====== Syndrome of inappropriate antidiuretic hormone secretion treatment ======

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===== Management =====

[[Management]] is based on the [[severity]] and [[duration]] of [[hyponatremia]], and the presence of [[symptom]]s. 

Two caveats:

1.  be sure that hyponatremia is not due to [[CSW]] before restricting [[fluid]]s.

2. avoid too rapid correction and avoid correcting to normal or supranormal (overcorrection) [[sodium]] to reduce the risk of [[osmotic demyelination syndrome]].

The only definitive treatment is treatment of the underlying cause

● if caused by [[anemia]]: usually responds to [[transfusion]].

● if caused by malignancy, may respond to antineoplastic therapy.

● most drug-related cases respond rapidly to discontinuation of the offending drug.
----
Aggressive treatment [[protocol]]. 

Indications 

1. severe [[hyponatremia]] (serum [Na+]<125 mEq/L).

2. AND either

a) duration known to be <48 hours

b) or severe symptoms ([[coma]], [[seizure]]s).

===== Treatment =====

● transfer patient to [[ICU]]. 

3% saline: start infusion 1–2 ml/kg body weight per hour (infusion rate may be doubled to 2– 4 ml/kg/hr for limited periods in patients with coma or seizures)
((Ellison DH, Berl T. Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007; 356:2064–2072))
and [[furosemide]] (Lasix®) 20 mg IVq d (furosemide accelerates the increase in [Na+] and prevents volume overload with subsequent increase in atrial natriuretic factor and resultant urinary dumping of the extra Na+ being administered).

● monitoring and adjustments

○ Check serum [Na+] every 2–3 hours and adjust infusion rate of 3% saline

– goal: raise serum sodium by 1–2 mEq/L/hr
((Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med. 2000; 342:1581–1589)) 
(use the lower end of the range for hyponatremia > 48 hours duration or unknown duration)

– limits: do not exceed 8–10 mEq/Lin 24 hrs and 18–25 mEq/Lin 48 hrs 
((Ellison DH, Berl T. Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007; 356:2064–2072))
(use the lower end of these ranges for hyponatremia >48 hours duration or unknown duration)

measure K+ lost in the urine and replace it accordingly

○ if symptoms of [[osmotic demyelination]] occur (early symptoms are lethargy and affective changes, usually after initial improvement): deficits may improve by stopping treatment and modestly relowering the serum sodium e.g. with [[DDAVP]]
((Soupart A, Ngassa M, Decaux G. Therapeutic relowering of the serum sodium in a patient after excessive correction of hyponatremia. Clin Nephrol. 1999; 51:383–386))
((Oya S, Tsutsumi K, Ueki K, Kirino T. Reinduction of
hyponatremia to treat central pontine myelinolysis.
Neurology. 2001; 57:1931–1932)).

Intermediate treatment protocol. 

Indications

1. symptomatic non severe hyponatremia (serum [Na+]=125–135mEq/L),or 

2. severe hyponatremia (serum [Na+]<125 mEq/L),AND

a) duration >48 hours or unknown AND

b) only moderate symptoms or nonspecific symptoms (e.g. H/A, or lethargy)

Treatment

1. interventions

a) 0.9%saline (normal saline) infusion

b) and furosemide(Lasix®)20 mgIV q d

c) consider conivaptan for refractory cases

2.
monitoring: check serum [Na+] every 4 hours and adjust infusion rate of normal saline 

goals: [Na+] increase of 0.5–2 mEq/L/hr

limits: do not exceed 8–10 mEq/Lin 24 hrs and 18–25 mEq/Lin 48 hrs
((Ellison DH, Berl T. Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007; 356:2064–2072))

Routine treatment protocol and maintenance therapy. 

Indications
: asymptomatic nonsevere hyponatremia (serum [Na+]=125–135 mEq/L),or
severe hyponatremia (serum [Na+]<125 mEq/L) AND

a) duration >48 hours or unknown AND

b) asymptomatic

Treatment
1. interventions

a) fluid restriction for adults, for peds: 1 L/m2/day) while encouraging use of dietary salt and protein. Caution restricting fluids in hyponatremia following SAH.

b) for refractory cases, consider

● demeclocycline: a tetracycline antibiotic that partially antagonizes the e ects of ADH on the
renal tubules
((De Troyer A, Demanet JC. Correction of antidiuresis by demeclocycline. N Engl 
J Med. 1975 Oct 30;293(18):915-8. PubMed PMID: 170519.
))
((Perks WH, Mohr P, Liversedge LA. Demeclocycline inInappropriateADHSyndrome.Lancet.1976;2))
((Forrest JN, Cox M, Hong C, et al. Superiority of Demeclocycline over Lithium in the Treatment of Chronic Syndrome of Inappropriate Secretion of Antidiuretic Hormone. N Engl J Med. 1978; 298:173–177))

Effects are variable,and nephrotoxicity may occur.300–600 mg POBID

● [[conivaptan]] (Vaprisol®): a nonpeptide antagonist of V1A & V2 vasopressin receptors. [[FDA]] approved for euvolemic and hypervolemic moderate-to-severe [[hyponatremia]] in hospitalized patients (NB: severe symptoms of seizures, coma, delirium... warrants aggressive treatment with hypertonic saline
((Ellison DH, Berl T. Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007; 356:2064–2072)).

Use in the neuro-ICU has been described for treating elevated ICP when serum [Na] is not responding to traditional methods
((Wright WL, Asbury WH, Gilmore JL, Samuels OB. Conivaptan for hyponatremia in the neurocritical care unit. Neurocrit Care. 2009; 11:6–13)) 
(off-label use – use with caution). loading dose of 20 mg IV over 30 minutes, followed by [[infusion]]s of 20 mg over 24 hours × 3 days. If serum [Na+] is not rising as desired, the infusion may be increased to the maximal dose of 40 mg over 24 hours. Use is approved for up to 4 days total. Caution re drug interactions

● [[lithium]]: not very effective and has many side effects. Not recommended

===== References =====