Fixed-Dose Hypertonic Saline Protocol for Symptomatic Hyponatremia
The neurologic sequelae of too rapid correction of hyponatremia, such as osmotic demyelination syndrome (ODS), is a feared complication of treatment. Thus, physicians are often hesitant to use 3% hypertonic saline. A recent study published in AJKD describes the use of a fixed protocol of 3% saline for symptomatic hyponatremia. Study authors Drs. Juan Carlos Ayus and Michael Moritz (JA&MM) discuss this article with Dr. Paul Phelan (eAJKD), eAJKD Contributor.
eAJKD: Can you summarize the main findings of your study?
JA&MM: The main findings of this study are that a uniform protocol of 500 mL of hypertonic saline is effective and safe in reversing the symptoms of hyponatremic encephalopathy. This protocol was safe and effective in high-risk patients with chronic hyponatremia, and in patients in the emergency department through a peripheral vein. There were no apparent complications at six months follow up.
eAJKD: The volume (500 mL) of 3% saline administered might be considered large by some. Did you have any resistance to implementing this protocol?
JA&MM: We did not meet resistance with this protocol, as our group has significant experience with the use of hypertonic saline to treat hyponatremic encephalopathy (see Ayus et al and Ayus & Arieff). It was our impression that a minimum of 500 mL of hypertonic saline was needed to reverse the neurologic symptoms of hyponatremia in most patients.
eAJKD: A small number of patients over-corrected their serum sodium concentration using your protocol. Looking back, is there anything that you may have done differently with these patients? Is it possible to predict who will over-correct?
JA&MM: Five patients had an over-correction of 25 – 32 mEq/L in the initial 48 hours of therapy (as opposed to the recommended <18 mEq/L increase in serum sodium in first 48 hours). In three of these patients, the hyponatremia was related to thiazide diuretic use. In these patients, we favor using 100 mL of 3% saline as the initial treatment, with repeat doses as needed until neurologic improvement.
eAJKD: Your protocol is a one-size-fits-all approach, and response was unsurprisingly different between patients. Should it be tailored to body size, serum sodium concentration, serum potassium concentration, or would this add too much complexity?
CA&MM: Our approach was found to be effective in 69 of 71 treated episodes, 97% of the cases. Except for very large or small patients, we believe that this approach will work for the majority of patients. It is still necessary to monitor serial serum sodium levels to confirm an adequate response.
eAJKD: You reported no cases of ODS, which was reassuring. Did this surprise you? Do you feel cases may have been missed?
CA&MM: Our findings and those from other large series in the literature (see Nzerue et al and Hoorn et al) reveal that demyelination is an extremely rare complication of hyponatremia. We believe that the term ODS is a misnomer as it implies that an excessive osmotic change is necessary for the development of demyelination. It is clear from the literature that demyelinating lesions can develop in the absence of hyponatremia or an overcorrection of hyponatremia.
eAJKD: An exclusion criterion in the study was presence of a brisk water diuresis, which heralds the switching off of ADH secretion and subsequent improvement in serum sodium. This is a very important point and frequently not appreciated by clinicians. Should we watch for development of a water diuresis in patients receiving hypertonic saline, with a view to slowing/stopping the infusion?
CA&MM: Any patient who has hyponatremia and reversible impairment in free water excretion (polydipsia, cortisol deficiency, hypothyroidism, thiazide or desmopressin use) is at significant risk for over-correction of hyponatremia with hypertonic saline. These patients need careful evaluation and treatment to avoid neurologic complications.
eAJKD: One third of your cohort had thiazide-induced hyponatremia, suggesting that they may have been volume deplete and responsive to isotonic saline. Would you like to comment on this?
CA&MM: While thiazide diuretics can induce a hypovolemic hyponatremia, the majority of these patients are euvolemic. While normal saline may be appropriate for the asymptomatic patient with thiazide-induced hyponatremia, it would not be appropriate for a patient with hyponatremic encephalopathy. It is also important to emphasize that these patients are at risk for a free water diuresis when the stimulus for ADH is suppressed by volume expansion. Therefore, close monitoring is needed to prevent over-correction.
eAJKD: Did you consider treatment with vaptans in any of your patients?
CA&MM: Our study only included patients with symptomatic hyponatremia. Vaptans are not indicated in these patients as it does not have sufficiently rapid onset of action. Vaptans may serve a role in patients who do not have an adequate response to hypertonic saline.
eAJKD: Are there other notable points you wish to add?
CA&MM: We are concerned that many patients with hyponatremic encephalopathy may not be receiving appropriate therapy with 3% sodium chloride due to unjustifiable fears of complications and potential barriers to administration. There is a widespread belief the 3% sodium chloride must be given through a central line or in an ICU setting. This can delay the initiation of therapy and result in death or neurologic complications from hyponatremic encephalopathy. It is our hope that this data will assist hospitals in establishing protocols to treat hyponatremic encephalopathy.
To view the article abstract or full-text (subscription required), please visit AJKD.org.
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