Hypernatremia
Na⁺ > 145 mEq/L -almost ALWAYS from free water deficit, not sodium excess. Causes: inadequate water intake (altered mental status, intubated, elderly), diabetes insipidus, osmotic diuresis, GI losses. Correct ≤10 mEq/L per 24 hours for chronic hypernatremia.
🔍 Overview
Definition
- Na > 145 mEq/L -almost always from free water deficit (not sodium excess)
- Serum osmolality is always elevated (> 295 mOsm/kg)
Causes
| Category | Examples |
|---|---|
| Inadequate water intake | Altered mental status, intubated patients without free water, elderly with impaired thirst, NPO without adequate IVF |
| Diabetes insipidus | Central DI: post-neurosurgery, pituitary injury, brain death. Nephrogenic DI: lithium, hypercalcemia, hypokalemia |
| Osmotic diuresis | Hyperglycemia (DKA/HHS), mannitol, urea (high-protein TPN) |
| GI losses | Diarrhea (especially osmotic diarrhea -lactulose), vomiting, NG suction |
| Renal losses | Loop diuretics, post-obstructive diuresis |
Clinical Manifestations by Severity
| Na Level | Symptoms | Urgency |
|---|---|---|
| 146-150 | Thirst, oliguria, concentrated urine. May be asymptomatic | Monitor, start free water |
| 150-160 | Lethargy, irritability, weakness, nausea | Urgent correction with D5W or free water |
| 160-170 | Confusion, disorientation, hyperreflexia, muscle twitching | Urgent. ICU monitoring recommended |
| >170 | Seizures, coma, intracranial hemorrhage (brain shrinkage tears bridging veins) | Emergency. ICU mandatory. Mortality 40-60% |
Key concept: Hypernatremia is almost always a disease of impaired thirst or impaired access to water, not excess sodium. A conscious patient with access to water will drink before Na rises significantly. The populations at highest risk are: intubated ICU patients, elderly with dementia, infants, and post-neurosurgical patients with DI. Adrogue & Madias, NEJM 2000
🚨 Management
Stepwise Approach
Step 1 -Calculate free water deficit
FWD = TBW × (Na/140 − 1)
TBW = weight (kg) × 0.5 (women) or 0.6 (men)
Example: 70 kg man, Na 160 → TBW = 42 L → FWD = 42 × (160/140 − 1) = 42 × 0.143 = 6 L deficit
TBW = weight (kg) × 0.5 (women) or 0.6 (men)
Example: 70 kg man, Na 160 → TBW = 42 L → FWD = 42 × (160/140 − 1) = 42 × 0.143 = 6 L deficit
Step 2 -Replace free water
D5W IV (250–500 mL/hr) or 0.45% NS or free water via NG/PO if able to take PO. Add ongoing losses to replacement calculation.
Step 3 -Correct at safe rate
≤10 mEq/L per 24 hours for chronic hypernatremia (> 48h). Overcorrection risk: cerebral edema. Acute hypernatremia (< 48h, e.g., ICU patient who missed free water) can be corrected faster.
Step 4 -Treat underlying cause
Desmopressin (DDAVP) for central DI. Stop offending drugs for nephrogenic DI (lithium, etc.). Treat hyperglycemia if osmotic diuresis.
Correct Na ≤10 mEq/L in 24 hours for chronic hypernatremia (> 48h). Rapid correction → cerebral edema → herniation. For acute hypernatremia (< 48h, e.g., ICU patient who missed free water), faster correction is safe.
Do NOT use NS (154 mEq/L Na) to correct hypernatremia if Na is > 154 -NS is hypotonic relative to the patient but still has a lot of sodium. Use D5W or 0.45% NS instead.
IV Fluid Selection Guide
| Fluid | Na Content | Free Water per Liter | When to Use |
|---|---|---|---|
| D5W | 0 mEq/L | 1000 mL | Best for pure free water deficit. Glucose metabolized, leaves pure water. First-line for most hypernatremia |
| 0.45% NS (half-normal) | 77 mEq/L | ~500 mL | Provides free water + some sodium. Good when patient is also volume depleted |
| 0.9% NS (normal saline) | 154 mEq/L | ~0 mL | Only for initial volume resuscitation in hypotensive patients. Does NOT correct hypernatremia efficiently |
| Free water (PO/NG) | 0 mEq/L | 1000 mL | Most physiologic route if patient has NG or can drink. Preferred when possible |
Practical tip: Adrogue & Madias, NEJM 2000 The Adrogue-Madias formula predicts the change in serum Na per liter of any IV fluid: Change in Na = (infusate Na - serum Na) / (TBW + 1). For D5W (infusate Na = 0) in a 70 kg man (TBW = 42): change = (0 - 160) / 43 = -3.7 mEq/L per liter of D5W. So ~2.7 L of D5W over 24h would lower Na by ~10 mEq/L.
🧪 Workup
| Test | Purpose |
|---|---|
| BMP | Na level, Cr (dehydration), glucose (osmotic diuresis) |
| Serum osmolality | Always elevated in true hypernatremia (> 295) |
| Urine osmolality | High (> 600): appropriate ADH response -not getting enough water. Low (< 300): DI -kidneys not concentrating urine |
| Urine Na | Helps differentiate renal vs extrarenal losses |
| Glucose | Rule out osmotic diuresis from hyperglycemia |
| Urine specific gravity | Low in DI, high in appropriate response |
Diabetes Insipidus Workup
- Urine osm < 300 → suspect DI
- Give DDAVP → if urine concentrates (osm > 600) = Central DI (responds to exogenous ADH)
- If no response to DDAVP = Nephrogenic DI (kidneys resistant to ADH)
💊 Medications
| Drug | Dose | Indication |
|---|---|---|
| D5W | 250–500 mL/hr IV (adjust to correction rate) | Primary free water replacement -no sodium |
| 0.45% NS (half-normal saline) | Variable rate IV | Alternative to D5W -provides some sodium + free water |
| Desmopressin (DDAVP) | 1–2 mcg IV or SQ | Central DI -replaces deficient ADH |
| Free water flushes | 200–500 mL via NG q4–6h | Enteral free water if NG access available -most physiologic |
📋 On Rounds
Pimp Questions
How do you calculate the free water deficit?
FWD = TBW × (Na/140 − 1). TBW = weight (kg) × 0.6 (men) or 0.5 (women). Example: 70 kg man, Na 160 → TBW = 42 L → FWD = 42 × (160/140 − 1) = 42 × 0.143 = 6 liters. Important: this estimates the deficit at a single point in time. You must also account for ongoing losses (urine, insensible) and recheck Na frequently. Replace the deficit over 48–72h to avoid overcorrection.
How do you differentiate central vs nephrogenic DI?
Both present with polyuria and dilute urine (urine osm < 300). Give DDAVP (exogenous ADH): if urine concentrates (> 600 mOsm) → Central DI (the pituitary isn't making ADH, but the kidneys can respond). If urine stays dilute → Nephrogenic DI (kidneys are resistant to ADH). Common causes: Central = post-neurosurgery, pituitary tumors, brain death. Nephrogenic = lithium (#1), hypercalcemia, hypokalemia.
Why not use NS to correct severe hypernatremia?
NS contains 154 mEq/L of sodium. If the patient's Na is > 154, NS is actually hypotonic relative to them and will technically lower Na -but very slowly because it still contains a lot of sodium. For efficient free water replacement, use D5W (distributes as pure free water once glucose is metabolized) or 0.45% NS (77 mEq/L Na -provides free water while maintaining some tonicity). D5W is preferred for significant hypernatremia.
What is the maximum correction rate for chronic hypernatremia?
≤10 mEq/L per 24 hours. In chronic hypernatremia (> 48h), brain cells generate idiogenic osmoles (organic osmolytes -taurine, glutamine, etc.) to prevent cellular dehydration. Rapid correction removes these osmoles faster than the brain can adapt → water shifts INTO brain cells → cerebral edema → herniation. For acute hypernatremia (< 48h), the brain hasn't had time to accumulate osmolytes, so faster correction (1–2 mEq/h) is safe.
What are idiogenic osmoles and why do they matter?
In chronic hypernatremia (>48h), brain cells generate organic osmolytes (taurine, glutamine, myo-inositol, sorbitol) to maintain intracellular tonicity and prevent cellular dehydration. These are called "idiogenic osmoles." They take 24-48 hours to accumulate and days to dissipate. If you correct Na too rapidly, water rushes into brain cells (still loaded with osmolytes) causing cerebral edema and herniation. This is why chronic hypernatremia must be corrected slowly (<=10 mEq/L per 24h). Adrogue & Madias, NEJM 2000
What is the most common cause of hypernatremia in hospitalized patients?
Inadequate free water administration, especially in patients who cannot drink independently: intubated patients, altered mental status, post-surgical NPO, elderly with impaired thirst. Hospital-acquired hypernatremia is associated with increased mortality (40-60% in ICU patients) and is considered a marker of poor care quality. Lindner et al, Crit Care 2013 Prevention: calculate maintenance free water needs for all patients who cannot drink (typically 25-30 mL/kg/day).
How does lithium cause nephrogenic DI?
Lithium enters collecting duct principal cells via ENaC channels and inhibits glycogen synthase kinase-3 (GSK3), which is required for aquaporin-2 (AQP2) trafficking to the apical membrane. Without AQP2 channels at the cell surface, the collecting duct cannot reabsorb water in response to ADH. Occurs in 20-40% of chronic lithium users. May be partially reversible if lithium is discontinued early, but prolonged use causes permanent tubulointerstitial fibrosis. Amiloride can help by blocking lithium entry into the cell via ENaC. Bedford et al, JASN 2003
Why is the free water deficit formula an underestimate?
The FWD formula (TBW x [Na/140 - 1]) calculates the static deficit at one point in time. It does NOT account for: (1) Ongoing losses - insensible losses (~500-1000 mL/day), urine free water losses (especially in DI where UOP can be 3-20 L/day), GI losses. (2) TBW is estimated, not measured - obese, elderly, and cachectic patients have different TBW fractions. (3) The formula assumes a closed system with no additional losses. Practical approach: calculate the deficit, add estimated ongoing losses, start replacement, and recheck Na every 4-6 hours to adjust the rate.
What is the approach to hypernatremia in the ICU patient on continuous tube feeds?
ICU patients on tube feeds are at high risk for hypernatremia because: (1) Tube feed formulas have high osmolar loads that require free water to excrete. (2) Patients cannot self-regulate thirst. (3) Loop diuretics, osmotic agents (mannitol), and insensible losses add to the deficit. Management: (1) Order scheduled free water flushes (200-500 mL q4-6h via NG/PEG), not just "PRN." (2) Calculate total free water content of the tube feed formula (typically 70-85% of volume). (3) Monitor Na q6-8h. (4) Consider switching to a lower-osmolality formula if persistent hypernatremia. Alansari et al, J Crit Care 2018
📣 Sample Presentation
One-Liner
"Mrs. Johnson is an 82-year-old woman from a nursing home, found lethargic with Na 162, BUN 45, Cr 1.8, urine osm 650 -hypernatremia from inadequate free water intake with appropriate ADH response."
Key Points to Cover on Rounds
Hypernatremia (Na 162) from inadequate oral intake. Urine osm 650 = appropriate ADH response (not DI). Free water deficit: ~5.3 L. Replacing with D5W at 250 mL/hr + free water via PO as tolerated. Target correction ≤10 mEq/24h. Na last check 4h ago: 158 (trending appropriately). Strict I&Os. Repeat Na in 4h. Addressing underlying cause: speech therapy for dysphagia evaluation, assisted feeding.
Monitoring
| Parameter | Frequency | Target / Action |
|---|---|---|
| Serum Na | q4–6h during correction | Decrease ≤10 mEq/24h for chronic. Faster OK if acute (< 48h). |
| I&Os | Strict | Track free water replacement and ongoing losses |
| Urine output | Hourly | Polyuria in DI (can be > 3–20 L/day) |
| Daily weights | Daily | Fluid balance tracking |
| Serum osmolality | q12–24h | Should normalize with Na correction |
Clinical Examples
📋 Case 1 - Hospital-Acquired Hypernatremia in Intubated Patient
Patient: 68M intubated for respiratory failure (pneumonia). Day 5 in ICU. BMP: Na 158 (was 140 on admission), Cr 1.0, BUN 28. Urine osm 750 (appropriately concentrated). On NS at 75 mL/hr for maintenance. No free water flushes ordered.
Assessment: Hospital-acquired hypernatremia from inadequate free water. Urine osm >600 = ADH is working (NOT DI). The patient is getting NS (154 mEq/L Na) as maintenance and cannot drink. Classic preventable ICU complication.
Free water deficit: TBW = 70 kg x 0.6 = 42 L. FWD = 42 x (158/140 - 1) = 42 x 0.129 = 5.4 L. Plus ~1.5 L/day ongoing insensible losses.
Management: Changed maintenance to D5W at 200 mL/hr. Added free water flushes 250 mL via NG q4h. Target correction: <=10 mEq/24h. Na rechecked q4h. Na 152 at 12h, 148 at 24h (on target). Continued D5W + free water until Na normalized.
📋 Case 2 - Central Diabetes Insipidus Post-Neurosurgery
Patient: 45F post-op day 1 from transsphenoidal pituitary adenoma resection. Nursing reports UOP 600 mL/hr x 3 hours. BMP: Na 151 (was 138 pre-op). Urine osm 85 (dilute). Urine specific gravity 1.001.
Assessment: Central DI from pituitary stalk manipulation/damage. Acute onset. Classic triad: polyuria (>300 mL/hr), dilute urine (osm <300), rising Na.
Workup: Gave DDAVP 1 mcg IV. Urine osm rose to 680 within 2h = central DI confirmed (kidneys respond to exogenous ADH).
Management: DDAVP 1 mcg IV q12h. D5W at 250 mL/hr to replace ongoing free water losses. Match IV rate to UOP. Na corrected to 143 by 24h. Post-surgical central DI may be transient (resolves in days-weeks) or permanent. Follow Na and UOP closely.
📋 Case 3 - Chronic Hypernatremia in Nursing Home Resident
Patient: 88F from nursing home, found lethargic. Na 172, Cr 2.8 (baseline 1.0), BUN 65, glucose 110. Urine osm 620. Mucous membranes dry, skin tenting, tachycardia.
Assessment: Severe chronic hypernatremia from dehydration (inadequate oral intake). Urine osm >600 = appropriate ADH response, kidneys are concentrating maximally. Prerenal AKI from volume depletion. Duration unknown but likely >48h (chronic).
Free water deficit: TBW = 50 kg x 0.5 = 25 L. FWD = 25 x (172/140 - 1) = 25 x 0.229 = 5.7 L. Plus significant volume depletion.
Management: First: NS bolus for hemodynamic stabilization (this patient is also volume depleted, not just free water depleted). Then: D5W at 150 mL/hr + free water via NG 200 mL q6h. Target: Na decrease <=10 mEq/24h. Too-rapid correction risks cerebral edema (idiogenic osmoles). Na trended: 172 -> 164 at 24h -> 156 at 48h -> 148 at 72h. AKI resolved with volume repletion.
⚡ Summary
It Is a Water Problem, Not a Salt Problem
Sodium above 145 is almost always free water deficit. A conscious patient with access to water will drink long before the sodium rises, so hypernatremia means impaired thirst or impaired access: the intubated, the elderly, the demented, infants, and anyone dependent on someone else for water.
Sort the Causes
Inadequate intake (altered mental status, intubated without free water, elderly). Renal losses: diabetes insipidus, central or nephrogenic, and osmotic diuresis from hyperglycemia, mannitol or high-protein feeds. GI losses: diarrhea, vomiting, nasogastric suction. Rarely true sodium excess, from hypertonic saline, sodium bicarbonate or salt ingestion.
Use the Urine to Localize It
Concentrated urine, osmolality above 700, means the kidney is responding appropriately and the losses are extrarenal or intake is inadequate. Inappropriately dilute urine in a hypernatremic patient means diabetes insipidus, and a water deprivation test with desmopressin then separates central (responds) from nephrogenic (does not).
Correct Chronic Hypernatremia Slowly
No more than 10 mEq/L in 24 hours when it has been present beyond 48 h. Brain cells generate idiogenic osmoles to survive the hypertonic state; lowering the serum osmolality faster than those clear draws water into the brain and causes cerebral edema and herniation. Acute hypernatremia developing within 48 h can be corrected faster, because the osmoles have not accumulated.
Pick the Right Fluid
D5W is pure free water and corrects fastest. 0.45% saline when volume also needs replacing. Enteral free water via the feeding tube is effective, cheap and safe and is under-used in tube-fed patients. Do not use normal saline to correct a sodium above 154: at 154 mEq/L it is only relatively hypotonic and it corrects glacially while loading sodium.
Restore Perfusion Before You Chase the Number
If the patient is hypotensive, give isotonic fluid first. Circulation takes priority over tonicity; the sodium can be addressed once the patient is perfused.
Calculate, Then Verify
Free water deficit = total body water × (serum Na / 140 − 1), using 0.5 × weight in men and 0.4 in women, less in the elderly. Adrogue-Madias predicts the change in sodium per liter of any fluid: (infusate Na − serum Na) / (TBW + 1). Both formulas ignore ongoing losses, so add maintenance and replace what continues to be lost, and treat the numbers as a starting rate rather than an answer.
Recheck Often and Fix the Cause
Sodium every 4 to 6 h while actively correcting, and adjust the rate on the measured trajectory, not on the calculation. Treat the underlying problem or it recurs: desmopressin for central DI, remove the offending drug and correct calcium and potassium in nephrogenic DI, control the glucose in osmotic diuresis, and write free water flushes into the tube feed orders.
Related Topics
Acid-Base DisordersCalciphylaxis (Calcific Uremic Arteriolopathy)Chronic Kidney Disease (CKD)Contrast-Induced NephropathyDialysis IndicationsHyponatremia