Can Osmotic Demyelination Syndrome Occur with Sodium Correction of 6 mmol/L per Day?
Yes, ODS can occur even when sodium correction is limited to 6 mmol/L per day, particularly in patients with severe hyponatremia (<115 mmol/L) and additional risk factors such as alcoholism, malnutrition, liver disease, or hypokalemia. 1
Evidence for ODS Despite Conservative Correction Rates
The most critical finding comes from a systematic review of 21 patients who developed ODS despite sodium correction rates ≤10 mmol/L per 24 hours 1. Among patients with initial sodium <115 mmol/L, ODS occurred even when correction was limited to 8 mmol/L in 24 hours 1. This demonstrates that the traditional "safe" threshold may not be protective in high-risk populations.
A recent meta-analysis of 26,710 hospitalized patients found that while rapid correction (>8-12 mmol/L per 24 hours) increases ODS risk 3-fold, some patients developed ODS without any rapid correction at all 2. The overall incidence of ODS was 0.23%, with 0.73% in rapid correction groups versus 0.10% in conservative correction groups 2.
High-Risk Features That Lower the Safe Correction Threshold
Even with correction rates of 6 mmol/L per day, ODS risk remains elevated when these factors are present:
- Severe hyponatremia with sodium <115 mmol/L (especially ≤105 mmol/L) 1
- Alcohol use disorder (present in 52% of ODS cases despite conservative correction) 1
- Malnutrition (present in 52% of ODS cases) 1
- Liver disease (present in 29% of ODS cases) 1
- Hypokalemia (present in 24% of ODS cases) 1
Recommended Correction Rates Based on Risk Stratification
For patients with severe hyponatremia (<115 mmol/L) and any high-risk features, limit correction to <8 mmol/L per 24 hours, with a target of 4-6 mmol/L per day 3, 1. The American Association for the Study of Liver Diseases specifically recommends 4-6 mmol/L per day (not exceeding 8 mmol/L per 24 hours) for high-risk patients including those with advanced liver disease, alcoholism, malnutrition, or prior encephalopathy 3, 4.
For average-risk patients, the target is 4-8 mmol/L per day, not exceeding 10-12 mmol/L in 24 hours 3.
Clinical Outcomes and Monitoring
Among the 21 patients who developed ODS despite conservative correction rates, outcomes were severe: 19% died, only 24% had full recovery, and 42% had permanent neurologic deficits 1. This underscores that even "safe" correction rates carry risk in vulnerable populations.
The typical presentation of ODS occurs 2-7 days after sodium correction, with initial seizure or encephalopathy, followed by short-term improvement, then clinical deterioration with dysarthria, dysphagia, oculomotor dysfunction, and quadriparesis 3.
Prevention Strategies Beyond Correction Rate
Thiamine supplementation is advisable for any patient with hyponatremia whose dietary intake has been poor, as this may provide additional protection against ODS 1.
If overcorrection occurs (even if still within the 8 mmol/L limit but in a high-risk patient), immediately discontinue current fluids, switch to D5W, and consider desmopressin to relower sodium levels 3, 4.
Critical Caveat
The absence of rapid correction does not guarantee protection from ODS 5, 6, 2. Case reports document ODS occurring with "optimal" correction rates, particularly when severe hyponatremia (<115 mmol/L) is combined with multiple risk factors 5. A meta-analysis confirmed that ODS can occur regardless of correction rate, though rapid correction increases risk approximately 4-fold 6.