Introduction We hypothesized that computed tomography angiography and conventional catheter‐guided angiography (CTA & DSA) would be able to accurately distinguish prolonged total areflexic coma induced by pentobarbital (PTB) from true progression to death by neurologic criteria (DNC) in patients with traumatic brain injuries (TBI) undergoing aggressive intracranial pressure (ICP) management. We also hypothesized that despite CTA being an imperfect tool in other cases of traumatic brain injury mimicking brain death, CTA helps triage which patients would benefit from resource‐intensive DSA as a part of their DNC evaluation. Methods We present a retrospective case series of three patients with severe TBI, treated with PTB coma as part of refractory ICP treatment. Patients displayed clinical and electroencephalographic findings that mimicked DNC. These clinical cases highlight the contributions of adjunct therapies ‐ propofol, midazolam, fentanyl, paralytics and therapeutic temperature management (TTM) ‐ and their exacerbating effects of PTB resulting in brainstem areflexia. In these cases, transcranial doppler (TCD) was used in addition to CTA to determine DNC. We also present a retrospective case series of three false negative CTAs in open or closed skull injuries undergoing DNC evaluation. Results This case series highlights the challenge in clinical decision‐making when managing severe TBI with high‐dose PTB. These victims have prolonged sedation from PTB enhanced by adjunctive therapies on top of the TBI‐related coma, resulting in total areflexic coma. They are also at risk of truly progressing to DNC from herniation or brainstem ischemia despite neurocritical care. Our findings suggest that imaging is key to distinguish true progression to DNC versus areflexic mimic. We used TCD to screen for abolished perfusion which then suggested the need for CTA to demonstrate cerebral circulatory arrest (CCA). We escalated to DSA as a formally accepted BDAT per the 2023 AAN guidelines. Other options for BDAT such as SPECT and EEG are less well suited in this TBI population with PTB coma. Conclusions: This study reaffirms the limitations of TCD and CTAs, especially in open skull cases, but their useful role for stewardship towards the proper and judicious choice of a brain death ancillary test (BDAT). The differentiation of a PTB‐induced coma from DNC in TBI patients is intricate and CCA needs to be sought precisely and absolutely to guide care. This study underscores the importance of understanding progression on imaging and the role for screening with TCD and CTA. The 2023 AAN guidelines on DNC posit DSA as the sole acceptable BDAT in these cases. We recommend serial TCD monitoring and deliberate reassessment post‐PTB washout to navigate potential misdiagnosis of DNC. In cases with unrealistic waiting periods, CTA followed by DSA, both with a focus on the brainstem and with venous scrutiny using French scoring systems, seems most appropriate. Our insights seek to inform clinical practice and guard against premature cessation or undue prolongation of aggressive care. We propose to study the difference between CTA and DSA with a brainstem venous focus, as DSA remains resource‐intensive and more dangerous for fragile ICU patients.
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