The Toronto prehospital hypertonic resuscitation-head injury and multi organ dysfunction trial (TOPHR HIT) - Methods and data collection tools

Abstract

BackgroundClinical trials evaluating the use of hypertonic saline in the treatment of hypovolemia and head trauma suggest no survival superiority over normal saline; however subgroup analyses suggest there may be a reduction in the inflammatory response and multiorgan failure which may lead to better survival and enhanced neurocognitive function. We describe a feasibility study of randomizing head injured patients to hypertonic saline and dextran vs. normal saline administration in the out of hospital setting.Methods/DesignThis feasibility study employs a randomized, placebo-controlled design evaluating normal saline compared with a single dose of 250 ml of 7.5% hypertonic saline in 6% dextran 70 in the management of traumatic brain injuries. The primary feasibility endpoints of the trial were: 1) baseline survival rates for the treatment and control group to aid in the design of a definitive multicentre trial, 2) randomization compliance rate, 3) ease of protocol implementation in the out-of-hospital setting, and 4) adverse event rate of HSD infusion.The secondary objectives include measuring the effect of HSD in modulating the immuno-inflammatory response to severe head injury and its effect on modulating the release of neuro-biomarkers into serum; evaluating the role of serum neuro-biomarkers in predicting patient outcome and clinical response to HSD intervention; evaluating effects of HSD on brain atrophy post-injury and neurocognitive and neuropsychological outcomes.DiscussionWe anticipate three aspects of the trial will present challenges to trial success; ethical demands associated with a waiver of consent trial, challenging follow up and comprehensive accurate timely data collection of patient identifiers and clinical or laboratory values. In addition all the data collection tools had to be derived de novo as none existed in the literature.Trial registration numberNCT00878631

ROC trials update on prehospital hypertonic saline resuscitation in the aftermath of the US-Canadian trials

“…However, patients were excluded if they received > 2000 ml of any fluid prior to receiving the test product. The feasibility of performing these studies in TBI patients was confirmed (44-45). The primary endpoints were 28 d survival in the hypovolemic shock patients and Extended Glasgow Outcome Scale (GOSE) score at 6 mo in the TBI study (43).…”

Resuscitation with Hypertonic Saline–Dextran Reduces Serum Biomarker Levels and Correlates with Outcome in Severe Traumatic Brain Injury Patients

“…Patients were eligible for the study if at any time during pre-hospital care the following were present: coma or loss of consciousness due to isolated blunt head trauma and=or a Glasgow Coma Scale (GCS) score of 8 (Morrison et al, 2006). Patients were excluded if they had primary penetrating injury, previous intravenous therapy !50 mL, a time interval between arrival at scene and intravenous access exceeding 4 h, age less than 16 years, were presumed to be pregnant at the scene, had an amputation or burn, or had vital signs absent prior to randomization.…”

“…We studied a subset of patients entered into a randomized control trial of the pre-hospital use of hypertonic saline in dextran (HSD) in patients following head trauma and demonstrating signs of severe injury at the scene (Morrison et al, 2006). This parent trial was a feasibility study that contributed to the design of a current large multicenter trial of HSD (Brasel et al, 2008).…”

Review article: Prehospital fluid management in traumatic brain injury

“…The findings of Morrison et al. were, however, presented as a conference proceeding; as such only the abstract was available 20 . Overall, there were only three multicentre RCTs 15,19,21 included in this review.…”