pissn: eissn: Allergy Asthma Respir Dis 6(2): , March ORIGINAL ARTICLE 만성병력없이

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1 pissn: eissn: (2): , March ORIGINAL ARTICLE 만성병력없이호흡보조를위해중환자실에입원한소아의특성및예후인자 정민영 1, 김민지 2, 이옥정 3, 최아영 4, 황태웅 4, 조중범 4 1 성균관대학교의과대학삼성서울병원소아청소년과, 2 한림대학교의과대학동탄성심병원소아청소년과, 3 서남대학교의과대학명지병원소아청소년과, 4 성균관대학교의과대학삼성서울병원중환자의학과 Characteristics and prognostic factors of previously healthy children who required respiratory support in a pediatric intensive care unit Minyoung Jung¹, Minji Kim 2, Ok Jeong Lee 3, Ah Young Choi 4, Taewoong Hwang 4, Joongbum Cho 4 1 Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul; 2 Department of Pediatrics, Hallym University Dongtan Sacred Heart Hospital, Hallym University School of Medicine, Hwaseong; 3 Department of Pediatrics, Myongji Hospital, Seonam University College of Medicine, Goyang; 4 Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Purpose: Comorbidities have been considered a mortality risk factor in pediatric critical care patients. We studied the characteristics and prognostic factors of children without comorbidities who were admitted to the intensive care unit (ICU) due to respiratory failure. Methods: We reviewed the medical charts of patients ( <18 years) admitted to the ICU for respiratory support in a single tertiary center between January 2006 and December Patients with comorbidities and perioperative statuses were excluded. Results: Of the 4,712 ICU patients, 73 (1.5%) were included in this study. The median age was 31 months (8 57) and 51 (69.9%) were boys. Twenty-nine patients (39.7%) presented with pneumonia, 14 (19.2%) with acute respiratory distress syndrome (ARDS), and 11 (15.1%) with obstructive airway disease. The median duration of ICU hospitalization was 5 days (2 14.5), and 45 of the 73 patients (61.6%) needed mechanical ventilation. Mortality was 13.7% (10/73). None of the patients with pneumonia or obstructive airway disease died. The most frequent cause of death was ARDS (5 of 10, 50%). In adjusted analysis, the extent of extrapulmonary organ dysfunction was significantly associated with mortality (odds ratio, 2.89; 95% confidence interval, ; P= 0.023). Conclusion: The mortality rate of previously healthy pediatric patients needing respiratory support in the ICU should not be negligible. Multiple organ dysfunctions might be a significant risk factor for mortality in such patients. ( 2018;6: ) Keywords: Child, Respiratory insufficiency, Comorbidity, Critical care, Mortality 서론호흡기감염은병원에입원하는소아의주된진단이며, 1 호흡기계의이상은중환자실에입원하는소아의가장흔한주진단중하나이다. 2 비호흡기계주진단까지포함하였을때중환자실에입실한소아환자의약 70% 이상이호흡기보조치료를받는다. 3 그러나중환자실에입원한소아는연령이나기저질환등에따라다양한경과를보이기때문에, 호흡기보조를받은환자의예후는다양하게나타난다. 호흡곤란으로중환자치료가필요했던환자들의 32% 58% 가선천성심장질환, 후천성면역저하또는만성폐질환등의복잡한기저질환을가지고있었으며, 4-7 이러한만성병력은사망의유의한위험인자로보고되었다. 8,9 급성폐손상으로입원한소아에서면역저하환자는정상면역환자에비해 6.3배의사망을보였으며, 기존에만성장기부전을가진급성폐손상환자는그렇지않은경우에비해 3배의사망위험을보였다. 4 만성의기저질환이호흡기질환에서중요한사망위험요인임에도불구하고이러한위험인자가없던건강한소아에서도호흡기계의악화는사망의중요한원인이다. 인플루엔자와관련된소아의 Correspondence to: Joongbum Cho Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea Tel: , Fax: , joongbum.cho@gmail.com Received: July 3, 2017 Revised: August 18, 2017 Accepted: August 23, The Korean Academy of Pediatric Allergy and Respiratory Disease The Korean Academy of Asthma, Allergy and Clinical Immunology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (

2 Jung M, et al. Respiratory support of previously healthy children 사망을분석한연구에서사망한환자의 43% 는고위험질환이없던건강한환자였고, 10 호흡기세포융합바이러스 (respiratory syncytial virus) 감염이원인이었던영유아사망의 30% 는만성병력이없는건강한환자였다. 11 따라서이전에건강하였다고해서소아의호흡기관련사망위험을무시할수없다. 만성병력이없는소아의경우중환자실에처음입원하는경우가많으며이때보호자의심리적스트레스는이전에입원경험이있던경우에비해의미있게높은것으로알려져있으며, 12 환자의상태에대해적시에정확한설명을해주는것은보호자에게매우중요하다. 13 그러나이전에건강하였던환자가호흡기악화에의해중환자실에입원한경우예후에대한연구는거의없는실정이어서정확한설명이어려운상태이다. 따라서이연구에서는호흡곤란으로중환자실에입원한환자중만성질환이없었던소아의임상적인특징과예후인자를분석하고자하였다. 대상및방법 1. 연구대상 2006년 1월 1일부터 2016년 12월 31일까지삼성서울병원소아중환자실에서산소치료를받은 18세미만환자 4,712명중진단코드및의무기록을후향적으로확인하여기저질환이없는환자를대상으로하였다. 기저질환의기준은주상병과부상병중에종양, 면역결핍, 선천성기형및증후군, 주산기질환, 만성폐질환, 천식, 난치성간질, 염증성장질환, 자가면역질환을한가지라도진단받은환자로정의하였다. 또한수술후관찰을위해중환자실에입원한환자도수술이필요한기저질환이있는것으로간주하여대상에서제외하였다. 본원소아중환자실의호흡기계입실기준은산소포화도 90% 이상유지하기위하여흡입산소분율이 0.5 이상필요한경우, 무호흡또는호흡수가나이에따른정상범위보다낮은경우, 진행하는호흡성산증또는생명을위협하는폐또는기도질환이있는경우, 이외중증혹은생명을위협할수있는폐및기도질환이있는경우이다. 2. 자료의수집입실당시의평가항목으로는연령, 성별, 몸무게, 전원유무, 진단명, 호흡중증도지표, 예측사망률들을수집하였다. 그리고원인병원체동정유무와종류, 입실기간동안최종적으로적용했던비침습적기계환기와침습적기계환기종류, 기계환기치료기간, 동반된장기부전의유무를조사하였다. 호흡보조는환자의중증도가증가됨에따라비강캐뉼라, 산소마스크, 비침습적기도환기, 기계환기, 고빈도진동환기 (high frequency oscillatory ventilation), 체외막순환장치 (extracorporeal membrane oxygenation) 의순서로적용하거나일부가생략되어적용하였다. 중환자실에서시행한 중재 (intervention), 중환자실입실기간과전체재원일수, 사망유무를조사하였다. 진단명은급성호흡곤란증후군 (acute respiratory distress syndrome, ARDS), 폐렴, 폐쇄성기도질환 ( 천식, 모세기관지염 ), 패혈증그리고신경질환 ( 뇌염, 뇌수막염, 대사성뇌증 ) 으로분류하였다. ARDS는 American-European Consensus Conference 14 정의를기준으로하여진단하였다. 패혈증과다발성장기부전은 Goldstein 등의연구 15 에서제안한기준을이용하여평가하였으며사망전 24 시간이내의장기부전이새로발생한경우는사망과정으로간주하고제외하였다. 심혈관계부전은한시간이내정맥내생리식염수 40 ml/kg 이상투여하였음에도불구하고나이정상범위의 5th percentile 혈압보다감소하거나, 정상범위의혈압을유지하기위해혈관수축제 (dopamine >5 μg/kg/min 또는모든용량의 dobutamine, epinephrine, norepinephrine) 가필요한경우, 또는다음중두가지이상해당하는경우로정의하였다. (1) 설명되지않은대사성산증 (base deficit >5.0 meq/l), (2) 동맥혈내젖산염 > 정상상위 2배, (3) 소변량 < 0.5 ml/kg/hr, (4) 모세혈관재충만시간 >5초, (5) 중심체온과말초체온의차이 >3 C. 신경학적부전은 Glasgow Coma Score가 11점미만이거나급격한의식변화가있으면서 Glasgow Coma Score가기저보다 3점이상낮아질때로정의하였다. 그리고혈액학적부전은혈소판이 80,000/mm 3 보다낮아지는경우또는 international normalized ratio이 2 이상인경우로정의하였다. 신부전은혈청크레아티닌 (creatinine) 이정상범위중상위값의 2배이상이거나기저치보다 2배이상증가한경우로정의하였다. 마지막으로간부전은총빌리루빈 (bilirubin) 값이 4 mg/dl 이상이거나 alanine aminotransferase 가정상값의 2배이상인경우로정의하였다. 호흡중증도의지표들로는입실당시호흡수, 입실 24시간이내와입실당시부터사망또는퇴실 24시간이전기간동안제일낮았던경피산소포화도 / 흡입산소분율 (saturation by pulse oxymeter [SpO 2]/fraction of inspiratory oxygen [FiO 2]) 의비, 동맥혈이산화탄소분율등을조사하였다. 동맥혈산소분압 / 흡입산소분율 (arterial partial pressure of oxygen [PaO 2]/FiO 2) 비는동맥혈가스검사결과가있는환자에서만조사하였다. 예측사망률은 Pediatric Index of Mortality 3 score 방법 16 으로계산하였다. 호흡보조치료는침습적, 비침습적으로나누었고비침습적환기방법의종류를조사하였다. 중환자실중재의종류는기계환기유무, 기계환기시작후부터사망또는기계환기이탈 24시간이전까지중제일높았던기계설정값, 고빈도진동환기요법, 산화질소, 근육이완제, 승압제, 체외막순환장치적용유무를확인하였다. 기계환기설정값은압력조절형방식에서호기말양압 (positive endexpiratory pressure, PEEP), 최대흡기압 (peak inspiratory pressure, PIP), above PEEP (PIP과 PEEP의차이 ) 등을조사하였다. 비 104

3 정민영외 만성병력이없던소아의중환자실예후 침습적환기치료는비강내캐뉼라, 산소마스크, 지속적호기말양압장치, 고유량산소캐뉼라로구분하였다. 원인병원체의확인은입원중감염이아닌중환자실입실당시시행한검체에서바이러스와세균감염이확인된경우로정의하였다. 바이러스감염은객담, 대변, 혈액, 뇌척수액등의중합연쇄반응 (polymerase chain reaction, PCR) 에서양성으로나온경우, 세균감염은객담이나혈액, 뇌척수액배양검사에서동정된경우로정의하였다. 3. 통계분석생존자와비생존자를비교할때성별, 전원유무, 진단, 원인병원체, 장기부전의수, 기계환기적용유무, 중환자실중재유무등은 chi-square test 또는 Fisher exact test를사용하였고, 연령, 중환자실재실기간, 예측사망률, 호흡중증도지표들은 Mann-Whitney U-test를이용하였다. P값이 0.05 미만일때통계적으로유의하다고판단하였다. 중환자실사망자의위험인자를구하기위하여단변량분석에서통계적으로유의했던변수들중혼란변수들 ( 예측사망률, 중환자실중재, 기계환기기간, 가장높았던이산화탄소분율 ) 을제외하였다. 성별, 진단의종류, 장기부전의수, above PEEP 등을이용하여다변량회귀분석을시행하였다. 모든통계분석은 IBM SPSS Statistics ver.23.0 (IBM Co., Armonk, NY, USA) 을이용하였다. 결과 1. 중환자실에입원한환자의임상적인특징 11년동안중환자실에입실한소아중호흡보조를받았던 4,712 명의환자중기저질환이있었던 4,639명을제외하고 73명 (1.5%) 이연구에포함되었다. 대상환자의연령은중앙값 ( 범위 ) 31 (8 57) 개월이었고남자는 51명 (69.9%) 이었다 (Table 1). 타병원으로부터전원받아직접중환자실에입실하는환자는 34명 (46.6%) 이었다. 호흡보조치료가필요한원인질환은폐렴이 29명 (39.7%) 으로빈도가제일높았고, ARDS, 폐쇄성기도질환, 패혈증, 신경계질환순으로있었다. 기계환기를시행한환자는 45명 (61.6%), 치료일수는중앙값 8 (4 18.5) 일이었다. 비침습적치료를한환자는 28명 (38.4%), 치료일수의중앙값은 2 (1 3) 일이었고그중비강내캐뉼라를제일많이사용하였다 (20/28, 71.4%). 호흡보조를받은전체환자의중환자실재원기간은중앙값 5 (2 14.5) 일, 병원입원일수는중앙값 11 (7 28.5) 일이었다. 14명의 ARDS 환아에서 PaO 2/FiO 2 비는중앙값 77 ( ) 이었고 Berline 정의에따라중증도를분류하였을때 7명이중증 (PaO 2/FiO 2 비 <100) 에속하였다. 호흡기바이러스는 46명, 단순포진바이러스는 2명, 장바이러스가 1명에서검출되었고, 2명에서호흡기바이러스중복감염이있었 Table 1. Clinical characteristics of admitted pediatric patients who required respiratory support in the intensive care unit (n= 73) Variable Demographics Value Age (mo) 31 (8 57) Male sex 51 (69.9) Body weight < 3rd percentile 65 (89.0) 3rd 95th percentile 6 (8.2) > 95th percentile 1 (1.4) Transfer from other hospitals 34 (46.6) Clinical characteristics Causes of respiratory support ARDS 14 (19.2) Pneumonia 29 (39.7) Airway obstructive disease 11 (15.1) Sepsis 10 (13.7) Neurologic disorder 9 (12.3) Identified pathogens 56 (76.7) Extrapulmonary organ dysfunction 28 (38.4) PICU LOS (day) 5 ( ) Hospital LOS (day) 11 ( ) Death 10 (13.7) Interventions Invasive MV 45 (61.6) HFOV 11 (24.4) ECMO 8 (17.8) Noninvasive 28 (38.4) Nasal cannula 21 (71.4) Mask with reservoir 4 (14.8) CPAP 2 (7.1) HFNC 1 (3.5) Respiratory parameters Respiratory rate at admission 40 (32 48) Worst SpO2/FiO2 within 24 hr 240 ( ) Worst SpO2/FiO2 during hospitalization 230 ( ) Highest PaCO2 during hospitalization 52 (41 68) PaO2/FiO2 ratio* 77 (53 143) Values are presented as median (interquartile range) or number (%). ARDS, acute respiratory distress syndrome; PICU, pediatric intensive care unit; LOS, length of stay; MV, mechanical ventilation; HFOV, high frequency oscillation ventilation; ECMO, extracorporeal membrane oxygenation; CPAP, continuous positive airway pressure; HFNC, high flow nasal cannula; SpO2, saturation by pulse oxymeter; FiO2, fraction of inspired oxygen; PaCO2, partial arterial pressure of carbon dioxide; PaO2, partial arterial pressure of oxygen. *Values are calculated in the patients with acute respiratory distress syndrome. 다. 호흡기바이러스중인플루엔자바이러스 17 명 (37%), 호흡기융 합바이러스 10 명 (21.7), 파라인플루엔자 7 명 (15.2%) 이발견되었다. 기계호흡치료와비침습적호흡치료의중증도를비교했을때 입실 24 시간이내제일낮았던 SpO 2/FiO 2 비는유의한차이가있었 105

4 Jung M, et al. Respiratory support of previously healthy children 다 ( 중앙값 180 [ ] vs. 중앙값 343 [ ], P < 0.001). 나 이, 성별, 입실당시호흡수는두그룹사이에유의한차이는보이 지않았다. 2. 소아중환자실사망의위험인자분석 이연구에포함된환자들의사망률은 13.7% (10/73) 이었다. 호흡 곤란의원인이폐렴과폐쇄성기도질환이었던환자는모두생존하 였다 (Table 2). 생존자와비생존자를비교하였을때사망군에서여 Table 2. Comparison between survivors and nonsurvivors in intensive care unit Variable Clinical characteristics Survivors (n= 63) Nonsurvivors (n= 10) P-value Age (mo) 17 (4 66) 37 (29 43) Male sex 48 (76.2) 3 (30.0) Transfer from other hospitals 27 (42.9) 7 (70.0) Cause of respiratory support ARDS 9 (14.3) 5 (50.0) Pneumonia 29 (46.0) 0 (0) Airway obstructive disease 11 (17.5) 0 (0) Sepsis 8 (12.7) 2 (20.0) Neurologic disorder 6 (9.5) 3 (30.0) Proven bacterial infection 12 (19.0) 1 (10.0) Proven viral infection 45 (71.4) 5 (50.0) ICU hospitalization 5 (2 9) 25 ( ) Probability of death (%)* 1.4 (0.3 5) 10.9 (2 41.6) Number of extrapulmonary organ dysfunction Interventions 0 (0 1) 2.5 (1 4.3) < Mechanical ventilation 35 (55.6) 10 (100) HFOV 6 (9.5) 5 (50.0) NO 7 (11.3) 6 (60.0) Neuromuscular blocker 52 (82.5) 4 (40.0) Vasoactive agent 12 (19.4) 9 (90.0) < ECMO 5 (7.9) 3 (30.0) Respiratory parameters Worst SpO2/FiO2 within 24 hr 244 ( ) 139 (83 294) Worst SpO2/FiO2 during hospitalization 244 ( ) 121 (69 230) PEEP 6 (5 9) 6 (5 9) Above PEEP, 10 (0 19) 21.5 ( ) Duration of mechanical 6 ( ) 25 ( ) ventilation Values are presented as median (interquartile range) or number (%). ARDS, acute respiratory distress syndrome; ICU, intensive care unit; HFOV, high frequency oscillation ventilation; NO, nitric oxide; ECMO, extracorporeal membrane oxygenation; SpO2, saturation by pulse oximeter; FiO2, faction of oxygen; PEEP, positive end expiratory pressure. *Values are calculated by the Pediatric Index of Mortality (PIM) 3 score. Values are calculated in the mechanically ventilated patients. Values are calculated in the mechanically ven (PIP) and PEEP in the pressure control mode. 성의비율 (76.2% vs. 30%, P = 0.007) 과장기부전의수 (0 [0 1] vs. 2.5 [1 4.3], P<0.001) 가생존군에비해서의미있게높았다. 입실 24 시간이내제일낮았던 SpO 2/FiO 2 비, PIP 과 PEEP 등의변수들은 사망군과생존군에서유의한차이는없었다. 대신입원기간중제 일낮았던 SpO 2/FiO 2 비의중앙값 (244 [ ] vs. 121 [69 230], P = 0.045) 과 above PEEP (10 [0 19] vs [ ], P = 0.007) 은두군에서유의한차이를보였다. 사망률과연관성이확인된임 상변수들을보정하여시행한다변량분석에서는사망위험도가폐 외장기부전수와의미있게상관있었으며 (adjusted odds ratio [OR], 2.89; 95% confidence interval [CI], ; P = 0.023) (Table 3) 다른변수들은유의한상관관계를보이지않았다. 3. 사망한환자들의임상적특징 사망한환자들은모두기계환기를적용하였다. 사망한환자들 중 ARDS 는 5 명이었고 ARDS 의원인은원인불명이 3 명, RSV 폐렴 1 명, 폐조직검사에서증명된 necrotizing bronchiolitis 가 1 명이었다 (Table 4). ARDS 가없이패혈증쇼크가있었던환자중 1 명은대변 에서장바이러스 PCR 이양성이었고, 1 명은혈액에서단순포진바 이러스 PCR 이양성으로나왔다. 신경질환으로는사망한환자는 뇌염 2 명과간성대사뇌증 1 명으로모두사망전뇌사에합당한소 견을보여치료를중단하였다. 고찰 저자들은기저질환이없었던소아환자들이호흡보조치료가 필요하여중환자실에입원하였을때임상적인경과와사망위험인 자에대해분석하였다. 연구대상자의전체사망률은 13.7% 였고원 인질환중 ARDS 가동반되지않은폐렴이전체입실중 39.7% 으 로제일많았다. ARDS 로진단받은 14 명의환자들은 5 명 (35.7%) 이 Table 3. Risk factors associated with mortality in previous healthy children who admitted to pediatric intensive care unit Variable OR (95% CI) P-value Male sex 0.09 ( ) ARDS 2.34 ( ) Sepsis 0.20 ( ) Neurologic disorder 4.65 ( ) No. of extrapulmonary organ dysfunction 2.89 ( ) Worst SpO2/FiO2 ratio during hospitalization 0.99 ( ) Above PEEP* 1.14 ( ) OR, odds ratio; CI, confidence interval; ARDS, acute respiratory distress syndrome; SpO2, saturation by pulse oxymeter; FiO2, fraction of inspired oxygen; PEEP, positive end expiratory pressure. *Difference between peak inspiratory pressure (PIP) and PEEP in the pressure control mode

5 정민영외 만성병력이없던소아의중환자실예후 Table 4. Clinical characteristics of nonsurvivors Subject Age (yr) Sex Diagnosis Pathogen PRD (%) ICU duration (day) Number of extrapulmonary organ failure Worst SpO2/FiO2 during hospitalization Highest above PEEP during hospitalization 1 3 F ARDS Unknown Other treatments 2 2 M ARDS RSV Veno-venous ECMO 3 4 M Encephalitis HSV, mycoplasma F ARDS Unknown F Septic shock Enterovirus F Encephalitis Unknown F ARDS Unknown Veno-venous ECMO 8 1 F Septic shock HSV M ARDS Unknown Veno-venous ECMO, Lung transplantation 10 2 F Reye syndrome Influneza B PRD, probability of death calculated by Pediatric Index of Mortality 3 score; ICU, intensive care unit; SpO2, saturation by pulse oxymeter; FiO2, fraction of oxygen; PEEP, positive end expiratory pressure; ARDS, acute respiratory distress syndrome; RSV; respiratory syncytial virus; ECMO, extracorporeal membrane oxygenation; HSV, herpes simplex virus. 사망하여높은사망률을보였다. 그리고다변량분석에서폐외장기부전의개수가증가할수록사망위험도가유의하게증가함을보였다. 이번연구의사망률은 13.7% 로, 기저질환이없는환자들의소아중환자실에대한자료는없어직접적으로국내연구들과비교하기어려운실정이다. 그러나국내소아중환자실의전체사망률이 8.5% 14.7% 16,17 로보고된연구들과비교하면, 호흡보조를위해중환자실에입실한경우기저질환이없어도상대적으로사망률이낮지않았다. 소아급성폐손상환자의사망위험인자가폐외다발성장기부전의개수라는결과는다른연구들에서도관찰할수있다 미국의 31개소아중환자실의호흡부전연구에서는폐외장기부전이사망률과관련있음을보였다. 19 추후소아에서장기부전점수시스템에대한연구가진행되어급성폐손상의중증도에반영하는것이필요하다는의견들이있다. 22 이연구에서는기존의연구가만성병력이없는호흡보조환자에도동일하게적용됨을보였다. 따라서이러한환자에서장기부전의진행을막고사망률을낮추기위하여저산소증이오래지속되지않도록급성폐손상환자에서기계환기전략을잘세우는노력과동시에다른장기기능을면밀하게살펴적절한관류를유지하는노력도필요할것으로보인다. 이연구에포함된대부분의환자에서는폐의환기-관류의불균형이동반된것으로추측되며, 신경질환환자에서는호흡구동 (respiratory drive) 저하가주된기전일것으로생각된다. 하지만중증환자들의특성및후향적분석방법을고려하였을때폐활량검사나폐확산능검사등객관적지표를이용한병태생리학적분류는시행할수없었다. 따라서임상적으로흔히사용되는진단명을이용하여호흡부전을분류하였다. 이연구의단변량분석에서진단명이 생존자와사망자에서유의한차이를보였는데이중 ARDS가사망자의 50% 를차지하였다. ARDS는직접적또는간접적인다양한원인으로비균질적인염증성급성폐손상을유발하며저산소증호흡부전으로진행하는질환이다. 23 이번연구에서는 ARDS 환자의 PaO 2/FiO 2 비중앙값은 77 ( ) 로 Berlin 기준 24 에따르면중증 (severe, PaO 2/FiO 2 비 <100) 에속하지만, 사망률은 35.7% 로국내단일기관들의 ARDS 사망률 37.5% 8.4% 21,25,26 보다는낮은사망률을보였다. 높은중증도를고려할때사망률이상대적으로낮았던이유는기관에따른차이일수도있으나, 기저질환이없었던환자만을대상으로한본연구의특징때문일수있다. 이연구는소아및후향적연구의특성상동맥혈가스분석을시행하지않은환자들이많아서저산소증의정도에따른영향을평가하기위해 SpO 2/FiO 2 비를분석에추가하였다. SpO 2/FiO 2 비는이전연구들에서소아급성폐질환에서 PaO 2/FiO 2 비와같이호흡중증도를나타내는지표로사용할수있음을보였다 Pediatric Acute Lung Injury Consensus Conference Group 22 에서도비침습적인환기치료하는환자의 ARDS 진단기준에 SpO 2/FiO 2 비를포함시켰다. 이연구에서기계호흡치료받은군이비침습적호흡기치료받은군보다 SpO 2/FiO 2 비가유의하게낮아저산소증의중증도차이가있음을알수있었다. 생존자군과비생존자군의 SpO 2/ FiO 2 비를비교했을때통계적으로의미있는차이를보였으나다변량분석에서는유의한사망의위험인자로나타나지않았다. 소아중환자실에서 SpO 2/FiO 2 비와사망률의연관성을보인연구는있지만 30 단일기관이며후향적연구이기때문에이에대한추가적인연구가필요할것으로보인다. 이연구의단변량분석에서성별의차이가생존자와비생존자의비교분석에서의미있게나타났다. 성별차이에따른진단명을확 107

6 Jung M, et al. Respiratory support of previously healthy children 인했을때남자가사망자가없었던폐렴과폐쇄성기도질환의빈도가여자보다의미있게높았다. 이와같은원인질환의차이때문에남자가상대적으로사망률이낮게나왔던것으로보인다. 소아중환자실에서성별의차이가사망위험인자일가능성을보여준연구는있지만 31,32 최근에는성별과직접적인연관성을찾기힘들다는연구가더많았다. 4,20,33 이번연구에서는비생존자의수가적었고다른인자들을보정했을때는성별의차이에서통계적인유의성이나타나지않아성별이여자일때사망위험인자라고하기에는한계가있다. 생존자와비생존자의기계환기지표들을단변량분석하였을때 above PEEP이유의한차이를보였다. 성인의급성폐손상에서는낮은일회호흡량 (low tidal volume), 높은 PEEP이생존율을높인다는보고 34 가있지만소아에서의데이터는아직부족한실정이다. 이연구대상들의데이터를분석했을때 pressure control mode를주로사용하였고, above PEEP으로일회호흡량을조절하였다. 최근 Amato 등 35 의연구에서는성인의 9개급성호흡곤란증후군임상연구들을 multilevel mediation analysis를시행하였는데, 일회환기량, 호기말양압등의단일지표보다실제적인기능적폐용량을반영하는 driving pressure (ΔP =VT/CRS; VT, tidal volume; CRS, respiratory-system compliance) 가사망률과유의한상관관계가있다고보고하였다. Driving pressure값은환자의자발적인흡기노력이없을때 plateau pressure와 PEEP차이인측정값이므로이연구의기계환기설정값인 above PEEP과는약간의차이가있다. 하지만 above PEEP값이사망한환아에서의미있게높았던이번연구의결과는 pressure control mode를사용하는소아중환자실에서 low tidal volume lung protective strategy로적용해볼수있다는점에서의미가있을수있다. 그러나이연구에서는동일한질환에동일한진료지침으로적용한값이아니어서중증도의결과로해석할지결과에영향을주는원인으로해석할지에대한구분이어려울것으로보이며, 다변량분석에서도유의한차이를보이지않았다. 따라서이에대한해석은추가적인연구가필요할것으로보인다. 이번연구는몇가지제한점을가지고있다. 첫째, 단일기관에서시행한연구이기때문에제한된수의환자를대상으로연구하였다. 둘째, 기저질환이없는환자가전체소아중환자입원의 1.5% 밖에되지않아삼차의뢰기관의특성이연구결과에반영되어선택적편향이있을수있다. 셋째, 후향적으로의무기록을보고연구하였기때문에호흡기질환의중증도를나타내는지표가제한적이며, 사망과관련된위험인자들은사망지표일수는있으나인과관계로확인하기는어렵다. 넷째, 이연구는가습기세정제연관폐손상이있었던기간 (2006년부터 2011년 ) 이포함되어있다. 관련코호트연구 36 에따르면기저질환이없었던아이들이 89.9% 이고중환자실에서침습적기계환기를 56.5% 환자가적용하였으므로이연구대 상자에도가습기세정제연관폐손상의환자가포함되었을가능성 이있으나의무기록으로는확인할수없었다. 결론적으로만성질환없이건강하게지내던소아가호흡보조를 위해중환자실에입원한경우사망률은 13.7% 로보호자에게양호 한예후로설명되기어려움을보였다. ARDS 가동반되지않은폐렴 이나기도폐쇄성질환의경우사망은없었으나, 폐이외에동반된장 기부전의개수가증가할수록사망의위험은증가하였다. 향후만 성병력이없이호흡보조를위해중환자실에입실한소아의경과및 예후에대한다기관연구가필요할것으로보인다. REFERENCES 1. Carville KS, Lehmann D, Hall G, Moore H, Richmond P, de Klerk N, et al. Infection is the major component of the disease burden in aboriginal and non-aboriginal Australian children: a population-based study. Pediatr Infect Dis J 2007;26: Crow SS, Undavalli C, Warner DO, Katusic SK, Kandel P, Murphy SL, et al. Epidemiology of pediatric critical illness in a population-based birth cohort in Olmsted County, MN. Pediatr Crit Care Med 2017;18:e Namachivayam P, Shann F, Shekerdemian L, Taylor A, van Sloten I, Delzoppo C, et al. Three decades of pediatric intensive care: who was admitted, what happened in intensive care, and what happened afterward. Pediatr Crit Care Med 2010;11: Erickson S, Schibler A, Numa A, Nuthall G, Yung M, Pascoe E, et al. Acute lung injury in pediatric intensive care in Australia and New Zealand: a prospective, multicenter, observational study. Pediatr Crit Care Med 2007;8: Randolph AG, Meert KL, O'Neil ME, Hanson JH, Luckett PM, Arnold JH, et al. The feasibility of conducting clinical trials in infants and children with acute respiratory failure. Am J Respir Crit Care Med 2003;167: Barreira ER, Munoz GO, Cavalheiro PO, Suzuki AS, Degaspare NV, Shieh HH, et al. Epidemiology and outcomes of acute respiratory distress syndrome in children according to the Berlin definition: a multicenter prospective study. Crit Care Med 2015;43: Edwards JD, Houtrow AJ, Vasilevskis EE, Rehm RS, Markovitz BP, Graham RJ, et al. Chronic conditions among children admitted to U.S. pediatric intensive care units: their prevalence and impact on risk for mortality and prolonged length of stay. Crit Care Med 2012;40: Spaeder MC, Custer JW, Bembea MM, Aganga DO, Song X, Scafidi S. A multicenter outcomes analysis of children with severe viral respiratory infection due to human metapneumovirus. Pediatr Crit Care Med 2013; 14: Randolph AG, Reder L, Englund JA. Risk of bacterial infection in previously healthy respiratory syncytial virus-infected young children admitted to the intensive care unit. Pediatr Infect Dis J 2004;23: Wong KK, Jain S, Blanton L, Dhara R, Brammer L, Fry AM, et al. Influenza-associated pediatric deaths in the United States, Pediatrics 2013;132: Byington CL, Wilkes J, Korgenski K, Sheng X. Respiratory syncytial virusassociated mortality in hospitalized infants and young children. Pediatrics 2015;135:e Nizam M, Norzila MZ. Stress among parents with acutely ill children. Med J Malaysia 2001;56: Bartel DA, Engler AJ, Natale JE, Misra V, Lewin AB, Joseph JG. Working 108

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