Sugar or salt (“SOS”): A protocol for a UK multicentre randomised trial of mannitol and hypertonic saline in severe traumatic brain injury and intracranial hypertension

Abstract

Hyperosmolar solutions are widely used to treat raised intracranial pressure following severe traumatic brain injury. Although mannitol has historically been the most frequently administered, hypertonic saline solutions are increasingly being used. However, definitive evidence regarding their comparative effectiveness is lacking. The Sugar or Salt Trial is a UK randomised, allocation concealed open label multicentre pragmatic trial designed to determine the clinical and cost-effectiveness of hypertonic saline compared with mannitol in the management of patients with severe traumatic brain injury. Patients requiring intensive care unit admission and intracranial pressure monitoring post-traumatic brain injury will be allocated at random to receive equi-osmolar boluses of either mannitol or hypertonic saline following failure of routine first-line measures to control intracranial pressure. The primary outcome for the study will be the Extended Glasgow Outcome Scale assessed at six months after randomisation. Results will inform current clinical practice in the routine use of hyperosmolar therapy as well as assess the impact of potential side effects. Pre-planned longer term clinical and cost effectiveness analyses will further inform the use of these treatments.

Hypertonic Saline Versus Other Intracranial-Pressure-Lowering Agents for Patients with Acute Traumatic Brain Injury: A Systematic Review and Meta-analysis

“…Despite a lack of clarity regarding the benefits of HTS in the management of acute TBI, a recent practice survey reported that most UK centers are moving to the use of HTS as first-line hyperosmolar therapy over mannitol [ 25 , 26 ]. Use of near-patient sodium monitoring (e.g., blood gas analysis) may, in part, make it easier for clinicians to use and titrate HTS.…”

“…There is a need for larger international and multicenter trials in a variety of settings to address the current lack of high-quality evidence and to determine whether there are preferred ICP-lowering therapies in specific patient populations. The ongoing Sugar or Salt phase III trial (including 25–28 ICUs across the United Kingdom) may provide further clarity on benefits or risks associated with the use of HTS in patients with acute TBI (ISRCTN16075091) [ 26 ].…”

Salted or sweet? Hypertonic saline or mannitol for treatment of intracranial hypertension

“…Further high-quality studies, like The Sugar or Salt Trial [25] that is planned to be finished in December 2023 funded by National Institute for Health Research in the United Kingdom, will probably bring more answers for individualized care of patients with intracranial hypertension.…”

The management of severe traumatic brain injury in the initial postinjury hours – current evidence and controversies

“…Lately, the COBI RCT showed that in moderate to severe TBI patients, continuous infusion of 20% HTS compared with standard care did not improve neurological outcome at 6 months postinjury [36]. An RCT in the UK entitled “Sugar or Salt” comparing the use of bolus HTS and mannitol for the management of elevated ICP in the neurointensive care unit (NICU) setting is currently underway [37 ▪▪ ]. However, there are no RCTs targeting the prehospital and ED settings.…”