【医学精品课件】以病程分期為依據之兒童腸病毒重症治療

以病程分期為依據之兒童腸病毒重症治療 The Stage Based Therapy ofCritically 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,A Cardiopulmonary disaster requiring multidisciplinary treatment,I. OutbreaksII. 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,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 (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 (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。,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。,EV 71 Outbreaks,Enterovirus type 71 was firstly isolated from the stool of an infant with encephalitis in US in 19691975, 44/705 were killed in Bulgaria1997, 30 were killed in Malaysia1998, 78 were killed in Taiwan1999, 8 were killed in Hong-Kong,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,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,I. OutbreaksII. 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,EV71(174)non71 EV(241),Uncomlicated casesHFMD/herpanginaViral exanthemFebrile illnessOthersComlicated casesMeningitisEncephalitis/myelitisPolio-like syndromePulmonary OedemaFatal casesSurvivors 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) 0.04weaknessLower limb7(64%) 11(29%) 4.3(2.0-9.2) 0.04weakness,Chang et al. Lancet 354(9191): 1682, 1999,Skin and Mucosa Lesions,Oral ulcers distributed not on soft palate only as typical hand-foot mouth diseaseVesicles on hand and foot were smaller (pin-point) than typical HFM diseaseSometimes the skin lesion consisted of petechiae-like clusters,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,分期標的,Stage 1: Oral ulcer, skin rash, feverStage 2: Neurological symptomsmyoclonic jerk, limb weakness, seizure, consciousness disturbanceStage 3A: Elevated BPStage 3B: Decreased BP, use of catecholaminesStage 4: Cessation of catecholamines.,Results,We observed a majority of patients (58% 14/24) presented different five clinical phases.Two patients developed PE without a HFM prodromeOne patient developed PE without previous CNS involvement signsIn six patients, hypertension phases were not observedThree patients did not develop hypotension phenomenon,Table A Severe Hypertension Criteria by Age,Modified from Hycan et al. Task Force on Blood Pressure control in Children. Pediatrics 79:1, 1987.,Table B. Normal Blood Pressure by Age,Hazinski MF: Nursing Care of the Critically Ill Child, 2nd ed. St.Louis, Mo: Mosby Year Book; 1992,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,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(150mg/dl),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(150mg/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,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(200mg/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,Lungs are congested,Red blood cells are found in small airways and alveoli,Parameters Sequence Around PE,Parameters Sequence (2),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。,I. OutbreaksII. 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,Pathophysiology of Pulmonary Oedema,Starlings formulaFlow=K(PcPis) (OncplOncis),Interstitium,Alveolus,Lymphatics,Pulmonary capillary,Pc,Pis,K,Oncpl,Oncis,O2,Hypotheses of the Mechanism of pulmonary oedema,SIRS/ARDSNeurogenic pulmonary edema Cardiogenic,Capillary permeabilitySystemic/pulmonary vasculer resistenceLV systolic dysfunctionLV diastolic dysfunction,Evidence Supporting SIRS,Lin et al.,Evidences Related to Neurogenic Pulmonary Oedema,CNS involvement preceeds pulmonary oedemaIncreased cortisol level and clinical evidences suggested an autonomic nervous system dysfunction(increased sympathetic tone)Lack of study of pulmonary capillary permeabilitySystemic vascular resistence does not increase significantly.,Diffuse inflammatory cell infiltration in Cerebrum, midbrain and brain stem,Perivascular cuffing was also common,Cortisol Level vs. Vital Signs,Evidences Related to Cardiogenic,Increased pulmonary artery wedge pressure?Echo revealed systolic and diastolic dysfunctionHypertension associatedInappropriate tachycardia associatedIncreased cardiac enzymesHowever, autopsy findings are against myocarditis,Initial Swan-Ganz Monitor Data,Echocardiography Evidences,Systolic dysfunction: The initial ejection fraction: 18-75%(meanSE=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 timeMitral annulus velocities: E/E, E=early diastolic annulus velocity(the rate of change in long-axis dimension and LV volume),Diastolic Function,PE: pulmonary oedema, HF: heart failure, HT: hypertension,Cardiac Enzymes,CKMB (normal16U/L): 4-92U/L, meanSE=31.177.73(n=12)Troponin I (normal2ng/ml): 0.4-50ng/ml, meanSE=21.924.36(n=17),Grossly, the heart is hypertrophic,Under microscope, there is no inflammatory change,I. OutbreaksII. 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,When Patient Becomes Very Critical,Neurological deterioratesGCS9Apnea, chokeUnable to protect airwayParadoxical respirationPulmonary oedema/hemorrhage developsCardiovascular system malfunctions: hypertension, tachycardia,Virus,SIRS,Cytokines,RV,LV,Neuromediator?,Change capillary permeability,Catecholamines,Diastolic dysfunction,Systemic vascular resistence,?Hypervolemia,?Systolic function,congestion,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,StageHand, foot & mouth disease and treatment,Characterized by fever, oral ulcer and skin rashSymptomatic treatmentAware high risk factors: age 39 lethargic vomiting limb weakness, seizure including myoclonic jerk hypertension?4.Admit suspicious children,Stage CNS InvolvementGeneral Treatment,1. Admit to PICU p.r.n.2. Monitor BP, HR, sugar, ABG, e, coma scale3. Intubate patient and provide mechanical ventilator for GCS 8cm H2O or MAP 15cm H2OChange 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?,00.20.40.60.81.01.21.4,Seconds,302520151086,Airway pressure(cmH2O),oscillator,PPV,Mean airway pressure,PIP,PEEP,P,Stage B Hypotension: treatment,Maintain adequate cerebral and vital organ perfusion during hypotension, optimize preload, afterload and myocardium contractilityInotropesdopamine5-20mcg/kg/minepinephrine0.05-0.4(?)mcg/kg/minDue to intrinsic catecholamine depletion, HIGH infusion rate of inotropes may be needed to keep adequate BP2. ECMO and ventricular assist device?,Stage B Hypotension: treatment,Wean ventilator as tolerated, switch back to conventional ventilator when MAP15cmH2OCNS evaluation: cerebral perfusion?Add glucose in IVF when sugar drops to about under 200mg%,Stage Convalescence-Treatment,Wean off inotropesTracheostomy for ventilator dependent patients Chest care is mandatory to avoid aspiration pneumoniaSwallowing disturbancetube feeding (gastric or duodenum)RehabilitationRefer to respiratory care center or home care,Outcome(2000-2001),*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.,Gr 1234p-value,CPR everAge(M)Neutral AbCSF WBCCKMB Troponin I EF% 0GCS 0 IEResuscitateFluid(ml/kg),7/81/500 0.01,36.411.815.62.412.33.79.02.2 0.05,88 11.770.4 15.753.3 37.3102 17 0.17,140.4 30.384 32.19.3 3.316.2 6.4 0.05,49.7 25.534.7 15.315 522.8 7.5 0.5,42.3 6.820.9 6.09.9 3.38.1 2.8 0.001,44.8 9.440.2 5.064 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,38.95.6856.93.833.35.810.33.4 200(h)HR