manifestations of children with severe forms of dengue

8/2/2019 Manifestations of Children With Severe Forms of Dengue

1/7


2/7

44S h r i s h u R . K a m a t h e t a l

T h e a i m o f t h e p r e s e n t s t u d y w a s t o r e v i e w p r e v i o u s l yd e s c r i b e d a s w e l l a s a t y p ic a l c li n ic a l f e a t u r e s a n d o u t c o m eo f c r i ti c a l ly u n w e l l c h i l d r e n w i t h s e v e r e D H F a n d d e n g u es h o c k s y n d r o m e ( D SS ) p r e s e n t i n g t o P I C U .

M A T E R IA L A N D M E T H O D S

T h e a u t h o r s e x a m i n e d t h e r e c o r d s o f 10 9 c o n s e c u t i v ep a t i e n t s w i t h c o m p l i c a t e d a n d s e r i ou s f o r m s o f D H FG r a d e s I I I a n d I V (D S S ) a d m i t t e d t o t h e P I C U o f t h eK a n c h i K a m a k o t i C H I L D S T r u s t H o s p i t a l , C h e n n a i , o v e ra 1 . 5 - y e a r p e r i o d b e g i n n i n g J u n e 2 0 01 . T h e c h a r t s w e r eo b t a i n e d f r o m t he m e d i c a l r e c o rd s d e p a r t m e n t a n d d a t aw a s e n t e r e d o n a s p r e a d s h e e t b y o n e o f t he a u t h o r s ( S R K )a n d c r o s s c h e c k e d f o r a c c u r a c y a n d c o m p l e t e n e s s b y S R .

C a s e D e f i n i ti o n : D u r i n g a p r e v a i l i n g e p i d e m i c , t h ec l i ni c a l d i a g n o s i s o f D H F i s b a s e d o n f o u r m a j o rc h a r a c t e r i s t i c m a n i f e s t a t i o n s 1,2 a h i s t o r y o f f e v e r l a s t i n gf o r 2 -7 d a y s , h e m o r r h a g i c m a n i f e s t a t i o n s ( p e t e c h i a e ,p a l a t a l o r g u m b l e e d s , h e m a t e m e s i s o r m a l a e n a ) ,t h r o m b o c y t o p e n i a ( p l a t e l e t c o u n t _


3/7

45Clinical Features, Com plications and Atypical Man ifestat ions of Chi ldren with Dengue Hem orrhagic F ever

Hemodynamic and Card iovascu lar Mani festat ionsT h e c o m m o n e s t c a r d i o v a s c u l ar c o m p l i c a ti o n e n c o u n t e r e dw a s p e r s i s te n t s h o c k d e s p i t e f l u i d a d m i n i s t r a ti o n i n t h eE m e r g e n c y R o o m i n a cc o r d a n c e w i t h t h e W H O r e g i m e n(Table 1).

T h i r t y - n i n e c h i l d r e n ( 37 .5 % ) r e m a i n e d i n s h o c kd e s p i t e a d m i n i s t r a t i o n o f a t le a s t 4 0 m l / K g o f f l u i d s a n db l o o d p r o d u c t s ( w h o l e b l o o d , p a c k e d r e d b l o o d c e ll s _+f r e s h f r o z e n p l a s m a a s i n d i c a te d ) . T h e s e p a t i e n t s w e r ei n i ti a t ed o n i n o t r o p e s a n d / o r v a s o p r e s s o r s a n d t h e i rm y o c a r d i a l f u n c ti o n a n d f i ll in g s t at u s w e r e a s s e s s e d b ye c h o c a r d i o g r a p h y .S e r ia l e c h o c a r d i o g r a p h i c e v a l u a t i o n b y a p e d i a t r i cc a r d io l o g i st w a s c a r r ie d o u t i n 4 3 c h i ld r e n , 3 o f w h o m h a dd i a s to l i c d y s f u n c t i o n n e c e s s i ta t i n g t h e r a p y w i t h al u s i t ro p i c a g e n t s u c h a s m i l r i n o n e . S y s t o l ic d y s f u n c t i o nw a s d o c u m e n t e d i n 2 p a t ie n t s . 3 c h i l d re n h a d s m a l lp e r i c a r d i a l e f f u s i o n s . R e p e a t e c h o c a r d i o g r a p h i ce v a l u a t i o n a t d i s c h a r g e f r o m t h e P I C U w a s n o r m a l i n a l lsu rv ivor s .T h i r t y - t w o o f t h e 39 p a t i e n t s w i t h p e r s i s t e n t s h o c ki m p r o v e d w i t h o n g o i n g s u p p o r t i v e t r e a t m e n t ( f u r t h e rf l u id s , b l o o d p r o d u c t s , v a s o a c t i v e a g e n t s a n d , w h e r ei n d i c a t e d , p o s i ti v e p r e s s u r e v e n t i l a t i o n ).T h e c a u s e o f f l u i d re f r a c t o r y s h o c k i n o n e p a t i e n t w a su n s t a b l e s u p r a v e n t r i c u l a r t a c h y c a r d i a ( SV T ) w h i c hr e v e r t e d w i t h a d e n o s i n e a n d t h e p a t i e n t s c i r c u l a t o r ys t a t u s n o r m a l i z e d . T w o c h i l d r e n r e f er r e d t o t h e h o s p i t a l i np u l s e l e s s D H F G r a d e I V sh o c k s u f f e r e d ac a r d i o p u l m o n a r y a r re s t i n t h e E m e r g e n c y R o o m , o n e w a ss u c c e s s fu l l y r e s u s c i t a te d a n d t r a n s f e r r e d t o t h e P I C U a n dr e c o v e r e d w i t h o n g o i n g s u p p o r t i v e t r e a t m e n t . S ixc h i l d r e n d i e d o f r e f r a c t o r y s h o c k . T h i s w a s c o m p l i c a t e db y A c u t e R e s p i r a t o r y D i s t r e s s S y n d r o m e ( A R D S ) 5 a n dd i s s e m i n a t e d i n t r a v a s c u l a r c o a g u l a t i o n ( D IC ) in 4p a t ie n t s ; 2 h a d D I C i n a d d i t i o n t o r e f r a ct o r y s h o c k .Abnormal F lu id Col l ec t ionA p a r t f r o m s h o c k , th i r d s p a c i n g w a s m a n i f e s t a s p l e u r a le f fu s ion i n 55 ch i l d re n (50 .4%) . 51 (46 .7%) h ad a sc i t i s , 8c h i ld r e n h a d p r o f o u n d g e n e r a l iz e d a n a s a r c a a n d 3c h i l d r e n h a d p e r i c a r d i al f l u i d a c c u m u l a t i o n a s d e s c r i b e dabove .C o m p a r t m e n t S y n d r o m eO f t h e 27 c h i l d re n w i t h D H F G r a d e I V , c o m p a r t m e n ts y n d r o m e w a s s e e n i n 3 c h i l d r e n a n d c o n t r i b u t e d t or e f r a c t o r y s h o c k . 6 T h e i n t r a - a b d o m i n a l p r e s s u r e w a se s t im a t e d b y m e a s u r i n g t h e b l a d d e r p r e s s u r e via a ni n d w e l l i n g F o l e y c a t h e te r . I m p r o v e m e n t i n c a rd i o -r e s p i r a t o r y f u n c t i o n o c c u r r e d i n 2 c h i l d r e n f o l l o w i n gc o n t r o l l e d r e le a s e o f t h e i n t r a - a b d o m i n a l p r e s s u r e b yp e r i t o n e a l d i a ly s i s w h i l e t h e t h i r d f a i l e d t o i m p r o v e a n dexp i red .

Hematolog ica l f eaturesA l t h o u g h a l l p a ti e n t s h a d p l a t e le t c o u n t s < 1 00 ,0 0 0 /cum in (pa r t o f c ase de f in i t i on o f DH F) , 69 pa t i en t s (63%)h a d e v i d e n c e o f h e m o r r h a g i c m a n i f e s t a t i o n s s u c h a ss p o n t a n e o u s s k i n a n d m u c u s m e m b r a n e b le e d s, u p p e r o rl o w e r g a s t r o - i n t e s ti n a l t ra c t (G I T) b l e e d s a n d p r o l o n g e do o z e f r o m v e n e p u n c t u r e s i t es . S ev e re h e m o r r h a g i cm a n i f e s t a t i o n s c o n t r i b u t i n g t o s h o c k d u e t o s p o n t a n e o u sG I T h e m o r r h a g e w a s s e e n i n 18 p a t i e n t s ( 16 .5 % ). O ft h e se , 2 p a t i e n t s r e m a i n e d i n s h o c k w i t h D I C a n d m a s s i v ef a ta l b l e e d i n g d e s p i t e m a x i m a l s u p p o r t i v e t r e a t m e n t a n dc o u l d n o t b e r e s u s c i t a t e d .

T h e m e a n h e m a t o c r i t a t p r e s e n t a ti o n w a s 3 5 . 5 + 8 . 1 % .T h e m e a n p l a t e l e t c o u n t w a s 5 4 ,4 4 3 ___ 3 9 , 6 2 3 / c u m m .T w e n t y c h i l d r e n h a d p l a te l e t c o u n t s b e l o w 2 0, 00 0 / c u m m .D i s o r d e r e d c o a g u l a t i o n ( p r o l o n g a t i o n o f t h ep r o t h r o m b i n a n d / o r p a r t i al th r o m b o p l a s t i n ti m e ) w a sseen i n 74 ch i l d ren (67 .8%) . 16 ch i l d ren h ad d i ssem ina t edi n t r a v a s c u l a r c o a g u l a t i o n ( D IC ) o f w h i c h 6 , th a t a l s o h a dre f rac to ry shock , d i ed .Resp iratory mani festat ionsIn add i t i on t o p l eu ra l e f fus ions i n 55 pa t i en t s , 10 ch i l d rens a t is f i e d t h e c r i te r i a f o r A R D S , a ll o f w h o m p r e s e n t e dw i t h G r a d e I V D H F a n d t h e r e w e r e 4 d e a t h s i n th i s g ro u p .29 ch i l d ren (26 .6%) we re ven t i l a t ed , t he i nd i ca t i ons be ingA R D S i n 10 p a t i e n t s , n e u r o l o g i c a l i n d i c a t i o n s i n 9,d e c o m p e n s a t e d s h o c k i n 9 a n d f o l l o w i n g c ar d i a c a rr e s t inone . M ean du ra t i o n o f ven t i l a t i on was 4 .3 +_ 2 .8 days .N e u r o l o g i c a l M a n i f e s t a t io n sT w e n t y - f o u r c h i l d re n h a d n e u r o l o g ic a l m a n i f e st a t io n s( T a b le 2 ) o f w h i c h o n l y 5 w e r e i n s h o c k . S e v e n t e e np a t i e n t s w i t h s u s p e c t e d d e n g u e e n c e p h a l o p a t h yp r e s e n t e d w i t h a l t e r e d m e n t a l s t a t u s a n d s e i z u r e s .F o l l o w i n g i m p r o v e m e n t o f t h e c a r d i o - r e s p i r a t o r y s ta t u s ,a ll p a t i e n t t h a t r e m a i n e d i n a l te r e d m e n t a l s t a t u su n d e r w e n t i m a g i n g w i t h c o m p u t e r i z e d t o m o g r a p h i c (C T )s c a n s a n d c e r e b r o s p i n a l f l u i d ( C SF ) a n a l y s is . T h e C S Fw a s a b n o r m a l i n t h r e e p a t i e n ts , 2 o f w h o m h a d r a i s e dp r o t e i n a n d l y m p h o c y t i c p l e o c y t o s is . O n e c h i l d w i t hG r a d e I I D H F h a d C S F fe a t u r e s o f a c u t e b a c te r i a lm e n i n g i t i s w h i c h w a s c o n f i r m e d o n c u l tu r e . D e n g u ea n t i b o d i e s w e r e n o t d e t e c t e d i n t h e C S F i n a n y c h i l d a n dTABLE2. N eurological Ma nifestations (Total- 24)Neurologica l Number of N um be r fmanifestations cases DeathsDengue encephalopathy 17Bacterial me ning itis 1Acute Disseminated 2Encephalomyelitis ADEM)Hepatic encephalopathy 2Sub-arachnoid hemo rrhage 1Cardiac arrest sequelle 1

Indian Journal of Pediat r ics, Volum e 73--O ctob er , 2006 891


4/7


t h e C T s c a n s w e r e u n r e m a r k a b l e a p a r t f r o m a s u b -a r a c h n o i d b l e e d i n o n e p a t i e n t a n d m o d e r a t e c e r e b r a le d e m a i n 8 c h i l d re n .T w o c h i l d r e n c o n t i n u e d t o h a v e p r o f o u n d a l t e r e dm e n t a l s t a t u s a n d n o l o c a l i z i n g s ig n s d e s p i t en o r m a l i z a t i o n o f t h e ir c a r d i o p u l m o n a r y a n d m e t a b o l icp a r a m e t e r s a n d s u b s i d e n c e o f s t i g m a t a o f D H F ( i . e . ,n o r m a l i z a t i o n o f p l a t e le t c o u n t s , r e s o l u t i o n o f p l e u r a le f f u s i o n s a n d s t a b l e h e m a t o c r i t) . M a g n e t i c R e s o n a n c eI m a g i n g ( M R I) o f t h e b r a i n w i t h d i f f u s io n w e i g h t e di m a g i n g ( c a r r ie d o u t o n w e e k 2 o f P I C U s t a y ) re v e a l e dh y p e r i n t e n s e l e s i on s s u g g e s t i v e o f A c u t e D i s s e m i n a t e dE n c e p h a l o m y e l i t i s ( A D E M ) . 7,s B o t h p a t i e n t s r e c e i v e dp u l s e s t e r o i d s . O n e p a t i e n t p r o g r e s s e d t o s e v e r e c e r e b r a le d e m a a n d b r a i n s te m d e a t h , t h e s e c o n d s u r v i v e d w i t hs i g n i f i c a n t n e u r o l o g i c a l r e s i d u a .

O t h e r n e u r o l o g i c al m a n i f e s t a ti o n s i n c l u d e d 2 c h i l d r e nw i t h D H F G r a d e I V a n d h e p a t i c e n c e p h a l o p a t h y ( o n ed e a t h ) a n d o n e w i t h a n e x t e n s i v e s u b - a r a c h n o i dh e m o r r h a g e t h a t e x p i r e d . O n e p a t i e n t r e s u s ci t a te d f r o mc a r d i ac a r r e st h a d h y p e r t o n i a a n d c o n v e r g e n t sq u i n t b u ti m p r o v i n g m e n t a l s t a t u s . O f t h e 21 s u r v i v o r s w i t hn e u r o l o g i c a l m a n i f e s t a ti o n s , 1 9 e x p e r i e n c e d a c o m p l e t er e c o v e r y .Renal issuesA c u t e r e n a l f a i l u re w a s e n c o u n t e r e d i n 5 c h i l d r e np r e s e n t i n g w i t h o l i g o - a n u r i a a n d a m e a n c r e a ti n i n e v a l u eo f 2 .2 0 .6 r a g / d l , a ll o f w h o m u n d e r w e n t p e r i t o n e a ld i a l y s i s a n d i m p r o v e d . P e r i t o n e a l d i a l y s i s w a s a l s oi n i t i a t e d i n 6 a d d i t i o n a l c h i l d r e n w i t h d i u r e t i c re s i s t a n tf l u i d o v e r l o a d a n d s e v e r e r e s p i r a t o r y d i s t re s s . T h r e e o ft h e se c h i ld r e n h a d c o m p a r t m e n t s y n d r o m e a n d o n ep a t i e n t d i e d a s d e s cr i b e d a b o v e .Hepatic dysfunctionH e p a t i c d y s f u n c t i o n w a s s e e n i n 4 0 c h i l d r e n ( 3 6.6 % ), a ll o fw h o m h a d g r e a t e r t h a n a t h r e e - f o l d e l e v a ti o n o f h e p a t i ct r a n s a m i n a s e s . 3 2 o f 4 0 c h i l d r e n w i t h l i v e r d y s f u n c t i o nh a d p r e s e n t e d i n D S S ( G r a d e I II o r I V D H F ) . T h e h i g h e s tv a l u e s o f t r a n s a m i n a s e s w e r e 1 0 ,5 00 I U / L ( A L T ) a n d 3 7 00I U / L ( A S T ) s e e n in o n e o f t w o c h i l d r e n w h o p r e s e n t e dw i t h f u l m i n a n t h e p a t i c fa i l u re a n d e x p i r e d . H e p a t i cp a r a m e t e r s o f a ll o t h e r c h i ld r e n w e r e n o r m a l a t t h e t i m eo f d i s c h a r g e f r o m t h e I C U .Co-infect ionsC o - i n f e c ti o n s w e r e s u s p e c t e d i n t h e p r e s e n c e o f u n u s u a lc l in i c al a n d / o r l a b o r a t o r y f e a t u r e s a n d w e r e c o n f i r m e d i n1 9 p a t i e n t s , a ll o f w h o m a l s o h a d p o s i t i v e d e n g u es e r o l o g y . 9 c h i l d r e n h a d l e p t o s p i r o s i s , 6 c h i l d r e n h a de n t e r i c f e v e r , t h r e e h a d m a l a r i a a n d o n e h a d b a c t e r i a lm e n i n g i t i s i n a d d i t i o n t o D H F . A l l c o - i n f e c t i o n sr e s p o n d e d t o a p p r o p r i a t e d r u g a n d s u p p o r t i v e t h e r a p y ina d d i t i o n t o f lu i d r e s u s c i t a ti o n .

D u r a t i o n o f P I C U s t a y : T h e m e a n d u r a t i o n o f P I C Us tay w as 4 .9 + 2 .9 days .

C a se f a t a l i t y r a t e ( C F R ) : N i n e o u t o f 1 0 9 c a s e s w i t hs e v e r e fo r m s o f D H F d i e d r e s u l t in g i n a n I C U C F R o f8 .3 % . T h e o v e r a l l h o s p i t a l C F R f o r al l fo r m s o f d e n g u ev i r a l i n f e c t io n s w a s 1 .0 5% . A p o s t - m o r t e m e x a m i n a t i o nw a s n o t p e r f o r m e d i n a n y p a t i e n t.

Cause o f d e a t h i n 9 c h i ld r e n : R e f r a c t o ry s h o c k w i t hD I C a n d A R D S - 4 (1 a l so h a d c o m p a r t m e n t s y n d r o m e )R e f r a c t o r y s h o c k w i t h D I C - 2F u l m i n a n t h e p a t i c f a il u r e w i t h e n c e p h a l o p a t h y - 1A c u t e d i s s e m i n a t e d e n c e p h a l o m y e l i t is - 1S u b - a ra c h n o i d h e m o r r h a g e - 1

D I S C U S S I O N

H e r e a re r e p o r t e d c o m p l i c a t e d a n d a t y p i c a lm a n i f e s t a t i o n s i n t h e l a r g e s t s e r i e s f o c u s i n g s p e c i f i c a l l yo n p a t i e n t s w i t h s e v e r e f o r m s o f D H F r e q u i r i n g P e d i a t r icI n t e n si v e C a r e. T h e c o m m o n e s t i n d i c a t i o n f o r P I C Ua d m i s s i o n w a s p e r s i s t e n t u n c o r r e c t e d s h o c k f o ll o w e d b yr e s p i r at o r y d i s tr e ss a n d n e u r o l o g ic a l s y m p t o m s . F i n d i n gsn o t p r e v i o u s l y d e s c r i b e d i n th e s e t ti n g o f D H F / D S Si n c lu d e a b d o m i n a l c o m p a r t m e n t s y n d r o m e ( A C S) ,d i a s to l i c d y s f u n c t i o n c o n t r i b u t i n g t o r e f r a c t o r y s h o c k a n dA c u t e D i s s e m i n a t e d E n c e p h a l o m y e l i t i s ( A D E M )w o r s e n i n g t h e n e u r o l o g i c a l s t a tu s .A l t h o u g h t h e r e w a s n o s e x p r e d i l e c t i o n , s e v e r e d i s e a s eo c c u r r e d m o s t o f t e n i n i n f a n ts f o l l o w e d b y t h e 1 - 5 y e a ra g e g r o u p . W h i l e s e v e r e d e n g u e i n f e c t i o n s h a v e b e e nr e p o r t e d i n i n f a n t s 9-1~, t h e p r e s e n t s t u d y r e s u l t s w e r e i nc o n t r a s t to a s t u d y f r o m a l l h o s p i t a l i z e d p a t i e n t s w i t hd e n g u e f e v e r a n d D H F i n t h e s a m e i n s t it u t i o n w h e r e t h ec o m m o n e s t a g e g r o u p w a s 5 -1 5 y e a rs . 12

W i t h r e s p e c t t o c i r c u l a t o r y c o m p l i c a t i o n s , 3 9 ( 3 7 . 7 % )p r e s e n t e d w i t h s h o c k r e f r a c to r y t o E m e r g e n c y R o o mf l u i d r e s u s c i ta t i o n A n i m p o r t a n t c a u s e o f p e r s i s t e n t s h o c ki n a p a t i e n t w i t h D S S w h o s e c i r c u l a t o r y s t a t u s f a i l s t oi m p r o v e d e s p i t e a d e q u a t e f l u i d s is i n t e r n a l h e m o r r h a g e 1,2,h e n c e a l l p a t ie n t s w i t h f l u id r e f r a c t o r y s h o c k r e c e i v e db l o o d t r a n s f u s i o n ( p a c k e d r e d b l o o d c e ll s a n d p l a s m a )u n l e s s h e m o c o n c e n t r a t i o n p e r s i s t e d o r a n o b v i o u s c a u s es u c h a s SV T w a s i d e n t i f i e d . F a i l u r e o f t h e s y s t e m i cp e r f u s i o n to i m p r o v e d e s p i t e fl u i d a n d b l o o d t r a n s f u si o nl e d to e c h o c a r d i o g r a p h i c e v a l u a t i o n o f t h e m y o c a r d i a lf u n c ti o n : a n u n e x p e c t e d f i n d i n g w a s t h e p r e s e n c e o fd i a st o l ic d y s f u n c t i o n 18 in 3 cases. This f ea tur e , a l th ou ghl i k el y d u e t o m y o c a r d i a l e d e m a i n t h e s e t t i n g o f g ro s sa n a sa r ca h a s b e e n p r e v i o u s l y r e p o r te d b y u s i n d e n g u e/~4}a n d h a s i m p o r t a n t i m p l i c a t i o n s f o r f l u i d r e s u sc i t a t io n .C h i l d r e n w i t h d i a s t o l i c d y s f u n c t i o n a r e a t a h i g h e r r i sk o fe l e v a t e d l e f t v e n t r i c u l a r f i l li n g p r e s s u r e s a n d r e s u l t a n tp u l m o n a r y e d e m a w i t h f l u id c h a l le n g e s , is T h e f i n d i n gm a y b e m i s se d u n l e s s D o p p l e r s t u d i e s a r e p e r f o r m e d b ya n e x p e ri e n c e d e c h o c a rd i o g r a p h e r a n d m a n a g e m e n ti n c l u d e s s m a l l v o l u m e f l u i d r e s u s c i t a t i o n a t s l o w e r ra t e s ,a v o i d a n c e o f t a c h y c a rd i a a n d u s e o f n o n - c a t e c h o la m i n el u s i t ro p i c a g e n t s s u c h a s t h e p h o s p h o - d i e s t e r a s e i n h i b i t o r

892 Indian Journal of Pediat r ics, Volum e 73- -Oc tob er , 2006


5/7

47C l i n i ca l F ea t u r es , C o m p l i ca t i o n s an d A t yp i ca l M an i f es t a t i o n s o f C h i l d r en w i t h D en g u e H em o r r h ag i c F ever

agent milrinone. Echocardiographic features of leftventricular dysfunction was obtained in only twopatients. This was probably a gross under-es timation asall patients with fluid and blood product refractory shockwere already on inotropes at the time ofechocardiography, which may have "normalized"abnormal left ventricular systolic function.A study of hemodynamic profiles in DHF fromThailand reported lowered cardiac index due todecreased ejection fraction and lowered preload 16 whilereports from New Delhi, India have repor ted globalhypo kinesia 17,18 but there were no prev ious reports ofdiastolic dysfunction in DHF. Pericardial effusions havebeen reported previously, but did not contribute to theshock status.19 Steroids were not used in cases of refractoryshock as there was no da ta supp orti ng it's use. 2~Unsurprisingly, all four patients with uncorrected shockand DIC expired.

The abdominal compartment syndrome (ACS)contributed to refractory shock in 3 children with DHFGrade IV that required large volume fluid resuscitation.ACS was defined as abdominal distention with intra-abdominal pressure (LAP) > 15 mm Hg, accompanied byat least two of the following: oliguria or anuria;respiratory decompensation; hypotens ion or shock;metabolic acidosis. 6 All of the above features may easilybe thought to be part of the clinical spectrum of criticallyunstable DSS with refrac tory shock and flu id overload:the diagnosis of co-existing ACS may be missed unlessspecifically considered. Relief of the elevate d intra-abdominal hypertension led to improved cardio-respiratory function in 2 children while the third died dueto co-existing complications. ACS in the sett ing of DSS hasnot been previously described.With respect to hematological complications, the meanhemat ocrit at pres entat ion was 35.5 +8.1%. Indi anchildren with DHF have a lower than expected rise inhematocrit during the p lasma leakage period: this hasbeen a ttributed to the high prevalence of iron deficiencyanemia in the general population.21a3

Platelet counts less than 50,000/cumm was noted in62.3%. DHF patients with a platelet count < 50,000/cummhave been reported to have a six-fold higher mortalit ythan those with platelet counts > 50,000/cumm24 an d inthe present study too, on ly two of nine deaths occurred inchildren with platelet counts greater than 50,000/cumm.Immune related platelet damage and inhibition of plateletaggregation contribute to the thrombopathy ,z5 Apart fromdecreased platelet numbe r and function, DHF patientscan have abnormal hemostasis (vasculopathy,coagulopathy and DI G) . 26'27DIC and massive fatalbleeding may be more frequent in children withprolonged shock. 27-29 In the present study, while frank DICwas seen in six cases, co-existing refractory shock resultedin death in 4 children.Twenty-nine children (26.6%) required ventilation, themain indica tion being increasing respira tory distress.

ARDS was seen in 10 children, 4 of whom died. All casesof ARDS occurred in children presenting with Grade IVshock and lung injury in these patients ma y have resultedfrom "shock lung" and/or increased capillarypermeab ility. B~The need for high airway pressuresrequired to ventilate patients w ith severe ARDS in DSScan easily further worsen the patients' already precarioushemodyna mics and it is not surprising that Dengueassociated ARDS is associated with a high mortality.B~Hepatic and neurological dysfu nction have beenclassified as "unu sual complications/manifesta tions" ofDHF. B2-34Hepatic dys function may be multifactorial - themost important causes are prolonged shock, associatedmetabolic acidosis and DIC with resultant ischemichepatit is , a2"Bg,s5 The liver ma y also be the major site ofdengue viral replication. B6-B9

Only one-fifth of the 24 children with neurologicalmanifestations were in shock. While children with DSSmay have abnormal neurology secondary to cerebralhypoperfu sion on account of shock leading to hypoxic-ischemic events a nd /o r intracra nial bleeds, B2othersignificant reasons for neurological presentations includecerebral edema, direct neurotropic effect of dengue virusresulting in encephalitis/encephalopathy, or secondary tohepatic dysfunction and metabolic derangements such ashypoglycemia and hyponatremia.1,z41-46

Cranial imaging and CSF analysis were normal in themajority. 2 patients had clinical and MRI featuressuggestive of ADEM. While ADEM may occur followingmany viral exanthems7,8and Guillain Barre syndrome hasbeen described in Indian children following dengueinfection, 47 there has been only a single previous repor t onthe occurrence of ADEM following dengue fever in anadult.4s

The 3 neurological deaths in the present study wererelated to ADEM, sub-arachnoid hemorrhage and hepaticencephalopathy . In most cases, complete neurologicalrecovery is t he rule. 42,43 and in the presen t st udy too,neurological recovery was complete in 19 of 21 survivors.Co-infections were seen in 17.4% and it is importa ntthat they be promp tly recognized. Co-infections canmodify the clinical presentation of dengue and result inmissed or delayed diagnosis and treatment of dengheshock. 49The limitations of the present study relate to theinherent weakness of a retrospective analysis. Thestrengths relate to the fact that all cases were seen at asingle centre by both the authors where the indications foradmission to the PICU and subsequent management wasstandardized. Although a total of 858 cases were admittedto the entire hospita l during the study period, 109 (12.7%)critically unstable cases of dengue fever were admitted tothe PICU, making the present one the largest descriptivestudy of children specifically with severe forms of DHF

requiring Intensive Care.The clinical implications of our findings relate to thefact that critically unwell patients with dengue fever,Indian Journal of Pediatrics, Volume 73- -O ctob er, 200 6 893


6/7


DHF and DSS m ay have com pl i ca t io ns s ing ly o r incom bina t ion r e la ted to v i r tua l ly every m ajo r s ys tem .E a r ly r e c o g n i t i o n i n c o n j u n c t i o n w i t h m e t i c u l o u sm oni to r ing and t a rge ted s u ppor t i ve ca re i s theco rner s tone o f a s ucces s fu l ou tcom e. However ,particula rly in children that pre sent late with refractoryshock, i t i s impo r tan t to be aware of ent i t ies such asdiastolic dysfunctio n and ACS which, unless recognizedand appropr ia te ly m anaged , m ay con t r ibu te a h igherCFR.

If appro priat ely mana ged, the CFR for all hospitali zedch il dre n wi th de ng ue fever m ay be as lo w as 0.2-5 % (1,2,35

with high er rates up to 12.6% in patie nts wi th DSS. 2~Mortal i ty f igures f rom Indian l i terature sugges t CFRra ng in g from 26 to 47%. 5~ A specific pro ble m was latereferrals in established shock and DIC. Child ren referredlate are harder to resuscitate24,53 In our study, the ICUmortali ty was 8.3% while the overall hospital CFR for allforms D HF was 1.05%.Severe refractory shock, DIC, ARDS, hepatic failureand neurological manifestations singly or in combinati onwere the comm ones t causes of death in our series.

C O N C L U S I O N

In conclusion, critically ill children with deng ue ma y havepro tean m an i fes ta t ions . Mos t com pl ica t ions s uch asestablished a nd refractory shock, diastolic dysfunction,abdom ina l com par tm en t s yndrom e, DIC, ARDS andh e p a t i c d y s f u n c t i o n w e r e m o r e f r e q u e n t i n se v e r eestablished shock. Neurologica l events, for the most parLwere unrela ted to the perfusion status.

Complications infrequently / not previously describedin the setting of critically ill child ren with deng ue virali n f e c t i o ns i n c l u d e d i a st o l i c d y s f u n c t i o n , a b d o m i n a lcompar tmen t syndrome and ADEM.

R E F E R E N C E S

1. WHO. D e n g u e H a e m o r r h a g i c F e v e r : D i a g n o s i s , T r e a t m e n t ,Prevent ion and Control , 2nd edn. Geneva: WHO, 1997.2. Prevention and control of Dengue and Dengue haemorrhagicfever. Comprehensive guidelines. W H O S E AR O , New Delhi:WHO1999; 23 : 10-15.3. Rodhain F. Situation of dengue in the world. Bul l Soc PatholExo t 1996; 89(2) : 87-90.4. Gibbons RV. Dengue: an escalating problem. B M J 2002; 324 :1563-1566.5. Bernard GR, Artigas A, Brighan KL et al. The American -European Consensus Conference on ARDS.Am J Resp ir Cr i tCare Me d 1994; 149: 818.6. Beck R, Halberthal M, Zonis Z al. Abdominal compartmentsyndrome in children. Pediatr Crit Care Med 2001; 2 (1) : 51-56.7. DaleRC. Acute Disseminated Encephalomyelitis. Semin PediatrIn fect Dis 2003; 14(2) : 90-95.8. Pena JA, Monti el-Nava C. Dissemin ated Acuteencephalomyelitis in children. Rev Neu ro l 2002; 34(2) : 163-168.

9. Pancharoen C, Thisyakorn U. Dengue virus infection duringinfancy. Trans R Soc Trop Med Hyg 2001; 95: 307-308.10. Hongi siri won S. Dengue hemorr hagic fever in infants.Southeast Asian J Trop Med Public Health 2002; 33(1): 49-55.11. Guzman MG, Kauri G, Bravo J, Valdes L, Vazquez S, HalsteadSB. Effect of age on outcome of secondary dengue virus 2infection. In t J In fect Dis 2002; 6(2) : 118-124.12. Kabilan K, Balasubramanian S, Keshava S M, Satyanarayana K.The 2001 dengue epidemic in Chennai. Indian J Pedia tr 2005;72 : 919-923.13. Methods for obta ining quant itati ve information from theechocardiographic examination. In Snider AR, et al.Echocardiography in Ped iatric He art Disease. 2no ed. St Louis.Mosby-year book, 1997; 195-22414. Ranjit S, Kissoon N, Jayakumar I. Aggressive management ofdengue shock syndrome may decrease mortality rate: asuggested protocol. Pediatr Cr it Care IVied2005; 6(4) : 412-419.15. Graham TP. Disorders of the circulation. In Fuhrman BP,Zim merm an JJ eds. Ped i a t r i c Cr i t i ca l Ca re 2nd ed, St LouisMosby, 1998; 261-271.16. Khongphathanayothin A, Suesaowalak M, Muangmingsook S,Bhattarakosol P, Pancharoen C. Hemodynamic profiles ofpatients with dengue hemorrhagic fever during toxic stage: anechocardiographic study. In t en s i ve Ca re Me d 2003; 29(4): 570-574.17. KabraSK, Juneja R, Madhulika et al. Myocardial dysfunction inchildren with dengue haemorrhagic fever. N a t l M e d J I n d ia1998; 11(2): 59-61.18. Wali JP, Biswas A, Chandra S. Cardiac involvement n denguehemorrhagic fever. Intl J Cardiol 1998; 64(1): 31-36.19. Pellupessy JM, AIlo ER, Jota S. Pericardial effusion in denguehaemorrhagic fever. Peduitr tndones 1989; 29(3-4) : 72-75.20. Tassniyom S, Vasanawathana S, Chirawatkul A, RojanasuphotS. Failure of high-dose methylpredn isolone in establisheddengue shock syndrome: a placebo-controlled, double-blindstudy. Pediatrics 1993 ; 92(1) : 111-115.21. Gomber S, Ramachandran VG, Kumar Set al. Hematologicalobservations as diagnostic markers in Dengue hemorrhagicfever - a reappraisal. Indian Pediatr 2001; 38(5) : 477-481.22. Aggarwal A, Chandra J, Aneja S, Patwari AK, Datta AK. Anepidemic of dengue hemorrhagic fever and dengue shocksyndrome in children in Delhi. Indian Pediatr 1998; (35): 727-732.23. Narayanan M, Aravind MA, Thilothammal Ne t at . DengueFever epidemic in Chennai- A stud~ of clinical profile andoutcome. Indian Pediatr 2002; 39 : 1027-1033.24. Chua MN, Molanida R, de Guzman M, Laberiza F.Prothrombin time and partial t hrombopIastin time as apredictor of bleeding in dengue hemorrhagic fever. SoutheastAsian J Trop Me d P ubl ic Heal th 1993; 24 Suppl 1 : 141-143.25. Hathirat P, lsarangkura P, Srichaukul P, Suvatte V, Mitrakul C.Abnormal hemostasis in dengue hemorrhagic fever. SoutheastAsian J Trop Me d P ubl ic Heal th 1993;24 Suppl 1 : 80-85.26. Srichaikul T, Nimmanitya. Hematology in dengue and denguehaemorrhagic fever. Baillieres Best Pract Res Clin H aemato12000Jun; 13(2) : 261-276.27. Wills BA, Oragui EE, Stephens AC et al. Coagulationabnormalities in dengue hemorrhagic fever: Serialinvestigations in 167 Vietnamese children with dengue shocksyndrome. Clin In fect Dis 2002; 35 (3) : 277-285.28. Mairuhu AT, Macgillavry MR., Setiati TE. Is clinical outcomeof dengue-vi rus infections influenced by coagulation andfibrinolysis? A critical review of the evidence. Lancet Infect Dis2003; 3(1) : 33-41.29. Krishnamurti C, Kaalayanarooj S, Cutting MA et al.Mechanisms of hemorrhage in dengue without circulatorycollapse. Am J Tro p Med H y f ; 2001; 65 (6) : 840-847.

894 Indian Journal of Pediat r ics, Volum e 73- -Oc tobe r , 2006


7/7

49Clinical Features, Complications and Atypical M anifestations of Chi ldren with Dengue Hem orrhagic F ever

3 0. G e o r g e R , L a m S K . D e n g u e v i r a l i n f e c t io n - t h e M a l a y s i a ne x p e r i e n c e . A n n Acad Med Singapore 1997; 26(6) : 815-819.3 J. L u m L C , T h o n g M K , C h e a h Y K et al. D e n g u e - a s s o c i a t e da d u l t r e s p i r a t o r y d i s t r e s s s y n d r o m e . Ann Trop Pediatr 1995;15(4) : 335-339.32 . N i m m a n n i t y a S , T h i s y a k o r n U , H e m s r i c h a r t V . D e n g u eh e m o r r h a g i c f e v e r w i t h u n u s u a l m a n i f e s t a t io n s . SoutheastAsian J Trop Med Public Health 1987; 18(3) : 398-405.33 . Geo r ge R , L iam C K, C hna C T . Un us ua l c li n i ca l man i f es t a t ionso f d e n g u e v i r u s i n f e c ti o n . Southeas t As ian J Trop Med Publ icHealth 1988; 19 : 585-590.

3 4. K a l a y a n a r o o j S , C h a n s i r i w o n g s V , N i m m a n i t y a S . D e n g u eBulletin 2002; 26 : 33-43.3 5. M o h a n B , P a t w a r i A K , A n a n d V K . H e p a t i c d y s f u n c t i o n i nc h i l d h o o d d e n g u e i n f e c ti o n s . J Trop Pediatr 2000; 46(1 ) : 40-43.30 . Kuo C H, T a i DI , C ha ng- C hien C S , L an C K, C h iou SS , L iaw YF .L i v e r b i o c h e m i c a l t e s t s a n d d e n g u e f e v e r . A m T ro p M e d H y g1992; 47(3) : 265-270.37 . Wa hid SF , Sanus i S , Z a wa wi M M , Al l R A. A com par i s on o f t hep a t t e rn o f li v e r i n v o l v e m e n t i n d e n g u e h e m o r r h a g i c f e v e r w i t hc l as s i c dengue f ever . Southeast Asian J Trop Med Public Health2000; 31(2): 259-263.

38 . L um L C S, L a in C K, Ge or ge R . Fu lm inan t hepa t i t i s i n den guein f ec t ion . Southeast Asian J Trop Med Public Health 1993; 24 (3):467-471.3 9. C o u v e l a r d A , M a r i a n n e a u P , B e d e l C et al. R e p o r t o f a f a ta lc a s e o f d e n g u e i n f e c t i o n w i t h h e p a t i ti s : d e m o n s t r a t i o n o fd e n g u e a n t i g e n s i n h e p a t o c y t e s a n d l i v e r a p o p t o s i s . s H u mPathol 1999; 30(9) : 1106-1110.40 . J ans s en HL , B ienf a i t HP , J ans en C L et al. F a t a l c e re b r a l e d e m aa s s o c i at e d w i t h p r i m a r y d e n g u e i n f e c t io n . J Infect 1998; 36(3):344-346.41 . L ur e L C , L a in SK, C h oy YS . De ngu e encepha l i t i s : a t r ue en t i t y?A m J T ro p M e d H y g 1996; 54 : 256-259.42 . Kank i r awatana P , C hok epha ib u lk i t K , Pu tha va tha na P , Yoks an

S , A p i n t a n a p o n g S , P o n g t h a p i s i t V . D e n g u e i n f e c t i o n sp r e s e n t i n g w i t h c e n t r al n e r v o u s s y s t e m m a n i f e s ta t i o n s . J ChildNeurol 2000; 15 (8) : 544-547.4 3. C a m B V , F o n s m a r k L , H u e N B , P h u o n g N T , P o u l s e n A ,H e e g a a r d E D . P r o s p e c t i v e c a s e - c o n t r o l s t u d y o fe n c e p h a l o p a t h y i n c h il d r e n w i t h d e n g u e h e m o r r h a g i c f e v e r.A m J T ro p M e d H y g 2001; 65(6): 848-851.4 4. T h i s y a k o r n U , T h i s y a k o r n C , L i m p i t i k u l W , N i s a l a k A .D e n g u e i n f e c ti o n w i t h c e n t r a l n e r v o u s s y s t e m m a n i f e s ta t i o n s.Southeast Asian J Trop Med Public Health 1999; 30(3): 504-506.4 5. P a n c h a r o e n s C , T h u s y a k o r n U . N e u r o l o g i c a l m a n i f e s t a ti o n s ind e n g u e p a t i e n t s. Southeast Asian J Trop Med P ublic Health 2001;32 : 341-345.4 6. H e n d a r t o S K , H a d i n e g o r o S R . D e n g u e e n c e p h a l o p a t h y . ActaPedaitr Jpn 1992; 34 (3) : 350-357.4 7. Y a m a m o t o Y , T a k a s a k i T , Y a m a d a K et al. A c u t e D i s s e m i n a t e dE n c e p h a l o m y e l i t i s f o l l o w i n g d e n g u e f e v e r . J Infect Chemother2002; 8 (2 ): 175-177.4 8. S u l e k h a C , K u m a r S , P h i l i p J. G u i l l a i n - B a r r e S y n d r o m ef o l l o w i n g D e n g u e F e v e r : R e p o r t o f 3 C a s e s . Indian Pediatr 2004;41: 948-950.4 9. P a n c h a r o e n C , T h i s y a k o r n U . C o i n f e c t i o n w i t h d e n g u epa t i en t s . Pediatr Infect Dis J 1998; 17 : 81-82.5 0. C h e r i a n T , P o n n u r a j E , K u r u v i l l a T et al. A n e p i d e m i c o fD e n g u e h a e m o r r h a g i c f e v e r a n d D e n g u e s h o c k s y n d r o m e i na n d a r o u n d V e l l o r e . hzdian J Med Res 1994; 100 : 51-56.5 1. P a n d e J N , K a b r a S K . D e n g u e h a e m o r r h a g i c f e v e r a n d s h o c ks y n d r o m e . Natl M ed J India 1996; 9: 256-258.5 2. A g a r w a l R , K a p o o r S , N a g a r R et a93A c l in i ca l s tudy o f pa t i en t sw i t h d e n g u e h a e m o r r h a g ic f e v e r d u r i n g t h e e p i d e m i c o f 1 99 6a t L u c k n o w , I n d i a . Southeast As ian J Trop Med Publ ic Heal th1999 ; 30 (4): 735-740.53 . De en J L . L a te p r es en ta t ion and incr ea s ed mor t a l i t y i n ch i ld r enw i t h d e n g u e h e m o r r h a g i c f e v e r . Trop Doct 2000; 30(4) : 227-228.

Indian Journal of Pediat r ics, Volum e 73--O ctob er , 2006 895

manifestations of children with severe forms of dengue

Documents