Administration of intravenous urea and normal saline for the treatment of hyponatremia in neurosurgical patients

Abstract

Hyponatremia frequently complicates the care of neurosurgical patients and requires prompt effective therapy. These patients commonly fulfill the laboratory criteria of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) or cerebral salt wasting; the classification depends on the volume status of the patient. The authors have been dissatisfied with the standard therapy of fluid restriction for the critically ill neurosurgical patient because of 1) slow rates of sodium correction; 2) poor applicability in patients requiring multiple intravenous medications and/or nutritional support; and 3) possible dangers of inducing or enhancing cerebral ischemia in patients who already may be fluid-depleted. Reported successes in the treatment of hyponatremia due to SIADH by administration of urea and normal saline led to the authors' routine use of this therapy for hyponatremic neurosurgical patients. A retrospective review of an 18-month period revealed 48 patients (3% of all neurosurgical inpatients) with hyponatremia from various causes who received 62 treatments of urea and normal saline. Treatment consisted of 40 gm urea dissolved in 100 to 150 ml normal saline as an intravenous drip every 8 hours and an intravenous infusion of normal saline at 60 to 100 ml/hr for 1 to 2 days. The mean pretreatment serum sodium level (+/- standard deviation) was 130 +/- 3 mmol/liter (range from 119 to 134 mmol/liter). There was a significant mean posttreatment elevation to 138 +/- 4 mmol/liter (range 129 to 148 mmol/liter) (p less than 0.001, Student's t-test). Average daily fluid intake and output on treatment days were 2719 +/- 912 and 2892 +/- 1357 ml, respectively. There were no treatment complications in this group. It is concluded that urea and saline administration results in a rapid, safe, and effective correction of hyponatremia, making this method superior to fluid restriction in many neurosurgical patients.

Clinical practice guideline on diagnosis and treatment of hyponatraemia

“…We identified no systematic reviews or randomised controlled trials evaluating the benefits and harms of urea, demeclocycline, lithium, mannitol, loop diuretics, phenytoin or fluid restriction. We found several case series demonstrating an increase in serum sodium concentration after 2-7 days for urea (202,203,204,205,206), demeclocycline (207), loop diuretics in combination with oral NaCl (123,125,208), phenytoin (209) and fluid restriction (210). We also identified case series of patients experiencing an increase in serum sodium over a longer time period of up to 12 months for urea (211,212,213), up to 3 weeks for demeclocycline (214,215,216,217,218,219), up to 20 weeks for lithium (220), up to 150 days for furosemide with oral NaCl (221) and up to 30 days in phenytoin (220).…”

Cerebral salt wasting syndrome distinct from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH)

“…Ishiguro et al 3 point out that intravenous hypertonic saline may cause volume expansion and successive loss in the urine, so that the enteral supply of salt appeared to be an appropriate treatment. Reeder et al 9 treated patients with hyponatraemia due to intracranial diseases by administering urea and saline for both SIADH and cerebral salt wasting. Their basic theory is that urea induced a mild osmotic diuresis and depressed urinary sodium excretion, while the supplemental salt restored sodium deficits.…”

Hyponatraemia

“…Isotonic saline has been used in the past, particularly in conjunction with urea, to treat hyponatraemia in neurosurgical intensive care units (Reeder & Harbaugh, 1989). Urea, in doses of 30±60 g daily, increases free water excretion by causing an osmotic diuresis and also decreases urinary sodium excretion .…”