Jags 2006;54:345; Nejm 2000;342:1581

Cause:

• Elevated antidiuretic hormone (ADH) from:
• Syndrome of inappropriate ADH (SIADH) (Nejm 2007;356:2064), most commonly, or tumor (Ann IM 1985;102:165)
• Drugs: vincristine, cytoxan, clofibrate, narcotics, nicotine, isoproterenol, vasopressin iv in ICU
• Hypovolemia
• Increased renal ADH sensitivity: chlorpropamide and other 1st- but not 2nd-generation hypoglycemics, NSAIDs esp ibuprofen and indomethacin (Nejm 1984;310:568), thiazides, carbamazepine, SSRI (GRS 2006)
• Lab error (pseudohyponatremia) (Nejm 2003;349:1465): check osmoles, measure Na directly w ABG machine; glucose, mannitol, post-TURP glycine bladder instillation
• Free water replacement of isotonic emesis, diarrhea, blood, serum; or idiopathically postop (Nejm 1986;314:1529)
• Hypothyroid hypo-osmolarity, Addison’s disease
• Psychiatric patients with polydipsia, inappropriate ADH syndrome (SIADH), and decreased renal-free water excretion (Nejm 1988;318:397)
• Postop (1-3 d), equal sex ratio, 1% incidence; caused by high vasopressin (ADH) levels and hypotonic or sometimes even isotonic (Ann IM 1997;126:20) iv fluids, but respiratory arrest and mortality much higher in menstruating women (Ann IM 1992;117:891)
• Rising danger with athletes replacing sweat with copious PO hypotonic hydration during athletic competitions, especially half- and full marathon length events (Nejm 2005;352:1550)

Pathophys:Cerebral edema causes CNS sx

Females > males; seen in marathon-running women from free water replacement of sweat loss (Ann IM 2000;132:711)

Sx:Confusion, HA, N⁺V, muscle cramps

Si:Seizures/confusion, depressed reflexes

r/o adrenal insufficiency, hypothyroidism

Labs: Chem:Na <125 mEq/L; uric acid <5 mg % with ADH-producing tumor or SIADH (Nejm 1979;301:528)

Rx:

Acutely stop drugs; give saline and furosemide (Lasix); if developed slowly, correct at <2.5 mEq/h, not >10 mEq/day (Ann IM 1997;126:57) with iso- or perhaps hypertonic (3% NaCl, thus 3× normal) saline and possibly iv furosemide, then go slowly to avoid pontine demyelination (Ann IM 1997;126:57); or go slowly over days, no benefit from rushing or using twice normal saline even when Na <110 (Ann IM 1987;107:656) unless symptomatic or very acute. Dialysis (hypertonic, intraperitoneal)

• Estimate effect of change in serum:
• Na by 1 L fluid = (infusate Na + infusate K) – serum Na / Total body water (24-Hour Requirements) + 1

Chronic (Na <130 for more than 2 d):

• if neurologic si: avoid hypoxia, then iv saline or hypertonic saline as above to improve outcome (Jama 1999;281:2342)
• if no neurologic si: 1st, restrict water and, if SIADH, give liberal salt diet or salt tablets; 2nd, salt tablets + loop diuretic; 3rd, demeclocycline (Declomycin, a tetracycline) 0.6-1.2 gm/day (Nejm 1978;298:173); 4th, lithium 300 mg po tid-qid; possibly tolvaptan 15-60 mg po daily, a vasopressin receptor antagonist (DBCT—Nejm 2006;355:2099)