I. Introduction and Scope

Severe hyponatremia (serum sodium <120 mEq/L) in critical care demands a delicate balance: rapid relief of acute symptoms (e.g., seizures, altered mental status due to cerebral edema) while meticulously avoiding iatrogenic neurologic injury from overly rapid correction. The primary concern is osmotic demyelination syndrome (ODS). This section outlines the importance of structured monitoring and timely rescue interventions.

II. Laboratory Monitoring Parameters

Frequent assessment of serum sodium and volume status is essential during active correction of hyponatremia, especially in the first 24–48 hours. This allows for timely adjustments to therapy and prevention of overcorrection.

III. Osmotic Demyelination Syndrome (ODS) Pathophysiology

ODS is a devastating iatrogenic complication resulting from rapid shifts in extracellular osmolality, primarily due to overly aggressive correction of chronic hyponatremia. The brain adapts to chronic hypo-osmolality by extruding intracellular osmolytes. If serum sodium (and thus osmolality) is raised too quickly, water moves out of brain cells before they can re-accumulate these osmolytes, leading to cell shrinkage, astrocyte injury, and demyelination, most classically affecting the pons (central pontine myelinolysis) but also extrapontine sites.

• Chronic Hypo-osmolality Adaptation: Brain cells lose inorganic electrolytes (Na, K, Cl) initially, followed by slower loss of organic osmolytes (e.g., myoinositol, taurine, glutamine) to reduce intracellular osmolality and prevent swelling.
• Rapid Correction Impact: When extracellular osmolality rises rapidly with sodium correction, an osmotic gradient forms, drawing water out of brain cells before they can re-synthesize or re-uptake these protective organic osmolytes.
• Cellular Injury: This cellular dehydration and shrinkage can disrupt the myelin sheath produced by oligodendrocytes, leading to demyelination. Astrocytes are particularly vulnerable.
• Delayed Clinical Onset: Neurological symptoms of ODS typically manifest 2–6 days after the period of rapid correction, which can make a causal link less immediately obvious.
• Clinical Features: These can be severe and irreversible, including dysarthria, dysphagia, spastic quadriparesis or quadriplegia, lethargy, coma, seizures, parkinsonism, dystonia, pseudobulbar palsy, and “locked-in syndrome.”

Risk Thresholds for ODS:

IV. Rescue Pharmacotherapy Strategies for Overcorrection

If serum sodium correction exceeds the recommended limits, prompt intervention is necessary to re-lower the serum sodium or slow the rate of rise, thereby mitigating the risk of ODS. The primary strategies involve administering hypotonic fluids and/or desmopressin (DDAVP).

A. Hypotonic Fluid Administration (e.g., Dextrose 5% in Water – D5W)

Mechanism:

Dextrose is metabolized to carbon dioxide and water, effectively providing electrolyte-free water. This free water dilutes the serum sodium, helping to lower it or slow its rise.

Indications:

• Serum sodium rise exceeding target limits (e.g., >8–10 mEq/L in 24 hours, or >0.5 mEq/L per hour consistently).
• Development of new neurologic signs suggestive of ODS during correction (though this is a late sign).

Agent Selection:

D5W is generally preferred. 0.45% NaCl (half-normal saline) can be considered if there are concerns about glycemic control or if a slower, more controlled provision of free water is desired, but it is less effective at rapidly lowering sodium than D5W.

Dosing:

• Bolus (for active re-lowering): 2-3 mL/kg of D5W (e.g., 150-250 mL for an average adult) IV over 30–60 minutes. May be repeated. Some protocols suggest up to 250-500 mL.
• Infusion (to slow ongoing rise or maintain): Start at a rate to match ongoing free water losses (e.g., urine output if aquaresis is occurring) or a fixed rate like 50-100 mL/h, titrated to serum sodium response. A common formula to estimate the effect of 1L of D5W is: Change in Na = (-Current Na) / (Total Body Water + 1).

Monitoring:

Serum sodium every 1-2 hours, close monitoring of volume status (fluid overload risk), neurologic exam, and blood glucose.

Contraindications/Cautions:

Decompensated heart failure (risk of fluid overload), uncontrolled hyperglycemia (D5W can worsen it), severe renal impairment (less effective).

B. Desmopressin (DDAVP)

Mechanism:

DDAVP is a synthetic analog of vasopressin (antidiuretic hormone, ADH). It acts as a V2 receptor agonist in the renal collecting ducts, increasing water reabsorption and thus reducing free water excretion (i.e., it causes an antidiuresis). This effectively “puts the brakes” on renal water loss.

Indications:

• Rapid ongoing correction of serum sodium, particularly if due to aquaresis (e.g., urine osmolality <100-200 mOsm/kg with high urine output).
• Prophylactic use in high-risk patients (e.g., very low initial sodium, history of overcorrection) to establish a controlled rate of rise, often in conjunction with hypertonic saline.
• To reverse overcorrection by allowing administered D5W to be retained.

Agent Selection:

IV route is preferred for acute situations due to rapid onset and reliable bioavailability. Subcutaneous (SC) route is an alternative. Intranasal route has more variable absorption and is less suitable for critical care rescue.

Dosing:

• Rescue: 1–2 µg IV or SC. May be repeated every 6–8 hours if aquaresis persists or recurs. Some protocols use up to 4 µg.
• Prophylactic (e.g., with hypertonic saline): 1–2 µg IV/SC every 6-8 hours to create a “DDAVP clamp,” allowing more predictable sodium correction with hypertonic saline.

Monitoring:

Serum sodium every 1-2 hours, strict urine output measurement, fluid balance, hemodynamics. Watch for rebound hyponatremia if DDAVP effect is too strong or prolonged relative to fluid intake.

Contraindications/Cautions:

Not indicated if hyponatremia is due to primary polydipsia or if there’s no evidence of aquaresis. Use with caution in heart failure due to potential for fluid retention.

C. Integration and Algorithmic Approach to Overcorrection

A stepwise approach is recommended when overcorrection is identified:

Editor’s Note: Detailed protocols for the proactive combined use of hypertonic saline and DDAVP (“DDAVP clamp”) for initial treatment of severe hyponatremia are complex and typically covered in specialized nephrology or critical care guidelines. The focus here is on rescue from inadvertent overcorrection.

V. Goals-of-Care Discussions

In certain clinical scenarios, particularly when severe hyponatremia (often due to Syndrome of Inappropriate Antidiuresis – SIADH) complicates a terminal illness, the intensity of monitoring and correction strategies must be aligned with the patient’s overall goals of care. Aggressive interventions may not be appropriate or desired if they impose significant burden without improving quality of life or aligning with prognostic realities.

• Identify Contexts: Common situations include refractory malignancy, advanced end-stage organ failure (e.g., heart, liver, kidney disease), or severe irreversible neurological conditions.
• Structured Communication: Employ established frameworks for goals-of-care conversations (e.g., SPIKES – Setting, Perception, Invitation, Knowledge, Emotions, Strategy/Summary). This ensures a patient-centered approach.
• Discuss Risks and Benefits: Clearly explain the potential benefits of sodium correction (symptom relief) versus the burdens (frequent blood draws, fluid restrictions, potential for ODS if not managed carefully, ICU admission).
• Document Preferences: Meticulously document the patient’s (or their surrogate’s) wishes regarding the intensity of interventions, limits on correction targets, and any do-not-escalate or do-not-resuscitate orders. This may include decisions to focus on symptomatic management (e.g., fluid restriction, oral urea) rather than aggressive IV therapies.