WHOLE1.indd ABSTRACT Objective: Our two main objectives are to assess the incidence and the outcome of severe hyponatremia in young hos- pitalized patients. Method: We retrospectively reviewed the incidence and outcome of severe hyponatremiac (Na <25 mmol/l) in- patients less than 8 years of age, admitted as consecutive admissions during one calender year. Psuedohyponatremia and artifactual hyponatremia were excluded. Patients’ demographics, clinical features, laboratory, treatment and outcomes were recorded. Results: Of 356 admissions of patients less than 8 years of age, 20 developed severe hyponatremia. Nausea, vomiting, irritability, clouded sensorium and seizures were the most common symptoms and signs. Underlying central nervous system disease, pneumonia and malignancy were major co-morbid conditions. The initial volume status was determined as hypervolemia (n=7), hypovolemia (n=7) and euvolemia (n=6). Iatrogenic (diuretics 5 and hypotonic fluids 7) hyponatremia accounted for 60% of all cases. Mortality was 20%. Conclusion: Patients receiving intravenous hypotonic fluids should be closely monitored for the development of hyponatremia. The common etiology of hyponatremia in our studied cohort of patients is iatrogenic. Keywords: Iatrogenic hyponatremia, high morbidity Incidence and Outcome of Severe Hyponatremia in Children and Young Adults A Single Institution Experience *Zakia Al-Lamki, Mahfooz A Farooqui and Saeed Ahmed SULTAN QABOOS UNIVERSITY MEDICAL JOURNAL JUNE 2006 VOL 6, NO. 1 SULTAN QABOOS UNIVERSITY© HYPONATREMIA (SERUM SODIUM <135 MMOL/L) has an incidence ranging from 15-20% in hospitalized patients.1 Severe hyponatremia is less common and studies addressing this particular issue in pediatric inpatients are few.2-13 Although the incidence of severe hyponatremia is not very high, this particular patient population is clinically significant due to associated predisposing conditions and adverse outcomes.2 Severe hyponatremia is also known to be a marker of serious illness in sick children.3 Department of Child Health, Sultan Qaboos University, College of Medicine and Health Sciences, P.O.Box 35, Al-Khod, Muscat 123, Sultanate of Oman *To whom correspondence should be addressed. Email: zakiya@squ.edu.om O R G I N A L S T U D Y ونتائجه الشديد الصوديوم انخفاض انتشار مدى معهد جتربة والشباب األطفال عند املرضى هذا االنخفاض عند نتائج ومعرفة الشديد الصوديوم انخفاض انتشار مدى تقييم وهما رئيسيني للدراسة هدفني امللخص: الهدف: هناك ١٢٥ ملي مول/ (أقل من الشديد الصوديوم انخفاض انتشار مدى حسبنا استعادية الطريقة: بصورة والشباب. األطفال من املستشفى في الراقدين نقص حاالت استبعاد مت واحدة. تقوميية سنة خالل متتابعة ملرات أدخلوا والذين ١٨ سنة، سن حتت املستشفى في الراقدين املرضى عند ونتائجه ليتر) النتائج: والعالج والنتائج. اتبرية واملعطيات الدميوغرافية والعالمات السريرية املعلومات تسجيل مت الفنية. عن األمور الناجتة احلقيقي غير الصوديوم والعالمات األكثر األعراض بني كان من الشديد. الصوديوم بانخفاض مصابا ٢٠ مريضا هناك كان ال١٨ سنة، حتت سن مرقدا ٣٥٦١ مريضا مجموع من اجلهاز أمراض فكانت لذلك املصاحبة األعراض أما والنوبات الصرعية. اخلارجي باحمليط اإلحساس وضعف االستقرار وعدم والتقيؤ انتشارا: الغثيان (٦ حاالت). وطبيعي (٧ حاالت) الطبيعي من وأقل (٧ حاالت) الطبيعي من حالة احلجم كانت أكثر تقدير الرئة واألورام اخلبيثة. املركزي وذات العصبي ٧ حاالت. في القليل) التركيز ذي (والسوائل ٥ حاالت، في للبول) املدرة األدوية - (استخدام احلاالت من ٪ ٦٠ في احلجم ألسباب طبية نقص لوحظ انخفاض حالة لكشف دقيقة بصورة الوريد طريق عن التركيز قليل سوائل يعطون الذين املرضى مراقبة ٢٠٪. اخلالصة: يجب الوفاة حاالت بلغت طبي املنشأ. هو في هذه الدراسة حلاالت نقص الصوديوم الرئيسي السبب الصوديوم. 14 Z A K I A A L - L A M K I , M A H F O O Z A FA R O O Q U I A N D S A E E D A H M E D No. Age Sex Pre- Fluids Lowest Na Volume Status Treatment Co- morbidities Symptoms Outcome 1 8 M None 110  D DCM SOB Died 2 5 M Hypo 123  NS DM N, V, I Discharged 3 3 M Hypo 107  NS SCD N, V Discharged 4 9 M None 124  FR BMT N, V Discharged 5 9 M None 122  None Surg, CNS I Discharged 6 8 M Hypo 124  NS, ABX SCD N, V, Sz Discharged 7 7 M None 122  NS CLD Ac, Hem Discharged 8 6 F Hypo 120  NS SCD Pain Discharged 9 2 M Hypo 111  D, HS Pneumonia N, V, I Discharged 10 1 M Hypo 123  ABX Down Synd, A-V Shunt, Sepsis N, V, Sz Discharged 11 2 M None 123  NS Pneumonia N Discharged 12 2 M Hypo 122  D Fanconi synd, Rickets None Discharged 13 <1 M Hypo 117  ABX Preterm, Sepsis None Discharged 14 <1 F None 117  NS Asphyxia, SAH Sz Died 15 <1 M NS 107  D CAH V, I Discharged 16 <1 F None 120  HS Inborn error of metabolism Sz Died 17 <1 M Hypo 123  D CNS V Discharged 18 <1 M Hypo 117  None Preterm Sz Discharged 19 <1 F Hypo 123  ABX CNS,Sepsis Sz Discharged 20 <1 M None 120  None Heart block, renal failure, DM None Died M= Male; F= Female; Pre-Fluids= Fluids administered before the development of hyponatremia; Hypo= Hypotonic fluids; =Hypervolemic; = Hypovolemic; = Euvolemic; D= Diuretics; NS= Normal saline; FR=Fluid restriction; ABX=Antibiotics; D=Diuretics; DCM= Dilated cardio- myopathy; DM=Diabetes mellitus; BMT= Bone marrow transplant; Surg= Surgical procedure performed; CNS= Central Nervous system disease; SCD= Sickle cell disease; CLD= Chronic liver disease; SAH= Subarachnoid hemorrhage; CAH= Congenital Adrenal Hyperplasia; SOB=Shortness of breath; N=Nausea; V=Vomiting, I=Irritability; AC=Altered level of consciousness; Hem=Hematemesis; Sz=Seizure Table 1. Patients’ demographics, clinical features, laboratory, treatment and outcome 15 INCIDENCE AND OUTCOME OF SEVERE HYPONATREMIA IN CHILDREN AND YOUNG ADULTS M E T H O D We retrospectively studied hospitalized patients <18 years old with severe hyponatremia (arbitrarily de- fined as serum sodium less than 125 mmol/l) admitted to Sultan Qaboos University Hospital from 1st January 1998 to 31st December 1998. These patients were iden- tified through the computerized hospital information system (HIS). Patients where hyponatremia was con- sidered to be artifactual (single serum sodium meas- urement of <125 mmol/l, which on repeat assessment within 6 hours, was normal >135 mmol/l without any therapeutic intervention) were excluded. Serum sodi- um was measured by indirect ion-selective electrode method (Beckman) and quality control values were set within 2%. Demographic data, physical signs and symptoms, laboratory data, treatment before and after the diag- nosis of severe hyponatremia, associated comorbid conditions and outcome were collected. Total number of pediatric admissions and deaths were also obtained for comparison. R E S U L T S There were 3561 admissions of patients less than 18 years of age in 1998. Twenty one patients had serum sodium of <125 mmol/l but one patient was exclud- ed due to artifactual hyponatremia. The remaining 20 patients were considered having true severe hy- ponatremia. Out of the 20 patients studied, 16 were male and 4 were females. All patients developed se- vere hyponatremia during hospitalization. Major co-morbid conditions included central nervous sys- tem disease 3, malignancy 2, pneumonia 2, diabetes mellitus 2, hypertension 2, and post-surgery 1. Nau- sea, vomiting, irritability and seizures were the most common clinical features. Seven patients were con- sidered as hypervolemic (hypertensive, elevated cen- tral venous pressure, edema and/ or use of diuretics). Seven patients were dehydrated (judged on the basis of clinical findings of dry mucus membranes, sunken eyes, hypotension and intravenous fluid requirement). Six patients were classified as euvolemic (not falling into either hypovolemic or hypervolemic categories). Use of hypotonic fluids was observed in 11 patients (35%) and diuretics in 5 (25%) prior to development of severe hyponatremia. None of the patients received antidiuretic hormone (ADH) analogs. Two patients were treated with hypertonic fluids; four were treated with isotonic fluids while the rest were managed with discontinuation of inciting agent (hypotonic fluids or diuretics). Of 3561 patients, thirty-one deaths were recorded for non-hyponatremic pediatric and young adult inpatients during the same period and four deaths in twenty patients with severe hyponatremia. Hence the mortality in general pediatric inpatients was 0.87% compared to 20% in patients with severe hyponatremia. Although we did not compare our pa- tients with a cohort of similar co-morbid conditions without hyponatremia, but comparison with unselect- ed non-hyponatremic patients showed mortality rate of 20 times high for hyponatremic patients. One pa- tient was discharged with residual neurological defi- cits and four patients (2 male and 2 female) died. D I S C U S S I O N Hyponatremia has been described with variable fre- quencies in children and young adults. The described frequency varies according to the level of hyponatrem- ia and age range under study. Iatrogenic factors are known to account for 40-66% of cases of hyponatremia.1 Common causes of iatro- genic hyponatremia include excessive water intake5 or intravenous administration of hypotonic fluids,6 use of antidiuretic hormone or its analogs,7 Carbamazepine,8 diuretics and postoperative hyponatremia.9 Admin- istration of hypotonic fluids and diuretics were com- mon causes in our series. Postoperative hyponatremia was seen in only one patient. Neurological symptoms such as irritability and seizures are dependant on the rate of development of hyponatremia. Chronic hyponatremia tends to be less symptomatic because of adaptation of cells in response to slowly developing hypoosmolality.10 Patients who developed seizures have a higher mortality. Routine anticonvulsants may be ineffective in seizures due to hyponatremia.11 Use of hypertonic saline to correct hyponatremia, if used judiciously, is known to be safe and effective. However, because of the risk of devel- opment of Osmotic Demyelination Syndrome (ODS), hypertonic saline should preferably be reserved for patients with acutely developing hyponatremia who become symptomatic. Acute hyponatremia should be corrected slowly and during the infusion of hypertonic saline serum levels should be monitored closely. In our series only two patients who had seizures were treated with hypertonic fluids and one of the two died. As these patients did not have autopsies, ODS was not diagnosed. Imaging studies such as CT and 16 Z A K I A A L - L A M K I , M A H F O O Z A FA R O O Q U I A N D S A E E D A H M E D MRI of brain may not show lesions typical of ODS for as long as a month. It may take 10 months for typical CT and MRI changes of ODS to appear.2 Mortality associated with hyponatremia is often high. It is difficult to determine the direct effect of hy- ponatremia to mortality rates due to the usual coex- istence of the other high risk co-morbid conditions. Dunn and Butt reported a mortality of 19% in their study of severe hyponatremia in pediatric inpatients,13 which is comparable to our observation. C O N C L U S I O N We confirm that severe hyponatremia in pediatric in- patients is associated with 20-times higher mortality when compared to unselected patients of the same age range. Caution should be exercised in administration of hypotonic feeds or fluids. Patients, who for some reason receive hypotonic fluids, should be monitored for development of hyponatremia. Hypotonic fluids need to be discontinued if hyponatremia develops. For symptomatic hyponatremia, hypertonic fluids should be considered and used judiciously. Serum so- dium should be monitored closely during therapy with hypertonic saline. In the presence of significant comorbid condi- tions, it is difficult to assess direct contribution of hy- ponatremia to death. 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