A 63 year old woman was admitted to the ICU from the Emergency Department with acute alcohol withdrawal, severe hyponatraemia (serum sodium level 114mmol/L), rhabdomyolysis (creatine kinase 46930u/L) and acute kidney injury (serum creatinine 262umol/L, urea 8.7mmol/L, potassium 4.6mmol/L, base excess -6.8 and anuric from the point of admission). Her corrected calcium level was 1.92mmol/L. She had been discovered on the floor at home after a presumed fall. It was unknown how long she had been on the floor, but there were extensive pressure injuries to the left elbow, buttocks and left leg. A CT scan of the brain had excluded significant acute intracranial pathology and a 12 lead ECG showed atrial fibrillation at a rate of 130 beats per minute.

The patient was intubated and mechanically ventilated to allow emergency treatment. She was sedated with remifentanil and propofol. Intravenous pabrinex and enteral chlordiazepoxide was given to treat her alcohol withdrawal, aiming for early extubation if possible. A low-dose noradrenaline infusion was required to maintain a mean arterial pressure ≥65mmHg. Calcium replacement was prescribed and full pressure relief measures were instituted. No specific treatment was given to rate control or cardiovert the patient.

The patient was clinically hypovolaemic, but since the duration of hyponatraemia was unknown (with suspicion of some chronicity related to alcohol dependence), aggressive fluid resuscitation was avoided. Continuous veno-veno haemodiafiltration (CVVHDF) was commenced using standard replacement fluid at a post-filter replacement rate of 10ml/kg/hr^-1 and dialysate flow rate of 10ml/kg/hr^-1 (blood pump at 200ml/hr). Concomitantly, a 5% dextrose infusion was administered; the rate of infusion and net fluid loss through ultrafiltration were adjusted constantly with a view to restoring euvolaemia over 24 hours while increasing serum sodium to a maximum level of 120mmol/L over the same time period. This strategy was continued the following day with a target sodium of 128mmol/L, thereafter tight control of sodium correction was relaxed.

She was extubated on day 3 and renal replacement was discontinued on day 4. The patient was discharged from ICU on day 6. At the point of discharge her serum sodium concentration was stable at 142mmol/L. She was neurologically intact.

What are the challenges in managing hyponatraemia in critically ill patients?

Christopher Westall

Hyponatraemia is one of the commonest electrolyte disorders among patients presenting to the Emergency Department, occurring in up to 10%.¹ The absolute sodium concentration and duration of hyponatraemia are both important in determining clinical manifestation. Symptoms may range from malaise, nausea, headaches and delirium to seizures and coma as cerebral oedema progresses and fatal cerebral herniation syndromes evolve. Seizures and significant cerebral oedema only commonly occur when severe hyponatraemia (serum [Na⁺] <120mmol/L) evolves rapidly (within 48 hours), sodium concentrations below this level may be tolerated remarkably well when they occur chronically.

The duration of hyponatraemia is important for setting treatment goals; too rapid correction of severe hyponatraemia can result in devastating osmotic demyelination syndromes (ODS). Most authorities agree that once hyponatraemia has been present for more than 24 hours, the maximum rate of correction should be limited to 8- 10mmol/L/24hrs^-1.² The presence of a high serum urea concentration may be protective from ODS in cases of severe hyponatraemia. The diffusion of urea across the blood-brain barrier from cerebral tissues is slow; a high concentration gradient of urea is maintained on the brain side, which mitigates water movement from cerebral tissues due to increasing serum sodium concentration.³  

Continuous renal replacement therapies are effective treatments for the management of acute kidney injury secondary to rhabdomyolysis. Serum creatine kinase (CK) accurately predicts the severity of rhabdomyolysis, but correlates poorly with serum myoglobin concentrations and the risk of acute kidney injury.⁴ Myoglobin is effectively removed by modern high flux dialysers with a sieving coefficient in the order of 0.55.⁵ However the high-flux dialyser remains less efficient at clearing myoglobin than the native kidney. For these reasons renal replacement therapy for acute kidney injury secondary to rhabdomyolysis should not be initiated purely based on the magnitude of CK rise, but be reserved for cases where urine output is poor and cannot be augmented with intravenous fluids and/or there are associated life threatening electrolyte abnormalities.⁴

Initiation of renal replacement therapy in a hyponatraemic patient is fraught. Commercially available replacement fluids for continuous-mode therapies (such as market leader Gambro’s PrismaSol and HemaSol solutions) have sodium concentrations of 140mmol/L.^6,7 There are no commercially available low-sodium solutions for this purpose. The risk therefore is rapid equilibration of serum sodium and replacement fluid concentrations.

There is actually little published literature relating to the management of sodium disorders in acute kidney injury requiring renal replacement therapy. There are two approaches described to control the rate of sodium correction; manipulation of replacement fluid sodium concentration through addition of sterile water or concentrated sodium chloride solution (if the patient is hypernatraemic) or simultaneous intravenous infusion of free water (in the form of 5% dextrose solution) while using ultrafiltration with net fluid removal to remove the excess fluid volume. The former approach, while more elegant, disturbs the composition of the replacement fluid bags with respect to other electrolytes, most importantly resulting in lower concentrations of bicarbonate and potassium. Consequently serum concentrations of bicarbonate and potassium must be monitored closely with supplementation as required, though in practice this is rarely problematic (replacement fluid bicarbonate usually remains >28mmol/L and potassium typically remains >3.2mmol/L).^3,8 There are two case reports where a patient has been successfully managed using modified replacement fluids, but no reports of sodium disorders managed using renal replacement with concomitant 5% dextrose or hypertonic saline infusions.^9,10

Throughout CVVH/ CVVHDF treatments, sodium concentration should be monitored carefully; should fluctuations in sodium exceed 2mmol/L in 6 hours (some suggest >0.5mmol/hr^-1), either the replacement fluid should be changed or the dose of renal replacement reduced. The dose of renal replacement can be reduced (depending on mode) by reducing dialysate flow rate or total effluent rate during filtration, though this would be undesirable if clearance of myoglobin is to be achieved (noting the sieving coefficient of 0.55).^3,8

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Lessons learnt

Hyponatraemia is a common electrolyte disturbance that must be carefully corrected to avoid risk of significant morbidity and mortality from osmotic demyelination syndromes. Renal replacement therapies pose a particular challenge in these patients, as the composition of commercially available replacement fluids will cause a rapid increase in the serum sodium concentration. Pragmatic solutions to adjust the composition of replacement fluids exist, but the impact on serum sodium concentration is not an exact science. In all cases extreme diligence is required.

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References

1. Arampatzis S, Frauchinger B, Fiedler GM, Leichtle AB, Buhl D, Schawrz C, Funck GC, Zimmerman H, Exadaktylos AK, Linder G. Characteristics, symptoms and outcome of severe dysnatraemias present on hospital admission. Am J Med, 2012; 125:1125e1-1125e7

2. Sterns RH. Disorders of plasma sodium- causes, consequences, and correction. N Engl J Med, 2015; 372:55-65

3. Hoste EAJ, Dhondt A. Clinical review: Use of renal replacement therapies in special groups of ICU patients. Critical Care,  2012; 16:201

5. Petejova N, Martinek A. Acute kidney injury due to rhabdomyolysis and renal replacement therapy: a critical review. Critical Care, 2014:18:224

5. Gambro AB. Prismaflex System Haemofilter Set [cited September 2015]. Available: http://www.gambro.com/PageFiles/7971/306100279_1%20(HCEN4794)%20(M60-100-150)%20specs.pdf?epslanguage=en

6. Gambro AB. PrismaSol CRRT replacement fluid [cited September 2015]. Available: http://www.gambro.com/pagefiles/7980/306100331_1_prismasolbrochure.pdf

7. Gambro AB. HemaSol B0. Bicarbonate- buffered solution for continuous haemodialysis, hemofiltration and hemodiafiltration [cited September 2015]. Available: http://www.gambro.com/PageFiles/6060/Hemosol%20B0,%20Produktdatablad.pdf?epslanguage=en

8. Ostermann M, Dickie H, Tovey L, Treacher D. Management of sodium disorders during continuous hemofiltration. Critical Care, 2010; 14:418

9. Bender FH. Successful treatment of severe hyponatraemia in a patient with renal failure using continuous venovenous haemodialysis. Am J Kidney Dis, 1998; 32:829-31

10. Vassallo D, Camilleri D, Moxham V, Ostermann M. Successful management of severe hyponatraemia during continuous renal replacement therapy. Clin Kidney J, 2012; 5: 155-57