Randomized Controlled Trial of Intravenous Fluid In Severely Injured Paediatric Trauma Patients: Comparison of Normal Saline Versus Ringer's Lactate

Background:

Trauma is the major killer of children and adolescents. The care of paediatric trauma patients is guided by the Advanced Trauma Life Support (ATLS) guidelines. Fluid resuscitation is a critical aspect of trauma resuscitation to avoid hypoperfusion and metabolic acidosis, and to maintain adequate oxygen delivery to tissues. ATLS recommends the use of either intravenous Normal Saline (NS) or Ringer's Lactate (RL) in trauma fluid resuscitation. There are currently no recommendations or any studies to suggest which of these two fluids are more appropriate for pediatric trauma patients and their ionic compositions do differ. As such, both solutions have potential benefits and potential complications.

There are three primary issues that relate to choice of solution.

1. Sodium concentration and risk of iatrogenic hyponatremia: NS has higher sodium content relative to RL (154 vs. 130 mmol/L, respectively; normal blood levels are 135-145 mmol/L). Maintenance of a normal or slightly elevated sodium level in paediatric trauma patients is often imperative, given that the vast majority of these patients have significant traumatic brain injury. Hyponatremia can worsen cerebral edema and increase intracranial pressure. In a previous study conducted by us at Children's Hospital, LHSC we reported that paediatric trauma patients in our centre received NS. Despite NS used as the resuscitation fluid, pediatric trauma patients all showed a trend towards low-normal levels of sodium in their blood. Given the lower content of sodium in RL, we question whether NS is superior for maintenance of blood sodium.
2. Chloride concentration and risk of iatrogenic hyperchloremic metabolic acidosis: NS contains significantly more chloride than RL to maintain electro-neutrality (154 vs. 109 mmol, respectively; normal blood levels are 98-108 mmol/L). In contrast, the RL solution replaces 28 mmol/L of chloride with equimolar lactate. As the elevated chloride content in NS is postulated to instigate the undesired consequences of driving blood bicarbonate lower and producing a hyperchloremic metabolic acidosis,6, 7 we question whether NS is inferior to RL for maintenance of blood pH.
3. Exacerbation of trauma-induced inflammation: Trauma results in a systemic inflammatory response (Fraser Lab, unpublished results). Exacerbation of the inflammatory state with non-optimal resuscitation practices might worsen overall outcome. Published data on non-trauma patients suggests that NS administration is pro-inflammatory relative to RL,9 but this possibility has not been studied in paediatric patients, or in any trauma patients. The inflammatory cascade can be assessed in blood by measuring the levels of global inflammatory markers [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)] and specific pro-inflammatory mediators elevated by multisystem trauma [interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte colony stimulating factor (G-CSF) and monocyte chemotactic protein-1 (MCP-1)]. Given the higher inflammatory potential that has been associated with NS, we question whether NS is inferior to RL for minimizing inflammatory cascades.

Hypothesis: