Food and Nutrition Sciences, 2013, 4, 709-714
http://dx.doi.org/10.4236/fns.2013.47090 Published Online July 2013 (http://www.scirp.org/journal/fns)
Predictors of Death in Under-Five Children with Sepsis
Attending an Urban Diarrheal Treatment Centre in
Bangladesh
K. M. Shahunja1, Abu Sadat Mohammad Sayeem Bin Shahid1, Hasan Ashraf1,2,
Abu Syeed Golam Faruque1, Sumon Kumar Das1, Md. Kamruzzaman3,
Farhana Pervin Flora1, Mohammod Jobayer Chisti1,2*
1Centre for Nutrition and Food Security, International Centre for Diarrhoeal Disease Research (icddr,b), Dhaka, Bangladesh;
2Clinical Service, Dhaka Hospital, International Centre for Diarrhoeal Disease Research (icddr,b), Dhaka, Bangladesh; 3Dhaka
Shishu (Children) Hospital, Dhaka, Bangladesh.
Email: *chisti@icddrb.org
Received May 10th, 2013; revised June 10th, 2013; accepted June 18th, 2013
Copyright © 2013 K. M. Shahunja et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
SETTING: Special Care Ward (SCW) of the Dhaka Hospital of icddr,b, Bangladesh. OBJECTIVE: To evaluate the
clinical and laboratory predictors of death in under-five children with clinically defined sepsis presenting with diarrhea.
METHODS: We prospectively enrolled all the diarrheal children (n = 151) aged 0 to 59 months with clinical sepsis
admitted in the SCW during September’2007 through December’2007. Comparison was made between deaths (n = 23)
and survivors (n = 128). Sepsis is defined as presence of inflammation [abnormal WBC count (>11 × 109/L or, <4 ×
109/L or, band and neutrophil ratio 0.10] plus presence or presumed presence of infection with thermo-instability
[hypo (35.0˚C) or hyperthermia (38.5˚C)], tachycardia, tachypnea, and/or the indications of altered organ function
(altered mental status and bounding pulse) in the absence of clinical dehydration or after correction of dehydration.
RESULTS: The median (inter-quartile range) age (months) of the children who survived and died was comparable [4.0
(2.0, 12.0) vs. 1.5 (0.8, 10.0); p = 0.703]. In the logistic regression analysis, after adjusting for potential confounders,
such as abnormal WBC count, use of intravenous fluid, patient with fatal outcome more often presented with hyperna-
tremia (odds ratio = 16.48, 95% confidence interval = 2.21 - 123.12; p = 0.006), lobar consolidation (odds ratio = 19.9,
95% confidence interval = 2.99 - 132.80; p = 0.002), hypoxemia (odds ratio = 14.78, 95% confidence interval = 1.38 -
157.90; p = 0.026) and severe under-nutrition (odds ratio = 7.57, 95% confidence interval = 1.24 - 46.11; p = 0.028).
CONCLUSIONS: Our data suggest that children under-five with clinical sepsis who present with lobar pneumonia,
hypoxaemia, severe acute malnutrition and hyperntaemia are at higher risk of death and identification of these simple
factors may help clinicians to take prompt initiative for the aggressive management of such children especially in a re-
source-limited setting like Bangladesh.
Keywords: Bangladesh; Diarrhea; Hypoxemia; Sepsis; Severe Malnutrition
1. Introduction
Sepsis is one of the most important causes of death in
under-five children in developing countries [1,2]. The
largest part of the global sepsis burden occurs in middle-
and low-income countries. Around 70% of the 7.6 mil-
lion global deaths in neonates and infants are attributable
to sepsis, with the majority of cases occurring in Asia
and sub-Saharan Africa [3]. There are between 77 to 240
new cases of sepsis per 100,000 population each year
[4,5] and the incidence may continue to increase by ap-
proximately 1.5% in every year, resulting in an addi-
tional 1 million cases per year by 2020 [4,6,7]. As sepsis
is the final common pathway in most of the pediatric
diseases and presence of sepsis in children with diarrhea
is often associated with high case-fatality [8], sepsis may
be considered the number one killer of children world-
wide [9]. Thus, clinicians as well as health workers in
resource limited settings should have understanding on
simple associated factors that may predict fatal outcome
*Corresponding and senior author.
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Predictors of Death in Under-Five Children with Sepsis Attending an Urban Diarrheal Treatment Centre in Bangladesh
710
in diarrheal children with sepsis. However, data are very
limited on the predicting factors of death in such popula-
tion.
In the Dhaka Hospital of icddr,b, a number of children
used to be admitted on a daily basis with diarrheal dis-
eases along with other co-morbidities such as severe
acute malnutrition, severe and very severe pneumonia,
with the consequence of sepsis, and often with fatal out-
come. The aim of our study was to identify the factors
that predict deaths in under-five children with sepsis ad-
mitted to urban diarrheal treatment centre.
2. Materials and Methods
2.1. Patient Enrollment
All the diarrheal children of either sex, aged 0 - 59
months, with clinical sepsis who required admission and
care to the Special Care Ward (SCW) of the Dhaka Hos-
pital of icddr,b from September, 2007 to December, 2007
were enrolled in this study. The hospital provides care
and treatment to around 110,000 patients of all ages each
year. The majority of the patients is residents of Dhaka
city or its suburbs and come from poor socio-economic
backgrounds. Nearly all patients attend the hospital with
diarrheal diseases, whether associated with complications
or other associated health problems. On arrival to the
hospital triage, nurses obtain the medical history and
perform a rapid assessment of the patients, focusing on
the nature and severity of diarrhea, including the magni-
tude of dehydration and any complications. Features of
any other health problems are also sought at presentation.
Following triage, patients are also examined and assess
by the attending physician for consultation or admission
for an appropriate ward of the hospital. Patients with
severe illnesses, including those with altered mental status,
convulsions, severe or very severe pneumonia, hypoxe-
mia, cyanosis and suspected sepsis, are admitted directly
to the SCW. On admission at SCW the attending physi-
cian again perform a thorough assessment of the patients,
organize any investigation necessary and determine the
management plan including drug and other supportive
therapies. Our study patients were admitted to SCW
having diarrhea and sepsis with or without other associ-
ated problems such as electrolytes imbalance, severe
acute malnutrition, features of severe/very severe pneu-
monia and hypoxemia.
2.2. Study Design
In this prospective cohort study, comparison of the clini-
cal and laboratory features of under-five diarrheal chil-
dren with sepsis was made who had and who did not
have fatal outcome. Consent was obtained from respec-
tive parents or the attending family members before chil-
dren were enrolled in the study and relevant clinical in-
formation were collected. Clinical management of all
children for the sepsis was done according to the stan-
dard management guidelines of the hospital based on the
surviving sepsis guideline [10]. These include manage-
ment by restoration of circulation, respiration, mainte-
nance of temperature and blood glucose level, appropri-
ate antimicrobial therapy to cover the possible causative
organism, appropriate feeding; and provision of micro-
nutrients, viatamins and minerals as required. The hospi-
tal follows the protocolized guidelines for the manage-
ment of children with severe protein-energy malnutrition
[11,12].
2.3. Recognizing the Septic Patient
2.3.1. Definition
Sepsis
Sepsis is defined as presence of inflammation [abnormal
WBC count (>11 × 109/L or, <4 × 109/L or, band and neu-
trophil ratio 0.10) plus presence or presumed presence
of infection with thermo-instability [hypothermia (
35.0˚C) or hyperthermia (38.5˚C)], tachycardia, tachyp-
nea, and/or the indications of altered organ function (al-
tered mental status and bounding pulse) in the absence of
clinical dehydration or after correction of dehydration [1].
2.3.2. Statistica l Methods
We used pretested case report forms (CRF) for data ac-
quisition. All CRFs were manually verified for com-
pleteness and errors, edited where necessary, and then
data entered onto a personal computer (PC). Data were
entered and analyzed using SPSS for Windows (version
17.0; SPSS Inc, Chicago, IL, USA) and Epi Info (version
6.0; USD, Stone Mountain, GA, USA). The differences
in proportions were compared by the chi-square test and
differences of means by Student’s t-test or Mann-Whit-
ney test, as appropriate. A probability of <0.05 was con-
sidered statistically significant.
Strength of association was determined by estimating
the odds ratio (OR) and the 95% confidence intervals
(CI). Univariate analysis and logistic regression were
both performed in identifying risk factors. The analyses
of socio-demographic data included age, sex, gestational
age, residence (in Dhaka or not), maternal and paternal
education, mothers’ occupation, breastfeeding status, not
use high-potency vitamin A capsule within 6 months
prior to admission, and use of antibiotics before admis-
sion. The analyses of clinical data included presence or
absence of dehydration, cyanosis, hypoxemia, fever, hy-
pothermia, severe malnutrition and requirement of IV
fluid after admission. The laboratory data analyses in-
cluded total peripheral white blood cell (WBC) count,
presence of immature neutrophils in blood such as band,
Copyright © 2013 SciRes. FNS
Predictors of Death in Under-Five Children with Sepsis Attending an Urban Diarrheal Treatment Centre in Bangladesh
Copyright © 2013 SciRes. FNS
711
serum electrolytes, blood glucose, radiological pneumo-
nia. Initially, univariate analyses of these factors were
performed to evaluate their association with fatal out-
come, and then logistic regression analysis was per-
formed to identify the independent predictors of death
where death was the dependent variable and the factors
that were significantly associated with deaths in the uni-
variate analysis acted as independent variables.
3. Results
Among the 151 under-five diarrheal children with sepsis
admitted to the SCW of the Dhaka hospital of icddr,b 23
(15%) had fatal outcome. In univariate analyses, children
who died more often had hypoxemia, severe under-nu-
trition, higher total leucocyte count, and lobar consolida-
tion compared to those who survived (Tables 1 and 2).
Proportionately higher children with fatal outcome pre-
sented with edematous malnutrition and immature poly
on admission compared to those who survived, but it was
not statistically significant (Tables 1 and 2). In logistic
regression analysis, after adjusting for potential con-
founders such as use of I/V fluid after admission and
total WBC count, severe under nutrition, hypoxemia,
lobar consolidation and hypernatremia were remained as
independent predictors of death in sepsis (Table 3).
Other parameters in Tables 1 and 2 were comparable
among the groups.
Table 1. Clinical characteristics of the under-five children with clinical sepsis who died (cases) and survived (controls).
Variables Deaths (n = 23) Survivors (n = 128) OR 95% CI p
Male gender 13 (57) 75 (59) 0.92 0.34 - 2.46 0.865
Age in months (Median, IQR) 1.5 (0.8, 10.0) 4.0 (2.0, 12.0) - - 0.703
Gestational age (weeks) (mean ± standard deviation) 38.0 ± 2.9 38.0 ± 3.7 - - 0.974
Not use of capsule vitamin-A within last 6 months 11 (50) 72 (56) 0.78 0.29 - 2.10 0.755
History of measles within last 6 months 2 (9) 20 (16) 0.52 0.08 - 2.59 0.530
Use of antibiotic before admission 13 (59) 52 (43) 1.92 0.70 - 5.32 0.245
Clinical dehydration (some/severe) 15 (65) 68 (53) 1.65 0.60 - 4.62 0.398
Cyanosis 4 (17) 14 (11) 1.71 0.42 - 6.4 0.481
Fever (38˚C) 19 (83) 111 (87) 0.73 0.20 - 2.88 0.530
Hypothermia on or after admission (Temp 35˚C) 2 (9) 5 (4) 2.34 0.29 - 15.08 0.289
Hypoxaemia (SpO2 < 90%) 19 (83) 52 (41) 6.94 2.06 - 25.73 <0.001
Oedematous malnutrition 5 (22) 10 (8) 3.28 0.86 - 12.16 0.055
HAZ (< 3 z score) 10 (44) 38 (30) 1.82 0.67 - 4.93 0.287
WAZ (< 3 z score) 16 (70) 48 (38) 3.81 1.35 - 11.10 0.008
WHZ (< 3 z score) 6 (26) 35 (27) 0.94 0.30 - 2.80 0.897
User of IV fluid 17 (74) 75 (59) 2.00 0.68 - 6.13 0.248
Figures represent n (%), unless specified. OR: odds ratio; CI: confidence interval; IQR: inter-quartile range; HAZ: height for age z score; WAZ: weight for age
z score; WHZ: weight for height z score; SpO2 = transcutaneously measured blood oxygen concentration.
Table 2. Laboratory characteristics of the under-five children with clinical sepsis who died (cases) and survived (controls).
Variables Cases (n = 23) Controls (n = 128) p
Total WBC count (number/cu. mm)
(Median, IQR) 11,000 (8900, 25,350) 14,500 (9300, 20,000) 0.046
Immature Poly (number/cu. mm) (Median, IQR) 00 (00, 1.00) 00 (00, 00) 0.087
Hyponatraemia (mmol/L) 5 (22) 33 (26) 0.880
0.80 (0.24 - 2.54)*
Hypernatraemia (mmol/L) 5 (22) 11 (9) 0.072
2.95 (0.78 - 10.74)*
Hypokalaemia (mmol/L) 8 (35) 34 (27) 0.577
1.47 (0.52 - 4.13)*
Hyperkalaemia (mmol/L) 3 (13) 9 (7) 0.395
1.98 (0.39 - 9.05)*
Lobar consolidation 9 (56) 6 (7) <0.001
16.93 (3.99 - 76.96)*
Hypoglycemia (RBS < 3 mmol/L) 3 (13) 17 (14) 1.00
0.96 (0.20 - 3.96)*
Growth on blood culture 1/15 (7) 12/111 (11) 1.00
0.57 (0.03 - 4.86)*
Figures represent n (%), unless specified. IQR: interquartile range; *OR (95% CI); RBS: Random blood sugar.
Predictors of Death in Under-Five Children with Sepsis Attending an Urban Diarrheal Treatment Centre in Bangladesh
712
Table 3. Results of logistic regression to explore the indepe nde nt pr e dic tor s of death in under-five childre n with sepsis.
Characteristics OR 95% CI p
Severe under nutrition 7.57 1.24 - 46.11 0.028
Hypoxemia 14.78 1.38 - 157.90 0.026
Lobar consolidation 19.9 2.99 - 132.80 0.002
Hypernatraemia 16.48 2.21 - 123.12 0.006
Total WBC count 1.00 1.00 - 1.00 0.156
User of IV fluid after admission 0.54 0.09 - 3.08 0.484
4. Discussion
Our finding of the association of severe malnutrition,
lobar pneumonia and hypoxemia as predictors of death in
SCW is similar to earlier reports [13,14]. Severely mal-
nourished children have depressed cell mediated as well
as humoral immune responses, and they are more sus-
ceptible to infection often with serious ramification such
as fatal outcome [15].
We observed that lobar consolidation in septic children
was one of the predictors of death. Lobar consolidation is
usually associated with bacterial pneumonia which is
often associated with fatal outcome especially in children
under five in developing countries like Bangladesh [13],
mostly due to overwhelming hypoxemia resulting from
ventilation perfusion mismatch from para-pneumonic
shunting. [14,16,17]. Sepsis may be the consequences of
lobar pneumonia, as observed in our cases, frequently
associated with high case-fatality rate [14].
Our observation of hypernatraemia as a predictor of
death is also understandable. Hypernatraemic dehydra-
tion is usually associated with high case fatality either
because of intracranial hemorrhage resulting from intra-
cellular dehydration or because of cerebral oedema as a
result of aggressive correction [18]. The observation of
high case fatality in children with hypernatraemia has
been reported earlier from Bangladesh [19]. The man-
agement of hypernatremic dehydration in diarrheal chil-
dren remains a challenge, and more works need to be
carried out into the treatment of this condition.
We observed that a higher proportion of children with
fatal outcome had a leucocytosis and immature neutro-
phils. Increased number of immature neutrophils in the
peripheral blood smears of children is an expression of
severe illness common in bacterial sepsis [1]. An earlier
study from Bangladesh reported that children with leu-
kocytosis and immature neutrophils in their peripheral
blood are more likely to be bacteremic and to have a
higher risk of death [1]. Thus, the presence of immature
neutrophils in peripheral blood in diarrheal children
should alert clinicians to look for sepsis in order to re-
duce morbidity and deaths in such population.
The number of children with fatal outcome in our
study was much smaller compared with the control chil-
dren. This might have reduced the power to identify fac-
tors that could actually have an independent association
with fatal outcome. Further studies using adequate num-
ber of cases could provide better insight.
In conclusion, our data suggest that under-five diar-
rheal children with clinical sepsis admitted to a special
care ward of a resource-limited setting in a developing
country, who present with severe malnutrition, hyperna-
traemia, lobar pneumonia and hypoxaemia are more
likely to have a fatal outcome. Thus, efforts should be
taken to specifically look for the presence of these fea-
tures in all hospitalized diarrheal children with clinical
sepsis to identify those with higher risk of death for the
institution of energetic and efficient antimicrobial and
other supportive therapy with the prospect of achieving a
better outcome.
5. Acknowledgements
We gratefully acknowledge the donors for their support
and commitment to icddr,b’s research efforts which cur-
rently provide unrestricted support to the centre’s re-
search efforts: Government of the People’s Republic of
Bangladesh, Canadian International Development Agency
(CIDA), Embassy of the Kingdom of the Netherlands
(EKN), Swedish International Development Cooperation
Agency (Sida) and the Department for International De-
velopment, UK (DFID). We offer our sincere gratitude to
all physicians including clinical fellows, nurses, mem-
bers of the feeding team and cleaners of SCW for their
invaluable contribution during patient enrollment and
data collection.
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Predictors of Death in Under-Five Children with Sepsis Attending an Urban Diarrheal Treatment Centre in Bangladesh
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Elaborati on o f Abbre vi a ti o ns:
CI: Confidence interval
CIDA: Canadian International Development Agency
CRF: Case report form
EKN: Embassy of the Kingdom of the Netherlands
HAZ: Height for age z score
IQR: Inter-quartile range
IV: Intra-venous
mmol/L: Milimol/Liter
OR: Odds ratio
RBS: Random blood sugar
SCW: Special care ward
Sida: Swedish International Development Cooperation
Agency
SpO2: Transcutaneously measured blood oxygen con-
centration
DFID: Department for International Development
WAZ: Weight for age z score
WBC: White blood count
WHZ: Weight for height/length z score
Copyright © 2013 SciRes. FNS