Evaluating the use of casuistry during moral case deliberation in the ICU: A multiple qualitative case study.

Intensive care unit (ICU) professionals engage in ethical decision making under conditions of high stakes, great uncertainty, time-sensitivity and frequent irreversibility of action. Casuistry is a way by which actionable knowledge is obtained through comparing a patient case to previous cases from experience in clinical practice. However, within the field of study as well as in practice, evidence-based medicine is the dominant epistemic framework. This multiple case study evaluated the use of casuistic reasoning by intensive care unit (ICU) professionals during moral case deliberation. It took place in two Dutch hospitals between June 2020 and June 2022. Twentyfive moral case deliberations from ICU practice were recorded and analyzed using discourse analysis. Additionally, 47 interviews were held with ICU professionals who participated in these deliberations, analyzed using thematic analysis. We found that ICU professionals made considerable use of case comparisons when discussing continuation, withdrawal or limitation. Analogies played a role in justifying or complicating moral judgements, and also played a role in addressing moral distress. The language of case-based arguments is most often not overtly normative. Rather, the data shows that casuistic reasoning deals with the medical, ethical and contextual elements of decisions in an integrated manner. Facilitators of MCD have an essential role in (supporting ICU professionals in) scrutinizing casuistic arguments. The data shows that during MCD, actual reasoning often deviated from principle- and rule-based reasoning which ICU professionals preferred themselves. Evidence-based arguments often gained the character of analogical arguments, especially when a patient-at-hand was seen as highly unique from the average patients in the literature. Casuistic arguments disguised as evidence-based arguments may therefore provide ICU professionals with a false sense of certainty. Within education, we should strive to train clinicians and ethics facilitators so that they can recognize and evaluate casuistic arguments.

Intensive glucose control in critically ill adults: a protocol for a systematic review and individual patient data meta-analysis / Controle intensivo da glicose em adultos em estado grave: um protocolo de revisão sistemática e metanálise de dados individuais de pacientes

ABSTRACT Objective: The optimal target for blood glucose concentration in critically ill patients is unclear. We will perform a systematic review and meta-analysis with aggregated and individual patient data from randomized controlled trials, comparing intensive glucose control with liberal glucose control in critically ill adults. Data sources: MEDLINE®, Embase, the Cochrane Central Register of Clinical Trials, and clinical trials registries (World Health Organization, clinical trials.gov). The authors of eligible trials will be invited to provide individual patient data. Published trial-level data from eligible trials that are not at high risk of bias will be included in an aggregated data meta-analysis if individual patient data are not available. Methods: Inclusion criteria: randomized controlled trials that recruited adult patients, targeting a blood glucose of ≤ 120mg/dL (≤ 6.6mmol/L) compared to a higher blood glucose concentration target using intravenous insulin in both groups. Excluded studies: those with an upper limit blood glucose target in the intervention group of > 120mg/dL (> 6.6mmol/L), or where intensive glucose control was only performed in the intraoperative period, and those where loss to follow-up exceeded 10% by hospital discharge. Primary endpoint: In-hospital mortality during index hospital admission. Secondary endpoints: mortality and survival at other timepoints, duration of invasive mechanical ventilation, vasoactive agents, and renal replacement therapy. A random effect Bayesian meta-analysis and hierarchical Bayesian models for individual patient data will be used. Discussion: This systematic review with aggregate and individual patient data will address the clinical question, 'what is the best blood glucose target for critically ill patients overall?' Protocol version 0.4 - 06/26/2023 PROSPERO registration: CRD42021278869

RESUMO Objetivo: Não está claro qual é a meta ideal de concentração de glicose no sangue em pacientes em estado grave. Realizaremos uma revisão sistemática e uma metanálise com dados agregados e de pacientes individuais de estudos controlados e randomizados, comparando o controle intensivo da glicose com o controle liberal da glicose em adultos em estado grave. Fontes de dados: MEDLINE®, Embase, Cochrane Central Register of Clinical Trials e registros de ensaios clínicos (Organização Mundial da Saúde, clinical trials.gov). Os autores dos estudos qualificados serão convidados a fornecer dados individuais de pacientes. Os dados publicados em nível de ensaio qualificado que não apresentem alto risco de viés serão incluídos em uma metanálise de dados agregados se os dados individuais de pacientes não estiverem disponíveis. Métodos: Critérios de inclusão: ensaios clínicos controlados e randomizados que recrutaram pacientes adultos, com meta de glicemia ≤ 120mg/dL (≤ 6,6mmol/L) comparada a uma meta de concentração de glicemia mais alta com insulina intravenosa em ambos os grupos. Estudos excluídos: aqueles com meta de glicemia no limite superior no grupo de intervenção > 120mg/dL (> 6,6mmol/L), ou em que o controle intensivo de glicose foi realizado apenas no período intraoperatório, e aqueles em que a perda de seguimento excedeu 10% até a alta hospitalar. Desfecho primário: Mortalidade intra-hospitalar durante a admissão hospitalar. Desfechos secundários: Mortalidade e sobrevida em outros momentos, duração da ventilação mecânica invasiva, agentes vasoativos e terapia de substituição renal. Utilizaremos metanálise bayesiana de efeito randômico e modelos bayesianos hierárquicos para dados individuais de pacientes. Discussão: Essa revisão sistemática com dados agregados e de pacientes individuais abordará a questão clínica: Qual é a melhor meta de glicose no sangue de pacientes graves em geral? Protocolo versão 0.4 - 26/06/2023 Registro PROSPERO: CRD42021278869

[Moral injury in medicine: recognition and guidance]. / Morele schade in de geneeskunde.

Moral injury signifies a permanent mental wound characterized by feelings of guilt, shame, anger or moral disorientation. Physicians may become morally injured whenever they act in a way that conflicts with deeply held, moral beliefs. During a pandemic, a war or whenever physicians provide care to large numbers of refugees, there is a heightened risk of moral injury. These circumstances cause conditions of scarcity of personnel and resources, and urge governments and societies to sometimes ask physicians to act in manners which conflict with their moral beliefs. Moral injury can have damning consequences for the professionals involved. That is why it is essential that physicians learn to recognize the signs of moral injury within themselves and with colleagues.

Value of EEG in outcome prediction of hypoxic-ischemic brain injury in the ICU: A narrative review.

Prognostication of comatose patients after cardiac arrest aims to identify patients with a large probability of favourable or unfavouble outcome, usually within the first week after the event. Electroencephalography (EEG) is a technique that is increasingly used for this purpose and has many advantages, such as its non-invasive nature and the possibility to monitor the evolution of brain function over time. At the same time, use of EEG in a critical care environment faces a number of challenges. This narrative review describes the current role and future applications of EEG for outcome prediction of comatose patients with postanoxic encephalopathy.

Effect of Structural Moral Case Deliberation on Burnout Symptoms, Moral Distress, and Team Climate in ICU Professionals: A Parallel Cluster Randomized Trial.

OBJECTIVES: Moral case deliberation (MCD) is a team-based and facilitator-led, structured moral dialogue about ethical difficulties encountered in practice. This study assessed whether offering structural MCD in ICUs reduces burnout symptoms and moral distress and strengthens the team climate among ICU professionals. DESIGN: This is a parallel cluster randomized trial. SETTING: Six ICUs in two hospitals located in Nijmegen, between January 2020 and September 2021. SUBJECTS: Four hundred thirty-five ICU professionals. INTERVENTIONS: Three of the ICUs organized structural MCD. In three other units, there was no structural MCD or other structural discussions of moral problems. MEASUREMENTS AND MAIN RESULTS: The primary outcomes investigated were the three burnout symptoms-emotional exhaustion, depersonalization, and a low sense of personal accomplishment-among ICU professionals measured using the Maslach Burnout Inventory on a 0-6 scale. Secondary outcomes were moral distress (Moral Distress Scale) on a 0-336 scale and team climate (Safety Attitude Questionnaire) on a 0-4 scale. Organizational culture was an explorative outcome (culture of care barometer) and was measured on a 0-4 scale. Outcomes were measured at baseline and in 6-, 12-, and 21-month follow-ups. Intention-to-treat analyses were conducted using linear mixed models for longitudinal nested data. Structural MCD did not affect emotional exhaustion or depersonalization, or the team climate. It reduced professionals' personal accomplishment (-0.15; p < 0.05) but also reduced moral distress (-5.48; p < 0.01). Perceptions of organizational support (0.15; p < 0.01), leadership (0.19; p < 0.001), and participation opportunities (0.13; p < 0.05) improved. CONCLUSIONS: Although structural MCD did not mitigate emotional exhaustion or depersonalization, and reduced personal accomplishment in ICU professionals, it did reduce moral distress. Moreover, it did not improve team climate, but improved the organizational culture.

Development of Moral Injury in ICU Professionals During the COVID-19 Pandemic: A Prospective Serial Interview Study.

OBJECTIVES: During the COVID-19 pandemic, ICU professionals have faced moral problems that may cause moral injury. This study explored whether, how, and when moral injury among ICU professionals developed in the course of the COVID-19 pandemic. DESIGN: This is a prospective qualitative serial interview study. SETTING: Two hospitals among which one university medical center and one teaching hospital in the Netherlands. SUBJECTS: Twenty-six ICU professionals who worked during the COVID-19 pandemic. INTERVENTIONS: None. MEASUREMENTS MAIN RESULTS: In-depth interviews with follow-up after 6 and 12 months. In total, 62 interviews were conducted. ICU professionals narrated about anticipatory worry about life and death decisions, lack of knowledge and prognostic uncertainty about COVID-19, powerlessness and failure, abandonment or betrayal by society, politics, or the healthcare organization, numbness toward patients and families, and disorientation and self-alienation. Centrally, ICU professionals describe longitudinal processes by which they gradually numbed themselves emotionally from patients and families as well as potentially impactful events in their work. For some ICU professionals, organizational, societal, and political responses to the pandemic contributed to numbness, loss of motivation, and self-alienation. CONCLUSIONS: ICU professionals exhibit symptoms of moral injury such as feelings of betrayal, detachment, self-alienation, and disorientation. Healthcare organizations and ICU professionals themselves should be cognizant that these feelings may indicate that professionals might have developed moral injury or that it may yet develop in the future. Awareness should be raised about moral injury and should be followed up by asking morally injured professionals what they need, so as to not risk offering unwanted help.

Free water corrected diffusion tensor imaging discriminates between good and poor outcomes of comatose patients after cardiac arrest.

OBJECTIVES: Approximately 50% of comatose patients after cardiac arrest never regain consciousness. Cerebral ischaemia may lead to cytotoxic and/or vasogenic oedema, which can be detected by diffusion tensor imaging (DTI). Here, we evaluate the potential value of free water corrected mean diffusivity (MD) and fractional anisotropy (FA) based on DTI, for the prediction of neurological recovery of comatose patients after cardiac arrest. METHODS: A total of 50 patients after cardiac arrest were included in this prospective cohort study in two Dutch hospitals. DTI was obtained 2-4 days after cardiac arrest. Outcome was assessed at 6 months, dichotomised as poor (cerebral performance category 3-5; n = 20) or good (n = 30) neurological outcome. We calculated the whole brain mean MD and FA and compared between patients with good and poor outcomes. In addition, we compared a preliminary prediction model based on clinical parameters with or without the addition of MD and FA. RESULTS: We found significant differences between patients with good and poor outcome of mean MD (good: 726 [702-740] × 10-6 mm2/s vs. poor: 663 [575-736] × 10-6 mm2/s; p = 0.01) and mean FA (0.30 ± 0.03 vs. 0.28 ± 0.03; p = 0.03). An exploratory prediction model combining clinical parameters, MD and FA increased the sensitivity for reliable prediction of poor outcome from 60 to 85%, compared to the model containing clinical parameters only, but confidence intervals are overlapping. CONCLUSIONS: Free water-corrected MD and FA discriminate between patients with good and poor outcomes after cardiac arrest and hold the potential to add to multimodal outcome prediction. KEY POINTS: • Whole brain mean MD and FA differ between patients with good and poor outcome after cardiac arrest. • Free water-corrected MD can better discriminate between patients with good and poor outcome than uncorrected MD. • A combination of free water-corrected MD (sensitive to grey matter abnormalities) and FA (sensitive to white matter abnormalities) holds potential to add to the prediction of outcome.

Complex interplay between moral distress and other risk factors of burnout in ICU professionals: findings from a cross-sectional survey study.

BACKGROUND: Burnout threatens intensive care unit (ICU) professionals' capacity to provide high-quality care. Moral distress is previously considered a root cause of burnout, but there are other risk factors of burnout such as personality, work-life balance and culture. This study aimed to disentangle the associations of ICU professionals' moral distress and other risk factors with the components of burnout-emotional exhaustion, depersonalisation and personal accomplishment-suggesting informed burnout prevention strategies. METHODS: Cross-sectional survey completed in 2019 of ICU professionals in two Dutch hospitals. The survey included validated measure for burnout (the Dutch Maslach Burnout Inventory), moral distress (Moral Distress Scale), personality (short Big Five Inventory), work-home balance (Survey Work-Home Interaction Nijmegen) and organisational culture (Culture of Care Barometer). Each of the three components of burnout was analysed as a separate outcome, and for each of the components, a separate regression analysis was carried out. RESULTS: 251 ICU professionals responded to the survey (response rate: 53.3%). Burnout prevalence was 22.7%. Findings showed that moral distress was associated with emotional exhaustion (ß=0.18, 95% CI 0.9 to 0.26) and depersonalisation (ß=0.19, 95% CI 0.10 to 0.28) and with increased emotional exhaustion mediated by negative work-to-home spillover (ß=0.09, 95% CI 0.04 to 0.13). Support from direct supervisors mitigates the association between moral distress and emotional exhaustion (ß=0.16, 95% CI 0.04 to 0.27). CONCLUSIONS: Understanding moral distress as a root cause of burnout is too simplified. There is an important interplay between moral distress and work-home imbalance. Interventions that support individual coping with moral distress and a work-home imbalance, and the support of direct supervisors, are paramount to prevent burnout in physicians and nurses.

Intensive glucose control in critically ill adults: a protocol for a systematic review and individual patient data meta-analysis.

OBJECTIVE: The optimal target for blood glucose concentration in critically ill patients is unclear. We will perform a systematic review and meta-analysis with aggregated and individual patient data from randomized controlled trials, comparing intensive glucose control with liberal glucose control in critically ill adults. DATA SOURCES: MEDLINE®, Embase, the Cochrane Central Register of Clinical Trials, and clinical trials registries (World Health Organization, clinical trials.gov). The authors of eligible trials will be invited to provide individual patient data. Published trial-level data from eligible trials that are not at high risk of bias will be included in an aggregated data meta-analysis if individual patient data are not available. METHODS: Inclusion criteria: randomized controlled trials that recruited adult patients, targeting a blood glucose of ≤ 120mg/dL (≤ 6.6mmol/L) compared to a higher blood glucose concentration target using intravenous insulin in both groups. Excluded studies: those with an upper limit blood glucose target in the intervention group of > 120mg/dL (> 6.6mmol/L), or where intensive glucose control was only performed in the intraoperative period, and those where loss to follow-up exceeded 10% by hospital discharge. PRIMARY ENDPOINT: In-hospital mortality during index hospital admission. Secondary endpoints: mortality and survival at other timepoints, duration of invasive mechanical ventilation, vasoactive agents, and renal replacement therapy. A random effect Bayesian meta-analysis and hierarchical Bayesian models for individual patient data will be used. DISCUSSION: This systematic review with aggregate and individual patient data will address the clinical question, 'what is the best blood glucose target for critically ill patients overall?'Protocol version 0.4 - 06/26/2023PROSPERO registration:CRD42021278869.

MRI markers of brain network integrity relate to neurological outcome in postanoxic coma.

AIM: Current multimodal approaches leave approximately half of the comatose patients after cardiac arrest with an indeterminate prognosis. Here we investigated whether early MRI markers of brain network integrity can distinguish between comatose patients with a good versus poor neurological outcome six months later. METHODS: We performed a prospective cohort study in 48 patients after cardiac arrest submitted in a comatose state to the Intensive Care Unit of two Dutch hospitals. MRI was performed at three days after cardiac arrest, including resting state functional MRI and diffusion-tensor imaging (DTI). Resting state fMRI was used to quantify functional connectivity within ten resting-state networks, and DTI to assess mean diffusivity (MD) in these same networks. We contrasted two groups of patients, those with good (n = 29, cerebral performance category 1-2) versus poor (n = 19, cerebral performance category 3-5) outcome at six months. Mutual associations between functional connectivity, MD, and clinical outcome were studied. RESULTS: Patients with good outcome show higher within-network functional connectivity (fMRI) and higher MD (DTI) than patients with poor outcome across 8/10 networks, most prominent in the default mode network, salience network, and visual network. While the anatomical distribution of outcome-related changes was similar for functional connectivity and MD, the pattern of inter-individual differences was very different: functional connectivity showed larger inter-individual variability in good versus poor outcome, while the opposite was observed for MD. Exploratory analyses suggested that it is possible to define network-specific cut-off values that could help in outcome prediction: (1) high functional connectivity and high MD, associated with good outcome; (2) low functional connectivity and low MD, associated with poor outcome; (3) low functional connectivity and high MD, associated with uncertain outcome. DISCUSSION: Resting-state functional connectivity and mean diffusivity-three days after cardiac arrest are strongly associated with neurological recovery-six months later in a complementary fashion. The combination of fMRI and MD holds potential to improve prediction of outcome.

Optimizing an existing prediction model for quality of life one-year post-intensive care unit: An exploratory analysis.

BACKGROUND: This study aimed to improve the PREPARE model, an existing linear regression prediction model for long-term quality of life (QoL) of intensive care unit (ICU) survivors by incorporating additional ICU data from patients' electronic health record (EHR) and bedside monitors. METHODS: The 1308 adult ICU patients, aged ≥16, admitted between July 2016 and January 2019 were included. Several regression-based machine learning models were fitted on a combination of patient-reported data and expert-selected EHR variables and bedside monitor data to predict change in QoL 1 year after ICU admission. Predictive performance was compared to a five-feature linear regression prediction model using only 24-hour data (R2  = 0.54, mean square error (MSE) = 0.031, mean absolute error (MAE) = 0.128). RESULTS: The 67.9% of the included ICU survivors was male and the median age was 65.0 [IQR: 57.0-71.0]. Median length of stay (LOS) was 1 day [IQR 1.0-2.0]. The incorporation of the additional data pertaining to the entire ICU stay did not improve the predictive performance of the original linear regression model. The best performing machine learning model used seven features (R2  = 0.52, MSE = 0.032, MAE = 0.125). Pre-ICU QoL, the presence of a cerebro vascular accident (CVA) upon admission and the highest temperature measured during the ICU stay were the most important contributors to predictive performance. Pre-ICU QoL's contribution to predictive performance far exceeded that of the other predictors. CONCLUSION: Pre-ICU QoL was by far the most important predictor for change in QoL 1 year after ICU admission. The incorporation of the numerous additional features pertaining to the entire ICU stay did not improve predictive performance although the patients' LOS was relatively short.

Morisprudence: a theoretical framework for studying the relationship linking moral case deliberation, organisational learning and quality improvement.

There is a claim that clinical ethics support services (CESS) improve healthcare quality within healthcare organisations. However, there is lack of strong evidence supporting this claim. Rather, the current focus is on the quality of CESS themselves or on individual learning outcomes. In response, this article proposes a theoretical framework leading to empirical hypotheses that describe the relationship between a specific type of CESS, moral case deliberation and the quality of care at the organisational level. We combine insights from the literature on CESS, organisational learning and quality improvement and argue that moral case deliberation causes healthcare professionals to acquire practical wisdom. At the organisational level, where improving quality is a continuous and collective endeavour, this practical wisdom can be aggregated into morisprudence, which is an ongoing formulation of moral judgements across cases encountered within the organisation. Focusing on the development of morisprudence enables refined scrutinisation of CESS-related quality claims.

Prognosis After Cardiac Arrest: The Additional Value of DWI and FLAIR to EEG.

BACKGROUND: Despite application of the multimodal European Resuscitation Council and European Society of Intensive Care Medicine algorithm, neurological prognosis of patients who remain comatose after cardiac arrest remains uncertain in a large group of patients. In this study, we investigate the additional predictive value of visual and quantitative brain magnetic resonance imaging (MRI) to electroencephalography (EEG) for outcome estimation of comatose patients after cardiac arrest. METHODS: We performed a prospective multicenter cohort study in patients after cardiac arrest submitted in a comatose state to the intensive care unit of two Dutch hospitals. Continuous EEG was recorded during the first 3 days and MRI was performed at 3 ± 1 days after cardiac arrest. EEG at 24 h and ischemic damage in 21 predefined brain regions on diffusion weighted imaging and fluid-attenuated inversion recovery on a scale from 0 to 4 were related to outcome. Quantitative MRI analyses included mean apparent diffusion coefficient (ADC) and percentage of brain volume with ADC < 450 × 10-6 mm2/s, < 550 × 10-6 mm2/s, and < 650 × 10-6 mm2/s. Poor outcome was defined as a Cerebral Performance Category score of 3-5 at 6 months. RESULTS: We included 50 patients, of whom 20 (40%) demonstrated poor outcome. Visual EEG assessment correctly identified 3 (15%) with poor outcome and 15 (50%) with good outcome. Visual grading of MRI identified 13 (65%) with poor outcome and 25 (89%) with good outcome. ADC analysis identified 11 (55%) with poor outcome and 3 (11%) with good outcome. EEG and MRI combined could predict poor outcome in 16 (80%) patients at 100% specificity, and good outcome in 24 (80%) at 63% specificity. Ischemic damage was most prominent in the cortical gray matter (75% vs. 7%) and deep gray nuclei (45% vs. 3%) in patients with poor versus good outcome. CONCLUSIONS: Magnetic resonance imaging is complementary with EEG for the prediction of poor and good outcome of patients after cardiac arrest who are comatose at admission.

Prediction of good neurological outcome in comatose survivors of cardiac arrest: a systematic review.

PURPOSE: To assess the ability of clinical examination, blood biomarkers, electrophysiology or neuroimaging assessed within 7 days from return of spontaneous circulation (ROSC) to predict good neurological outcome, defined as no, mild, or moderate disability (CPC 1-2 or mRS 0-3) at discharge from intensive care unit or later, in comatose adult survivors from cardiac arrest (CA). METHODS: PubMed, EMBASE, Web of Science and the Cochrane Database of Systematic Reviews were searched. Sensitivity and specificity for good outcome were calculated for each predictor. The risk of bias was assessed using the QUIPS tool. RESULTS: A total of 37 studies were included. Due to heterogeneities in recording times, predictor thresholds, and definition of some predictors, meta-analysis was not performed. A withdrawal or localisation motor response to pain immediately or at 72-96 h after ROSC, normal blood values of neuron-specific enolase (NSE) at 24 h-72 h after ROSC, a short-latency somatosensory evoked potentials (SSEPs) N20 wave amplitude > 4 µV or a continuous background without discharges on electroencephalogram (EEG) within 72 h from ROSC, and absent diffusion restriction in the cortex or deep grey matter on MRI on days 2-7 after ROSC predicted good neurological outcome with more than 80% specificity and a sensitivity above 40% in most studies. Most studies had moderate or high risk of bias. CONCLUSIONS: In comatose cardiac arrest survivors, clinical, biomarker, electrophysiology, and imaging studies identified patients destined to a good neurological outcome with high specificity within the first week after cardiac arrest (CA).

Treating Rhythmic and Periodic EEG Patterns in Comatose Survivors of Cardiac Arrest.

BACKGROUND: Whether the treatment of rhythmic and periodic electroencephalographic (EEG) patterns in comatose survivors of cardiac arrest improves outcomes is uncertain. METHODS: We conducted an open-label trial of suppressing rhythmic and periodic EEG patterns detected on continuous EEG monitoring in comatose survivors of cardiac arrest. Patients were randomly assigned in a 1:1 ratio to a stepwise strategy of antiseizure medications to suppress this activity for at least 48 consecutive hours plus standard care (antiseizure-treatment group) or to standard care alone (control group); standard care included targeted temperature management in both groups. The primary outcome was neurologic outcome according to the score on the Cerebral Performance Category (CPC) scale at 3 months, dichotomized as a good outcome (CPC score indicating no, mild, or moderate disability) or a poor outcome (CPC score indicating severe disability, coma, or death). Secondary outcomes were mortality, length of stay in the intensive care unit (ICU), and duration of mechanical ventilation. RESULTS: We enrolled 172 patients, with 88 assigned to the antiseizure-treatment group and 84 to the control group. Rhythmic or periodic EEG activity was detected a median of 35 hours after cardiac arrest; 98 of 157 patients (62%) with available data had myoclonus. Complete suppression of rhythmic and periodic EEG activity for 48 consecutive hours occurred in 49 of 88 patients (56%) in the antiseizure-treatment group and in 2 of 83 patients (2%) in the control group. At 3 months, 79 of 88 patients (90%) in the antiseizure-treatment group and 77 of 84 patients (92%) in the control group had a poor outcome (difference, 2 percentage points; 95% confidence interval, -7 to 11; P = 0.68). Mortality at 3 months was 80% in the antiseizure-treatment group and 82% in the control group. The mean length of stay in the ICU and mean duration of mechanical ventilation were slightly longer in the antiseizure-treatment group than in the control group. CONCLUSIONS: In comatose survivors of cardiac arrest, the incidence of a poor neurologic outcome at 3 months did not differ significantly between a strategy of suppressing rhythmic and periodic EEG activity with the use of antiseizure medication for at least 48 hours plus standard care and standard care alone. (Funded by the Dutch Epilepsy Foundation; TELSTAR ClinicalTrials.gov number, NCT02056236.).

Near-Infrared Spectroscopy-Derived Dynamic Cerebral Autoregulation in Experimental Human Endotoxemia-An Exploratory Study.

Cerebral perfusion may be altered in sepsis patients. However, there are conflicting findings on cerebral autoregulation (CA) in healthy participants undergoing the experimental endotoxemia protocol, a proxy for systemic inflammation in sepsis. In the current study, a newly developed near-infrared spectroscopy (NIRS)-based CA index is investigated in an endotoxemia study population, together with an index of focal cerebral oxygenation. Methods: Continuous-wave NIRS data were obtained from 11 healthy participants receiving a continuous infusion of bacterial endotoxin for 3 h (ClinicalTrials.gov NCT02922673) under extensive physiological monitoring. Oxygenated-deoxygenated hemoglobin phase differences in the (very)low frequency (VLF/LF) bands and the Tissue Saturation Index (TSI) were calculated at baseline, during systemic inflammation, and at the end of the experiment 7 h after the initiation of endotoxin administration. Results: The median (inter-quartile range) LF phase difference was 16.2° (3.0-52.6°) at baseline and decreased to 3.9° (2.0-8.8°) at systemic inflammation (p = 0.03). The LF phase difference increased from systemic inflammation to 27.6° (12.7-67.5°) at the end of the experiment (p = 0.005). No significant changes in VLF phase difference were observed. The TSI (mean ± SD) increased from 63.7 ± 3.4% at baseline to 66.5 ± 2.8% during systemic inflammation (p = 0.03) and remained higher at the end of the experiment (67.1 ± 4.2%, p = 0.04). Further analysis did not reveal a major influence of changes in several covariates such as blood pressure, heart rate, PaCO2, and temperature, although some degree of interaction could not be excluded. Discussion: A reversible decrease in NIRS-derived cerebral autoregulation phase difference was seen after endotoxin infusion, with a small, sustained increase in TSI. These findings suggest that endotoxin administration in healthy participants reversibly impairs CA, accompanied by sustained microvascular vasodilation.

Targeting Autoregulation-Guided Cerebral Perfusion Pressure after Traumatic Brain Injury (COGiTATE): A Feasibility Randomized Controlled Clinical Trial.

Managing traumatic brain injury (TBI) patients with a cerebral perfusion pressure (CPP) near to the cerebral autoregulation (CA)-guided "optimal" CPP (CPPopt) value is associated with improved outcome and might be useful to individualize care, but has never been prospectively evaluated. This study evaluated the feasibility and safety of CA-guided CPP management in TBI patients requiring intracranial pressure monitoring and therapy (TBIicp patients). The CPPopt Guided Therapy: Assessment of Target Effectiveness (COGiTATE) parallel two-arm feasibility trial took place in four tertiary centers. TBIicp patients were randomized to either the Brain Trauma Foundation (BTF) guideline CPP target range (control group) or to the individualized CA-guided CPP targets (intervention group). CPP targets were guided by six times daily software-based alerts for up to 5 days. The primary feasibility end-point was the percentage of time with CPP concordant (±5 mm Hg) with the set CPP targets. The main secondary safety end-point was an increase in therapeutic intensity level (TIL) between the control and intervention group. Twenty-eight patients were randomized to the control and 32 patients to the intervention group. CPP in the intervention group was in the target range for 46.5% (interquartile range, 41.2-58) of the monitored time, significantly higher than the feasibility target specified in the published protocol (36%; p < 0.001). There were no significant differences between groups for TIL or for other safety end-points. Conclusively, targeting an individual and dynamic CA-guided CPP is feasible and safe in TBIicp patients. This encourages a prospective trial powered for clinical outcomes.