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1981;67;79PediatricsA.R.M.A Alim and David A. Sack

Robert E. Black, Michael H. Merson, Philip R. Taylor, Robert H. Yolken, Md. Yunus,with Rotavirus-Associated Diarrhea

Glucose vs Sucrose in Oral Rehydration Solutions for Infants and Young Children

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P E D IA T R IC S V o l 6 7 N o Ja n u a ry 9 8 79

G lu cose vs Suc ro se in O ra l R ehyd ra tion

So lu tion s fo r In fan ts and Young C h ild ren w ith

R o tav irus -A ssoc ia ted D ia rrhea

Robert E . B la ck M D M PH M ich ae l H . Merson MD

Ph ilip R . Tay lo r

M D R obe rt H . Y olken M D M d.

Yunu s MBBS

A .R .M .A A Iim BS and D av id A . S ack

MD

F rom the In te rna tiona l C en tre fo r D ia rrhoea l D isease R esea rch , B ang ladesh fo rm e rly

C ho le ra R esea rch Labo ra to ry , D acca , B ang ladesh , B u reau o f E p idem io logy , C en te r

fo r D isease C on tro l, A tlan ta , Labo ra to ry o f In fe c tious D iseases , N a tiona l In s titu te s o f

A lle rgy and In fec tious D iseases , B e thesda , M a ry land , and D iv is ion o f G eog raph ic

M ed ic ine , Johns H opk in s U n ive rs ity , B a ltim o re

ABSTRACT . T h e u se o f o ra l re hyd rat ion so lu tion s con -

ta in in g essen tia l elec tro ly tes an d eithe r g lucose o r sucrose

o f eq ua l osm ola lity w as com pared in a doub le -b lin d se -

qu en tial tr ia l o f 784 ch ild ren w ith ro tav iru s-a ssoc iated

d ia rrhea trea ted a t a cen ter in ru ra l B ang ladesh . T he ora l

flu id fa ilu re rate w as 1 1 .5 fo r the sucrose -con ta in ing

so lu tion gro up an d 7 .3 fo r the g lu co se-con tain ing gro up

P

= N S). V om iting w as a

sign if ican t ly

m o re com m on

cau se o f failu re fo r th e g roup treated w ith su crose -co n-

tam in g ora l rehyd ra tion so lu tion and w as assoc ia ted w ith

an increased ra te o f in take of the sw eete r su cro se -con-

tam ing so lu tion . The p urg ing ra te w as n o t d ifferen t fo r

the tw o gro ups . T he ora l flu id fa ilu re ra tes fo r ch ild ren in

the m ost un derw eigh t ca tegory (<60 o f exp ected w eigh t

fo r age) w ere n o t d ifferen t from th ose fo r o ther g rou ps,

a lth ough , as assessed b y pu rg ing ra te an d in itia l d eh ydra -

tion , th e s to o l lo sses o f m em bers o f th is g roup con stitu ted

a grea te r p ro portion o f the ir bo dy w eigh t. G lu cose is th e

pre fe rred carboh ydra te fo r o ral e lectro ly te so lu tions , a -

though su crose can be subs titu ted w ith on ly m in im um

loss o f e fficacy .

Ped ia tr ic s 67:7 9-8 3 , 198 1; g lucose -e lec -

tro ly te so lu tio n ro tav irus m alnu trition and d ia rrhea

sucro se -e lectro ly te so lu tion ora l reh ydra tion .

O ra l rehyd ra tion the rapy w ith a so lu tion co n ta in -

ing g luco se an d e lec tro ly te s has b een su ccessfu lly

used fo r treatm en t o f deh ydra tion resu lting from

acu te d ia rrhea from a ll cau ses in a ll age g rou ps.’ A

few qu estio ns are still unansw ered abou t us in g it

Received fo r pub lic atio n A p ril 4 ,

1980 ; accep ted M ay 12 , 19 80 .

Reprin t reques ts to (R .E .B .) C en te r fo r V acc ine D eve lopm ent,

U n iversity o f M ary land S choo l o f M edic ine , 29 S G reene S t,

B a ltim ore , M D 21201 .

PED IA TR IC S (ISSN 0031 4005). C opy righ t ©

1981 by th e

A m erican A cad em y o f Ped iatr ics ,

g lob ally . O n e of these is w he ther sucro se can be

subs titu ted fo r g luco se in preparing the so lu tion ;

th is q uestion is im portan t s in ce , in som e coun tries,

suc rose is less expen sive and m ore read ily ava ilab le

than g lu co se . A num ber o f sm a ll, w ell-con tro lled

s tu d ies ca rried ou t to address th is ques tion ind ica te

tha t w h ile su crose can b e subs titu ted , g lucose is

p re fe rab le.25 W e rep ort he re o n the use o f g lucose -

and suc ro se -con tain ing ora l reh ydra tion so lu tio ns

as the rapy fo r a large num ber of ch ild ren w ith

ro tav irus-as soc ia ted d ia rrhea trea ted p rim arily b y

p aram ed ical w ork ers a t a h ealth cen ter in ru ral

B ang lad esh . W e a lso de te rm ined th e fa ilu re ra te s

fo r ch ild ren o f d iffe rin g n u tr itiona l sta te and the

e ffect o f nu trition al sta tu s on the course o f ro tav i-

m s -a sso cia ted d ia rrhea .

MATER IA LS AND METHODS

Pa tien t Popu la tion and Adm iss ion A ssessm en t

T he stu dy w as conduc ted a t th e M atlab T rea t-

m en t C en te r o f th e In terna tion al C en tre fo r D ia r-

rh oea l D isease R esearch , B ang ladesh (IC D D R B )

(fo rm erly the C ho le ra R esea rch Labo ra to ry ) . T h is

cen te r p rov id es trea tm en t fo r gastro in te stin al ill-

n esses to the appro x im ate ly 2 69 ,000 residen ts o f the

f ield re search a rea . M ed ical care a t th e C en te r is

p ro v ided by a pa ram ed ica l s ta ff su pe rv ised by a

phy sic ian . W hen the p atien ts v isited the trea tm en t

cen ter , a b rief h is to ry w as o b ta ined and a physica l

exam ina tion , inc lud in g de term in atio n of body

w eig h t, w as pe rfo rm ed . S e rum sp ec if ic g rav ity w as

de te rm in ed w ith a re frac tom e te r fo r a sm a ll, ran -

dom sam ple o f p atien ts o n adm is sion . O n N ov 17 ,










A R T IC L E S 8

TABLE

Treated

1

.

w it

A dm issi on C haracte

h G lucose or Sucrose

ri sti cs of Patients

O ral R ehy dr ati on

w i th R otav i rus-A ssociated D iarrhea

Solution

Characteri sti cs O ral Rehydrati on Soluti on

G lucose (n = 385) Sucrose (n = 399)

12.0 (0.25) 12.1 (0.26)

2 4 8 1 3 6 2 6 2 1 3 7

9 7 1 9 8 4

1.6 (0.1) 1.6 (0.08)

1.2 (0.05) 1.3 (0.07)

1.027 (.<0.001)t 1.028 (< 0.001)

9.7 9.0

71.0 (0.5) 71.4 (0.5)

M o n t h s

of age

Sex (M /F)

V om i ti ng bef ore adm issi on (% )

D ay s of diarrhea bef ore adm issi on

D ay s of vom i ti ng bef ore adm ission

A dm issi on speci f i c grav i ty

O ther pathogens (% )

Percent w eight for age

M ean (1 SEM ).

t

n

= 70.

:j : n

= 27.

§

Sa lmone lla , Shige lla , enterotoxigemc Escherichia co li, Vibrio cho lerae .

II

D ischarge w eight as a percentage of H arvard m edian w eight f or chi l d’ s age.

TABLE 2 . O ra l Rehydrati on Fai l ures by D ehy drati on

Status

of Patients* w i th Rotav i rus-A ssociated D iar rhea

T reated w i th Oral Soluti on

Dehydration

Status

O ral Rehydr ati on Soluti on

G lucose Sucrose

N o. of

C a s e s

Failures

No .

N o. of

Cases

Failures

N o .

N one to m i ld

M oderate to

217

42

14 6.5

5 11.9

201

33

22 10.9

5 15.2

severe

T otal 259 19 7.3

234

27 11.5

I ncludes only patients w i th diarrhea w hi l e hospi tal i zed.

i ng rate, si x in each group; (2) inadequate correcti on

of ini ti al dehy drati on, tw o in each group; (3) v om-

i ti ng, one in glucose group and 12 in sucrose group;

and (4) abdom inal di stention or combinations of

these causes, ten in glucose group and seven in

sucrose group. V om i ti ng, by i tsel f , w as signi f i cantl y

more comm on reason f or f ai l ure for the SO RS

group than for the G O RS group

(x =

6.6,

P

<.025).

Th is w as parti cularl y the case f or the nondehy -

drated to m i ldl y dehydrated patients, among w hom

there w ere one of 14 GO RS f ai l ures and ten of 22

SO RS f ai l ures because of vom i ti ng P =

.016,

Fisher ’ s ex act test, one tai l ed). I n f act, signi f i cantl y

m ore of the SO RS-treated patients (47.4%) than of

the G O RS-treated cases (36.6% ) vom i ted w hi le hos-

pi tal i zed (x 2 = 8.8, P

< .001).

H ow ev er , 88 o f t h e

patients w ho vom i ted in the hospi tal w ere success-

f ul l y treated w i th one of the oral rehydrati on solu-

tions.

A compari son of oral f l uid intake rates dur ing the

total course of therapy show ed one possible mech-

anism for the increased rate of vom i ti ng for the

SO RS groups. T he nondehy drated to m i ldl y dehy-

drated patients receiv ing the SO RS soluti on drank

at a signi f i cantl y faster rate (6.9 ± 0.3 m l/k g/hr)

than those receiv ing the GO RS soluti on (5.9

±

0.3

ml/kg /hr) t = 2.1,

P

< .05). A m ong m oderatel y to

sev erel y dehydrated patients, the SO RS group alsO

tended to consume the f luid f aster, but the rates for

the tw o groups (6.2

±

.06

vs 4.9 ± 0.4) w ere not

signi f i cantl y di f f erent. Furthermore, the mean in-

take rate in the f i rst eight hours of therapy for ten

of the patients w i th no or m i ld dehydrati on w ho

w ere SO RS f ai l ures w as 16.1 ni l /kg/hr. T his w as

almost tw ice that of that group as a w hole (t = 1.94,

P

< .10). T he purging rates for both dehydrati on

categor ies of the tw o treatment groups w ere sim i lar

(T able 3).

W hen the chi l dren w i th rotav i rus-associated diar-

rhea w ere grouped by thei r w eight at di scharge as

a percentage of the ref erence populati on median

w eight f or thei r age, each category had sim i lar

f ai l ure rates w i th G O RS and SORS. Furthermore,

the fai l ure rates f or al l the nutr i ti onal categories

w ere sim i lar f or G ORS, SO RS, or the tw o combined

(T able 4).

Chi l dren in each of the f our nutri ti onal categor ies

had sim i lar m ean durati ons of diarrhea before and

during thei r hospi tal i zati on. T here w as a trend to-

w ard a higher purging rate in the f i rst eight hours

of therapy in underw eight chi l dren w hen patients

w ere grouped by body w eight. T his trend may

correlate w i th the observ ation that the low er the

category of nutr i ti onal status the higher the pro-

porti on of moderatel y to sev erel y dehydrated pa-

ti ents as assessed on adm ission and by percentage

gain in body w eight af ter rehydrati on (T able 4).

IS USSION

W i th a large study populati on, w e conf i rmed re-

sui ts obtained in earl i er studies of much few er pa-

ti ents cared f or pr imari l y by phy sicians. B oth these

resul ts and ours indicate that sucrose can be sub-

sti tuted f or glucose in the oral rehy drati on treat-








TA B L E 4 .

N utritional Status, Severity of D iarrhea, and Rates at W hich O ral Rehydration Therapy Failed for

Patients w ith R otavirus-A ssociated D iarrhea

Weight/Age

)

Total

Patients

M oderate-Severe

D ehydration (% ) Purging

Rate First 8 hr T otal D iarrhea

D uration (hr)

O ral T herapy

Failure (% )

A ssessed on G ain of 5% ml/hr

nd/hr/kg

A dmission B ody W eight

< 60.0 57 26* 25t 27 (3) 4.9 (0.6) 64

5.3

60.0-69.9 158 15 14

27 (2) 4.3 (0.6) 62 9.5

70.0-79.9

168

18 21 29 (2) 4.1 (0.3) 63

10.1

80.0

90 6 9

30 (3) 4.1 (0.5) 59 10.0

Percentage of patients w ith moderate-severe dehydration greater for < 60 group vs allother (Fisher’ s exact test [FET ]

= .01) or < 60 group vs 80 group (FET = .0004).

t

Percentage of patients w ith moderate-severe dehydration greater for < 60 groups vs all other (FET

= .04) or

< 60

group vs 80 group (FET = .007).

:j : M ean

(1 SEM ).

82 G L UCOSE

VS SUCRO SE IN OR L REHYDR T ION SO LUT IONS

TA B L E 3 .

Purging Rates (ml/kg/hr) for Patients w ith Rotavirus-A ssociated D iarrhea

by D ehydration Status and O ral R ehydration Solution U sed

T ime Period D ehydration Status

N one to M ild M oderate to Severe

Glucose Sucrose G lucose Sucrose

(n = 217) (n = 201) (n = 42) (n = 33)

First 8-hr period 3.7 (0.3)* 4.2 (0.3) 5.7 (0.7) 5.7 (0.7)

First day 3.5 (0.2) 3.6 (0.2) 5.7 (0.5) 5.6 (0.6)

T otal treatment period 3.2 (0.2) 3.4 (0.2) 4.6 (0.4) 4.7 (0.4)

M ean (1 SEM ); no significant differences betw een glucose- and sucrose-treated patients

in any time period in either category of cases by dehydration status.

ment solution with only a minimal loss of eff icacy.25

T he trend w e observed tow ard a slightly larger

number of failures for the SORS- treated group w as

similar

to that observed by other investigators in

these smaller studies, but even with our much larger

population the failure rates w ere not signif icantly

different.

I n our study, treatment w ith SO RS was associ-

ated for the first time w ith signif icantly higher rates

of vomiting. T his largely accounted for the higher

number of SO RS failures, especially for the non-

dehydrated to mildly dehydrated patients. T he

vomiting may have resulted from an increased rate

of intake of the sucrose-containing solution because

of its greater sw eetness and thus more appealing

taste. Rapid intake in a few cases may have led to

gastric distention and vomiting. A n alternative ex-

planation could be that rapid enzymatic hydrolysis

of sucrose could result in double the number of

osmoles in the upper intestine than w ould occur

from the glucose solution. Resultant intraluminal

fluid accumulation and intestinal distention could

have caused vomiting. A lthough vomiting w as an

important cause of oral rehydration failures,

88% of the children who vomited in the hospital

were successfully treated w ith oral therapy. A s ob-

served by others studying rotavirus2 and entero-

toxin-associated arr4’ w e found no difference

in purging rates for the tw o solutions despite the

fact that patients receiving SOR S tended to drink

faster.

W e also confirmed earlier reports2’3”2 that a glu-

cose- or sucrose-containing electrolyte solution can

be used to treat rotavirus-associated and secretory

diarrhea w ith similar success. T his is reasurring

since rotavirus is the leading cause of diarrhea in

infants and young children at our treatment center.9

O ur overall rates of patients requiring intravenous

therapy after treatment w ith the oral solutions are

a little higher than those reported from other stud-

ies of rotavirus-associated diarrhea, w hich probably

can be attributed to the more difficult circum-

stances in the rural center w here our paramedical

personnel w ere faced w ith treating more patients

w ith less supervision.

D espite the fact that children w ith rotavirus-as-

sociated diarrhea have comparable durations of

diarrhea regardless of their nutritional status, the

fluid lost in diarrheal stool may represent a greater

proportionate loss in children with a low body

weight due to young age or malnutrition. T he con-

sequent greater dehydration puts the underweight

child at higher risk of death and in more need of

effective rehydration therapy. T he equal success of

oral rehydration for children of varied nutritional

status should further support the use of this therapy

for chronically undernourished children w ith diar-

rhea in developing countries.








A R T IC L E S 83

I MP L I T I ONS

T he w orld heal th com muni ty i s currentl y try ing

to promote w idespread use of oral rehydrati on ther-

apy as an integral part of prim ary heal th care.’ 3

T he decision of w hether to use glucose-or sucrose-

containing soluti ons in country program s must be

based on a num ber of f actors including cost and

avai l abi l i ty of i ngredients and comparati ve ef f i cacy .

Our study conf i rms the f inding of others that, al -

though glucose is preferred, sucrose can be used in

an oral soluti on w hich is saf e and ef fecti ve f or

treatment of diarrhea.

KNOWLEDGMEN T S

W e w ould l i k e to acknow ledge the support of the

I nternational C entre f or D iar rhoea D i seases Research,

B angladesh (f orm erl y the Cholera R esearch L aboratory )

and the I nternati onal Center f or M edi cal Research (N a.

tional I nsti tutes of H eal th Grant 5R 07A 110048-17).

W e

al so w ish to express our grati tude f or the technical

assi stance of M r S. H uda and M r S. Rahm an and the

nursing

care prov ided by the staf f of the M atlab T reat-

m ent C enter .

R E F E R EN E S

1. Pierce N F, H i rschhorn N : O ral f l uid-A si mple w eapon

against dehy dration in diarrhea. WHO Chron 31:87, 1977

2. Sack D A , Chow dhury A M A K , Eusof A , et al : Rehydration

i n rotav i rus diarrhoea: A double-bl ind com pari son of sucrose

w ith glucose electrol y te soluti on. Lancet

2:280, 1978

3. N al i n D R ,

Lev ine M M , M at s L , e t a l: C o m par ison o f su cr ose

w ith glucose in oral therapy of i nf anti le diarrhoea. Lancet

2:

277, 1978

4. Palm er D L , K oster V T ,

Islam

A FM , et al : Com pari son of

sucrose and glucose in the oral electrol y te therapy of cholera

and other sev ere di arrheas.

N Eng l JMed 297:1107, 1977

5. Chatterj ee A , M ahalanabi s D , Jalan K N , et al : Evaluation

of a sucrose/el ectrol y te soluti on f or oral rehydrati on

in

acute

i nf ant il e di ar rhea.

Lancet

1:1333, 1977

6. Y ol ken RH , K im H W , C hen T , et al : Enzym e-l inked im m u-

noassay (EL I SA ) f or detecti on of hum an reov i rus-l i ke agent

o f i nf an ti l e g ast ro en ter it is.

Lancet

1:263, 1977

7. Y ol ken RH , W yatt RG , K apik ian A Z . El i sa for rotavirus.

Lancet 2:819, 1977

8. M erson M H , Sack RB , K ibria A K M B , et al : E f f i cacy of

pool i ng strai ns f or l aboratory diagnosi s of enterotox i geni c

Escherichia co li (E TE C) di arrhoea. J Clin Microbio l 9:493,

9 9

9. B lack RE, M erson M H , Row e B , et al : Epidem iology of

enterotoxigenic Escherichia co li i n rural

Bangladesh.

Pro -

ceedings o fthe 14 th Jo int Conference on Cho lera , US-Japan

Cooperati ve M edical Science Program , K aratsu,

1978

10. Y olk en RH , Stopa RI . A nalysi s of nonspeci f i c reactions in

enzyme-linked

immunosorbent

assay

testi ng f or hum an ro-

tavirus. J Cliii Micro bio l 10:703, 1979

11. Sack D A , I slam 5, B row n K H , et al : Oral therapy i n chi ldren

w i th cholera: A double bl ind com pari son of sucrose w i th

glucose electrol y te oral soluti on.

J P edi atr

96:20, 1980

12. Tay lor PR, M erson M H , B lack R E, et a : O ral rehydrati on

therapy f or treatm ent of rotav i rus diarrhea in a rural treat-

m ent center i n B angl adesh. Arch D is Child 55:376, 1980

13. C ontrol of d iarrheal

diseases:

W H O ’ s program m e takes

shape. WHO Chron 32:369, 1978

O N E V LU TING THE TE H ING O F R E D ING

Y ou can teach w hat i s testable and test w hat

reassured that you have accom pl i shed something

i s teachable and be f al sel y

Edi torial note: T his comm ent appl i es equal l y w el l to pediatri c recerti f i cati on.

From T eacher speak ing, Optio ns in Educa tion, N ati onal Publ i c R adio.

Submi tted by E.K .M .








1981;67;79Pediatrics

A.R.M.A Alim and David A. Sack Robert E. Black, Michael H. Merson, Philip R. Taylor, Robert H. Yolken, Md. Yunus,

with Rotavirus-Associated DiarrheaGlucose vs Sucrose in Oral Rehydration Solutions for Infants and Young Children

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