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Time to speed up–the rate at which we correct hypernatremia

Published:November 05, 2020DOI:https://doi.org/10.1016/j.ejim.2020.10.005
      Hypernatremia is a common electrolyte disorder. It is defined as a serum sodium concentration > 145 mmol/L and is a hyperosmolar state in which there is a deficit in total body volume relative to electrolytes. Hospitalized patients with altered mental status, restricted access to water, or impaired thirst are particularly at risk to develop hypernatremia. In the ICU hypernatremia is independently associated with mortality, although it is unknown whether prevention, or correction of hypernatremia improves outcomes [
      • Funk G.C.
      • Lindner G.
      • Druml W.
      • Metnitz B.
      • Schwarz C.
      • Bauer P.
      • et al.
      Incidence and prognosis of dysnatremias present on ICU admission.
      ,
      • Lindner G.
      • Funk G.C.
      • Schwarz C.
      • Kneidinger N.
      • Kaider A.
      • Schneeweiss B.
      • et al.
      Hypernatremia in the critically ill is an independent risk factor for mortality.
      ].
      Treatment of hypernatremia should involve addressing the underlying cause and correcting hypertonicity. Guidelines recommend a correction of no more than 8–10 mmol/L per 24 h with a maximal rate of 0.5 mmol/L/h in chronic hypernatremia, requiring regular evaluation of the serum sodium concentration during the correction phase [
      • Sterns R.H.
      Evidence for managing hypernatremia: is it just hyponatremia in reverse?.
      ]. These recommendations are based on the supposition that rapid correction is associated with an increased risk of cerebral edema [
      • Adrogue H.J.
      • Madias N.E
      Hypernatremia.
      ]. However, current recommendations for the treatment of hypernatremia in adults are based on observations in infants, which probably do not apply, and may even be harmful in adults [
      • Sterns R.H.
      Evidence for managing hypernatremia: is it just hyponatremia in reverse?.
      ,
      • Blum D.
      • Brasseur D.
      • Kahn A.
      • Brachet E.
      Safe oral rehydration of hypertonic dehydration.
      ,
      • Kahn A.
      • Brachet E.
      • Blum D.
      Controlled fall in natremia and risk of seizures in hypertonic dehydration.
      ].
      Current treatment recommendations in adults are based on case-control studies in infants aged 0–6 months. Infants who developed seizures after correction of hypernatremia had a faster decrease in sodium levels, although the rate of correction exceeded 0.5 mmol/L/h even in those without seizures [
      • Blum D.
      • Brasseur D.
      • Kahn A.
      • Brachet E.
      Safe oral rehydration of hypertonic dehydration.
      ,
      • Kahn A.
      • Brachet E.
      • Blum D.
      Controlled fall in natremia and risk of seizures in hypertonic dehydration.
      ]. In contrast to these observations in infants, there are no published case-reports of cerebral edema after rapid correction of chronic hypernatremia in non-hyperglycemic adults [
      • Lindner G.
      • Funk G.C.
      • Schwarz C.
      • Kneidinger N.
      • Kaider A.
      • Schneeweiss B.
      • et al.
      Hypernatremia in the critically ill is an independent risk factor for mortality.
      ]. It is therefore doubtful whether these observations in infants are generalizable to adults. Infants are also more prone to febrile convulsions than adults. An increased tendency to develop seizures might therefore simply reflect the fact that the infant's brain is more vulnerable.
      Recently, a retrospective study compared slow and rapid correction of hypernatremia in adults to determine the association between correction rate and mortality or neurologic outcomes. Both patients with hypernatremia on admission (n = 122) and those who developed hypernatremia during admission (n = 327) were included. The correction rate exceeded 0.5 mmol/L/h in 142 of those patients. Mortality did not differ significantly between the two groups with a slow versus rapid correction rate, nor did they find any increase in neurologic adverse events related to the correction of hypernatremia on the basis of a review of daily progress notes, discharge summaries, imaging reports, or annual reviews op ICD9 codes [
      • Chauhan K.
      • Pattharanitima P.
      • Patel N.
      • Duffy A.
      • Saha A.
      • Chaudhary K.
      • et al.
      Rate of correction of hypernatremia and health outcomes in critically ill patients.
      ].
      A French retrospective study has demonstrated that current practice leads to undertreatment of patients. 24 h after initiating treatment, sodium levels worsened in 34% and remained stable in 8% of patients. After three days, hypernatremia had normalized in only 32% of patients [
      • Bataille S.
      • Baralla C.
      • Torro D.
      • Buffat C.
      • Berland Y.
      • Alazia M.
      • et al.
      Undercorrection of hypernatremia is frequent and associated with mortality.
      ]. Another study in 180 patients with hospital-acquired hypernatremia, showed that 9.4% of patients with hospital-acquired hypernatremia, subsequently progressed to a severe hypernatremia of 160 mmol/L [
      • Ranjan R.
      • Lo S.C.
      • Ly S.
      • Krishnananthan V.
      • Lim A.K.H.
      Progression to severe hypernatremia in hospitalized general medicine inpatients: an observational study of hospital-acquired hypernatremia.
      ]. Several studies found an association between undercorrection of hypernatremia and mortality [
      • Bataille S.
      • Baralla C.
      • Torro D.
      • Buffat C.
      • Berland Y.
      • Alazia M.
      • et al.
      Undercorrection of hypernatremia is frequent and associated with mortality.
      ,
      • Ranjan R.
      • Lo S.C.
      • Ly S.
      • Krishnananthan V.
      • Lim A.K.H.
      Progression to severe hypernatremia in hospitalized general medicine inpatients: an observational study of hospital-acquired hypernatremia.
      ,
      • Alshayeb H.M.
      • Showkat A.
      • Babar F.
      • Mangold T.
      • Wall B.M.
      Severe hypernatremia correction rate and mortality in hospitalized patients.
      ].
      In conclusion, cerebral edema has never been reported after correcting chronic hypernatremia in non-hyperglycemic adults and there are no data to support restriction of the correction rate to less than 8–10 mmol/L per 24 h. Additionally, current recommendations result in undertreatment in the majority of patients. As this is associated with increased mortality, current guidelines are potentially harmful.
      Awaiting revised guidelines, a common sense approach would be to aim for a correction of 12 mmol/L over 24 h instead of pursuing an hourly correction rate. Serum sodium should be checked mainly to prevent a further progression of hypernatremia and to intensify treatment accordingly. If the correction rate is inadvertently exceeded, therapeutic reraising of the sodium concentration should certainly be avoided [
      • Sterns R.H.
      Evidence for managing hypernatremia: is it just hyponatremia in reverse?.
      ]. A rate of 12 mmol/L per 24 h might still be too conservative, but more aggressive recommendations should await future studies. Additionally, this target might better address the problem of undercorrection, which is currently occurring frequently.

      Declaration of Competing Interest

      There are no conflicts of interest.

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