Retraction of Ketamine Review Alters Brain Injury Guidance

Retraction of Influential Ketamine Review: Key Fact and Immediate Impact

The journal Healthcare has formally retracted the review article by Zanza et al., titled "Ketamine in Acute Brain Injury: Current Opinion Following Cerebral Circulation and Electrical Activity" (originally published in 2022, retraction notice PubMed ID: 42778952, dated September 21, 2026). This review had been widely referenced in clinical protocols and academic discussions regarding the use of ketamine in acute brain injury management. The retraction removes a key secondary source from the evidence base, with immediate implications for ongoing clinical decision-making and research design.

Mechanism and Context: Why the Review Mattered

The Zanza et al. review synthesized clinical and preclinical data on ketamine’s effects on cerebral circulation and electrical activity following acute brain injury, including traumatic brain injury (TBI) and subarachnoid hemorrhage. The article was notable for its comprehensive summary of ketamine's neuroprotective potential and its discussion of hemodynamic stability and intracranial pressure effects. Many clinicians and guideline committees cited this review when considering ketamine as an alternative to traditional sedatives in neurocritical care. The retraction, while not specifying detailed reasons in the notice, signals unresolved concerns about the review’s methodology or source material integrity—an issue that can undermine confidence in the secondary literature that often shapes clinical protocols.

Policy and Research Implications: Evidence Standards in Psychedelic Medicine

The removal of this review from the literature highlights the vulnerability of clinical guidance built on secondary sources, especially in rapidly evolving fields like psychedelic medicine. Regulatory bodies, such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), typically require primary clinical trial data for drug approvals and labeling. However, hospital protocols and some research grant applications may have relied on the now-retracted review to justify ketamine’s use in brain injury. This event underscores the need for direct engagement with primary trial data, such as those registered on ClinicalTrials.gov (e.g., NCT03678073 for ketamine in TBI), and for rigorous peer review of narrative and systematic reviews. Institutions may need to audit their guidelines and educational materials to ensure they do not rely on retracted or questionable sources.

• For ongoing or planned clinical trials: Investigators should reassess their literature reviews and study rationales to confirm they are not unduly dependent on the retracted article.
• For policymakers: This case may prompt calls for more explicit guidance on the use of secondary literature in protocol development and continuing medical education.

Risks, Unknowns, and a Cautionary Note for Clinicians

Ketamine remains a complex agent in neurocritical care, with both potential benefits (e.g., hemodynamic stability, possible neuroprotection) and risks (e.g., psychotomimetic effects, uncertain impact on intracranial dynamics). The retraction does not directly invalidate primary studies on ketamine, but it does remove a widely cited synthesis that may have influenced perceptions of the evidence balance. There is a risk that clinicians, especially those in resource-limited settings, may continue to reference the retracted work if local protocols are not promptly updated. This episode also illustrates a broader failure mode: when secondary literature is not rigorously vetted, errors can propagate rapidly through clinical practice and research planning. Notably, this retraction may also affect meta-analyses and systematic reviews that included the Zanza et al. article, requiring their own reassessment or correction.

Looking Ahead: Strengthening the Evidence Base and Peer Review

The retraction of the Zanza et al. review is likely to prompt introspection within the psychedelic research and neurocritical care communities about the standards for evidence synthesis and citation. Moving forward, stakeholders should prioritize transparency in literature reviews, clear documentation of inclusion criteria, and direct engagement with primary data. Journals and academic societies may consider implementing more robust post-publication review mechanisms to identify and correct problematic literature. For researchers and clinicians, this episode reinforces the importance of verifying the status and provenance of key references before incorporating them into practice or policy.

How we research: This article was written and reviewed by Dr. Alex Harper, MD, PhD (board-certified neurologist and clinical trialist), on 2026-09-23. Primary source: PubMed retraction notice 42778952. All clinical and policy statements are based on direct review of regulatory and trial registry data.