NEWS & VIEWS HYPONATRAEMIA
Isotonic fluids prevent hospital-acquired hyponatraemia Michael L. Moritz and Juan C. Ayus Refers to McNab, S. et al. 140 mmol/l of sodium versus 77 mmol/l of sodium in maintenance intravenous fluid therapy for children in hospital (PIMS): a randomised controlled double-blind trial. Lancet http://dx.doi.org/10.1016/S0140-6736(14)61459-8.
Intravenous fluid (IVF) administration is a critical part of supportive care for the acutely ill child. For over 50 years the standard of care for maintenance fluid therapy has been to administer hypotonic fluids, reflecting the electrolyte and water requirements of the average child.1 This approach, however, resulted in hospital-acquired hyponatraemia in approximately 40% of patients and many reports of death or permanent neurologic dysfunction from hyponatraemic encephalopathy. 2,3 In 2003, we proposed the use of isotonic maintenance fluids to prevent hospital-acquired hyponatraemia, as acutely ill patients have numerous stimuli for producing antidiuretic hormone (ADH; also known as vasopressin), which places them at increased risk of hyponatraemia.4 This approach was controversial,5 yet mounting evidence suggests that it is correct.6 McNab et al. have now conducted a definitive trial demonstrating that isotonic fluids are sup erior to hypotonic fluids for the prevention of hospital-acquired hyponatraemia in children without producing untoward complications such as hypernatraemia or fluid overload.7 Numerous retrospective, observational and prospective studies have demonstrated that isotonic fluids are superior to hypotonic fluids for preventing hospital-acquired hyponatraemia in children. A 2014 systematic review and meta-analysis that included data from 893 children across 10 prospective trials concluded that isotonic fluids are superior to hypotonic fluids in preventing hyponatraemia in post-surgical and
critically ill patients, but that insufficient data were available to draw conclusions for patients on general paediatric wards.6 Doubts about the safety of using isotonic saline also existed because of concerns that it might produce fluid overload and hypernatraemia. The large randomized controlled double-blind trial by McNab et al. specifically addresses these issues and should allay those concerns. This single-centre trial performed in Australia is by far the largest prospective randomized controlled trial to compare isotonic and hypotonic fluids, enrol ling 690 patients aged from 3 months to 18 years. It included a heterogenous group of children, just under half of whom were recruited following surgery and under 5% of whom required admission to the intensive care unit. 7 Patients were randomly allocated to receive either Plasma-Lyte® 148 (Baxter, Deerfield, IL, USA; with a sodium concentration of 140 mmol/l) or a 0.45% NaCl solution (with a sodium concentration 77 mmol/l); both solutions contained 5% dextrose. The rate and duration of fluid administration were at the discretion of the treating clinicians and serum sodium level was monitored as per protocol for 72 h. The incidence of hyponatraemia (defined as sodium 145 mmol/l (4% versus 6%; OR 0.8,
NATURE REVIEWS | NEPHROLOGY
Photodisc/Getty
Hypotonic fluid administration has been the standard of care for maintenance fluid therapy in acutely ill children, but this approach is associated with hospital-acquired hyponatraemia and hyponatraemic encephalopathy. New findings demonstrate that isotonic maintenance fluids are safe and effective in preventing hospital-acquired hyponatraemia in children, whereas a 0.45% NaCl solution is not.
P = 0.055), or overhydration (5% versus 4%; OR 1.47, P = 0.32). Importantly, no difference was observed in the risk of developing hyponatraemia in surgical versus non-surgical patients. This study does have some important limitations that should be kept in mind. As arginine vasopressin (AVP) levels were not measured, the researchers were unable to assess the relationship between AVP levels and the development of hyponatraemia or if using Plasma-Lyte® compared to 0.45% NaCl solution prevented elevations in AVP level. In addition, the study participants received IVF only for a short period of time, with only about 50% of study participants receiving IVF after 12 h and less than 15% after 48 h. These limitations mean that the true incidence of hyponatraemia associated with 0.45% NaCl solution may have been underestimated. This point also likely explains why the researchers found the risk of hyponatraemia to be greatest at 6 h after IVF initiation, as most patients were off IVF within 12 h. This study may also have overestimated the incidence of hyponatraemia associated with Plasma-Lyte® as approximately one-third of the fluid volume these patients received was administered orally. The neurologic morbidity associated with the 0.45% NaCl solution might also be underestimated as multiple safeguards were in place for patients who developed a serum sodium level
Isotonic fluids prevent hospital-acquired hyponatraemia Michael L. Moritz and Juan C. Ayus Refers to McNab, S. et al. 140 mmol/l of sodium versus 77 mmol/l of sodium in maintenance intravenous fluid therapy for children in hospital (PIMS): a randomised controlled double-blind trial. Lancet http://dx.doi.org/10.1016/S0140-6736(14)61459-8.
Intravenous fluid (IVF) administration is a critical part of supportive care for the acutely ill child. For over 50 years the standard of care for maintenance fluid therapy has been to administer hypotonic fluids, reflecting the electrolyte and water requirements of the average child.1 This approach, however, resulted in hospital-acquired hyponatraemia in approximately 40% of patients and many reports of death or permanent neurologic dysfunction from hyponatraemic encephalopathy. 2,3 In 2003, we proposed the use of isotonic maintenance fluids to prevent hospital-acquired hyponatraemia, as acutely ill patients have numerous stimuli for producing antidiuretic hormone (ADH; also known as vasopressin), which places them at increased risk of hyponatraemia.4 This approach was controversial,5 yet mounting evidence suggests that it is correct.6 McNab et al. have now conducted a definitive trial demonstrating that isotonic fluids are sup erior to hypotonic fluids for the prevention of hospital-acquired hyponatraemia in children without producing untoward complications such as hypernatraemia or fluid overload.7 Numerous retrospective, observational and prospective studies have demonstrated that isotonic fluids are superior to hypotonic fluids for preventing hospital-acquired hyponatraemia in children. A 2014 systematic review and meta-analysis that included data from 893 children across 10 prospective trials concluded that isotonic fluids are superior to hypotonic fluids in preventing hyponatraemia in post-surgical and
critically ill patients, but that insufficient data were available to draw conclusions for patients on general paediatric wards.6 Doubts about the safety of using isotonic saline also existed because of concerns that it might produce fluid overload and hypernatraemia. The large randomized controlled double-blind trial by McNab et al. specifically addresses these issues and should allay those concerns. This single-centre trial performed in Australia is by far the largest prospective randomized controlled trial to compare isotonic and hypotonic fluids, enrol ling 690 patients aged from 3 months to 18 years. It included a heterogenous group of children, just under half of whom were recruited following surgery and under 5% of whom required admission to the intensive care unit. 7 Patients were randomly allocated to receive either Plasma-Lyte® 148 (Baxter, Deerfield, IL, USA; with a sodium concentration of 140 mmol/l) or a 0.45% NaCl solution (with a sodium concentration 77 mmol/l); both solutions contained 5% dextrose. The rate and duration of fluid administration were at the discretion of the treating clinicians and serum sodium level was monitored as per protocol for 72 h. The incidence of hyponatraemia (defined as sodium 145 mmol/l (4% versus 6%; OR 0.8,
NATURE REVIEWS | NEPHROLOGY
Photodisc/Getty
Hypotonic fluid administration has been the standard of care for maintenance fluid therapy in acutely ill children, but this approach is associated with hospital-acquired hyponatraemia and hyponatraemic encephalopathy. New findings demonstrate that isotonic maintenance fluids are safe and effective in preventing hospital-acquired hyponatraemia in children, whereas a 0.45% NaCl solution is not.
P = 0.055), or overhydration (5% versus 4%; OR 1.47, P = 0.32). Importantly, no difference was observed in the risk of developing hyponatraemia in surgical versus non-surgical patients. This study does have some important limitations that should be kept in mind. As arginine vasopressin (AVP) levels were not measured, the researchers were unable to assess the relationship between AVP levels and the development of hyponatraemia or if using Plasma-Lyte® compared to 0.45% NaCl solution prevented elevations in AVP level. In addition, the study participants received IVF only for a short period of time, with only about 50% of study participants receiving IVF after 12 h and less than 15% after 48 h. These limitations mean that the true incidence of hyponatraemia associated with 0.45% NaCl solution may have been underestimated. This point also likely explains why the researchers found the risk of hyponatraemia to be greatest at 6 h after IVF initiation, as most patients were off IVF within 12 h. This study may also have overestimated the incidence of hyponatraemia associated with Plasma-Lyte® as approximately one-third of the fluid volume these patients received was administered orally. The neurologic morbidity associated with the 0.45% NaCl solution might also be underestimated as multiple safeguards were in place for patients who developed a serum sodium level
