儿童重症肠病毒感染救治课件.ppt

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1、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 treatmentI.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(2)醫生說：這是典型手足口

2、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。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

3、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EV71(174)non71EV(241)UncomlicatedcasesHFMD/herpanginaViral exanthemFebrile illnessOthersComlicatedcasesMeningitisEncephalitis/myelitisPolio-like syndromePulmonary OedemaFatalcasesSurvivorswithsevereneur

4、ologicalsequela119(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*Leukocytosis 9(82%)12(32%)9.7(2.9-34)0.003#Upper limb4(36%)4(11%)4.9(2.6-9.2)0.04w

5、eaknessLower limb7(64%)11(29%)4.3(2.0-9.2)0.04weaknessChang et al.Lancet 354(9191):1682,1999Skin and Mucosa LesionsOral 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 cons

6、isted of petechiae-like clustersPhases 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 disturbanc

7、eStage 3A:Elevated BPStage 3B:Decreased BP,use of catecholaminesStage 4:Cessation of catecholamines.Table A Severe Hypertension Criteria by AgeAgeGroupSystolic(mmHg)Diastolic(mmHg)NB7days1068-20days110Infants2yo11882Children3-5yo118846-9yo1308610-12yo1349013-15yo1449216-18yo15096Modified from Hycan

8、et al.Task Force on Blood Pressure control in Children.Pediatrics 79:1,1987.Table B.Normal Blood Pressure by AgeAgeSystolic(mmHg)Diastolic(mmHg)Neonate60-9020-60Infant(6mo)87-10553-66Toddler(2yr)95-10553-662-7yo97-11257-717-15yo112-12866-80HazinskiMF:NursingCareoftheCriticallyIllChild,2nded.St.Louis

9、,Mo:MosbyYearBook;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 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

10、癒，或許有後遺症Lungs are congestedRed blood cells are found in small airways and alveoli,Parameters Sequence Around PEParameters 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

11、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 OedemaStarlings formulaFlow=K(PcPis)(OncplOncis)InterstitiumAlveolusLymphaticsPulmonary capillaryPcPisKOncplOncisO2Hypotheses of the Mechanism of pulmonary oedemaSIRS/ARDSNeurogenic pulmonary

12、edema CardiogenicCapillary permeabilitySystemic/pulmonary vasculer resistenceLV systolic dysfunctionLV diastolic dysfunctionEvidence Supporting SIRSGroupEncephalitis with Pulmonary Oedema(N=8)Encephalitis(N=8)Uncomplicated(N=170)Normal Control(N=21)P-value*WBC(109/L)28.3+7.615.5+6.812.3+4.7-0.0001CR

13、P(mg/L)18.5+16.331.0+35.815.9+29.1-0.49Glucose(mg/dL)501+186165+117103+15-0.0001IL-1(pg/ml)48.4+85.24.9+10.11.6+0.91.8+1.00.006IL-6(pg/ml)947+12394.9+3.12.8+1.91.9+0.50.0001TNF-(pg/ml)22.4+29.55.3+1.05.6+1.66.8+1.50.004Lin et al.Evidences Related to Neurogenic Pulmonary OedemaCNS involvement preceed

14、s 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 Cereb

15、rum,midbrain and brain stemPerivascular cuffing was also commonCortisol Level vs.Vital SignsEvidences Related to CardiogenicIncreased pulmonary artery wedge pressure?Echo revealed systolic and diastolic dysfunctionHypertension associatedInappropriate tachycardia associatedIncreased cardiac enzymesHo

16、wever,autopsy findings are against myocarditis Initial Swan-Ganz Monitor Data#123Age1y5m10m1y6mPAWP(mmHg)262222CVP(mmHg)10813CI(L/min/m2)5.63.63.8SI(mL/beat/m2)25.920.219.8SVRI(dyne-s-cm-5)129614391363PVRI(dyne-s-cm-5)7967168Echocardiography EvidencesSystolic dysfunction:The initial ejection fractio

17、n: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 an

18、nulus velocity(the rate of change in long-axis dimension and LV volume)Diastolic Function#12345ClinicalPE+HFPE+HFMild PEHT onlyHT onlyE/A3.20.862.94mergedDT(ms)48.1973.0954.6152.6IVRT(ms)54.2220.0844.860.24E/E15.1114.769.7577.4CommentRestrictive physiologyRestrictive physiologyRelaxation impairmentA

19、dequate diastoleAdequate diastoleOutcomeDiedSevere sequelaMild sequelaRecover completelyRecover completelyPE:pulmonary oedema,HF:heart failure,HT:hypertensionCardiac EnzymesCKMB(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

20、 hypertrophicUnder microscope,there is no inflammatory changeI.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 CriticalNeurological deterioratesGCS9Apnea,chokeUnable to protect airwayParadoxical respirationPulmonary oedema/hemorrhage developsCardiovascular system malfunctions

21、:hypertension,tachycardiaVirusSIRSCytokinesRVLVNeuromediator?Change capillary permeabilityCatecholaminesDiastolic dysfunctionSystemic vascular resistence?Hypervolemia?Systolic functioncongestionVirusSIRSCytokinesRVLVNeuromediator?Changed capillary permeabilityCatecholaminesDiastolic dysfunctionSyste

22、mic vascular resistence?Hypervolemia?Systolic functionIVIGdiureticsDobutamine,milrinone?vasodilatorVaccine?PPVcongestionSteroid?clonidineStage Hand,foot&mouth disease and treatment1.Characterized by fever,oral ulcer and skin rash2.Symptomatic treatment3.Aware high risk factors:age 39 lethargic vomit

23、ing limb weakness,seizure including myoclonic jerk hypertension?4.Admit suspicious childrenStage CNS InvolvementGeneral Treatment1.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 H2O3.Change IVF to NS when glu

24、cose 200mg%,and shift to D2.5HS when glucose drops to 200mg%4.Anticipate the drop of BP when hyperglycemia corrects.5.Steroids?Central Antisympathetics?00.20.40.60.81.01.21.4Seconds302520151086Airway pressure(cmH2O)oscillatorPPVMean airway pressurePIPPEEPPStage B Hypotension:treatment1.Maintain adeq

25、uate cerebral and vital organ perfusion during hypotension,optimize preload,afterload and myocardium contractility2.Inotropesdopamine5-20mcg/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 vent

26、ricular assist device?Stage B Hypotension:treatment1.Wean ventilator as tolerated,switch back to conventional ventilator when MAP15cmH2O2.CNS evaluation:cerebral perfusion?3.Add glucose in IVF when sugar drops to about under 200mg%Stage Convalescence-Treatment1.Wean off inotropes2.Tracheostomy for v

27、entilator dependent patients 3.Chest care is mandatory to avoid aspiration pneumonia4.Swallowing disturbancetube feeding(gastric or duodenum)5.Rehabilitation6.Refer to respiratory care center or home careOutcome(2000-2001)Group1234Patients7737Age(mo)31.712.514.11.912.33.79.72.5ICU stay(days)6.93.136

28、3.343.76.115.95.9Tracheostomy1631CPR6100Outcome*Reposition6 in RCC,1 home1 home,2 in RCCAll 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 w

29、ard.Gr 1234p-valueCPR everAge(M)Neutral AbCSF WBCCKMB Troponin I EF%0GCS 0 IEResuscitateFluid(ml/kg)7/81/500 0.0136.411.815.62.412.33.79.02.2 0.0588 11.770.4 15.753.3 37.3102 17 0.17140.4 30.384 32.19.3 3.316.2 6.4 0.0549.7 25.534.7 15.315 522.8 7.5 0.542.3 6.820.9 6.09.9 3.38.1 2.8 0.00144.8 9.440.

30、2 5.064 1.759.2 5.1 0.059.3 1.312.6 0.98.6 0.710.2 1.28 0.21the first value around admission to PICU or ER,IE(inotrope equivalent)=infusion rate of dopamine+dobutamine+100 xepinephrne+10 xmilrinone mcg/kg/min38.95.6856.93.833.35.810.33.4 200(h)HR 0 HR180hP/F 0 P/F minP/F300h2.4 1.25.6 2.04.3 2.876.4

31、 30.7 0.0593.6 42.3200.9 34.4149.1 35.735.6 14.3 0.052.6 0.85.1 1.42.8 1.55.7 2.4 0.521.3 13.638.7 8.210.1 3.210.4 3.1 0.2453.1 20.9106.35 53.527.33 1.551.0 30.6 0.593.9 4.0118 14.2118 9.0124 10.20.05373.1 58.9281.6 47.5226 29.2233.7 38.70.05171.5 16.0158.8 20.0176.7 21.2174.3 15.7 0.9134 33.2329.0

32、61.9167.4 31.3203.6 27.9 0.05the first value around admission to PICU or ER,P/F=PaO2FiO2,*P=0.05583.7 18.1*128.6 37.799 47.6203 27.940,significantly compromised systolic/diastolic function and shock.Conclusion(3)The following actions are important in managing the respiratory failure on children with

33、 EV 71 infection1.Hospitalize children with risky clinical signs.2.Early identification of the development of pulmonary oedema and hemorrhage3.Anticipation of heart failure and optimize the use of inotropes4.Prevent recurrent pneumonia in convalescent stage.5.Vaccination may be the way out to avoid repeated tragedies every year.