以病程分期为依据之儿童肠病毒重症治疗概要课件

按一下以編輯母片標題樣式,按一下以編輯母片本文樣式,第二層,第三層,第四層,第五層,*,以病程分期为依据之儿童肠病毒重症治疗概要课件,1,以病程分期為依據之兒童腸病毒重症治療,The Stage Based Therapy of,Critically Ill Children with EV 71 Infection,林口長庚兒童醫院,兒童加護科夏紹軒 吳昌騰,兒童心臟科黃茂盛 鍾宏濤,兒童神經科林光麟 王傳育,兒童呼吸胸腔科黃健燊,兒童感染科張鑾英 黃玉成 邱政洵 林奏延,以病程分期為依據之兒童腸病毒重症治療 The Sta,2,A Cardiopulmonary disaster requiring multidisciplinary treatment,A Cardiopulmonary disaster re,3,I. Outbreaks,II.,臨床分期及其表現,III.,呼吸衰竭的病生理學,IV.,治療的考量,V.,結論,I. Outbreaks,4,Outbreaks (1),民國八十七年五月初,一個一歲兩個月大的小女孩被帶到門診，主訴是,fever with oral ulcers and vesicles on hands, feet and knees,.,母親對於小朋友的,高燒不退、躁動不安、食慾減退、入睡困難、無力站立,非常擔心。,Outbreaks (1)民國八十七年五月初,5,Outbreaks (2),醫生說：這是典型手足口病症狀，只要吃一些退燒藥，多休息、多喝水就好了。,第二天，小女孩被帶回急診，已經發生,意識不清、發紺,等症狀，當時，急診醫師為她插上氣管內管，,大量粉紅色泡沫狀液體,從氣管內冒出。,Outbreaks (2)醫生說：這是典型手足口病症狀，只要,6,Outbreaks (3),小女孩被送到,PICU.,發生心肺衰竭，,CPR,無效後，被宣布死亡。,此後一個月，共有七名兒童因同一症狀死在本院，,醫師立即通報疾病管制局，並發現幾乎全台灣各大醫學中心都有類似案例。,Outbreaks (3)小女孩被送到 PICU. 發生心肺,7,Enetrovirus type 71,腸病毒七十一型分別在糞便、咽喉、及腦脊髓液檢體中被培養出來。,Enetrovirus type 71 腸病毒七十一型分別,8,EV 71 Outbreaks,Enterovirus type 71 was firstly isolated from the stool of an infant with encephalitis in US in 1969,1975, 44/705 were killed in Bulgaria,1997, 30 were killed in Malaysia,1998, 78 were killed in Taiwan,1999, 8 were killed in Hong-Kong,EV 71 OutbreaksEnterovirus typ,9,1998,腸病毒流行之統計,估計約一百萬至兩百萬人口被感染？！,查有實據者129106人為,EV71,感染,405人為重症,78人死亡,80%死於,肺水腫與肺出血,1998 腸病毒流行之統計估計約一百萬至兩百萬人口被感染？！,10,腸病毒的傳染途徑,飛沫傳染,唾液與呼吸道分泌物在痊癒之後2-3,weeks,仍可分離出,EV71,病毒,糞口傳染,糞便在痊癒之後6-8,weeks,仍可分離出,EV71,病毒,病毒離開人體可存活8小時左右,腸病毒的傳染途徑飛沫傳染,11,I. Outbreaks,II.,臨床分期及其表現,III.,呼吸衰竭的病生理學,IV.,治療的考量,V.,結論,I. Outbreaks,12,EV71(174)non71 EV(241),Uncomlicated cases,HFMD/herpangina,Viral exanthem,Febrile illness,Others,Comlicated cases,Meningitis,Encephalitis/myelitis,Polio-like syndrome,Pulmonary Oedema,Fatal cases,Survivors with severe neurological sequela,119(68%),108(63%),2(1.1%),7(4%),2(1.1%),55(32%),13(7.5%),26(14.5%)#,4(2.3%),12(6.9%)#,14(8.0%)#,5(2.8%)#,187(78%),105(43%),5(2%),18(7.4%),59(24%),54(22%),44(18%),5(2.1%),0(0%),0(0%),0(0%),0(0%),#:,p1509(82%) 4(11%)38(6-211)0.001 *,Leukocytosis9(82%) 12(32%) 9.7(2.9-34) 0.003 #,Upper limb4(36%) 4(11%) 4.9(2.6-9.2) 0.04,weakness,Lower limb7(64%) 11(29%) 4.3(2.0-9.2) 0.04,weakness,Chang et al. Lancet 354(9191): 1682, 1999,Table 4: Risk factors associat,15,Skin and Mucosa Lesions,Oral ulcers distributed not on soft palate only as typical hand-foot mouth disease,Vesicles on hand and foot were smaller (pin-point) than typical HFM disease,Sometimes the skin lesion consisted of petechiae-like clusters,Skin and Mucosa LesionsOral ul,16,以病程分期为依据之儿童肠病毒重症治疗概要课件,17,以病程分期为依据之儿童肠病毒重症治疗概要课件,18,以病程分期为依据之儿童肠病毒重症治疗概要课件,19,以病程分期为依据之儿童肠病毒重症治疗概要课件,20,Phases Based Therapy of Critical EV-71 Infection,腸病毒重症之臨床分期,第一期：上呼吸道感染手足口病,第二期：神經症狀腦膜腦脊髓炎,第三,A,期：高血壓肺水腫出血自主神經失調,第三,B,期：低血壓心臟衰竭？心肌炎？,SIRS?,第四期：逐漸恢復神經後遺症,Phases Based Therapy of Critic,21,分期標的,Stage 1: Oral ulcer, skin rash, fever,Stage 2: Neurological symptoms,myoclonic jerk, limb weakness, seizure, consciousness disturbance,Stage 3A: Elevated,BP,Stage 3B: Decreased,BP, use of catecholamines,Stage 4: Cessation of,catecholamines.,分期標的Stage 1: Oral ulcer, skin,22,Results,We observed a majority of patients (58% 14/24) presented different five clinical phases.,Two patients,developed PE,without a HFM prodrome,One,patient developed PE without,previous,CNS,involvement signs,In,six patients,hypertension phases,were not observed,Three patients,did not develop,hypotension,phenomenon,ResultsWe observed a majority,23,Table,A Severe Hypertension Criteria by Age,Age Group,Systolic(mmHg),Diastolic(mmHg),NB,7days,106,8-20,days,110,Infants,2yo,118,82,Children 3-5yo,118,84,6-9,yo,130,86,10-12,yo,134,90,13-15,yo,144,92,16-18,yo,150,96,Modified from Hycan et al. Task Force on Blood Pressure control in Children. Pediatrics 79:1, 1987.,Table A Severe Hypertension Cr,24,Table B. Normal Blood Pressure by Age,Age,Systolic(mmHg),Diastolic(mmHg),Neonate,60-90,20-60,Infant(6mo),87-105,53-66,Toddler(2yr),95-105,53-66,2-7,yo,97-112,57-71,7-15,yo,112-128,66-80,Hazinski MF: Nursing Care of the Critically Ill Child, 2,nd,ed. St.Louis, Mo: Mosby Year Book; 1992,Table B. Normal Blood Pressure,25,第一期：手足口病,持續約數天,可能發高燒,類手足口病,Hand-Foot-Mouth disease,類皰疹性咽峽炎,Herpangina,大多數病人可自然痊癒，無後遺症,手足水泡較典型手足口病小約針尖大小,高危險群可能向後期發展,第一期：手足口病持續約數天,26,重症病例之前趨症狀及危險因子,I,重症病例,前趨症狀,四肢反射性抖動(,myoclonic jerk),嘔吐,嗜睡,中樞神經,受侵犯之危險因子,年齡小於三歲,高燒超過39度,燒超過3天,嗜睡、抽筋、頭痛,嘔吐,高血糖(150,mg/dl),重症病例之前趨症狀及危險因子 I重症病例前趨症狀中樞神經受侵,27,重症病例之前趨症狀及危險因子,II,重症病例中,肺水腫,之危險因子,年齡小於三歲,高血糖(150,mg/dl),肢體無力,白血球升高,重症包含中樞神經受侵犯及肺水腫,重症病例之前趨症狀及危險因子 II重症病例中肺水腫之危險因子,28,第二期：腦膜腦炎,持續數天,包括,睡眠易驚醒,startling、,手足抖動,myoclonic jerk、,肢體無力,weakness,可能,嘔吐、嗜睡,可能發生痙攣,腦脊髓液可能有發炎跡象亦可能無,到此仍可能自然痊癒，或許有後遺症,第二期：腦膜腦炎持續數天,29,第三,A,期：高血壓肺水腫出血,自主神經失調？,持續約數小時至一天左右，民國八十七年肺水腫出血為最主要死因,血壓上升為最早徵兆、高燒、心搏過快200/,min,以上、呼吸急促、出冷汗。,高血糖(200,mg/dl),肺水腫、肺泡出血、血氧含量降低,神經症狀持續惡化，昏迷指數降低、四肢更無力,第三A期：高血壓肺水腫出血自主神經失調？持續約數小時至一,30,以病程分期为依据之儿童肠病毒重症治疗概要课件,31,以病程分期为依据之儿童肠病毒重症治疗概要课件,32,Lungs are congested,Red blood cells are found in small airways and alveoli,Lungs are congestedRed blood c,33,Parameters Sequence Around PE,Parameters Sequence Around PE,34,Parameters Sequence (2),Parameters Sequence (2),35,第三,B,期：低血壓：心臟衰竭,持續約二至七天,心搏速率漸降但,血壓可能更低,肺水腫出血漸好轉但仍需呼吸器，自呼能力差,血糖正常化,神經症狀之變化：垂直眼震顫、斜視、肢體無力、抽筋等，此期間腦灌流可能變差造成缺氧缺血性腦病變。,第三B期：低血壓：心臟衰竭持續約二至七天,36,第四期：逐漸恢復,持續？月？年,心臟功能幾乎完全恢復,肺功能可能不好但足堪負擔換氣，然而病人,自呼、吞嚥功能不好,有嚴重影響，所以仍需呼吸器支持。,漸漸甦醒，神經可能有,嚴重後遺症,可能發生反覆性肺炎。,第四期：逐漸恢復持續？月？年,37,I. Outbreaks,II.,臨床分期及其表現,III.,呼吸衰竭的病生理學,IV.,治療的考量,V.,結論,I. Outbreaks,38,Pathophysiology of Pulmonary Oedema,Starlings formula,Flow=K(P,c,P,is,) (Onc,pl,Onc,is,),Interstitium,Alveolus,Lymphatics,Pulmonary capillary,P,c,P,is,K,Onc,pl,Onc,is,O2,Pathophysiology of Pulmonary O,39,Hypotheses of the Mechanism of pulmonary oedema,SIRS/ARDS,Neurogenic pulmonary edema,Cardiogenic,Capillary permeability,Systemic/pulmonary vasculer resistence,LV systolic dysfunction,LV diastolic dysfunction,Hypotheses of the Mechanism of,40,Evidence Supporting SIRS,Group,Encephalitis with Pulmonary Oedema (N=8),Encephalitis (N=8),Uncomplicated (N=170),Normal Control (N=21),P-value*,WBC(10,9,/L),28.3,+,7.6,15.5,+,6.8,12.3,+,4.7,-,0.0001,CRP(mg/L),18.5,+,16.3,31.0,+,35.8,15.9,+,29.1,-,0.49,Glucose (mg/dL),501,+,186,165,+,117,103,+,15,-,0.0001,IL-1(pg/ml),48.4,+,85.2,4.9,+,10.1,1.6,+,0.9,1.8,+,1.0,0.006,IL-6(pg/ml),947,+,1239,4.9,+,3.1,2.8,+,1.9,1.9,+,0.5,0.0001,TNF- (pg/ml),22.4,+,29.5,5.3,+,1.0,5.6,+,1.6,6.8,+,1.5,0.004,Lin et al.,Evidence Supporting SIRSGroupE,41,Evidences Related to Neurogenic Pulmonary Oedema,CNS involvement preceeds pulmonary oedema,Increased cortisol level and clinical evidences suggested an autonomic nervous system dysfunction(increased sympathetic tone),Lack of study of pulmonary capillary permeability,Systemic vascular resistence does not increase significantly.,Evidences Related to Neurogeni,42,Diffuse inflammatory cell infiltration in Cerebrum, midbrain and brain stem,Perivascular cuffing was also common,Diffuse inflammatory cell infi,43,以病程分期为依据之儿童肠病毒重症治疗概要课件,44,Cortisol Level vs. Vital Signs,Cortisol Level vs. Vital Signs,45,Evidences Related to Cardiogenic,Increased pulmonary artery wedge pressure?,Echo revealed systolic and diastolic dysfunction,Hypertension associated,Inappropriate tachycardia associated,Increased cardiac enzymes,However, autopsy findings are against myocarditis,Evidences Related to Cardioge,46,Initial Swan-Ganz Monitor Data,#,1,2,3,Age,1,y5m,10,m,1,y6m,PAWP(mmHg),26,22,22,CVP(mmHg),10,8,13,CI(L/min/m,2,),5.6,3.6,3.8,SI(mL/beat/m,2,),25.9,20.2,19.8,SVRI(dyne-s-cm,-5,),1296,1439,1363,PVRI(dyne-s-cm,-5,),79,67,168,Initial Swan-Ganz Monitor Data,47,Echocardiography Evidences,Systolic,dysfunction: The initial ejection fraction: 18-75%(mean,SE=51.5 3.6%)(n=18),Diastolic,dysfunction:,Mitral flow velocities: E/A, DT, IVRT,E=peak velocity of the early filling wave, A=peak velocity of the late filling wave due to atrial contraction, DT=deceleration time, IVRT=isovolumic relaxation time,Mitral annulus velocities: E/E,E=early diastolic annulus velocity(the rate of change in long-axis dimension and LV volume),Echocardiography EvidencesSyst,48,Diastolic Function,#,1,2,3,4,5,Clinical,PE+HF,PE+HF,Mild PE,HT only,HT only,E/A,3.2,0.86,2.94,merged,DT(ms),48.19,73.09,54.6,152.6,IVRT(ms),54.22,20.08,44.8,60.24,E/E,15.11,14.76,9.75,7,7.4,Comment,Restrictive physiology,Restrictive physiology,Relaxation impairment,Adequate diastole,Adequate diastole,Outcome,Died,Severe sequela,Mild sequela,Recover completely,Recover completely,PE: pulmonary oedema, HF: heart failure, HT: hypertension,Diastolic Function#12345Clinic,49,Cardiac Enzymes,CKMB,(normal16U/L):,4-92U/L, mean,SE=31.177.73(n=12),Troponin I,(normal2ng/ml):,0.4-50ng/ml, meanSE=21.924.36(n=17,),Cardiac EnzymesCKMB (normal16,50,Grossly, the heart is hypertrophic,Under microscope, there is no inflammatory change,Grossly, the heart is hypertro,51,I. Outbreaks,II.,臨床分期及其表現,III.,呼吸衰竭的病生理學,IV.,治療的考量,V.,結論,I. Outbreaks,52,When Patient Becomes Very Critical,Neurological deteriorates,GCS9,Apnea, choke,Unable to protect airway,Paradoxical respiration,Pulmonary oedema/hemorrhage develops,Cardiovascular system malfunctions: hypertension, tachycardia,When Patient Becomes Very Crit,53,Virus,SIRS,Cytokines,RV,LV,Neuromediator?,Change capillary permeability,Catecholamines,Diastolic dysfunction,Systemic vascular resistence,?,Hypervolemia,?,Systolic function,congestion,VirusSIRSCytokinesRVLVNeuromed,54,Virus,SIRS,Cytokines,RV,LV,Neuromediator?,Changed capillary permeability,Catecholamines,Diastolic dysfunction,Systemic vascular resistence,?,Hypervolemia,?,Systolic function,IVIG,diuretics,Dobutamine, milrinone,?,vasodilator,Vaccine?,PPV,congestion,Steroid?,?,clonidine,VirusSIRSCytokinesRVLVNeuromed,55,Stage,Hand, foot & mouth disease,and treatment,Characterized by fever, oral ulcer and skin rash,Symptomatic,treatment,Aware high risk factors:, age 39, lethargic vomiting, limb weakness, seizure including myoclonic jerk, hypertension?,4.Admit suspicious children,StageHand, foot & mouth dise,56,Stage,CNS InvolvementGeneral Treatment,1.,Admit to,PICU,p.r.n.,2. Monitor BP, HR, sugar, ABG, e, coma scale,3. Intubate patient and provide mechanical ventilator for,GCS 8cm H,2,O or MAP 15cm H,2,O,Change IVF to NS when,glucose, 200mg%, and shift to D2.5HS when glucose drops to 200mg%,Anticipate the drop of BP,when hyperglycemia corrects.,Steroids? Central Antisympathetics?,Stage A: TreatmentMechanicall,60,00.20.40.60.81.01.21.4,Seconds,30,25,20,15,10,8,6,Airway pressure(cmH2O),oscillator,PPV,Mean airway pressure,PIP,PEEP,P,00.20.40.60.81.01.21.4S,61,以病程分期为依据之儿童肠病毒重症治疗概要课件,62,Stage B Hypotension:,treatment,Maintain adequate cerebral and vital organ perfusion during hypotension, optimize preload, afterload and myocardium contractility,Inotropes,dopamine,5-20mcg/kg/min,epinephrine,0.05-0.4(?)mcg/kg/min,Due to intrinsic catecholamine depletion, HIGH infusion rate of inotropes may be needed to keep adequate BP,2. ECMO and ventricular assist device?,Stage B Hypotension: treatme,63,Stage B Hypotension:,treatment,Wean ventilator as tolerated, switch back to conventional ventilator when MAP15cmH2O,CNS evaluation:,cerebral perfusion?,Add,glucose,in IVF when sugar drops to about under 200mg%,Stage B Hypotension: treatme,64,Stage,Convalescence-Treatment,Wean off inotropes,Tracheostomy for ventilator dependent patients,Chest care is mandatory to avoid aspiration pneumonia,Swallowing disturbance,tube feeding (gastric or duodenum),Rehabilitation,Refer to respiratory care center or home care,Stage Convalescence-Trea,65,以病程分期为依据之儿童肠病毒重症治疗概要课件,66,以病程分期为依据之儿童肠病毒重症治疗概要课件,67,Outcome(2000-2001),Group,1,2,3,4,Patients,7,7,3,7,Age(mo),31.7,12.5,14.1,1.9,12.3,3.7,9.7,2.5,ICU stay(days),6.9,3.1,36,3.3,43.7,6.1,15.9,5.9,Tracheostomy,1,6,3,1,CPR,6,1,0,0,Outcome,*,*,*,*,Reposition,6 in RCC,1 home,1,home, 2 in,RCC,All home,1 in RCW,*,died or vegetate state, withdrawn, *moderate sequela, ventilator dependent, *mild to moderate sequela, partial ventilator dependent, *minimal sequela, RCC: respiratory care center, RCW: respiratory care ward.,Outcome(2000-2001)Group1234Pat,68,Gr 1234p-value,CPR ever,Age(M),Neutral Ab,CSF WBC,CKMB ,Troponin I ,EF% 0,GCS 0 ,IE,Resuscitate,Fluid(ml/kg),7/8,1/500 0.01,36.4,11.8,15.6,2.4,12.3,3.7,9.0,2.2 0.05,88,11.770.4 15.753.3 37.3102 17 0.17,140.4,30.384 32.1,9.3 3.316.2 6.4 0.05,49.7,25.534.7 15.315 522.8 7.5 0.5,42.3,6.8,20.9 6.09.9 3.38.1 2.8 0.001,44.8,9.440.2 5.0,64 1.759.2 5.1 0.05,9.3,1.312.6 0.98.6 0.710.2 1.28 0.21,the first value around admission to PICU or ER, IE(inotrope equivalent)=infusion rate of dopamine+dobutamine+100xepinephrne+10xmilrinone mcg/kg/min,38.95.68,56.93.8,33.35.810.33.4 200(h),HR 0 ,HR180h,P/F 0 ,P/F min,P/F300h,2.4 1.2,5.6 2.04.3 2.876.4 30.7 0.05,93.6 42.3200.9 34.4149.1 35.735.6 14.3 0.05,2.6 0.85.1 1.42.8 1.55.7 2.4 0.5,21.3 13.638.7 8.210.1 3.210.4 3.1 0.24,53.1 20.9106.35 53.527.33 1.551.0 30.6 0.5,93.9,4.0,118 14.2118 9.0124 10.20.05,373.1,58.9,281.6 47.5226 29.2233.7 38.70.05,171.5,16.0158.8 20.0176.7 21.2174.3 15.7 0.9,134,33.2,329.0 61.9167.4 31.3203.6 27.9 0.05,the first value around admission to PICU or ER, P/F=PaO2,FiO2, *P=0.055,83.7 18.1*128.6 37.799 47.6,203 27.9,40, significantly compromised systolic/diastolic function and shock.,Conclusions(2)Almost all patie,72,Conclusion(3),The following actions are important in managing the respiratory failure on children with EV 71 infection,Hospitalize children with risky clinical signs.,Early identification,of the development of pulmonary oedema and hemorrhage,Anticipation,of heart failure and optimize the use of inotropes,Prevent recurrent pneumonia in convalescent stage.,Vaccination may be the way out to avoid repeated tragedies every year.,Conclusion(3)The following act,73,以病程分期为依据之儿童肠病毒重症治疗概要课件,74,