title: Evidence summary - Neonatal Intensive Care Drug Manual
text: IV correction for severe and/or symptomatic hyponatraemia
  The body of evidence to base recommendations in this clinical setting is extremely limited, particularly in neonatal populations. Recommendations are based on expert opinion, which have been extrapolated from adult consensus guidelines6,7 and take into account specific neonatal safety concerns (see Safety below). In acute hyponatraemia, where the risk of sequelae is greater than that of osmotic demyelination, the correction should be rapid.8
  Aim to increase sodium by 1–2 mmol/L per hour until symptoms abate or a safe level of sodium is achieved (≥ 120 mmol/L).9 Once the safe level is achieved, suggested subsequent goals are 6–8 mmol/L in 24 hours, 12–14 mmol/L in 48 hours and 14–16 mmol/L in 72 hours.10 (LOE IV, GOR C)
  Dosage and infusion rate recommendations in this formulary are extrapolated from the rate of rise expected with sodium chloride 3%2 and are as follows:
  0.5 mmol/mL of sodium chloride (i.e. sodium chloride 3%), when administered at 1 mL/kg, will raise serum sodium by 1 mmol/L.
  0.4 mmol/mL of sodium chloride (i.e. diluted sodium chloride in this formulary), when administered at 1 mL/kg, will raise serum sodium by 0.8 mmol/L.
  Sodium deficit calculation
  Deficit in mmol = (desired sodium – serum sodium) x total body water
  Total body water is traditionally calculated as weight x 0.6 in children. Greater total body water content in newborns should be considered and therefore should be calculated as weight x 0.75.2,5 (LOE IV, GOR C)
  Oral supplementation
  A randomised, controlled trial of 4 mmol/kg/d (0.4 mL/kg per dose of 2.5 mmol/mL sodium chloride) of sodium versus placebo from DOL 7 to 35 in infants born 24–31 weeks (53 infants) showed higher sodium levels and increased weight gain in the intervention group.11 A randomised, controlled trial of 4 mmol/kg/d (concentration not specified) of sodium versus placebo from DOL 4 to 14 in infants born at 29–34 weeks (20 infants) showed higher sodium levels and increased weight gain in the intervention group.12 There are also three case–control studies that report similar findings with respect to sodium levels and growth in preterm infants supplemented with oral sodium.13-15 A systematic review comparing higher versus lower sodium intake for preterm infants is in progress.16 These findings support the use of oral sodium supplements to correct hyponatraemia and potentially improve growth. (LOE II, GOR B)
  Safety
  An historical, case-control study identified 42/350 ELBW NICU admissions with an episode of hyponatraemia (Na < 125 mmol/L [range 113–124]) that lasted > 6 hours (median 1.5 days).17 Rates of abnormal head ultrasound (IVH or PVL) and abnormal neurological examination were higher in the hyponatraemic group (p < 0.03; p < 0.001 respectively). Correction ≥ 0.5 mmol/L/h showed a trend toward higher rates of abnormal neurological examination. In paediatric and adult populations, multiple cohort studies and reviews have concluded that in patients with chronic hyponatraemia (≥ 48 hours), neurologic sequelae due to osmotic demyelination are associated with more rapid rates of correction.7,9
  In summary, rapid correction of hyponatraemia may be detrimental to neurological outcome during myelination of the newborn brain.17 In adult populations, osmotic demyelination syndrome can usually be avoided by limiting correction of chronic hyponatraemia to < 10 to 12 mmol/L in 24 hours and to < 18 mmol/L in 48 hours. These estimates should be regarded as approximate limits and not goals of therapy.7 (LOE IV, GOR C)
  Osmolarity and Osmolar load
  A retrospective, matched-cohort study of 352 children ≤ 18 years evaluated the incidence of phlebitis or infiltration associated with peripheral administration of parenteral nutrition with an osmolarity > 1000 mOsm/L vs ≤ 1000 mOsm/L.18 There were 151 neonates in the study. There were no differences between patients who did or did not develop adverse events in terms of age or weight. Administration of PPN with osmolarity > 1000 mOsm/L vs ≤ 1000 mOsm/L significantly increased infiltration (17% vs 7%; odds ratio [OR, 2.47]; 95% confidence interval [CI], 1.24–4.94; p = 0.01) and the combined composite end point of phlebitis or infiltration (45% vs 34%; OR, 1.65; 95% CI, 1.07–2.54; p = 0.02). In multivariate analysis, osmolarity > 1000 mOsm/L vs ≤ 1000 mOsm/L was an independent risk factor for developing complications (OR, 1.67; 95% CI, 1.08–2.52; p = 0.02).18 (LOE III, GOR C)
  A prospective, observational study in adults suggests that osmolar load (i.e. number of milliosmoles per hour, calculated as osmolarity x infusion rate) is a better predictor than osmolarity alone for phlebitis.19 They found an osmolarity rate of 84–99 mOsm/hour was associated with 4–27% rate of phlebitis. They did not report on other injuries such as extravasation. The infusion rates suggested in our formulary have low osmolar load and are considered to carry minimal risk of phlebitis (Consensus opinion).
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