Trial Of Normal Saline Versus Ringer's Lactate In Paediatric Trauma Patients
Condition: Trauma
MeSH terms: Wounds and Injuries
Study type: Interventional
Phase: Phase 4

Summary: 
      Background: Trauma is a major cause of death in children and teenagers. When young patients
      have suffered major traumatic injuries, they require intravenous (iv) fluids to keep their
      blood vessels full and ensure blood flow to vital organs. Current fluid guidelines by
      International Trauma Committees recommend either Normal Saline (NS) or Ringer's Lactate (RL)
      as the fluid of choice for these patients. Although these solutions share some similarities
      in their composition, there are also some significant differences in sodium, chloride and
      lactate concentrations. Despite these differences in fluid composition, there has never been
      a study comparing these two fluids in paediatric trauma patients to determine which is
      optimal. In this study, the investigators aim to determine the optimal fluid choice for
      trauma resuscitation of young patients.

      Hypothesis: The investigators hypothesize that severely injured paediatric trauma patients
      resuscitated with NS will have optimal blood sodium levels compared to patients resuscitated
      with RL.

      Methods: The investigators will study 50 paediatric trauma patients that will be randomized
      so that half will randomly receive NS and half will receive RL as their only iv fluid for 24
      hours. After 24 hours, the investigators will compare in blood the sodium level, the amount
      of acid, and the concentrations of inflammation molecules in relation to those whom received
      NS versus RL.

      Expected Results and Significance: Maintaining optimal levels of these biochemical markers is
      imperative in reducing morbidity and mortality in severely injured paediatric patients. If
      significant differences are present, the investigators will be able to determine which fluid
      is preferred and expect these data to complement current trauma resuscitation guidelines.
    

Detailed description: 
      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:

      We hypothesize that severely injured paediatric trauma patients resuscitated with NS will
      have optimal blood sodium levels compared to patients resuscitated with RL, but at the
      expense of hyperchloremic metabolic acidosis and exaggerated inflammation.

      Methodology:

      This study will be a prospective, single-blinded, RCT of severely injured paediatric trauma
      patients admitted to the Children's Hospital, London Health Sciences Centre. While the
      clinical staff treating the patient will be aware of treatment group, the patient, as well as
      the laboratory technicians determining the serum changes will be blinded to the fluid
      administered.

      Randomization:

      Patients will be immediately randomized to either receive NS or RL as their resuscitation and
      maintenance fluid for the first 24 hours. Randomization, via selection of sealed envelope
      based on a computer-generated list, will be done by the trauma resuscitation room intravenous
      access nurse without delay on arrival. Intravenous access and solution administration occurs
      as a priority within minutes of arrival to the trauma room.

      Clinical Data and Blood Analyses:

      All patients included in this study will be entered into the LHSC Trauma Database, comprised
      of over 400 data elements, by a single, trained Trauma Data Analyst. The database regularly
      undergoes quality monitoring to ensure the data is complete and is of highest quality.
      Descriptive analyses and epidemiologic profiles on demographic, clinical and injury data will
      be undertaken, as we have published previously. A baseline trauma blood panel will be drawn
      upon presentation to our resuscitation room (Time "0"), and then repeated at 24 hours. Blood
      measurements for analyses will include serum sodium, chloride, bicarbonate, base excess,
      osmolality, blood gas, ESR and CRP. An extra blood vial will be taken and stored for batch
      analyses of pro-inflammatory cytokines by multiplex assay (IL- 6, IL-8, G-CSF and MCP-1).
      Other interventions will be carried out as per standard of care at the discretion of the
      Trauma most responsible physician. Any medications or any additional fluids the patients
      receive will be recorded. The total amount of intravenous fluid received in the first 24
      hours will be measured for all patients.

      Data Analysis:

      Descriptive analyses and epidemiologic profiles on demographic, clinical and injury data will
      be undertaken, as we have published previously.

      Treatment groups will be compared using Mann Whitney U test for the outcome measures at 24
      hours, as they are continuous. This will include the primary outcome variable (serum sodium)
      and the secondary outcome variables (serum chloride, bicarbonate, pH and inflammatory
      markers: ESR, C-RP, IL-6, Il-8, G-CSF, MCP-1).
    

Intervention name(s): Normal Saline; Ringer's Lactate
Intervention type(s): Drug; Drug
Intervention description(s): Patients randomized to Normal Saline arm, will receive intravenous normal saline for all resuscitation and maintenance fluid for a period of 24 hours commencing on presentation to hospital.; Patients randomized to Ringer's Lactate arm, will receive intravenous Ringer's Lactate for all resuscitation and maintenance fluid for a period of 24 hours commencing on presentation to hospital.
Other intervention name(s): 0.9% Normal Saline; Lactated Ringers
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Trauma; Pediatric; Intravenous Fluid; Normal Saline; Ringer's Lactate