대한응급의학회지제 25 권제 3 호 Volume 25, Number 3, June, 2014 Toxicology 일산화탄소중독에서횡문근융해증발병예측인자 원 저 부산대학교의학전문대학원응급의학교실 임재황 염석란 한상균 이성화 박순창 조석주 박성욱 Predicting Factors for the Development of Rhabdomyolysis in the Carbon Monoxide Poisoning Jae Hawng Im, M.D., Seok Ran Yeom, M.D., Sang Kyoon Han, M.D., Sung Hwa Lee, M.D., Soon Chang Park, M.D., Suck Joo Cho, M.D., Sung Wook Park, M.D. Purpose: Carbon monoxide (CO) poisoning can cause rhabdomyolysis and acute kidney injury (AKI). However, until recently, studies regarding CO-induced rhabdomyolysis were rarely reported. This study was conducted in order to determine the risk factors for prediction of development of CO-induced rhabdomyolysis. Methods: We retrospectively reviewed the medical records of 70 CO poisoned patients who presented to an emergency department from January 2010 to December 2012. CO poisoning related parameters, patient demographics, and laboratory data were analyzed. Results: Rhabdomyolysis and AKI were observed in 11 patients (15.7%) and six (8.6%) patients, respectively. Time of exposure to CO, age, Glasgow coma scale, and leukocyte count differed significantly between patients who developed rhabdomyolysis and patients who did not. Exposure time to CO was the only risk factor for predicting development of rhabdomyolysis (odds ratio, 1.365; 95% confidence interval, 1.014-1.836; p=0.040). Conclusion: The frequency of rhabdomyolysis in CO poisoning was 15.7% and fluid therapy was very effective in treatment of CO-induced rhabdomyolysis and prevention of AKI progression. An exposure time to CO of over 5 hours was a factor with high potential for predicting development of CO-induced rhabdomyolysis. Along with patients symptoms and signs, this factor should be considered in assessment of patients with CO poisoning. Key Words: Carbon monoxide, Rhabdomyolysis, Acute kidney injury Department of Emergency Medicine, Pusan National University Hospital, Busan, Korea Article Summary What is already known in the previous study Rhabdomyolysis is a common complication of carbon monoxide (CO) poisoning and can lead to development of acute kidney injury (AKI). Tissue hypoxia and direct toxic effect of CO at the cellular level are suggested mechanisms of CO-induced rhabdomyolysis. What is new in the current study This study showed that exposure time to CO of over 5 hours was a factor for predicting development of CO-induced rhabdomyolysis. The fluid therapy was sufficient for treatment of rhabdomyolysis and prevention of AKI. 책임저자 : 박성욱부산광역시서구구덕로 179 부산대학교의학전문대학원응급의학교실 Tel: 051) 240-7503, Fax: 051) 253-6472 E-mail: psu52156@naver.com 접수일 : 2014년 2월 14일, 1차교정일 : 2014년 2월 17일게재승인일 : 2014년 3월 10일 본연구는 2014 년도부산대학교병원임상연구비지원으로이루어졌음. 261 서 횡문근융해증 (rhabdomyolysis) 은다양한원인에의하여횡문근이파괴되어세포내의잠재적인독성물질이혈장으로유출되어발생하는증후군이다 1). 성인에서는근력의약화, 근육통, 짙은소변색깔과같은특징적인증상을보이며횡문근융해증이발생될경우생명을위협할수있는급성신손상 (acute kidney injury) 이나파종성혈관내 론
262 / 대한응급의학회지 : 제 25 권제 3 호 2014 응고장애 (disseminated intravacular cogaulation) 를일으킬수있어환자의예후에나쁜영향을미칠수있다 2,3). 이중급성신손상은전세계적으로문제가되고있으며사망률은 40%~90% 까지이르는것으로보고되고있다 4-6). 수십년전부터급성신손상에대한예방가능한위험인자들이밝혀지고있고, 치료방법이향상되고있지만급성신손상이진행하여신부전단계에이르게될경우현실적으로환자가의존할수있는치료는신대체요법 (renal replacement therapy) 이외에는없는실정이다. 일산화탄소중독은횡문근융해증의한원인으로병태생리학적으로골격근의괴사를일으키고심한경우급성신부전까지일으켰던경우가여러증례에서보고되고있다 7-11). 최근에증가하고있는일산화탄소중독환자들을고려했을때횡문근융해증의발생가능성이있는환자를조기에발견하여초기에적극적으로치료한다면급성신손상의진행을막는데많은도움이될것으로생각된다. 하지만최근까지일산화탄소중독환자에서횡문근융해증의발생빈도나발생위험성이있는환자의특성등에대한연구는거의이루어지지않고있다. 이에저자들은일산화탄소중독으로진단된환자를대상으로횡문근융해증및급성신손상의발생빈도및환자의특성, 그리고횡문근융해증의발병을조기에예측할수있는위험인자를밝혀내기위해이연구를시행하였다. 일산화탄소발생원, 환자의발견장소등중독과관련된여러인자를포함한대상환자의자료를의무기록을통해후향적으로조사하였다. 횡문근융해증의진단은본원의 creatine kinase (CK) 의참고수치의상한선인 217 U/L 의 5배인 1085 U/L 이상인경우로하였으며급성신손상의진단은 2012년 KDIGO Clinical Practice Guideline for Acute Kidney Injury을참고하여다음과같은경우로정의하였다 13,14). 1) 혈청 creatinine이 48시간내에 0.3 mg/dl 이상상승하는경우 2) 기저수치보다 1.5배이상상승하는경우 3) 소변량이 6시간동안 0.5 ml/kg/hour 미만으로감소하는경우단, 환자의기저 creatinine 수치를알수없고만성신장병의병력이없는환자의경우, 본원혈청 creatinine의참고수치의상한선인 1.2 mg/dl을기저수치로가정하였다. 고압산소치료 (hyperbaric oxygen therapy) 는내원당시 COHb 수치가 25% 이상인경우, 의식의저하가있었던경우, 대사성산증이나 CK 상승등의혈액검사상이상소견이있는경우에동일한방식 (3회, 12시간간격, 30분동안 ) 으로실시하였다. 대상과방법 1. 연구대상 2010년 1월부터 2012년 12월까지부산지역의일개대학병원의응급의료센터에일산화탄소중독으로내원한 18 세이상의환자를대상으로의무기록을조사하였다. 연구기간동안내원한환자는총 152명으로이중에서타병원에서전원된 71명의환자의경우 COHb 수치를포함한여러혈액검사를확인할수없었고병력청취내용이충분하지않은경우가많아연구대상에서제외하였다. 또한본병원에서의의무기록자료가불충분했던 5명과다른약물을복용하여이번연구결과에영향을끼칠수있었다고판단된 6 명의환자를제외하여총 70명의환자를대상으로연구를진행하였다. 일산화탄소중독의진단은일산화탄소에대한노출병력이있으면서응급실내원시일산화탄소헤모글로빈 (carboxyhemoglobin; COHb) 농도가흡연자의경우 10% 이상, 비흡연자의경우 5% 이상인경우로하였다 12). 2. 연구방법인구학적특성, 실험실검사결과그리고의도성유무, 3. 통계분석대상환자를횡문근융해증이발병한군 (rhabdomyolysis group) 과발생하지않은군 (non-rhabdomyolysis group) 으로분류하였다. 이두군에대하여수집한자료를연속형변수의경우정규성검정을실시하여정규분포를띄는변수는평균값 ± 표준편차로표시하고 Student t test를사용하여비교분석하였고, 정규분포를띄지않는변수는중앙값과사분위값으로표시하고 Mann-Whiteny U test를사용하였다. 비연속형변수의경우빈도수와백분율로표시하고 chi-square test 또는 Fisher s extact를사용하였다. 단변량분석에서통계적으로유의한변수중에서횡문근융해증의발병을예측할수있는독립적인위험인자를밝히기위해다변량로지스틱회귀분석 (multivariate logistic regression analysis) 을실시하였고, 여기서확인된위험인자에대한수신자조작특성 (receiver operating characteristic, ROC) 곡선분석을통해횡문근융해증발병에대한예측력을평가하였다. 통계분석은윈도우용 PASW statistics 18.0 (IBM corporation, Armork, NY, USA) 과 Medcalc 7.4 (Medcalc software, Mariakerke, Belgium) 를이용하여분석하였고 p값이 0.05 미만인경우통계적으로유의하다고판단하였다.
임재황외 : 일산화탄소중독에서횡문근융해증발병예측인자 / 263 결과 1. 대상환자의일반적및중독학적특성연구에포함된총 70명의환자중남자는 39명 (55.7%), 여자는 31명 (44.3%) 이었고평균나이는 42.6±18.4세였다. 횡문근융해증이발생한환자는 11명 (15.7%), 발생하지않은환자는 59명 (84.3%) 이었다. 성별은두군에서유의한차이를보이지않았으나, 나이는횡문근융행증군에서 51.4±20.9세로비횡문근융해증군의 40.4±17.3세 보다많았다 (p=0.045). 일산화탄소에노출된시간은횡문근융해증군에서평균 12.0시간으로비횡문근용해증군의 2.0시간보다통계적으로유의하게길었으나 (p<0.001), 노출종료후부터응급의료센터에도착까지의시간은차이가없었다. 그밖의자살목적유무, 일산화탄소의발생원인과장소는두군에서통계적으로차이가나지않았다. 혈중알코올농도측정은총 42명의환자에서시행되었는데본원의알코올섭취기준인 30 mg/dl를초과한경우는총 9명이었다. 이들환자를제외한후분석한 GCS (Glasgow Coma Scale) 는횡문근융해증군에서 8.5 Table 1. Poisoning related characteristics and demographic findings in carbon monoxide poisoned patients. Rhabdomyolysis (n=11) Non-rhabdomyolysis (n=59) p-value Male, n (%) 05 (45.5%) 34 (57.6%) <0.456 Age (years)* 51.4±20.9 40.4±17.3 <0.045 Exposure time (hour) 12.0 (11.0-14.5) 2.0 (0.5-4.0). <0.001 Time elapsed between exposure 1.2 (01.0-1.5) 1.0 (0.7-1.5). <0.108 cessation and ED admission (hour) Admission route, n (%) <0.671 by 119 rescuers 10 (90.9%) 51 (86.4%) by witness 01 (09.1%) 08 (13.6%) Suicide attempt, n (%) 05 (45.5%) 30 (50.8%) <0.743 Alcohol ingestion, n (%) 0 (0%)0. 09 (15.3%) <0.165 Blood alcohol level, mg/dl 2.0 (00.9-6.2) 0.4.7 (2.0-112.3) <0.086 Sources of CO, n (%) <0.119 Fire-related 0 (0%)0. 11 (18.6%) Non-fire-related 11 (100%). 48 (81.4%) Briquette 03 17 Ignition charcoal 04 19 Charcoal 00 01 Wood burning boiler 01 04 Briquette boiler 01 02 Gas boiler 00 02 Red clay 02 03 Gasoline 00 00 Place, n <0.609 Home 11 47 Car 00 07 Accomodation 00 01 Work place 00 03 Restaurant 00 01 Glasgow Coma Scale, 8.5 (5.8-15)0. 15 (8-15)00 <0.028 SBP (mmhg) 110 (90-130)0. 110 (100-130) <0.368 HBO therapy, n (%) <0.932 Yes 06 (54.5%) 33 (55.9%) No 05 (45.5%) 26 (44.1%) * Mean±Standard deviation Median (interquartile range) Alcohol ingestion was defined when blood alcohol level was more than 30 mg/dl Glasgow Coma Scale was calcualted after excluing 9 alcohol ingestion patients. ED: emergency department, CO: carbon monoxide, SBP: systolic blood pressure, HBO: hyperbaric oxygen
264 / 대한응급의학회지 : 제 25 권제 3 호 2014 (5.8-15), 비횡문근융해증군에서 15 (8-15) 점으로의미있는차이를보였다 (p=0.028). 고압산소치료는횡문근융해증군에서 6명 (54.5%), 비횡문근융해증군에서 33명 (55.9%) 의환자에서시행되어통계학적인차이는없었다 (Table 1). 의료진이고압산소치료가필요하다고판단했지만시행되지못한이유로는치료거부, 환자의비협조, 환자의불안정한상태등이있었다. 2. 대상환자의검사학적특성내원당시평균 COHb은두군에서각각 22.4±11.6% 21.8±16.3% 로차이를보이지않았다. 동맥혈검사항목인 ph, 이산화탄소분압, 염기결핍, 젖산수치등에서도의미있는차이는관찰되지않았다. 하지만내원당시백혈구수치 (p=0.002) 와근육과관련된효소인혈청 myolglobin (p<0.001), CK (p<0.001), troponin I (p<0.001) 그리고최고 creatinine (p=0.005) 은모두통계적으로유의하게횡문근융해증군에서높았으며급성신손상의발생빈도도횡문근융해증군에서 5명 (45.5%) 으로비횡문근융해증군의 1명 (1.7%) 보다많았다 (p<0.001) (Table 2). 3. 횡문근융해증발생과관련된변수두군사이에서통계적으로의미있는차이를보인변수중에서횡문근융해증과직접관련이있는 myoglobin, CK 를제외하고나이, 일산화탄소노출시간, GCS, Troponin I, WBC 를대상으로다변량로지스틱회귀분석을시행한결과일산화탄소노출시간 (Odds ration, 1.365; 95% confidence interval, 1.014-1.836, p=0.040) 만이통계적으로의미있는것으로확인되었다 (Table 3). 일산화탄소노출시간의횡문근융해증발병에대한예측능력을확인하기위해 ROC 분석을시행한결과곡선하면적 (area under curve, AUC) 은 0.892 (95% CI, 0.790~0.955) 로측정되었으며 cut-off 값인 5시간에서민감도 91.7%, 특이도 83.0%, 양성예측도 55.0%, 음성예측도 97.8% 를보였다 (Fig. 1). 고찰일산화탄소중독의병태생리학적기전은다양한데이중에서가장중요한기전은산소보다 200배이상의친화도로 Table 2. Laboratory findings in carbon monoxide poisoned patients. Rhabdomyolysis (n=11) Non-rhabdomyolysis (n=59) p-value COHb (%)* 022.4±11.6 21.8±16.3 <0.892 ph 7.39 (7.31-7.44)00 7.42 (7.39-7.46) <0.197 PCO 2 (mmhg)* 27.8±6.9 29.5±4.70 <0.407 BE (mmol/l) -5.05 (-8.13 - -1.13) -2.90 (-4.73 - -0.98) <0.103 Lactic acid (mmol/l) 3.10 (2.23-9.40)00 2.60 (1.50-4.60) <0.156 White blood cell (mm 3 ) 17600 (10407-22760). 0009640 (7542.5-12293) <0.002 Myoglobin (ng/ml) 3128.9 (774.0-4013.9)0 20.2 (14.8-47.0) <0.001 CK (U/L) 3578.0 (1991.5-7771.3) 114.0 (79.0-163.0) <0.001 Troponin I (ng/ml) 0.58 (0.20-2.38)00 0.00 (0.00-0.03) <0.001 Maximum Cr (mg/dl) 1.14 (0.83-2.24)00 0.85 (0.66-1.00) <0.005 Acute kidney injury, n (%) 5 (45.5%) 1 (1.7%) <0.001 * Mean±Standard deviation Median (interquartile range) COHb: carboxy hemoglobin, BE: base excess, CK: creatine kinase, Cr: creatinine Table 3. Multiple logistic regression analysis for acute kidney injury in carbon monoxide poisoned patients. Factors p-value Odds ratio 95% CI of odds ratio Lower Upper Age 0.493 1.019 0.965 1.077 Exposure time 0.040 1.365 1.014 1.836 Glasgow Coma Scale 0.390 1.133 0.846 1.364 Troponin I 0.067 192.3 0.690 53573.8 White blood cell 0.549 1.000 1.000 1.000 CI: confidence interval
임재황외 : 일산화탄소중독에서횡문근융해증발병예측인자 / 265 헤모글로빈에결합한후 COHb을생성하고산소해리곡선을왼쪽으로이동시켜세포의저산소증을일으키는것이다 15-17). 일산화탄소는헤모글로빈이외에도 heme을포함하는다른단백질에도결합할수있는데 cytochrome c oxydase (CCO) 와결합하여근육세포내의산소호흡 (aerobic respiration) 을불활성화시키고 myoglobin과결합하여산소와의결합을방해하여산소의이용을저하시킨다 18-20). 이런기전으로일산화탄소중독은골격근의괴사를일으키고횡문근융해증을발생시키는데이에관한연구는현재까지는증례보고형식으로만보고되고있다 7-11). 이번연구에서 CK는전체대상환자 70명중 18명 (25.7%) 의환자에서정상치이상으로상승하였고 15.7% 인 11명의환자에서횡문근융해증의진단기준치이상으로상승하였다. 11명의횡문근융해증환자에서 10명은응급의료센터내원시에, 나머지 1명은입원이후에진단기준치이상으로상승하였다. 응급실에서수액치료가시작된후 CK는 5명에서계속감소하였고 3명에서는 24시간또는 48시간까지상승한후감소하는패턴을보여수액치료가효과가있었다. 반면 3명의환자에서는응급실에서부터혈역학적으로불안정한상태가지속되어중환자실에서사망하였다. 횡문근융해증으로인한증상은응급의료센터에서 11명의환자중 9명의환자에서기계호흡시행으로인한진정제사용으로증상을확인하기가어려웠다. 횡문근융해증은일산화탄소중독효과로인한것이겠지만 3명의횡문근융해증환자에서피부의화상이관찰되었고 1명의환자에서국소적인다리의압통이관찰되어의식소실당시 Fig. 1. Receiver operating characteristic curve of the exposure time to carbon monoxide for the prediction of rhabdomyolysis. The area under the curve of exposure time is 0.892 (95% confidence interval: 0.790-0.955). The cutoff value is 5 hours and its sensitivity is 91.7% and specificity is 83.0%. 화상또는조직의압박으로인해횡문근융해증의발병이더촉발되었을가능성이있다. 급성신손상은횡문근융해증의합병증으로발생할수있는데이것은근육손상으로인한체액의유출및순환체액량의감소그리고교감신경계와레닌-안지오텐신시스템의활성화로인한신장및세뇨관에대한허혈성손상과 myoglobin 자체에의한산화적손상에기인한다. 또한 myoglobin과결합한단백물질에의한세뇨관의폐쇄도급성신손상의발생에기여하는요소이다 21). 이번연구에서급성신손상은비횡문근융해증군에비해횡문근융해증군에서더높은빈도로발생하였는데이결과로유추해볼때일산화탄소중독환자에서의급성신손상은횡문근융해증, 즉근육손상에인한이차적인것으로사료된다. 다수의과거사례보고에서도일산화탄소중독환자에서급성신손상의원인으로횡문근융해증과관련짓고있으나일산화탄소가혈관손상을일으켜직접으로신손상에관여한다는보고도있어일산화탄소의신장에대한직접적인독성을완전히배제할수는없을것으로생각된다 22). 횡문근융해증에의한급성신부전의정확한발생빈도는알려지지않았으나 4~33% 정도인것으로추정되고있으며, 혈중 CK 수치가 5,000 U/L이상인경우심한근육손상이발생할수있으며 16,000 U/L이상으로상승할경우신부전의발생가능성이높은것으로알려져있다 23,24). 이번연구에서횡문근융해증환자의 45.5% 에서급성신손상이발생하였지만신부전으로진행한환자는없었다. 이것은횡문근융해증환자의혈중최고 CK 수치가대다수 (9명) 에서 5,000 U/L 이하로측정되어내원당시의급성신손상의 grade가낮아수액치료만으로도효과가있었던것으로사료된다. 또한비횡문근융해증환자에서도환자의악화가발견되지않았는데이것으로볼때일산화탄소중독으로인한횡문근융해증과급성신손상의예후는수액치료와산소치료가조기에시작된다면양호할것으로사료된다. 이번연구에서임상적으로중요한다른결과는일산화탄소에노출시간이 5시간이상될경우횡문근융해증의발병가능성이높았다는점이다. 이결과는실제임상에서 COHb이측정되지않는의료기관이있다는점과일산화탄소중독의중등도평가에서 COHb의유용성이낮다는점에서고압산소치료시행여부나입원치료의여부를결정하는데있어서객관적인기준으로활용될수있는의미있는결과로생각된다. 다만현재까지일산화탄소에노출된시간이일산화탄소중독의예후와관련이있다는보고는있으나노출시간에대한자료가없어이번연구결과와비교할수없었다 25). 따라서이번연구결과의수치가실제임상에서신뢰도가높은지표로활용되기위해서는이후에도추가적인연구가진행되어야할것으로생각된다. 일반적으로나이가들수록일산화탄소의반감기가증가한다고알려져있다. 이번연구에서횡문근융해증군의환
266 / 대한응급의학회지 : 제 25 권제 3 호 2014 자가더나이가많고일산화탄소에노출된시간이길었음에도불구하고 COHb은유의한차이가나지않았다. 이결과는환자가일산화탄소에노출될당시의장소의넓이, 밀폐정도, 일산화탄소발생원의연소정도를반영하지못한점이결과에영향을끼쳤을가능성이있다. 또한 Coburn- Forster-Kane Model 26) 등에의하면일정한농도의일산화탄소에지속적으로노출될경우체내의 COHb이계속증가하지않고일정수준에서머무는항정상태 (steady state) 에도달한다고하였는데이런생리학적인기전이 COHb의결과에작용했을가능성도있다. 일산화탄소에노출시의식의저하정도가심할수록체위의존적부위 (dependent portion) 의국소적인압박또는화상에대한인지가저하되어이차적으로횡문근융해증이발생할가능성이있다. 이런이유로 GCS는이번연구에서횡문근융해증발생예측의독립적인인자로확인되지는않았지만추후연구에서횡문근융해증발생과관련된인자로고려될수있을것으로생각된다. 이전연구에서도 GCS는 COHb보다중증도예측에있어서우월하다고알려져있으며초기에낮은 GCS를보일수록신경학적손상가능성이높다는결과가보고되고있다 27,28). 일산화탄소중독환자의혈액내백혈구수의증가는혈소판에서유리되는일산화질소 (nitric oxide) 에의한것으로, 일산화탄소는혈소판에서일산화질소의유리를촉진시키는역할을한다 29,30). 따라서이번연구에서백혈구수의증가가횡문근융해증군에서더컸던것은일산화탄소의독성작용이횡문근융해증군에서더심했음을간접적으로시사하는것으로사료된다. 본연구에는몇가지제한점이있다. 첫째연구대상환자가일개대학병원응급센터로내원한환자로제한되어대상환자의수가충분하지않았다는점이다. 둘째, 앞에서도언급했지만환자가일산화탄소에노출된장소의넓이, 밀폐정도, 일산화탄소발생원의연소정도, 연소시발생될수있는다른유해가스에대한정보는환자의증상과 COHb 수치에영향을줄수있는중요한정보였지만후향적연구의한계로인해확인할수없었다는점이다. 셋째, 일산화탄소에노출되기시작한시점을정확하게알수없었을경우, 환자의노출시작시점을마지막으로목격된시점부터로계산하였는데이로인해노출기간이정확하지않았을가능성이있다. 마지막으로환자들의기저 creatinine의수치가부정확하고근육손상이 creatinine의수치에영향을줄수있기때문에 neutrophil gelatinase-associated lipocalin (NGAL) 같은생화학적표지자가포함되지않은이번연구에서급성신손상의발생빈도는부정확할수있다. 결론이번연구에서일산화탄소에노출된시간이 5시간이상 일경우횡문근융해증의발생가능성이높은것으로나타났다. 따라서일산화탄소중독이의심되는환자에서 COHb 수치및임상양상과더불어일산화탄소에노출된시간을반드시고려하여잠재적으로합병증의위험성이있는환자를간과하지않도록하여야할것이다. 참고문헌 01. Beetham R. Biochemical investigation of suspected rhabdomyolysis. Ann Clin Biochem. 2000;37:581-7. 02. Cervellin G, Comelli I, Lippi G. Rhabdomyolysis: historical background, clinical, diagnostic and therapeutic features. Clin Chem Lab Med. 2010;48:749-56. 03. Vanholder R, Sever MS, Erek E, Lameire N. Rhabdomyolysis. J Am Soc Nephrol. 2000;11:1553-61. 04. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11:R31. 05. Ostermann M, Chang RW. Acute kidney injury in the intensive care unit according to RIFLE. Crit Care Med. 2007;35:1837-43. 06. Levy EM, Viscoli CM, Horwitz RI. The effect of acute renal failure on mortality: a cohort analysis. JAMA. 1996;275:1489-94. 07. Wolff E. Carbon monoxide poisoning with severe myonecrosis and acute renal failure. Am J Emerg Med. 1994;12:347-9. 08. Florkowski CM, Rossi ML, Carey MP, Poulton K, Dickson GR, Ferner RE. Rhabdomyolysis and acute renal failure following carbon monoxide poisoning: two case reports with muscle histopathology and enzyme activities. J Toxicol Clin Toxicol. 1992;30:443-54. 09. Herman GD, Shapiro AB, Leikin J. Myonecrosis in carbon monoxide poisoning. Vet Hum Toxicol. 1988;30:28-30. 10. Jha R, Kher V, Kale SA, Jain SK, Arora P. Carbon monoxide poisoning: an unusual cause of acute renal failure. 1994;16:775-9. 11. Bessoudo R, Gray J. Carbon monoxide poisoning and nonoliguric acute renal failure. Can Med Assoc J. 1978; 119:41-4. 12. Pozzoli G, Mancuso C, Mirtella A, Preziosi P, Grossman AB, Navarra P. Carbon monoxide as a novel neuroendocrine modulator: inhibition of stimulated corticotropinreleasing hormone release from acute rat hypothalamic explants. Endocrinology. 1994;135:2314-7. 13. Elsayed EF, Reilly RF. Rhabdomyolysis: a review, with emphasis on the pediatric population. Pediatr Nephrol. 2010;25:7-18.
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