Śmierć mózgowa – Rokowania, prognozy i postęp choroby

Śmierć mózgowa
Rokowania, prognozy i postęp choroby

Przewidywanie rozwoju śmierci mózgowej (BD) u pacjentów po pozaszpitalnym zatrzymaniu krążenia (OHCA) jest kluczowe zarówno dla rokowania, jak i potencjalnego dawstwa narządów. Śmierć mózgowa diagnozowana jest u około 1/6 pacjentów umierających w szpitalu, z medianą czasu do diagnozy wynoszącą 6 dni (IQR 5,0-7,0) po ROSC. Biomarkery takie jak S100B, GFAP i UCH-L1, szczególnie wzrost S100B po 72 godzinach, oraz wczesne badania obrazowe (CT z oceną cysterny ambiens i wklinowania mózgu) stanowią istotne narzędzia prognostyczne. Elektroencefalografia (EEG) i somatosensoryczne potencjały wywołane (SSEP), zwłaszcza brak fali N20, dostarczają dodatkowych informacji o ciężkości niedotlenienia mózgu. Modele predykcyjne, takie jak skala OHCA-BD (AUROC 0,831) i BD-N, umożliwiają wczesną identyfikację pacjentów z wysokim ryzykiem rozwoju BD, co jest istotne dla optymalizacji opieki i planowania dawstwa narządów.

Śmierć mózgowa – Prognoza (przewidywanie wyniku)

Przewidywanie rozwoju śmierci mózgowej (BD, brain death) jest istotnym elementem opieki nad pacjentami w stanie krytycznym, zarówno pod kątem informowania rodziny o rokowaniu, jak i potencjalnego dawstwa narządów. Wczesna identyfikacja pacjentów, u których może rozwinąć się śmierć mózgowa, ma kluczowe znaczenie dla procesu pozyskiwania narządów, szczególnie w kontekście światowego niedoboru narządów do przeszczepów.¹²

Czas i częstotliwość występowania śmierci mózgowej

Według badań nad pacjentami po pozaszpitalnym zatrzymaniu krążenia (OHCA) z zastosowaniem terapeutycznej hipotermii (TTM), śmierć mózgowa diagnozowana jest u około jednej szóstej wszystkich pacjentów umierających w szpitalu. Mediana czasu do ustalenia prawnej diagnozy śmierci mózgowej wynosiła 6 dni (przedział międzykwartylowy 5,0-7,0) po przywróceniu spontanicznego krążenia (ROSC).³⁴ To istotna informacja, ponieważ wskazuje, że znaczna liczba przypadków śmierci mózgowej może być zdiagnozowana po zakończeniu terapeutycznej hipotermii i przeprowadzeniu multimodalnej prognostykacji zalecanej przez wytyczne resuscytacji krążeniowo-oddechowej.⁵

Warto podkreślić, że chociaż wytyczne dotyczące prognostyki neurologicznej zalecają ocenę nie wcześniej niż 72 godziny po ROSC, to w przypadku śmierci mózgowej nie jest konieczne oczekiwanie aż 72 godzin. Wytyczne dotyczące śmierci mózgowej zalecają jednak odczekanie 24 godzin po zatrzymaniu krążenia przed jej stwierdzeniem. Jeśli jednak badanie pomocnicze wykaże brak przepływu krwi do mózgu (zatrzymanie krążenia mózgowego), dalsze oczekiwanie może być zbędne.⁶

Markery i czynniki predykcyjne śmierci mózgowej

Biomarkery serologiczne

Badania wykazały, że stężenia w surowicy krwi białka S100B, GFAP (kwaśne białko włókienkowe gleju) i UCH-L1 (ubikwitynowa hydrolaza karboksykońcowa L1) mierzone w ciągu 32 godzin od pourazowego i niedotlenieniowego uszkodzenia mózgu mogą być wykorzystane w prognozowaniu śmierci mózgowej. Biomarkery te mogą również pomóc w rozróżnieniu mechanizmu urazu – czy jest on niedotlenieniowy (zatrzymanie krążenia/zatrzymanie oddychania) czy urazowy/nieznany (rozlane uszkodzenie aksonalne i uraz czołowy).⁷⁸

Szczególnie poziom białka S100B w surowicy krwi po 72 godzinach od zatrzymania krążenia wykazuje gwałtowny wzrost u pacjentów rozwijających śmierć mózgową, co jest zgodne z wcześniejszymi badaniami pokazującymi, że pomiary S100B były znacząco wyższe w grupie z potwierdzoną śmiercią mózgową w porównaniu z innymi grupami.⁹

Badania obrazowe

Wczesne wyniki tomografii komputerowej mózgu mają potencjalną rolę w identyfikacji pacjentów, u których może rozwinąć się śmierć mózgowa.¹⁰ W diagnostyce śmierci mózgowej standardowe badania MR lub CT są mniej istotne, natomiast angiografia CT i w mniejszym stopniu angiografia MR przyczyniają się jako testy pomocnicze do diagnostyki śmierci mózgowej, chociaż jej diagnoza pozostaje kliniczna.¹¹

Szczególnie istotne są wyniki badań obrazowych pokazujące nieobecność cysterny ambiens i obecność wklinowania mózgu, które są silnymi predyktorami śmierci mózgowej. Badania wykazały, że nieobecność cysterny ambiens (iloraz szans [OR] = 11,96, 95% CI 1,59-89,78, P = 0,016) i obecność wklinowania mózgu (OR = 16,28, 95% CI 2,25-117,73, P = 0,006) na obrazach CT mózgu były związane ze śmiercią mózgową w ciągu 7 dni.¹²¹³

Badania elektrofizjologiczne

Elektroencefalografia (EEG) dostarcza cennych informacji o ciężkości niedotlenienia mózgu. Ciężkość niedokrwienno-niedotlenieniowego uszkodzenia mózgu (HIBI, hypoxic-ischemic brain injury) koreluje z przeważającą częstotliwością i ciągłością tła EEG, prowadząc do wysoce złośliwych wzorców, takich jak supresja lub cisza-wybuch w najcięższych przypadkach HIBI.¹⁴

Somatosensoryczne potencjały wywołane (SSEP) są również istotnym narzędziem prognostycznym. Obustronny brak odpowiedzi N20 SSEP jest jednym z najbardziej swoistych elementów dla przewidywania złego rokowania, odzwierciedlając uszkodzenia pierwszorzędowej kory somatosensorycznej i pętli wzgórzowo-korowej.¹⁵ Ponadto, amplitudy odpowiedzi SSEP, a mianowicie N20-baseline (N20-b) i N20P25, mogą przewidywać zarówno dobry, jak i zły wynik neurologiczny z wysoką specyficznością, ale niską do umiarkowanej czułością.¹⁶

Dla przewidywania dobrego wyniku, próg amplitudy N20-baseline ≥2 μV i N20P25 ≥3,2 μV rejestrowany 72 godziny po zatrzymaniu krążenia był najlepszym kompromisem między wysoką swoistością a akceptowalną czułością. W przypadku przewidywania złego wyniku, próg 0,88 μV dla amplitudy N20-baseline i 1 μV dla N20P25 wydawał się być najlepszym kompromisem.¹⁷

Modele predykcyjne śmierci mózgowej

Opracowano kilka modeli predykcyjnych mających na celu wczesną identyfikację pacjentów z ryzykiem rozwoju śmierci mózgowej. Jednym z takich modeli jest skala OHCA-BD, która wykorzystuje niezależne predyktory śmierci mózgowej po pozaszpitalnym zatrzymaniu krążenia, takie jak wiek, czas niskiego przepływu (low-flow time), pH i etiologia.¹⁸ Model ten wykazał dobrą zdolność predykcyjną z obszarem pod krzywą ROC (AUROC) wynoszącym 0,831 (95% przedział ufności [CI], 0,786-0,876).¹⁹

Innym modelem jest skala neurologiczna BD-N, opracowana w celu przewidywania prawdopodobieństwa progresji do śmierci mózgowej po samoistnym zatrzymaniu oddychania. Model ten przyznaje po 1 punkcie za: brak odruchu źrenicznego, anizokorie lub obustronnie rozszerzone źrenice, brak odpowiedzi ruchowej na ból, brak cysterny ambiens i obecność wklinowania mózgu. Prawdopodobieństwo śmierci mózgowej w ciągu 7 dni po samoistnym zatrzymaniu oddychania wzrasta wraz ze wzrostem wyniku.²⁰

Warto również wspomnieć o modelach wykorzystujących uczenie maszynowe, które mogą dokładnie przewidywać krótkoterminową śmiertelność i funkcję neurologiczną u pacjentów przyjętych na oddział intensywnej terapii z powodu urazowego uszkodzenia mózgu. Modele te wykorzystują informacje dostępne w pierwszych 24 godzinach intensywnej opieki.²¹²²

Podejście multimodalne w prognostyce

Obecne wytyczne zalecają podejście multimodalne łączące wiele testów prognostycznych, aby zminimalizować ryzyko fałszywie pesymistycznego przewidywania.²³²⁴ Najbardziej solidne predyktory (wskaźnik fałszywie dodatnich FPR ≤5% dla prognozy złego wyniku z wąskim przedziałem ufności udokumentowanym w 5 badaniach od co najmniej trzech różnych grup badaczy) powinny być oceniane w pierwszej kolejności. Należą do nich obustronnie nieobecne odruchy źreniczne 72 godziny po ROSC i/lub obustronnie nieobecna fala N20 SSEP po ogrzaniu.²⁵

Prognostyka powinna być oparta na łączeniu wielu źródeł informacji, w tym badania klinicznego, badań neurofizjologicznych (elektroencefalogram, somatosensoryczne potencjały wywołane), biologicznych (swoista enolaza neuronowa, NSE) i neuroradiologicznych (tomografia komputerowa lub rezonans magnetyczny). Gdy wszystkie źródła informacji są zgodne, może to zwiększyć pewność prognozy.²⁶²⁷

Wyzwania i ograniczenia w prognostyce śmierci mózgowej

Prognostyka może być utrudniona przez różne czynniki zakłócające, takie jak leki sedatywne, hipotermia, zaburzenia metaboliczne czy inne przyczyny zmiany stanu psychicznego.²⁸ Dlatego aktualne wytyczne zalecają przeprowadzanie prognostyki nie wcześniej niż 72 godziny po powrocie spontanicznego krążenia u wszystkich pacjentów w śpiączce z brakiem reakcji motorycznej lub reakcją wyprostną na ból, po wykluczeniu czynników zakłócających, takich jak pozostałości sedacji, które mogą interferować z badaniem klinicznym.²⁹

Wyzwaniem w prognostyce jest identyfikacja markerów o najwyższej swoistości i najniższym wskaźniku fałszywie dodatnich (FPR), aby zminimalizować możliwość błędnej prognozy.³⁰ Nadmiernie pesymistyczna prognostyka mogłaby prowadzić do przedwczesnego wycofania opieki u pacjenta z potencjałem do wyzdrowienia. Z drugiej strony, zbyt optymistyczna prognostyka może prowadzić do kontynuowania wsparcia przez dni lub tygodnie w beznadziejnej sytuacji.³¹

Znaczenie wczesnej prognostyki śmierci mózgowej

Wczesna charakterystyka ciężkości i trajektorii klinicznej może otworzyć okno dla ukierunkowanych interwencji w celu poprawy wyników u pacjentów z umiarkowanym i ciężkim urazowym uszkodzeniem mózgu.³² Ponadto, wczesna identyfikacja pacjentów z wysokim ryzykiem rozwoju śmierci mózgowej może ułatwić proces pozyskiwania narządów dawcy.³³

Przewidywanie wyniku neurologicznego u pacjentów w śpiączce po zatrzymaniu krążenia jest ważne, aby dostarczyć prawidłowych informacji krewnym pacjenta, uniknąć nieproporcjonalnej opieki u pacjentów z nieodwracalnym niedokrwienno-niedotlenieniowym uszkodzeniem mózgu (HIBI) i nieodpowiedniego wycofania opieki u pacjentów z możliwym korzystnym powrotem do zdrowia neurologicznego.³⁴

Badania pokazały, że u pacjentów po pozaszpitalnym zatrzymaniu krążenia, którzy zmarli przed wypisem ze szpitala, 19 ze 121 pacjentów przeszło w kierunku śmierci mózgowej w medianie 6 dni po ROSC i miało pobrane narządy.³⁵ To podkreśla znaczenie wczesnej identyfikacji potencjalnych dawców narządów dla zwiększenia dostępności narządów do transplantacji.

Perspektywy i przyszłe kierunki badań

Przyszłe badania z systemami o wyższej gęstości elektrod mogą poprawić dodatnią wartość predykcyjną dla prognozowania dobrego wyniku.³⁶ Ponadto, skojarzenie amplitud N20 SSEP z innymi markerami prognostycznymi wydaje się zwiększać swoistość przy zachowaniu akceptowalnej czułości, przemawiając za multimodalnym podejściem do prognostyki pacjentów w śpiączce po zatrzymaniu krążenia.³⁷

Modele predykcyjne, takie jak skala OHCA-BD i skala BD-N, wymagają dalszej prospektywnej walidacji w celu potwierdzenia ich skuteczności w praktyce klinicznej.³⁸³⁹ Rozwój i walidacja dokładniejszych modeli predykcyjnych mogą przyczynić się do poprawy wczesnej identyfikacji pacjentów z ryzykiem rozwoju śmierci mózgowej, co może mieć istotne znaczenie dla zwiększenia dostępności narządów do transplantacji.

Kolejne rozdziały

Zapraszamy do dalszego czytania naszego leksykonu.

Wybierz kolejny rozdział z menu poniżej, aby otworzyć nową podstronę kompedium wiedzy i uzyskać szczegółowe informację o leku, substancji lub chorobie.

Materiały źródłowe

#1 Early prediction model of brain death in out-of-hospital cardiac arrest patients: a single-center retrospective and internal validation analysis | BMC Emergency Medicine | Full Text
https://bmcemergmed.biomedcentral.com/articles/10.1186/s12873-022-00734-1
A shortage of donor organs amid high demand for transplantable organs is a worldwide problem, and an increase in organ donation would be welcomed by the global healthcare system. Patients with brain death (BD) are potential organ donors, and early prediction of patients with BD may facilitate the process of organ procurement. […] We developed and internally validated a new prediction model for BD after OHCA, which could aid in the early identification of potential organ donors for early donor organ procurement. […] Logistic regression analysis confirmed that age, low-flow time, pH, and etiology were independent predictors of BD. […] The developed prediction score (OHCA-BD score) is presented in Table 3. […] Consequently, we created a linearised logarithmic function model using this score.
#2 Predictive Factors of Brain Death in Acute Neurocritical Patients Identified as Potential Organ Donors
https://clinmedjournals.org/articles/ijbdt/international-journal-of-brain-disorders-and-treatment-ijbdt-2-014.php?jid=ijbdt
Reliable prediction of brain death after no-therapy decision in acute neurocritical patients is of specific interest for organ donation after brain death (DBD). […] We aimed to establish a neurological scoring system (the BD-N score) to predict the probability of progression to brain death after spontaneous respiratory arrest. […] Multivariable logistic regression analysis showed that absent pupil reflex (OR = 7.43, 95% CI 1.62-33.99, P = 0.010), anisocoria or bilaterally dilated pupil (OR = 6.25, 95% CI 1.21-32.22, P = 0.028), absent motor response to pain (OR = 15.89, 95% CI 3.04-82.93, P = 0.001), absent cisterna ambiens (OR = 11.96, 95% CI 1.59-89.78, P = 0.016) and present of brain herniation (OR = 16.28, 95% CI 2.25-117.73, P = 0.006) on brain CT imagine were associated with brain death within 7 days.
#3 Brain Death and Its Prediction in Out-of-Hospital Cardiac Arrest Patients Treated with Targeted Temperature Management
https://pmc.ncbi.nlm.nih.gov/articles/PMC9140750/
Evolution toward brain death (BD) in out-of-hospital cardiac arrest patients with targeted temperature management (TTM) provides opportunities for organ donation. […] We explored the process of evolution toward BD and its predictors by comparing the serial measurements of clinical variables and the results of various prognostic tests between the two groups. […] In conclusion, approximately one-sixth of all in-hospital deaths were diagnosed with BD at a median of 6 days after cardiac arrest. […] The use of GWR and serial S100B measurements may help to screen potential BD. […] However, knowledge of the evolution of these patients to BD is very limited. […] It is unclear whether the prognostication tools recommended by international guidelines for post-resuscitation care to predict neurological outcomes can also predict the evolution toward BD.
#4 Brain Death and Its Prediction in Out-of-Hospital Cardiac Arrest Patients Treated with Targeted Temperature Management
https://pmc.ncbi.nlm.nih.gov/articles/PMC9140750/
The primary aim of the current study was to evaluate the process of evolution toward BD in OHCA patients with TTM. […] The secondary aim was to identify prognostic tools related to evolution toward BD. […] The median time to a legal BD diagnosis was 6.0 (IQR, 5.07.0) days. […] Four patients who had PLR at 24 h and 48 h after ROSC finally progressed to BD. […] Among various outcome predictors, early brain CT findings and serial measurement of serum S100B, especially the results at 72 h, had a potential role in the identification of patients who could evolve toward BD. […] Our results revealed that a significant number of BDs can be diagnosed after completing TTM and multimodal prognostication recommended by the CPR guidelines. […] The serum level of S100B at 72 h was abruptly elevated in BD patients, consistent with previous studies reporting that S100B measurements were significantly higher in the group with confirmed BD than in the other group. […] Our study showed that 19 of 121 patients who died before hospital discharge progressed toward BD at a median of 6 days after ROSC and had organs retrieved.
#5 Brain Death and Its Prediction in Out-of-Hospital Cardiac Arrest Patients Treated with Targeted Temperature Management
https://pmc.ncbi.nlm.nih.gov/articles/PMC9140750/
The primary aim of the current study was to evaluate the process of evolution toward BD in OHCA patients with TTM. […] The secondary aim was to identify prognostic tools related to evolution toward BD. […] The median time to a legal BD diagnosis was 6.0 (IQR, 5.07.0) days. […] Four patients who had PLR at 24 h and 48 h after ROSC finally progressed to BD. […] Among various outcome predictors, early brain CT findings and serial measurement of serum S100B, especially the results at 72 h, had a potential role in the identification of patients who could evolve toward BD. […] Our results revealed that a significant number of BDs can be diagnosed after completing TTM and multimodal prognostication recommended by the CPR guidelines. […] The serum level of S100B at 72 h was abruptly elevated in BD patients, consistent with previous studies reporting that S100B measurements were significantly higher in the group with confirmed BD than in the other group. […] Our study showed that 19 of 121 patients who died before hospital discharge progressed toward BD at a median of 6 days after ROSC and had organs retrieved.
#6 Neuroprognostication after cardiac arrest – EMCrit Project
https://emcrit.org/ibcc/np/
Patients often sustain severe neurologic injury during cardiac arrest. […] Prognostication is extraordinarily important. Excessively pessimistic prognostication could lead to a premature withdrawal of care in a patient with the potential to recover. However, overly optimistic prognostication may lead to ongoing support for days or weeks in a hopeless situation. […] There is no need to wait 72 hours to declare a patient brain dead. Brain death guidelines do recommend waiting 24 hours after arrest to declare brain death. However, if an ancillary test demonstrates lack of blood flow to the brain (cerebral circulatory arrest), then any further waiting may be unnecessary. […] Prognostication can be confounded by any cause of altered mental status. […] In the absence of confounding factors, neurologic function tends to track out along various curves as shown above. As time progresses, it becomes increasingly clear where the patient will end up neurologically.
#7 Serum Markers Predict Brain Death Due to Trauma and Hypoxia Within 32 hours of Injury | medRxiv
https://www.medrxiv.org/content/10.1101/2021.02.13.21251369v1.full-text
Objective Brain death is a controversial construct because proving irreversible cessation of neurologic function is difficult, and ascertaining the timepoint at which irreversibility has occurred is not currently possible. The ability to predict which traumatic (TBI) and hypoxic brain injuries will progress to brain death is also limited. We investigated how accurately neurologic serum markers can predict brain death and differentiate its etiology. […] Serum concentrations of GFAP, UCH-L1, and S100B measured within 32 hours of traumatic and hypoxic brain injury have utility in prognosticating brain death by mechanism of injury as either hypoxic (CA/RA) or traumatic/unknown (DAI and FD). […] The aim of this study was to determine whether or not brain death could be predicted by serum levels of GFAP, UCH-L1 and S100B following traumatic and atraumatic head injury.
#8 Serum Markers Predict Brain Death Due to Trauma and Hypoxia Within 32 hours of Injury | medRxiv
https://www.medrxiv.org/content/10.1101/2021.02.13.21251369v1.full-text
We conclude that serum levels of GFAP, UCH-L1 and S100B drawn within 32 hours post traumatic or non-traumatic brain injury can accurately identify patients who are at significant risk of developing brain death. Importantly, our model can distinguish those who suffered brain death from those who suffered a survived TBI with positive head CT or non-traumatic brain injury, highlighting the potential utility of our model to inform a challenging prognosis. Furthermore, these levels can also categorize brain death subjects by mechanism of injury into either CA/RA or FD and DAI.
#9 Brain Death and Its Prediction in Out-of-Hospital Cardiac Arrest Patients Treated with Targeted Temperature Management
https://pmc.ncbi.nlm.nih.gov/articles/PMC9140750/
The primary aim of the current study was to evaluate the process of evolution toward BD in OHCA patients with TTM. […] The secondary aim was to identify prognostic tools related to evolution toward BD. […] The median time to a legal BD diagnosis was 6.0 (IQR, 5.07.0) days. […] Four patients who had PLR at 24 h and 48 h after ROSC finally progressed to BD. […] Among various outcome predictors, early brain CT findings and serial measurement of serum S100B, especially the results at 72 h, had a potential role in the identification of patients who could evolve toward BD. […] Our results revealed that a significant number of BDs can be diagnosed after completing TTM and multimodal prognostication recommended by the CPR guidelines. […] The serum level of S100B at 72 h was abruptly elevated in BD patients, consistent with previous studies reporting that S100B measurements were significantly higher in the group with confirmed BD than in the other group. […] Our study showed that 19 of 121 patients who died before hospital discharge progressed toward BD at a median of 6 days after ROSC and had organs retrieved.
#10 Brain Death and Its Prediction in Out-of-Hospital Cardiac Arrest Patients Treated with Targeted Temperature Management
https://pmc.ncbi.nlm.nih.gov/articles/PMC9140750/
The primary aim of the current study was to evaluate the process of evolution toward BD in OHCA patients with TTM. […] The secondary aim was to identify prognostic tools related to evolution toward BD. […] The median time to a legal BD diagnosis was 6.0 (IQR, 5.07.0) days. […] Four patients who had PLR at 24 h and 48 h after ROSC finally progressed to BD. […] Among various outcome predictors, early brain CT findings and serial measurement of serum S100B, especially the results at 72 h, had a potential role in the identification of patients who could evolve toward BD. […] Our results revealed that a significant number of BDs can be diagnosed after completing TTM and multimodal prognostication recommended by the CPR guidelines. […] The serum level of S100B at 72 h was abruptly elevated in BD patients, consistent with previous studies reporting that S100B measurements were significantly higher in the group with confirmed BD than in the other group. […] Our study showed that 19 of 121 patients who died before hospital discharge progressed toward BD at a median of 6 days after ROSC and had organs retrieved.
#11 Neuroimaging for Coma Outcome Prediction and Determination of Brain Death | SpringerLink
https://link.springer.com/10.1007/978-3-319-61423-6_97-1
Coma and brain death are two related conditions, with devastating consequences for patients and families. […] In patients with possible brain death, the situation is typically more acute in light of potential organ donorship. Here, clinical neuroradiology plays an important role. Standard MR or CT is less relevant, and CT angiography and to a lesser degree MR angiography contribute as ancillary tests to the diagnosis of brain death, although its diagnosis remains clinical. […] Determination of brain death/death by neurologic criteria: the world brain death project. […] Prognostic value of brain diffusion-weighted imaging after cardiac arrest. […] Comatose patients with cardiac arrest: predicting clinical outcome with diffusion-weighted MR imaging.
#12 Predictive Factors of Brain Death in Acute Neurocritical Patients Identified as Potential Organ Donors
https://clinmedjournals.org/articles/ijbdt/international-journal-of-brain-disorders-and-treatment-ijbdt-2-014.php?jid=ijbdt
Reliable prediction of brain death after no-therapy decision in acute neurocritical patients is of specific interest for organ donation after brain death (DBD). […] We aimed to establish a neurological scoring system (the BD-N score) to predict the probability of progression to brain death after spontaneous respiratory arrest. […] Multivariable logistic regression analysis showed that absent pupil reflex (OR = 7.43, 95% CI 1.62-33.99, P = 0.010), anisocoria or bilaterally dilated pupil (OR = 6.25, 95% CI 1.21-32.22, P = 0.028), absent motor response to pain (OR = 15.89, 95% CI 3.04-82.93, P = 0.001), absent cisterna ambiens (OR = 11.96, 95% CI 1.59-89.78, P = 0.016) and present of brain herniation (OR = 16.28, 95% CI 2.25-117.73, P = 0.006) on brain CT imagine were associated with brain death within 7 days.
#13 Predictive Factors of Brain Death in Acute Neurocritical Patients Identified as Potential Organ Donors
https://clinmedjournals.org/articles/ijbdt/international-journal-of-brain-disorders-and-treatment-ijbdt-2-014.php?jid=ijbdt
The BD-N score can be used to predict time of brain death after spontaneous respiratory arrest in acute neurocritical patients. However, further prospective validation is needed. […] We created the BD-N score (Table 4) to predict the chance of brain death within 7 days after spontaneous respiration arrest on the basis of odds ratios for every variable, assigning 1 points for absent pupil light reflex, anisocoria or bilaterally dilated pupil, absent motor response, absent cisterna ambiens and present of brain herniation. […] The probability of BD within 7 days after spontaneous respiration arrest increased as the score increased (Table 5). […] Our study clearly corroborates the validity of cisterna ambiens and brain herniation in its ability to predict early mortality in acute neurocritical patients.
#14 Prognostication after cardiac arrest: how EEG and evoked potentials may improve the challenge | Annals of Intensive Care | Full Text
https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-022-01083-9
The challenge is to identify markers with the highest specificity and the lowest false positive rate (FPR), to minimize the possibility of wrong prediction. […] However, a recent study highlighted that this algorithm allows a classification as poor outcome likely in 32%, the outcome remaining indeterminate in 68%. […] The severity of HIBI is correlated with the predominant frequency and background continuity of EEG leading to highly malignant patterns as suppression or burst suppression in the most severe HIBI. […] Importantly, some brain regions have an increased susceptibility to these different phenomena. In the extreme, all structures can be potentially affected, explaining the very broad spectrum of clinical manifestations described in patients with HIBI, ranging from transient and totally reversible loss of consciousness to unreactive coma, and even brain death.
#15 SSEP N20 and P25 amplitudes predict poor and good neurologic outcomes after cardiac arrest | Annals of Intensive Care | Full Text
https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-022-00999-6
To assess in comatose patients after cardiac arrest (CA) if amplitudes of two somatosensory evoked potentials (SSEP) responses, namely, N20-baseline (N20-b) and N20P25, are predictive of neurological outcome. […] In comatose patient after CA, both N20-b and N20P25 amplitudes could predict both good and poor outcomes with high specificity but low to moderate sensitivity. […] The recommended strategy is to apply a multimodal prognostication approach combining clinical examination, neurophysiological investigations (electroencephalogram (EEG); somatosensory evoked potentials (SSEPs)), biological (Neuron specific enolase, NSE), and neuroradiological (CT scan or MRI) tools. […] Bilateral absence of N20 SSEP responses is one of the most specific elements for poor outcome forecast, reflecting the primary somato-sensory cortex and the thalamo-cortical loop injuries.
#16 SSEP N20 and P25 amplitudes predict poor and good neurologic outcomes after cardiac arrest | Annals of Intensive Care | Full Text
https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-022-00999-6
To assess in comatose patients after cardiac arrest (CA) if amplitudes of two somatosensory evoked potentials (SSEP) responses, namely, N20-baseline (N20-b) and N20P25, are predictive of neurological outcome. […] In comatose patient after CA, both N20-b and N20P25 amplitudes could predict both good and poor outcomes with high specificity but low to moderate sensitivity. […] The recommended strategy is to apply a multimodal prognostication approach combining clinical examination, neurophysiological investigations (electroencephalogram (EEG); somatosensory evoked potentials (SSEPs)), biological (Neuron specific enolase, NSE), and neuroradiological (CT scan or MRI) tools. […] Bilateral absence of N20 SSEP responses is one of the most specific elements for poor outcome forecast, reflecting the primary somato-sensory cortex and the thalamo-cortical loop injuries.
#17 SSEP N20 and P25 amplitudes predict poor and good neurologic outcomes after cardiac arrest | Annals of Intensive Care | Full Text
https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-022-00999-6
In patients still comatose 72 h after CA, we found that the N20-baseline and N20P25 SSEPs amplitudes could be used to predict both good and poor outcome. […] For good outcome prediction, we found that a threshold of N20-baseline2 V and N20P253.2 V recording at 72 h after CA was the best compromise between a high specificity and acceptable sensitivity. […] Regarding poor outcome prediction, a threshold of 0.88 V for N20-baseline and 1 V for N20P25 amplitudes seemed to be the best compromise. […] Our results are in agreement with previous data. […] The prognostic value of high SSEP amplitude for good outcome prediction has been described with different thresholds. […] Our study has several strengths. […] This study also has some limitations. […] Future studies with higher electrode density systems could improve the positive predictive value for good outcome prediction. […] Finally, the association of N20 SSEP amplitudes with other prognostic markers seems to increase specificity while maintaining an acceptable sensitivity, pleading for a multimodal approach for prognostication of comatose patients after CA.
#18 Early prediction model of brain death in out-of-hospital cardiac arrest patients: a single-center retrospective and internal validation analysis | BMC Emergency Medicine | Full Text
https://bmcemergmed.biomedcentral.com/articles/10.1186/s12873-022-00734-1
A shortage of donor organs amid high demand for transplantable organs is a worldwide problem, and an increase in organ donation would be welcomed by the global healthcare system. Patients with brain death (BD) are potential organ donors, and early prediction of patients with BD may facilitate the process of organ procurement. […] We developed and internally validated a new prediction model for BD after OHCA, which could aid in the early identification of potential organ donors for early donor organ procurement. […] Logistic regression analysis confirmed that age, low-flow time, pH, and etiology were independent predictors of BD. […] The developed prediction score (OHCA-BD score) is presented in Table 3. […] Consequently, we created a linearised logarithmic function model using this score.
#19 Early prediction model of brain death in out-of-hospital cardiac arrest patients: a single-center retrospective and internal validation analysis | BMC Emergency Medicine | Full Text
https://bmcemergmed.biomedcentral.com/articles/10.1186/s12873-022-00734-1
The AUROC for this model was 0.831 (95% confidence interval [CI], 0.7860.876). […] This scoring model was evaluated by internal validation and was shown to be a good predictor for BD. […] To increase the rate of organ donation and decide on the clinical course after OHCA, this scoring model may be a useful tool in the early setting after OHCA. […] In conclusion, a new predictive model for BD after OHCA was developed and internally validated. By using this scoring model, patients at high risk of BD after OHCA may be identified at early stages.
#20 Predictive Factors of Brain Death in Acute Neurocritical Patients Identified as Potential Organ Donors
https://clinmedjournals.org/articles/ijbdt/international-journal-of-brain-disorders-and-treatment-ijbdt-2-014.php?jid=ijbdt
The BD-N score can be used to predict time of brain death after spontaneous respiratory arrest in acute neurocritical patients. However, further prospective validation is needed. […] We created the BD-N score (Table 4) to predict the chance of brain death within 7 days after spontaneous respiration arrest on the basis of odds ratios for every variable, assigning 1 points for absent pupil light reflex, anisocoria or bilaterally dilated pupil, absent motor response, absent cisterna ambiens and present of brain herniation. […] The probability of BD within 7 days after spontaneous respiration arrest increased as the score increased (Table 5). […] Our study clearly corroborates the validity of cisterna ambiens and brain herniation in its ability to predict early mortality in acute neurocritical patients.
#21 Digital signatures for early traumatic brain injury outcome prediction in the intensive care unit | Scientific Reports
https://www.nature.com/articles/s41598-021-99397-4
Traumatic brain injury (TBI) is a leading neurological cause of death and disability across the world. Early characterization of TBI severity could provide a window for therapeutic intervention and contribute to improved outcome. […] We demonstrate that information available in the first 24 h of intensive care is predictive of mortality and neurological function at ICU discharge, and that machine learning models can accurately model this relationship. […] These results demonstrate that computational models leveraging clinical and physiological data from the first 24 h of intensive care accurately predict short-term mortality and neurological function in patients admitted to the ICU for management of TBI. […] The performance of our models suggests that these additional features contain predictive information not available in the older prognostic scores.
#22 Digital signatures for early traumatic brain injury outcome prediction in the intensive care unit | Scientific Reports
https://www.nature.com/articles/s41598-021-99397-4
In ICU stratum TBI patients, parsimonious computational models trained with data available in the first 24 h after admission accurately predict ICU discharge mortality and neurological responsiveness. […] Timely characterization of severity and clinical trajectories could open a window for targeted interventions to ameliorate outcomes in patients with moderate and severe TBI.
#23 Prognostication after cardiac arrest | Critical Care | Full Text
https://ccforum.biomedcentral.com/articles/10.1186/s13054-018-2060-7
Hypoxicischaemic brain injury (HIBI) is the main cause of death in patients who are comatose after resuscitation from cardiac arrest. A poor neurological outcome defined as death from neurological cause, persistent vegetative state, or severe neurological disability can be predicted in these patients by assessing the severity of HIBI. […] Current guidelines recommend performing prognostication no earlier than 72 h after return of spontaneous circulation in all comatose patients with an absent or extensor motor response to pain, after having excluded confounders such as residual sedation that may interfere with clinical examination. A multimodal approach combining multiple prognostication tests is recommended so that the risk of a falsely pessimistic prediction is minimised. […] To avoid premature WLST in patients with a chance of neurological recovery, the risk of a falsely pessimistic prediction should be kept to a minimum.
#24 Prognostication after cardiac arrest | Critical Care | Full Text
https://ccforum.biomedcentral.com/articles/10.1186/s13054-018-2060-7
The latest version of the Utstein guidelines on outcome reporting after OHCA suggested that when dichotomising neurological outcome the CPC 35 threshold (or mRS 46) should be used for defining poor outcome. […] The timing of neurological outcome assessment also affects its measured values, since in initially comatose cardiac arrest survivors neurological status can improve for up to 6 months after the event. […] The most robust predictors (FPR5% for prediction of poor outcome with narrow confidence interval documented in 5 studies from at least three different groups of investigators) should be evaluated first. These include bilaterally absent pupillary reflexes at 72 h after ROSC and/or a bilaterally absent N2O SSEP wave after rewarming. […] A multimodal approach combining multiple prognostication tests is recommended by current guidelines so that the risk of a falsely pessimistic prediction is minimised.
#25 Prognostication after cardiac arrest | Critical Care | Full Text
https://ccforum.biomedcentral.com/articles/10.1186/s13054-018-2060-7
The latest version of the Utstein guidelines on outcome reporting after OHCA suggested that when dichotomising neurological outcome the CPC 35 threshold (or mRS 46) should be used for defining poor outcome. […] The timing of neurological outcome assessment also affects its measured values, since in initially comatose cardiac arrest survivors neurological status can improve for up to 6 months after the event. […] The most robust predictors (FPR5% for prediction of poor outcome with narrow confidence interval documented in 5 studies from at least three different groups of investigators) should be evaluated first. These include bilaterally absent pupillary reflexes at 72 h after ROSC and/or a bilaterally absent N2O SSEP wave after rewarming. […] A multimodal approach combining multiple prognostication tests is recommended by current guidelines so that the risk of a falsely pessimistic prediction is minimised.
#26 Neuroprognostication after cardiac arrest – EMCrit Project
https://emcrit.org/ibcc/np/
Prognostic tests often have specific time windows in which they reveal the most information. […] Often, 72 hours post arrest (or post completion of therapeutic hypothermia) will be needed for definitive prognostication. However, malignant EEG patterns may alert the clinician after 24 hours that the patient is unlikely to recover. […] Prognostic tests can be roughly grouped in terms of: Structural tests radiologic tests looking at brain structure. […] Prognostic tests are generally superior, although they may be more susceptible to confounding (e.g., due to medications). […] Absence of a cough reflex (e.g., following endotracheal tube suctioning) after 48 hours was 100% specific for poor neurologic outcome in a few studies. […] Bilateral absence of a cortical signal more than 24 hours after arrest strongly predicts a poor outcome. […] Elevated and rising levels of NSE predict poor outcome. […] Neuroprognostication should be based on combining multiple sources of information. […] When all sources of information are in agreement, this may increase confidence.
#27 SSEP N20 and P25 amplitudes predict poor and good neurologic outcomes after cardiac arrest | Annals of Intensive Care | Full Text
https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-022-00999-6
To assess in comatose patients after cardiac arrest (CA) if amplitudes of two somatosensory evoked potentials (SSEP) responses, namely, N20-baseline (N20-b) and N20P25, are predictive of neurological outcome. […] In comatose patient after CA, both N20-b and N20P25 amplitudes could predict both good and poor outcomes with high specificity but low to moderate sensitivity. […] The recommended strategy is to apply a multimodal prognostication approach combining clinical examination, neurophysiological investigations (electroencephalogram (EEG); somatosensory evoked potentials (SSEPs)), biological (Neuron specific enolase, NSE), and neuroradiological (CT scan or MRI) tools. […] Bilateral absence of N20 SSEP responses is one of the most specific elements for poor outcome forecast, reflecting the primary somato-sensory cortex and the thalamo-cortical loop injuries.
#28 Neuroprognostication after cardiac arrest – EMCrit Project
https://emcrit.org/ibcc/np/
Patients often sustain severe neurologic injury during cardiac arrest. […] Prognostication is extraordinarily important. Excessively pessimistic prognostication could lead to a premature withdrawal of care in a patient with the potential to recover. However, overly optimistic prognostication may lead to ongoing support for days or weeks in a hopeless situation. […] There is no need to wait 72 hours to declare a patient brain dead. Brain death guidelines do recommend waiting 24 hours after arrest to declare brain death. However, if an ancillary test demonstrates lack of blood flow to the brain (cerebral circulatory arrest), then any further waiting may be unnecessary. […] Prognostication can be confounded by any cause of altered mental status. […] In the absence of confounding factors, neurologic function tends to track out along various curves as shown above. As time progresses, it becomes increasingly clear where the patient will end up neurologically.
#29 Prognostication after cardiac arrest | Critical Care | Full Text
https://ccforum.biomedcentral.com/articles/10.1186/s13054-018-2060-7
Hypoxicischaemic brain injury (HIBI) is the main cause of death in patients who are comatose after resuscitation from cardiac arrest. A poor neurological outcome defined as death from neurological cause, persistent vegetative state, or severe neurological disability can be predicted in these patients by assessing the severity of HIBI. […] Current guidelines recommend performing prognostication no earlier than 72 h after return of spontaneous circulation in all comatose patients with an absent or extensor motor response to pain, after having excluded confounders such as residual sedation that may interfere with clinical examination. A multimodal approach combining multiple prognostication tests is recommended so that the risk of a falsely pessimistic prediction is minimised. […] To avoid premature WLST in patients with a chance of neurological recovery, the risk of a falsely pessimistic prediction should be kept to a minimum.
#30 Prognostication after cardiac arrest: how EEG and evoked potentials may improve the challenge | Annals of Intensive Care | Full Text
https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-022-01083-9
The challenge is to identify markers with the highest specificity and the lowest false positive rate (FPR), to minimize the possibility of wrong prediction. […] However, a recent study highlighted that this algorithm allows a classification as poor outcome likely in 32%, the outcome remaining indeterminate in 68%. […] The severity of HIBI is correlated with the predominant frequency and background continuity of EEG leading to highly malignant patterns as suppression or burst suppression in the most severe HIBI. […] Importantly, some brain regions have an increased susceptibility to these different phenomena. In the extreme, all structures can be potentially affected, explaining the very broad spectrum of clinical manifestations described in patients with HIBI, ranging from transient and totally reversible loss of consciousness to unreactive coma, and even brain death.
#31 Neuroprognostication after cardiac arrest – EMCrit Project
https://emcrit.org/ibcc/np/
Patients often sustain severe neurologic injury during cardiac arrest. […] Prognostication is extraordinarily important. Excessively pessimistic prognostication could lead to a premature withdrawal of care in a patient with the potential to recover. However, overly optimistic prognostication may lead to ongoing support for days or weeks in a hopeless situation. […] There is no need to wait 72 hours to declare a patient brain dead. Brain death guidelines do recommend waiting 24 hours after arrest to declare brain death. However, if an ancillary test demonstrates lack of blood flow to the brain (cerebral circulatory arrest), then any further waiting may be unnecessary. […] Prognostication can be confounded by any cause of altered mental status. […] In the absence of confounding factors, neurologic function tends to track out along various curves as shown above. As time progresses, it becomes increasingly clear where the patient will end up neurologically.
#32 Digital signatures for early traumatic brain injury outcome prediction in the intensive care unit | Scientific Reports
https://www.nature.com/articles/s41598-021-99397-4
In ICU stratum TBI patients, parsimonious computational models trained with data available in the first 24 h after admission accurately predict ICU discharge mortality and neurological responsiveness. […] Timely characterization of severity and clinical trajectories could open a window for targeted interventions to ameliorate outcomes in patients with moderate and severe TBI.
#33 Early prediction model of brain death in out-of-hospital cardiac arrest patients: a single-center retrospective and internal validation analysis | BMC Emergency Medicine | Full Text
https://bmcemergmed.biomedcentral.com/articles/10.1186/s12873-022-00734-1
The AUROC for this model was 0.831 (95% confidence interval [CI], 0.7860.876). […] This scoring model was evaluated by internal validation and was shown to be a good predictor for BD. […] To increase the rate of organ donation and decide on the clinical course after OHCA, this scoring model may be a useful tool in the early setting after OHCA. […] In conclusion, a new predictive model for BD after OHCA was developed and internally validated. By using this scoring model, patients at high risk of BD after OHCA may be identified at early stages.
#34 Prognostication after cardiac arrest: how EEG and evoked potentials may improve the challenge | Annals of Intensive Care | Full Text
https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-022-01083-9
About 80% of patients resuscitated from CA are comatose at ICU admission and nearly 50% of survivors are still unawake at 72 h. Predicting neurological outcome of these patients is important to provide correct information to patients relatives, avoid disproportionate care in patients with irreversible hypoxicischemic brain injury (HIBI) and inappropriate withdrawal of care in patients with a possible favorable neurological recovery. […] The crucial question is to know how we could improve the assessment of both unfavorable but also favorable outcome prediction. […] Predicting neurological outcome of these patients is important to provide correct information to the patients relatives, to avoid disproportionate care in patients with irreversible HIBI, and to avoid inappropriate withdrawal of care in patients with a possible favorable neurological recovery.
#35 Brain Death and Its Prediction in Out-of-Hospital Cardiac Arrest Patients Treated with Targeted Temperature Management
https://pmc.ncbi.nlm.nih.gov/articles/PMC9140750/
The primary aim of the current study was to evaluate the process of evolution toward BD in OHCA patients with TTM. […] The secondary aim was to identify prognostic tools related to evolution toward BD. […] The median time to a legal BD diagnosis was 6.0 (IQR, 5.07.0) days. […] Four patients who had PLR at 24 h and 48 h after ROSC finally progressed to BD. […] Among various outcome predictors, early brain CT findings and serial measurement of serum S100B, especially the results at 72 h, had a potential role in the identification of patients who could evolve toward BD. […] Our results revealed that a significant number of BDs can be diagnosed after completing TTM and multimodal prognostication recommended by the CPR guidelines. […] The serum level of S100B at 72 h was abruptly elevated in BD patients, consistent with previous studies reporting that S100B measurements were significantly higher in the group with confirmed BD than in the other group. […] Our study showed that 19 of 121 patients who died before hospital discharge progressed toward BD at a median of 6 days after ROSC and had organs retrieved.
#36 SSEP N20 and P25 amplitudes predict poor and good neurologic outcomes after cardiac arrest | Annals of Intensive Care | Full Text
https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-022-00999-6
In patients still comatose 72 h after CA, we found that the N20-baseline and N20P25 SSEPs amplitudes could be used to predict both good and poor outcome. […] For good outcome prediction, we found that a threshold of N20-baseline2 V and N20P253.2 V recording at 72 h after CA was the best compromise between a high specificity and acceptable sensitivity. […] Regarding poor outcome prediction, a threshold of 0.88 V for N20-baseline and 1 V for N20P25 amplitudes seemed to be the best compromise. […] Our results are in agreement with previous data. […] The prognostic value of high SSEP amplitude for good outcome prediction has been described with different thresholds. […] Our study has several strengths. […] This study also has some limitations. […] Future studies with higher electrode density systems could improve the positive predictive value for good outcome prediction. […] Finally, the association of N20 SSEP amplitudes with other prognostic markers seems to increase specificity while maintaining an acceptable sensitivity, pleading for a multimodal approach for prognostication of comatose patients after CA.
#37 SSEP N20 and P25 amplitudes predict poor and good neurologic outcomes after cardiac arrest | Annals of Intensive Care | Full Text
https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-022-00999-6
In patients still comatose 72 h after CA, we found that the N20-baseline and N20P25 SSEPs amplitudes could be used to predict both good and poor outcome. […] For good outcome prediction, we found that a threshold of N20-baseline2 V and N20P253.2 V recording at 72 h after CA was the best compromise between a high specificity and acceptable sensitivity. […] Regarding poor outcome prediction, a threshold of 0.88 V for N20-baseline and 1 V for N20P25 amplitudes seemed to be the best compromise. […] Our results are in agreement with previous data. […] The prognostic value of high SSEP amplitude for good outcome prediction has been described with different thresholds. […] Our study has several strengths. […] This study also has some limitations. […] Future studies with higher electrode density systems could improve the positive predictive value for good outcome prediction. […] Finally, the association of N20 SSEP amplitudes with other prognostic markers seems to increase specificity while maintaining an acceptable sensitivity, pleading for a multimodal approach for prognostication of comatose patients after CA.
#38 Early prediction model of brain death in out-of-hospital cardiac arrest patients: a single-center retrospective and internal validation analysis | BMC Emergency Medicine | Full Text
https://bmcemergmed.biomedcentral.com/articles/10.1186/s12873-022-00734-1
The AUROC for this model was 0.831 (95% confidence interval [CI], 0.7860.876). […] This scoring model was evaluated by internal validation and was shown to be a good predictor for BD. […] To increase the rate of organ donation and decide on the clinical course after OHCA, this scoring model may be a useful tool in the early setting after OHCA. […] In conclusion, a new predictive model for BD after OHCA was developed and internally validated. By using this scoring model, patients at high risk of BD after OHCA may be identified at early stages.
#39 Predictive Factors of Brain Death in Acute Neurocritical Patients Identified as Potential Organ Donors
https://clinmedjournals.org/articles/ijbdt/international-journal-of-brain-disorders-and-treatment-ijbdt-2-014.php?jid=ijbdt
The BD-N score can be used to predict time of brain death after spontaneous respiratory arrest in acute neurocritical patients. However, further prospective validation is needed. […] We created the BD-N score (Table 4) to predict the chance of brain death within 7 days after spontaneous respiration arrest on the basis of odds ratios for every variable, assigning 1 points for absent pupil light reflex, anisocoria or bilaterally dilated pupil, absent motor response, absent cisterna ambiens and present of brain herniation. […] The probability of BD within 7 days after spontaneous respiration arrest increased as the score increased (Table 5). […] Our study clearly corroborates the validity of cisterna ambiens and brain herniation in its ability to predict early mortality in acute neurocritical patients.