What is dehydration and how it is treated?
Children with acute diarrhoea or gastroenteritis who get severely dehydrated require intravenous (into a vein) rehydration with fluids (called intravenous correction). The most common intravenous solutions used for this purpose are the so-called crystalloids, which are solutions of mineral salts (e.g. electrolytes such as sodium, potassium, or chloride). The most commonly used crystalloid for rehydrating children is 0.9% saline solution. It is unclear whether this solution is the best intervention for these children because, when compared to other fluids in other diseases and conditions, 0.9% saline use has been associated with generating or worsening established metabolic acidosis and increasing the length of hospital stay.
What is metabolic acidosis?
Metabolic acidosis is defined as a reduction in low serum pH caused by different diseases, including dehydration. The pH is a measure of how acidic/basic solutions (such as water or the body fluids) are. Another measure of the degree of the acidosis is serum bicarbonate levels. Bicarbonate is a body buffer that helps to compensate the pH when metabolic acidosis occurs. The lower the level of serum bicarbonate, the more severe the acidosis. Metabolic acidosis is a common complication of dehydration, which may cause vomiting and hamper food intake in children recovering from dehydration, which may increase the hospital length of stay. When metabolic acidosis is severe (very low pH) and not treated, it affects metabolic body functions. Another fear of using 0.9% saline is the potential increase in the risk of hypokalaemia (low potassium levels in the blood), commonly affecting dehydrated children. Hypokalaemia may hamper children's capacity to receive oral fluids and feeding, amongst other complications, due to muscular weakness and a decrease in gastrointestinal motility.
What is not known about the treatment of severe dehydration in children with diarrhoea?
The alternatives to 0.9% saline solution are the so-called balanced solutions, which are defined as intravenous fluids having an electrolyte composition close to that of human plasma (a component of blood). In comparison to the 0.9% saline solution, which only contains sodium and chloride, balanced solutions have a composition of electrolytes (sodium, potassium, and chloride) similar to the composition of human plasma, including additional cations (calcium, potassium, or magnesium), and anions such as lactate, acetate, or gluconate. A composition more similar to human plasma is expected to be more beneficial for rehydrating than the traditional 0.9% saline solution. This Cochrane Review aimed to determine whether rehydrating dehydrated children with balanced solutions results in better outcomes when compared to 0.9% saline.
What did we want to find out?
We wanted to know whether there were any differences between rehydrating a child with severe dehydration due to diarrhoea with 0.9% saline solution and doing so with balanced solutions.
What did we do?
We searched medical databases and identified five studies that evaluated 465 children. These studies randomly compared balanced solutions (Ringer's lactate or Plasma-Lyte) with 0.9% saline solutions for severely dehydrated children with acute diarrhoea. Studies were conducted in India, Pakistan, the USA, and Canada.
What did we find?
In severely dehydrated children with diarrhoea, rehydration with balanced solutions likely results in a slight reduction in the time children are in hospital, while we are very uncertain about their effect on deaths during hospitalization when compared to rehydration with 0.9% saline.
Balanced solutions may produce a higher increase in blood pH and bicarbonate levels after correction, which may indicate a faster improvement of metabolic acidosis. However, balanced solutions produce no changes in the need for additional intravenous fluids after the initial correction; in the volume of fluids given; and in the average change of electrolytes and creatinine (a waste product that comes from muscles) levels.
Also, in terms of side effects, balanced solutions likely reduce the risk of hypokalaemia after intravenous correction (that is, fewer children with low values of serum potassium) after the intravenous correction, and they probably make no difference the incidence of hyponatraemia (low blood sodium levels), when compared to 0.9% saline.
Our results are mostly applicable to Ringer's lactate as most of the evidence came from studies comparing 0.9% saline to this solution. The evidence on Plasma-Lyte (another balanced solution) is scarce and warrants more studies.
What are the limitations of the evidence?
The evidence comparing 0.9% saline solution and balanced solutions is scarce. The available studies evaluated very low numbers of children and is possible that people involved in the studies were aware of which treatment the children received, which gives us little confidence in the results.
How up to date is this evidence?
This review summarized the evidence up to 4 May 2022.
The evidence is very uncertain about the effect of balanced solutions on mortality during hospitalization in severely dehydrated children. However, balanced solutions likely result in a slight reduction of the time in the hospital compared to 0.9% saline. Also, balanced solutions likely reduce the risk of hypokalaemia after intravenous correction.
Furthermore, the evidence suggests that balanced solutions compared to 0.9% saline probably produce no changes in the need for additional intravenous fluids or in other biochemical measures such as sodium, chloride, potassium, and creatinine levels. Last, there may be no difference between balanced solutions and 0.9% saline in the incidence of hyponatraemia.
Although acute diarrhoea is a self-limiting disease, dehydration may occur in some children. Dehydration is the consequence of an increased loss of water and electrolytes (sodium, chloride, potassium, and bicarbonate) in liquid stools. When these losses are high and not replaced adequately, severe dehydration appears. Severe dehydration is corrected with intravenous solutions. The most frequently used solution for this purpose is 0.9% saline. Balanced solutions (e.g. Ringer's lactate) are alternatives to 0.9% saline and have been associated with fewer days of hospitalization and better biochemical outcomes. Available guidelines provide conflicting recommendations. It is unclear whether 0.9% saline or balanced intravenous fluids are most effective for rehydrating children with severe dehydration due to diarrhoea.
To evaluate the benefits and harms of balanced solutions for the rapid rehydration of children with severe dehydration due to acute diarrhoea, in terms of time in hospital and mortality compared to 0.9% saline.
We used standard, extensive Cochrane search methods. The latest search date was 4 May 2022.
We included randomized controlled trials in children with severe dehydration due to acute diarrhoea comparing balanced solutions, such as Ringer's lactate or Plasma-Lyte with 0.9% saline solution, for rapid rehydration.
We used standard Cochrane methods. Our primary outcomes were 1. time in hospital and 2. mortality. Our secondary outcomes were 3. need for additional fluids, 4. total amount of fluids received, 5. time to resolution of metabolic acidosis, 6. change in and the final values of biochemical measures (pH, bicarbonate, sodium, chloride, potassium, and creatinine), 7. incidence of acute kidney injury, and 8. adverse events. We used GRADE to assess the certainty of the evidence.
Characteristics of the included studies
We included five studies with 465 children. Data for meta-analysis were available from 441 children. Four studies were conducted in low- and middle-income countries and one study in two high-income countries. Four studies evaluated Ringer's lactate, and one study evaluated Plasma-Lyte. Two studies reported the time in hospital, and only one study reported mortality as an outcome. Four studies reported final pH and five studies reported bicarbonate levels. Adverse events reported were hyponatremia and hypokalaemia in two studies each.
Risk of bias
All studies had at least one domain at high or unclear risk of bias. The risk of bias assessment informed the GRADE assessments.
Compared to 0.9% saline, the balanced solutions likely result in a slight reduction of the time in hospital (mean difference (MD) −0.35 days, 95% confidence interval (CI) −0.60 to −0.10; 2 studies; moderate-certainty evidence). However, the evidence is very uncertain about the effect of the balanced solutions on mortality during hospitalization in severely dehydrated children (risk ratio (RR) 0.33, 95% CI 0.02 to 7.39; 1 study, 22 children; very low-certainty evidence).
Balanced solutions probably produce a higher increase in blood pH (MD 0.06, 95% CI 0.03 to 0.09; 4 studies, 366 children; low-certainty evidence) and bicarbonate levels (MD 2.44 mEq/L, 95% CI 0.92 to 3.97; 443 children, four studies; low-certainty evidence). Furthermore, balanced solutions likely reduces the risk of hypokalaemia after the intravenous correction (RR 0.54, 95% CI 0.31 to 0.96; 2 studies, 147 children; moderate-certainty evidence).
Nonetheless, the evidence suggests that balanced solutions may result in no difference in the need for additional intravenous fluids after the initial correction; in the amount of fluids administered; or in the mean change of sodium, chloride, potassium, and creatinine levels.