Brain Injuries study on BDC (2,220 participants)

phs003777 — Resuscitation Outcomes Consortium (ROC) Hypertonic Saline (HS) Trial    Shock Study and Traumatic Brain Injury Study (TBI)    (ROC-HS/TBI-BioLINCC)

Data Access NOTE Please refer to the "Authorized Access" section below for information about how access to the data from this accession. Access differs from many other dbGaP accessions.Objectives <ul><li>Shock: To determine if prehospital administration of 7.5% hypertonic saline with 6% Dextran-70 (HSD) or 7.5% hypertonic saline alone (HS), compared to current standard therapy with normal saline (NS), as an initial resuscitation fluid, affects survival following traumatic injury with hypovolemic shock.</li><li>TBI: To determine whether out-of-hospital administration of hypertonic fluids improves neurologic outcome following severe traumatic brain injury (TBI).</li></ul>Background Trauma is the leading cause of death among North Americans between the ages of 1 and 44 years. The majority of these deaths result from hypovolemic shock or severe brain injury. Participants in hypovolemic shock develop a state of systemic tissue ischemia then a subsequent reperfusion injury at the time of fluid resuscitation. Conventional resuscitation involves the IV administration of a large volume of isotonic or slightly hypotonic (lactated ringers, LR) solutions beginning in the prehospital setting. Although not conclusive, prior studies have suggested that alternative resuscitation with hypertonic saline (7.5%) solutions may reduce morbidity or mortality in these participants. Furthermore, hypertonic fluids may have specific advantages in the brain-injured participant, as they may aid in the rapid restoration of cerebral perfusion and prevent extravascular fluid sequestration, thereby limiting secondary brain injury. In addition, recent studies have demonstrated that hypertonicity significantly alters the activation of inflammatory cells, an effect that may reduce subsequent organ injury from ischemia-reperfusion and decrease nosocomial infection. The majority of previous clinical trials have focused on the use of HSD. The potential for 7.5% saline alone (HS) to have similar effects has not been well studied. Removal of the dextran component may enhance the anti-inflammatory effects of this solution, which could improve secondary outcomes such as acute respiratory distress syndrome (ARDS), multiple organ failure syndrome (MOFS) and rates of nosocomial infections. Participants <ul><li>Shock: There were 893 participants that were randomized (853 enrolled).</li><li>TBI: There were 1282 participants enrolled and 6-month outcomes data were available for 1087 (85%).</li></ul>Design <ul><li>Shock: Multicenter, randomized, blinded clinical trials involving 114 emergency medical services agencies in North America within the Resuscitation Outcomes Consortium were conducted from May 2006 to August 2008. Initial resuscitation fluid, 250 mL of either 7.5% saline per 6% dextran 70 (hypertonic saline/dextran, HSD), 7.5% saline (hypertonic saline, HS), or 0.9% saline (normal saline, NS) administered by out-of-hospital providers. Primary outcome was 28-day survival. On the recommendation of the data and safety monitoring board, the study was stopped early (23% of proposed sample size) for futility and potential safety concern.</li><li>TBI: Multicenter, double-blind, randomized, placebo-controlled clinical trials involving 114 North American emergency medical services agencies within the Resuscitation Outcomes Consortium were conducted between May 2006 and May 2009. A single 250-mL bolus of 7.5% saline/6% dextran 70 (HSD), 7.5% saline (HS), or 0.9% saline (NS) initiated in the out-of-hospital setting. The main outcome measure was a six-month neurologic outcome based on the Extended Glasgow Outcome Scale (GOSE) (dichotomized as >4 or ≤4). The study was terminated by the data and safety monitoring board after randomization of 1331 participants, having met prespecified futility criteria.</li></ul>Conclusions <ul><li>Shock: Among injured participants with hypovolemic shock, initial resuscitation fluid treatment with either HS or HSD, compared with NS, did not result in superior 28-day survival. However, interpretation of these findings is limited by the early stopping of the trial (<a href="https://pubmed.ncbi.nlm.nih.gov/21178763/">PMID: 21178763</a>).</li><li>TBI: Among participants with severe TBI not in hypovolemic shock, initial resuscitation with either HS or HSD, compared with normal saline, did not result in superior 6-month neurologic outcome or survival (<a href="https://pubmed.ncbi.nlm.nih.gov/20924011/">PMID: 20924011</a>).</li></ul>