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BACKGROUND: Identifying candidates for extracorporeal cardiopulmonary resuscitation (eCPR) is challenging, and novel predictive markers are urgently needed. Hyperfibrinolysis is linked to tissue hypoxia and is associated with poor outcomes in out-of-hospital cardiac arrest (OHCA). Rotational thromboelastometry (ROTEM) can detect or rule out hyperfibrinolysis, and could, therefore, provide decision support for initiation of eCPR. We explored early detection of hyperfibrinolysis in patients with refractory OHCA referred for eCPR. METHODS: We analysed ROTEM results and resuscitation parameters of 57 adult patients with ongoing OHCA who presented to our ICU for eCPR evaluation. RESULTS: Hyperfibrinolysis, defined as maximum lysis ≥15%, was present in 36 patients (63%) and was associated with higher serum lactate, lower arterial blood pH, and increased low-flow intervals. Of 42 patients who achieved return of circulation, 28 had a poor 30-day outcome. The incidence of hyperfibrinolysis was higher in the poor outcome group compared with patients with good outcomes (75% [21 of 28] vs 7.1% [1 of 14]; P<0.001). The ratio of EXTEM A5 to lactate concentration showed good predictive value in detecting hyperfibrinolysis (AUC of 0.89 [95% confidence interval 0.8-1]). CONCLUSIONS: Hyperfibrinolysis was common in patients with refractory cardiac arrest, and was associated with poor prognosis. The combination of high lactate with early clot firmness values, such as EXTEM A5, appears promising for early detection of hyperfibrinolysis. This finding could facilitate decisions to perform eCPR, particularly for patients with prolonged low-flow duration but lacking hyperfibrinolysis.
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Reanimação Cardiopulmonar , Fibrinólise , Parada Cardíaca Extra-Hospitalar , Tromboelastografia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Tromboelastografia/métodos , Reanimação Cardiopulmonar/métodos , Prognóstico , Idoso , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/sangue , Parada Cardíaca Extra-Hospitalar/complicações , Fibrinólise/fisiologia , Oxigenação por Membrana Extracorpórea/métodos , Adulto , Ácido Láctico/sangue , Estudos RetrospectivosRESUMO
Background: This study investigates the association between the mean arterial blood pressure (MAP), vasopressor requirement, and severity of hypoxic-ischemic encephalopathy (HIE) after cardiac arrest (CA). Methods: Between 2008 and 2017, we retrospectively analyzed the MAP 200â h after CA and quantified the vasopressor requirements using the cumulative vasopressor index (CVI). Through a postmortem brain autopsy in non-survivors, the severity of the HIE was histopathologically dichotomized into no/mild and severe HIE. In survivors, we dichotomized the severity of HIE into no/mild cerebral performance category (CPC) 1 and severe HIE (CPC 4). We investigated the regain of consciousness, causes of death, and 5-day survival as hemodynamic confounders. Results: Among the 350 non-survivors, 117 had histopathologically severe HIE while 233 had no/mild HIE, without differences observed in the MAP (73.1 vs. 72.0â mmHg, pgroup = 0.639). Compared to the non-survivors, 211 patients with CPC 1 and 57 patients with CPC 4 had higher MAP values that showed significant, but clinically non-relevant, MAP differences (81.2 vs. 82.3â mmHg, pgroup < 0.001). The no/mild HIE non-survivors (n = 54), who regained consciousness before death, had higher MAP values compared to those with no/mild HIE (n = 179), who remained persistently comatose (74.7 vs. 69.3â mmHg, pgroup < 0.001). The no/mild HIE non-survivors, who regained consciousness, required fewer vasopressors (CVI 2.1 vs. 3.6, pgroup < 0.001). Independent of the severity of HIE, the survivors were weaned faster from vasopressors (CVI 1.0). Conclusions: Although a higher MAP was associated with survival in CA patients treated with a vasopressor-supported MAP target above 65â mmHg, the severity of HIE was not. Awakening from coma was associated with less vasopressor requirements. Our results provide no evidence for a MAP target above the current guideline recommendations that can decrease the severity of HIE.
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BACKGROUND: Selective water uptake by neurons and glial cells and subsequent brain tissue oedema are key pathophysiological processes of hypoxic-ischemic encephalopathy (HIE) after cardiac arrest (CA). Although brain computed tomography (CT) is widely used to assess the severity of HIE, changes of brain radiodensity over time have not been investigated. These could be used to quantify regional brain net water uptake (NWU), a potential prognostic biomarker. METHODS: We conducted an observational prognostic accuracy study including a derivation (single center cardiac arrest registry) and a validation (international multicenter TTM2 trial) cohort. Early (<6 h) and follow-up (>24 h) head CTs of CA patients were used to determine regional NWU for grey and white matter regions after co-registration with a brain atlas. Neurological outcome was dichotomized as good versus poor using the Cerebral Performance Category Scale (CPC) in the derivation cohort and Modified Rankin Scale (mRS) in the validation cohort. RESULTS: We included 115 patients (81 derivation, 34 validation) with out-of-hospital (OHCA) and in-hospital cardiac arrest (IHCA). Regional brain water content remained unchanged in patients with good outcome. In patients with poor neurological outcome, we found considerable regional water uptake with the strongest effect in the basal ganglia. NWU >8% in the putamen and caudate nucleus predicted poor outcome with 100% specificity (95%-CI: 86-100%) and 43% (moderate) sensitivity (95%-CI: 31-56%). CONCLUSION: This pilot study indicates that NWU derived from serial head CTs is a promising novel biomarker for outcome prediction after CA. NWU >8% in basal ganglia grey matter regions predicted poor outcome while absence of NWU indicated good outcome. NWU and follow-up CTs should be investigated in larger, prospective trials with standardized CT acquisition protocols.
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Biomarcadores , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Idoso , Prognóstico , Biomarcadores/metabolismo , Biomarcadores/análise , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/diagnóstico por imagem , Parada Cardíaca/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Hipóxia-Isquemia Encefálica/metabolismo , Edema Encefálico/etiologia , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/metabolismo , Sistema de RegistrosRESUMO
Objective: To establish a deep learning model for the detection of hypoxic-ischemic encephalopathy (HIE) features on CT scans and to compare various networks to determine the best input data format. Methods: 168 head CT scans of patients after cardiac arrest were retrospectively identified and classified into two categories: 88 (52.4%) with radiological evidence of severe HIE and 80 (47.6%) without signs of HIE. These images were randomly divided into a training and a test set, and five deep learning models based on based on Densely Connected Convolutional Networks (DenseNet121) were trained and validated using different image input formats (2D and 3D images). Results: All optimized stacked 2D and 3D networks could detect signs of HIE. The networks based on the data as 2D image data stacks provided the best results (S100: AUC: 94%, ACC: 79%, S50: AUC: 93%, ACC: 79%). We provide visual explainability data for the decision making of our AI model using Gradient-weighted Class Activation Mapping. Conclusion: Our proof-of-concept deep learning model can accurately identify signs of HIE on CT images. Comparing different 2D- and 3D-based approaches, most promising results were achieved by 2D image stack models. After further clinical validation, a deep learning model of HIE detection based on CT images could be implemented in clinical routine and thus aid clinicians in characterizing imaging data and predicting outcome.
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AIM: To evaluate neuron-specific enolase (NSE) thresholds for prediction of neurological outcome after cardiac arrest and to analyze the influence of hemolysis and confounders. METHODS: Retrospective analysis from a cardiac arrest registry. Determination of NSE serum concentration and hemolysis-index (h-index) 48-96 hours after cardiac arrest. Evaluation of neurological outcome using the Cerebral Performance Category score (CPC) at hospital discharge. Separate analyses considering CPC 1-3 and CPC 1-2 as good neurological outcome. Analysis of specificity and sensitivity for poor and good neurological outcome prediction with and without exclusion of hemolytic samples (h-index larger than 50). RESULTS: Among 356 survivors three days after cardiac arrest, hemolysis was detected in 28 samples (7.9%). At a threshold of 60 µg/L, NSE predicted poor neurological outcome (CPC 4-5) in all samples with a specificity of 92% (86-95%) and sensitivity of 73% (66-79%). In non-hemolytic samples, specificity was 94% (89-97%) and sensitivity 70% (62-76%). At a threshold of 100 µg/L, specificity was 98% (95-100%, all samples) and 99% (95-100%, non-hemolytic samples), and sensitivity 58% (51-65%) and 55% (47-63%), respectively. Possible confounders for elevated NSE in patients with good neurological outcome were ECMO, malignancies, blood transfusions and acute brain diseases. Nine patients with NSE below 17 µg/L had CPC 5, all had plausible death causes other than hypoxic-ischemic encephalopathy. CONCLUSIONS: NSE concentrations higher than 100 µg/L predicted poor neurological outcome with high specificity. An NSE less than 17 µg/L indicated absence of severe hypoxic-ischemic encephalopathy. Hemolysis and other confounders need to be considered. INSTITUTIONAL PROTOCOL NUMBER: The local ethics committee (board name: Ethikkommission der Charité) approved this study by the number: EA2/066/23, approval date: 28th June 2023, study title "'ROSC' - Resuscitation Outcome Study."
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Parada Cardíaca , Hipóxia-Isquemia Encefálica , Parada Cardíaca Extra-Hospitalar , Humanos , Biomarcadores , Parada Cardíaca/terapia , Hemólise , Parada Cardíaca Extra-Hospitalar/terapia , Fosfopiruvato Hidratase , Prognóstico , Estudos Prospectivos , Estudos RetrospectivosRESUMO
OBJECTIVE: Bilaterally absent cortical somatosensory evoked potentials (SSEPs) reliably predict poor outcome in comatose cardiac arrest (CA) patients. Cortical SSEP amplitudes are a recent prognostic extension; however, amplitude thresholds, inter-recording, and inter-rater agreement remain uncertain. METHODS: In a retrospective multicenter cohort study, we determined cortical SSEP amplitudes of comatose CA patients using a standardized evaluation pathway. We studied inter-recording agreement in repeated SSEPs and inter-rater agreement by four raters independently determining 100 cortical SSEP amplitudes. Primary outcome was assessed using the cerebral performance category (CPC) upon intensive care unit discharge dichotomized into good (CPC 1-3) and poor outcome (CPC 4-5). RESULTS: Of 706 patients with SSEPs with median 3 days after CA, 277 (39.2%) had good and 429 (60.8%) poor outcome. Of patients with bilaterally absent cortical SSEPs, one (0.8%) survived with CPC 3 and 130 (99.2%) had poor outcome. Otherwise, the lowest cortical SSEP amplitude in good outcome patients was 0.5 µV. 184 (42.9%) of 429 poor outcome patients had lower cortical SSEP amplitudes. In 106 repeated SSEPs, there were 6 (5.7%) with prognostication-relevant changes in SSEP categories. Following a standardized evaluation pathway, inter-rater agreement was almost perfect with a Fleiss' kappa of 0.88. INTERPRETATION: Bilaterally absent and cortical SSEP amplitudes below 0.5 µV predicted poor outcome with high specificity. A standardized evaluation pathway provided high inter-rater and inter-recording agreement. Regain of consciousness in patients with bilaterally absent cortical SSEPs rarely occurs. High-amplitude cortical SSEP amplitudes likely indicate the absence of severe brain injury.
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Coma , Parada Cardíaca , Humanos , Estudos de Coortes , Coma/diagnóstico , Coma/etiologia , Parada Cardíaca/complicações , Estudos Retrospectivos , Potenciais Somatossensoriais Evocados/fisiologia , PrognósticoRESUMO
OBJECTIVES: This study aims to describe physicians' perspectives on the use of computed tomography (CT) in patients with sepsis. METHODS: In January 2022, physicians of a large European university medical center were surveyed using a web-based questionnaire asking about their views on the role of CT in sepsis. A total of 371 questionnaires met the inclusion criteria and were analyzed using work experience, workplace, and medical specialty of physicians as variables. Chi-square tests were performed. RESULTS: Physicians considered the ability to detect an unknown focus as the greatest benefit of CT scans in sepsis (70.9%, n = 263/371). Two clinical criteria - "signs of decreased vigilance" (89.2%, n = 331/371) and "increased catecholamine demand" (84.7%, n = 314/371) - were considered highly relevant for a CT request. Elevated procalcitonin (82.7%, n = 307/371) and lactate levels (83.6%, n = 310/371) were consistently found to be critical laboratory values to request a CT. As long as there is evidence of infection in one organ region, most physicians (42.6%, n = 158/371) would order a CT scan based on clinical assessment. Combined examination of the chest, abdomen, and pelvis was favored (34.8%, n = 129/371) in cases without clinical clues of an infection source. A time window of ≥ 1-6 h was preferred for both CT examinations (53.9%, n = 200/371) and CT-guided interventions (59.3%, n = 220/371) in patients with sepsis. CONCLUSION: Despite much consensus, there are significant differences in attitudes towards the use of CT in septic patients among physicians from different workplaces and medical specialties. Knowledge of these perspectives may improve patient management and interprofessional communication. KEY POINTS: Despite interdisciplinary consensus on the use of CT in sepsis, statistically significant differences in the responses are apparent among physicians from different workplaces and medical specialties. The detection of a previously unknown source of infection and the ability to plan interventions and/or surgery based on CT findings are considered key advantages of CT in septic patients. Timing of CT reflects the requirements of specific disciplines.
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Médicos , Sepse , Humanos , Sepse/diagnóstico por imagem , Sepse/etiologia , Centros Médicos Acadêmicos , Tomografia Computadorizada por Raios X , Inquéritos e QuestionáriosRESUMO
PURPOSE: Chronic obstructive pulmonary disease (COPD) is a risk factor for acquiring multiple drug resistant bacteria. The main objective of this analysis was to question a beneficial outcome in the routine use of antipseudomonal antibiotics in the empiric treatment of severe AECOPD in Intensive Care Unit patients. MATERIAL AND METHODS: We report a retrospective, observational cohort study in adult patients with severe AECOPD admitted to ICU at a tertiary care university hospital. Antibiotic treatment on admission as well as microbiology samples were analyzed. The influence of SOFA score at admission, age, sex and antibiotic choice upon survival was investigated by multivariable analysis. RESULTS: 437 patients were included. Mean age was 68 years (±10), 46.5% were female. 271/437 patients (62%) were initially treated with antibiotics covering Pseudomonas aeruginosa. Overall, positive microbiology samples were found in 107 patients (24.5%). P. aeruginosa was only found in 3.7%. There was no significant difference in 30-day ICU mortality after adjusting for age, sex and severity of illness (20.4% ± 11.6 in patients with Pseudomonas inactive antibiotics versus 29.3% ± 10.8 in patients with PAA, p=0.113). CONCLUSIONS: Empiric use of antipseudomonal antibiotics did not result in improved ICU survival in this retrospective analysis.
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Antibacterianos , Doença Pulmonar Obstrutiva Crônica , Adulto , Idoso , Antibacterianos/uso terapêutico , Feminino , Humanos , Unidades de Terapia Intensiva , Pseudomonas aeruginosa , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Estudos RetrospectivosRESUMO
Drugs intoxications often lead to severe vasoplegia and cardiogenic shock, and VA-ECMO represents a viable therapy option. However, as cardiopulmonary support is not contributing to the removal of the causal agent from the blood, detoxification by a new hemoadsorption device (CytoSorb) could represent a potential therapeutic tool due to its highly efficient elimination capacity of endogenous but also exogenous hydrophobic substances for which otherwise no effective antidote exist. In this case series, four anecdotal cases of acute intoxications requiring VA-ECMO support used as extracorporeal cardiopulmonary resuscitation after intoxication-induced out-of-hospital cardiac arrest (OHCA) are presented, who were additionally treated with CytoSorb hemoadsorption in combination with renal replacement therapy. Combined treatment was associated with a considerable decrease in plasma levels of the overdosed drugs. Additionally, the combination of applied techniques was safe, practical, and technically feasible with no adverse or any device-related side effects documented during or after the treatment sessions. Based on the reported dramatic decline in drug levels during treatment, that fits in the device's characteristics, we strongly suggest to further investigate the potentially lifesaving role of CytoSorb therapy in patients with acute intoxications requiring multiple organ support techniques.
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Reanimação Cardiopulmonar , Oxigenação por Membrana Extracorpórea , Terapia Combinada , Oxigenação por Membrana Extracorpórea/efeitos adversos , Humanos , Choque Cardiogênico/induzido quimicamente , Choque Cardiogênico/terapiaRESUMO
OBJECTIVE: Optimal management of out of hospital circulatory arrest (OHCA) remains challenging, in particular in patients who do not develop rapid return of spontaneous circulation (ROSC). Extracorporeal cardiopulmonary resuscitation (eCPR) can be a life-saving bridging procedure. However its requirements and feasibility of implementation in patients with OHCA, appropriate inclusion criteria and achievable outcomes remain poorly defined. DESIGN: Prospective cohort study. SETTING: Tertiary referral university hospital center. PATIENTS: Here we report on characteristics, course and outcomes on the first consecutive 254 patients admitted between August 2014 and December 2017. INTERVENTION: eCPR program for OHCA. MESUREMENTS AND MAIN RESULTS: A structured clinical pathway was designed and implemented as 24/7 eCPR service at the Charité in Berlin. In total, 254 patients were transferred with ongoing CPR, including automated chest compression, of which 30 showed or developed ROSC after admission. Following hospital admission predefined in- and exclusion criteria for eCPR were checked; in the remaining 224, 126 were considered as eligible for eCPR. State of the art postresuscitation therapy was applied and prognostication of neurological outcome was performed according to a standardized protocol. Eighteen patients survived, with a good neurological outcome (cerebral performance category (CPC) 1 or 2) in 15 patients. Compared to non-survivors survivors had significantly shorter time between collaps and start of eCPR (58 min (IQR 12-85) vs. 90 min (IQR 74-114), p = 0.01), lower lactate levels on admission (95 mg/dL (IQR 44-130) vs. 143 mg/dL (IQR 111-178), p < 0.05), and less severe acidosis on admission (pH 7.2 (IQR 7.15-7.4) vs. 7.0 (IQR6.9-7.2), p < 0.05). Binary logistic regression analysis identified latency to eCPR and low pH as independent predictors for mortality. CONCLUSION: An eCPR program can be life-saving for a subset of individuals with refractory circulatory arrest, with time to initiation of eCPR being a main determinant of survival.
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Reanimação Cardiopulmonar/métodos , Oxigenação por Membrana Extracorpórea , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/terapia , Acidose/complicações , Adulto , Idoso , Berlim/epidemiologia , Estudos de Coortes , Procedimentos Clínicos , Feminino , Humanos , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Tempo para o TratamentoRESUMO
BACKGROUND: Comatose patients admitted after out-of-hospital cardiac arrest frequently experience haemodynamic instability and anoxic brain injury. Targeted temperature management is used for neuroprotection; however, targeted temperature management also affects patients' haemodynamic status. This study assessed the haemodynamic status of out-of-hospital cardiac arrest survivors during prolonged (48 hours) targeted temperature management at 33°C. METHODS: Analysis of haemodynamic and vasopressor data from 311 patients included in a randomised, clinical trial conducted in 10 European hospitals (the TTH48 trial). Patients were randomly allocated to targeted temperature management at 33°C for 24 (TTM24) or 48 (TTM48) hours. Vasopressor and haemodynamic data were reported hourly for 72 hours after admission. Vasopressor load was calculated as norepinephrine (µg/kg/min) plus dopamine(µg/kg/min/100) plus epinephrine (µg/kg/min). RESULTS: After 24 hours, mean arterial pressure (mean±SD) was 74±9 versus 75±9 mmHg (P=0.19), heart rate was 57±16 and 55±14 beats/min (P=0.18), vasopressor load was 0.06 (0.03-0.15) versus 0.08 (0.03-0.15) µg/kg/min (P=0.22) for the TTM24 and TTM48 groups, respectively. From 24 to 48 hours, there was no difference in mean arterial pressure (Pgroup=0.32) or lactate (Pgroup=0.20), while heart rate was significantly lower (average difference 5 (95% confidence interval 2-8) beats/min, Pgroup<0.0001) and vasopressor load was significantly higher in the TTM48 group (Pgroup=0.005). In a univariate Cox regression model, high vasopressor load was associated with mortality in univariate analysis (hazard ratio 1.59 (1.05-2.42) P=0.03), but not in multivariate analysis (hazard ratio 0.77 (0.46-1.29) P=0.33). CONCLUSIONS: In this study, prolonged targeted temperature management at 33°C for 48 hours was associated with higher vasopressor requirement but no sign of any detrimental haemodynamic effects.
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BACKGROUND: Comatose patients admitted after out-of-hospital cardiac arrest frequently experience haemodynamic instability and anoxic brain injury. Targeted temperature management is used for neuroprotection; however, targeted temperature management also affects patients' haemodynamic status. This study assessed the haemodynamic status of out-of-hospital cardiac arrest survivors during prolonged (48 hours) targeted temperature management at 33°C. METHODS: Analysis of haemodynamic and vasopressor data from 311 patients included in a randomised, clinical trial conducted in 10 European hospitals (the TTH48 trial). Patients were randomly allocated to targeted temperature management at 33°C for 24 (TTM24) or 48 (TTM48) hours. Vasopressor and haemodynamic data were reported hourly for 72 hours after admission. Vasopressor load was calculated as norepinephrine (µg/kg/min) plus dopamine(µg/kg/min/100) plus epinephrine (µg/kg/min). RESULTS: After 24 hours, mean arterial pressure (mean±SD) was 74±9 versus 75±9 mmHg (P=0.19), heart rate was 57±16 and 55±14 beats/min (P=0.18), vasopressor load was 0.06 (0.03-0.15) versus 0.08 (0.03-0.15) µg/kg/min (P=0.22) for the TTM24 and TTM48 groups, respectively. From 24 to 48 hours, there was no difference in mean arterial pressure (Pgroup=0.32) or lactate (Pgroup=0.20), while heart rate was significantly lower (average difference 5 (95% confidence interval 2-8) beats/min, Pgroup<0.0001) and vasopressor load was significantly higher in the TTM48 group (Pgroup=0.005). In a univariate Cox regression model, high vasopressor load was associated with mortality in univariate analysis (hazard ratio 1.59 (1.05-2.42) P=0.03), but not in multivariate analysis (hazard ratio 0.77 (0.46-1.29) P=0.33). CONCLUSIONS: In this study, prolonged targeted temperature management at 33°C for 48 hours was associated with higher vasopressor requirement but no sign of any detrimental haemodynamic effects.
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BACKGROUND: Transiently increased transaminases is a common finding after cardiac arrest but little is known about the functional liver capacity (LiMAx) during the post-cardiac arrest syndrome and treatment in the intensive care unit (ICU). The aim of this trial was to evaluate liver function capacity in post-cardiac arrest survivors undergoing targeted temperature management (TTM) in ICU. METHODS: Thirty-two post-cardiac arrest survivors were prospectively included with all patients undergoing TTM at 33°C for 24 hours. Blood samples were collected, and LiMAx testing was performed at days 1, 2, 5, and 10 post-cardiac arrest. LiMAx is a non-invasive, in vivo, dynamic breath test determining cytochrome P450 1A2 (CYP1A2) capacity using intravenous (IV) 13 C-methacetin, thus reflecting maximum liver function capacity. Static liver parameters were determined and compared to LiMAx values. RESULTS: A typical pattern of transiently, mildly increased transaminases was demonstrated without fulfilling the criteria for hypoxic hepatitis (HH). CYP1A2 activity was reduced with slow normalization over 10 days (lowest median 48 hours after cardiac arrest: 228.5 (25-75 percentile 105.2-301.7 µg/kg/h, P < .05). Parameters reflecting the liver synthetic function were not impaired, as assessed by, in standard laboratory testing. CONCLUSION: Liver functional capacity is impaired in patients after cardiac arrest undergoing TTM at 33°C. More data are needed to determine if liver functional capacity may add relevant information, especially in the context of pharmacotherapy, to individualize post-cardiac arrest care.
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Acetamidas/metabolismo , Testes Respiratórios/métodos , Parada Cardíaca/fisiopatologia , Parada Cardíaca/terapia , Hipotermia Induzida/métodos , Fígado/fisiopatologia , Idoso , Feminino , Humanos , Testes de Função Hepática/métodos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos ProspectivosRESUMO
AIM: Glutamine and glutamate are major mediators of secondary brain cell death during post-cardiac arrest syndrome. As there is an equilibrium between brain tissue and plasma concentrations of glutamine and glutamate, their elimination from systemic circulation by extracorporeal blood purification may ultimately lead to reduced secondary cell death in the brain. We hypothesized that systemic glutamine and glutamate can be significantly reduced by continuous venovenous hemodiafiltration (CVVHDF). METHODS: This was a prospective, randomized clinical trial in post cardiac-arrest survivors evaluating standard of care or additional CVVHDF over 72â¯h immediately after admission. Glutamine and glutamate plasma concentrations were analyzed at eight time points in both groups. Primary endpoint was reduction of glutamine and glutamate plasma concentrations. The trial has been registered at clinical trial.gov (NCT02963298). RESULTS: In total, 41 patients were randomized over a period of 12â¯months (control nâ¯=â¯21, CVVHDF nâ¯=â¯20). The primary aim reduction of glutamine and glutamate plasma concentrations by CVVHDF, was not achieved; both groups-maintained concentrations within a normal range over the study period (glutamate: 4.7-11.1â¯mg/dL; glutamine: 0.2-3.7â¯mg/dL). However, post-filter concentrations of glutamine and glutamate in CRRT patients were significantly decreased as compared to pre-filter concentrations (glutamate: pre-filter median 8.85â¯mg/dL IQR 7.1-9.6; post-filter 0.95â¯mg/dL IQR 0.5-2; pâ¯<â¯0.001; glutamine: pre-filter 0.7â¯mg/dL IQR 0.6-1; post-filter 0.2â¯mg/dL IQR 0-0.2; pâ¯<â¯0.001). CONCLUSION: In this trial, CVVHDF was not able to statistically significantly lower systemic plasma glutamine and glutamate levels. Post-cardiac arrest patients had plasma glutamine and glutamate levels within the normal range.
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Terapia de Substituição Renal Contínua , Ácido Glutâmico/sangue , Glutamina/sangue , Síndrome Pós-Parada Cardíaca/sangue , Síndrome Pós-Parada Cardíaca/terapia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Síndrome Pós-Parada Cardíaca/mortalidade , Estudos Prospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The aim of this study was to explore the performance and outcomes for intravascular (IC) versus surface cooling devices (SFC) for targeted temperature management (TTM) after out-of-hospital cardiac arrest. METHODS: A retrospective analysis of data from the Time-differentiated Therapeutic Hypothermia (TTH48) trial (NCT01689077), which compared whether TTM at 33 °C for 48 h results in better neurologic outcomes compared with standard 24-h duration. Devices were assessed for the speed of cooling and rewarming rates. Precision was assessed by measuring temperature variability (TV), i.e., the standard deviation (SD) of all temperature measurements in the cooling phase. Main outcomes were overall mortality and poor neurological outcome, including death, severe disability, or vegetative status. RESULTS: A total of 352 patients had available data and were included in the analysis; of those, 218 (62%) were managed with IC. A total of 114/218 (53%) patients with IC and 61/134 (43%) with SFC were cooled for 48 h (p = 0.22). Time to target temperature (≤ 34 °C) was significantly shorter for patients treated with endovascular devices (2.2 [1.1-4.0] vs. 4.2 [2.7-6.0] h, p < 0.001), but temperature was also lower on admission (35.0 [34.2-35.6] vs. 35.3 [34.5-35.8]°C; p = 0.02) and cooling rate was similar (0.4 [0.2-0.8] vs. 0.4 [0.2-0.6]°C/h; p = 0.14) when compared to SFC. Temperature variability was significantly lower in the endovascular device group when compared with SFC methods (0.6 [0.4-0.9] vs. 0.7 [0.5-1.0]°C; p = 0.007), as was rewarming rate (0.31 [0.22-0.44] vs. 0.37 [0.29-0.49]°C/hour; p = 0.02). There was no statistically significant difference in mortality (endovascular 65/218, 29% vs. others 43/134, 32%; p = 0.72) or poor neurological outcome (endovascular 69/218, 32% vs. others 51/134, 38%; p = 0.24) between type of devices. CONCLUSIONS: Endovascular cooling devices were more precise than SFC methods in patients cooled at 33 °C after out-of-hospital cardiac arrest. Main outcomes were similar with regard to the cooling methods.
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Hipotermia Induzida/métodos , Parada Cardíaca Extra-Hospitalar/terapia , Idoso , Análise de Variância , Superfície Corporal , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/normas , Feminino , Humanos , Hipotermia Induzida/normas , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the clinical course and early prognostic markers in cardiac arrest (CA) patients discharged from the intensive care unit (ICU) in an unresponsive wakefulness syndrome (UWS) or coma. METHODS: 89 patients were identified from a prospective CA database. Follow-up was conducted by telephone interviews with legal guardians, evaluation of re-admission and rehabilitation reports assessing core elements of the coma recovery scale-revised (CRS-R). Somatosensory evoked potential (SSEP) and electroencephalography (EEG) original recordings were re-analyzed, the gray-white-matter ratio (GWR) was determined from brain computed tomography (CT) and neuron-specific enolase (NSE) serum concentrations were retrieved. RESULTS: Follow-up was successful for 32/50 (64%) patients admitted between 2001-2009 and 31/39 (79%) between 2009-2015. Median ICU stay was 27 days (IQR 20-36). Neurological improvement beyond UWS was found in 2 of 63 patients. Among 61 patients with successful follow-up and no improvement, NSE serum concentrations within the reference range, SSEP amplitudes above 2.5⯵V or continuous reactive EEG were found in 5%, 3% and 2% of those tested. NSEâ¯>â¯90⯵g/L, SSEPâ¯≤â¯0.3⯵V, highly malignant EEG or GWRâ¯<â¯1.10 were found in 44%, 49%, 35% and 22% of those tested. CONCLUSIONS: Neurological recovery was rare in CA patients discharged in UWS after prolonged ICU treatment. Status epilepticus requiring prolonged deep sedation is one potential reason for delayed awakening. Sensitivity for established poor outcome parameters to predict persistent UWS early after CA was moderate. SSEP, EEG and NSE may indicate absence of severe HIE early after CA.