Neurocritical Care Topics

Question 1

Classification of Hyponatremia

Answer 1

< 135 mild
< 130 moderate
< 125 severe

Question 2

Typical Causes of Hyponatremia in Neurosurgical Pts

Answer 2

1) SIADH: dilutional hyponatremia with normal or elevated intravascular volume (most common cause in neurosurgical pts)
- Usually Tx with fluid restriction
- May be associated with numerous intracranial abnormalities and following transsphenoidal surgery

2. Cerebral salt wasting: inappropriate natriuresis with volume depletion
   - Tx with volume replacement (opposite to SIADH) and sodium (symptoms from derangements due to cerebral salt wasting may be exacerbated by fluid restriction)
   - This is cause of hyponatremia in 6% of cases following aneurysmal SAH

Other etiologies of hyponatremia less likely:

• renal failure
• volume overload (eg CHF)
• pseudohyponatremia (osmotically active solutes such as glucose, mannitol, marked hyperlipidemia, or hyperproteinemia which can occur in multiple myeloma) draw water from cells and also reduce the water fraction of plasma and produce artifactually low sodium values (an artifact of indirect lab techniques); for every increase in glucose of 100 mg/dl, the serum sodium conc decreases by 1.6-2.4 mEq/L; must measure serum osmolality to r/o pseudohyponatremia

Question 3

How glucose levels affect sodium levels

Answer 3

For every increase in glucose of 100 mg/dl, the serum sodium concentration decreases by 1.6-2.4 mEq/L

Question 4

Effective osmolality equation

Answer 4

Effective osmolality = measured osmolality - [BUN] (mg/dl) / 2,8

Question 5

Etiologies of SIAD

includes due to ADH and other conditions of increased responsiveness to ADH

Answer 5

1. Malignant tumors: bronchogenic small-cell Ca, tumors of GI or GU tract, lymphomas, Ewing’s sarcoma
2. CNS disorders:
   - infection (encephalitis, meningitis esp in peds, TB meningitis, AIDS, brain abscess)
   - Head trauma (4.6% prevalence)
   - Increased ICP: hydocephalus, SDH
   - SAH
   - Brain tumors
   - Cavernous sinus thrombosis
   - Post craniotomy (esp for pituitary tumors, craniopharyngioma, hypothalamic tumors)
   - MS
   - GBS
   - Shy-Drager
   - Delerium tremens
3. Pulmonary disorders
   - Infection: pneumonia (bacterial and viral), abscess, TB, aspergillosis
   - Asthma
   - Resp failure associated with positive pressure respiration
4. Drugs that release ADH or potentiate it
   - Chlorpropramide (Diabinese) increases renal sensitivity to ADH
   - Carbamazepine (Tegretol), even more common with oxcarbazepine
   - HCTZ
   - SSRIs, TCAs
   - Clofibrate
   - Vincristine
   - Antipsychotics
   - NSAIDs
   - MDMA
5. Drugs that are ADH analogs
   - DDAVP
   - Oxytocin: ADH cross-activity, may also be contaminated with ADH
6. Endocrine disturbances
   - Adrenal insufficiency
   - Hypothyroidism
7. MISC
   - Anemia
   - Stress, severe pain, nausea or hypotension (all can stimulate ADH release)
   - Post operative state
   - Acute intermittent porphyria (AIP)

Question 6

Work up of hyponatremia

Answer 6

1. Effective serum osmolality (AKA tonicity)
   -Use equation if BUN is abnormal; if BUN is normal (7-18), just subtract 5 from the measured osmolality
   < 275 suggests hypotonic hyponatremia
   275-290 suggests isotonic hyponatremia (paraprotenemia or hypertriglyceridemia)
   > 290 suggests hypertonic hyponatremia (AKA pseudohyponatremia)
2. Urine osmolality
   < 100 mOsm/kg (appropriate response, suggests water intoxication/psychogenic polydipsia)
   > 100 mOsm/kg (inappropriately high for serum tonicity < 275 mOsm/kg)
3. Volume status
   -Normovolemia: SIADH, K+ loss, or endocinopathies
4. Check urinary [Na] if volume status is high or low
   -Low volume status:
   –Urine sodium < 10 mEq/L: extra-renal solute loss (GI tract, skin)
   –Urine sodium > 20 mEq/L: cerebral salt wasting, diuretics, or Addison disease
   -High volume status:
   –Urine sodium < 10 mEq/L: CHF or cirrhosis
   –Urine sodium > 20 mEq/L: renal failure

Question 7

Diagnosis of SIAD

Answer 7

1. Decreased effective serum osmolality (< 275 mOsm/kg)
2. Urine osmolality > 100 mOsm/kg
3. Clinical euvolemia
   - No clinical signs of extracellular volume depletion (orthostasis, tachycardia, decreased skin turgor, dry mucus membranes)
   - No clinical signs of excess extracellular volume (edema, ascites, weight trending up)
4. Urinary sodium concentration > 40 mEq/L with normal dietary Na intake
5. Normal thyroid and adrenal function
6. No recent diuretic use

Supplemental features

• Plasma [uric acid] < 4 mg/dl
• BUN < 10 mg/dl
• FeNA > 1%
• FeUrea > 55%
• NS infusion test: failure to correct hyponatremia with IV infusion of 2 L NS over 24-48 hrs
• Correction of hyponatremia with fluid restriction
• Abnormal result on water load test: A. < 80% excretion of 20 ml of water/kg body weight over 5 hours, or, B. inadequate urinary dilution (< 100 mOsm/kg of water)
• Elevated plasma [ADH] with hyponatremia and euvolemia (note that water load test and ADH levels are rarely recommended)

Question 8

SIADH Key Concepts

Answer 8

Def: release of ADH in absence of physiologic (osmotic) stimuli

• Results in hyponatremia with hypervolemia (or euvolemia) and inappropriately high urine osmolality (> 100 mOsm/L)
• May be seen with certain malignancies and many intracranial abnormalities
• Crucial to distinguish from cerebral salt wasting!! CSW produces hypovolemia

Treatment:

• Avoid rapid correction or overcorrection to reduce risk of osmotic demyelination
• Check serum [Na] q2-4 hours and do not exceed 1 mEq/L per hour, or 8 mEq/L in 24 hrs or 18 mEq/L in 48 hrs
• If severe hyponatremia of < 48 hrs duration or with severe symptoms (coma or seizure) start 3% saline at 1-2 ml/kg body weight/hr plus furosemide 20 mg IV qd
• If severe hyponatremia of > 48 hrs duration or unknown duration without severe symptoms, start NS infusion at 100 ml/hr plus furosemide 20 mg IV qd
• Chronic or unknown duration and asymptomatic: fluid restriction with dietary salt and protein, and if necessary, adjuvant drugs (demeclocycline, conivaptan, …)

Question 9

Demeclcyline

Answer 9

Tetracycline antibiotic that partially antagonizes effects of ADH on renal tubule

• Variable effects in treatment of SIADH and may cause nephrotoxicity
• Rx is 300-600 mg PO BID

Question 10

Conivaptan (Vaprisol)

Answer 10

Nonpeptide antagonist of V1A and V2 vasopressin receptors

• FDA approved for euvolemic and hypervolemic moderate-to-severe hyponatremia in hospitalized pts
• Note that severe symptoms (coma, seizures, delirium) warrants aggressive treatment with hypertonic saline
• Use in neuro-ICU has been described for treating elevated ICP when serum [Na] is not responding to traditional methods (off-label use)
• Rx is loading dose 20 mg IV over 30 min, followed by infusions of 20 mg over 24 hrs x 3 days; if serum [Na] are not rising as desired, the infusion may be increased to max dose of 40 mg over 24 hrs; use approved up to 4 days total
• Caution re drug interactions

Question 11

Fluid restriction recommendations in SIADH

Answer 11

Use solute ratio = Urinary [Na] + urinary [K] / plasma [Na]

Solute ratio > 1 : < 500 ml/d
Solute ratio 1 : 500-700 ml/d
Solute ratio < 1 : < 1 L/d