Management of hyponatremia ranges from stopping inappropriate water intake to using sophisticated V2-antagonist drugs to abolish the effects of vasopressin on the cortical collecting duct. The college loves this topic, because inevitably hypertonic saline comes up as a topic of discussion. With it, one can ask about calculation of the sodium deficit, and possibly also about the complications of rapid correction (i.e. osmotic demyelination). The reason for this interest is largely due to the frequency with which hyponatremia becomes an ICU issue. Referrals are made by endocrinologists who have a hyponatremic patient. The endocrinologist is anxious and wants to replace sodium, but does not wish to take responsibility for the myelinolysis. It is much easier to defer the matter to intensive care doctors, who will make all the decisions and take all the blame when the patient's white matter structures dissolve into a jelly.
Historical past paper SAQs on this topic have been numerous:
In this context, the classification of hyponatremia by volume status is actualy helpful. The reason is that it can now guide management. For instance, it helps decide whether you restrict fluid intake or replace volume with isotonic saline.
The best literature reference for management options is probably the recent overview of published guidelines by Verbalis et al (2014).
This is the management of choice for patients with euvolemic and hypervolemic hyponatremia. Essentially, in SIADH and in the organ system failure states (eg. CCF, cirrhosis and nephrotic syndrome) the body water volume is inappropriately elevated, and the only appropriate response is to decrease the mount of water intake. Also, restricting fluid intake for the psychogenic water drinker and the beer potomaniac seems like a sensible thing to do.
What features might give you the impression that fluid restriction by itself is not going to work?
This is the manegement of choice for patients with hypovolemic hyponatremia. Their hyponatremia is in part due to the escalation of ADH secretion in response to their low circulating volume. Without volume replacement, sodium replacement in these people is going to be ineffective. Question 5.1 from the second paper of 2011 presents just such a scenario, where a thiazide-poisoned woman is managed with isotonic saline. Once volume is corrected, the stimulus for ADH secretion will cease; the osmostat will then restore tonicity by massive diuresis.
It is straightforward: one wants to replace the missing electrolyte. However, it may not be the first line therapy.
In brief summary:
In their answer to Question 24 from the first paper of 2016, the college recommend to raise the sodium level by 2-4% over 30 minutes if the patient is symptomatic, i.e. confused or having seizures. This is consistent with the recent European guidelines (Spasovski et al, 2014). The guideline development group felt that the risk of brain oedema outweighs the risk of osmotic demyelination syndrome. Specifically, they recommend the infusion of 150ml of 3% saline over 20 minutes, then checking the sodium, and then repeating the infusion.
One review of 3% saline among neuroICU patients has a nice table (Table 1) which lists the potential adverse effects of hypertonic saline administration. I will reproduce the relevant parts of this table below. As you can see, the college answer for this section relies significantly on a source either identical to this one, or very closely resembling it.
In Question 24.3 from the first paper of 2019, examiners rewarded the trainee who correctly identified the threat of dialysis to the hyponatremic patient. Dialysate usually has about 145 mmol/L of sodium in it. This sodium will gladly exchange into the patient via the dialysis filter. When dialysed, a patient with a sodium level of 104 will rapidly correct. Bender et al (1998) report that with intermittent haemodialysis, the rate of correction would be 5mmol/hr, surely leading to catastrophic demyelination. However, with some modifications, it is possible to do this safely.
In fact, rather than just being mitigated against, Bender et al reported on a case where hyponatremia was actually treated with haemodialysis. The 72 year old woman in their case report was volume-overloaded and required dialysis, but had a sodium level of 108 mmol/L. The investigators decided to correct her sodium by dialysis, and had to create a custom dialysate to fit this purpose:
"Each 2 liters of dialysate was prepared by mixing 1 liter of 5% dextrose and 0.45% NaCl (half normal saline) with 1 liter of 0.675% NaCl (three-quarters normal saline) to which 50 mEq NaHCO3 was added; the final sodium concentration was thus 121 mEq/L"
"The patient never developed abnormal neurological signs or symptoms", the authors gloated. The resulting sodium level was 119 mol/L at the end of a 28 hour run of CVVHDF with a dose of about 12ml/kg/hr and 100ml/hr fluid removal.
Question 14 from the first paper of 2005 and Question 9.4 from the first paper of 2019 asked the candidates to calculate the sodium deficit.
The equation is reasonably straightforward:
Sodium deficit = 0.6 ×body weight × (desired concentration - current concentration)
The multiplier of body weight is 0.6 for men and 0.5 for women (whose fraction of body water is smaller)
Thus, a elderly 70kg lady whose sodium is 100mmol/L and whom you want to be around 130 mmol/L will require around 35 × 30 mmol of sodium, or around 1050mmol in total. That would be around 300ml of 20% concentrated saline.
A generic rule of thumb is that a 70kg person (whatever the gender) will require about 10ml (34mmol) of 20% saline for every 1mmol rise in sodium, all other things being equal; and therefore a sensible safe rate of replacement is about 4-5ml/hr of 20% saline for the first 24 hours. That would be wbout 25-35 ml/hr of 3% saline, if that is all you have available.
Now, the attentive reader may at this stage complain that sodium is confined to the extracellular fluid, and so it makes no logical sense to use total body water to calculate the deficit. Shouldn't we be using the extracellular fluid volume instead? Though this reasoning may be correct, the sodium deficit formula is ubiquitous, and apparently empirically validated. It is also known as the Adrogué–Madias (A-M) formula, and it comes from this 1997 paper. To summarise the author's reasoning, the use of total body water is resorted to because the intracellular and extracellular fluid are in osmotic equilibrium, and hypertonic saline results in so much water shift from the intracellular fluid that it effectively accesses total body water anyway, even though it is only supposed to distribute into ECF. Rather than incorporate the maths of a changing compartment volume into the formula, it was easier to just assume that the hypertonic saline will expand the ECF volume as much as it needs to, and therefore is effectively distributing into some amorphous compartment that may as well have the dimensions of total body water. In short, extracellular sodium will change as if it were distributing into total body water, not into the extracellular compartment.
This is the major danger of correcting sodium too quickly.
A few points:
Risk factors for pontine myelinolysis?
The first study (1959) which described this syndrome found it among alcoholic and malnourished patients. Later works extended the range of risk factors. In summary, they are as follows:
Almost all patients who develop osmotic demyelination presented with a sodium of under 120, which means that this should probably be the threshold for concern. Of those who develop it at a sodium of over 120, the majority of cases are in patients undergoing liver transplantation.
Clinical manifestations are usually delayed for a few days (2-6 days), and are usually irreversible:
The key issue is rate of correction.
In hypervolemic states (eg. cirrhosis and heat failure) loop diuretics will help with the hyponatremia at the same time as managing cardiac preload and exerting other advantageous effects. There just happens to be a greater excretion of water than of salt, particularly if you have not disabled the aldosterone receptors with spironolactone. In that sense, loop diuretics remain an effective therapy for hyponatremia. Unfortunately they sip water straight from the circulating volume, and the "apparent" decrease in this volume is the potent stimulus for ADH release in hypervolemic hyponatremia. In that sense, diuretics may be counterproductive.
Corticosteroids have a mineralocorticoid effect. Hydrocortisone is cheap, and can be used for such an effect. One might questio the use of a steroid drug purely to have the benefit of its side effects, but this has been done. Katayama et al (2007) used it to promote volume retention in SAH patients treated with the now-defunct HHH therapy. Nothing exciting happened to mortality (probably because HHH therapy is useless) but the sodium was certainly normal in both survivors and non-survivors.
As a synthetic mineralocorticoid, fluidrocortisone represents a form of cheating. It will cause sodium retention to outpace water retention. The only situation where it is indicated is cerebral salt wasting syndrome, where it encourages sodium retention.
These are discussed at greater length in the SIADH chapter. In brief, these therapies are:
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