Exploring conservative avenues in subacute subdural hematoma: the potential role of atorvastatin and dexamethasone as lifesaving allies

Title: Exploring conservative avenues in subacute subdural hematoma: the potential role of atorvastatin and dexamethasone as lifesaving allies Authors: Tao Liu et al. DOI: 10.1186/s41016-025-00393-8 PMID: 40176171

This is a retrospective case series involving five patients with subacute subdural hematoma (sASDH), who were managed conservatively using atorvastatin and low-dose dexamethasone without surgical intervention. It also includes a non-systematic narrative review of existing literature, lacking formal meta-analytic methodology.

  • The article raises an important question: can we optimize conservative treatment for sASDH in inoperable patients?
  • A novel hypothesis is proposed, leveraging two commonly available pharmacologic agents.

1. Sample Size and Selection Bias

The study is limited to five hand-picked cases, all of whom refused surgery. There is no control groupno randomization, and no standardization in patient selection. This introduces massive selection bias and confounding, rendering the findings anecdotal at best.

2. Lack of Statistical Power

With only five patients, the study is grossly underpowered to draw any conclusions on safety or efficacy. Even if all patients improved, the positive predictive value is negligible.

3. Absence of Mechanistic Evidence

The article alludes vaguely to the “possible mechanisms” of action of atorvastatin and dexamethasone but fails to elaborate with any molecular, imaging, or biomarker-based support. The hypothesized synergy is speculative and not experimentally validated.

4. Cherry-Picking Literature

The review portion pulls from only six studies without PRISMA methodology, inclusion/exclusion criteria, or risk-of-bias assessments. This is not a systematic review but rather a collection of cherry-picked studies to support a preconceived narrative.

5. Logical Fallacy: Post Hoc Ergo Propter Hoc

The authors infer that improvement after administration of atorvastatin and dexamethasone implies causality. This is a classic post hoc fallacy. No causation can be inferred from such a weak observational structure.

6. Ethical and Practical Concerns

Presenting this treatment strategy without rigorous evidence could mislead cliniciansdelay necessary surgery, or foster false confidence in a pharmacological approach for a condition where deterioration can be catastrophic.

The article is a speculative and weakly documented case series attempting to repurpose two drugs in the treatment of sASDH. While the intention is noble, the scientific execution is fundamentally flawed. No clinical decisions should be influenced by this paper. What is needed is a properly designed randomized controlled trial, not a narrative built on five anecdotal successes.

See also: subdural_hematomaconservative_managementevidence_based_medicine

Disparities and Variability in Hospital Management of Mild Traumatic Brain Injury

Disparities and Variability in Hospital Management of Mild Traumatic Brain Injury

Insurance status significantly influences management decisions:

Uninsured patients are less likely to be admitted, even when clinical factors may justify observation.

Privately insured or Medicare/Medicaid-covered individuals often receive more resource-intensive care, including imaging, neurosurgical consults, and longer admissions.

Non-White, non-Black, non-Hispanic patients may experience:

Lower odds of discharge to home

Longer hospital stays but not necessarily associated with better outcomes

Potential underuse or delayed access to follow-up care (rehabilitation, neuropsychology)

Wide differences exist between hospitals in:

Admission rates for mTBI

Length of stay (LOS) for admitted patients

Discharge disposition (home vs. skilled nursing facility vs. rehab)

Level 1 trauma centers tend to have longer LOS, but paradoxically, their patients are less likely to be discharged home, possibly reflecting:

More cautious or protocol-driven care

Complex patient populations

System inefficiencies or defensive medicine practices

Rural vs. urban hospitals may differ in resource availability:

Rural centers might discharge more patients directly from the ED due to lack of neuroimaging or neurosurgical backup.

Urban or academic centers may admit more patients for observation and follow-up care coordination.

Variability is also driven by a lack of standardization:

Some centers use evidence-based decision rules (e.g., Canadian CT Head Rule), while others rely on individual clinician judgment.

Institutional differences in admission criteria for elderly patients, those on anticoagulants, or those with minor CT findings.

Disparities in mTBI care may lead to:

Under-treatment of vulnerable populations

Over-utilization in low-risk cases due to defensive medicine

Inefficient use of hospital resources

There’s a growing need for:

Nationally standardized care pathways

Cultural competence training

Policy reform targeting access and equity

Quality benchmarking across institutions

scoping review, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, was used to explore three electronic databases- PubMed, Medline, and CINAHL. Searches identified peer-reviewed empirical literature addressing aspects of the Social determinants of health and HDs related to TBI. A total of 123 records were identified and reduced to 27 studies based on the inclusion criteria. Results revealed that race/ethnicity was the most commonly reported Social determinant of health impacting TBI, followed by an individual’s insurance status. Health disparities were noted to occur across the continuum of TBI, including TBI risk, acute hospitalization, rehabilitation, and recovery. The most frequently reported HD was that Whites are more likely to be discharged to inpatient rehabilitation compared to racial/ethnic minorities. Health disparities associated with TBI are most commonly associated with the race/ethnicity SDoH, though insurance status and socioeconomic status commonly influence health inequities as well. The additional need for evidence related to the impact of other, lesser-researched SDoH is discussed, as well as clinical implications that can be used to target intervention for at-risk groups using an individual’s known Social determinants of health 1)

A total of 122,406 patients with mTBI were included.

Vattipally et al. performed hierarchical logistic regression to investigate associations of patient-level variables with inpatient admission. Among hospitalized patients, a hierarchical linear regression was constructed for associations with LOS, including hospitals as a random effects term. Based on random effects coefficients, hospitals were classified as high-LOS outliers or non-outliers.

Main measures: Univariable comparisons on facility characteristics were performed. Patients were propensity score matched across hospital outlier status, and a multivariable logistic regression for associations with discharge to home was performed.

Results: The median age was 63 years (interquartile range [IQR], 42-77 years), and 111 306 (91%) patients experienced inpatient admission. Uninsured status was associated with lower odds of inpatient admission (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.65-0.76; P < .001). After excluding very low-volume hospitals, 80,258 admitted patients were treated across 469 hospitals, and 98 were designated as high-LOS outliers. These were more likely to be Level 1 trauma centers (76% vs. 26%; P < .001). After matching, patients treated at high-LOS outlier hospitals were less likely to experience home discharge (OR, 0.89; 95% CI, 0.85-0.93; P < .001). This effect was amplified for patients identifying as non-White, non-Black, non-Hispanic other races (P = .003).

Inpatient admission after mTBI varies by insurance status, with uninsured patients less likely to be admitted. There is significant interhospital variation in LOS, with Level 1 trauma centers more likely to be high-LOS outliers. Despite their longer LOS, patients treated at outlier hospitals experienced lower odds of home discharge 2).


This study provides valuable evidence on disparities and variability in the hospital management of patients with mild traumatic brain injury (mTBI) in the United States. Using a large national dataset and robust statistical methods, the authors demonstrate that factors such as insurance status, hospital type, and patient race/ethnicity significantly influence decisions around hospital admissionlength of stay (LOS), and likelihood of discharge to home.

However, the retrospective design and reliance on administrative data limit causal interpretation and prevent adjustment for key clinical variables. The classification of hospitals as LOS outliers should also be interpreted with caution, as longer stays may reflect more comprehensive care or greater patient complexity, rather than inefficiency.

Overall, the study highlights the urgent need for healthcare policies aimed at reducing inequities and standardizing care criteria for mTBI, while still respecting patient-level nuances and hospital contexts. Future research should integrate more detailed clinical data and explore targeted interventions to improve both equity and efficiency in mTBI care.


A secondary analysis of ED visits in the National Hospital Ambulatory Medical Care Survey for the years 1998 through 2000 was performed. Cases of mTBI were identified using ICD-9 codes 800.0, 800.5, 850.9, 801.5, 803.0, 803.5, 804.0, 804.5, 850.0, 850.1, 850.5, 850.9, 854.0, and 959.01. ED care variables related to imaging, procedures, treatments, and disposition were analyzed along racial, ethnic, and gender categories. The relationship between race, ethnicity, and selected ED care variables was analyzed using multivariate logistic regression with control for associated injuries, geographic region, and insurance type.

The incidence of mTBI was highest among men (590/100,000), Native Americans/Alaska Natives (1026.2/100,000), and non-Hispanics (391.1/100,000). After controlling for important confounders, Hispanics were more likely than non-Hispanics to receive a nasogastric tube (OR, 6.36; 95% CI = 1.2 to 33.6); nonwhites were more likely to receive ED care by a resident (OR, 3.09; 95% CI = 1.9 to 5.0) and less likely to be sent back to the referring physician after ED discharge (OR, 0.47; 95% CI = 0.3 to 0.9). Men and women received equivalent ED care.

There are significant racial and ethnic but not gender disparities, in ED care for mTBI. The causes of these disparities and the relationship between these disparities and post-mTBI outcome need to be examined 3).


1)

Johnson LW, Diaz I. Exploring the Social Determinants of Health and Health Disparities in Traumatic Brain Injury: A Scoping Review. Brain Sci. 2023 Apr 23;13(5):707. doi: 10.3390/brainsci13050707. PMID: 37239178; PMCID: PMC10216442.
2)

Vattipally VN, Jiang K, Weber-Levine C, Kramer P, Davidar AD, Hersh AM, Winkle M, Byrne JP, Azad TD, Theodore N. Patient and Hospital Factors Associated With Hospital Course for Patients With Mild Traumatic Brain Injury. J Head Trauma Rehabil. 2025 Apr 1. doi: 10.1097/HTR.0000000000001056. Epub ahead of print. PMID: 40167490.
3)

Bazarian JJ, Pope C, McClung J, Cheng YT, Flesher W. Ethnic and racial disparities in emergency department care for mild traumatic brain injury. Acad Emerg Med. 2003 Nov;10(11):1209-17. doi: 10.1111/j.1553-2712.2003.tb00605.x. PMID: 14597497.

Salovum for severe traumatic brain injury

Salovum for severe traumatic brain injury

J.Sales-Llopis

Neurosurgery Department, General University Hospital AlicanteSpain



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.

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.

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.

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.

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 caresevere 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, randomizedplacebo-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).


1)

Réen L, Cederberg D, Marklund N, Visse E, Siesjö P. Antisecretory factor in severe traumatic brain injury (AFISTBI): protocol for an exploratory randomized placebo-controlled trial. Trials. 2025 Feb 7;26(1):43. doi: 10.1186/s13063-025-08760-7. PMID: 39920739.
2)

Cederberg D, Harrington BM, Vlok AJ, Siesjö P. Effect of antisecretory factor, given as a food supplement to adult patients with severe traumatic brain injury (SASAT): protocol for an exploratory randomized double blind placebo-controlled trial. Trials. 2022 Apr 23;23(1):340. doi: 10.1186/s13063-022-06275-z. PMID: 35461285; PMCID: PMC9034076.
3)

Gatzinsky K, Johansson E, Jennische E, Oshalim M, Lange S. Elevated intracranial pressure after head trauma can be suppressed by antisecretory factor-a pilot study. Acta Neurochir (Wien). 2020 Jul;162(7):1629-1637. doi: 10.1007/s00701-020-04407-5. Epub 2020 May 22. PMID: 32445122; PMCID: PMC7295841.
4)

Cederberg D, Hansson HA, Visse E, Siesjö P. Antisecretory Factor May Reduce ICP in Severe TBI-A Case Series. Front Neurol. 2020 Mar 6;11:95. doi: 10.3389/fneur.2020.00095. PMID: 32210902; PMCID: PMC7067821.