Salovum for severe traumatic brain injury
Neurosurgery Department, General University Hospital Alicante, Spain
Antisecretory Factor and Salovum® in Severe Traumatic Brain Injury: A New Frontier in Neurocritical Care
Severe traumatic brain injury (TBI) remains a leading cause of disability and mortality worldwide despite continuous advancements in neuroimaging, neurocritical care, and surgical techniques. Elevated intracranial pressure (ICP) is a major contributor to secondary brain injury, often determining patient prognosis. Current treatments, including hyperosmolar therapy, decompressive craniectomy, and sedation, provide variable efficacy with significant risks.
A promising new approach involves the use of antisecretory factor (AF), a naturally occurring protein with anti-inflammatory and fluid-regulating properties, commercially available as Salovum®. Recent studies suggest that AF may play a crucial role in reducing ICP and improving clinical outcomes in severe TBI.
Clinical Evidence Supporting Antisecretory Factor in Severe TBI
The AFISTBI and SASAT Trials
Two exploratory randomized, placebo-controlled clinical trials are currently evaluating the role of AF in severe TBI. The AFISTBI trial (ClinicalTrials.gov NCT04117672) is a single-center phase 2 study conducted at Skane University Hospital, Sweden. This trial examines the impact of Salovum® supplementation for five days in adults with severe TBI (GCS < 9) requiring ICP monitoring and microdialysis catheter insertion. The primary endpoint is ICP reduction, while secondary endpoints include inflammatory mediator levels in plasma and cerebrospinal fluid.
Similarly, the SASAT trial (ClinicalTrials.gov NCT03339505) is a phase 2, double-blind, randomized trial conducted at Tygerberg University Hospital, South Africa. It evaluates 30-day mortality, treatment intensity level (TIL), and ICP control in 100 patients randomized to receive either Salovum® or placebo.
Pilot Studies and Case Series
Several preliminary studies have demonstrated the potential of AF in reducing ICP. A pilot study by Gatzinsky et al. investigated four patients with severe TBI and refractory intracranial hypertension treated with Salovum®. The study found that when administered rectally, AF significantly reduced ICP without adverse events, offering a novel delivery route for neurocritical care patients with impaired gastric emptying.
Additionally, a case series by Cederberg et al. evaluated five patients with severe TBI who received Salovum® via nasogastric tube for five days. Three patients exhibited successful ICP control without the need for barbiturates, while four had favorable long-term outcomes. Importantly, no toxicity or adverse effects were observed, underscoring the safety of AF therapy in this population.
Mechanism of Action and Potential Therapeutic Implications
AF exerts its effects by modulating fluid balance and inflammatory responses in the brain. Preclinical models suggest that AF can suppress excessive cerebrospinal fluid production, reduce blood-brain barrier permeability, and attenuate neuroinflammation, all critical mechanisms in controlling ICP and secondary brain injury.
The ability of AF to reduce ICP through non-invasive means could have profound implications for the management of TBI. In resource-limited settings where advanced neurosurgical interventions may not be readily available, Salovum® presents a cost-effective adjunct to standard neurocritical care.
Challenges and Future Directions
While preliminary data are promising, larger, multicenter randomized controlled trials (RCTs) are needed to validate these findings. Understanding the optimal dosing, administration route, and long-term effects of AF therapy remains crucial. Additionally, integrating AF into current TBI treatment protocols will require further evaluation of its interactions with existing therapies.
Conclusion
Antisecretory factor, as delivered via Salovum®, represents an exciting new frontier in TBI management. With ongoing trials exploring its efficacy, AF has the potential to become a groundbreaking adjunctive therapy for reducing ICP and improving outcomes in severe TBI patients. If confirmed in larger studies, the use of Salovum® could redefine the standard of care in neurocritical care settings, providing a safer and more accessible treatment alternative for ICP control.
Despite recent advances in neuroimaging and neurocritical care, severe traumatic brain injury (TBI) is still a major cause of severe disability and mortality, with increasing incidence worldwide. Antisecretory factor (AF), commercially available as Salovum®, has been shown to lower intracranial pressure (ICP) in experimental models of, e.g., TBI and herpes encephalitis. A study by Réen et al. aims to assess the effect of antisecretory factors in adult patients with severe TBI on ICP and inflammatory mediators in extracellular fluid and plasma.
In a single-center, randomized, placebo-controlled clinical phase 2 trial, investigating the clinical superiority of Salovum® given as a food supplement for 5 days to adults with severe TBI (Glasgow Coma Scale (GCS) < 9), admitted to the neurocritical intensive care unit (NICU) at Skane university hospital. All patients with GCS < 9 and clinical indication for insertion of ICP-monitor and microdialysis catheter will be screened for inclusion and assigned to either the treatment group (n = 10) or placebo group (n = 10). In both groups, the primary outcome will be ICP (mean values and change from baseline during intervention), registered from high-frequency data monitoring for 5 days. During trial treatment, secondary outcomes will be inflammatory mediators in plasma and intracerebral microdialysis perfusate days 1, 3, and 5.
Trial registration: ClinicalTrials.gov NCT04117672. Registered on September 17, 2017. Protocol version 6 from October 24, 2023 1).
A study aims to assess the effect as measured by 30-day mortality, treatment intensity level (TIL), and intracranial pressure (ICP).
This single-center, double-blind, randomized, placebo-controlled clinical phase 2 trial, investigating the clinical superiority of Salovum® given as a food supplement to adults with severe TBI (GCS < 9), presenting to the trauma unit at Tygerberg University Hospital, Cape Town, South Africa, that are planned for invasive ICP monitoring and neurointensive care, will be screened for eligibility, and assigned to either treatment group (n = 50) or placebo group (n = 50). In both groups, the primary outcome will be 30-day mortality, recorded via hospital charts, follow-up phone calls, and the population registry. Secondary outcomes will be treatment intensity level (TIL), scored from hospital charts, and ICP registered from hospital data monitoring.
Trial registration: ClinicalTrials.gov NCT03339505 . Registered on September 17, 2017. Protocol version 3.0 from November 13, 2020 2)
Four patients with severe TBI (Glasgow Coma Scale < 9) that required neurointensive care with ICP monitoring due to signs of refractory intracranial hypertension were investigated. One hundred milliliters of Salovum®, a commercially available egg yolk powder with high contents of AF peptides, was administrated either via nasogastric (patients 1 and 2) or rectal tube (patients 2, 3, and 4) every 8 h for 2 to 3 days as a supplement to the conventional neurointensive care. ICP was registered continuously. Plasma levels of AF were measured by enzyme-linked immunosorbent assay (ELISA) to confirm that Salovum® was absorbed appropriately into the bloodstream.
Results: In the first two patients, we observed that when delivered by the nasogastric route, there was an accumulation of the Salovum® solution in the stomach with difficulties to control ICP due to impaired gastric emptying. Therefore, we tested to administer Salovum® rectally. In the third and fourth patients, who both showed radiological signs of extensive brain edema, ICP could be controlled during the course of rectal administration of Salovum®. The ICP reduction was statistically significant and was accompanied by an increase in blood levels of AF. No adverse events that could be attributed to AF treatment or the rectal approach for Salovum® administration were observed.
Conclusions: The outcomes suggest that AF can act as a suppressor of high ICP induced by traumatic brain edema. Use of AF may offer a new therapeutic option for targeting cerebral edema in clinical practice 3).
A case series of five adult patients with severe TBI, treated with Salovum. The objective of the intervention was to evaluate safety and, if possible, its effect on intracranial pressure and outcome. Patients received 1 g Salovum per kilo of body weight divided into six doses per 24 h. Each dose was administered through the nasogastric tube. Patients were scheduled for 5 days of treatment with Salovum. Intracranial pressure was controlled in all patients. In three of five patients, intracranial pressure could be controlled with Salovum and deep sedation (no barbiturates), except during periods of gastroparesis. Five of five patients had a favorable short-term outcome, and four of five patients had a favorable long-term outcome. No toxicity was observed. We conclude that at least three of the five treated patients experienced an effect of Salovum with signs of reduction of intracranial pressure and signs of clinical benefit. To validate the potential of antisecretory factors in TBI, a prospective, randomized, double-blind, placebo-controlled trial with Salovum has been initiated. The primary outcome for the trial is 30-day mortality; secondary outcomes are treatment intensity level, intracranial pressure, and number of days at the neurointensive care unit 4).