Improving Outcomes After Post-Cardiac Arrest Brain Injury: A Scientific Statement From the International Liaison Committee on Resuscitation.

This scientific statement presents a conceptual framework for the pathophysiology of post-cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post-cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post-cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post-cardiac arrest brain injury.

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.).

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.

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.

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.

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.

Adult Advanced Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations for advanced life support includes updates on multiple advanced life support topics addressed with 3 different types of reviews. Topics were prioritized on the basis of both recent interest within the resuscitation community and the amount of new evidence available since any previous review. Systematic reviews addressed higher-priority topics, and included double-sequential defibrillation, intravenous versus intraosseous route for drug administration during cardiac arrest, point-of-care echocardiography for intra-arrest prognostication, cardiac arrest caused by pulmonary embolism, postresuscitation oxygenation and ventilation, prophylactic antibiotics after resuscitation, postresuscitation seizure prophylaxis and treatment, and neuroprognostication. New or updated treatment recommendations on these topics are presented. Scoping reviews were conducted for anticipatory charging and monitoring of physiological parameters during cardiopulmonary resuscitation. Topics for which systematic reviews and new Consensuses on Science With Treatment Recommendations were completed since 2015 are also summarized here. All remaining topics reviewed were addressed with evidence updates to identify any new evidence and to help determine which topics should be the highest priority for systematic reviews in the next 1 to 2 years.

Coronavirus Disease 2019 Immediately Increases Burnout Symptoms in ICU Professionals: A Longitudinal Cohort Study.

OBJECTIVES: ICU professionals are at risk of developing burnout due to coronavirus disease 2019. This study assesses the prevalence and incidence of burnout symptoms and moral distress in ICU professionals before and during the coronavirus disease 2019 crisis. DESIGN: This is a longitudinal open cohort study. SETTING: Five ICUs based in a single university medical center plus another adult ICU based on a separate teaching hospital in the Netherlands. SUBJECTS: All ICU professionals were sent a baseline survey in October-December 2019 (252 respondents, response rate: 53%), and a follow-up survey was sent in May-June 2020 (233 respondents, response rate: 50%). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Burnout symptoms and moral distress measured with the Maslach Burnout Inventory and the Moral Distress Scale, respectively. The prevalence of burnout symptoms was 23.0% before coronavirus disease 2019 and 36.1% at postpeak time, with higher rates in nurses (38.0%) than in physicians (28.6%). Reversely, the incidence rate of new burnout cases among physicians was higher (26.7%) than nurses (21.9%). Higher prevalence of burnout symptoms was observed in the postpeak coronavirus disease 2019 period (odds ratio, 1.83; 95% CI, 1.32-2.53), for nurses (odds ratio, 1.77; 95% CI, 1.03-3.04), for professionals working overtime (odds ratio 2.11; 95% CI, 1.48-3.02), and for professionals directly engaged with care for coronavirus disease 2019 patients (odds ratio, 1.87; 95% CI, 1.35-2.60). Physicians were more likely than nurses to develop burnout symptoms due to coronavirus disease 2019 (odds ratio, 3.56; 95% CI, 1.06-12.21). CONCLUSIONS: This study shows that overburdening of ICU professionals during an extended period of time leads to symptoms of burnout. Working long hours and under conditions of scarcity of staff, time, and resources comes at the price of ICU professionals' mental health.

Electroencephalographic reactivity as predictor of neurological outcome in postanoxic coma: A multicenter prospective cohort study.

OBJECTIVE: Outcome prediction in patients after cardiac arrest (CA) is challenging. Electroencephalographic reactivity (EEG-R) might be a reliable predictor. We aimed to determine the prognostic value of EEG-R using a standardized assessment. METHODS: In a prospective cohort study, a strictly defined EEG-R assessment protocol was executed twice per day in adult patients after CA. EEG-R was classified as present or absent by 3 EEG readers, blinded to patient characteristics. Uncertain reactivity was classified as present. Primary outcome was best Cerebral Performance Category score (CPC) in 6 months after CA, dichotomized as good (CPC = 1-2) or poor (CPC = 3-5). EEG-R was considered reliable for predicting poor outcome if specificity was ≥95%. For good outcome prediction, a specificity of ≥80% was used. Added value of EEG-R was the increase in specificity when combined with EEG background, neurological examination, and somatosensory evoked potentials (SSEPs). RESULTS: Of 160 patients enrolled, 149 were available for analyses. Absence of EEG-R for poor outcome prediction had a specificity of 82% and a sensitivity of 73%. For good outcome prediction, specificity was 73% and sensitivity 82%. Specificity for poor outcome prediction increased from 98% to 99% when EEG-R was added to a multimodal model. For good outcome prediction, specificity increased from 70% to 89%. INTERPRETATION: EEG-R testing in itself is not sufficiently reliable for outcome prediction in patients after CA. For poor outcome prediction, it has no substantial added value to EEG background, neurological examination, and SSEPs. For prediction of good outcome, EEG-R seems to have added value. ANN NEUROL 2019.

Death after awakening from post-anoxic coma: the "Best CPC" project.

BACKGROUND: In patients who recover consciousness after cardiac arrest (CA), a subsequent death from non-neurological causes may confound the assessment of long-term neurological outcome. We investigated the prevalence and causes of death after awakening (DAA) in a multicenter cohort of CA patients. METHODS: Observational multicenter cohort study on patients resuscitated from CA in eight European intensive care units (ICUs) from January 2007 to December 2014. DAA during the hospital stay was extracted retrospectively from patient medical records. Demographics, comorbidities, initial CA characteristics, concomitant therapies, prognostic tests (clinical examination, electroencephalography (EEG), somatosensory evoked potentials (SSEPs)), and cause of death were identified. RESULTS: From a total 4646 CA patients, 2478 (53%) died in-hospital, of whom 196 (4.2%; ranges 0.6-13.0%) had DAA. DAA was less frequent among out-of-hospital than in-hospital CA (82/2997 [2.7%] vs. 114/1649 [6.9%]; p < 0.001). Median times from CA to awakening and from awakening to death were 2 [1-5] and 9 [3-18] days, respectively. The main causes of DAA were multiple organ failure (n = 61), cardiogenic shock (n = 61), and re-arrest (n = 26). At day 3 from admission, results from EEG (n = 56) and SSEPs (n = 60) did not indicate poor outcome. CONCLUSIONS: In this large multicenter cohort, DAA was observed in 4.2% of non-survivors. Information on DAA is crucial since it may influence epidemiology and the design of future CA studies evaluating neuroprognostication and neuroprotection.

Quantification of Macrocirculation and Microcirculation in Brain Using Ultrasound Perfusion Imaging.

OBJECTIVE: The aim of this study was to investigate the feasibility of simultaneous visualization of the cerebral macrocirculation and microcirculation, using ultrasound perfusion imaging (UPI). In addition, we studied the sensitivity of this technique for detecting changes in cerebral blood flow (CBF). MATERIALS AND METHODS: We performed an observational study in ten healthy volunteers. Ultrasound contrast was used for UPI measurements during normoventilation and hyperventilation. For the data analysis of the UPI measurements, an in-house algorithm was used to visualize the DICOM files, calculate parameter images and select regions of interest (ROIs). Next, time intensity curves (TIC) were extracted and perfusion parameters calculated. RESULTS: Both volume- and velocity-related perfusion parameters were significantly different between the macrocirculation and the parenchymal areas. Hyperventilation-induced decreases in CBF were detectable by UPI in both the macrocirculation and microcirculation, most consistently by the volume-related parameters. The method was safe, with no adverse effects in our population. CONCLUSIONS: Bedside quantification of CBF seems feasible and the technique has a favourable safety profile. Adjustment of current method is required to improve its diagnostic accuracy. Validation studies using a 'gold standard' are needed to determine the added value of UPI in neurocritical care monitoring.

Request for organ donation without donor registration: a qualitative study of the perspectives of bereaved relatives.

BACKGROUND: In the Netherlands, consent from relatives is obligatory for post mortal donation. This study explored the perspectives of relatives regarding the request for consent for donation in cases without donor registration. METHODS: A content analysis of narratives of 24 bereaved relatives (14 in-depth interviews and one letter) of unregistered, eligible, brain-dead donors was performed. RESULTS: Relatives of unregistered, brain-dead patients usually refuse consent for donation, even if they harbour pro-donation attitudes themselves, or knew that the deceased favoured organ donation. Half of those who refused consent for donation mentioned afterwards that it could have been an option. The decision not to consent to donation is attributed to contextual factors, such as feeling overwhelmed by the notification of death immediately followed by the request; not being accustomed to speaking about death; inadequate support from other relatives or healthcare professionals, and lengthy procedures. CONCLUSION: Healthcare professionals could provide better support to relatives prior to donation requests, address their informational needs and adapt their message to individual circumstances. It is anticipated that the number of consenting families could be enlarged by examining the experience of decoupling and offering the possibility of consent for donation after circulatory death if families refuse consent for donation after brain-death.

The Involvement of Danger-Associated Molecular Patterns in the Development of Immunoparalysis in Cardiac Arrest Patients.

OBJECTIVES: After cardiac arrest, patients are highly vulnerable toward infections, possibly due to a suppressed state of the immune system called "immunoparalysis." We investigated if immunoparalysis develops following cardiac arrest and whether the release of danger-associated molecular patterns could be involved. DESIGN: Observational study. SETTING: ICU of a university medical center. PATIENTS: Fourteen post-cardiac arrest patients treated with mild therapeutic hypothermia for 24 hours and 11 control subjects. MEASUREMENTS AND MAIN RESULTS: Plasma cytokines showed highest levels within 24 hours after cardiac arrest and decreased during the next 2 days. By contrast, ex vivo production of cytokines interleukin-6, tumor necrosis factor-α, and interleukin-10 by lipopolysaccharide-stimulated leukocytes was severely impaired compared with control subjects, with most profound effects observed at day 0, and only partially recovering afterward. Compared with incubation at 37°C, incubation at 32°C resulted in higher interleukin-6 and lower interleukin-10 production by lipopolysaccharide-stimulated leukocytes of control subjects, but not of patients. Plasma nuclear DNA, used as a marker for general danger-associated molecular pattern release, and the specific danger-associated molecular patterns (EN-RAGE and heat shock protein 70) were substantially higher in patients at days 0 and 1 compared with control subjects. Furthermore, plasma heat shock protein 70 levels were negatively correlated with ex vivo production of inflammatory mediators interleukin-6, tumor necrosis factor-α, and interleukin-10. Extracellular newly identified receptor for advanced glycation end products-binding protein levels only showed a significant negative correlation with ex vivo production of interleukin-6 and tumor necrosis factor-α and a borderline significant inverse correlation with interleukin-10. No significant correlations were observed between plasma nuclear DNA levels and ex vivo cytokine production. INTERVENTIONS: None. CONCLUSIONS: Release of danger-associated molecular patterns during the first days after cardiac arrest is associated with the development of immunoparalysis. This could explain the increased susceptibility toward infections in cardiac arrest patients.

Decision making on organ donation: the dilemmas of relatives of potential brain dead donors.

BACKGROUND: This article is part of a study to gain insight into the decision-making process by looking at the views of the relatives of potential brain dead donors. Alongside a literature review, focus interviews were held with healthcare professionals about their role in the request and decision-making process when post-mortal donation is at stake. This article describes the perspectives of the relatives. METHODS: A content-analysis of 22 semi-structured in-depth interviews with relatives involved in an organ donation decision. RESULTS: Three themes were identified: 'conditions', 'ethical considerations' and 'look back'. Conditions were: 'sense of urgency', 'incompetence to decide' and 'agreement between relatives'. Ethical considerations result in a dilemma for non-donor families: aiding people or protecting the deceased's body, especially when they do not know his/her preference. Donor families respect the deceased's last will, generally confirmed in the National Donor Register. Looking back, the majority of non-donor families resolved their dilemma by justifying their decision with external arguments (lack of time, information etc.). Some non-donor families would like to be supported during decision-making. DISCUSSION: The discrepancy between general willingness to donate and the actual refusal of a donation request can be explained by multiple factors, with a cumulative effect. Firstly, half of the participants (most non-donor families) stated that they felt that they were not competent to decide in such a crisis and they seem to struggle with utilitarian considerations against their wish to protect the body. Secondly, non-donor families refused telling that they did not know the deceased's wishes or contesting posthumous autonomy of the eligible. Thirdly, the findings emphasise the importance of Donor Registration, because it seems to prevent dilemmas in decision-making, at least for donor families. CONCLUSION: Discrepancies between willingness to consent to donate and refusal at the bedside can be attributed to an unresolved dilemma: aiding people or protect the body of the deceased. Non-donor families felt incompetent to decide. They refused consent for donation, since their deceased had not given any directive. When ethical considerations do not lead to an unambiguous answer, situational factors were pivotal. Relatives of unregistered eligible donors are more prone to unstable decisions. To overcome ambivalence, coaching during decision-making is worth investigation.

Effects of viscosity on cerebral blood flow after cardiac arrest.

OBJECTIVES: To determine blood viscosity in adult comatose patients treated with mild therapeutic hypothermia after cardiac arrest and to assess the relation between blood viscosity, cerebral blood flow, and cerebral oxygen extraction. DESIGN: Observational study. SETTING: Tertiary care university hospital. PATIENTS: Ten comatose patients with return of spontaneous circulation after out-of-hospital cardiac arrest. INTERVENTION: Treatment with mild therapeutic hypothermia for 24 hours followed by passive rewarming to normothermia. MEASUREMENTS AND MAIN RESULTS: Median viscosity at shear rate 50/s was 5.27 mPa · s (4.29-5.91 mPa · s) at admission; it remained relatively stable during the first 12 hours and decreased significantly to 3.00 mPa · s (2.72-3.58 mPa · s) at 72 hours (p < 0.001). Median mean flow velocity in the middle cerebral artery was low (27.0 cm/s [23.8-30.5 cm/s]) at admission and significantly increased to 63.0 cm/s (51.0-80.0 cm/s) at 72 hours. Median jugular bulb saturation at the start of the study was 61.5% (55.5-75.3%) and significantly increased to 73.0% (69.0-81.0%) at 72 hours. Median hematocrit was 0.41 L/L (0.36-0.44 L/L) at admission and subsequently decreased significantly to 0.32 L/L (0.27-0.35 L/L) at 72 hours. Median C-reactive protein concentration was low at admission (2.5 mg/L [2.5-6.5 mg/L]) and increased to 101 mg/L (65-113.3 mg/L) in the following hours. Median fibrinogen concentration was increased at admission 2,795 mg/L (2,503-3,565 mg/L) and subsequently further increased to 6,195 mg/L (5,843-7,368 mg/L) at 72 hours. There was a significant negative association between blood viscosity and the mean flow velocity in the middle cerebral artery (p = 0.0008). CONCLUSIONS: Changes in blood viscosity in vivo are associated with changes in flow velocity in the middle cerebral artery. High viscosity early after cardiac arrest may reduce cerebral blood flow and may contribute to secondary brain injury. Further studies are needed to determine the optimal viscosity during the different stages of the postcardiac arrest syndrome.

Seventy-two hours of mild hypothermia after cardiac arrest is associated with a lowered inflammatory response during rewarming in a prospective observational study.

INTRODUCTION: Whole-body ischemia and reperfusion trigger a systemic inflammatory response. In this study, we analyzed the effect of temperature on the inflammatory response in patients treated with prolonged mild hypothermia after cardiac arrest. METHODS: Ten comatose patients with return of spontaneous circulation after pulseless electrical activity/asystole or prolonged ventricular fibrillation were treated with mild therapeutic hypothermia for 72 hours after admission to a tertiary care university hospital. At admission and at 12, 24, 36, 48, 72, 96 and 114 hours, the patients' temperature was measured and blood samples were taken from the arterial catheter. Proinflammatory interleukin 6 (IL-6) and anti-inflammatory (IL-10) cytokines and chemokines (IL-8 and monocyte chemotactic protein 1), intercellular adhesion molecule 1 and complement activation products (C1r-C1s-C1inhibitor, C4bc, C3bPBb, C3bc and terminal complement complex) were measured. Changes over time were analyzed with the repeated measures test for nonparametric data. Dunn's multiple comparisons test was used for comparison of individual time points. RESULTS: The median temperature at the start of the study was 34.3°C (33.4°C to 35.2°C) and was maintained between 32°C and 34°C for 72 hours. All patients were passively rewarmed after 72 hours, from (median (IQR)) 33.7°C (33.1°C to 33.9°C) at 72 hours to 38.0°C (37.5°C to 38.1°C) at 114 hours (P <0.001). In general, the cytokines and chemokines remained stable during hypothermia and decreased during rewarming, whereas complement activation was suppressed during the whole hypothermia period and increased modestly during rewarming. CONCLUSIONS: Prolonged hypothermia may blunt the inflammatory response after rewarming in patients after cardiac arrest. Complement activation was low during the whole hypothermia period, indicating that complement activation is also highly temperature-sensitive in vivo. Because inflammation is a strong mediator of secondary brain injury, a blunted proinflammatory response after rewarming may be beneficial.