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Cardiac arrest survivors suffer the repercussions of anoxic brain injury, a critical factor influencing long-term prognosis. This injury is characterised by profound and enduring metabolic impairment. Ketone bodies, an alternative energetic resource in physiological states such as exercise, fasting, and extended starvation, are avidly taken up and used by the brain. Both the ketogenic diet and exogenous ketone supplementation have been associated with neuroprotective effects across a spectrum of conditions. These include refractory epilepsy, neurodegenerative disorders, cognitive impairment, focal cerebral ischemia, and traumatic brain injuries. Beyond this, ketone bodies possess a plethora of attributes that appear to be particularly favourable after cardiac arrest. These encompass anti-inflammatory effects, the attenuation of oxidative stress, the improvement of mitochondrial function, a glucose-sparing effect, and the enhancement of cardiac function. The aim of this manuscript is to appraise pertinent scientific literature on the topic through a narrative review. We aim to encapsulate the existing evidence and underscore the potential therapeutic value of ketone bodies in the context of cardiac arrest to provide a rationale for their use in forthcoming translational research efforts.
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Parada Cardíaca , Corpos Cetônicos , Corpos Cetônicos/metabolismo , Humanos , Parada Cardíaca/metabolismo , Animais , Dieta CetogênicaRESUMO
BACKGROUND: Nociceptive assessment in deeply sedated patients is challenging. Validated instruments are lacking for this unresponsive population. Videopupillometry is a promising tool but has not been established in intensive care settings. AIM/OBJECTIVE: To test the discriminate validity of pupillary dilation reflex (PDR) between non-noxious and noxious procedures for assessing nociception in non-neurological intensive care unit (ICU) patients and to test the criterion validity of pupil dilation using recommended PDR cut-off points to determine nociception. METHODS: A single-centre prospective observational study was conducted in medical-surgical ICU patients. Two independent investigators performed videopupillometer measurements during a non-noxious and a noxious procedure, once a day (up to 7 days), when the patient remained deeply sedated (Richmond Agitation-Sedation Scale score: -5 or -4). The non-noxious procedures consisted of a gentle touch on each shoulder and the noxious procedures were endotracheal suctioning or turning onto the side. Bivariable and multivariable general linear mixed models were used to account for multiple measurements in same patients. Sensitivity and specificity, and areas under the curve of the receiver operating characteristic curve were calculated. RESULTS: Sixty patients were included, and 305 sets of 3 measurements (before, during, and after), were performed. PDR was higher during noxious procedures than before (mean difference between noxious and non-noxious procedures = 31.66%). After testing all variables of patient and stimulation characteristics in bivariable models, age and noxious procedures were kept in the multivariable model. Adjusting for age, noxious procedures (coefficient = -15.14 (95% confidence interval = -20.17 to -15.52, p < 0.001) remained the only predictive factor for higher pupil change. Testing recommended cut-offs, a PDR of >12% showed a sensitivity of 65%, and a specificity of 94% for nociception prediction, with an area under the receiver operating curve of 0.828 (95% confidence interval = 0.779-0.877). CONCLUSIONS: In conclusion, PDR is a potentially appropriate measure to assess nociception in deeply sedated ICU patients, and we suggest considering its utility in daily practices. REGISTRATION: This study was not preregistered in a clinical registry. TWEETABLE ABSTRACT: Pupillometry may help clinicians to assess nociception in deeply sedated ICU patients.
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Cuidados Críticos , Nociceptividade , Humanos , Medição da Dor/métodos , Reflexo Pupilar/fisiologia , Pupila/fisiologia , Unidades de Terapia IntensivaRESUMO
BACKGROUND: Traumatic brain injury (TBI) is associated with the tauopathies Alzheimer's disease and chronic traumatic encephalopathy. Advanced immunoassays show significant elevations in plasma total tau (t-tau) early post-TBI, but concentrations subsequently normalise rapidly. Tau phosphorylated at serine-181 (p-tau181) is a well-validated Alzheimer's disease marker that could potentially seed progressive neurodegeneration. We tested whether post-traumatic p-tau181 concentrations are elevated and relate to progressive brain atrophy. METHODS: Plasma p-tau181 and other post-traumatic biomarkers, including total-tau (t-tau), neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), were assessed after moderate-to-severe TBI in the BIO-AX-TBI cohort (first sample mean 2.7 days, second sample within 10 days, then 6 weeks, 6 months and 12 months, n=42). Brain atrophy rates were assessed in aligned serial MRI (n=40). Concentrations were compared patients with and without Alzheimer's disease, with healthy controls. RESULTS: Plasma p-tau181 concentrations were significantly raised in patients with Alzheimer's disease but not after TBI, where concentrations were non-elevated, and remained stable over one year. P-tau181 after TBI was not predictive of brain atrophy rates in either grey or white matter. In contrast, substantial trauma-associated elevations in t-tau, NfL, GFAP and UCH-L1 were seen, with concentrations of NfL and t-tau predictive of brain atrophy rates. CONCLUSIONS: Plasma p-tau181 is not significantly elevated during the first year after moderate-to-severe TBI and levels do not relate to neuroimaging measures of neurodegeneration.
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Doença de Alzheimer , Lesões Encefálicas Traumáticas , Encefalopatia Traumática Crônica , Humanos , Biomarcadores , Proteínas tau , Imageamento por Ressonância Magnética , Ubiquitina Tiolesterase , Atrofia , Peptídeos beta-AmiloidesRESUMO
The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest.
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Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca , Humanos , American Heart Association , Parada Cardíaca/diagnóstico , Parada Cardíaca/terapia , Cuidados Críticos/métodosRESUMO
The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest.
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Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca , Estados Unidos , Humanos , Reanimação Cardiopulmonar/métodos , American Heart Association , Parada Cardíaca/terapia , Cuidados Críticos/métodosRESUMO
BACKGROUND: Deep sedation may be indicated in the intensive care unit (ICU) for the management of acute organ failure, but leads to sedative-induced delirium. Whether processed electroencephalography (p-EEG) is useful in this setting is unclear. METHODS: We conducted a single-centre observational study of non-neurological ICU patients sedated according to a standardized guideline of deep sedation (Richmond Agitation Sedation Scale [RASS] between -5 and -4) during the acute phase of respiratory and/or cardio-circulatory failure. The SedLine (Masimo Incorporated, Irvine, California) was used to monitor the Patient State Index (PSI) (ranging from 0 to 100, <25 = very deep sedation and >50 = light sedation to full awareness) during the first 72 h of care. Delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). RESULTS: The median duration of PSI monitoring was 43 h. Patients spent 49% in median of the total PSI monitoring duration with a PSI <25. Patients with delirium (n = 41/97, 42%) spent a higher percentage of total monitored time with PSI <25 (median 67% [19-91] vs. 47% [12.2-78.9]) in non-delirious patients (p .047). After adjusting for the cumulative dose of analgesia and sedation, increased time spent with PSI <25 was associated with higher delirium (odds ratio 1.014; 95% CI 1.001-1.027, p = .036). CONCLUSIONS: A clinical protocol of deep sedation targeted to RASS at the acute ICU phase may be associated with prolonged EEG suppression and increased delirium. Whether PSI-targeted sedation may help reducing sedative dose and delirium deserves further clinical investigation. RELEVANCE TO CLINICAL PRACTICE: Patients requiring deep sedation are at high risk of being over-sedated and developing delirium despite the application of an evidence-based sedation guideline. Development of early objective measures are essential to improve sedation management in these critically ill patients.
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BACKGROUND: Improving the prognostication of acute brain injury is a key element of critical care. Standard assessment includes pupillary light reactivity testing with a hand-held light source, but findings are interpreted subjectively; automated pupillometry might be more precise and reproducible. We aimed to assess the association of the Neurological Pupil index (NPi)-a quantitative measure of pupillary reactivity computed by automated pupillometry-with outcomes of patients with severe non-anoxic acute brain injury. METHODS: ORANGE is a multicentre, prospective, observational cohort study at 13 hospitals in eight countries in Europe and North America. Patients admitted to the intensive care unit after traumatic brain injury, aneurysmal subarachnoid haemorrhage, or intracerebral haemorrhage were eligible for the study. Patients underwent automated infrared pupillometry assessment every 4 h during the first 7 days after admission to compute NPi, with values ranging from 0 to 5 (with abnormal NPi being <3). The co-primary outcomes of the study were neurological outcome (assessed with the extended Glasgow Outcome Scale [GOSE]) and mortality at 6 months. We used logistic regression to model the association between NPi and poor neurological outcome (GOSE ≤4) at 6 months and Cox regression to model the relation of NPi with 6-month mortality. This study is registered with ClinicalTrials.gov, NCT04490005. FINDINGS: Between Nov 1, 2020, and May 3, 2022, 514 patients (224 with traumatic brain injury, 139 with aneurysmal subarachnoid haemorrhage, and 151 with intracerebral haemorrhage) were enrolled. The median age of patients was 61 years (IQR 46-71), and the median Glasgow Coma Scale score on admission was 8 (5-11). 40â071 NPi measurements were taken (median 40 per patient [20-50]). The 6-month outcome was assessed in 497 (97%) patients, of whom 160 (32%) patients died, and 241 (47%) patients had at least one recording of abnormal NPi, which was associated with poor neurological outcome (for each 10% increase in the frequency of abnormal NPi, adjusted odds ratio 1·42 [95% CI 1·27-1·64]; p<0·0001) and in-hospital mortality (adjusted hazard ratio 5·58 [95% CI 3·92-7·95]; p<0·0001). INTERPRETATION: NPi has clinically and statistically significant prognostic value for neurological outcome and mortality after acute brain injury. Simple, automatic, repeat automated pupillometry assessment could improve the continuous monitoring of disease progression and the dynamics of outcome prediction at the bedside. FUNDING: NeurOptics.
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Lesões Encefálicas Traumáticas , Lesões Encefálicas , Hemorragia Subaracnóidea , Humanos , Pessoa de Meia-Idade , Idoso , Pupila , Hemorragia Subaracnóidea/diagnóstico , Estudos Prospectivos , Lesões Encefálicas/diagnóstico , Lesões Encefálicas Traumáticas/diagnóstico , Hemorragia CerebralRESUMO
BACKGROUND: Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed. OBJECTIVE: To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion. METHODS: We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis). Monitor insertion decisions were yes, no, or unsure (traffic light approach). We analyzed their responses for weighting of the presenting signs in decision-making using univariate regression. RESULTS: Heatmaps constructed from the choices of 41 panel members revealed wider ICP monitor use than predicted by guidelines. Clinical examination (GCS) was by far the most important characteristic and differed from guidelines in being nonlinear. The modified Marshall computed tomography classification was second and pupils third. We constructed a heatmap and listed the main clinical determinants representing 80% ICP monitor insertion consensus for our recommendations. CONCLUSION: Candidacy for ICP monitoring exceeds published indicators for monitor insertion, suggesting the clinical perception that the value of ICP data is greater than simply detecting and monitoring severe intracranial hypertension. Monitor insertion heatmaps are offered as potential guidance for ICP monitor insertion and to stimulate research into what actually drives monitor insertion in unconstrained, real-world conditions.
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Lesões Encefálicas Traumáticas , Lesões Encefálicas , Hipertensão Intracraniana , Humanos , Pressão Intracraniana/fisiologia , Lesões Encefálicas Traumáticas/diagnóstico , Hipertensão Intracraniana/diagnóstico , Escala de Coma de Glasgow , Monitorização Fisiológica/métodosRESUMO
OBJECTIVES: Prognostic guidelines after cardiac arrest (CA) focus on unfavorable outcome prediction; favorable outcome prognostication received less attention. Our aim was to identify favorable outcome predictors and combine them into a multimodal model. DESIGN: Retrospective analysis of prospectively collected data (January 2016 to June 2021). SETTING: Two academic hospitals (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Brigham and Women's Hospital, Boston, MA). PATIENTS: Four hundred ninety-nine consecutive comatose adults admitted after CA. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: CA variables (initial rhythm, time to return of spontaneous circulation), clinical examination (Full Outline of UnResponsiveness [FOUR] score at 72 hr, early myoclonus), electroencephalography (EEG) (reactivity, continuity, epileptiform features, and prespecified highly malignant patterns), somatosensory-evoked potentials, quantified pupillometry, and serum neuron-specific enolase (NSE) were retrieved. Neurologic outcome was assessed at 3 months using Cerebral Performance Category (CPC); 1 and 2 were considered as favorable outcome. Predictive performance of each variable toward favorable outcomes were calculated, and most discriminant items were combined to obtain a multimodal prognostic score, using multivariable ordinal logistic regression, receiving operator characteristic curves, and cross-validation. Our analysis identified a prognostic score including six modalities (1 point each): 1) early (12-36 hr) EEG not highly malignant, 2) early EEG background reactivity, 3) late (36-72 hr) EEG background reactivity and 4) continuity, 5) peak serum NSE within 48 hours less than or equal to 41 µg/L, and 6) FOUR score greater than or equal to 5 at 72 hours. At greater than or equal to 4 out of 6 points, sensitivity for CPC 1-2 was 97.5% (95% CI, 92.9-99.5%) and accuracy was 77.5% (95% CI, 72.7-81.8%); area under the curve was 0.88 (95% CI, 0.85-0.91). The score showed similar performances in the validation cohort. CONCLUSIONS: This study describes and externally validates a multimodal score, including clinical, EEG and biological items available within 72 hours, showing a high performance in identifying early comatose CA survivors who will reach functional independence at 3 months.
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Coma , Parada Cardíaca , Adulto , Humanos , Feminino , Estudos de Coortes , Coma/diagnóstico , Estudos Retrospectivos , Prognóstico , Eletroencefalografia , Fosfopiruvato HidrataseRESUMO
Abstract Best practice guidelines have advanced severe traumatic brain injury (TBI) care; however, there is little that currently informs goals of care decisions and processes despite their importance and frequency. Panelists from the Seattle International severe traumatic Brain Injury Consensus Conference (SIBICC) participated in a survey consisting of 24 questions. Questions queried use of prognostic calculators, variability in and responsibility for goals of care decisions, and acceptability of neurological outcomes, as well as putative means of improving decisions that might limit care. A total of 97.6% of the 42 SIBICC panelists completed the survey. Responses to most questions were highly variable. Overall, panelists reported infrequent use of prognostic calculators, and observed variability in patient prognostication and goals of care decisions. They felt that it would be beneficial for physicians to improve consensus on what constitutes an acceptable neurological outcome as well as what chance of achieving that outcome is acceptable. Panelists felt that the public should help to define what constitutes a good outcome and expressed some support for a "nihilism guard." More than 50% of panelists felt that if it was certain to be permanent, a vegetative state or lower severe disability would justify a withdrawal of care decision, whereas 15% felt that upper severe disability justified such a decision. Whether conceptualizing an ideal or existing prognostic calculator to predict death or an unacceptable outcome, on average a 64-69% chance of a poor outcome was felt to justify treatment withdrawal. These results demonstrate important variability in goals of care decision making and a desire to reduce this variability. Our panel of recognized TBI experts opined on the neurological outcomes and chances of those outcomes that might prompt consideration of care withdrawal; however, imprecision of prognostication and existing prognostication tools is a significant impediment to standardizing the approach to care-limiting decisions.
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Lesões Encefálicas Traumáticas , Pessoas com Deficiência , Humanos , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/terapia , Prognóstico , Consenso , Planejamento de Assistência ao PacienteRESUMO
BACKGROUND: Hemoadsorption (HA) might mitigate the systemic inflammatory response associated with post-cardiac arrest syndrome (PCAS) and improve outcomes. Here, we investigated the feasibility, safety and efficacy of HA with CytoSorb® in cardiac arrest (CA) survivors at risk of PCAS. METHODS: In this pilot randomized controlled trial, we included patients admitted to our intensive care unit following CA and likely to develop PCAS: required norepinephrine (> 0.2 µg/kg/min), and/or had serum lactate > 6 mmol/l and/or a time-to-return of spontaneous circulation (ROSC) > 25 min. Those requiring ECMO or renal replacement therapy were excluded. Eligible patients were randomly allocated to either receive standard of care (SOC) or SOC plus HA. Hemoadsorption was performed as stand-alone therapy for 24 h, using CytoSorb® and regional heparin-protamine anticoagulation. We collected feasibility, safety and clinical data as well as serial plasma cytokines levels within 72 h of randomization. RESULTS: We enrolled 21 patients, of whom 16 (76%) had out-of-hospital CA. Median (IQR) time-to-ROSC was 30 (20, 45) minutes. Ten were assigned to the HA group and 11 to the SOC group. Hemoadsorption was initiated in all patients allocated to the HA group within 18 (11, 23) h of ICU admission and conducted for a median duration of 21 (14, 24) h. The intervention was well tolerated except for a trend for a higher rate of aPTT elevation (5 (50%) vs 2 (18%) p = 0.18) and mild (100-150 G/L) thrombocytopenia at day 1 (5 (50%) vs 2 (18%) p = 0.18). Interleukin (IL)-6 plasma levels at randomization were low (< 100 pg/mL) in 10 (48%) patients and elevated (> 1000 pg/mL) in 6 (29%). The median relative reduction in IL-6 at 48 h was 75% (60, 94) in the HA group versus 5% (- 47, 70) in the SOC group (p = 0.06). CONCLUSIONS: In CA survivors at risk of PCAS, HA was feasible, safe and was associated with a nonsignificant reduction in cytokine plasma levels. Future trials are needed to further define the role of HA after CA. Those studies should include cytokine assessment to enrich the study population. TRIAL REGISTRATION: NCT03523039, registered 14 May 2018.
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Parada Cardíaca Extra-Hospitalar , Síndrome Pós-Parada Cardíaca , Humanos , Citocinas , Projetos Piloto , Interleucina-6 , Parada Cardíaca Extra-Hospitalar/induzido quimicamenteRESUMO
Following traumatic brain injury (TBI), cerebral metabolic dysfunction, characterized by an elevated cerebral microdialysis (CMD) lactate/pyruvate (LP) ratio, is associated with poor outcome. However, the exact pathophysiological mechanisms underlying this association are not entirely established. In this pre-planned analysis of the BIOmarkers of AXonal injury after Traumatic Brain Injury (BIO-AX-TBI) prospective study, we investigated any associations of LP ratio with brain structure volume change rates at 1 year. Fourteen subjects underwent acute-phase (0-96 h post-TBI) CMD monitoring and had longitudinal magnetic resonance imaging (MRI) quantification of brain volume loss between the subacute phase (14 days to 6 weeks) and 1 year after TBI, recalculated as an annual rate. On average, CMD showed an elevated (>25) LP ratio (31 [interquartile range (IQR) 24-34]), indicating acute cerebral metabolic dysfunction. Annualized whole brain and total gray matter (GM) volume change rates were abnormally reduced (-3.2% [-9.3 to -2.2] and -1.9% [-4.4 to 1.7], respectively). Reduced annualized total GM volume correlated significantly with elevated CMD LP ratio (Spearman's ρ = -0.68, p-value = 0.01) and low CMD glucose (ρ = 0.66, p-value = 0.01). After adjusting for age, admission Glasgow Coma Scale (GCS) score and CT Marshall score, CMD LP ratio remained strongly associated with 1-year total GM volume change rate (p < 0.001; multi-variable analysis). No relationship was found between WM volume changes and CMD metabolites. We demonstrate a strong association between acute post-traumatic cerebral metabolic dysfunction and 1-year gray matter atrophy, reinforcing the role of CMD LP ratio as an early biomarker of poor long-term recovery after TBI.
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Encefalopatias , Lesões Encefálicas Traumáticas , Humanos , Estudos Prospectivos , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Escala de Coma de Glasgow , BiomarcadoresRESUMO
BACKGROUND AND OBJECTIVES: Neurologic complications have been associated with COVID-19, including delirium. Such complications have been reported to be frequent among intensive care unit (ICU)-admitted patients. We hypothesized that the rate of neurologic complications would be higher in COVID-19 associated acute respiratory distress syndrome (ARDS) than those who develop ARDS from a different cause. METHODS: We conducted a retrospective cohort study in the adult ICU of Lausanne University Hospital, including all consecutive patients fulfilling the Berlin criteria for ARDS hospitalized between December 2017 and June 2021, stratifying exposure between COVID-19 or not. The primary outcome was delirium onset during ICU stay, defined by the confusion assessment method (CAM-ICU). Exploratory outcomes included development of neurologic complications of the central nervous system (stroke, hemorrhage, and vasculitis), critical illness weakness, and 30- and 180-day all-cause mortality. RESULTS: Three hundred eleven patients were included in the study (253 with COVID-19 and 58 with other causes) and CAM-ICU could be assessed in 231 (74.3% in COVID-19 vs 74.1% in non-COVID-19). The proportion of patients developing delirium was similar in patients with COVID-19 and controls in univariate comparison (69.1% vs 60.5%, p = 0.246). Yet, patients with COVID-19 had a higher body mass index, lower ICU severity, longer mechanical ventilation, and higher sedation doses (propofol and dexmedetomidine). After adjusting for these factors in a multivariable analysis, the risk of delirium remained comparable across groups (adjusted OR [95% CI]: 0.86 [0.35-2.1]). Similarly, COVID-19-related ARDS had no effect on all-cause mortality at 30 days (adjusted OR: 0.87 [0.39-1.92]) and 180 days (adjusted OR: 0.67 [0.33-1.35]). Finally, neurologic complications affecting the CNS (adjusted OR: 1.15 [0.25-5.29]) and critical illness weakness (adjusted OR: 2.99 [0.97-9.1]) were not higher in the COVID-19 group. DISCUSSION: Compared with other etiologies, patients with COVID-19 did not have higher incidence of delirium and other neurologic complications, after accounting for underlying disease severity in patients with ARDS. Management of COVID-19-associated ARDS needed longer invasive ventilation and higher sedation, which could explain higher rates of delirium in uncontrolled studies.
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COVID-19 , Delírio , Síndrome do Desconforto Respiratório , Humanos , Adulto , Estado Terminal , Estudos Retrospectivos , COVID-19/complicações , Síndrome do Desconforto Respiratório/epidemiologia , Síndrome do Desconforto Respiratório/etiologia , Unidades de Terapia Intensiva , Respiração Artificial , Delírio/epidemiologia , Delírio/etiologiaRESUMO
AIMS OF THE STUDY: Awake prone positioning (aPP) in non-intubated patients with severe SARS-CoV-2-related pneumonia improves oxygenation and reduces the intubation rate, but no early predictors for success or failure of the strategy have been described. The main objective of this study was to assess whether response to the first aPP in terms of PaO2/FiO2, alveolar-arterial gradient (Aa-O2), respiratory rate and PaCO2 could predict the need for intubation. As secondary objective, we assessed the effects of aPP on the same parameters for all the sessions considered together. METHODS: Retrospective analysis of consecutive SARS-CoV-2 pneumonia patients suffering from acute respiratory failure with moderate to severe hypoxaemia for whom aPP was performed for at least 45 minutes based on the prescription of the clinician in charge according to predefined criteria. Respiratory rate, blood gases and oxygenation parameters (PaO2/FiO2 and Aa-O2), before and after the first aPP were compared between patients who were subsequently intubated or not. Effects of all the aPP sessions together were also analysed. RESULTS: One hundred and sixty-six patients were admitted for SARS-CoV-2 pneumonia during the study period. Among them, 50 received aPP lasting at least 45 minutes. Because 17 denied consent for data analysis and 2 were excluded because of a "do not intubate order", 31 patients (for a total of 116 aPP sessions without any severe adverse events reported) were included. Among them, 10 (32.3%) were intubated. Mean age ± standard deviation (SD) was 60 ± 12 years. At ICU admission, respiratory rate was 26 ± 7/minute, median PaO2/FiO2 94 (interquartile range [IQR] 74-116) mm Hg and median Aa-O2 412 (IQR 286-427) mm Hg (markedly increased). Baseline characteristics did not statistically differ between patients who subsequently needed intubation or not. During the first aPP, PaO2/FiO2 increased and Aa-O2 decreased. When comparing patients who later where intubated or not, we observed, in the non intubated group only, a clinically significant decrease in median Aa-O2, from 294 (280-414) to 204 (107-281) mm Hg, corresponding to a 40% (26-56%) reduction, and a PaO2/FiO2 increase, from 103 (84-116) to 162 (138-195), corresponding to an increase of 48% (11-93%). The p value is <0.005 for both. When all the aPP sessions (n = 80) were considered together, aPP was associated with a significant increase in PaO2/FiO2 from 112 (80-132) to 156 (86-183) mm Hg (p <0.001) and Aa-O2 decrease from 304 (244-418) to 224 (148-361) mm Hg (p = 0.001). CONCLUSIONS: Awake pronation in spontaneously breathing patients is feasible, and improves PaO2/FiO2 and Aa-O2. Response to the first session seems to be associated with lower intubation rate.
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COVID-19 , Síndrome do Desconforto Respiratório , Insuficiência Respiratória , COVID-19/complicações , COVID-19/terapia , Humanos , Hipóxia/complicações , Hipóxia/terapia , Intubação Intratraqueal/efeitos adversos , Decúbito Ventral , Síndrome do Desconforto Respiratório/terapia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Estudos Retrospectivos , SARS-CoV-2 , VigíliaRESUMO
INTRODUCTION: We evaluated the concordance of the Neurological pupil Index (NPi) with other predictors of outcome after cardiac arrest (CA). METHODS: Post hoc analysis of a prospective, international, multicenter study including adult CA patients. Predictors of unfavorable outcome (UO, Cerebral Performance Category of 3-5 at 3 months) included: a) worst NPi ≤ 2; b) presence of discontinuous encephalography (EEG) background; c) bilateral absence of N20 waves on somatosensory evoked potentials (N20ABS); d) peak neuron-specific enolase (NSE) blood levels > 60 mcg/L; e) myoclonus, which were all tested in a subset of patients who underwent complete multimodal assessment (MMM). RESULTS: A total of 269/456 (59 %) patients had UO and 186 (41 %) underwent MMM. The presence of myoclonus was assessed in all patients, EEG in 358 (78 %), N20 in 186 (41 %) and NSE measurement in 228 (50 %). Patients with discontinuous EEG, N20ABS or high NSE had a higher proportion of worst NPi ≤ 2. The accuracy for NPi to predict a discontinuous EEG, N20ABS, high NSE and the presence of myoclonus was moderate. Concordance with NPi ≤ 2 was high for NSE, and moderate for discontinuous EEG and N20ABS. Also, the higher the number of concordant predictors of poor outcome, the lower the observed NPi. CONCLUSIONS: In this study, NPi ≤ 2 had moderate to high concordance with other unfavorable outcome prognosticators of hypoxic-ischemic brain injury. This indicates that NPi measurement could be considered as a valid tool for coma prognostication after cardiac arrest.
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Parada Cardíaca , Mioclonia , Adulto , Parada Cardíaca/complicações , Parada Cardíaca/diagnóstico , Parada Cardíaca/terapia , Humanos , Fosfopiruvato Hidratase , Prognóstico , Estudos Prospectivos , Pupila/fisiologiaRESUMO
Traumatic brain injury (TBI) remains one of the most fatal and debilitating conditions in the world. Current clinical management in severe TBI patients is mainly concerned with reducing secondary insults and optimizing the balance between substrate delivery and consumption. Over the past decades, multimodality monitoring has become more widely available, and clinical management protocols have been published that recommend potential interventions to correct pathophysiological derangements. Even while evidence from randomized clinical trials is still lacking for many of the recommended interventions, these protocols and algorithms can be useful to define a clear standard of therapy where novel interventions can be added or be compared to. Over the past decade, more attention has been paid to holistic management, in which hemodynamic, respiratory, inflammatory or coagulation disturbances are detected and treated accordingly. Considerable variability with regards to the trajectories of recovery exists. Even while most of the recovery occurs in the first months after TBI, substantial changes may still occur in a later phase. Neuroprognostication is challenging in these patients, where a risk of self-fulfilling prophecies is a matter of concern. The present article provides a comprehensive and practical review of the current best practice in clinical management and long-term outcomes of moderate to severe TBI in adult patients admitted to the intensive care unit.
Assuntos
Lesões Encefálicas Traumáticas , Adulto , Lesões Encefálicas Traumáticas/complicações , Humanos , Pressão Intracraniana/fisiologiaRESUMO
BACKGROUND: According to international guidelines, neuroprognostication in comatose patients after cardiac arrest (CA) is performed using a multimodal approach. However, patients undergoing extracorporeal membrane oxygenation (ECMO) may have longer pharmacological sedation and show alteration in biological markers, potentially challenging prognostication. Here, we aimed to assess whether routinely used predictors of poor neurological outcome also exert an acceptable performance in patients undergoing ECMO after CA. METHODS: This observational retrospective study of our registry includes consecutive comatose adults after CA. Patients deceased within 36 h and not undergoing prognostic tests were excluded. Veno-arterial ECMO was initiated in patients < 80 years old presenting a refractory CA, with a no flow < 5 min and a low flow ≤ 60 min on admission. Neuroprognostication test performance (including pupillary reflex, electroencephalogram, somatosensory-evoked potentials, neuron-specific enolase) toward mortality and poor functional outcome (Cerebral Performance Categories [CPC] score 3-5) was compared between patients undergoing ECMO and those without ECMO. RESULTS: We analyzed 397 patients without ECMO and 50 undergoing ECMO. The median age was 65 (interquartile range 54-74), and 69.8% of patients were men. Most had a cardiac etiology (67.6%); 52% of the patients had a shockable rhythm, and the median time to return of an effective circulation was 20 (interquartile range 10-28) minutes. Compared with those without ECMO, patients receiving ECMO had worse functional outcome (74% with CPC scores 3-5 vs. 59%, p = 0.040) and a nonsignificant higher mortality (60% vs. 47%, p = 0.080). Apart from the neuron-specific enolase level (higher in patients with ECMO, p < 0.001), the presence of prognostic items (pupillary reflex, electroencephalogram background and reactivity, somatosensory-evoked potentials, and myoclonus) related to unfavorable outcome (CPC score 3-5) in both groups was similar, as was the prevalence of at least any two such items concomitantly. The specificity of each these variables toward poor outcome was between 92 and 100% in both groups, and of the combination of at least two items, it was 99.3% in patients without ECMO and 100% in those with ECMO. The predictive performance (receiver operating characteristic curve) of their combination toward poor outcome was 0.822 (patients without ECMO) and 0.681 (patients with ECMO) (p = 0.134). CONCLUSIONS: Pending a prospective assessment on a larger cohort, in comatose patients after CA, the performance of prognostic factors seems comparable in patients with ECMO and those without ECMO. In particular, the combination of at least two poor outcome criteria appears valid across these two groups.
Assuntos
Encéfalo , Coma , Oxigenação por Membrana Extracorpórea , Parada Cardíaca , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/enzimologia , Encéfalo/fisiopatologia , Coma/etiologia , Coma/fisiopatologia , Coma/terapia , Eletroencefalografia , Feminino , Parada Cardíaca/complicações , Humanos , Masculino , Fosfopiruvato Hidratase/metabolismo , Prognóstico , Estudos Prospectivos , Estudos RetrospectivosRESUMO
In this study, we examined the early value of automated quantitative pupillary examination, using the Neurological Pupil index (NPi), to predict the long-term outcome of acute brain injured (ABI) patients. We performed a single-centre retrospective study (October 2016−March 2019) in ABI patients who underwent NPi measurement during the first 3 days following brain insult. We examined the performance of NPialone or in combination with other baseline demographic (age) and radiologic (CT midline shift) predictorsto prognosticate unfavourable 6-month outcome (Glasgow Outcome Scale 1−3). A total of 145 severely brain-injured subjects (65 traumatic brain injury, TBI; 80 non-TBI) were studied. At each time point tested, NPi <3 was highly predictive of unfavourable outcome, with highest specificity (100% (90−100)) at day 3 (sensitivity 24% (15−35), negative predictive value 36% (34−39)). The addition of NPi, from day 1 following ABI to age and cerebral CT scan, provided the best prognostic performance (AUROC curve 0.85 vs. 0.78 without NPi, p = 0.008; DeLong test) for 6-month neurological outcome prediction. NPi, assessed at the early post-injury phase, has a superior ability to predict unfavourable long-term neurological outcomes in severely brain-injured patients. The added prognostic value of NPi was most significant when complemented with baseline demographic and radiologic information.