This document discusses a case of a 56-year-old female patient presenting with bilateral lower leg cellulitis and hyponatremia. She has a history of epilepsy, intellectual disability, and is on multiple medications including Moduretic. Initial workup found sodium of 118 mmol/L. She was started on IV saline and diuretics. Carbamazepine was identified as a potential cause of drug-induced hyponatremia and was replaced with levetiracetam. She was discharged on frequent sodium monitoring. The document then reviews hyponatremia causes, presentation, evaluation, and treatment considerations including the risk of rapid correction.

1. A case of Hyponatraemia Phyo Aung & Li-ni Lin

2. Ms JH 56yo female referred from GP for bilateral lower leg cellulitis - unresponsive to Augmentin DF Prior to presentation at Angliss hospital 3 weeks of gross bilateral ankle oedema 2 weeks of bilateral lower limb cellulitis 4 days since commencing Moduretic Hyperactive behaviour at night Recently noted to be unsteady on feet.

3. Other medical conditions Epilepsy Intellectual disability secondary to SSPE measles Depression

4. Medications Premarin 300mcg mane Premia 1tab mane Sodium valproate 1000mg TDS Carbamazepine 400mg BD Citalopram 20mg nocte Olanzapine 10mg nocte Augmentin Duo Forte Amiloride 5mg/Hydrochlorothiazide 50mg mane Haloperidol 0.5mg nocte PRN Paracetamol 1g QID PRN

5. Social History lives in supported accommodation for mentally disabled

6. On examination HR 73, BP 120/70, RR 16, Temp 36.6 SaO2 99% on RA Patient alert but confused Chest clear JVPNE S1 and S2 heard, no murmurs Abdomen soft and non tender

7. Lower limbs Erythematous Warm to touch Pitting oedema up to knees (left more than right) No ulcers or breaks in skin

8. Investigations Na 118 K 3.7 Cl 83 Bicarbonate 27 Urea 4.4 Creatinine 34 FBE 103 /5.7/384

9. Bilirubin 3 ALP 114 GGT 54 ALT 12 TP 64 Albumin 30 Lipase 24 Ca 2.27 Mg 0.88 Phos 1.26

10. CRP 31 BSL 6.3 TSH 1.93 Vitamin B12 737 Folate 19 Serum osmolality 260 (280-300)

11. Urine Na 49 Urine K 37 Urine osmolality 370 Urine MCS no WBC no RBC no significant growth

12. CXR

13. CXR The lungs are clear. No consolidation is seen. There is no pleural effusion. Cardiomediastinal contour is within normal limits. CT Brain Unremarkable

14. Assessment 1. Bilateral lower limb cellulitis and oedema 2. Hyponatraemia Differential diagnoses: Drug-induced hyponatraemia +/- SIADH

15. Initial Management Free Water restriction Daily body weights Slow iv N/Saline 12/24 Moduretic ceased, commenced on frusemide orally 20mg daily iv cephazolin 2g TDS

16. iv N/Saline infusion started

17. iv N/Saline infusion ceased

18. After discussion with Neurology registrar: carbamazepine ceased and replaced with levetiracetam 500mg BD for 5days then 1g BD

19. Carbamazepine ceased, commenced on levetiracetam

20. Sodium levels during admission iv N/Saline infusion started iv N/Saline infusion ceased carbamazepine ceased, levetiracetam started

21. Further investigations US Doppler of both legs: On both sides the deep venous system is patent and compressible with no evidence for a thrombus. The great saphenous vein is also patent on both sides.

22. Echocardiogram Possible left diastolic dysfunction and mildly elevated PA pressure Left atrium mildly dilated Right atrium mildly dilated Trivial MR and TR

23. On Discharge Discussion with GP, who agreed to frequent U&E monitoring

24. 1997 Commenced on carbamazepine 100mg BD Major seizure requiring iv diazepam Several partial seizures requiring phenytoin infusion Patient already on sodium valproate 1200mg BD

25. Why Sodium disorder ? Important and most common electrolyte abnormality Has potential for significant morbidity and mortality Its homeostasis is vital to normal physiologic function of cells Most dominant extracellular cation Normal level is 135  145 mmol /L Hyponatremia is defined as < 135 mmol/L Severe hyponatremia < 125 mmol/L

28. Clinical Presentation Symptoms ranging from nausea and malaise (Mild Reduction) to confusion, seizures and coma (Severe Reduction) Neurological symptoms =due to intracerebral osmotic fluid shift and cerebral edema Neurological symptoms depends upon rapidity and severity of the serum sodium drops Can also find symptoms of associated medical conditions eg.CCF, Liver Failure, Renal Failure

29. Assessing Fluid Status Features of fluid overload Elevated JVP Crackles over lung bases Odema Features of reduced extracellular fluid dry mucous membrane tachycardia postural hypotension oliguria increased urine specific gravity

30. Investigations Urine Sodium and Osmolarity Urine:Plasma osmolarity normal ( >1.3:1) Serum Osmolarity and electrolytes Thyroid Function tests Liver function tests Urea and Creatinine Serum albumin,triglycerides,Serum cortisol levels Imaging tests s/a CT Scan,Ultrasound,CXR

31. Treatment of Hyponatremia Acute Onset < 3 days Symptoms ++ Tolerate rapid correction Needs hypertonic solution Chronic Onset Longer period Sometimes asymptomatic Slow correction needs rapid correction can damage brain by demyelination Usually treated with free water restriction and treat underlying cause

32. Treatment of severe acute hyponatremia Use of hypertonic solutions depends upon Duration and Magnitude of Hyponatremia Degree and Severity of Clinical Symptoms If Hypertonic saline is used, Na+ should be checked 2 to 4 hourly The desired increase in Na+ is 0.5 to 1.0 mol/L per hour Na+ deficit = 0.5 x Body Wt x (Desired – Current Na+ level) 0.5 x 60 kg x (125- 110) 0.5 x 60 x 15 = 450 mmol /L Normal Saline 0.9 % contains 150 mmol /L 3% Saline contains 500 mmol / L

33. Danger of rapid correction Osmotic myelinosis ( Central Pontine Myelinosis) rapid correction of Na in chronic hyponatremic patients  Increasing extracellular tonicity  Brain Cells compensate by losing water  if hypertonic saline continue  drives water out of cells  myelinosis Clinical Symptoms Spastic quadriparesis Difficulty in swallowing Speech problems Diplopia Delirium+Coma Deficits can be permanent.

35. Medical Treatments Frusemide Increase free water excretion and sodium absorption. Demelcocycline (Hypotonic Hyponatremia caused by SIADH) cause insensitivity of distal renal tubules to the action of ADH and produce a nephrogenic diabetes insipidus. Dose 600 – 900 mg/day Needs renal physician consult Lithium Arginine Vasopressin antagonists (for Hypervolemic Hyponatremia) Aquaresis effect( increase urine output of mostly free water, with little electrolyte loss

36. Anti diuretic hormone

37. Syndrome of Inappropriate ADH Secretion Drugs Carcinoma Miscellaneous Pulmonary Diseases Neurological SIADH

38. Diagnosis Criteria for SIADH Hyponatremia (< 130 mmol/l) 118 mmol/l Low plasma osmolarity(<270 mmol /kg) 260 mmol/kg High urinary sodium(>30 mmol/l) 49 mmol/l High urinary osmolarity(>150 mmol /kg) 370 mmol/kg Low/Normal plasma urea+creatiine Normal Cardiac, Liver , Thyroid functions

39. Drugs commonly associated with hyponatremia Class Drug Mechanism Diuretic Amiloride /Hydrochlorothiazide Indapamide Depletion total body sodium SSRI Sertraline Citalopram and others SIADH MAOI Moclobemide SIADH Anticonvulsant Carbamazepine SIADH Antipsychotic olanzipine SIADH

40. Summary Hyponatremia is a common medical condition Management depends upon severity of clinical symptoms , duration and magnitude of sodium loss Need to remember the danger of osmotic myelinosis Drug induced hyponatremia is common Polypharmacy make prevalence of drug induced hyponatremia likely to increase.

41. References Therapeutic Guidelines Australia Prescriber Magazine Vol.26 No.5 2003 Harrison’s 17 edition MIMS Online eMedicine N Eng Journal Med 2000 , Hyponatremia Dysnatremia management ,Acute Care Medicine Course Clinical Physiology of electrolyte disorder