An Observational Study of Serum Electrolyte Abnormalities (Na+ & K+) in Patients Admitted to a Tertiary Care Pediatric Intensive Care Unit

An Observational Study of Serum Electrolyte Abnormalities

(Na+& K+) in Patients Admitted to a Tertiary Care

Pediatric Intensive Care Unit.

Introduction & Purpose of the Study:

Electrolytes (in the body) are electrically charged minerals such as Na+,K+,Ca2+,PO43-, and Mg2+ which are critical for nerve and muscle cell function. Electrolyte abnormalities are common in children who need intensive care.1They occur in a variety of conditions, may remain unrecognized and result in morbidity and mortality irrespective of the primary problem/ diagnosis.2

Definitions3,4

Normal sodium value is 135 - 145 mEq/l

a. Hyponatremia         <135 mEq/l

b. Hypernatremia        >145 mEq/l

Normal potassium value is 3.5- 5.5 mEq/l

a. Hypokalemia          < 3.5 mEq/l

b. Hyperkalemia         >5.5 mEq/l

Mild(mEq/L)

Moderate(mEq/L)

Severe(mEq/L)

|Hyponatremia

130-134 mEq/L

120-129 mEq/L

|Hypernatremia

146-149 mEq/L

150-169 mEq/L

/=170 mEq/L

|Hypokalemia

<3.5 mEq/L

2.5-3 mEq/L

<2.5 mEq/L

|Hyperkalemia

<6 mEq/L

6-7 mEq/L

7 mEq/L

Sodium is the predominant cation in the extracellular fluid. It is the major determinant of serum osmolality and hence, is responsible for maintenance of intravascular volume.2,3,5,13The presence of either hypernatremia or hyponatremia (i.e. dysnatremias) in the intensive care unit (ICU) are an independent risk factor for poor prognosis on admission or during ICU stay.1,6,7

Five possible mechanisms for the occurrence ofelectrolyte imbalance are the:

·       Underlying disease process

·       End organ injury

·       Fluid and electrolyte interventions

·       Use of medications with potential of electrolyte derangements, and

·       Application of critical care technology i.e. positive pressure ventilation.3,4

 Critical care provision via the pediatric intensive care units (PICU) is aimed at maintaining‘homeostasis’ in the body, which is vital for theorgan’s support and optimal function. This involvesnot only fluids but also the electrolyte balance.8Electrolyte imbalance (Na+/K+) in either direction, i.e. lower or higher than normal values can affect the cellular and metabolic processes, which may result in cardiac and neurologic complications, thus altering patient’s status in terms of morbidity and mortality.9These electrolyte imbalances also result in longer stay in hospital, thus adding significantly to the cost of the stay and medical management in the hospital.10,14Electrolyte imbalance can significantly affect the quality of life of the patient.Timely recognition, a high index of suspicion and a thorough understanding of common electrolyte abnormalities is necessary to ensure their correction.Early recognition & intervention to correct these imbalances is essential to avoid poor outcomes.11,12 These electrolyte disturbances may aid in diagnosis of the illness and can also act as markers of disease severity and potential of recovery from disease.2,3There is a need to understand the different etiologiesof electrolyte imbalances and their outcomes in our pediatric ICU patient population. Hence, we have decided to undertake the present study.

Review of Literature:

[1] Rao SSD, Thomas B. Electrolyte abnormalities in children admitted to pediatric intensive care unit. Indian Pediatr. 2000;37(12):1348-1353.

Electrolyte abnormalities were observed in 32.4% of children getting admitted to PICU. Hyperkalemia was the commonest abnormality. In this study, hypokalemia was almost evenly distributed in diseases of various systems. Hyperkalemia was found usually associated with renal diseases and infectious diseases.The morbidity was significantly higher in patients with hyponatremia when compared to those with normonatremia. Mortality rates in patients with mixed electrolyte abnormalities were higher when compared to those with single electrolyte abnormality.Electrolyte abnormalities were common even in children without diarrheal diseases, who are admitted to PICU. They contributed significantly to the mortality and morbidity. The authors state that since the specific symptoms of electrolyte abnormality often merge with the underlying disease, close monitoring and correction of electrolyte abnormalities is important to reduce morbidity and mortality.1

[2]Naseem F, Saleem A, Mahar IA, Arif F. Electrolyte imbalance in critically ill paediatric patients. Pak J Med Sci. 2019;35(4):1093-1098.

Presence of electrolyte imbalance at the time of admission is an important prognostic indicator in critically ill children irrespective of primary disease process and needs to be addressed aggressively.In this study, overall electrolyte abnormalities were found to be around 85%. Since the five electrolytes were considered together and imbalance among any of them was noted, this might be the reason for the high incidence. Majority had respiratory, neurological and infective/sepsis etiology.Although majority had abnormality of a single electrolyte, mixed disorders with combination of two, three, four and all five electrolytes were also seen.Hypocalcemia was the most frequent abnormality. The presence of dysnatremias (either hypo- or hyper-natremia) in intensive care unit has been reported to be around 30%.Hypokalemia and hyperkalemia were observed in 31% and 19% cases respectively.Morbidity was significantly observed in these cases with ventilatory requirement of 82% of cases.It was observed in this study that medications commonly used in intensive care units may contribute to the electrolyte disturbances.Morbidity in terms of complications was also significant in such cases i.e. AKI, MODS, CCF, and SIADH were seen exclusively in patients having electrolyte imbalance.3

[3]Rukesh CC, Shalini B. Correlation between serum electrolytes and clinical outcome in children admitted to PICU. IOSR J Dent Med Sci. 2017;16:11:24-27.

This study showed that there is prolonged duration of stay in case of electrolyte abnormalities (>5 days). This study found that hyponatremia leads to prolonged stay. This study also showed that hyperkalemia with primary illness leads to high mortality rate, in comparison to hypokalemia and other electrolyte disturbances. In this study maximum mortality rate i.e. 30.77% was found in hyperkalemia.Hyponatremia was the most commonly encountered dyselectrolytemia and was mostly found associated with respiratory illnesses. The authors concluded that mortality in PICU is mainly linked to primary illness, but abnormality of serum sodium and potassium remain significant predictors of mortality.9

[4]Panda I, Save S. Study of association of mortality with electrolyte abnormalities in children admitted in pediatric intensive care unit. Int J Contemp Pediatr. 2018;5:1097-1103.

This study had demonstrated significant association of electrolyte abnormalities at admission in PICU with mortality and primary organ system involvement. The prevalence of electrolyte abnormality in terms of sodium or potassium abnormality in this study was 44.3%. Hyponatremia  followed by hypokalemia  was the most common electrolyte abnormality. The mortality in children with electrolyte abnormality was found to be 28.8%, which was significantly higher than mortality in those without electrolyte abnormality. Maximum children with hyponatremia had central nervous system involvement and those with hypernatremia had gastrointestinal involvement. Hypokalemia was most frequently observed with gastrointestinal involvement and hyperkalemia with renal involvement.10

[5]Routray M, Kishore SV, Champatiray J, SatpathySK. Demographic variation of electrolyte imbalance in a tertiary care pediatric intensive care unit**. Int J Contemp Pediatr. 2020 Feb;7(2):224-229.**

This study shows that the incidence of electrolyte imbalance is high in children with critical illness, which is at 37.91% of the total admission. Hyperkalemia followed by hyponatremia was found to be the commonest. Children between the age of 1 to 5years had a higher incidence of electrolyte disturbance. Patients with pathology in central nervous system followed by respiratory system were more often involved. Higher degree of suspicion regarding SIADH must be kept in mind when electrolyte imbalance pertaining to euvolemic hyponatremia patients, especially with respect to respiratory system illness followed by central nervous system.11

[6]Sachdev A, Pandharikar N, Gupta D, Gupta N, Gupta S, Venkatraman ST. Hospital- acquired Hyponatremia (HAH) in Pediatric Intensive Care Unit. Indian J Crit Care Med. 2017;21(9):599-603.

HAH is common in the PICU patients, and postsurgical status, use of ADH-stimulating drugs, and fluid intake were significant risk factors for the development of HAH. The patients with HAH had prolonged PICU stay and longer mechanical ventilation days.The incidence of HAH in this study was 19.3% in all the children admitted to the PICU. The study included only those patients who were isonatremic at admission.The incidence of acute hyponatremia (<48 h) in the study was 52%.Majority of the patients in the study had mild hyponatremia.Patients in hyponatremic group had a higher intake of fluids when compared to isonatremic group.Postoperative patients were predisposed to hyponatremia due to various reasons such as occult hypovolemia and non-osmotic stimuli such as nausea, vomiting, pain, anesthesia, and opioid analgesics.With regards to IV fluids, majority of the patients in the hyponatremic group had received half-saline (0.45% NaCl with 5% dextrose), but there was no significant difference in the type of IVF used between the two groups. Even patients who received isotonic fluids had developed hyponatremia. Children in hyponatremic group had a higher length of PICU stay and ventilator.13

[7]Singhi S, Jayashree M. Free water excess is not the main cause for hyponatremia in critically ill children receiving conventional maintenance fluids. Indian Pediatrics. 2009 Jul 1;46(7):577-583.

This study has taken the lower cut off value of hyponatremia(<130mEq/L), hence the incidence of hyponatremia in this study population was 3.5 episodes/100 patient days.The authors found that though the hyponatremic children were hypo-osmolar with a net positive fluid balance, the magnitude of the positive fluid balance, sodium balance and natriuresis in the days preceding hyponatremia in these patients was similar to that of post-hyponatremic phase and those having serum sodium >130 mEq/L group. Over expansion of intravascular space and dilutional hyponatremia usually results from either an increased EFW intake or an impaired water excretion.In fact the EFW intake and fluid balance was lower in the hyponatremic group compared to the normo-natremic group.14

[8]Singhi S, Marudkar A. Hypokalemia in a pediatric intensive care unit. Indian Pediatrics. 1996 Jan 1;33:9-14.

This study concluded that predisposing factors for hypokalemia include- the nature of primary disease (renal disease,septicemia, acute diarrhea, heart disease with congestive failure, and meningoencephalitis), malnutrition (weight for age less than 80%) and therapy with drugs (diuretics, corticosteroids and antiasthma drugs).Patients received 4-6 mEq potassium per 100 ml of intravenous fluids (slow correction) for correction.The overall mortality among patients with hypokalemia was significantly higher than that among the remaining PICU patients.All the patients receiving rapid correction survived.15

[9]Cummings BM, Macklin EA, Yager PH, Sharma A, Noviski N. Potassium abnormalities in a pediatric intensive care unit: frequency and severity. Journal of Intensive Care Medicine. 2014 Sep;29(5):269-74.

In this study one-third of patients had abnormal values of potassium, out of which  hypokalemia was the most common abnormality seen. Mild potassium abnormality was found to be common in PICU. On analysis,it was found that severity of hypokalemia was associated with mortality. Guidance in monitoring frequencies of potassium abnormalities in pediatric critical care is needed according to the authors.16

[10]Agarwal N, Rao YK, Saxena R, Acharya R. Profile of serum electrolytes in critically ill children: A prospective study. Indian Journal of Child Health. 2018 Jan 29:128-32.

This study showed a high incidence of electrolyte abnormalities in acutely ill children admitted to PICU. The authors state that since the specific symptoms of electrolyte abnormality often merge with the underlying disease, they remain unrecognized and contribute significantly to the morbidity and mortality besides the primary illness.17

[11]Sadeghi-Bojd S, Noori NM, Damani E, Teimouri A. Electrolyte disturbances in PICU: A cross sectional study. Nephro-Urology Monthly. 2019;11(2).

The study showed that the frequency of electrolytes was significantly different in deceased children compared to alive children. Prevalence of hypokalemia and hyperkalemia were higher in girls compared with boys. However, hyperkalemia was significantly higher in children with diuretic use than in other children. Therefore, the authors state that “it is much necessary to measure these electrolytes in course of hospitalizationâ€.18

[12]Paidy AR, Thapar RK, Gupta RK. Electrolyte disturbances in critically ill children admitted to paediatric tertiary care centre. J Evol Med Dent Sci (JEMDS). 2017 May 22;6:3269-73.

Hyponatraemia was the most common electrolyte abnormality in this study.1 month - 4 years age was found to be susceptible age group to electrolyte disturbances with mean age of 4.36 ± 4.10 yrs. Spectrum of illness in hyponatraemia included CNS disorders, GI disorders and sepsis. In hypernatraemia, the spectrum included CNS disorders only. In hypokalaemia group, the spectrum included CNS disorders, GI disorders, sepsis and renal disorders. In hyperkalaemia group, the spectrum included CNS and GI disorders.Mortality was 1.9 times higher in children with hyponatraemia and 1.2 times higher in children with hypokalaemia compared to normal serum levels.19

[13]Octavia AC, Setyaningtyas A, Edwar PP. Electrolytes Profile of Critically Ill Patients Admitted To Pediatric Intensive Care Unit (PICU) Dr. Soetomo General Hospital. Indonesian Journal of Anesthesiology and Reanimation. 2020 Jan 30;2(1):1-7.

The majority of the patients with electrolyte abnormality were in the age group of infants or 1-12 months old.The common main diagnoses in most patients were digestive system disorders followed by the central nervous system, respiratory system, kidney, and cardiovascular disorders. Most frequent electrolyte disorders were hypocalcemia followed by hypokalemia followed by hyponatremia and the least was hypochloremia. In patients with hyponatremia, the most common primary diagnosis was central nervous system disorders (meningoencephalitis, seizures), respiratory system disorders (pneumonia), and others (leukemia, diabetic ketoacidosis due to type 1 diabetes mellitus).In patients with hypokalemia, the most common primary diagnosis was respiratory system disorder and the most common primary diagnosis of patients with hyperkalemia were endocrine and metabolic system disorders. Critically ill patients with electrolyte disorders admitted to the Pediatric Intensive Care Unit (PICU) were tend to experience low electrolyte levels. The most frequent were hypocalcemia, hypokalemia, hyponatremia, and hypochloremia.20

[14]Elala G, Shimelis D. Patterns of electrolyte abnormalities in children 0-15 years of age admitted to pediatric emergency and intensive care units of a tertiary hospital. IOSR Journal of Dental and Medical Sciences. 2018;17(2):12-6.

Most common electrolyte abnormality observed was hyponatremia followed by hypokalemia. The most common causes of hyponatremia were cardiovascular disease, renal abnormality and central nervous system problem. Hypernatremia contributed to long hospital stay and significant mortality. Eight times increase in mortality was observed in hyperkalemic children. Electrolyte abnormalities are common in children admitted to the emergency and intensive care units with an underlying medical illness and contribute to significant morbidity and mortality. Preventive measures in high risk patients and early treatment would decrease morbidity and mortality.21

[15]Das A, Sil A, Biswas S, Gupta AK. Serum electrolyte level as a marker of morbidity in critically sick children: a study from a rural tertiary care hospital. International Journal of Scientific Research. 2019 Jul 8;8(2).

Electrolyte abnormalities were found mostly in infants and the cause of admission in PICU in the majority was due to respiratory illnesses.Hyponatremia followed by hypokalemia is the most common electrolyte involved. This study showed that electrolyte abnormalities are common in critically ill children and contribute to significant morbidity. The authors state that timely recognition through regular monitoring and appropriate correction of electrolyte abnormalities will help in improving the outcome besides the usual management of the primary disease**.**22

Aims and Objectives**:**

The Aims and Objectives of the present study are –

Primary objectives:

1.     To determine the frequency of patients with electrolytes (Na+& K+) abnormalities among patients who get admitted to the pediatric intensive care unit (PICU).

2.     To determine the frequency of patients who develop electrolytes (Na+& K+) abnormalities during their PICU stay.

3.     To determine the primary organ system involved and primary diagnosis in children with electrolyte (Na+& K+) abnormalities (both the above categories of patients, i.e. those who present with electrolyte abnormalities & require PICU admission and those who develop electrolyte abnormalities during their PICU stay.

4.     To determine the possible etiology/cause of the electrolyte (Na+& K+) abnormalities.

Secondary objectives:

1.     To determine the severity of the electrolyte (Na+/ K+) abnormality.

2.     To determine the mean duration in which the Na+/K+ abnormality gets corrected.

3.     To determine the outcome in children with Na+/K+ abnormality.

Materials &Methods:

Ethics**:** The study will be initiated after seeking approval from Institutional Ethics Committee of Seth G.S. Medical College & KEM hospital.

Consent & Assent**:**Case enrolment will be done after obtaining a written informed consent from the parent/guardian. Since patients in the PICU are critically ill, waiver of assent will berequested for (from the IEC).

Study design**:**Prospective, non-interventional, observational, single centre, cohort study.

Study duration: The enrollment in this study will be conducted over a period of 12 months (prospectively) after institutional ethics committee approval. Each patient will be in the study till their stay in the PICU or till death in the PICU.

Study site**:**The study will be conducted in patients admitted to the Pediatric ICU (PICU) of K.E.M Hospital, Mumbai. This PICU is a tertiary care ICU with state of art facilities for delivering critical care. It is a fifteen bedded PICU and is manned by resident medical officers and fellows round the clock. One Professor and Additional Professor look after the day to day clinical and administrative matters of the PICU and they are assisted by one Associate Professor & one Assistant Professor.

**Total number of patients to be studied (Sample size calculation):**It has been noticed that the average number of admissions to the KEM Pediatric ICU is estimated to be around 300 per year for the next one-two years (considering the COVID pandemic), of which nearly 30% patientsare expected to show electrolyte (Na+ & K+) abnormalities. So, taking e as 0.05; p = 0.4; N = 300; z = 1.96, the sample size is calculated to be 155.

Z= 1.96,

N= number of PICU admissions per year=300

e= margin of error=0.05

p= prevalence of Na+ and K+ abnormalities in PICU = 30%

Inclusion Criteria**:**All consecutive patients admitted to the PICU will be enrolled in the study. No patients will be excluded except those whose parents/ guardians do not consent to participate in this study.

**Confidentiality:**The participant’s details will not be disclosed at any point of time. Also, during publication of the data, all care will be taken so as to not disclose the details of the individual participants/ subjects.

Data Recording**:** Following data/ information will be recorded in a pre-designed case record form (from the patient’s hospital case-sheets/ indoor medical papers) –

·       age, sex, date of admission to hospital and PICU, duration of PICU & hospital stay, primary diagnosis (etiology) and system affected,

·       serum sodium i.e. Na+ and serum potassium i.e. K+ level at the time of admission to PICU, serum Na+ and K+ level at subsequent intervals (as and when they are done as per PICU protocols, no additional collections will be done apart from those required as per routine management of the patient as per existing PICU protocols),

·       day on which any serum Na+ and K+ level abnormality first detected (for patients already admitted to PICU),

·       reason (if any) for the serum Na+ and K+ level abnormality,

·       time in hours in which the serum Na+ and K+ electrolyte abnormality gets corrected,

·       treatment given for correction of the Na+ and K+  abnormality,

·       any complication/s  due to the Na+/K+ imbalance, and

·       the final outcome (Survival / Death).

The enrolled patient’s medical record will be scrutinized on daily basis until discharge from PICU or until death of the patient or transfer of the patient back to the Pediatric ward, whichever is earlier. Each PICU admission will be considered as fresh patient enrolled for purpose of inclusion in this study, even for patients who get readmitted to the PICU. All the collected data will be derived from routinely recorded data in the PICU indoor sheets and no additional blood collection or investigations will be done for the purpose of this study alone. Patients will not incur any extra / additional costs/ expenses or visits for the study purpose.

Statistical Analysis:

Results of the quantitative variables will be expressed in terms of mean, median and mode. The frequency of patients with Na+/K+ abnormalities during PICU admissions and the patients who develop Na+/K+ abnormalities during PICU stay will be listed as percentage of total patients.The possible etiology or cause of electrolyte (Na+/K+) abnormality will also be listed as percentage of total patients. Duration (hours) in which the Na+/K+ abnormality get corrected will be expressed as mean, median and mode. The final outcome will be compared between patients with and without electrolyte abnormalities who died from patients and those who survived (Chi square test).

Expected outcomes of the study:

It is hoped that this study will help in-

• Understanding how common electrolyte (Na+/K+) abnormalities are in our hospital medical PICU settings.
• To understand different etiologies that causes Na+/K+ abnormalities in KEM hospital PICU.
• To understand whether Na+/K+ abnormalities affect the outcome.

References:

1.     Rao SSD, Thomas B. Electrolyte abnormalities in children admitted to pediatric intensive care unit. Indian Pediatr. 2000;37:1348-53.

2.     Greenbaum LA. Pathophysiology of body fluids and fluid therapy. In: Kliegman RM, Stanton BF, St Geme III JW, Schor NF, editors. Nelson’s Textbook of Pediatrics. 20th ed. Canada: Elsevier; 2016:350-363.

3.     Naseem F, Saleem A, Mahar IA, Arif F. Electrolyte imbalance in critically ill paediatric patients. Pak J Med Sci. 2019;35(4):1093-1098.

4.     Hauser GJ, Kulick AF. Electrolyte disorders in the PICU. In: Wheeler DS et al, eds. Pediatric critical care medicine. London: Springer-Verlag; 2014;13:147-61.

5.     Patel S. Sodium balance-an integrated physiological model and novel approach. Saudi J Kidney Dis Transpl. 2009;20:560-9.

6.     Barron R, Freebairn R. Electrolyte disorders in the critically ill. Anaesth Intensive Care Med. 2010;11(12):523-8.

7.     Gibbs R, Macnaughton P. Electrolyte and metabolic disturbances in critically ill patients. AnaesthIntens Care Med. 2007;8(12):529-33.

8.     Balci AK, Koksal O, Kose A, Armagan E, Ozdemir F, InalT, et al. General characteristics of patients with electrolyte imbalance admitted to emergency department. World J Emerg Med. 2011;4(2):113-116.

9.     Rukesh CC, Shalini B. Correlation between serum electrolytes and clinical outcome in children admitted to PICU. IOSR J Dent Med Sci. 2017;16:11:24-27.

10.  Panda I, Save S. Study of association of mortality withelectrolyte abnormalities in children admitted in pediatricintensive care unit. Int J ContempPediatr. 2018;5:1097-1103.

11.  Routray M, Kishore SV, Champatiray J, SatpathySK. Demographic variation of electrolyte imbalance in a tertiary care pediatric intensive care unit. Int J ContempPediatr. 2020 Feb;7(2):224-229.

12.  Singhi S, Prasad SVSS, Chugh KS. Hyponatremia in sick Children: a marker of Serious illness. Indian Pediatr. 1994;31:19-23.

13.  Sachdev A, Pandharikar N, Gupta D, Gupta N, Gupta S, Venkatraman ST. Hospital- acquired Hyponatremia in Pediatric Intensive Care Unit. Indian J Crit Care Med. 2017;21(9):599-603.

14.  Singhi S, Jayashree M. Free water excess is not the main cause for hyponatremia in critically ill children receiving conventional maintenance fluids. Indian Pediatrics. 2009 Jul 1;46(7):577-583.

15.  Singhi S, Marudkar A. Hypokalemia in a pediatric intensive care unit. Indian Pediatrics. 1996 Jan 1;33:9-14.

16.  Cummings BM, Macklin EA, Yager PH, Sharma A, Noviski N. Potassium abnormalities in a pediatric intensive care unit: frequency and severity. Journal of Intensive Care Medicine. 2014 Sep;29(5):269-74.

17.  Agarwal N, Rao YK, Saxena R, Acharya R. Profile of serum electrolytes in critically ill children: A prospective study. Indian Journal of Child Health. 2018 Jan 29:128-32.

18.  Sadeghi-Bojd S, Noori NM, Damani E, Teimouri A. Electrolyte disturbances in PICU: A cross sectional study. Nephro-Urology Monthly. 2019;11(2).

19.  Paidy AR, Thapar RK, Gupta RK. Electrolyte disturbances in critically ill children admitted to paediatric tertiary care centre. J Evol Med Dent Sci (JEMDS). 2017 May 22;6:3269-73.

20.  Octavia AC, Setyaningtyas A, Edwar PP. Electrolytes Profile of Critically Ill Patients Admitted To Pediatric Intensive Care Unit (PICU) Dr. Soetomo General Hospital. Indonesian Journal of Anesthesiology and Reanimation. 2020 Jan 30;2(1):1-7.

21.  Elala G, Shimelis D. Patterns of electrolyte abnormalities in children 0-15 years of age admitted to pediatric emergency and intensive care units of a tertiary hospital. IOSR Journal of Dental and Medical Sciences. 2018;17(2):12-6.

22.  Das A, Sil A, Biswas S, Gupta AK. Serum electrolyte level as a marker of morbidity in critically sick children: a study from a rural tertiary care hospital. International Journal of Scientific Research. 2019 Jul 8;8(2).