Predictors of Death in Under-Five Children with Sepsis Attending an Urban Diarrheal Treatment Centre in Bangladesh

doi:10.4236/fns.2013.47090

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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: *[email protected]

Received May 10th, 2013; revised June 10th, 2013; accepted June 18th, 2013

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.

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,

Predictors of Death in Under-Five Children with Sepsis Attending an Urban Diarrheal Treatment Centre in Bangladesh

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