1

EVALUATION OF BLOOD GLUCOSE LEVELS IN UNDER-

FIVES PRESENTING AT THE EMERGENCY PAEDIATRIC

UNIT OF FEDERAL MEDICAL CENTRE, OWERRI.

DISSERTATION SUBMITTED TO THE NATIONAL POST

GRADUATE MEDICAL COLLEGE OF NIGERIA, IN PART

FULFILMENT OF THE REQUIREMENT FOR THE AWARD OF

FELLOWSHIP OF THE COLLEGE IN PAEDIATRICS

BY

DR OSUJI, AUGUSTINE EMEKA

MBBS 2008 (ABSU)

MAY 2017

2

DECLARATION

It is hereby declared that this work is original unless otherwise acknowledged. It has not been

presented to any other College for a Fellowship, nor has it been submitted elsewhere for

publication. There is no conflict of interest as study was completely self-sponsored and all

equipment and materials were purchased from the open market.

DR OSUJI A.E.

3

CERTIFICATION

The study reported in this dissertation was done by Dr Osuji Augustine Emeka of the

Department of Paediatrics, Federal Medical Centre Owerri under our supervision. We have also

supervised the writing of the dissertation.

………………………………………………………………………………………

Dr. F.U. IREGBU

Consultant Paediatrician

Federal Medical Centre (FMC)

Owerri.

………………………………………………………………………………………….

PROFESSOR O.F. NJOKANMA

Consultant Paediatrcian

Lagos State University Teaching Hospital (LASUTH),

Lagos.

4

TABLE OF CONTENTS

PAGE

Declaration i

Certification ii

Table of contents iii

Dedication v

Acknowledgement vi

List of Abbreviations vii

List of figures viii

List of tables ix

Definition of terms x

Summary xi

Introduction 1

Justification 3

Research questions 5

Literature Review 6

Aim and Objectives 28

Patients and Methods 29

Results 43

Discussion 57

Conclusion 63

Recommendations 64

Limitation 65

Lines of Future Research 66

5

References 67

Appendices 78

6

DEDICATION

This work is dedicated to my beloved Aunty, late Mrs. Echefu Emilia, whose contribution to my

life is immeasurable.

7

ACKNOWLEDGEMENTS

My immense gratitude goes to my supervisors, Professor O.F. Njokanma and Dr. F.U. Iregbu

for their patience and availability throughout the study period. I owe gratitude to the entire

members of Paediatrics Department of Federal Medical Centre (FMC) Owerri. I thank all the

consultants especially Dr E.C. Nwolisa and Dr Nathan Nwokeforo for their mentorship.

I want to thank the registrars and house officers in the emergency room as well as the research

assistants who helped me with sample collection when I was not on call. My thanks also go to

the laboratory scientist Mr. Ezekwesili Cletus who assisted me in laboratory analysis. I also want

to thank Dr Benedict Nwogoh, Dr Ifeoma Ejelonu and Dr Franklin Emerenini for their assistance

in data analysis. Finally, I want to thank the parents/caregivers and the children who participated

in the study.

THANK YOU ALL

8

LIST OF ABBREVIATIONS

AIDS Acquired Immune Deficiency Syndrome

DFLM Duration From Last Meal

DOI Duration Of Illness

EPU Emergency Paediatric Unit

FMC Federal Medical Centre

GCBG Glucometer Capillary Blood Glucose

GVBG Glucometer Venous Blood Glucose

HIV Human Immunodeficiency Virus

IMCI Integrated Management of Childhood Illnesses

IMSUTH Imo State University Teaching Hospital

LabBG Laboratory Blood Glucose

NPV Negative Predictive Value

NADP Nicotinamide Adenine Dinucleotide

OSUTH Osun State University Teaching Hospital

PPV Positive Predictive Value

PEM Protein Energy Malnutrition

SD Standard Deviation

SPSS Statistical Package for Social Sciences

TCA Tricarboxylic Acid cycle

UBTH University of Benin Teaching Hospital

UCTH University of Calabar Teaching Hospital

UPTH University of Port Harcourt Teaching Hospital

χ2 chi Square

9

LIST OF FIGURES

Figures Page

1. A Ring Chain form of D-glucose 7

2. Metabolic Pathways involved in glucose metabolism 9

3. A pathway showing the hormonal control of glucose 12

10

LIST OF TABLES

Table Page

I Gender and Socioeconomic Status of subjects 44

II Frequency of occurrence of clinical diagnosis in the children studied 45

III Mean, median and Ranges of Random Blood glucose 46

IV Comparison of mean blood glucose from One-Touch Glucometer

And laboratory analysis 47

V Correlation among, GCBG, GVBG and LabBG 48

VI Correlations between Blood Glucose estimation and Duration of illness and

Duration from last meal 49

VII False negative, true negative, false positive and true positive readings

by the glucometer for hypoglycaemic patients 51

VIII Sensitivity, Specificity and predictive values of GCBG and GVBG

using glucometer to laboratory method 52

IX Risk factors for hypoglycaemia 54

X Association between Patient Clinical Features and Treatment Outcome 55

XI Association between specific diagnosis and Hypoglycaemia 56

11

DEFINITION OF TERMS

Hypoglycaemia: This is currently defined as plasma glucose value less than 2.6mmol/L

(47mg/dl).3,4

Gastroenteritis: This is as the inflammation of the gastrointestinal

tracthttps://en.wikipedia.org/wiki/Human_gastrointestinal_tract that involves the stomach and small

intestines.110:

Sepsis: This is defined as proven infection or a conglomeration of clinical symptoms/signs and

laboratory findings associated with high probability of infection. Such findings include fever,

hypothermia, tachycardia, tachypnea, localized inflammatory signs, leukocytosis, leukopaenia

and high band neutrophil count.111

Severe sepsis: sepsis plus one of the following:

1. Cardiovascular organ dysfunction.

2. Acute respiratory distress syndrome.

OR sepsis plus two or more organ dysfunctions (respiratory, renal, haematologic or hepatic)

Septic shock: Sepsis plus cardiovascular organ dysfunction.111

12

SUMMARY

Hypoglycaemia is known to complicate many childhood illnesses. It also contributes

significantly to morbidity and mortality. Early diagnosis and treatment are necessary to avoid the

complications.

This study sought to evaluate the prevalence, clinical diagnoses and risk factors associated with

hypoglycaemia at the point of admission into the Emergency Paediatric Unit (EPU) of Federal

Medical Centre (FMC) Owerri. Blood glucose levels obtained with glucometer were compared

to standard laboratory values. Also compared were values obtained from venous blood with

those of capillary blood using the One-Touch Ultra 2® glucometer.

Four hundred children aged one to 59 months admitted consecutively into the EPU of FMC

participated in the study. Blood glucose was analyzed using the glucometer and standard

laboratory techniques. Glucometer analysis for each patient was done using samples from venous

blood as well as from capillary blood. Hypoglycaemia was defined as blood glucose <2.6mmol/L

(47mg/dl).

The subjects included 232 (58%) males and 168 (42%) females with a mean age of 16.9 ± 15.1

months and a median of 12 months. The mean (range) of blood glucose using the glucose

oxidase method was 106 ±53.3 mg/dl (20mg/dl to 461mg/dl). The mean blood glucose using the

13

venous and capillary blood were 110.5 ± 55.7 and 112.5 ± 56.9 respectively. Using the values

from laboratory method, 30 (7.5%) patients were hypoglycaemic. Twenty six (6.5%) patients

were hypoglycaemic by capillary blood and 28 (7.0%) using venous blood. There was a

significant positive correlation between capillary blood glucose and venous blood glucose

estimations (r=0.981, p < 0.001). Similarly, there were significant positive correlations between

capillary and laboratory readings (r = 0.906, p < 0.001) and also between venous and laboratory

readings (r = 0.925, p < 0.001). The sensitivity of capillary and venous blood glucose

measurements relative to the laboratory method was 86.7% and 93.3% respectively. Both

capillary and venous readings had 100% specificity and high positive predictive values for

detecting hypoglycaemia. Protein energy malnutrition, sepsis, gastroenteritis, meningitis and

malaria were the predominant diagnoses associated with hypoglycaemia. Significant risk factors

associated with hypoglycaemia include age < 12 months (χ2 =5.05, p = 0.025) and low

socioeconomic status (χ2 = 9.279, p = 0.002). Hypoglycaemia was significantly associated with

increased mortality (χ2 = 18.488; p < 0.001).

The prevalence of hypoglycaemia in the emergency room dictates the maintenance of a high

index of suspicion, moreso in younger children and those from low socioeconomic classes.

Patients presenting with protein energy malnutrition, suspected sepsis, gastroenteritis, meningitis

or malaria should also receive extra attention. The point of care tool (glucometer) used in the

study produced sufficiently high sensitivity, specificity, positive predictive and negative

predictive values to merit its recommendation for routine use.

14

INTRODUCTION

Glucose is the primary fuel for cellular metabolism.1 Adequate supplies are therefore necessary

to maintain health.2 Hypoglycaemia implies low blood glucose levels and is currently defined as

plasma glucose value less than 2.6mmol/L (47mg/dl).3,4 It is a manifestation of an underlying

abnormality, which is usually related to poor availability, or excessive utilization of glucose in

the body.1 The prevalence of hypoglycaemia in children admitted to the hospital after the

neonatal period ranges between 3.2% to 7.3% in developing countries.5-8

Risk factors for hypoglycaemia include food restriction as usually seen in patients with

diarrhoea because mothers erroneously fear that diarrhoea may worsen with feeding.7 Long

intervals between feeds of up to twelve hours, severe illnesses and age less than five years are

also risk factors.5-7 Diseases like malaria, septicaemia, malnutrition, meningitis and diarrhoea in

developing countries have been associated with hypoglycaemia in childhood.5-7,9,10 In

Southwestern Nigeria, the use of cow’s urine concoction in convulsing patients has been

associated with hypoglycaemia.11

Hypoglycaemia is usually asymptomatic, but symptoms like sweating, jitteriness, anxiety,

nervousness, headache, visual impairment, lethargy, restlessness, mental confusion and

convulsion may occur.12 Long term neurological sequelae like mental retardation, cognitive

dysfunction, recurrent seizures and varying degrees of personality disorders may result from

hypoglycaemia.13-15 The incidences of these sequelae range from 15% to 51%.16 It has been

documented that the mortality associated with hypoglycaemia in hospitalized patients is between

15

20% and 30% in treated patients with hypoglycaemia and up to 100% in untreated

hypoglycaemic patients.5,7 Reliance on symptoms to make a diagnosis may therefore result in

missed diagnosis since symptoms do not usually occur. In order to avoid missed diagnosis and

attendant consequences, deliberate efforts must be made to detect the presence of hypoglycaemia

in acutely ill children presenting to emergency units.17,18

Blood glucose can be estimated in the laboratory using the glucose oxidase method, estimated

with a glucometer using venous or capillary blood. Laboratory analysis of blood glucose is the

gold standard but its use is restricted by poor electricity and water supply obtainable in low-

income economies like Nigeria because laboratory estimation of blood glucose requires constant

electricity and water supply which are not readily available in most health facilities. On the other

hand, point-of-care glucometers provide instant results without the need for electricity supply

and water for washing equipment. Glucometers utilize venous or capillary blood thus providing

options for the clinician.

The prevalence of hypoglycaemia in children aged 1-59 months in Owerri is not known and it is

equally uncertain the clinical conditions associated with hypoglycaemia in these children. It may

be useful to compare blood glucose values obtained by the glucose oxidase method and those

derived through the use of glucometers.

The purpose of the study is to determine the prevalence of and clinical conditions associated

with hypoglycaemia in children aged one to 59 months admitted to the Emergency Paediatric

Unit of Federal Medical Centre Owerri and to compare results from laboratory analysis with

those obtained using point-of-care glucometers.

16

JUSTIFICATION

Hypoglycaemia is common in ill children presenting to emergency units with illnesses like

severe malaria, sepsis, and severe bronchopneumonia.5,19 However, many affected children do

not manifest with symptoms referable to hypoglycaemia and as such, the diagnosis may be

missed.19,20 The presence of hypoglycaemia complicates these illnesses with significant negative

outcome of morbidity or mortality.5,13,15

Estimation of blood glucose is thus an important part of the evaluation of sick children

presenting in the emergency room. This can be done by laboratory analysis21,22 or by using point-

of-care (bedside) glucometers.23-25 The need for urgent and prompt intervention in cases of

hypoglycaemia favours the use of glucometers because of the ease with which results are

obtained. The advantages of rapidity increase when there is a need for repeated analysis. Added

to this, is the non-reliance on manpower and electricity supply. Thus prompt determination as

facilitated by bedside test, improves the chances of early intervention and hence improved

outcome.22

The yearly admission rate into the Emergency Paediatric Unit of Federal Medical Centre Owerri

is about two thousand four hundred and eighty. The prevalence of hypoglycaemia in hospitalized

children in Africa ranges between 3.2% and 7.3%7,8 while in Nigeria, the prevalence is about

6.4%. The prevalence of hypoglycaemia could as well be high in the Emergency Paediatric Unit

of Federal Medical Centre Owerri. This study was designed to find out the exact prevalence in

the centre.

17

Despite the stated advantages, laboratory determination of blood glucose remains the gold

standard for determination of blood glucose. It may be important to assess the performances of

other methods like the glucometers against the standard laboratory method. Also, it may be

important to evaluate the concordance of results obtained using venous and capillary blood.

18

RESEARCH QUESTIONS

1. What is the prevalence of hypoglycaemia in children aged one to 59 months admitted

into the Emergency Paediatric Unit of Federal Medical Centre Owerri?

2. What are the clinical diagnoses commonly associated with hypoglycaemia?

3. What are the probable risk factors associated with hypoglycaemia?

4. Is there any comparison between plasma glucose values obtained with use of glucometer

and standard laboratory measurements using glucose oxidase method?

5. Is there any comparison between glucose values obtained using venous blood and those

from capillary blood using glucometer?

19

LITERATURE REVIEW

BACKGROUND

Glucose is the major free sugar circulating in the blood of higher animals.26 It is the preferred

fuel of the brain. Glucose is a monosaccharide with the chemical formula C6H12O6. It is found in

the nervous system, as well as red blood cells (erythrocytes).26

As a universal substrate (a molecule upon which an enzyme acts) for the production of cellular

energy, glucose is of central importance in the metabolism of all life forms. It is one of the main

products of photosynthesis, the process by which photoautotrophs such as plants and algae

convert energy from sunlight into potential chemical energy to be used by the cell. Glucose is

also a major starting point for cellular respiration, in which the chemical bonds of energy-rich

molecules are converted into energy usable for life processes.22,26

Glucose stands out as a striking example of the complex interplay between plants and animals:

the plant converts solar energy into glucose molecule, and then to more complex forms (starch or

cellulose) that is eaten by animals, which recover the original glucose units, deliver it to their

cells, and eventually use that stored solar energy for their own metabolism. Milk cows, for

example, graze on grass as a source of cellulose, which they break down to glucose using their

four-chambered stomachs. Some of that glucose then goes into the milk we drink.13,26

20

All major dietary carbohydrates contain glucose, either as their only building block, or in

combination with another monosaccharide, as in sucrose (“table sugar”) and lactose, the primary

sugar found in milk.13,22,26

As glucose is vital for the human body and for the brain, it is important to maintain constant

blood glucose levels.

Figure 1.

A ring chain form of D-glucose.22

21

GLUCOSE METABOLISM

The metabolism of the sugar glucose is one of the central metabolic processes in the body.26,27 It

serves to generate energy for the body, as well as provide starting materials for other metabolic

pathways (e.g., the production of nucleic acids, fatty acids, and neurotransmitters).27 In addition,

other metabolic pathways also feed into the reactions that occur during glucose metabolism,

further emphasizing the central roles that the reactions involved in glucose metabolism play in

ensuring the body's functioning and well-being.22,27,28

Glucose metabolism can proceed along several alternative pathways, depending on the body's

needs at the time. The following are three main sets of reactions associated with glucose

metabolism.28

Glycolysis, the citric acid cycle; and the pentose phosphate pathway

During glycolysis, glucose is converted in several reactions into a molecule called pyruvate,

which can be either metabolized further into lactate, that is then transported out of the cell, or

which stays in the cell. Pyruvate is converted (through the actions of the thiamine-dependent

enzyme pyruvate dehydrogenase) into a molecule called acetyl-CoA, which can then be fed into

the second set of reactions, the citric acid cycle (also known as the tricarboxylic acid [TCA]

cycle). Alternatively, acetyl-CoA may serve as a precursor for fatty acid synthesis.28

22

Figure 2

23

Metabolic pathways involved in glucose metabolism.28

In the subsequent citric acid cycle, the acetyl-CoA is linked to a compound called oxaloacetate to

form citric acid. The latter is then metabolized in a series of steps to form α-ketoglutarate, which

is then transformed further to yield oxaloacetate again so that the cycle can continue.28 These

24

reactions also involve a thiamine-dependent enzyme, α-ketoglutarate dehydrogenase. In addition,

the various reactions of the citric acid cycle yield several metabolites that either serve as

cofactors in other biochemical reactions or can be fed into other reactions yielding energy

required by the cell to function normally.22,26,28

The citric acid cycle plays a central role not only in carbohydrate metabolism but also in protein

and lipid metabolism, because both amino acids and fatty acids can be broken down into acetyl-

CoA that enters the citric acid cycle.22,26,28

The pentose phosphate pathway of glucose metabolism is an alternative pathway to glycolysis

and the citric acid cycle that serves to generate both a co-factor that is required by many

enzymatic reactions (reduced nicotinamide adenine dinucleotide phosphate [NADPH]) and sugar

molecules containing five carbons (rather than the six-carbon sugars, such as glucose), which are

needed, for example, for nucleic acid synthesis.26,28 The pentose phosphate pathway has two

distinct phases, an oxidative phase, during which the NADPH is generated (as well as sugar

called ribulose-5-phosphate), and a nonoxidative phase, during which the ribulose-5-phosphate is

converted further into other five-carbon sugars. The nonoxidative phase also can serve as a

“link” to glycolysis by generating fructose-6-phosphate and glyceraldehyde-3-phosphate. Several

reactions of the nonoxidative phase involve the thiamine-dependent enzyme transketolase.

The relative contributions of all these pathways to glucose metabolism depend on the body's

needs at the time.

BLOOD GLUCOSE HOMEOSTASIS

Glucose is the transport carbohydrate in animals, and its concentration in the blood affects every

cell in the body.29 Its concentration is therefore strictly controlled within the range 80-100mg/dl

25

of blood, and very low levels (hypoglycaemia) or very high levels (hyperglycaemia) are both

serious and can lead to complications.30,31

Blood glucose concentration is controlled by the pancreas. The pancreas has glucose receptor

cells which monitor the concentration of glucose in the blood, as well as endocrine cells (called

the Islets of Langerhans) which secrete hormones.31 The α-cells secrete the hormone glucagon,

while the β-cells secrete the hormone insulin. These two hormones are antagonistic, and have

opposite effects on blood glucose.29

• insulin stimulates the uptake of glucose by cells for respiration, and in the liver it stimulates

the conversion of glucose to glycogen (glycogenesis) for storage in the liver and muscles

for future use. This ultimately decreases blood glucose.

• glucagon stimulates the breakdown of glycogen to glucose in the liver (glycogenolysis),

and in extreme cases it can also stimulate the synthesis of glucose from pyruvate

therefore increasing blood glucose.

Figure 3

26

A pathway showing the hormonal control of glucose22

DEFINITION OF HYPOGLYCAEMIA

27

Glucose is the principal substrate for cerebral metabolism.32 It is the most important carbohydrate

for human energy needs with the bulk of carbohydrate being absorbed and used in this form.33

Hypoglycaemia is the most common metabolic problem in critically ill children.34-36

Hypoglycaemia means blood glucose level below normal. There has been a lot of controversies

on the cut off for normal blood glucose level. Older definitions of hypoglycaemia were from

population-based studies that resulted in cut off levels of blood glucose of 20mg/dl and 30 mg/dl

for preterm and term infants respectively.37

Previous definitions factored in age of the patients whereby hypoglycaemia was defined as blood

glucose levels below 1.1mmol/l (20mg/dl) for infants with birth weight below 2,500grammes,

1.7mmol/l (30mg/dl) for normal birth weight infants in the first 72 hours and 2.2mmol/l

(40mg/dl) thereafter.38 Most studies on hypoglycaemia available in the literature are based on

these cut-off values.10,18,33,39 However, these definitions have been abandoned as a result of the

adverse consequences associated with blood sugar level below 2.2mmol/l(40mg/dl) in children

irrespective of weight or postnatal age. There is no evidence that lower postnatal weight confers

any special protection against the consequences of low blood sugar.40

Hypoglycaemia is currently defined as plasma blood glucose concentration below 2.6mmol/L

(47mg/dl) in any age group. This recently proposed definition of hypoglycaemia as a corrected

blood glucose value of less than 2.6mmol/l(47mg/dl )41,42 has become acceptable to several

workers.32,42,43

PREVALENCE OF HYPOGLYCAEMIA IN CHILDREN

28

The prevalence of hypoglycaemia clearly varies with definition chosen, the population studied,

method and timing of feeding and the type of glucose assay utilized44 as well as the pattern of

care. Studies show reduced incidence with increasing age.1,45 In the neonatal period, prevalence

ranges from 9.5 to 38%.22,46,47 Out of 304 neonates studied in the University of Port Harcourt

Teaching Hospital (UPTH)21 between January and May 2006, 86 (28%) were found to be

hypoglycaemic at birth. This gave a prevalence of 28.3%. This study was done in the labour

ward where cord blood specimen were taken from placental end of the cord at delivery and

assayed for plasma glucose. Hypoglycaemia was defined as cord blood glucose level below

2.2mmol/l(40mg/dl).20 A study in Ogun State University Teaching Hospital (OSUTH) Sagamu

in 1994 by Njokanma and Fagbule47 reported an incidence of 9.5% among 675 admitted

newborns. For the study, hypoglycaemia was defined as blood glucose level below 2.2mmol/l.

The OSUTH47 study reported a highest prevalence of 25.8% in babies of gestational age below

32weeks. This was similar to the findings in the Port Harcourt study21 which reported a

prevalence of 29.1% among preterm neonates and 27.9% in low birth weight babies. In an earlier

study at the University of Benin Teaching Hospital (UBTH), Benin City in 1977, Omene19 had

reported an incidence of 6.6% for neonatal hypoglycaemia, with an incidence of 7.9% in low

birth weight babies. This Benin study used an earlier definition of hypoglycaemia as blood sugar

level of 20mg/dl for preterm, 30mg/dl for term infants in the first 72 hours of life and 40mg/dl

thereafter according to Cornblath and Schwartz.3 The lower cut-off levels may account for the

lower incidence reported in the study by Omene.19

The prevalence of hypoglycaemia after the neonatal period was found to be 6.4% among 392

patients by Elusiyan et al5 in 2006. This study was carried out in Paediatric Emergency Ward of

Obafemi Awolowo University Teaching Hospital Ile-Ife. Hypoglycaemia was defined as plasma

29

glucose concentration below 2.5mmol/L. Malaria, septicaemia, pneumonia and protein energy

malnutrition were the leading diagnoses associated with hypoglycaemia in this study. In an

observational study done in Kenya by Osier et al7 in 2003, a prevalence of 7.3% was recorded in

3214 children beyond the neonatal period. Hypoglycaemia was defined as blood glucose

concentration below 2.2mmol/L and severe illness, malnutrition, last meal taken more than 12

hours before evaluation and positive malaria slide were independently associated with

hypoglycaemia. The large sample size and the fact that this study was done in a rural area might

have accounted for the higher prevalence compared to the study by Elusiyan et al.5 This is so

because children in the rural areas are more prone to malnutrition and more likely to present late

for care. The findings in the Ife study by Elusiyan et al5 are comparable to the study by Solomon

et al6 in Mozambique which observed a prevalence of 7.1% in 603 children. The leading cause of

hypoglycaemia in children was malaria. Hypoglycaemia was also found to complicate protein-

energy malnutrition, pneumonia, encephalitis, intestinal parasite infection and nephritic

syndrome.6

The prevalence of hypoglycaemia in specific disease conditions have been studied by some

authors. A study in children with diarrhoea by Bhattacharya et al48 in Calcutta, India done over a

two month period reported a prevalence of 40%. Only 10 out of 79 children that had acute

watery diarrhea were screened and 4 had hypoglycaemia. The small sample size might have

accounted for the high prevalence rate reported. The short duration of the study could also

account for the high prevalence. Onyiriuka et al49 at St Philomena Catholic Hospital, Benin City,

Nigeria reported a prevalence of 7.7% among 183 children aged one month to 59 months who

presented with acute diarrhoea. In 2012, Ntia et al50 in University of Calabar Teaching Hospital

(UCTH), Calabar reported a prevalence of 4% among 150 under-five children presenting with

30

acute watery diarrhoea. This difference in prevalence between the two studies could have been as

a result of the definition of hypoglycaemia used. The Benin study defined hypoglycaemia as

blood glucose levels below 2.6mg/dl in contrast to the Calabar study that used cut off level of

2.2mg/dl and this may explain why Onyiriuka et al49 in Benin reported a higher prevalence.

The prevalence of hypoglycaemia has also been studied in specific disease conditions like

malaria. In a prospective study done in Benin City by Onyiriuka et al51 in 2012, 92 out of 502

children below five years of age that had malaria (18%) were found to be hypoglycaemic. The

cut-off blood glucose level adopted was 2.6mmol/l (47mg/dl) at the point of admission. Out of

the 502 children in that study51, 23% (78 out of 339) were children below 36months compared to

8.6% (14 out of 163) children aged 36months and above. This prevalence value of 18% is

comparable to the 16% prevalence reported by English et al52 in Kenya in 1996 in children with

moderate to severe malaria. The prevalence found by Onyiriuka et al51 is equally comparable to

the value obtained in the study done by Nwosu et al33 among 107 children aged 8 months to 10

years with severe malaria in Lagos University Teaching Hospital in 2001. In this study, a

prevalence of 17% was reported. White et al39 in Gambia in 1983 reported a prevalence 32% in

47 children aged 18 months to eight years with severe chloroquine sensitive falciparum malaria.

The higher prevalence rate reported by White et al39 may be as a result of their small sample size

compared to sample sizes used by Onyiriuka et al49, English et al52 and Nwosu et al.33

RISK FACTORS ASSOCIATED WITH HYPOGLYCAEMIA

Hypoglycaemia is common in critically ill children and is associated with increased mortality

rates.53-55 Faustino et al54 concluded that hypoglycaemia may be a marker of severity of illness

following a finding that hypoglycaemia was associated with worsening organ function. Chisti et

31

al50 also noted that infants with evidence of serious illness like sclerema requiring admission

into the critical care unit in an urban diarrhoea hospital were at risk of having hypoglycaemia. In

another study, Chisti et al56 also reported that patients with enteric encephalopathy having fatal

outcome more often presented with hypoglycaemia.56 In developing countries, documented risk

factors include infectious diseases,5,10,57 last meal more than twelve hours before

presentation,5,7,10 use of herbal mixtures,23,57,58 poor nutritional status10,44,54 and conditions with

alteration of level of consciousness.5,10,23,57 Additional risk factors implicated in hypoglycaemia

in children are long duration of illness,5 and night admission to hospital.5 Oyedeji et al59-61

reported that socioeconomic status may contribute to hypoglycaemia by affecting the health

seeking behavior of the parents hence delaying presentation and prolonging the duration of

illness. Low socioeconomic status also affects child’s nutritional status and feeding thus

increasing the risk of hypoglycaemia.

PATHOPHYSIOLOGY OF HYPOGLYCAEMIA

There are several mechanisms by which hypoglycaemia occurs in different disease states. In

severe malnutrition, there is impaired glucose absorption and this correlates with oxidative stress

in sick children who need admission into the Paediatric critical care unit.62 Severely

malnourished children are prone to infections which may manifest with diarrhoea and

vomiting.63 They also have failure of gluconeogenesis64,65 which potentially may be responsible

for hypoglycaemia.

Malaria causes impaired hepatic gluconeogenesis even in the presence of adequate supply of

precursors like lactate and alanine.52,66,67 White el al66 reported increased levels of lactate and

alanine in hypoglycaemic children with severe malaria which suggested impairment of

32

gluconeogenesis. In Malawi in 1988, 95 children with severe malaria were studied by Taylor et

al67 and increased concentration of lactate, alanine and 5’nucleotidase were found in children

with hypoglycaemia. This observation agrees with the fact that impaired gluconeogenesis

contributes to the pathogenesis of hypoglycaemia in children with malaria.67 Accelerated tissue

metabolism,21 the metabolic requirements of parasites and malabsorption of glucose probably

due to changes in splanchnic blood flow due to heavy parasite load in the vessel also contribute

to hypoglycaemia.68,69 There is sequestration of parasitized red blood cells in the venules and the

capillaries of deep tissues which may reduce local circulation and may stimulate anaerobic

respiration which increases glucose consumption.70-72 Finally, reduced dietary intake, vomiting

and increased metabolic requirement caused by fever in malaria are other suggested

pathophysiologic mechanisms of hypoglycaemia in malaria.66

Filkins and Cornell73 reported that impaired gluconeogenesis was responsible for hypoglycaemia

in children with septicaemia. Endotoxins produced by organisms during an infection have been

reported to cause increased insulin production hence causing hypoglycaemia.18,73,74 Hypotension

in septic shock causes reduced tissue perfusion and a switch to anaerobic respiration which

results in increased glucose utilization.75 There is equally increased metabolism as a result of

fever during an infection; this causes an increased peripheral glucose utilization especially in

neonates with bacteremia.76,77

Children with diarrhoeal diseases are prone to hypoglycaemia because of reduced intake,

hypoxia, malnutrition, ketosis and impairment of gluconeogenesis.10,73 Certain drugs like

quinine4,78-80 and excessive use of salicylates (6g/day),81,82 ethanol12 have been associated with

hypoglycaemia. Three to five percent of children with alcohol intoxication will develop

hypoglycaemia.83 Alcohol exerts a substantial influence on pancreatic microcirculation by

33

evoking massive redistribution of pancreatic blood flow from exocrine pancreas into the

endocrine (insulin producing part) through a mechanism mediated by messenger molecule nitric

oxide and the vagus nerve, augmenting late phase insulin secretion and thereby evoking

hypoglycaemia. Oral hypoglycaemic agents as well as insulin overdose can also cause

hypoglycaemia.84,85 Cow urine concoction widely used in western part of Nigeria with the belief

that it cures convulsion has been associated with severe hypoglycaemia.58,86,87

CLINICAL FEATURES OF HYPOGLYCAEMIA

Hypoglycaemia may be symptomatic or asymptomatic. In asymptomatic hypoglycaemia, there

are no clinical symptoms while in symptomatic ones, symptoms resolve with increased blood

glucose concentration.21,41,43 Clinical features can result from a combination of adrenergic

stimulation or from decreased availability of glucose for the central nervous system.3 Unlike

older children, infants are not able to talk hence they stand at higher risk of hypoglycaemia.88

The older children are able to complain of symptoms like headache, blurring of vision, diplopia,

hence hypoglycaemia can be suspected. The features that are as a result of the activation of the

autonomic nervous system are anxiety, tremulousness, diaphoresis, tachycardia, pallor, hunger,

nausea and vomiting.89 The symptoms that result from neuroglycopenia include headache,

mental confusion, delirium, lethargy, irritability, staring, behavioral changes, difficulty

concentrating, visual disturbances (decreased acuity, diplopia), dysarthria, seizures, ataxia,

somnolence, stroke (hemiplegia, aphasia), coma, paresthesia, dizziness, amnesia, decerebrate or

decorticate posturing.89 Other non specific symptoms include dry mouth, poor coordination,

impatience, nightmares, palpitation, numbness in the mouth and tongue, mouth tingling and

blurred vision.89 Hypoglycaemia is also associated with increased risk of death. This was

supported by a study carried out in Melbourne in Australia by Moritoki et al90 which reported

34

36.6% mortality in children who had hypoglycaemia on admission as against 19.7% in non

hypoglycaemic children. Onyiriuka et al49 in Benin and Ntia et al44 in Calabar reported that

children with hypoglycaemia are at a significantly greater risk of death.

BLOOD GLUCOSE ESTIMATION

Glucose supply to the cells depends on extracellular (plasma) concentrations. It is more

preferable to measure plasma glucose level than that of the whole blood. The whole blood

glucose level is a function of haematocrit.91-93 This is because although glucose is freely

diffusible between plasma and erythrocytes and is in the same concentration in erythrocyte

water, there is a difference between the water content of erythrocytes and plasma; about

72g/100ml in erythrocytes and 94g/100ml in plasma.

Plasma glucose is about 15% higher than whole blood glucose and even more when haematocrit

is higher.88 Arterial and capillary blood sample may overestimate plasma glucose concentration

by 10%.3 Capillary blood samples when used for glucose monitoring usually fall between those

of venous whole blood and venous plasma.91 Capillary samples from cold heel may lead to

underestimation of venous blood glucose level because of stasis. There is as much as a decline in

glucose level by 18mg/dl after one hour of sample collection at room temperature as a result of

ongoing glycolysis.91 This is usually prevented by putting sample into a fluoride oxalate

container to halt glycolysis.

The gold standard technique in the determination of blood glucose level is laboratory analysis

using the glucose oxidase methods.22 Glucose oxidase catalyses the oxidation of glucose to

produce glucuronic acid and hydrogen peroxide.92 The concentration of hydrogen peroxide

produced is measured using a peroxide step coupled to a coloured oxygen acceptor or

35

electrode.94 These reactions are the basis for both reagent strip and bench top glucose electrode

method. This method is specific for glucose and hence results are reliable.92,93

Another method of plasma glucose estimation is the Hexokinase method. The phosphorylation of

glucose by ATP is catalysed by the Hexokinase enzyme. The NADPH/H produced from the

reduction of Glucose-6 phosphate by glucose dehydrogenase is then measured by a

spectrophotometric indicator system. Results obtained by this method are reliable since the

reactions are specific to glucose.43,94

The reductiometric method is based on the reducing property of glucose. This method is

susceptible to positive errors caused by other non glucose-reducing substances in blood. These

non glucose reducing substances include glutathione, creatinine, uric acid, ascorbic acid, some

amino acids and glucuronic acid.93 This method is no longer used in clinical practice since the

enzymatic methods give more reliable results.

The requirements for ideal method for measurement of blood glucose concentrations are

accuracy, precision and rapid analysis of small samples. The method must be as simple as

possible for medical and nursing personnel to carry out without extensive training in laboratory

skills.43 The type of sample used influences the result depending on the type of analysis used.93

Capillary sample is not reliable if peripheral blood flow is reduced.43 Sample must always be

free-flowing because squeezing the extremity causes haemolysis which interferes with the assay

unless deproteinization is performed.

Some substances in the blood can interfere with the enzymatic method and alter the result. A

process called deproteinization is usually performed to remove these substances.43,93,94 When the

methods are applied directly to serum or plasma, the problem of inhibitors is still present.93,94,96

36

Negative errors are caused by ascorbic acid concentrations greater than 5mg/dl and haemolysis.

Uric acid causes negative error of about 1mg/dl for each mg of uric acid/dl.91,93,94

The alcohol used in skin preparation before obtaining sample can contaminate the sample giving

erroneously higher value.94-96 Glucometers are prone to errors that may lead to underestimation

of hypoglycaemia.3,43

Reflectance meters (glucometers) used in the past gave values of blood glucose in whole blood.

Current glucometers in use have inbuilt formulae in them that give values as plasma glucose

which correlates with the gold standard measured in the laboratory. Elusiyan et al25 in evaluating

the validity of bedside method in detecting hypoglycaemia studied 392 hospitalized children.

Venous blood samples were sent to the laboratory for analysis of blood glucose and also

estimated blood glucose in the same sample using glucometer. Hypoglycaemia was noted in 38

(9.7%) children with the glucometer and 25 (6.4%) by laboratory estimation. The glucometer

gave a predictive index of a positive test as 63.12% and of a negative test as 99.72%. The study

concluded that glucometer was highly sensitive and specific and its results correlate with

laboratory methods.

TREATMENT OF HYPOGLYCAEMIA

Hypoglycaemia should be treated as soon as possible to prevent complications of neurologic

damage. Hypoglycaemia is treated with bolus administration of 2-4ml/kg of 10% dextrose water.

This is followed by continuous infusion of 10% dextrose to provide 6-8mg/kg/minute of glucose

(3.4-4.8ml/kg/hr).91,92 Blood sugar should be checked after one hour and if normal, regular and

adequate oral feeds should be commenced. If still abnormally low, a repeat of bolus dextrose

water administration should be given while the concentration of the dextrose infusion should be

37

increased to 12.5% by addition of appropriate volume of 50% dextrose water. Hourly monitoring

of blood glucose should continue until two normoglycaemic results are obtained after which

interval of sampling should be increased serially to 2, 4, 6, 12 and 24 hours.

Patients who require more than 10-12mg/kg/min to maintain blood glucose should be further

investigated for other possible causes and the use of other treatment modalities considered. Other

treatment modalities to be considered include the use of diazoxide, octreotide, glucagon and

surgery.

Diazoxide aims to increase blood glucose by inhibiting pancreatic insulin release and possibly

through an extrapancreatic effect.3 Effect starts within an hour and usually lasts maximum of

eight hours with normal renal function.97 It is given orally at a dose of 25-35mg/kg/day.3

Octreotide is a long-acting analogue of somatostatin that suppresses insulin secretion for short

term management of hypoglycaemia.88,97 It is given subcutaneously at a dose of 20-50ug per

dose 6-12 hourly. Glucagon is used in treatment of hypoglycaemia secondary to

hyperinsulinaemia93. Hydrocortisone 10mg/kg in two divided doses may also be used.12,91 Both

glucagon and hydrocortisone stimulate hepatic gluconeogenesis and glycogenolysis and

ultimately increase blood glucose concentration.

Surgical intervention is considered in severely affected neonates who are unresponsive to

glucose and somatostatin therapy.93 Surgery involves pancreatectomy and removal of

extrapancreatic tumours that cause hypoglycaemia. Dietary management is also an important

adjunct for the management of hypoglycaemia. The use of frequent small feeds will help reduce

the duration of fast. Breast milk is also beneficial in preventing hypoglycaemia as it has a good

38

caloric base.98 The fat component is considered beneficial as fat promotes ketogenesis and

reduces uptake of glucose by cell.98

Specifically, if hypoglycaemia is found to be as a result of starvation (ketotic), glycogen storage

disorders or free fatty acid metabolism defect, frequent feeding or use of specially designed diet

is the mainstay of treatment.91,98 Octreotide, diazoxide or calcium channel blockers like

nifedipine are used in the treatment of hypoglycaemia due to hyperinsulinism.97 Pancreatectomy

is equally indicated for hypoglycaemia due to hyperinsulinism that does not respond to medical

treatment.93 Growth hormone or cortisol is used in the treatment of hypoglycaemia as result of

hypopituitrism or adrenal insufficiency.

PROGNOSIS OF HYPOGLYCAEMIA

The prognosis of hypoglycaemia is good with prompt treatment.91 However hypoglycaemia

recurs in 10-15% of infants after adequate treatment.99 Rebound hypoglycaemia occurs if

intravenous fluid is extravasated or discontinued too abruptly. It may also occur if oral glucose is

not offered after intravenous administration of glucose especially in severe acute malnutrition.93

Remission of congenital hyperinsulinism generally does not occur, but severity of the disease

may reduce with time.3 The prognosis for intellectual function could be worse if the symptoms

stay for prolonged duration and are associated with neurological sequelae.99,100

PREVENTION OF HYPOGLYCAEMIA IN CHILDREN

Hypoglycaemia has long term adverse effects on brain development which makes its prevention

very important. Inadequate food intake and delay in proper treatment of very ill children result in

hypoglycaemia in most cases. Most cases of hypoglycaemia are asymptomatic, therefore,

39

prevention requires a high index of suspicion. In line with this, the Integrated Management of

Childhood illness (IMCI) encourages the use of glucose water and breast milk in ill children

before referral to avoid hypoglycaemia. Elusiyan et al25 also advocated routine blood glucose

monitoring in ill children with a glucometer.

COMPLICATIONS OF HYPOGLYCAEMIA

There are predictable consequences on brain metabolism and growth when the brain is deprived

of its major energy source as a result of hypoglycaemia.13,99,100 The deprivation can lead to such

consequences as increased breakdown of endogenous structural components to release amino

acids and free fatty acids and ultimate destruction of functional membrane integrity.13 All these

factors may cause impaired brain growth and function.

Previous studies have reported a strong association between hypoglycaemia and increased

mortality/morbidity in children.5,6,7 A study done in Ile-Ife Nigeria by Elusiyan et al5 reported

that among 35 patients that died in the study, 10(28%) were hypoglycaemic compared to

15(4.2%) of the 350 that survived. They concluded that patients that had hypoglycaemia were

more likely to die than those with normal glucose level. A study done in Benin City Nigeria by

Onyiriuka et al51 in children with malaria reported that the presence of hypoglycaemia at the

point of admission was associated with a significant increase in case fatality.51 A study done in

children with diarrhoea in Calabar Nigeria by Ntia et al50 reported a 33% case fatality in children

with diarrhoea and hypoglycaemia.

40

In the study by Solomon et al6, seven (16%) out of 43 children who had hypoglycaemia died

compared to 18 (3.2%) of 560 children who had normal glucose levels. This finding is similar to

those in the study by Wintergerst et al101 that reported that 30 (16.5%) of 182 patients who had

blood glucose levels less than 65mg/dl died. Osier et al7 also reported a strong association

between hypoglycaemia and mortality. In their study, almost a third of the children who had

hypoglycaemia died despite a protocol of urgent detection and treatment of hypoglycaemia.

Studies have shown that hypoglycaemia is an indicator of poor prognosis in different disease

conditions.10,33,96,102-104 Nwosu et al33 reported that children who had cerebral malaria and

hypoglycaemia had increased risk of mortality. The most frequently occurring sequelae were

cortical blindness, monoparesis, aphasia and cerebellar ataxia.33 In Kenya, Idro et al103 in a

retrospective study examined the hospital records of 143 children aged six to nine years

previously admitted with cerebral malaria. The children were assessed at least 20 months after

discharge to detect motor, speech, language and other cognitive (memory, attention and non

verbal functioning) impairments. It was found that hypoglycaemia was independently associated

with speech and language impairments and impaired non verbal functioning.101 Taylor et al67

reported a higher morbidity and mortality among patients with cerebral malaria who had

hypoglycaemia before treatment. In this group, seven out of 19 (36.8%) died and five of 12

survivors (41.6%) had sequelae which included hemiparesis in two, generalized hypotonia and

inability to walk in one, decerebrate syndrome with generalized spasticity of the limbs in one and

cerebellar ataxia in one.101-104

Hypoglycaemia has been found to be a major risk factor for mortality in children with

gastrointestinal infection.10 In a study done in Benin on among children with diarrhoea by

Onyiriuka et al49 a very strong association between hypoglycaemia and mortality was reported.

41

Five (62.5%) out of the 8 children that died had hypoglycaemia. The study also compared the

mortality rate between the hypoglycaemic group and normoglycaemic group and it was found to

be 35.7% (5/14) versus 1.8% (3/169). In another study by Bennish et al,10 16 (34.8%) of the 46

patients with diarrhoea who had hypoglycaemia died as compared to three (12%) of 25 who were

normoglycaemic. Two of the 30 hypoglycaemic patients that survived had neurological deficits.

One was blind and the other one had recurrent focal seizures.10

A retrospective multicentre study by Lucas et al32 reported that moderate hypoglycaemia may

have serious developmental consequences if present for more than five days in the first two

months of life. Fluge105 followed up 37 children who had hypoglycaemia in their neonatal

period. Four patients that had symptomatic hypoglycaemia had convulsion after neonatal period,

one had infantile spasm and had severe mental retardation with spastic diplegia and epilepsy.105

There was also a case of blindness as a result of optic nerve atrophy and four cases of cerebral

palsy were detected in this group.105

42

AIM AND OBJECTIVES

AIM

The aim of the study is to evaluate hypoglycaemia in children aged one to 59 months admitted to

the Emergency Paediatric Unit (EPU) of Federal Medical Centre (FMC) Owerri.

SPECIFIC OBJECTIVES

The specific aims of the study are to:

1. determine the prevalence of hypoglycaemia in children aged one to 59 months

admitted into the Emergency Paediatric Unit of Federal Medical Centre Owerri.

2. identify clinical conditions associated with hypoglycaemia.

3. determine probable risk factors associated with hypoglycaemia.

4. compare plasma glucose values obtained with use of glucometer to oxidase method.

5. compare glucose values obtained using venous blood to that from capillary blood

using glucometer.

43

PATIENTS AND METHODS

STUDY LOCATION

The study was carried out at the Federal Medical Centre (FMC) Owerri. Owerri is the Capital of

Imo State in Southeastern Nigeria. The State has a population of about 3.93 million with about

401,873 people living in Owerri.106

Federal Medical Centre (FMC) is located in Owerri Municipal Local Government Area and

provides tertiary health care to people in Imo State and its environs like Abia, Rivers and

Anambra States. The other tertiary health facility in the State is the Imo State University

Teaching Hospital (IMSUTH) Orlu about 40km away. The Emergency Paediatric unit has 34

beds with total annual admissions of about 2480. About 72% of the total admissions per annum

fall between the ages of one month to five years. FMC has modern laboratory facilities with

qualified laboratory personnel.

STUDY DESIGN

The study is prospective and cross sectional.

STUDY DURATION

The present study was carried out over a period of six months (November 2015 to May 2016).

STUDY TIME

Subjects were recruited consecutively round the clock as patients present to the Emergency

Paediatric Unit.

44

MANPOWER FOR RESEARCH

Sample collections were done by the researcher in the Emergency Paediatric Unit of Federal

Medical Centre, Owerri. Some patients were admitted outside normal working hours or when

researcher was not on call. In order to avoid missing these subjects, trained research assistants

and paediatric registrars helped with subject recruitment. In preparation, paediatric registrars

doing their Emergency Paediatric Unit posting were trained. The registrars were trained on

correct administration of the study questionnaire as well as on correct use of the glucometer

using the manufacturer’s manual. Techniques of blood sampling and the need to take enough

samples were stressed.

STUDY POPULATION

The study subjects were children between the ages of one to 59 months admitted to the

Emergency Paediatric Unit during the study period who met the inclusion criteria.

INCLUSION CRITERIA

1. Children aged one to 59 months.

2. Informed parental/care-giver’s consent.

EXCLUSION CRITERIA

1. Use of glucose containing intravenous fluid less than six hours before admission.

2. Children on steroid therapy.

3. Children on drugs like insulin, glucagon etc.

45

N/B: These situations are known to alter glucose homeostasis and hence may alter the outcome

this study if subjects were included.

SAMPLE SIZE

The exact prevalence of hypoglycaemia in Nigerian children aged one to 59 months admitted

into the emergency room is unknown to the author because most studies done in the emergency

rooms focused on children between one month and eighteen years. An assumed rate of 50% was

therefore used to calculate the required sample size for the study.107 A minimum sample size for

the study was calculated using the standard formula for estimation of proportions.107

n = 𝑧2×𝑝(1−𝑝)

𝑑2

n = Sample size

z = Standard normal deviate, 1.96 at 95% confidence interval.

p = Estimated prevalence rate 50% (0.50) because no earlier study was on hypoglycaemia

in children between one month to five years.

d = Absolute precision required on either side of the proportion (5%)

n = (1.96)2 x 0.5 (1-0.5)/ (0.05)2

n = 384

In anticipation of unforeseen circumstances like wastage of samples or inadequate sample, an

attrition rate of 10% built in used and the total sample size was calculated as thus;

46

384 + 38 = 422.

ETHICAL APPROVAL AND INFORMED CONSENT

Ethical approval (appendix I) for the study was obtained from the Ethics Committee of the

Federal Medical Centre, Owerri. Written informed consent (appendix II) was obtained from the

parents/guardians of the study participants.

RECRUITMENT OF STUDY SUBJECTS

All children aged between one to 59 months admitted to the Emergency Paediatric Unit who met

the inclusion criteria were recruited consecutively into the study at the point of admission.

STUDY PROCEDURE: At the point of admission into the Emergency Paediatric Unit, a

proforma (Appendix III) was used to obtain information on personal data, sociodemographic

data, presenting complaints, duration of illness, time of last meal and treatment(s) received

before presentation. Socioeconomic status of the parents were determined using the Oyedeji’s108

social classification system (Appendix IV). Subjects who scored I and II were further classified

as upper class, III as middle class while those that scored IV and V were further classified as

lower class109. Subjects were examined and findings including anthropometric measurements

recorded.

ASSESSMENT OF ANTHROPOMETRIC INDICES OF STUDY SUBJECTS

The anthropometric indices that were obtained included: weight (kilogram), length/height

(centimeter) and mid arm circumference (centimeter). A SALTER weighing scale model 180

47

(England) was used for children that were not yet able to stand. SURGIFIELD stadiometer sm-

160 was used to weigh children that could stand.

Length of children less than twenty four months of age was measured with a non-stretchable tape

with child lying on flat surface, firmly immobilized with the aid of an assistant. For children

above twenty four months, height was obtained using a stadiometer fitted with sliding headpiece

at right angle to the upright which could be lowered onto the child’s head with the aid of an

assistant. Mid-arm circumference was measured using a non-stretchable tape at a point midway

between the acromion and the olecranon process. An average of three measurements of the mid-

arm circumference was recorded.

SAMPLE COLLECTION IN THE EMERGENCY PAEDIATRIC UNIT

A needle prick was made at the patient’s heel or the tip of the thumb after cleansing with alcohol

and capillary blood was obtained for blood glucose estimation using One-Touch Ultra 2®

glucometer. A convenient peripheral vein was punctured to collect about 2mls of blood after

cleansing the overlying skin with alcohol. A drop of this blood was used for blood glucose

estimation using One-Touch Ultra 2® glucometer while the rest was placed in fluoride oxalate

bottle and sent to the Chemical Pathology laboratory of Federal Medical Centre (FMC), Owerri

for blood glucose analysis.

CLINICAL DIAGNOSIS OF STUDY SUBJECTS

The clinical diagnoses expressed in this dissertation were those of the managing team based on

the Departmental protocol and case definitions. For example:

48

Gastroenteritis

This diagnosis was based on a history of diarrhoea and/or vomiting for which there was no other

obvious systemic cause. Presence and severity of dehydration were based on signs as contained

in the table below:

Symptoms associated with dehydration.110

Symptom Mild dehydration.

<5% loss of body

weight

Moderate

dehydration. 5-9%

loss of body weight

Severe dehydration.

˃9% loss of body

weight

Mental status Well; alert Irritable, fatigued or

restless.

Apathetic, lethargic or

unconscious

Thirst Drinks eagerly Thirsty Drinks poorly; unable

to drink

Tears Present Decreased Absent

Mucous membranes Moist Dry Perched

Eyes Normal Slightly sunken Deeply sunken

Skin fold Instant recoil Recoil in < 2sec Recoil in ˃ 2 sec

Urine output Normal Decreased Minimal

Heart rate Normal Increased Tachycardia with

bradycardia in severe

cases

Blood pressure Normal Hypotension Hypotension

Capillary refill Normal Prolonged Prolonged; minimal

Quality of pulse Normal Normal to decreased Weak, thread,

impalpable

Extremities Normal Cool Cold, mottled,

cyanotic

49

Malaria: A definite diagnosis of malaria was made by demonstration of parasitaemia on

microscopy.

Sepsis: Diagnosis was made based on evidence of systemic inflammatory response syndrome

(SIRS).111

Meningitis: The diagnosis was made based on compatible clinical features and findings in the

cerebrospinal fluid i.e. hypoglycorrhacchia, elevated protein, leukocytosis, finding of pathogens

on Gram stain and positive bacterial culture.

Protein Energy Malnutritioncv (PEM): The modified Wellcome classification112 was used to

diagnose children with PEM and to classify them into marasmus, marasmic kwashiorkor,

underweight kwashiorkor and kwashiorkor.

BLOOD GLUCOSE MEASUREMENTS

At the point of admission, estimation of blood glucose concentration using venous and capillary

blood samples were carried out by the researcher with a glucometer. The laboratory estimation of

blood glucose concentration was done by a qualified medical laboratory personnel who is a staff

of Federal Medical Centre (FMC) Owerri assisted by the researcher. The glucose oxidase method

of glucose estimation is the method used in the laboratory.22 The blood in the fluoride oxalate

bottle was immediately transferred to a test tube and centrifuged at a speed of 4000 revolutions

per minute (rpm) for ten minutes following which the blood separated into natant blood cells and

supernatant plasma.

The test principle: Glucose oxidase is an enzyme extracted from the growth medium of

Aspergillus niger. Glucose oxidase catalyses the oxidation of Beta D- glucose present in the

50

plasma to D glucono -1 ,5 - lactone with the formation of hydrogen peroxide; the lactone is then

slowly hydrolysed to D-gluconic acid, while the hydrogen peroxide produced is then broken

down to oxygen and water by a peroxidase enzyme. Oxygen then reacts with an oxygen acceptor

such as ortho toluidine which itself is converted to a coloured compound, the amount of which

can be measured colorimetrically.

The test procedure: Four test tubes labeled 1, 2, 3 and 4 were used each containing one

milliliter of glucose reagent (glucose oxidase and a buffer). Ten micro liters each of plasma,

standard, control and distilled water were added to each of the test tubes 1, 2, 3 and 4 containing

glucose reagent respectively. The solutions were mixed very well and incubated in a water bath

at a temperature of 37°C for ten minutes. After incubation, the samples were read with a

spectrophotometer at a wavelength of 540nm. The depth of colour change is a function of blood

glucose concentration. The blood glucose concentration is calculated as follows:

𝐵𝑙𝑜𝑜𝑑 𝑔𝑙𝑢𝑐𝑜𝑠𝑒 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 =absorbence of sample

𝑎𝑏𝑠𝑜𝑟𝑏𝑒𝑛𝑐𝑒 𝑠𝑡𝑎𝑛𝑑𝑎𝑟𝑑 x concentration of standard

(The standard has a fixed concentration depending on the reagent.

The blank or distilled water is used to standardize the machine. The blank is usually used to

bring the equipment to zero mark before every use to ensure proper standardization.

The control has known glucose concentration which is used to standardize both the machine and

the reagent.)

The glucometer: The principle behind blood glucose meters is based on reactions that are

analyzed by electrochemical sensors that measure blood glucose concentration according to the

amount of colour change.22 On each strip, there are about 10 layers, including a stiff plastic base

51

plate, and other layers containing chemicals or acting as spacers. For instance, there is a layer

containing two electrodes (silver or other similar metal). There is also a layer of the immobilized

enzyme, glucose oxidase, and another layer containing microcrystalline potassium ferricyanide.

Specifically, the reaction of interest is between glucose and glucose oxidase. The glucose in the

blood sample reacts with the glucose oxidase to form gluconic acid, which then reacts with

ferricyanide to form ferrocyanide. The electrode oxidizes the ferrocyanide, and this generates a

current directly proportional to the glucose concentration and glucose value displays on the

display screen.22

The One Touch Ultra 2® brand of glucometer was used because it is widely available, the strips

are readily available and relatively affordable compared to other meters in the market. The cost

of all blood glucose estimations were borne by the researcher.

Below is the procedure on how the One-Touch Ultra 2® glucometer was used.

One-Touch Ultra 2® glucometer testing procedure.

The “One Touch” Glucometer measures blood glucose between 10 to 600mg/dl. A measurement

below 10mg/dl will read “LO” and any reading above 600mg/dl will read as “HI”. In compliance

with the manufacturer’s instruction, the following steps were followed:

1. The test strip was inserted into appropriate slot to automatically activate the glucometer.

2. The test strip was advanced until it clicked into place.

3. When the drop symbol flashed in the display panel, a drop of blood was placed on the

designated section of the test strip.

4. In about five seconds, the result was digitally displayed along with date and time of test.

52

COMMON CAUSES OF ERROR WHILE USING THE ONE TOUCH

ULTRA 2 GLUCOMETER

Problem Results Recommendation

Test strip not fully inserted into meter false low always be sure test strip is fully

inserted in meter

Patient sample site (for example, the fingertip)

is contaminated with sugar

false high always clean and dry test site before

sampling

Not enough blood applied to strip false low repeat test with a new sample

Batteries low on power error codes change batteries and repeat sample

collection

Test strips/Control solutions stored at

temperature extremes

false

high/low

store kit and components according to

directions

Patient is dehydrated false high stat venous sample on main lab

analyzer

Patient in shock false low stat venous sample on main lab

analyzer

Squeezing fingertip too hard because blood is

not flowing

false low repeat test with a new sample from a

new stick

Sites other than fingertips high/low results from alternative sites may not

match finger stick results

Test strip/Control solution vial cracked false

high/low

always inspect package for cracks,

leaks, etc.

Anemia/decrease hematocrit false high venous sample on main lab analyzer

Polycythemia/increased hematocrit false low venous sample on main lab analyzer

53

USEFUL TIPS ON HOW TO INCREASE THE ACCURACY OF THE ONE

TOUCH ULTA 2 GLUCOMETER

Follow the One Touch Ultra 2

instructions about quantity of

blood (one micro liter of blood).

Repeat the test if you have any

doubt that enough blood was

added.

If there is insufficient blood on the test strip, the meter may

not be able to read the glucose level accurately.

insert the test strip completely

into the meter guides.

When a test strip is not fully inserted into the meter, the

meter cannot read the entire strip area.

keep the meter clean. Even small amounts of blood, grease, or dirt on the meter’s

lens can alter the reading.

check the test strip package to

make sure the strips are

compatible with your meter.

Test strips are not always interchangeable, and meters

cannot always detect incompatible strips. Test strips that

look alike may have different chemical coatings. Small

variations in strip dimensions can also affect results.

check the expiration date on the

test strips.

As a test strip ages, its chemical coating breaks down. If

the strip is used after this time, it may give inaccurate

results.

enter the correct calibration

code (25) from the outside of

the strip bottle each time you

run a test (if applicable).

Results can vary significantly between manufactured lots

of reagent strips; the calibration codes help the meter

compensate for these variations.

run quality control as directed. Running quality control is typically the only way to know

when test strips have gone bad. Test strips do not always

last until the expiration date on the bottle. This may be

because the manufacturer has over-estimated the dating or

because the cap was not replaced promptly after use.

check the results from your

meter against laboratory results

as often as possible.

Over time, test systems can drift apart. Since results from

either test system maybe used to treat your patients, it is

important for the systems to remain synchronized.

question results that are not

consistent with physical

symptoms. If a test result seems

wrong, have a blood sample

tested by the main laboratory.

There may be many reasons why a test result is incorrect.

In addition to the items above, some physiological

conditions such as dehydration, hyperosmolarity, high

hematocrit, or shock may significantly affect test results.

54

TREATMENT OF HYPOGLYCAEMIA

All patients diagnosed to have hypoglycaemia (plasma glucose <2.6mml/L) were given

immediate bolus of 2-4mls/kg of 10% dextrose water (2mls/kg for asymptomatic and 4mls/kg for

symptomatic patients). This was followed by continuous dextrose infusion at 6-8mg/kg/min (3-

5ml/kg/hour) over one hour after which plasma glucose level is rechecked. Glucose infusions are

discontinued after obtaining two normal consecutive glucose values (measured 30 minutes apart)

and patient was feeding well.

DATA ANALYSIS

The collected data were analyzed using the Statistical Package for Social Sciences (SPSS)

version 19. Continuous variables like age, length or height and weight were summarized with

descriptive statistics such as mean and standard deviation. Probability (p) value less than 0.05

was taken as significant. Categorical variables were compared using Pearson chi-square test or

Fisher exact test (when expected cell values are small) while Student t-test was used to compare

the means. Sensitivity, specificity, predictive values and efficiency were defined as follows:

Sensitivity = 𝑇𝑟𝑢𝑒 𝑝𝑜𝑠𝑖𝑡𝑖𝑣𝑒

(𝑇𝑟𝑢𝑒 𝑝𝑜𝑠𝑖𝑡𝑖𝑣𝑒+𝐹𝑎𝑙𝑠𝑒 𝑛𝑒𝑔𝑎𝑡𝑖𝑣𝑒)

Specificity = 𝑇𝑟𝑢𝑒 𝑛𝑒𝑔𝑎𝑡𝑖𝑣𝑒

(𝑇𝑟𝑢𝑒 𝑛𝑒𝑔𝑎𝑡𝑖𝑣𝑒+𝐹𝑎𝑙𝑠𝑒 𝑝𝑜𝑠𝑖𝑡𝑖𝑣𝑒)

Predictive value of a positive test = 𝑇𝑟𝑢𝑒 𝑝𝑜𝑠𝑖𝑡𝑖𝑣𝑒

(𝑇𝑟𝑢𝑒 𝑝𝑜𝑠𝑖𝑡𝑖𝑣𝑒+𝐹𝑎𝑙𝑠𝑒 𝑝𝑜𝑠𝑖𝑡𝑖𝑣𝑒)

Predictive value of a negative test = 𝑇𝑟𝑢𝑒 𝑛𝑒𝑔𝑎𝑡𝑖𝑣𝑒

(𝑇𝑟𝑢𝑒 𝑛𝑒𝑔𝑎𝑡𝑖𝑣𝑒+𝐹𝑎𝑙𝑠𝑒 𝑛𝑒𝑔𝑎𝑡𝑖𝑣𝑒)

55

Efficiency = 𝑇𝑟𝑢𝑒 𝑝𝑜𝑠𝑖𝑡𝑖𝑣𝑒+𝑇𝑟𝑢𝑒 𝑛𝑒𝑔𝑎𝑡𝑖𝑣𝑒

𝑇𝑜𝑡𝑎𝑙 𝑠𝑢𝑏𝑗𝑒𝑐𝑡𝑠

56

RESULTS

Demographic Parameters and Clinical History

Four hundred and twenty two children one to 59 months enrolled. Twenty two were dropped due

to sample wastages. The 400 subjects who completed the study included 232 (58.0%) males and

168 (42.0%) females; 222 (55.5%) infants (1 – 12 months), 126 (31.5%) toddlers (13 – 36

months) and 52 (13.0%) preschool children (37 – 59 months) making infants the predominant

age group. The mean age of the children was 16.9 ± 15.1 months and a median age of 12 months.

Two hundred and thirty eight (59.5%) subjects belonged to the upper socioeconomic class, 104

(26.0%) and 58 (14.5%) belonged to the middle and lower socioeconomic class respectively.

(Table 1).

The mean ± standard deviation and median duration of illness were 9.8 ± 1.9 hours and 4 hours

respectively while the average ± standard deviation and median duration from the last meal were

3.5 ± 0.2hours and 3.0 hours respectively.

57

Table I: Age, gender and family Socioeconomic Status of Subjects.

Characteristics Frequency (%)

Age(months)

1 – 12 222 (55.5)

13 – 36 126 (31.5)

37 – 59 52 (13.0)

Gender

Male 232(58.0)

Female 168(42.0)

Socioeconomic Class

Upper Socioeconomic Class (I-II) 238(59.5)

Middle Socioeconomic Class (III) 104(26.0)

Lower Socioeconomic Class (IV-V) 58(14.5)

NOTE: The Oyedeji classification was used to classify subjects into classes I to V.

A modification was then applied to regroup these classes into Upper (I and II),

Middle (III) and Lower (IV and V).109

Clinical diagnoses

Table II shows the clinical diagnoses made in the children studied. Acute gastroenteritis, sepsis,

severe malaria, bronchopneumonia and meningitis in order of decreasing frequency were the

leading clinical diagnoses reported in 89 (22.3%), 86 (21.5%), 64 (16.0%), 37 (9.3%) and 26

(6.5%) children, respectively. Others included two cases each of (AIDS with HIV

Encephalopathy, encephalitis, gastritis), two each of (encephalitis, gastritis, kerosene poisoning

and tetanus) and one each of (septic shock, kerosene poisoning, tetanus).

58

Table II: Frequency of occurrence of clinical diagnosis in the children studied.

Diagnosis Frequency (%)

Gastroenteritis 89 (22.25)

Sepsis 86 (21.50)

Severe Malaria 64 (16.00)

Bronchopneumonia 37 (9.25)

Meningitis 26 (6.50)

Febrile convulsion 13 (3.25)

Bronchiolitis 10 (2.50)

Sickle cell crisis 10 (2.50)

Upper respiratory tract infection 9 (2.25)

Anaemic heart failure 9 (2.25)

Acute severe asthma 8 (2.00)

Intussuception 8 (2.00)

Acute renal failure 6 (1.50)

Haemolytic uraemic syndrome

Gastritis

6 (1.50)

3 (0.75)

Kwashiorkor 3 (0.75)

Nephrotic syndrome 3 (0.75)

Afebrile seizures

AIDS with HIV encephalopathy

Encephalitis

Kersene poisoning

Tetanus

Marasmus

3 (0.75)

2 (0.50)

2 (0.50)

1 (0.25)

1 (0.25)

1 (0.25)

59

Blood glucose results

The mean, median and ranges of blood glucose estimations done on the children from their

capillary and venous blood samples using One-Touch Ultra 2® glucometer and the standard

laboratory colorimetric glucose estimations methods are shown in table III.

Table III: Mean, median and ranges of blood glucose values obtained in the study.

Blood glucose at admission (mg/dl) �̅� ± SD Median Range

Glucometer

Capillary blood 112.5 ± 56.9 101.0 22.0 – 495.0

Venous 110.5 ± 55.7 99.5 21.0 – 487.0

Laboratory method 106.6 ± 53.5 94.5 20.0 – 461.0

60

comparison of mean blood glucose from One-Touch Glucometer and

Laboratory analyses

Table IV shows the mean blood glucose levels derived from the glucometer (capillary and

venous) and from the laboratory. The mean capillary blood glucose using a glucometer was

higher than that of venous sample, but the difference was not statistically significant (p = 0.73).

The capillary and venous sample blood glucose estimations using glucometer were also higher

than the laboratory method, but the differences were not statistically significant (p = 0.29 and

0.48 respectively).

Table IV: comparison of mean blood glucose from One-Touch Glucometer and Laboratory

analysis

Blood glucose at

admission (mg/dl)

�̅� ± SD

t-test

p-value

GCBG

GVBG

112.5 ± 56.9

110.5 ± 55.7

0.35

0.73

GCBG

LabBG

112.5 ± 56.9

106.6 ± 53.5

1.06

0.29

GVBC

LabBG

110.5 ± 55.7

106.6 ± 53.5

0.71

0.48

GCBG = Glucometer Capillary Blood Glucose.

GVBG = Glucometer Venous Blood Glucose.

LabBG = Laboratory Blood Glucose.

61

Correlations among mean blood glucose estimations using different methods:

Glucometer (capillary sample), Glucometer (venous sample) and standard

laboratory methods

Table V shows that there was a significant positive correlation between capillary blood glucose

and venous blood glucose estimations using glucometer (r = 0.981, p < 0.001). Similarly, there

were significant positive correlations between capillary and laboratory readings (r = 0.906, p <

0.001) and between venous and laboratory readings (r = 0.925, p < 0.001).

Table V: Correlation among, GCBG, GVBG, LabBG.

GCBG GVBG LabBG

GCBG R 1.00 0.981 0.906

0.000 0.000

GVBG R 1.000 0.925

0.000

LabBG R 1.000

GCBG = Glucometer Capillary Blood Glucose

GVBG = Glucometer Venous Blood Glucose

LabBG = Laboratory Blood Glucose

62

Correlations between Blood Glucose values and Duration of illness and

Duration from last meal

There was no statistically significant correlation between point of admission blood glucose

estimation by any of the methods with duration of last meal and duration of illness as shown in

table VI

Table VI: Correlation among LabBG, DOI and DFLM

LabBG DOI DFLM

LabBG R 1.000 -0.095 0.080

0.181 0.260

DOI R 1.000 -0.057

0.422

DFLM R 1.000

LabBG = Laboratory blood glucose

DOI = Duration of illness

DFLM = Duration from last meal

63

Prevalence of Hypoglycaemia

Using the laboratory method, thirty children had random blood glucose reading less than

2.6mmol/L (47mg/dl) giving a hypoglycaemia prevalence rate of 7.5%. Using One-Touch Ultra

2®, 26 (6.5%) of the capillary and 28 (7.0%) of venous samples had readings in the

hypoglycaemic range. A prevalence of 7.5% as recorded in the laboratory was used in this study.

Capillary samples had four (4) false negatives while venous samples had two (2) false negatives.

Neither the venous nor capillary samples by glucometer estimation had any false positives as

shown in Table VII. The laboratory estimation recorded 43, 40, 38 and 45(mg/dl), the venous

estimation recorded 47, 44, 45 and 52 (mg/dl), while the capillary estimation recorded 49, 50, 51

and 54 (mg/dl respectively) among the four subjects.

64

Table VII: False negative, True negative, False positive, True positive readings by the

glucometer for hypoglycaemic patients using laboratory method as reference standard.

TABLE VIIa

LabBG

Positive negative Total

GCBG Positive 26 0 26

Negative 4 370 374

Total 30 370 400

TABLE VIIb

LabBG

positive negative Total

GVBG Positive 28 0 28

Negative 2 370 372

Total 30 370 400

65

Table VIII: Sensitivity, specificity and predictive value of capillary and

venous samples comparing values by glucometer to values derived by

laboratory method.

The sensitivities of capillary and venous blood random blood glucose measurement relative to

the laboratory method were therefore 86.7% and 93.3% respectively. Both methods had 100%

specificity and positive predictive values for detecting hypoglycaemia as shown in Table VIII.

Table VIII: Sensitivity, specificity and predictive values of glucometer capillary and venous

samples using laboratory method as standard.

Glucometer Sensitivity Specificity PPV NPV

Capillary sample 86.7% 100.0% 100.0% 98.9%

Venous sample 93.3% 100.0% 100.0% 99.5%

PPV = Positive predictive value

NPV = Negative predictive value

66

Risk factors for hypoglycaemia

Table IX shows the association between hypoglycaemia and age group, sex and socioeconomic

class. The frequency of occurrence of hypoglycaemia decreased with increasing age. None of

the pre-school children was hypoglycaemic. A chi square analysis did not show any significant

age difference [among the three age stratifications] (χ2 = 4.979; p = 0.083). However, infants had

a significantly higher prevalence of hypoglycaemia than preschool children (Fisher exact test: p

= 0.0176). Similarly, toddlers also had a significantly higher prevalence of hypoglycaemia than

preschool children (Fisher exact test: p = 0.0357). On the other hand, the difference between the

prevalence of hypoglycaemia in infants and toddlers was not statistically significant (χ2 =0.017; p

= 0.68).

The frequency of hypoglycaemia was higher in males than females (7.8% versus 7.1%), but the

difference was not statistically significant (χ2 =0.053; p = 0.817). The frequency of

hypoglycaemia was higher in children belonging to the lower socioeconomic class (17.2%). This

prevalence was significantly higher than the figure in the upper and middle classes put together

(χ2 = 9.279; p = 0.002).

67

Table IX: Risk factors for hypoglycaemia

Hypoglycaemic Non

Hypoglycaemic

Total χ2 p value

Age groups

≤12 20 (9.0) 202 (91.0) 222 (100.0)

13 to 36 10 (7.9) 116 (92.1) 126 (100.0) 4.979 0.083

37 to 60 0 (0.0) 52 (100.0) 52 (100.0)

Sex

Male 18 (7.8) 214 (92.2) 232 (100.0) 0.053 0.817

Female 12 (7.1) 156 (92.9) 168 (100.0)

SEC

Upper 16 (6.8) 222 (93.2) 238 (100.0)

Middle 4 (3.8) 100 (96.2) 104 (100.0) 10.142 0.006

Lower 10 (17.2) 48 (82.8) 58 (100.0)

SEC = Socio-economic classification

Association between hypoglycaemia, clinical features and treatment outcome

Table X shows the association between patients’ symptoms, physical findings and treatment

outcome. Hypoglycaemia was found significantly more commonly among patients who had

fever, vomiting, diarrhoea or dehydration. It was also significantly more common among patients

who had convulsed, were unconscious or had ingested herbal concoctions. Of the 30 patients

with hypoglycaemia, two were discharged against medical advice and were lost to follow up. Of

the 28 that were fully treated to conclusion, 12 died giving a case fatality rate of 42.9%. The

corresponding fatality rate among patients without hypoglycaemia was 12.40% (46/370). Thus

the presence of hypoglycaemia was associated with a higher mortality rate (χ2 =18.5; p < 0.001).

Thus overall, a total of 330 (82.5%) subjects responded well to treatment and were discharged,

12 (3.0%) were discharged against medical advice while 58 (14.5%) died in the hospital. The

68

diagnoses for the subjects that were discharged against medical advice were meningitis 4

(33.3%), severe sepsis 3 (25.0%), malaria with severe anaemia 3 (25.0%), (8.3%), haemolytic

uraemic syndrome 1 (8.3%), and viral hepatitis 1 (8.3%).

Table X: Association between hypoglycaemia, patients’ clinical features and treatment

outcome

Variables

Symptoms

Hypoglycaemic

n=30

Non Hypoglycaemic

n=370

χ2 p value

Fever (346) 30 (100.0) (85.4) 5.062 0.024

Vomiting (216) 26 (86.7) (51.3) 12.547 0.000

Diarrhoea (166) 18 (60.0) (40.0) 4.572 0.030

Herbal treatment(76) 16 (53.3) (16.2) 24.841 0.000

Pallor (118) 14 (46.7) (28.1) 2.865 0.090

Unconsciousness (64) 14 (46.7) (13.5) 22.694 0.000

Convulsions (70) 12 (41.1) (15.7) 4.776 0.030

Cough (116) 8 (26.7) (29.1) 0.086 0.770

Respiratory distress

(108)

Treatment outcome

Died (58)

DAMA (12)

Discharged (330)

6 (20.0)

12 (40.0)

2 (16.7)

14 (4.2)

(27.6)

46 (12.4)

10 (83.3)

316 (95.7)

0.806

18.488

0.373

0.000

DAMA = Discharged Against Medical Advice.

69

Association between specific diagnosis and hypoglycaemia

Table XI shows the frequency of hypoglycaemia in specific disease conditions. The frequency of

hypoglycaemia was highest among patients with PEM (50%), followed by sepsis 12 (14.3%),

gastroenteritis 8 (9.0%), meningitis 2 (8.3%), and malaria 4 (6.3%).

Table XI: Association between specific diagnosis and incidence of hypoglycaemia

Diagnosis No of cases

with

hypoglycaemia

n= 30

No of cases

without

hypoglycaemic

n=370

Total χ2 P value

Sepsis 12 (40.0) 72 (19.4) 86 (100.0) 15.322 0.009

Gastroenteritis 8 (26.7) 81 (21.9) 89 (100.0) 13.240 0.021

Malaria 4 (13.3) 60 (16.2) 64 (100.0) 11.328 0.045

Meningitis 2 (6.7) 22 (5.9) 26 (100.0) 19.981 0.001

PEM 2 (6.7) 2 (0.5) 4 (100.0) 23.117 0.000

Others include severe bronchopneumonia, acute bronchiolitis, acute severe asthma, anaemic

heart failure, intussusceptions, haemolytic uraemic syndrome, afebrile seizures, etc.

70

DISCUSSION

The prevalence of hypoglycaemia of 7.5% found in the present study is comparable to figures

from earlier studies from Nigeria and elsewhere in Africa which ranged from 6.5% to7.3%.5-7 It

is however, much higher than 0.007% reported from Alabama in the United States of

America.113 The marked difference from the Alabama study could be explained by difference in

methodology. While the subjects of the current study were children who were ill enough to be

hospitalized, the Alabama study recruited all children who presented to the Emergency room

irrespective of illness severity. Expectedly, more subjects of the current study would be prone to

more co morbidities like hypoglycaemia.

On the other hand, the prevalence herein reported was much lower than 18.0% found in a

California study.101 This difference probably resulted from the differences in cut-off values used

for the definition of hypoglycaemia. While a level of 2.6mmol/L (47mg/dl) was used to define

hypoglycaemia in the present study, a higher cut-off of 3.6mmol/L (65mg/dl) was adopted in the

California study. The obvious implication is that some subjects who would have been classified

as within normal limits in the current study would have been classified as hypoglycaemic in the

California study. A second explanation is that the California study was conducted in the

Intensive Care Unit among very ill children who were highly prone to co-morbidities like

hypoglycaemia. The California study did not state the age range of the studied subjects. The

prevalence of hypoglycaemia in any given setting depends on the blood glucose level used in the

definition of hypoglycaemia.

Hypoglycaemia was found to be commonly associated with protein energy malnutrition (PEM),

sepsis, gastroenteritis, meningitis and malaria in the present study. This observation is

71

comparable to the findings noted by Oyenusi et al114 in Lagos that reported hypoglycaemia to be

more commonly associated with multisystemic infection (sepsis), severe malaria, gastroenteritis

and respiratory infections. Elusiyan5 in Ile-Ife also reported high prevalence of hypoglycaemia in

children who were diagnosed with severe malaria, septicaemia, pneumonia and PEM and their

observations are in tandem with findings in the present study. Similarly, the common disease

conditions found to have the highest prevalence of hypoglycaemia in the present study are

similar to the range noted in the Mozambique6 study which found the prevalence to be highest in

children with PEM, pneumonia, encephalitis and intestinal parasitic infections. It is therefore

important to screen for hypoglycaemia in children who present to the Emergency Room with

these illnesses.

Specifically, hypoglycaemia was recorded in half of the children with PEM in the present study.

This is comparable to the prevalence rate noted by Elusiyan et al.5 The higher prevalence could

be explained by the depletion of gluconeogenic amino acids in malnourished children as reported

by Bennish et al.10 Furthermore, hypoglycaemia could be caused by a defect in glycogenolytic

pathway and limited lipolysis in malnourished children. Thus it is very important to screen for

hypoglycaemia in malnourished children to allow for prompt correction and subsequent

maintenance of caloric requirement of the patient.

Hypoglycaemia was prevalent in children who had sepsis. The prevalence rate is comparable to

values recorded in the studies in Ile-Ife5 and Lagos.114 Endotoxins produced by organisms during

infection have been reported to cause increased insulin production hence causing

hypoglycaemia.18,73,74 Hypotension in septic shock causes reduced tissue perfusion and a switch

to anaerobic respiration which results in increased glucose utilization.75 There is equally

increased metabolism as a result of fever during an infection; this causes an increased peripheral

72

glucose utilization especially in neonates with bacteremia.76,77 There is need therefore to suspect

and screen for hypoglycaemia in children we suspect to have sepsis.

The current study also reported a high prevalence of hypoglycaemia in children that had

gastroenteritis. This observation is in tandem with what was noted in the study in Benin49 which

reported a prevalence of 7.7%. This observation is however in contrast to what was noted in a

study that was done in Calabar50 which reported a prevalence of 4.0%. The difference in

prevalence could have been as a result of the difference in the definition of hypoglycaemia used.

The cut-off blood glucose used in the Calabar study50 was 2.2mmol/l (40mg/dl) while the current

study used a cut-off of 2.6mmol/l (47mg/dl). The association between hypoglycaemia and

diarrhoeal diseases in the current study is in contrast with the findings noted in the study by

Elusiyan et al5 which documented no hypoglycaemia in all 14 subjects with diarrhoea. Elusiyan

et al attributed their findings to the use of oral rehydration therapy in the subjects. The sample

size was also small in the Elusiyan et al’s study compared to the current study and this may also

account for the findings. A study done in India in children who had diarrhoea reported a higher

prevalence of hypoglycaemia than what is observed in the current study.48 The current study

tested consecutive patients while the Indian study tested 10 out of 28 cases of cholera. The

higher prevalence rate could have been as a result of the fact cholera is more debilitating illness

than simple gastroenteritis, and withholding of feeds is commonly used as a measure in cholera.

Hypoglycaemia is common in children with diarrhoeal diseases because there is reduced food

intake as mothers fear that feeding may worsen diarrhoea. Therefore, the continued promotion of

oral rehydration therapy at home in children who have diarrhoea should be encouraged.

The present study found a hypoglycaemia prevalence rate of 6.3% in children who had severe

malaria. This observation is similar to that noted in a Kenyan7 study which reported a prevalence

73

of hypoglycaemia of 8.4% in children who were diagnosed to have malaria. A significant

association was found between incidence of hypoglycaemia and loss of consciousness. When

children are unconscious, they are made to fast for a prolonged period of time. This prolonged

fasting or the primary disease that led to unconsciousness may predispose them to

hypoglycaemia.

Dehydration was also significantly associated with hypoglycaemia in the present study. This

finding is similar to the report by Ntia et al50 in Calabar study. The occurrence of hypoglycaemia

in dehydrated children may be due to reduced blood supply to the liver and subsequent reduction

in glucose metabolism.53

Age less than twelve months was found to be a risk factor for hypoglycaemia. This is

comparable to the finding by Elusiyan et al5 showing hypoglycaemia to be more in children aged

one to three years. Hypoglycaemia occurs more in younger infants as observed in this study

because their capacity for glucose homeostasis is limited. As compared to older children and

adults, infants have limited reserves of liver glycogen and muscle protein coupled with their

relative higher rate of glucose utilization due to their larger brain to body ratio.12 Assessment of

blood glucose should be done once infants and toddlers present to the emergency room.

Low socioeconomic status was found to be another risk factor for hypoglycaemia. This may be

due to the fact that these are children who are exposed to hunger and malnutrition and hence

reduced liver and muscle glycogen. The stress of illness leads to faster depletion of these

glycogen stores hence increased risk of hypoglycaemia.12 Clinicians should therefore maintain

high index of suspicion of hypoglycaemia when children drawn from low socioeconomic status

present to the Emergency Room.

74

It was observed also that mortality was higher in children who were hypoglycaemic. This is also

in keeping with the contents of previous studies.5,114 The predominant diagnoses with high

mortality in children with hypoglycaemia in the present study were meningitis, acute

gastroenteritis, sepsis, and severe malaria. These are also in keeping with reports from other

previous studies. These diseases are intrinsically associated with high mortality and occurrence

with hypoglycaemia would only have worsened the situation.

The results obtained with a glucometer were comparable with laboratory results. With reference

to the diagnosis of hypoglycaemia, the glucometer compared to glucose oxidase test had 100%

specificity and 100% positive predictive value. The sensitivity and negative predictive values

were also very high for both capillary and venous samples. The overall implication of these is

that the user of a glucometer is assured that a diagnosis of hypoglycaemia using a glucometer is

accurate. It therefore could be used as a tool for bedside diagnosis.

Comparison of the results from capillary blood with venous samples revealed negligible

differences in their values. In the main, capillary sample gave higher results but the differences

were not statistically significant. The implication is that results obtained with either sample are

reliable and the physician is at liberty to choose any of the methods as may be convenient.

In conclusion, the prevalence of hypoglycaemia in the emergency room dictates the maintenance

of a high index of suspicion. The index should be higher in younger children and those from low

socioeconomic classes. Patients presenting with protein energy malnutrition, suspected sepsis,

gastroenteritis, meningitis or malaria should also receive extra attention. The bedside tool

(glucometer) used in the study produced sufficiently high sensitivity, specificity, positive

predictive value and negative predictive value results to merit recommendation for routine use.

75

Both capillary and venous glucometer samples produced reliable results; hence either sample can

be used to assess blood glucose level in the emergency room as may be convenient.

76

CONCLUSIONS

1. The prevalence of hypoglycaemia in children at admission in the Emergency Paediatric

Unit of FMC Owerri is high (7.5%).

2. The prevalence of hypoglycaemia was higher in younger children (aged below three

years).

3. Protein-energy malnutrition, sepsis, gastroenteritis and severe malaria were associated

with high prevalence of hypoglycaemia.

4. Hypoglycaemia is associated with increased mortality.

5. There is a strong positive correlation between capillary blood glucose, venous blood

glucose estimated using glucometer and glucose oxidase method.

6. Venous blood glucose and capillary blood glucose measured with “One-Touch” Ultra 2®

have 100% specificity and high positive predictive values for detecting hypoglycaemia.

They also have high sensitivity values.

77

RECOMMENDATIONS

1. Random blood glucose estimation should be done routinely for all sick under-5 children

on admission in emergency rooms.

2. Glucometers including the One-Touch Ultra 2® is recommended for screening and

monitoring of hypoglycaemia in children admitted into the emergency room.

78

LIMITATION

Children who had received glucose containing intravenous fluids within 6 hours before admision

were excluded from the study.

79

LINES OF FUTURE RESEARCH

1. A study of hyperglycaemia in emergency admissions and evaluation of its effects on

morbidity and mortality is advocated.

2. A longitudinal study incorporating follow up of the patients who had hypoglycaemia

could be invaluable.

80

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92

APPENDIX II

CONSENT FORM

Sir/ Madam,

My name is Dr Osuji Augustine Emeka of the Paediatrics Department of Federal Medical Centre, Owerri.

I am doing a study on Hypoglycaemia also known as low blood sugar in Children admitted into the

Emergency Paediatric Unit of FMC, Owerri. Low blood sugar is common in children who are sick

enough to be admitted and can worsen the final outcome of the illness. In this research, I am trying to find

out the number of admitted patients that have hypoglycaemia. If it is found that your child has

hypoglycaemia, it will be corrected immediately to prevent complications that come with it. This is

because low blood sugar can delay recovery or lead to a poor outcome even after recovery, but if

detected and corrected early, there is usually better outcome. This test will be done once and will not

affect your child’s treatment for the illness that brought him.

I will need to ask questions about you and your family, your child’s illness, how long the child has been

sick and the treatment received before presentation. A needle prick will be made at your child’s heel to

get a drop of blood for blood sugar estimation. I will also collect 2mls of blood, for further blood sugar

estimation. Blood sugar estimation is one of the necessary tests your child should do on admission and it

is safe and will not cause any harm to your child except slight pain from needle prick during blood

collection. Both the test that will be done here and the one that will be done at the laboratory will be at no

cost to you and your child. Please be informed that your child must not take part in this study and not

taking part in the study will not affect his treatment in any way. You are also free to withdraw your child

at any stage of the study.

If you have understood the explanations, and you are willing to allow your child to participate in the

study, kindly sign at the end of this letter. Feel free visit me at the department of Paediatrics, Federal

Medical Centre, Owerri in case you have any question subsequently. You can also contact me through

this number: 08037977010.

Name of Child

……………………………………………………………………………………………………………

Name of parent/ guardian

………………………………………………………………………………………………………………

Signature of parent/ guardian……………………………………………………………………….

Date……………………………………………………………………

93

APPENDIX III

PROFORMA

PREVALENCE OF AND RISK FACTORS FOR HYPOGLYCAEMIA IN CHILDREN AGED

1 MONTH TO 59 MONTHS ADMITTED INTO THE EMERGENCY PAEDIATRICS UNIT

OF FEDERAL MEDICAL CENTRE OWERRI.

A. Bio-data

- Folder number

- Age

- Sex

- Phone number of parent/guardian

B. Anthropometry

- Weight ( )kg

- Length/height ( )cm

- Mid arm circumference [MAC] ( )cm

- Chest Circumference ( )cm

C. Demographic data of parents

Father’s

occupation…………………………………………………………………………….

Father’s highest educational

Attainment………………………………………………………………………………

…….....

Mother’s

occupation…………………………………………………………………………..

Mother’s highest educational

Attainment…………………………………………………………………………

D. Clinical findings

94

Presenting Complaints

i Fever

ii Vomiting

iii Diarrhoea

iv Convulsion

v cough

Others…………………………………………………………………………………

Time of last meal ……………………………(duration………………) hours

Duration of illness

………………………………………………………………………………………..

Home treatments offered

I Drugs

Ii Herbal treatments

Iii Enema

Others…………………………………………………………………………………

Important examination Findings

I Unconsciousness

Ii Fever

Iii Respiratory distress

Iv Palor

V Dehydration

Others………………………………………………………………………………

1. Treatment History

Drug history

………………………………………………………………………………………

2. Results

Capillary blood glucose using glucometer mg/dl

Venous Blood Glucose using glucometer mg/dl

Laboratory Blood Glucose mg/dl

3. Diagnosis

Provisional

Diagnosis……………………………………………………………………………

Final Diagnosis

……………………………………………………………………………………

4. Outcome

Discharged Against Medical Advice (DAMA) [ ]

Discharged Home [ ]

Died [ ]

95

APPENDIX IV

CLASSIFICATION OF SOCIAL CLASS108

A. Demographic data of parents

1. Mother or Father’s occupation

Senior Public Servant (I)

Professional Managers/ Large Scale Trader, Intermediate Grade Public Servants (II)

Senior School Teachers, Junior School Teachers/ Drivers/ ArtisanS (III)

Petty Traders/ Labourers/ Messengers (IV)

Unemployed/ Full Time Housewife/ Students (V)

2. Mother or Father’s Educational Attainment

University Graduate Equivalent (I)

School Certificate Holder with Professional Training (II)

School Certificate or its Equivalent (III)

Modern Junior Secondary 3 and Primary 6 Certificate Holder(IV)

Illiterate (V)

3. Social Class Of Parents

Father’s score (score in 1+score in 2) + Mother’s score (score in 1+score in 2)/4

Social Class = I

Social Class = II

Social Class = III

Social Class = IV

Social Class = V

96