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Paper text:
moderate to severe hyponatremia ( serum sodium < 125 mmol / l ) , when it occurs , is often an iatrogenic occurrence during hospitalization with significant associated morbidity .
seizures , cerebral edema and death resulting from cerebral edema have been described in some cases of water intoxication .
hyponatremia occurs from a variety of pathogenic processes , including the use of medications which affect water metabolism .
one such medication with reported hyponatremia is duloxetine , a selective serotonin reuptake inhibitor ( ssri ) and selective norepinephrine reuptake inhibitor ( snri ) approved in the usa for treatment of major depressive disorder , diabetic neuropathic pain , stress urinary incontinence and fibromyalgia .
we report here an instance of asymptomatic hyponatremia occurring during duloxetine treatment that became symptomatic during the course of a glomerular filtration rate ( gfr ) test that involved water loading the subject .
a 48-year - old caucasian woman with past medical history of systemic lupus erythematosus , type 2 diabetes mellitus , hypertension , migraine , gastroparesis , fibromyalgia , mitral valve prolapse , hypothyroidism and hyperprolactinemia was scheduled for an i - iothalamate gfr testing as part of a research study .
the participant consumed ~ 2 l of fluids at home following instructions from the staff recommending hydration before the test .
she received five drops of super - saturated potassium iodide ( sski ) in 2 oz of water to block the thyroid uptake . at baseline , blood
blood and urine were collected to serve as background values to compare with the serial blood and urine tests during the iothalamate gfr testing .
the participant was asked to drink additional water per the protocol based on the background urine specific gravity .
the gfr test was uneventful for the first 2 h. then , the subject complained of acute onset of generalized headache described as  56 out of 10 with nausea and vomiting .
her heart rate was 5060/min , blood pressure rose to 160170 mmhg systolic and 90108 mmhg diastolic , oxygen saturation registered 100% on room air and finger - stick blood glucose values were 99102 mg / dl .
an intravenous solution of 0.9% saline was initiated , and the subject was transferred to the emergency department for further management . during the gfr testing ,
an intake of 3300 ml of water and a urine volume of 1325 ml were recorded .
her home medications included naratriptan , amitriptyline , cabergoline , propranolol , sitagliptin , meloxicam , hydroxychloroquine , pravastatin , lansoprazole , levothyroxine , vitamin d , azelastine , polyethylene glycol , aspirin and duloxetine .
the serum sodium measured 3 months after the increase in the dose of duloxetine was 137 mmol / l . in the emergency department
, she had normal pupil reactivity , a supple neck , and normal pulmonary , cardiovascular and abdominal examinations .
neurological examination showed the patient to be responsive but confused with intact deep tendon reflexes .
a computerized tomography ( ct ) scan of the brain showed diffuse cerebral edema with basal cistern effacement .
her intravenous solution was altered to 3% hypertonic saline ( 212 ml of 3% saline = 109 mmol of sodium chloride ) , and she was administered furosemide 40 mg intravenously ( iv ) , zofran 4 mg iv and lorazepam 1 mg iv .
serial serum sodium levels were checked , and the rate of hypertonic saline was adjusted accordingly . symptoms and mental status improved with gradual increase in serum sodium ( figure 1 ) .
she was discharged to home after 4 days with advice to taper the dose and then discontinue duloxetine .
gfr is considered the best measure of kidney function in health and disease . in large clinical studies , i - iothalamate
the test requires water loading , multiple blood draws and 68 h of time . despite the significant water loading
recommended to achieve the most accurate gfr results , hyponatremia has not been reported previously during gfr testing .
renal capacity for free water excretion is up to 28 l / day . as a result , under normal physiological conditions ,
, our subject had undergone uneventful i - iothalamate testing in the past without complications prior to receiving duloxetine . in previously reported cases of duloxetine - related hyponatremia ,
the time course of developing hyponatremia was acute as compared with our subject whose serum sodium was normal even after 6 months of duloxetine usage .
it is likely that the pre - admission water load specified in the gfr protocol provoked hyponatremia in our subject , which was worsened by the added water ingestion during the gfr procedure .
our patient illustrates the need for vigilance during water loading , even when well tolerated previously , especially when medications such as antidepressant and antipsychotic are in use .
a stat serum sodium blood test could be performed prior to exposing the subject to water loading when such a situation like ours occurs in a clinical research setting .
our case illustrates the value of a detailed medication history when performing water loads and supports the need for vigilance when studying subjects who take an antidepressant or antipsychotic medication despite a documented history of eunatremia on such therapies .
hyponatremia affects nearly one in five of all hospitalized patients . 
 severe hyponatremia is associated with significant morbidity and mortality , and is therefore important to recognize . 
 prior reports have linked duloxetine with hyponatremia , but it is uncommon . in this case report , we describe a research subject taking duloxetine who developed severe symptomatic hyponatremia during glomerular filtration rate testing despite having undergone such testing uneventfully in the past .