Table 1 Eligibility criteria for the systematic review (expanded detail provided in Additional file 3)

Population

We will include all studies examining acute brain injury (human and in vivo animal brain injury models) with treatment initiation within the first 7 days post-injury. We are targeting acute primary neurological diagnoses such as traumatic brain injury, stroke, hemorrhage, or post-neurosurgical care.

Intervention

The intervention of interest is the intravenous use of relatively hypotonic crystalloid resuscitation fluids. These include Ringer’s lactate, Hartmann’s or Plasma Lyte® fluids. These can be administered as bolus or maintenance infusions. There will be no limits on dose or frequency of administration.

Comparator(s)

The main comparator of interest is an isotonic crystalloid resuscitation fluid, specifically normal saline (0.9%), which will serve as the prototypical control. Other crystalloid resuscitation fluids (e.g., hypertonic saline (3–23.4%)) will also be included as an additional comparator of interest. These can be administered as bolus or maintenance infusions. There will be no limits on dose or frequency of administration.

Outcome(s)

The primary outcomes of interest are:

• Intracranial pressure (ICP; mmHg) and cerebral perfusion pressure (CPP; mmHg)

Secondary outcomes include:

• Cerebral edema (mL H₂O/g dry), serum and/or brain electrolyte concentrations (Na+, Cl−; mmol/L) and osmolarity (mOsmol/L [29]), clinical outcomes as assessed by any of modified Rankin Scale (mRS), Glasgow Outcome Scale (GOS), extended Glasgow Outcome Scale (eGOS), mortality; and

Tertiary outcomes include:

• Any adverse events as defined by the study authors

Study design

We will include all completed publications reporting the intravenous use of crystalloid fluids in acute brain injury.

• Clinical: randomized controlled trials, quasi-randomized trials, and retrospective and prospective studies that include a control group for comparison

• Pre-clinical: randomized laboratory studies

There will be no date or language restrictions applied. In-progress studies and letters to the editor identified will be included in a qualitative analysis. Case reports, case series, editorial reviews, and guidelines will be excluded.