Who is afraid of Osmotic Demyelination Syndrome?

Posted on RFN and Last Updated on November 2020

Severe hyponatremia – limits, goals and clamps

From early physiology courses in medical school, everyone learns to beware of correcting the blood sodium too rapidly in the care of a patient with hyponatremia if its duration is chronic or unknown. But was this concern always present?

In the pathology literature, the anatomical and histological description of central pontine myelinolysis was first reported in 1969. There, 4 different cases with similar lesions were reported. They were all patients which had a background of alcohol use and malnutrition and developed neurological symptoms and died shortly thereafter. At that point the correlation with hyponatremia was not made, perhaps because the basic metabolic panel was not routine.

In the 80’s, there was considerable discussion about brain damage and hyponatremia. You were either of the belief that comorbidities were responsible or that the hyponatremia itself had some blame in the game. Yet in 1986, a report from Arieff dimplicated the rapid correction of hyponatremia as the cause of brain injury in 15 different cases of women with no comorbidities who developed hyponatremia after surgery. In this report, the women who developed seizures in the setting of acute onset of severe hyponatremia with a mean sodium of be 108 mEq/L. In the cases described, a vast range of possibilities were considered and multiple different specialties were consulted – even psychiatry was involved and 2 brain biopsies completed! Therapy for hyponatremia was delayed about 16h due to the broad investigation. The correction rate aim was about 0.5 mEq/h for most patients, which was considered a “slow correction” at the time. All of the patients in the report had some degree of brain damage, ranging from death to permanent disability. A subset of the women had an unusual pattern of neurologic changes that featured– IMPROVEMENT- a LUCID INTERVAL –then WORSENING NEUROLOGICAL STATUS following sodium correction. Notably, these patients achieved rapid sodium correction within 22 hours in comparison to the other patients who enjoyed a better clinical course and whose correction required 48h.

This review on NEJM by Sterns described the connection between rapid correction of hyponatremia and neurological demise and stipulated that patients who had a correction rate < 12 mEq/day did not suffer ODS. Another case series review in 1993 lowered those stakes to 10-12 mEq in 24hours and 18 in 48h. One caveat is that all of these recommendations come from retrospective observational data rather than stricter study designs

While there were multiple other center specific case series trying to tackle the same question, in the 2010 era the advent of “clamping” came about, describing the use of desmopressin as a clamp to avoid overcorrection in hyponatremia. First Sterns described the use of desmopressin clamp in a QI designed trial. Then a systematic review in 2015 found desmopressin use described as “proactive”, “reactive” and “rescue”. This paper offers special insight on which strategy might be better for which patient profile – for example proactive for high-risk patients.

To better understand who is considered high risk take a look at this paper https://pubmed.ncbi.nlm.nih.gov/29871886/

Further questions in hyponatremia management such as bolus vs infusion of hypertonic saline still need to be answered!

Take a look at this other resources

• Reviews https://pubmed.ncbi.nlm.nih.gov/29295830/

• American Guidelines https://pubmed.ncbi.nlm.nih.gov/24074529/

• NephMadness Hyponatremia Bracket 2018 – https://ajkdblog.org/2018/03/15/nephmadness-2018-hyponatremia-region/#USGuidelines

Post by : Larissa Kruger

Reviewed by: Jeffrey William, Melanie Hoenig and Stewart Lecker