|Year : 2014 | Volume
| Issue : 1 | Page : 18-21
The serum electrolytes, urea and creatinine values in children with chronic heart failure on diuretic therapy
Wilson E Sadoh1, Osajie J Idemudia2, Patrick A Ekpebe1, Paul Aikhoriojie2
1 Department of Child Health, University of Benin Teaching Hospital, Benin City, Edo State, Nigeria
2 Department of Chemical Pathology, University of Benin Teaching Hospital, Benin City, Edo State, Nigeria
|Date of Web Publication||7-Apr-2014|
Wilson E Sadoh
Department of Child Health, University of Benin Teaching Hospital, PMB 1111, Benin City, Edo State
Source of Support: None, Conflict of Interest: None
Background: The response to chronic heart failure (CHF) involves activation of neurohormonal mechanisms that may alter the water and electrolytes homeostasis. Diuretic therapy also influences the electrolytes and water balance.
Objective: This study aims to evaluate the electrolytes, urea and creatinine levels in children with CHF on diuretic therapy in comparison with controls who do not have heart failure and are not on diuretics.
Methods: This cross-sectional study involved children with congenital heart disease on high ceiling diuretic, spironolatone and captopril with their age and sex matched controls. The electrolytes, urea and creatinine values were determined in standard fashion and compared between subjects and controls.
Results: There were 25 each of subjects and controls recruited for the study. The differences in the mean electrolytes, urea and creatinine values between subjects and controls were not significantly different, P > 0.05. There was no case of hypokalemia in either subject or control. There were more subjects than controls who had hyponatremia, P = 0.25. The mean electrolytes, urea and creatinine in subjects on therapy for <6 months were not significantly different from those on therapy for ≥6 months, P > 0.05.
Conclusion: The combination of high ceiling diuretic, spironolactone and captopril was able to maintain most electrolytes, urea and creatinine levels in children with CHF. However, subjects were more likely to have hyponatremia than controls. Regular electrolyte determination to exclude hypotremia is therefore recommended in children with CHF on diuretic therapy.
Keywords: Chronic heart failure, diuretic therapy, electrolytes
|How to cite this article:|
Sadoh WE, Idemudia OJ, Ekpebe PA, Aikhoriojie P. The serum electrolytes, urea and creatinine values in children with chronic heart failure on diuretic therapy. Nig J Cardiol 2014;11:18-21
|How to cite this URL:|
Sadoh WE, Idemudia OJ, Ekpebe PA, Aikhoriojie P. The serum electrolytes, urea and creatinine values in children with chronic heart failure on diuretic therapy. Nig J Cardiol [serial online] 2014 [cited 2019 May 19];11:18-21. Available from: http://www.nigjcardiol.org/text.asp?2014/11/1/18/130049
| Introduction|| |
Heart failure is a common cause of morbidity and mortality in children.  This is more so in developing countries like Nigeria where it is responsible for 5.8% and 15.5% of all hospital admissions. , Uncorrected congenital heart diseases with left to right shunts are common causes of chronic heart failure (CHF). , Heart failure is a syndrome of signs and symptoms that develop in response to the inability of the heart to pump adequate cardiac output to meet bodily requirements or dispose of the venous return.  The signs and symptoms result from a complex interplay of disorders of neurohormonal activation in an effort to maintain the circulatory homeostasis. 
The vasoactive neurohormonal renin angiotensin aldosterone system (RAAS) is central to the salt and water homeostasis. , The RAAS in part also activates the sympathetic nervous system (SNS) and arginine vaso pressin (AVP) system. In the RAAS system, the enzyme renin cleaves angiotensin I from angiotensinogen, which is further converted to angiotensin II by angiotensin converting enzyme (ACE). Angiotensin II causes vasoconstriction and activates the release of aldosterone which increases sodium and water retention in the distal tubules.  The SNS and AVP also contribute to salt and water retention, all leading to increase in blood volume in an attempt to correct the reduced cardiac output.  The general salt and water retention causes low electrolyte levels especially those of sodium, chloride and potassium. In the short-term, these compensatory mechanisms are able to maintain cardiac output and blood pressure. These compensatory mechanisms unchecked become deleterious to the body with disturbance of fluid and electrolyte homeostasis.
The treatment of childhood heart failure often involves the use of diuretics, ACE inhibitors and digoxin. ,, These medicines on their own also influence the salt and water balance; the high ceiling diuretics which are used because of their efficacy in reducing fluid retention also causes hypokalemia, hyponatremia and hypomagnesaemia.  In situations of CHF , spironolactone is often added to the loop diuretic to prevent hypokalemia. Spironolactone is recommended for patient management in 2001 European Society of Cardiology guidelines.  Spironolactone causes hyperkalemia, hyponatremia, mild acidosis and transient elevation of serum urea nitrogen. 
Children with uncorrected congenital heart disease who have CHF, are often placed on a combination of high ceiling diuretic and spironolactone. , There is a paucity of works evaluating the long-term outcome of diuretic therapy in children with CHF. The present study is conducted to evaluate the electrolyte, urea and creatinine profile of children with CHF on diuretic therapy in comparison with age and sex matched controls.
| Materials and Methods|| |
A convenient sample size of 25 subjects and controls each were recruited for the study. The subjects were children with echocardiographically diagnosed congenital heart disease attending the pediatric cardiology clinic at the University of Benin Teaching, Benin City. The controls were children attending the follow-up clinic for febrile illnesses such as non-severe malaria, pharyngitis and otitis media. In each case, the child would have been afebrile for at least 2 weeks prior to recruitment. The controls should also not have had diarrhea nor received diuretic therapy in the preceding 2 weeks.
Information on bio data of the subjects and controls were obtained with the aid of a proforma. The weight, type of anti-failure medicines including diuretics and duration of diuretic therapy were also noted. The patients received 2 mg/kg body weight per day of furosemide, Hydrochlorothiazide and spironolactone. Captopril was given at a dose of 0.3-3 mg/kg body weight per day in divided doses. The socio-economic class of the study population was determined using the method described by Olusanya et al. 
Sample collection and preparation
About 3-4 ml of venous blood was obtained from each participant and put into an anticoagulant bottle containing lithium heparin. The blood was centrifuge for 15 min at 3000 revolution/min, the plasma was separated and stored at −20°C until analysis was carried out usually within 1 week of collection.
The plasma sodium, potassium, bicarbonate and chloride were analyzed using the ion selective electrode system (ISE4000), the urea was estimated using the urease method whereas the plasma creatinine was analyzed using the modified Jaffe's method and o-cresol phthalein complexone method was used to estimate plasma calcium. 
The following values stated below were considered normal electrolyte ranges:
Data was entered into and analyzed using SPSS version 16.0 (Chicago, IL, USA). Continuous variables were presented as means ± standard deviations. The differences in means were compared using the Student t-test. The differences in proportions were tested using the Chi-square. Statistically significant P values was set at <0.05.
| Results|| |
A total of 25 subjects and 25 controls were recruited for the study. The subjects consisted of 16 (64.0%) males and 9 (36.0%) females. Their mean age was 24.1 ± 25.5 (range; 3-84) months while their mean weight was 9.0 ± 6.2 (range; 3.2-22.0) kg. Majority of the subjects (11 [44.0%]) were in middle socio-economic status (SES) and the least (6 [24.0%]) were in low SES.
The 25 controls consisted of 15 (60%) males and 10 (40%) females. The difference in the gender distribution of the subjects and controls was not statistically significantly, P = 0.77. Their mean age was 25.3 ± 27.4 (range; 3-98) months, it was not significantly different from the value in the subjects, P = 0.87. The mean weight and SES distribution of the controls are shown in [Table 1].
The underlying cardiac conditions causing heart failure in the subjects are shown in [Table 2]. Ventricular septal defect was the most common cardiac lesion occurring in 14 (56.0%). The least common were congenital mitral incompetence and corrected transposition of the great arteries in 1 (4.0%) each. The mean duration of anti-failure therapy was 6.3 ± 6.2 months (range; 3 weeks to 26 months). A total of 13 subjects had received anti-failure therapy for < 6 months and 12 subjects for ≥ 6 months.
[Table 3] shows the mean differences in values of the serum electrolytes, urea and creatinine between subjects and controls. The mean plasma chloride of the subjects (95.3 ± 5.0 mmol/l) was significantly lower than the value in the controls (102.8 ± 3.9 mmol/l), P ≤ 0.0001. Both values were however within the normal limit. The difference in mean values of the other electrolytes, urea and serum creatinine were not significantly different between subjects and control. None of the subjects had hypokalemia (potassium levels < 3 mmol/l). 6 (24.0%) subjects and 2 (8.0%) controls had hyponatramia, P = 0.25. Hypochloremia was present in one (4.0%) subject while no control had Hypochloremia. The mean plasma urea of subjects on anti-failure for <6 months 24.8 ± 12.9 mmol/l was significantly higher than the value obtained in those for ≥ 6 months 19.1 ± 4.3 mmol/l, P ≤ 0.0001 [Table 4].
|Table 3: Comparison of mean serum electrolytes, urea and creatinine in subjects and controls|
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|Table 4: Mean serum electrolytes, urea and creatinine levels by duration of diuretic therapy|
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| Discussion|| |
In the use of high ceiling diuretic, hypokalemia and its effects on the heart is a very important side-effect.  The mean potassium levels of subjects and controls were not significantly different neither were the mean levels in subjects and controls either lower or higher than normal suggesting the standard therapy for heart failure in children is able to prevent the hypokalemia associated with diuretic therapy. Besides this important function of maintaining normal potassium level, spironolactone although a weak diuretic, potentiates the effect of thiazide diuretics in the loss of water and sodium.  The side-effect of hyperkalemia in aldosterone therapy appears to be mitigated by the hypokalemia caused by the high ceiling diuretic. This finding in this study further justifies the inclusion of aldosterone in combination with a high ceiling diuretic as standard medicine in long-term diuretic therapy in CHF in children.
The maintenance of normal electrolyte profile by the regimen employed in this study appears to be effective irrespective of the duration of diuretic therapy. This is very important as most of these patients with congenital heart diseases in resource limited settings are on chronic diuretic therapy for a very long time until they are able to afford surgery, get sponsorship for their surgery or die from their condition.
Although the mean values of sodium between subjects and controls were not statistically significantly different, the mean values were in the hyponatremia range. However, there were more subjects than controls who had hyponatremia, suggesting that hyponatremia is commoner in children with CHF on diuretic therapy compared to children without heart failure and diuretic therapy. , It is noteworthy, that the subjects did not have severe hyponatremia that could have resulted in complications such as convulsions. Assessment of sodium level would appear to be a strong reason for regular electrolyte checks in children with congenital heart disease who are on diuretics.
Calcium homeostasis is important in heart failure as its abnormalities could result in myocardial contractile dysfunction and compound the pump failure. Furosemide is known to inhibit the Na-K-2Cl transporter and increase the urinary excretion of calcium while thiazide diuretic blocks the NaCl transporter and decreases urinary excretion of calcium. Thus furosemide and thiazide can alter serum calcium levels.  However, in this study, there was no child with abnormal calcium value suggesting that the anti-failure regimen used in this study is able to maintain normal calcium level. Heart failure is also known to adversely affect the renal functions because of the reduced cardiac output.  Furthermore, high ceiling diuretic therapy without potassium sparing has been reported to cause deterioration in renal functions in some adult hypertensive patients.  However, in this study, the renal functions of the subjects and controls were normal irrespective of the duration of therapy as measured by the serum creatinine. The possible effect of renal damage from diuretic therapy as reported in adults did not occur in children with CHF on diuretic therapy in this study, perhaps because the children were on combined high ceiling and potassium sparing diuretics. The small sample size in this study is acknowledged as a limitation.
| Conclusion|| |
The standard anti-failure therapy in childhood heart failure that includes high ceiling diuretic in combination with spironolactone and captopril is able to maintain most electrolytes especially potassium and calcium at normal levels. There is no associated renal damage irrespective of duration of therapy as shown by the normal creatinine levels. There are however, more subjects than controls with hyponatremia. The regular electrolyte check for hyponatremia in children with CHF who are on diuretic is therefore recommended.
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[Table 1], [Table 2], [Table 3], [Table 4]