome trials testing low tidal volumes. Am J Respir Crit Care Med 2002;166:

Allergy Asthma Respir Dis Kim SY, et al. Berlin definition in pediatric ARDS sive Care Medicine 의주관하에국제적자문을통한개정작업을거쳐 ARDS의새로운정의에대한초안이발제되어이를 Berlin 정의

Allergy Asthma Respir Dis Kim SY, et al. Berlin definition in pediatric ARDS sive Care Medicine 의주관하에국제적자문을통한개정작업을거쳐 ARDS의새로운정의에대한초안이발제되어이를 Berlin 정의 pissn: 2288 0402 eissn: 2288 0410 Allergy Asthma Respir Dis 4(4):257-263, July 2016 http://dx.doi.org/10.4168/aard.2016.4.4.257 ORIGINAL ARTICLE 소아급성호흡곤란증후군에서의 Berlin 정의 김수연, 김윤희, 설인숙, 김민정, 윤서희, 김경원, 손명현,