 |
|
Case Reports Indian Pediatrics 2001; 38: 1410-1412 |
||
|
Severe Hyponatremia in a Neonate – An Unusual Association |
||
|
K. Srinivasan S.K. Patole J.S. Whitehall
Association of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and severe hyponatremia during theophylline therapy has been reported in a neonate(1). A similar association with thiazide therapy has been reported in adults but not in neonates(2,3). We report a neonate who developed severe hyponatremia (Na <100 meq/litre) and findings suggestive of SIADH while on therapy with theophylline and thiazide. Case Report A 28-year-G1P0 mother delivered twins at 26 weeks of gestation following an elective Caesarean section for oligohydramnios and minimal end diastolic doppler flow in the second twin. First and the second twin weighed 790 and 1275 grams, respectively. Endotracheal intubation and positive pressure ventilation was required for the first twin at delivery. Apgar scores were 3 and 7 at 1 and 5 minutes, respectively. Recovery from respira-tory distress syndrome (RDS) after three doeses of surfactant allowed progressive weaning of mechanical ventilation and extubation to nasopharyngeal continuous positive airway pressure (CPAP) on day 4. Aminophylline was then commenced to prevent apnea of prematurity. Frequent apnea and bradycardia with desaturation necessitated reintubation on day 10. Follow-ing recovery from severe pulmonary hemorr-hage complicating a patent ductus arteriosus (PDA) and Staphylococcus epidermidis sepsis on day 11, he was on minimal ventila-tory support by day 16 [Peak inspiratory pressure/Positive end expiratory pressure: 12/4, rate 10/minute, oxygen: 21%]. Intravenous aminophylline (loading dose: 8 mg/kg, maintenance: 4 mg/kg/dose 12 hourly) restarted on day 15 was changed over to oral theophylline on day 24 at the same mainte-nance dose. (serum levels: 16 mg/liter). Chlorthiazide (25 mg/kg/dose 12 hourly) and spironolactone (1 mg/kg/dose 12 hourly) therapy was commenced on day 28 due to need for supplementary oxygen (30%) and continued dependency on CPAP (5 cm H2O). Serum sodium and potassium levels were 133 meq/liter and 4 meq/litre on day 29. The total fluid intake was 150 ml/kg/day of expressed breast milk from day 20 onwards whereas urine output and blood sugar levels ranged from 2-4 ml/kg/hour and 3-6 mmol/liter, respectively. Routine investigations on day 29 revealed serum sodium levels <100 meq/liter. The low levels were confirmed in the laboratory and also by using the blood gas machine (ABL 625 Radiometer, Copenhagen). Serum potassium, chloride, osmolarity, urea and creatinine were 3 meq/liter, 75 meq/litre, 204 mmol/liter, 13 mg/dl and 0.08 mmol/liter, respectively. Weight gain of 25 mg was noted along with a fall in urine output to 0.5 ml/kg/hour from 4 ml/kg/hour for previous 2 days. Urinary sodium, potassium and osmolarity and specific gravity were 25 meq/liter, 10 meq/liter, 357 mmol/liter and 1025, respectively. Blood sugar levels were between 4-6 mmol/liter during this entire phase of illness. No glucose was detected in the urine. Blood CSF and urine cultures did not indicate sepsis. Clinical examination was normal with no evidence of seizure activity. Systemic blood pressure, arterial oxygen saturation and blood gas analysis were within normal range. Cranial ultrasound was normal with no evidence of cerebral edema. Replacement therapy was commenced using intravenous 3% sodium chloride infusion. Serum sodium level of 119 meq/liter was reached at 19 hours from starting the replacement therapy. No abnormal neurological signs were noted during correction of hyponatremia. On day 31 the serum sodium level was 136 meq/liter. Follow up cranial ultrasound on day 65 was normal and he was transferred to a regional hospital on day 70 for ongoing care. Discussion Association of SIADH and severe hyponatremia with theophylline therapy has been reported in a neonate(1). Enhancement of antidiuretic hormone action by phosphodiesterase inhibition is the postulated mechanism for this association(1). Thiazide-induced hyponatremia has been reported in adults(2,3). Diuretic-induced hyponatremia stimulates the classic features of SIADH like low serum sodium level and osmolarity, relatively elevated urine sodium and osmolority, normal renal function and absence of edema or signs of extracellular fluid volume depletion(2). Diuretic-induced hyponatremia is also usually accompanied by hypokalemia(2). In absence of confirmatory diagnostic tests severe hyponatremia and SIADH in our case was most probably related to theophylline and/or thiazide therapy. There was no obvious cause like infection or intracranial pathology predisposing to hyponatremia or SIADH. Parameters of renal function were normal and he was not receiving any other medications except oral diuretics and theophylline known to be associated with hyponatremia and SIADH. To our knowledge thiazide-induced SIADH and subsequent hyponatremia has not been reported in neonates. Similar to the previously reported neonate (29 weeks gestation, serum sodium 110 meq/liter), theophylline level was normal in our case and hyponatremia (or its correction) was asymptomatic despite its severity (serum sodium <100 meq/liter)(1). Rapidity at which hyponatremia develops determines occurrence or otherwise of symptoms due to cerebral edema and increased cerebral interstitial pressure. The risk of development of increased cerebral interstitial pressure is less in neonates due to the open fontanels especially if hyponatremia does not develop acutely (within 24 hours)(4). Although the classification of onset of hyponatremia as acute or chronic is arbitrary, the neonate we report probably had a subacute (over 36 hours) onset of hyponatremia. Treatment of severe hyponatremia by hypertonic saline has been a controversial issue, more so if it is asymptomatic(4-6). Whether pontine demyelination in such cases is due to hyponatremia per se or due to its rapid correction using hypertonic saline is not clearly understood(4-6). In addition the desirable "safe" speed of correction is not known. Elevation of serum sodium levels to 120meq/litre over 20-24 hours is regarded as safe in prevention of neurological symptoms during correction of hyponatremia. Sudden onset of severe neurological symptoms (mainly convulsions) in a previously stable patient with severe hyponatremia has been reported(4). Despite lack of abnormal neurological signs we decided to treat our patient with hypertonic saline due to the dangerously low levels of serum sodium, aiming for the "comfort zone" of 120-130 meq/litre. The issue whether fluid restriction and frusemide alone would have corrected the sodium levels while avoiding the possible risk of cerebral injury related to hypertonic saline therapy is open for debate. In summary, we have reported a preterm neonate with severe hyponatremia and SIADH associated with theophylline and thiazide therapy. Close monitoring of electro-lytes during use of these medications is warranted in view of this association. Contributors: KS performed the literature search and wrote the first draft which was revised by SKP and JSW. SKP will act as guarantor for the manuscript. Funding: None. Competing interests: None stated.
| ||
| References | ||
|
