Transcranial Doppler Ultrasonography as a Complementary Exam in Brain Death Determination: Impact on Protocol Duration and ICU Length of Stay

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Transcranial Doppler ultrasonography (TCD) is accepted as a confirmatory exam for BD in Brazil and several international guidelines, yet its operational impact on protocol efficiency remains poorly characterized. We evaluated whether TCD use is associated with shorter BD protocol duration, reduced ICU length of stay (LOS), and higher organ donation rates. Methods : Retrospective cross-sectional study at a tertiary public ICU in Belo Horizonte, Brazil (December 2017–December 2023). We included 178 patients (≥ 18 years) with completed BD protocols, stratified by complementary exam: TCD (n = 141) or non-TCD (n = 37; EEG and/or angiography). Primary outcome was BD protocol duration (hours); secondary outcomes were ICU LOS (days) and organ donation rate. Negative binomial regression adjusted for age, Charlson Comorbidity Index (CCI), SAPS III, and sex. Results : Groups were comparable in age, CCI, SAPS III, and sex (all p > 0.05). TCD was the only independent predictor of shorter protocol duration: median 9h (IQR 5–23) vs 35h (IQR 20–66); OR 0.45 (95% CI 0.32–0.65); p < 0.001; 54.8% reduction. ICU LOS was also shorter in the TCD group: 4 days (IQR 2–6) vs 5 days (IQR 3–9); OR 0.66 (95% CI 0.51–0.86); p 0.05). Conclusions : TCD use was independently associated with substantially shorter BD protocol duration and ICU LOS, supporting broader implementation in institutions with trained practitioners. Organ donation was not associated with TCD use, consistent with its multifactorial nature. transcranial Doppler ultrasonography brain death brain death protocol organ donation intensive care unit Figures Figure 1 Figure 2 INTRODUCTION The determination of brain death (BD) represents one of the most consequential and time-sensitive processes in critical care medicine. Legally defining the irreversible cessation of all encephalic functions, including cerebral cortex and brainstem activity, BD diagnosis directly impacts clinical management, family counseling, and the potential for organ donation.¹⁻² Current protocols, while essential for diagnostic accuracy, frequently require prolonged observation periods and sequential testing, generating significant logistical, ethical, and emotional burdens for healthcare teams and families alike.³ In Brazil, BD diagnosis is regulated by the Federal Council of Medicine Resolution No. 2,173/2017, which requires two clinical examinations with a minimum one-hour interval, an apnea test, and at least one confirmatory complementary exam demonstrating the absence of cerebral blood flow, metabolic activity, or electrical activity.⁴ Accepted complementary methods include cerebral angiography, scintigraphy, electroencephalography (EEG), and transcranial Doppler ultrasonography (TCD).⁴ TCD is a non-invasive bedside technique introduced by Aaslid in 1982 that evaluates blood flow velocities in the major intracranial arteries.⁵ When strict criteria are applied, TCD demonstrates sensitivity of 88–91% and specificity of 100% for BD confirmation, compared with cerebral angiography as the reference standard.⁶⁻⁷ Recognized patterns indicative of cerebral circulatory arrest include absent flow, reverberant flow (alternating systolic-diastolic), and isolated systolic spikes.⁸ The 2012 Brazilian guidelines, aligning with the World Federation of Neurology (WFN) 1998 consensus, formally endorsed TCD as a confirmatory method and proposed it as the preferred non-invasive standard for this indication.⁹ Despite its technical advantages — including portability, repeatability, absence of radiation, and bedside availability — TCD remains underutilized compared to EEG in many Brazilian institutions, partly due to the limited number of trained practitioners.⁹ Moreover, although TCD’s diagnostic accuracy for BD has been extensively studied, its impact on the operational efficiency of BD protocols — specifically, the time required to complete the diagnostic process — has received comparatively little attention in the literature. We hypothesized that, given the inherent time constraints of EEG (minimum 30-minute recording with prior sedation washout requirements) and the scheduling demands of cerebral angiography, the use of TCD as the complementary exam may be associated with a substantially shorter BD protocol duration. Shorter protocols may in turn reduce ICU occupancy and potentially improve organ donation logistics. In this retrospective study, we evaluated the association between TCD use as a complementary exam and BD protocol duration, ICU length of stay (LOS) after protocol initiation, and organ donation rates in a single tertiary public hospital in Brazil over a six-year period. METHODS Study Design and Setting This was a retrospective cross-sectional study conducted at Hospital Metropolitano Doutor Célio de Castro (HMDCC), a 100% publicly funded (SUS) tertiary referral hospital in the metropolitan region of Belo Horizonte, Minas Gerais, Brazil. The institution operates 80 ICU beds, including 20 dedicated to neurological patients, and serves as a regional stroke reference center receiving patients from municipal and neighboring Emergency Care Units (UPAs). All ICU admissions are regulated through a centralized bed management system. The study was approved by the institutional Research Ethics Committee (Protocol No. 98/2024, Núcleo de Ensino e Pesquisa — NEPE) and registered on the Plataforma Brasil national platform. Given the retrospective and non-interventional nature of the study, individual informed consent was waived. The study was conducted in accordance with the 1964 Declaration of Helsinki and its later amendments. For this type of study, formal patient consent is not required. Study Population We included all patients aged 18 years or older with a completed BD protocol documented at HMDCC between December 2017 and December 2023. Patients were identified through the standardized BD declaration form (Termo de Declaração de Morte Encefálica, TDME) used by the MG Transplantes regional coordination, which is mandatorily completed for all suspected BD cases. Patients were excluded if the TDME was unavailable in the electronic medical record or if critical protocol timestamps were missing. Brain Death Protocol BD protocols followed the Brazilian Federal Council of Medicine Resolution No. 2,173/2017. Prerequisites included a known, irreversible cause of brain injury; core temperature > 35°C; SaO₂ >94%; systolic blood pressure ≥ 100 mmHg or mean arterial pressure ≥ 65 mmHg; and a minimum observation period of 6 hours (24 hours for hypoxic-ischemic encephalopathy). Two clinical examinations (assessing absence of photomotor, corneopalpebral, oculocephalic, vestibulo-caloric reflexes, and cough reflex) were performed at a minimum 1-hour interval, followed by apnea testing (PaCO₂ ≥55 mmHg endpoint). All patients also underwent a mandatory confirmatory complementary exam. TCD Examination All TCD examinations performed during the study period were conducted by a single certified neurologist with expertise in neurosonology, using a probe operating at 2–4 MHz. Insonation was performed through transtemporal and suboccipital windows targeting both anterior and posterior circulation vessels. Criteria for BD confirmation were: absent arterial flow, reverberant (to-and-fro) flow, or isolated systolic spikes in the middle cerebral artery and/or posterior circulation vessels, as per WFN 1998 criteria and Brazilian 2012 guidelines.⁹ Non-TCD protocols used EEG (minimum 30-minute isoelectric recording at sensitivity ≥ 2 µV) or cerebral angiography (absence of intracranial flow in the Circle of Willis). The TCD examiner was blinded to clinical outcome decisions. Variables and Outcomes The primary outcome was BD protocol duration (hours), defined as the interval between the first protocol examination (clinical or complementary) and the last exam performed — identical to the timestamp on the death certificate (Declaração de Óbito). Secondary outcomes were: ( 1 ) ICU LOS after protocol initiation (days), calculated from protocol opening to ICU discharge; ( 2 ) organ donation rate, defined as transfer to the operating room for organ retrieval following BD confirmation. Explanatory variables included: age (years), sex, neurological diagnosis at protocol opening (categorized as ischemic [ischemic stroke, hypoxic-ischemic encephalopathy, cerebral venous thrombosis, status epilepticus] or hemorrhagic [intracerebral hemorrhage, subarachnoid hemorrhage, subdural hematoma]), CCI score, and SAPS III score. Comorbidities were extracted from the electronic medical record. Complementary exam type was classified as TCD (Doppler, DP) or non-TCD (non-Doppler, NDP). Statistical Analysis Continuous variables with normal distribution were described as mean ± standard deviation and compared using Student's t-test; non-normally distributed variables were described as median (interquartile range, IQR) and compared using the Mann-Whitney U test. The Shapiro-Wilk test was applied to evaluate normality. Categorical variables were expressed as absolute and relative frequencies and compared using Pearson's chi-square test. The Kruskal-Wallis test with Conover post-hoc correction was used for comparisons of ICU LOS across SAPS III strata. Negative binomial regression was used to evaluate independent predictors of protocol duration and ICU LOS; binary logistic regression (logit link) was used for organ donation. Stepwise variable selection (forward and backward) guided by the Akaike Information Criterion (AIC) was applied to identify the best-fitting models. Spearman correlation matrices were generated to assess relationships between continuous predictors and outcomes. Model fit was assessed through residual analysis, including identification of influential points and leverage. Significance was set at α = 0.05 (two-tailed). All analyses were performed in R statistical software. RESULTS Patient Characteristics A total of 178 patients with completed BD protocols were included (TCD group [DP]: n = 141; non-TCD group [NDP]: n = 37). Within the non-TCD group, 32 patients (86%) underwent EEG and 5 (14%) underwent cerebral angiography as the confirmatory exam. Given the primary study objective of comparing TCD against all alternative methods, and the limited number of angiography cases (n = 5) precluding meaningful subgroup analysis, NDP patients were analyzed as a single comparison group. Figure 1 shows the patient stratification flowchart. Baseline characteristics are presented in Table 1 . The two groups were comparable in all pre-specified adjustment variables: median age (54.5 years [IQR 44–63] in DP vs 52.0 [IQR 49–60] in NDP; p > 0.05), CCI (2.0 vs 1.0; p > 0.05), SAPS III (74.8 [66–85] vs 70.5 [63–78]; p > 0.05), and sex distribution (p > 0.05). Both groups exhibited a predominance of male patients and a high prevalence of acute organ dysfunction at ICU admission, as reflected by the elevated SAPS III scores. The most prevalent comorbidities were systemic arterial hypertension (~ 40%), tobacco use (~ 35%), and diabetes mellitus (~ 17%), distributed similarly between groups. Ischemic stroke and hypoxic-ischemic encephalopathy were the most common neurological diagnoses; subarachnoid hemorrhage was proportionally more frequent in the NDP group, while ischemic stroke predominated in the DP group. No patient in either group had undergone decompressive craniectomy prior to BD protocol initiation. Table 1 Baseline demographic and clinical characteristics stratified by complementary exam group Variable NDP (n = 37) DP (n = 141) p-value 95% CI Age, years — median (IQR) 52.0 (49–60) 54.5 (44–63) > 0.05 −6.66; 1.81 Charlson Comorbidity Index — median (IQR) 1.0 2.0 > 0.05 −0.99; 0.00 SAPS III — median (IQR) 70.5 (63–78) 74.8 (66–85) > 0.05 −8.83; 0.21 Sex, n (%) > 0.05 Male 17 (46) 102 (57) Female 20 (54) 76 (43) NDP, non-Doppler group (EEG and/or cerebral angiography); DP, Doppler group (transcranial Doppler); IQR, interquartile range; SAPS III, Simplified Acute Physiology Score III; CCI, Charlson Comorbidity Index. Continuous variables: median (IQR). Tests applied: Student's t-test (age, SAPS III), Mann-Whitney U (CCI), Pearson chi-square (sex). p-values > 0.05 indicate no significant difference between groups. Primary Outcome — Protocol Duration TCD use was the sole independent predictor of protocol duration in the negative binomial regression model (Table 2 ). The median protocol duration in the TCD group was 9 hours (IQR 5–23) versus 35 hours (IQR 20–66) in the non-TCD group (OR 0.45, 95% CI 0.32–0.65; p < 0.001), representing a 54.8% reduction. Seventy-five percent of TCD-based protocols were completed within 24 hours. Age strata (18–35, 36–55, 56–75, ≥ 76 years), CCI strata (low/moderate/high), SAPS III strata (low/moderate/high/very high), and sex did not significantly affect protocol duration (all p > 0.05). The Spearman correlation matrix confirmed that the complementary exam method had the strongest correlation with protocol duration (ρ = −0.42), while SAPS III (ρ = −0.16), age (ρ = −0.09), and CCI (ρ = 0.02) showed weak and non-significant associations. Table 2 Primary and secondary outcomes by complementary exam group Variable NDP (n = 37) DP (n = 141) p-value 95% CI Protocol duration, hours — median (IQR) 35 (20–66) 9 (5–23) < 0.001 14.00–29.99 ICU LOS after protocol opening, days — median (IQR) 5 ( 3 – 9 ) 4 ( 2 – 6 ) 0.05 Yes 14 (38) 49 (35) > 0.05 NDP, non-Doppler group; DP, Doppler group; ICU, intensive care unit; LOS, length of stay; IQR, interquartile range. Tests applied: Mann-Whitney U (protocol duration, ICU LOS), Pearson chi-square (organ donation). Secondary Outcomes ICU LOS after protocol initiation was significantly shorter in the TCD group: median 4 days (IQR 2–6) versus 5 days (IQR 3–9) in the non-TCD group (OR 0.66, 95% CI 0.51–0.86; p 0.05). The SAPS III ≥ 70 stratum showed a borderline association (OR 0.59, 95% CI 0.35–1.00; p = 0.05) but did not reach significance. Table 3 Negative binomial regression — independent predictors of protocol duration and ICU LOS Variable OR Reduction (%) p-value 95% CI Protocol duration TCD vs non-TCD (reference) 0.45 54.8 0.05 — CCI strata (all) — — > 0.05 — SAPS III strata (all) — — > 0.05 — ICU LOS after protocol opening TCD vs non-TCD (reference) 0.66 33.7 0.05 — CCI strata (all) — — > 0.05 — SAPS III ≥ 70 pts 0.59 40.9 0.05 0.35–1.00 OR, odds ratio; CCI, Charlson Comorbidity Index; SAPS III, Simplified Acute Physiology Score III; ICU, intensive care unit; LOS, length of stay; TCD, transcranial Doppler ultrasonography. Reference category for complementary exam: non-TCD group. Dashes indicate no significant association across all strata for that variable. Model selection by stepwise AIC (forward and backward). Organ donation did not differ significantly between groups: 49/141 (35%) in the TCD group versus 14/37 (38%) in the non-TCD group (p > 0.05). Binary logistic regression confirmed no independent association between TCD use and organ donation after adjustment for covariates. DISCUSSION In this retrospective cohort of 178 BD protocols conducted over six years at a single Brazilian tertiary ICU, TCD use as the confirmatory complementary exam was independently associated with a 54.8% reduction in protocol duration and a 33.7% reduction in ICU LOS, even after adjustment for age, disease severity, comorbidity burden, and sex. These findings were robust, with TCD being the only variable achieving statistical significance in both regression models, and are among the first to quantify the operational impact of TCD choice on BD protocol efficiency at the institutional level. The diagnostic accuracy of TCD for BD confirmation has been well established. Petty et al. first reported a sensitivity of 91.3% and specificity of 100%.⁷ A 2006 meta-analysis by Monteiro et al. (9 studies, 449 patients) confirmed pooled sensitivity of 89% and specificity of 99%.¹⁰ More recently, Chang et al. (2015) performed a systematic review and meta-analysis of 26 studies and found sensitivity of 86% and specificity of 98%, reinforcing TCD as a reliable confirmatory tool.¹⁰ These data formed the basis for its endorsement in the 2012 Brazilian guidelines as the recommended method for confirmation of cerebral circulatory arrest, with specificity reaching 100% under strict protocol adherence.⁹ The operational advantage we observed likely stems from two structural differences between TCD and the alternative methods. First, EEG requires a minimum 30-minute isoelectric recording but is heavily influenced by residual sedative effects, often necessitating a waiting period before the exam can be validly interpreted — a process that can delay protocol completion by many hours.¹⁰ Second, cerebral angiography, while definitive, is an invasive and logistically demanding procedure that requires specialized personnel, contrast agents, and radiation-capable facilities, with scheduling often adding further delays. TCD, by contrast, can be performed at the bedside within minutes once the examiner is available, yielding an immediate result. This operational distinction likely explains the substantial difference in median protocol duration: 9 hours with TCD versus 35 hours without. The observed 33.7% reduction in ICU LOS is clinically and economically meaningful. In a 100% publicly funded hospital system such as HMDCC, unnecessary ICU occupancy represents a direct cost burden and may limit bed availability for other critically ill patients. Shorter BD protocols also reduce the duration of invasive monitoring and intensive interventions in patients with no therapeutic prospect, with potential benefits for family emotional burden and ethical alignment with principles of patient dignity.¹ The absence of a significant association between TCD use and organ donation rates deserves careful interpretation. Our data showed virtually identical donation rates (35% vs 38%; p > 0.05), consistent with the understanding that organ donation is a complex, multicausal outcome influenced by factors well beyond the diagnostic method, including family consent rates, donor hemodynamic stability, organ viability, regional transplant coordination capacity, and administrative processes. The relatively small NDP group (n = 37) also limits statistical power for this secondary outcome. Our findings neither support nor contradict the hypothesis that faster BD protocols improve donation rates; a larger, prospective study with detailed donation workflow data would be required to address this question adequately. Several limitations of this study warrant discussion. First, the retrospective single-center design limits causal inference and generalizability. The imbalance between groups (141 TCD vs 37 non-TCD) reflects an institution-level shift in practice over the study period rather than random assignment, which, although controlled for statistically through adjustment of baseline variables and confirmed group comparability, may introduce unmeasured confounding. Second, all TCD examinations were performed by a single certified neurosonologist — a critical limitation affecting external validity. TCD requires substantial technical expertise, and our results may not be reproducible in settings without trained practitioners. This underscores the need for structured TCD training programs in ICU environments. Third, the non-TCD group comprised predominantly EEG cases (n = 32, 86%) with a small number of cerebral angiography cases (n = 5, 14%). The primary study objective was explicitly to compare TCD against all currently available alternative methods as used in routine practice, and the low angiography count precluded a statistically powered subgroup analysis. However, given that EEG and angiography carry distinct operational constraints — EEG requiring sedation washout and minimum recording time, angiography requiring invasive scheduling — future studies with larger samples should analyze these subgroups separately to isolate method-specific contributions to protocol duration. Fourth, we did not collect data on TCD technical failure rates (e.g., due to inadequate acoustic windows), which may affect real-world performance. Fifth, cost analysis was beyond the scope of the present study, though the economic implications of the LOS reduction are potentially substantial and merit formal evaluation. Notwithstanding these limitations, our results align with and extend the existing literature on TCD in BD protocols. The Brazilian setting provides a unique perspective: in a resource-constrained public health system, the ability to reduce ICU LOS by one-third while maintaining diagnostic accuracy carries substantial systemic implications. Policy recommendations emerging from this data include: prioritizing TCD acquisition in ICUs with high BD protocol volumes; establishing formal certification pathways for intensivists in neurosonology; and creating standardized electronic documentation templates to facilitate prospective multi-center data collection. CONCLUSIONS In this single-center retrospective study of 178 BD protocols, TCD use as the complementary confirmatory exam was independently associated with a 54.8% reduction in protocol duration and a 33.7% reduction in post-initiation ICU LOS, with groups comparable in disease severity, comorbidity burden, age, and sex. These findings support the preferential adoption of TCD in BD protocols where trained practitioners are available, and highlight the need for expanded neurosonology training in intensive care settings. Organ donation rates were not significantly associated with the choice of complementary exam, consistent with the multifactorial nature of this outcome. Declarations 1. Compliance with Instructions to Authors The authors confirm that this manuscript complies with all Instructions to Authors of Neurocritical Care (February 2025 guidelines). The manuscript is an Original Work (Clinical Investigation). 2. Individual Author Contributions Matheus Rabelo de Freitas: Conception and design of the study; data acquisition; statistical analysis and interpretation; drafting of the manuscript; final approval of the version to be published; accountable for all aspects of the work. André Ferreira de Lima: Conception and design; critical revision of the manuscript for important intellectual content; final approval of the version to be published; accountable for all aspects of the work. Cerise Coutinho: Contribution to data acquisition and interpretation; critical revision of the manuscript; final approval of the version to be published; accountable for all aspects of the work. 3. Authorship Confirmation All authors meet the ICMJE criteria for authorship. The final manuscript was reviewed and approved by all authors. 4. Originality and Exclusivity This manuscript has not been published previously (in whole or in part) and is not currently under consideration by another journal. The data were collected at Hospital Metropolitano Doutor Célio de Castro and presented in abstract form at the 2024 AMIB (Brazilian Association of Intensive Care Medicine) Congress. 5. Ethical Approvals This retrospective study was approved by the institutional Research Ethics Committee of Hospital Metropolitano Doutor Célio de Castro (Protocol No. 98/2024) and registered on the Plataforma Brasil national system. The study was conducted in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. Given the retrospective and non-interventional nature of the study, formal patient consent was waived by the ethics committee. 6. Conflicts of Interest The authors declare that they have no conflicts of interest relevant to the subject matter of this manuscript. 7. Reporting Checklist The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist for cross-sectional studies has been completed and is included as a supplemental file. 8. Sources of Funding This study received no external funding. No financial support was received from any public, commercial, or not-for-profit agency. 9. Artificial Intelligence Disclosure Claude (Anthropic), an AI language model, was used to assist in translation from Portuguese to English and in editorial revision of the manuscript text. The AI did not contribute to study design, data collection, statistical analysis, or interpretation of results. All scientific content was generated and verified by the authors, who take full responsibility for the accuracy and integrity of the work. References Corrêa Neto Y. Morte encefálica: cinquenta anos além do coma profundo. Rev Bras Saude Mater Infant. 2010;10(suppl 2):s355–61. https://doi.org/10.1590/S1519-38292010000600013 . Wijdicks EF. 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Supplementary Files NeurocriticalCareSTROBEChecklist.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 06 Mar, 2026 Reviewers invited by journal 06 Mar, 2026 Editor invited by journal 05 Mar, 2026 Editor assigned by journal 04 Mar, 2026 First submitted to journal 03 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9024571","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":601922494,"identity":"8c7da2df-893b-4e21-aae6-16e2677fa6ae","order_by":0,"name":"Matheus Rabelo de Freitas","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6ElEQVRIiWNgGAWjYFACxgcMDAZAmr35IJDFwMNHWAszUL0BEPMcSwbp5GEjTgvIGokcMwkQn6AW3dmH2T58KPgjL9+QYFb5NcdOho2B+eGjG3i0mJ1LZp45w8DAcMOBA2m3ZbclAx3GZmycg0/LGf7DzDwGBowbGBuO3ZbcxgzUwsMmjV8LMzPzHwMD+/nNjG3FktvqidQCDLHEhmPMbIwftx0mTgtjj4Fx8oYzbMzSjNuO87AxE/QL0JIff+Rs589///Hjz23V9vzszQ8f49OCAph5wCSxykGA8QcpqkfBKBgFo2DEAADrnkHqY5ffnQAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-9236-735X","institution":"Hospital Metropolitano Doutor Celio de Castro","correspondingAuthor":true,"prefix":"","firstName":"Matheus","middleName":"Rabelo","lastName":"de Freitas","suffix":""},{"id":601922495,"identity":"5ddde525-c264-4533-b542-8c20c264ad8d","order_by":1,"name":"André Ferreira de Lima","email":"","orcid":"","institution":"Hospital Metropolitano Doutor Celio de Castro","correspondingAuthor":false,"prefix":"","firstName":"André","middleName":"Ferreira","lastName":"de Lima","suffix":""},{"id":601922496,"identity":"cbfc71d2-1d28-4944-89f5-23cd7a4fd4b5","order_by":2,"name":"Cerise Frade Azeredo Coutinho","email":"","orcid":"","institution":"Hospital Metropolitano Doutor Celio de Castro","correspondingAuthor":false,"prefix":"","firstName":"Cerise","middleName":"Frade Azeredo","lastName":"Coutinho","suffix":""}],"badges":[],"createdAt":"2026-03-04 01:28:38","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9024571/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9024571/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104547182,"identity":"448444d2-d09a-4386-be32-cb2d5e32c62c","added_by":"auto","created_at":"2026-03-13 07:33:54","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1491654,"visible":true,"origin":"","legend":"\u003cp\u003ePatient stratification flowchart. Of 178 patients with completed brain death protocols documented at HMDCC between December 2017 and December 2023, 141 were assigned to the TCD (Doppler) group and 37 to the non-TCD (non-Doppler) group (EEG and/or cerebral angiography). Primary and secondary outcomes were compared between groups. HMDCC, Hospital Metropolitano Doutor Célio de Castro; TCD, transcranial Doppler; EEG, electroencephalogram; ICU, intensive care unit.\u003c/p\u003e","description":"","filename":"Figure1Flowchart1.png","url":"https://assets-eu.researchsquare.com/files/rs-9024571/v1/9ff1579e64e9b784649d26fe.png"},{"id":104547183,"identity":"4359d617-a753-46b1-bef6-6db3ec3713e0","added_by":"auto","created_at":"2026-03-13 07:33:54","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2345791,"visible":true,"origin":"","legend":"\u003cp\u003eSpearman correlation matrices. (A) Correlation matrix between BD protocol duration and predictor variables. The complementary exam method (TCD vs non-TCD) showed the strongest correlation with protocol duration (ρ = −0.42; p\u0026lt;0.001), while SAPS III (ρ = −0.16), age (ρ = −0.09), and CCI (ρ = 0.02) did not reach significance. (B) Correlation matrix between ICU LOS and predictor variables. TCD use showed the strongest correlation with ICU LOS (ρ = −0.20). BD, brain death; ICU, intensive care unit; LOS, length of stay; TCD, transcranial Doppler; SAPS III, Simplified Acute Physiology Score III; CCI, Charlson Comorbidity Index.\u003c/p\u003e","description":"","filename":"Figure2SpearmanMatrices1.png","url":"https://assets-eu.researchsquare.com/files/rs-9024571/v1/ea640f0ac9ec5991014b3675.png"},{"id":104547208,"identity":"22ea3aec-a271-4c62-a30e-a7be094781d6","added_by":"auto","created_at":"2026-03-13 07:34:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4782080,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9024571/v1/2171f862-4996-4cda-9778-9640fe54a056.pdf"},{"id":104547184,"identity":"2f111331-e022-4ee8-9fe6-4719f4aaa640","added_by":"auto","created_at":"2026-03-13 07:33:54","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":12034,"visible":true,"origin":"","legend":"","description":"","filename":"NeurocriticalCareSTROBEChecklist.docx","url":"https://assets-eu.researchsquare.com/files/rs-9024571/v1/3a2431f539c8efcc9d13ce0b.docx"}],"financialInterests":"","formattedTitle":"Transcranial Doppler Ultrasonography as a Complementary Exam in Brain Death Determination: Impact on Protocol Duration and ICU Length of Stay","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eThe determination of brain death (BD) represents one of the most consequential and time-sensitive processes in critical care medicine. Legally defining the irreversible cessation of all encephalic functions, including cerebral cortex and brainstem activity, BD diagnosis directly impacts clinical management, family counseling, and the potential for organ donation.\u0026sup1;⁻\u0026sup2; Current protocols, while essential for diagnostic accuracy, frequently require prolonged observation periods and sequential testing, generating significant logistical, ethical, and emotional burdens for healthcare teams and families alike.\u0026sup3;\u003c/p\u003e \u003cp\u003eIn Brazil, BD diagnosis is regulated by the Federal Council of Medicine Resolution No. 2,173/2017, which requires two clinical examinations with a minimum one-hour interval, an apnea test, and at least one confirmatory complementary exam demonstrating the absence of cerebral blood flow, metabolic activity, or electrical activity.⁴ Accepted complementary methods include cerebral angiography, scintigraphy, electroencephalography (EEG), and transcranial Doppler ultrasonography (TCD).⁴\u003c/p\u003e \u003cp\u003e TCD is a non-invasive bedside technique introduced by Aaslid in 1982 that evaluates blood flow velocities in the major intracranial arteries.⁵ When strict criteria are applied, TCD demonstrates sensitivity of 88\u0026ndash;91% and specificity of 100% for BD confirmation, compared with cerebral angiography as the reference standard.⁶⁻⁷ Recognized patterns indicative of cerebral circulatory arrest include absent flow, reverberant flow (alternating systolic-diastolic), and isolated systolic spikes.⁸ The 2012 Brazilian guidelines, aligning with the World Federation of Neurology (WFN) 1998 consensus, formally endorsed TCD as a confirmatory method and proposed it as the preferred non-invasive standard for this indication.⁹\u003c/p\u003e \u003cp\u003eDespite its technical advantages \u0026mdash; including portability, repeatability, absence of radiation, and bedside availability \u0026mdash; TCD remains underutilized compared to EEG in many Brazilian institutions, partly due to the limited number of trained practitioners.⁹ Moreover, although TCD\u0026rsquo;s diagnostic accuracy for BD has been extensively studied, its impact on the operational efficiency of BD protocols \u0026mdash; specifically, the time required to complete the diagnostic process \u0026mdash; has received comparatively little attention in the literature.\u003c/p\u003e \u003cp\u003eWe hypothesized that, given the inherent time constraints of EEG (minimum 30-minute recording with prior sedation washout requirements) and the scheduling demands of cerebral angiography, the use of TCD as the complementary exam may be associated with a substantially shorter BD protocol duration. Shorter protocols may in turn reduce ICU occupancy and potentially improve organ donation logistics.\u003c/p\u003e \u003cp\u003eIn this retrospective study, we evaluated the association between TCD use as a complementary exam and BD protocol duration, ICU length of stay (LOS) after protocol initiation, and organ donation rates in a single tertiary public hospital in Brazil over a six-year period.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Setting\u003c/h2\u003e \u003cp\u003eThis was a retrospective cross-sectional study conducted at Hospital Metropolitano Doutor C\u0026eacute;lio de Castro (HMDCC), a 100% publicly funded (SUS) tertiary referral hospital in the metropolitan region of Belo Horizonte, Minas Gerais, Brazil. The institution operates 80 ICU beds, including 20 dedicated to neurological patients, and serves as a regional stroke reference center receiving patients from municipal and neighboring Emergency Care Units (UPAs). All ICU admissions are regulated through a centralized bed management system.\u003c/p\u003e \u003cp\u003eThe study was approved by the institutional Research Ethics Committee (Protocol No. 98/2024, N\u0026uacute;cleo de Ensino e Pesquisa \u0026mdash; NEPE) and registered on the Plataforma Brasil national platform. Given the retrospective and non-interventional nature of the study, individual informed consent was waived. The study was conducted in accordance with the 1964 Declaration of Helsinki and its later amendments. For this type of study, formal patient consent is not required.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy Population\u003c/h3\u003e\n\u003cp\u003eWe included all patients aged 18 years or older with a completed BD protocol documented at HMDCC between December 2017 and December 2023. Patients were identified through the standardized BD declaration form (Termo de Declara\u0026ccedil;\u0026atilde;o de Morte Encef\u0026aacute;lica, TDME) used by the MG Transplantes regional coordination, which is mandatorily completed for all suspected BD cases. Patients were excluded if the TDME was unavailable in the electronic medical record or if critical protocol timestamps were missing.\u003c/p\u003e\n\u003ch3\u003eBrain Death Protocol\u003c/h3\u003e\n\u003cp\u003eBD protocols followed the Brazilian Federal Council of Medicine Resolution No. 2,173/2017. Prerequisites included a known, irreversible cause of brain injury; core temperature\u0026thinsp;\u0026gt;\u0026thinsp;35\u0026deg;C; SaO₂ \u0026gt;94%; systolic blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;100 mmHg or mean arterial pressure\u0026thinsp;\u0026ge;\u0026thinsp;65 mmHg; and a minimum observation period of 6 hours (24 hours for hypoxic-ischemic encephalopathy). Two clinical examinations (assessing absence of photomotor, corneopalpebral, oculocephalic, vestibulo-caloric reflexes, and cough reflex) were performed at a minimum 1-hour interval, followed by apnea testing (PaCO₂ \u0026ge;55 mmHg endpoint). All patients also underwent a mandatory confirmatory complementary exam.\u003c/p\u003e\n\u003ch3\u003eTCD Examination\u003c/h3\u003e\n\u003cp\u003eAll TCD examinations performed during the study period were conducted by a single certified neurologist with expertise in neurosonology, using a probe operating at 2\u0026ndash;4 MHz. Insonation was performed through transtemporal and suboccipital windows targeting both anterior and posterior circulation vessels. Criteria for BD confirmation were: absent arterial flow, reverberant (to-and-fro) flow, or isolated systolic spikes in the middle cerebral artery and/or posterior circulation vessels, as per WFN 1998 criteria and Brazilian 2012 guidelines.⁹ Non-TCD protocols used EEG (minimum 30-minute isoelectric recording at sensitivity\u0026thinsp;\u0026ge;\u0026thinsp;2 \u0026micro;V) or cerebral angiography (absence of intracranial flow in the Circle of Willis). The TCD examiner was blinded to clinical outcome decisions.\u003c/p\u003e\n\u003ch3\u003eVariables and Outcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was BD protocol duration (hours), defined as the interval between the first protocol examination (clinical or complementary) and the last exam performed \u0026mdash; identical to the timestamp on the death certificate (Declara\u0026ccedil;\u0026atilde;o de \u0026Oacute;bito). Secondary outcomes were: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) ICU LOS after protocol initiation (days), calculated from protocol opening to ICU discharge; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) organ donation rate, defined as transfer to the operating room for organ retrieval following BD confirmation.\u003c/p\u003e \u003cp\u003eExplanatory variables included: age (years), sex, neurological diagnosis at protocol opening (categorized as ischemic [ischemic stroke, hypoxic-ischemic encephalopathy, cerebral venous thrombosis, status epilepticus] or hemorrhagic [intracerebral hemorrhage, subarachnoid hemorrhage, subdural hematoma]), CCI score, and SAPS III score. Comorbidities were extracted from the electronic medical record. Complementary exam type was classified as TCD (Doppler, DP) or non-TCD (non-Doppler, NDP).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eContinuous variables with normal distribution were described as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and compared using Student's t-test; non-normally distributed variables were described as median (interquartile range, IQR) and compared using the Mann-Whitney U test. The Shapiro-Wilk test was applied to evaluate normality. Categorical variables were expressed as absolute and relative frequencies and compared using Pearson's chi-square test. The Kruskal-Wallis test with Conover post-hoc correction was used for comparisons of ICU LOS across SAPS III strata.\u003c/p\u003e \u003cp\u003eNegative binomial regression was used to evaluate independent predictors of protocol duration and ICU LOS; binary logistic regression (logit link) was used for organ donation. Stepwise variable selection (forward and backward) guided by the Akaike Information Criterion (AIC) was applied to identify the best-fitting models. Spearman correlation matrices were generated to assess relationships between continuous predictors and outcomes. Model fit was assessed through residual analysis, including identification of influential points and leverage. Significance was set at α\u0026thinsp;=\u0026thinsp;0.05 (two-tailed). All analyses were performed in R statistical software.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003ePatient Characteristics\u003c/h2\u003e \u003cp\u003eA total of 178 patients with completed BD protocols were included (TCD group [DP]: n\u0026thinsp;=\u0026thinsp;141; non-TCD group [NDP]: n\u0026thinsp;=\u0026thinsp;37). Within the non-TCD group, 32 patients (86%) underwent EEG and 5 (14%) underwent cerebral angiography as the confirmatory exam. Given the primary study objective of comparing TCD against all alternative methods, and the limited number of angiography cases (n\u0026thinsp;=\u0026thinsp;5) precluding meaningful subgroup analysis, NDP patients were analyzed as a single comparison group. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the patient stratification flowchart.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBaseline characteristics are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The two groups were comparable in all pre-specified adjustment variables: median age (54.5 years [IQR 44\u0026ndash;63] in DP vs 52.0 [IQR 49\u0026ndash;60] in NDP; p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), CCI (2.0 vs 1.0; p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), SAPS III (74.8 [66\u0026ndash;85] vs 70.5 [63\u0026ndash;78]; p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), and sex distribution (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Both groups exhibited a predominance of male patients and a high prevalence of acute organ dysfunction at ICU admission, as reflected by the elevated SAPS III scores. The most prevalent comorbidities were systemic arterial hypertension (~\u0026thinsp;40%), tobacco use (~\u0026thinsp;35%), and diabetes mellitus (~\u0026thinsp;17%), distributed similarly between groups. Ischemic stroke and hypoxic-ischemic encephalopathy were the most common neurological diagnoses; subarachnoid hemorrhage was proportionally more frequent in the NDP group, while ischemic stroke predominated in the DP group. No patient in either group had undergone decompressive craniectomy prior to BD protocol initiation.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline demographic and clinical characteristics stratified by complementary exam group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNDP (n\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDP (n\u0026thinsp;=\u0026thinsp;141)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years \u0026mdash; median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.0 (49\u0026ndash;60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.5 (44\u0026ndash;63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026minus;6.66; 1.81\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharlson Comorbidity Index \u0026mdash; median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026minus;0.99; 0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSAPS III \u0026mdash; median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.5 (63\u0026ndash;78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74.8 (66\u0026ndash;85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026minus;8.83; 0.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMale\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e102 (57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eFemale\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76 (43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003eNDP, non-Doppler group (EEG and/or cerebral angiography); DP, Doppler group (transcranial Doppler); IQR, interquartile range; SAPS III, Simplified Acute Physiology Score III; CCI, Charlson Comorbidity Index. Continuous variables: median (IQR). Tests applied: Student's t-test (age, SAPS III), Mann-Whitney U (CCI), Pearson chi-square (sex). p-values\u0026thinsp;\u0026gt;\u0026thinsp;0.05 indicate no significant difference between groups.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePrimary Outcome \u0026mdash; Protocol Duration\u003c/h2\u003e \u003cp\u003eTCD use was the sole independent predictor of protocol duration in the negative binomial regression model (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The median protocol duration in the TCD group was 9 hours (IQR 5\u0026ndash;23) versus 35 hours (IQR 20\u0026ndash;66) in the non-TCD group (OR 0.45, 95% CI 0.32\u0026ndash;0.65; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), representing a 54.8% reduction. Seventy-five percent of TCD-based protocols were completed within 24 hours. Age strata (18\u0026ndash;35, 36\u0026ndash;55, 56\u0026ndash;75, \u0026ge;\u0026thinsp;76 years), CCI strata (low/moderate/high), SAPS III strata (low/moderate/high/very high), and sex did not significantly affect protocol duration (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The Spearman correlation matrix confirmed that the complementary exam method had the strongest correlation with protocol duration (ρ = \u0026minus;0.42), while SAPS III (ρ = \u0026minus;0.16), age (ρ = \u0026minus;0.09), and CCI (ρ\u0026thinsp;=\u0026thinsp;0.02) showed weak and non-significant associations.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePrimary and secondary outcomes by complementary exam group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNDP (n\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDP (n\u0026thinsp;=\u0026thinsp;141)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProtocol duration, hours \u0026mdash; median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (20\u0026ndash;66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (5\u0026ndash;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e14.00\u0026ndash;29.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU LOS after protocol opening, days \u0026mdash; median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (\u003cspan additionalcitationids=\"CR3 CR4 CR5\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.0001\u0026ndash;2.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOrgan donation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92 (65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003eNDP, non-Doppler group; DP, Doppler group; ICU, intensive care unit; LOS, length of stay; IQR, interquartile range. Tests applied: Mann-Whitney U (protocol duration, ICU LOS), Pearson chi-square (organ donation).\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSecondary Outcomes\u003c/h2\u003e \u003cp\u003eICU LOS after protocol initiation was significantly shorter in the TCD group: median 4 days (IQR 2\u0026ndash;6) versus 5 days (IQR 3\u0026ndash;9) in the non-TCD group (OR 0.66, 95% CI 0.51\u0026ndash;0.86; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), a 33.7% reduction (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). As with protocol duration, no adjustment variable reached statistical significance in the regression model for ICU LOS (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The SAPS III\u0026thinsp;\u0026ge;\u0026thinsp;70 stratum showed a borderline association (OR 0.59, 95% CI 0.35\u0026ndash;1.00; p\u0026thinsp;=\u0026thinsp;0.05) but did not reach significance.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNegative binomial regression \u0026mdash; independent predictors of protocol duration and ICU LOS\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReduction (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProtocol duration\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTCD vs non-TCD (reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.32\u0026ndash;0.65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge strata (all)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCCI strata (all)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSAPS III strata (all)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eICU LOS after protocol opening\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTCD vs non-TCD (reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.51\u0026ndash;0.86\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge strata (all)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCCI strata (all)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSAPS III\u0026thinsp;\u0026ge;\u0026thinsp;70 pts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.35\u0026ndash;1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003eOR, odds ratio; CCI, Charlson Comorbidity Index; SAPS III, Simplified Acute Physiology Score III; ICU, intensive care unit; LOS, length of stay; TCD, transcranial Doppler ultrasonography. Reference category for complementary exam: non-TCD group. Dashes indicate no significant association across all strata for that variable. Model selection by stepwise AIC (forward and backward).\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOrgan donation did not differ significantly between groups: 49/141 (35%) in the TCD group versus 14/37 (38%) in the non-TCD group (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Binary logistic regression confirmed no independent association between TCD use and organ donation after adjustment for covariates.\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this retrospective cohort of 178 BD protocols conducted over six years at a single Brazilian tertiary ICU, TCD use as the confirmatory complementary exam was independently associated with a 54.8% reduction in protocol duration and a 33.7% reduction in ICU LOS, even after adjustment for age, disease severity, comorbidity burden, and sex. These findings were robust, with TCD being the only variable achieving statistical significance in both regression models, and are among the first to quantify the operational impact of TCD choice on BD protocol efficiency at the institutional level.\u003c/p\u003e \u003cp\u003eThe diagnostic accuracy of TCD for BD confirmation has been well established. Petty et al. first reported a sensitivity of 91.3% and specificity of 100%.⁷ A 2006 meta-analysis by Monteiro et al. (9 studies, 449 patients) confirmed pooled sensitivity of 89% and specificity of 99%.\u0026sup1;⁰ More recently, Chang et al. (2015) performed a systematic review and meta-analysis of 26 studies and found sensitivity of 86% and specificity of 98%, reinforcing TCD as a reliable confirmatory tool.\u0026sup1;⁰ These data formed the basis for its endorsement in the 2012 Brazilian guidelines as the recommended method for confirmation of cerebral circulatory arrest, with specificity reaching 100% under strict protocol adherence.⁹\u003c/p\u003e \u003cp\u003eThe operational advantage we observed likely stems from two structural differences between TCD and the alternative methods. First, EEG requires a minimum 30-minute isoelectric recording but is heavily influenced by residual sedative effects, often necessitating a waiting period before the exam can be validly interpreted \u0026mdash; a process that can delay protocol completion by many hours.\u0026sup1;⁰ Second, cerebral angiography, while definitive, is an invasive and logistically demanding procedure that requires specialized personnel, contrast agents, and radiation-capable facilities, with scheduling often adding further delays. TCD, by contrast, can be performed at the bedside within minutes once the examiner is available, yielding an immediate result. This operational distinction likely explains the substantial difference in median protocol duration: 9 hours with TCD versus 35 hours without.\u003c/p\u003e \u003cp\u003eThe observed 33.7% reduction in ICU LOS is clinically and economically meaningful. In a 100% publicly funded hospital system such as HMDCC, unnecessary ICU occupancy represents a direct cost burden and may limit bed availability for other critically ill patients. Shorter BD protocols also reduce the duration of invasive monitoring and intensive interventions in patients with no therapeutic prospect, with potential benefits for family emotional burden and ethical alignment with principles of patient dignity.\u0026sup1;\u003c/p\u003e \u003cp\u003eThe absence of a significant association between TCD use and organ donation rates deserves careful interpretation. Our data showed virtually identical donation rates (35% vs 38%; p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), consistent with the understanding that organ donation is a complex, multicausal outcome influenced by factors well beyond the diagnostic method, including family consent rates, donor hemodynamic stability, organ viability, regional transplant coordination capacity, and administrative processes. The relatively small NDP group (n\u0026thinsp;=\u0026thinsp;37) also limits statistical power for this secondary outcome. Our findings neither support nor contradict the hypothesis that faster BD protocols improve donation rates; a larger, prospective study with detailed donation workflow data would be required to address this question adequately.\u003c/p\u003e \u003cp\u003eSeveral limitations of this study warrant discussion. First, the retrospective single-center design limits causal inference and generalizability. The imbalance between groups (141 TCD vs 37 non-TCD) reflects an institution-level shift in practice over the study period rather than random assignment, which, although controlled for statistically through adjustment of baseline variables and confirmed group comparability, may introduce unmeasured confounding. Second, all TCD examinations were performed by a single certified neurosonologist \u0026mdash; a critical limitation affecting external validity. TCD requires substantial technical expertise, and our results may not be reproducible in settings without trained practitioners. This underscores the need for structured TCD training programs in ICU environments. Third, the non-TCD group comprised predominantly EEG cases (n\u0026thinsp;=\u0026thinsp;32, 86%) with a small number of cerebral angiography cases (n\u0026thinsp;=\u0026thinsp;5, 14%). The primary study objective was explicitly to compare TCD against all currently available alternative methods as used in routine practice, and the low angiography count precluded a statistically powered subgroup analysis. However, given that EEG and angiography carry distinct operational constraints \u0026mdash; EEG requiring sedation washout and minimum recording time, angiography requiring invasive scheduling \u0026mdash; future studies with larger samples should analyze these subgroups separately to isolate method-specific contributions to protocol duration. Fourth, we did not collect data on TCD technical failure rates (e.g., due to inadequate acoustic windows), which may affect real-world performance. Fifth, cost analysis was beyond the scope of the present study, though the economic implications of the LOS reduction are potentially substantial and merit formal evaluation.\u003c/p\u003e \u003cp\u003eNotwithstanding these limitations, our results align with and extend the existing literature on TCD in BD protocols. The Brazilian setting provides a unique perspective: in a resource-constrained public health system, the ability to reduce ICU LOS by one-third while maintaining diagnostic accuracy carries substantial systemic implications. Policy recommendations emerging from this data include: prioritizing TCD acquisition in ICUs with high BD protocol volumes; establishing formal certification pathways for intensivists in neurosonology; and creating standardized electronic documentation templates to facilitate prospective multi-center data collection.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eIn this single-center retrospective study of 178 BD protocols, TCD use as the complementary confirmatory exam was independently associated with a 54.8% reduction in protocol duration and a 33.7% reduction in post-initiation ICU LOS, with groups comparable in disease severity, comorbidity burden, age, and sex. These findings support the preferential adoption of TCD in BD protocols where trained practitioners are available, and highlight the need for expanded neurosonology training in intensive care settings. Organ donation rates were not significantly associated with the choice of complementary exam, consistent with the multifactorial nature of this outcome.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e1. Compliance with Instructions to Authors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors confirm that this manuscript complies with all Instructions to Authors of Neurocritical Care (February 2025 guidelines). The manuscript is an Original Work (Clinical Investigation).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2. Individual Author Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMatheus Rabelo de Freitas: Conception and design of the study; data acquisition; statistical analysis and interpretation; drafting of the manuscript; final approval of the version to be published; accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003eAndr\u0026eacute; Ferreira de Lima: Conception and design; critical revision of the manuscript for important intellectual content; final approval of the version to be published; accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003eCerise Coutinho: Contribution to data acquisition and interpretation; critical revision of the manuscript; final approval of the version to be published; accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003e3. Authorship Confirmation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors meet the ICMJE criteria for authorship. The final manuscript was reviewed and approved by all authors.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003e4. Originality and Exclusivity\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis manuscript has not been published previously (in whole or in part) and is not currently under consideration by another journal. The data were collected at Hospital Metropolitano Doutor C\u0026eacute;lio de Castro and presented in abstract form at the 2024 AMIB (Brazilian Association of Intensive Care Medicine) Congress.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003e5. Ethical Approvals\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study was approved by the institutional Research Ethics Committee of Hospital Metropolitano Doutor C\u0026eacute;lio de Castro (Protocol No. 98/2024) and registered on the Plataforma Brasil national system. The study was conducted in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. Given the retrospective and non-interventional nature of the study, formal patient consent was waived by the ethics committee.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003e6. Conflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest relevant to the subject matter of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003e7. Reporting Checklist\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist for cross-sectional studies has been completed and is included as a supplemental file.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003e8. Sources of Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study received no external funding. No financial support was received from any public, commercial, or not-for-profit agency.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003e9. Artificial Intelligence Disclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClaude (Anthropic), an AI language model, was used to assist in translation from Portuguese to English and in editorial revision of the manuscript text. The AI did not contribute to study design, data collection, statistical analysis, or interpretation of results. All scientific content was generated and verified by the authors, who take full responsibility for the accuracy and integrity of the work.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCorr\u0026ecirc;a Neto Y. Morte encef\u0026aacute;lica: cinquenta anos al\u0026eacute;m do coma profundo. 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Time dependent validity in the diagnosis of brain death using transcranial Doppler sonography. J Neurol Neurosurg Psychiatry. 2006;77(5):646\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1136/jnnp.2005.076406\u003c/span\u003e\u003cspan address=\"10.1136/jnnp.2005.076406\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"neurocritical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"neca","sideBox":"Learn more about [Neurocritical Care](http://link.springer.com/journal/12028)","snPcode":"12028","submissionUrl":"https://www.editorialmanager.com/neca/default2.aspx","title":"Neurocritical Care","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"transcranial Doppler ultrasonography, brain death, brain death protocol, organ donation, intensive care unit","lastPublishedDoi":"10.21203/rs.3.rs-9024571/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9024571/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground/Objective\u003c/b\u003e: Brain death (BD) determination is a critical process in intensive care with significant clinical and logistical implications. Transcranial Doppler ultrasonography (TCD) is accepted as a confirmatory exam for BD in Brazil and several international guidelines, yet its operational impact on protocol efficiency remains poorly characterized. We evaluated whether TCD use is associated with shorter BD protocol duration, reduced ICU length of stay (LOS), and higher organ donation rates.\u003c/p\u003e \u003cp\u003e \u003cb\u003eMethods\u003c/b\u003e: Retrospective cross-sectional study at a tertiary public ICU in Belo Horizonte, Brazil (December 2017\u0026ndash;December 2023). We included 178 patients (\u0026ge;\u0026thinsp;18 years) with completed BD protocols, stratified by complementary exam: TCD (n\u0026thinsp;=\u0026thinsp;141) or non-TCD (n\u0026thinsp;=\u0026thinsp;37; EEG and/or angiography). Primary outcome was BD protocol duration (hours); secondary outcomes were ICU LOS (days) and organ donation rate. Negative binomial regression adjusted for age, Charlson Comorbidity Index (CCI), SAPS III, and sex.\u003c/p\u003e \u003cp\u003e \u003cb\u003eResults\u003c/b\u003e: Groups were comparable in age, CCI, SAPS III, and sex (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). TCD was the only independent predictor of shorter protocol duration: median 9h (IQR 5\u0026ndash;23) vs 35h (IQR 20\u0026ndash;66); OR 0.45 (95% CI 0.32\u0026ndash;0.65); p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; 54.8% reduction. ICU LOS was also shorter in the TCD group: 4 days (IQR 2\u0026ndash;6) vs 5 days (IQR 3\u0026ndash;9); OR 0.66 (95% CI 0.51\u0026ndash;0.86); p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; 33.7% reduction. Seventy-five percent of TCD protocols were completed within 24 hours. Organ donation rates did not differ significantly (35% vs 38%; p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cb\u003eConclusions\u003c/b\u003e: TCD use was independently associated with substantially shorter BD protocol duration and ICU LOS, supporting broader implementation in institutions with trained practitioners. Organ donation was not associated with TCD use, consistent with its multifactorial nature.\u003c/p\u003e","manuscriptTitle":"Transcranial Doppler Ultrasonography as a Complementary Exam in Brain Death Determination: Impact on Protocol Duration and ICU Length of Stay","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-13 07:33:49","doi":"10.21203/rs.3.rs-9024571/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2026-03-06T14:28:29+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-06T13:49:08+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Neurocritical Care","date":"2026-03-05T18:05:32+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-04T12:48:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"Neurocritical Care","date":"2026-03-03T20:27:58+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"neurocritical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"neca","sideBox":"Learn more about [Neurocritical Care](http://link.springer.com/journal/12028)","snPcode":"12028","submissionUrl":"https://www.editorialmanager.com/neca/default2.aspx","title":"Neurocritical Care","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"c09ce890-e53f-4db5-aafe-a82801e0b23d","owner":[],"postedDate":"March 13th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-13T07:33:49+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-13 07:33:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9024571","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9024571","identity":"rs-9024571","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}