Efficacy and Safety of Rapid Intermittent Compared With Slow Continuous Correction in Severe Hyponatremia Patients

Moderate to severe symptomatic hyponatremia requires prompt treatment with hypertonic saline. The extent and rate of increase in serum sodium (sNa) levels during treatment are critical. Several methods for continuous infusion of hypertonic saline were used to guide rate of fluid administered to achieve the required serum sodium target. As based on static model, they had a bias to over-correction of hyponatremia. Alternative approach to treatment with hypertonic fluid is to use small, fixed boluses to achieve controlled increments in sNa. However, there was no high quality evidence on whether hypertonic saline are best given in continuous infusion (preferred by most) or bolus injection. The aim of present study, a multi-center (Seoul National University Bundang Hospital [2016.8~], Seoul National University Boramae Medical Center [2016. 9~], Hallym University Dongtan Sacred Heart Hospital [2017.7~]), randomized, open labelled, controlled clinical trial, is to investigate efficacy and safety of rapid intermittent correction compared with slow continuous correction with hypertonic saline in patient with moderately severe or severe symptomatic severe hyponatremia. A total 178 patients, who suffer from symptomatic severe hyponatremia, will be enrolled and randomly assigned to receive either intermittent bolus infusion or slow continuous infusion by 3% hypertonic saline. Subjects will take different rate of 3% hypertonic saline for 24-48 hours stratified by severity of clinical symptoms. Serum sodium will be measured at every six hours during two days.

Inclusion criteria

• In emergency setting (2016.6-) and/or inpatients at ward (2018.9-)
• Glucose corrected serum sodium ≤125 mmol/L
• Patients with moderately severe or severe symptom

• Moderately severe

:Nausea without vomiting Drowsy, Headache General weakness, myalgia

• Severe :Vomiting, Stupor, Seizures, Coma (Glasgow Coma Scale ≤8)
• written consent

Exclusion criteria

• Pseudohyponatremia: serum osmolality > 275 mOsm/kg

• If the serum osmolality is > 275 mOsm/kg but the BUN is ≥ 30 mg/dL, the patients can be registered if calculated serum osmolality (2 x plasma [Na] + [Glucose]/18) is <275 mOsm/kg
• Primary polydipsia: urine osmolality ≤ 100 mOsm/kg
• Glucose corrected serum sodium >125 mmol/L
• Arterial hypotension (SBP <90mmHg and MAP <70mmHg)
• Anuria or urinary outlet obstruction
• Liver disease

• transaminase levels >3 times the upper limit normal
• Known LC with ascites or diuretics use or PSE Hx or Varix Hx
• Uncontrolled diabetes mellitus (HbA1C > 9%)
• Women who are pregnant or breast feeding
• History of cardiac surgery excluding PCA, acute myocardial infarction, sustained ventricular tachycardia, ventricular fibrillation, acute coronary syndrome, cebrovascular trauma, and increased intracranial pressure within the 3 months prior to randomization