Transcript 腸病毒感染嚴重患者靜脈注射免疫球蛋白之適應症

Pediatric ED
morbidity & mortality
conference
Presenter: R2 劉潔玲
Supervisor:吳孟書醫師
Moderator:管仁澤主任
July 22nd, 2008
2008-05-23 20:43
• LK PER
• Triage 4級
• 檢傷紀錄:發燒，無
病容(表現活動力佳)
• Vital sign :
–
–
–
–
–
BT 38.6℃
HR 166 /min
RR 22 /min
BP ?
SpO2 : 99%
• Gender: Male
• Age: 3-year-2-monthold
• BW: 12kg(<3rd
percentile)
• BH: 91cm(3rd-10th
percentile)
• GCS: E4V5M6
Chief complaint
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Fever and vomiting since today
Present illness
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Fever(+) up to 38.9 'c, chills(-)
Cough(-), Rhinorrhea(-), Sore throat(-),
Odynophagia(-), Ear-scratch(-)
Hoarseness(-), SOB(-), Wheezing(-), Skin rashes(-)
Vomiting(+)x several :nonbilious, postprandial
Diarrhea(-)
Headache(-)
Abdominal pain(-)
Urinary Frequency(-), Urgency(-)
Activity: Well
Appetite: Well
Past History
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Admission history:
AGE x 3 and tonsillitis x 1 at our hospital
Chronic disease:
α-thalassemia (α-thal-1 of SEA type, heterozygous) ;
Failure to thrive ; no frequent or severe bacterial
infection
Operation history:nil
Birth history: G1P1, term, C/S, BBW 2960gm, no
perinatal insult
Vaccination: up to date
Development: as milestones
Allergy: no known allergy to food or drug
Primary survey
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PAT: unstable
外觀
呼吸
Ill-looking
正常
循環
Tachycardia
Skin and CRT not
document
Physical Examination
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CONSCIOUSNESS:alert
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HEENT: Eye:injected conjuctiva(-)
Ear: injected ear drum(-); Nose: grossly normal
Throat: injected / Tonsil:not enlarged/ Oral:no ulcers
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NECK: Lymphadenopathy:(-)
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CHEST: Respiratory distress:(-), Abnormal sound:(-)
B/S: clear, no crackle , no wheezing
HEART:RHB, no murmur
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ABDOMEN: soft and flat, B/S:normoactive
Tenderness:(-); Rebound pain(-); Muscle guarding(-)
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SKIN: Rashes(-)
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EXTREMITIES: Pitting edema:(-), Deformity(-)
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What else do you what about history or
physical examination?
Life-threatening Causes of
Vomiting
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Other GI causes, especially appendicitis
Neurologic—mass lesions
Renal—uremia
Infectious—meningitis, sepsis
Metabolic—diabetic ketoacidosis, Reye's
syndrome, adrenal insufficiency
Toxins, drugs—aspirin, ipecac,
theophylline, digoxin, iron, lead
More to ask in history and PE?
Original Hx
• Diarrhea(-)
• Headache(-)
More Information
• Constipation?
• Stool shape and
color
• myoclonic jerk?
• Seizure attack?
• travel Hx?
• Contact Hx
• Drug Hx?
More to ask in history and PE?
Original PE
• NECK:
Lymphadenopathy:(-)
• HEART: tachycardia
More Information
• Neck movement?
• Meningeal sign?
• Lack neurological
examination
• EKG?cardiac enzyme
• Recheck vital sign
• Lack dehydration sign:
skin touch?buccal
mucosa?lip?tears?capil
lary refill?urine output?
ER Order on 21:08(25mins later)
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Plane abdomen
CBC/DC
Sugar
BUN, Cr
Do you agree these order?
AST, ALT
Na, K, Cl
U/A
Tachycardia
Causes of Childhood Hypertension
According to Age Group
-American Family Physician Vol.73 No9(May 1, 2006)
Age
Causes
One to six years
Renal parenchymal disease; renal vascular
disease; endocrine causes; coarctation of
the aorta; essential hypertension
Six to 12 years
Renal parenchymal disease; essential
hypertension; renal vascular disease;
endocrine causes; coarctation of the aorta;
iatrogenic illness
12 to 18 years
Essential hypertension; iatrogenic illness;
renal parenchymal disease; renal vascular
disease; endocrine causes; coarctation of
the aorta
More to do in order?
S/S
More Order
• Tachycardia
• EKG
• Cardiac enzyme
• Recheck vital
sign, especial BP
• Check endocrine
Normal range of pediatric vital sign
Resp Rate
Heart Rate
Blood Pressure
Infant (1 mo 1.5 y/o)
25 – 35
120
74-100 / 50-70
Child ( 1.5 - 5
y/o)
20 – 30
100 – 120
82-110 / 50-78
21:12
5 – 12 y/o
RR 25/min, HR 166/min, BP 179 / 90 mmHg
15 – 25
90 – 100
84-120 / 54-80
Physical Findings Indicative of a
Secondary Cause for Childhood
Hypertension
-Pediatrics 2004; 114(2 suppl 4th report):564.
Diaphoresis
Pheochromocytoma
Flushing
Pheochromocytoma
Growth retardation
Chronic renal failure
Hirsutism
Cushing's syndrome
Joint swelling
Systemic lupus erythematosus
Malar rash
Systemic lupus erythematosus
Moon facies
Cushing's syndrome
Murmur
Coarctation of the aorta
Muscle weakness
Hyperaldosteronism
Obesity (general)
Association with primary hypertension
Obesity (of the face,
neck, or trunk)
Cushing's syndrome
Tachycardia
Hyperthyroidism; pheochromocytoma; neuroblastoma
Thyromegaly
Hyperthyroidism
What is your initial impression now?
Fever
Tachycardia
and
hypertension
Vomiting
Flow chart of vomiting
Lab datus
Sugar
133
WBC
10000
Seg
74.5
Lym
18
Bun/Cr
10/0.6
Na
138
Mono
7
K
4
Band
1.0
AST/ALT
35/15
RBC
5.99
Hb
11.1
Cl
105
Hct
36
MCV
60.1
Plt
275k
CRP
1.62
Plane abdomen
Supine abdominal film
shows :
Fecal retention in the
colon.
Flow chart of vomiting
Non obstructive GI causes---gastroenteritis with
dehydration
Neurologic—mass lesions
Renal—uremia, pheomochrocytoma
Infectious—meningitis, sepsis, myocarditis
Metabolic—diabetic ketoacidosis, Reye's syndrome,
adrenal insufficiency, hyperthyroidism
Toxins, drugs
Disposition
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Impression: acute gastritis
Plan:
IVF with D5 1/4S run + ¼ primparen run
60cc/hr
OBS
2008-05-24 03:02
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MBD
Medication: Primparan 1cc qid
Lactobacillus 1pc bid
Scanol 6cc qid
Do you agree this decision?
Keep in mind
Recheck vital sign was necessary before
patient going home.
=>for this case, the lastest vital sign was on
5/24 1:08 BT 36.5, pulse 97, RR 22 BP 90/42
mmHg. But he left ER on 3:08
 In children, tachycardia may result from
many of the adult causes.
What should we educate the parent when
leaving ER?
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Initial Impression?
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Fever, vomiting, tachycardia
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r/o Infectious—meningitis
r/o GI causes—gastroenteritis
r/o Endocrine-hyperthyroidism
r/o Toxins or drugs overdose
When to seek help
-from uptodate
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Bile(green) or blood-tinged vomit
Vomiting continues for more than 24 hrs
Moderate to severe dehydration(dry mouth, no tears
when crying, not urinating)
Abdominal pain that is severe, whether or not it
comes in waves
Fever greater than 39℃once or 38.4 ℃ for more than
3 days
Behavior changes, including lethargy or decreased
responsiveness
Revisit PER on 2008-05-24 10:02
(8hrs)
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Triage 3級
檢傷紀錄:發燒，無病容(表現活動力佳)，腸病
毒
Vital sign :
– BT 37.8℃
– HR 156 /min
– RR 28 /min
– BP 94/66 mmHg
E4V5M6
Chief complaint
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Fever up to 39 ℃ for 2 day
Present illness
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Frequent non-billious vomiting for 2 days
Mild abdominal fullness
No diarrhea
ER visited yesterday
Activity: poor
Appetite: poor
Physical Examination
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CONCIOUSNESS: clear,E4V5M6
HEENT：CONJUNCTIVA: not injected, not pale
THROAT:injected, not enlarged, exudate(-),
ulcer(-)
EARDRUM: not injected
NECK: supple, no lymphadenopathy
CHEST: symmetric expansion, no retraction
clearBS, crackle(-), wheezing(-), rhonchi(-)
HEART: regular heart beat, no murmur
ABDOMEN：soft&flat, normoactive BS
tenderness(-), no rebounding pain
EXTREMITY: freely, perfusion: OK
NE：NORMAL
Disposition
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Impression: Acute gastritis
Mild dehydration
Plan: admission to GI ward
Do you agree this plan?
Should we need survey again?
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Prolonged vomiting (>12 hours in a neonate,
>24 hours in children younger than 2 years of
age, or >48 hours in older children) should not
be ignored. Screening laboratories should
include a complete blood count, electrolytes,
blood urea nitrogen, urinalysis, urine culture,
and stool studies.
The clinical presentation of myocarditis is
variable. Tachycardia and metabolic acidosis
may be important indicators of the extent of
myocardial involvement.
Hospitalization(ward)
5/24
5/25
5/26
Vomiting(-)
Fever(+)
Cons change
fever(+)
Frequent myoclonic jerk (+)
Low limbs spasiticity
Occasional myoclonic jerk
Mild lethargy
Oral ulcer?
especially when sleeping
Irrelevant speech and
visual halluciation noted
at night
IVF hydration
Primperan
Empiric antibiotics
Glycerol
Lactobacillus
Consult Neurologist: EV 71 was suspected
and suggest IVIG
Control fever
Transfer to PICU
Hospitalization(PICU)
Brain echo:
IICP
On endo: foamy and
milkly pink sputum
5/26 13:35
Cons drowsy, E4V1M6,
pupil:2.5/2.5
Tachycardia(117beats/mins)
Hypertension(124/80mmHg)
Hyperglycemia(429)
Urine output: 0
vertical/horizontal nystagmus
Irregular respiraton and cyanosis
17:55
2D echo:
EF 37%
18:25
Hypotension(80/60mmHg)
Spaticitiy,
Tremor
Add milrinone and
dopamine
No myoclonic jerk
vancomycin + fortum + acyclovir
IVIG
Mannitol
通報腸病毒重症, throat/rectal swab
ECMO and
CPCR
5/27
Dilated pupil without L/R
WARD
PICU
intubation
Pulmonary edema/hemorrhage
Hospitalization(PICU)
2D echo:
EF 60-70%
6/6
EEG:silence
6/7
Coma
Unstable hemodynamic status
Central DI
Hypothroidism
Inotropes and vasopressors
thyroixin
cortisone
Remove ECMO
6/20
DNR – expired
Travel and contact Hx
(retrospectively)
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Residence:桃園蘆竹鄉 School:kindergarten
南投指南宮;竹北
5/18
夜市
5/21
•幼稚園有兩位同學有發燒，但確定
不是腸病毒
•隔壁賣衣服的老闆娘兒子５月份腸
病毒住院後出院
急診
admission
5/24
5/26
廣東粥店裡的一位
工讀生打電話告知
發燒,嘴破,醫師診
斷為腸病毒感染
Impressions
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Enterovirus infection with CNS involvement
and autonomic dysfunction (stage IIIb)
Myocarditis
pulmonary edema
meningoencephalitis
Acute renal failure
cardiopulmonary failure
Expired on 2008/6/20 AM 10:17
Discussion
Enterovirous
簡介
-from Taiwan CDC
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大多是無症狀感染，或只有發燒等類似一般感
冒。
三歲以下幼童感染，併發嚴重中樞神經症狀之
比率較高。
盛行於夏天與秋天
傳染途徑：飛沫、糞口, 接觸傳染 (急性出血
性結膜炎)
潛伏期：3-5天(2天 - 2週)
傳染力：始於發病之前幾天
各年齡層感染的危險程度
容易導致重症的腸病毒
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腸病毒71型：腦幹腦炎、肺水腫
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克沙奇病毒B型(Coxsackieviruses B): 心肌
炎、心包膜炎、新生兒感染
伊科病毒(Echoviruses)：新生兒感染
小兒麻痺病毒(Polioviruses)：延腦型腦炎、
脊柱前角神經炎
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腸病毒71型常見症狀
發燒時間較長
–常超過3天，體溫可超過39℃
 多有手足口症狀出現
–在手部、足部及口腔黏膜出現如針頭大小紅點
的疹子或水泡
 容易有中樞神經併發症
–嗜睡、持續嘔吐、肌躍型抽搐、意識不清
–嚴重併發症多發生於發病5日內
–出現肺水腫時，死亡率高
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腸病毒感染併發重症之前驅病徴
一、有嗜睡、意識不清、活力不佳、手腳無力應
即早就醫，上述一般神經併發症是在發疹2至
4天後出現。
二、肌躍型抽搐（類似受到驚嚇的突發性全身肌
肉收縮動作）。
三、持續嘔吐。
四、持續發燒、活動力降低、煩躁不安、意識變
化、昏迷、頸部僵硬、肢體麻痺、抽搐、呼吸
急促、全身無力、心跳加快或心律不整等。
病例通報
依據傳染病防治法，腸病毒感染併發重症屬於第三類
傳染病，醫師或醫療（事）機構於診治或發現符合或
疑似下述定義之病人時，應於一週內向當地衛生局報
告。病例須符合下列兩項中至少一項：
一、出現典型的手足口病或疱疹性咽峽炎，或與病例有
流行病學上相關的腸病毒感染個案，同時有肌抽躍
（myoclonic jerks）之症狀或併發腦炎、急性肢體麻
痺症候群、急性肝炎、心肌炎、心肺衰竭等嚴重病例。
 二、出生三個月內嬰兒，出現心肌炎、肝炎、腦炎、
血小板下降、多發性器官衰竭等敗血症徵候，並排除
細菌等其他常見病原感染者。
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處理與治療
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絕大多數症狀輕微，7 到10 天自然痊癒。
無特殊之治療方法，醫師大多給予對抗症狀之
支持性療法，疑似重症患者給予免疫球蛋白。
小心處理病患之排泄物(糞便、口鼻分泌物)，
且處理完畢須立即洗手。
特別注意腸病毒重症前兆病徵，如嗜睡、持續
性嘔吐、肌抽躍等。
腸病毒感染嚴重患者靜脈注射免疫球蛋白
之適應症
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一、靜脈注射免疫球蛋白對於腸病毒感染併發
重症病人的治療效果，目前仍有待確認。
二、不鼓勵使用於 5歲以上患者。
三、建議劑量為 1 gm/kg 靜脈滴注 12小時，
共一次。
（一）肌抽躍合併無明顯誘發因素之心率過速（心跳每分鐘超過150
次）=>註 2：只有肌抽躍症狀者不符合使用條件。
（二）急性肢體麻痺。
（三）急性腦炎，尤其是供伴隨局部特異性腦幹神經症狀：失調
（ataxia）、對側偏癱（cross hemiplegia）、特定腦神經損
害（specific cranial Ns lesion）或腦幹自主神經機能障
礙（brainstem dysautonomia）=>註 3：只有腦膜炎而無腦
炎或類小兒麻痺症者，及非腸病毒引起的腦炎患者不符合使
用條件。
（四）肺功能衰竭，如急性肺水腫、肺出血、成人型呼吸窘迫症。
（五）心臟功能衰竭。
（六）敗血症候群（Sepsis syndrome）=>註 4：併發多發性器官
衰竭之患者因使用效果不佳，故不建議使用。
Modulation of cytokine production by IVIG
in patients with enterovirus 71-associated
brainstem encephalitis
-Journal of Clinical Virology 37 (2006) 47–52
1.
2.
3.
4.
It was too late for patients to commence IVIG
when patient deteriorated from ANS
dysregulation to pulmonary edema
In patients experienced pulmonary edema
the case fatality may reach as high as 90%.
All fatal patients died within 6–12 h after
admission if without prompt management.
It is possible that a more favorable survival
might have been obtained by earlier therapy
or larger doses of IVIG.
Survival after pulmonary edema
due to enterovirus 71 encephalitis
-Neurology 2003;60;1651-1656
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Faster neurologic recovery was associated with
less long-term deficit.
Long-term outcome was similar in patients
treated with and without pleconaril or IV
immunoglobulin.
Three long-term survivors treated with IV
corticosteroids had less severe long-term
neurologic disability than two not treated with
steroids.
R
Review ~From林口兒童長庚醫院
Stages
Clinical manifestations
Landmarks
Treatment
I
Hand, foot, and
mouth disease
Vesicles and ulcers on
skin and mucosa
II
Central nervous
system involvements
Neurological dysfunctions:
consciousness disturbance,
limb weakness, myoclonic
jerks, seizures
Identifying patients in
risk
Closely observe coma
scale, fluid restriction,
IVIG
III
Cardiopulmonary
failure
Pulmonary
edema/hemorrhage
and hypertension
IIIA
IIIB
IV
Systolic blood pressure
higher than severe
hypertension criteria
Positive pressure
mechanical ventilation,
milrinone
Cardiovascular
decompensation
Systolic blood pressure
lower than normal blood
pressure for age
Inotropes and
vasopressors.
Extracorporeal life
support?
Convalescence
Cessation of inotropes
Key to remember
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Detail PE and history can differentiate most
of the child’s causes of vomiting.
In children, tachycardia may result from
many of the adult causes.
Educated parents with vomiting child how to
home care and when to seek help
持續昏睡、持續嘔吐與肌躍型抽搐」為腸病毒
重症三大前兆，應該囑咐家屬特別注意觀察這
三種重症前兆。
Thank You for Your Time!
Refenrence
1.
Emergency Medicine-A comprehensive study 7th ed. J.E. Tintinalli
et al.
2.
Nelson Textbook of Pediatrics, 18th ed. Kliegman et al.
Shih-Min Wang a,c, Huan-Yao Lei d, Mei-Chih Huang e, Ling-Yao Su
b,d, Hui-Chen Lin b, Chun-Keung Yu d, Jung-Lung Wang b, ChingChuan Liu b, Modulation of cytokine production by intravenous
immunoglobulin in patients with enterovirus 71-associated brainstem
encephalitis : Journal of Clinical Virology 37 (2006) 47–52
M. A. Nolan, M. E. Craig, M. M. Lahra, W. D. Rawlinson, P. C. Prager,
G. D. Williams, A. M.E. Bye and P. I. Andrews Survival after
pulmonary edema due to enterovirus 71 encephalitisNeurology
2003;60;1651-1656
3.
4.
5.
Textbook of Pediatric Emergency Medicine Fleisher et al. 2006.
6.
臨床兒科學 第六版 黃富源主編