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Hyponatremia - 9/11/2012

posted Sep 11, 2012, 8:37 AM by Rohit Das   [ updated Dec 27, 2012, 6:55 AM by Purnema Madahar ]

I’d like to focus on hyponatremia today, the topic of today’s intern morning report. This is an extremely common electrolyte abnormality. If defined by a serum Sodium of < 136 mEq/L, the prevalence of hyponatremia (present at admission and hospital acquired) is around 50%!! At lower values, such as < 126, the prevalence is much lower, but still significant, around 7%. 

Hyponatremia can be categorized into the low osmolality causes (the large majority) versus the normal/high osmolality causes. Subsequently, it is important to sub-categorize the former by volume status – hypovolemic, euvolemic, or hypervolemic hyponatremia.

  • In both the hypovolemic and hypervolemic causes, the overall physiology is the same – effective arterial blood volume is depleted, which leads to stimulation of ADH secretion (via carotid artery barocreceptors that sense a reduction in blood volume), water reabsorption, and subsequent hyponatremia. In heart failure AND cirrhosis, hyponatremia is also important prognostically and correlates with severity of disease.
  • Euvolemic hyponatremia with a low serum osmolality = SIADH. This phenomenon has a myriad of causes, including various malignancies, lung/CNS diseases, and drugs. Table 1 of the SIADH review article provides a good overview (the table is sideways…makes my head hurt). As this article describes, there are four types of ADH, characterized by how ADH is secreted in relation to serum osmolality. The overall pathophysiology is the same – ADH regulation is impaired; though in different ways, thus giving four different types.
  • Hyponatremia, with a low osmolality, can also occur in an ADH suppressed state – this includes mainly primary polydipsia and a very low solute diet (alcoholics). Such patients have a normal effective arterial blood volume and intact ADH regulation. Since they are hypo-osmol, their ADH is suppressed.
  • Finally, on the flip side of the osmolality coin, HIGH/NORMAL osmolality hyponatremia occurs in hyperglycemia, advanced renal failure, and pseudohyponatremia (due to hyperlipid/protein-emia) – a phenomenon in which lower plasma water leads to a falsely low serum sodium concentration.

So, in terms of evaluation, how can we differentiate between these different processes? Well, history and physical is most important and should be especially focused on assessment of volume status. If done at initial time of assessment, some studies can be helpful:

  • Serum osmolality confirms true hyponatremia, versus hyperosmotic hyponatremia and pseudohyponatremia.
  • Urine osmolality differentiates between ADH suppressed hypoNa cases (of which only primary polydipsia and low solute intake are important), versus ADH elevated states. In euvolemic patients with excessive water intake who have normal normal ADH regulation (like you and me), ADH will be suppressed, and urine should be maximally dilute, with a urine osmolality < 100.
  • Urine sodium and serum uric acid are helpful lab measurements that differentiate between hypovolemic hypoNa and SIADH. In hypovolemic/hypervolemic, urine sodium will usually be < 25 (though will be confounded in the context of diuretics…), where as in SIADH it is usually > 40. For similar volume status related reasons, SIADH also leads to decreased uric acid (<4) and serum BUN (<10, though hard to use this criteria in older patients who will most likely have some degree of impaired GFR).
  • Table 2 of the SIADH review article provides a good diagnostic scheme, which reinforces what’s mentioned above. In addition, it’s important to exclude endocrine causes – hypothyroidism and adrenal insufficiency, as other potential causes of hyponatremia.

The manifestations of acute hyponatremia (physiologically within the first 24 hours) are directly related to cerebral edema – nausea/malaise initially, and with worsening levels, coma, obtundation and respiratory arrest can occur. Within a few days, cerebral adaptation leads to “chronic hyponatremia.” Though some patients may be asymptomatic even at low sodium levels, nonspecific symptoms can still be present. However, the severe symptoms we think about – seizures, coma, etc., are very rare in chronic hyponatremia.

 

Management is really dependent on the cause and severity of the hyponatremia. In severe cases, hypertonic saline is the fluid of choice. For mild to moderate symptoms:

  • In volume depletion, replacing volume with isotonic saline will decrease ADH secretion and correct hyponatremia.
  • In SIADH, the mainstays of treatment are fluid restriction and salt tablets, sometimes in conjunction with a loop diuretic to lower urine osmolality and increase free water excretion.
  • Of note, isotonic saline alone is not recommended in SIADH as it may actually WORSEN hyponatremia. Based on physiology that’s difficult to teach via me typing, at conceptually “fixed” urine osmolalities, some degree of the water that's put in is inevitably retained. Obviously, in SIADH, treating the specific underlying cause is most important.
  • Treating asymptomatic chronic hyponatremia is somewhat debatable. The SALT trial (attached) showed that treatment of chronic hyponatremia with vasopressin receptor antagonists improved mental survery scores. In addition, there is some data to support that chronic hyponatremia is associated with increased falls in elderly patients. Overall, this data suggests that treating asymptomatic hyponatremia in SIADH to a goal of > 130 MIGHT be some benefit. However, in hyponatremic patients due to cirrhosis or heart failure, treatment is virtually of little to no benefit, as their overall prognosis is dismal. 

The rate of correction of sodium is a debated topic. There are no good studies that outline optimal strategies of correcting hyponatremia, and the related risk of osmotic demyelination syndrome (ODS) with overly rapid correction. Couple of points on ODS and rate of sodium correction:

  • ODS presents with neurologic symptoms a few days AFTER rapid correction. Risk factors include a sodium of <120 at presentation (VERY rare otherwise), the duration of hyponatremia (ODS does not occur within the acute setting…but since the duration is usually not known, best to assume that hyponatremia is always past 24 hours) and the rate of correction (most common when raised >20 meQ/L in 24 hours, and very rare when raised <10meQ/L in 24 hours). In patients who are overly rapidly corrected with the above risk factors, it is recommended to RELOWER sodium levels with free water and/or desmopressin.
  • Recommendations are to increase sodium levels at a rate no greater than 8-10 meQ/24 hours. However, this can often be difficult in volume depletion, as once ADH is turned off, hyponatremia will rapidly correct, independent of the infusate’s direct impact on sodium levels. Though there are some formulas to guide us (Table 2 in the Hyponatremia review), removal of the ADH stimulus is the most important factor, and the point at which this happens is very difficult to predict and does NOT correlate well with an estimated sodium deficit. However, ODS in hypovolemic hypoNa is usually not a major concern, as sodium levels are rarely <120. 
  • When treating severe SIADH with hypertonic saline, things become more predictable (the ADH stimulus doesn’t get turned off…). Table 4 of the SIADH article provides some useful formulas, and the recommendations for the ideal rate of correction remains around the same, at 8 meQ in the first 24 hours.

On the longer side today…hopefully that compensates for the lack of a daily tomorrow (I’ll be at an interview). Hope this was useful; the attached review articles are good reads – hyponatremia is an IM topic that’s worth becoming VERY familiar with, so use these papers as tools for that purpose…Till next time…

 

Hyponatremia
Adrogue et. al., NEJM 2006, Volume 342 (21): 1581-89

Ellison et. al., NEJM 2007, Volume 356: 2064-72

Schrier et. al., NEJM 2006, Volume 355: 2099-112

Courtesy of Dr. Lief:
Vaidya et. al., Cleve Clin J of Med, Volume 77 (10): 715-726
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