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Background Coagulopathy after traumatic brain injury (TBI) is associated with poor prognosis. Purpose To assess the prevalence and association with outcomes of early thrombocytopenia in patients with TBI treated in the intensive care unit (ICU). Methods This is a retrospective multicenter study of adult TBI patients admitted to ICUs during 2003–2019. Thrombocytopenia was defined as a platelet count 9/L during the first day. The association between thrombocytopenia and hospital and 12-month mortality was tested using multivariable logistic regression, adjusting for markers of injury severity. Results Of 4419 patients, 530 (12%) had early thrombocytopenia. In patients with thrombocytopenia, hospital and 12-month mortality were 26% and 48%, respectively; in patients with a platelet count > 100 × 109/L, they were 9% and 22%, respectively. After adjusting for injury severity, a higher platelet count was associated with decreased odds of hospital mortality (OR 0.998 per unit, 95% CI 0.996–0.999) and 12-month mortality (OR 0.998 per unit, 95% CI 0.997–0.999) in patients with moderate-to-severe TBI. Compared to patients with a normal platelet count, patients with thrombocytopenia not receiving platelet transfusion had an increased risk of 12-month mortality (OR 2.2, 95% CI 1.6–3.0), whereas patients with thrombocytopenia receiving platelet transfusion did not (OR 1.0, 95% CI 0.6–1.7). Conclusion Early thrombocytopenia occurs in approximately one-tenth of patients with TBI treated in the ICU, and it is an independent risk factor for mortality in patients with moderate-to-severe TBI. Further research is necessary to determine whether this is modifiable by platelet transfusion.

IMPORTANCE: Brain injury biomarkers released into circulation from the injured neurovascular unit are important prognostic tools in patients with cardiac arrest who develop hypoxic ischemic brain injury (HIBI) after return of spontaneous circulation (ROSC). OBJECTIVE: To assess the neuroprognostic utility of bloodborne brain injury biomarkers in patients with cardiac arrest with HIBI. DATA SOURCES: Studies in electronic databases from inception to September 15, 2021. These databases included MEDLINE, Embase, Evidence-Based Medicine Reviews, CINAHL, Cochrane Database of Systematic Reviews, and the World Health Organization Global Health Library. STUDY SELECTION: Articles included in this systmatic review and meta-analysis were independently assessed by 2 reviewers. We included studies that investigated neuron-specific enolase, S100 calcium-binding protein β, glial fibrillary acidic protein, neurofilament light, tau, or ubiquitin carboxyl hydrolase L1 in patients with cardiac arrest aged 18 years and older for neurologic prognostication. We excluded studies that did not (1) dichotomize neurologic outcome as favorable vs unfavorable, (2) specify the timing of blood sampling or outcome determination, or (3) report diagnostic test accuracy or biomarker concentration. DATA EXTRACTION AND SYNTHESIS: Data on the study design, inclusion and exclusion criteria, brain biomarkers levels, diagnostic test accuracy, and neurologic outcome were recorded. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. MAIN OUTCOMES AND MEASURES: Summary receiver operating characteristic curve analysis was used to calculate the area under the curve, sensitivity, specificity, and optimal thresholds for each biomarker. Risk of bias and concerns of applicability were assessed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. RESULTS: We identified 2953 studies, of which 86 studies with 10 567 patients (7777 men [73.6] and 2790 women [26.4]; pooled mean [SD] age, 62.8 [10.2] years) were included. Biomarker analysis at 48 hours after ROSC demonstrated that neurofilament light had the highest predictive value for unfavorable neurologic outcome, with an area under the curve of 0.92 (95% CI, 0.84-0.97). Subgroup analyses of patients treated with targeted temperature management and those who specifically had an out-of-hospital cardiac arrest showed similar results (targeted temperature management, 0.92 [95% CI, 0.86-0.95] and out-of-hospital cardiac arrest, 0.93 [95% CI, 0.86-0.97]). CONCLUSIONS AND RELEVANCE: Neurofilament light, which reflects white matter damage and axonal injury, yielded the highest accuracy in predicting neurologic outcome in patients with HIBI at 48 hours after ROSC. TRIAL REGISTRATION: PROSPERO Identifier: CRD42020157366

Publisher Copyright: © 2021 Elsevier Ltd As more people are surviving cardiac arrest, focus needs to shift towards improving neurological outcomes and quality of life in survivors. Brain injury after resuscitation, a common sequela following cardiac arrest, ranges in severity from mild impairment to devastating brain injury and brainstem death. Effective strategies to minimise brain injury after resuscitation include early intervention with cardiopulmonary resuscitation and defibrillation, restoration of normal physiology, and targeted temperature management. It is important to identify people who might have a poor outcome, to enable informed choices about continuation or withdrawal of life-sustaining treatments. Multimodal prediction guidelines seek to avoid premature withdrawal in those who might survive with a good neurological outcome, or prolonging treatment that might result in survival with severe disability. Approximately one in three admitted to intensive care will survive, many of whom will need intensive, tailored rehabilitation after discharge to have the best outcomes.

his is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed. This is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed.

Informed by a series of systematic reviews, scoping reviews and evidence updates from the International Liaison Committee on Resuscitation, the 2021 European Resuscitation Council Guidelines present the most up to date evidence-based guidelines for the practice of resuscitation across Europe. The guidelines cover the epidemiology of cardiac arrest; the role that systems play in saving lives, adult basic life support, adult advanced life support, resuscitation in special circumstances, post resuscitation care, first aid, neonatal life support, paediatric life support, ethics and education.

Background Hypotension is common after cardiac arrest (CA), and current guidelines recommend using vasopressors to target mean arterial blood pressure (MAP) higher than 65 mmHg. Pilot trials have compared higher and lower MAP targets. We will review the evidence on whether higher MAP improves outcome after cardiac arrest. Methods This systematic review and meta-analysis will be conducted based on a systematic search of relevant major medical databases from their inception onwards, including MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL), as well as clinical trial registries. We will identify randomised controlled trials published in the English language that compare targeting a MAP higher than 65-70 mmHg in CA patients using vasopressors, inotropes and intravenous fluids. The data extraction will be performed separately by two authors (a third author will be involved in case of disagreement), followed by a bias assessment with the Cochrane Risk of Bias tool using an eight-step procedure for assessing if thresholds for clinical significance are crossed. The outcomes will be all-cause mortality, functional long-term outcomes and serious adverse events. We will contact the authors of the identified trials to request individual anonymised patient data to enable individual patient data meta-analysis, aggregate data meta-analyses, trial sequential analyses and multivariable regression, controlling for baseline characteristics. The certainty of the evidence will be assessed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. We will register this systematic review with Prospero and aim to redo it when larger trials are published in the near future. Conclusions This protocol defines the performance of a systematic review on whether a higher MAP after cardiac arrest improves patient outcome. Repeating this systematic review including more data likely will allow for more certainty regarding the effect of the intervention and possible sub-groups differences. Sigrid Juselius Stifelse [8050]; Academy of Finland [341277]

This2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendationsfor 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.

Aim The efficiency of rapid response teams (RRTs) is decreased by delays in activation of RRT (afferent limb failure, ALF). We categorized ALF by organ systems and investigated correlations with the vital signs subsequently observed by the RRT and associations with mortality. Methods International, multicentre, retrospective cohort study including adult RRT patients without treatment limitations in 2017–2018 in one Australian and two Finnish tertiary hospitals. Results A total of 5,568 RRT patients’ first RRT activations were included. In 927 patients (17%) ALF was present within 4 h before the RRT call, most commonly for respiratory criteria (419 patients, 7.5%). In 3516 patients (63%) overall, and in 756 (82%) of ALF patients, the RRT observed abnormal vital signs upon arrival. The organ-specific ALF corresponded to the RRT observations in 52% of cases for respiratory criteria, in 60% for haemodynamic criteria, in 55% for neurological criteria and in 52% of cases for multiple organ criteria. Only ALF for respiratory criteria was associated with increased hospital mortality (OR 1.71, 95% CI 1.29–2.27), whereas all, except haemodynamic, criteria at the time of RRT review were associated with increased hospital mortality. Conclusions Vital signs were rarely normal upon RRT arrival in patients with ALF, while organ-specific ALF corresponded to subsequent RRT observations in just over half of cases. Our results suggest that systems mandating timely responses to abnormal respiratory criteria in particular may have potential to improve deteriorating patient outcomes.

Background: Our aim was to assess the occurrence and risk factors for psychotropic medication use after pediatric traumatic brain injury treated in the intensive care unit. Methods: We combined data from the Finnish Intensive Care Consortium database, data on reimbursed medications from the Social Insurance Institute, and individual electronic health care data. We analyzed data on children aged five to 17 years treated for traumatic brain injury in intensive care units of four university hospitals in Finland during 2003 to 2013 and being alive six months after injury with no history of psychotropic medication use before traumatic brain injury. Results: We identified 248 patients of whom 46 (19%) were prescribed a new psychotropic medication after traumatic brain injury. In multivariable logistic regression, a higher age associated with a higher probability for use of any psychotropic medication. Subgroup analyses showed that higher age associated with an increased risk of antidepressant and antipsychotic use but with a decreased risk of stimulant use. Apart from age, we found no other clinical, radiological, or treatment-related factors that significantly associated with subsequent use of psychotropics. Psychotropic medication was most common (45%) in children aged 12 to 17 years and had moderate disability at six-month follow-up. Conclusions: One fifth of children treated in the intensive care unit for traumatic brain injury were prescribed a new psychotropic medication during a median follow-up of three years and five months. Psychotropic medication was most common among teenagers with moderate post-traumatic disability. The need and use of psychotropics postinjury seem multifactorial and not related to any traumatic brain injury type. (C) 2020 Elsevier Inc. All rights reserved.

Background The benefits of early surgery in cases of superficial supratentorial spontaneous intracerebral hemorrhage (ICH) are unclear. This study aimed to assess the association between early ICH surgery and outcome, as well as the cost-effectiveness of early ICH surgery. Methods We conducted a retrospective, register-based multicenter study that included all patients who had been treated for supratentorial spontaneous ICH in four tertiary intensive care units in Finland between 2003 and 2013. To be included, patients needed to have experienced supratentorial ICHs that were 10–100 cm3 and located within 10 mm of the cortex. We used a multivariable analysis, adjusting for the severity of the illness and the probability of surgical treatment, to assess the independent association between early ICH surgery (≤ 1 day), 12-month mortality rates, and the probability of survival without permanent disability. In addition, we assessed the cost-effectiveness of ICH surgery by examining the effective cost per 1-year survivor (ECPS) and per independent survivor (ECPIS). Results Of 254 patients, 27% were in the early surgery group. Overall 12-month mortality was 39%, while 29% survived without a permanent disability. According to our multivariable analysis, early ICH surgery was associated with lower 12-month mortality rates (odds ratio [OR] 0.22, 95% confidence intervals [CI] 0.10–0.51), but not with a higher probability of survival without permanent disability (OR 1.23, 95% CI 0.59–2.56). For the early surgical group, the ECPS and ECPIS were €111,409 and €334,227, respectively. For the non-surgical cohort, the ECPS and ECPIS were €76,074 and €141,471, respectively. Conclusions Early surgery for superficial ICH is associated with a lower 12-month mortality risk but not with a higher probability of survival without a permanent disability. Further, costs were higher and cost-effectiveness was, thus, worse for the early surgical cohort.

Background Randomised clinical trials with a factorial design may assess the effects of multiple interventions in the same population. Factorial trials are carried out under the assumption that the trial interventions have no interactions on outcomes. Here, we present a protocol for a simulation study investigating the consequences of different levels of interactions between the trial interventions on outcomes for the future 2×2×2 factorial designed randomised clinical Sedation, TEmperature, and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial in comatose patients after out-of-hospital cardiac arrest. Methods By simulating a multisite trial with 50 sites and 3278 participants, and a presumed six-month all-cause mortality of 60% in the control population, we will investigate the validity of the trial results with different levels of interaction effects on the outcome. The primary simulation outcome of the study is the risks of type-1 and type-2 errors in the simulated scenarios, i.e. at what level of interaction is the desired alpha and beta level exceeded. When keeping the overall risk of type-1 errors ≤ 5% and the risk of type-2 errors ≤ 10%, we will quantify the maximum interaction effect we can accept if the planned sample size is increased by 5% to take into account possible interaction between the trial interventions. Secondly, we will assess how interaction effects influence the minimal detectable difference we may confirm or reject to take into account 5% (small interaction effect), 10% (moderate), or 15% (large) positive interactions in simulations with no ‘true’ intervention effect (type-1 errors) and small (5%), moderate (10%), or large negative interactions (15%) in simulations with ‘true’ intervention effects (type-2 errors). Moreover, we will investigate how much the sample size must be increased to account for a small, moderate, or large interaction effects. Discussion This protocol for a simulation study will inform the design of a 2×2×2 factorial randomised clinical trial of how potential interactions between the assessed interventions might affect conclusions. Protocolising this simulation study is important to ensure valid and unbiased results. Trial registration Not relevant

During the COVID-19 pandemic, prehospital and hospital services were put under great stress because of limited resources and increased workloads. One expected effect was the increased number of out-of-hospital (OHCA) and in-hospital (IHCA) cardiac arrests that occurred during 2020 compared to previous years. Both direct and indirect mechanisms were involved. In the former case, although the exact mechanisms by which SARS-CoV-2 causes cardiac arrest (CA) are still unknown, severe hypoxia, a dysregulated immune host response and sepsis are probably implicated and are often seen in COVID-19 patients with poor outcomes. In the latter case, the strain on hospitals, changes in treatment protocols, governments' actions to limit the spread of the disease and fear of the contagion naturally affected treatment efficacy and disrupted the CA chain of survival; as expected in OHCA, only a small proportion of patients were positive to COVID-19, and yet reported outcomes were worse during the pandemic. CA patient characteristics were reported, along with modifications in patient management. In this review, we summarize the evidence to date regarding OHCA and IHCA epidemiology and management during the COVID-19 pandemic.

SCOPUS: no.j, info:eu-repo/semantics/published

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2022. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2022 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .

BACKGROUND: Electrolyte disturbances can result from targeted temperature treatment (TTM) in out-of-hospital cardiac arrest (OHCA) patients. This study explores electrolyte changes in blood and urine in OHCA patients treated with TTM.METHODS: This is a sub-study of the TTH48 trial, with the inclusion of 310 unconscious OHCA patients treated with TTM at 33°C for 24 or 48 h. Over a three-day period, serum concentrations were obtained on sodium potassium, chloride, ionized calcium, magnesium and phosphate, as were results from a 24-h diuresis and urine electrolyte concentration and excretion. Changes over time were analysed with a mixed-model multivariate analysis of variance with repeated measurements.RESULTS: On admission, mean ± SD sodium concentration was 138 ± 3.5 mmol/l, which increased slightly but significantly (p < .05) during the first 24 h. Magnesium concentration stayed within the reference interval. Median ionized calcium concentration increased from 1.11 (IQR 1.1-1.2) mmol/l during the first 24 h (p < .05), whereas median phosphate concentration dropped to 1.02 (IQR 0.8-1.2) mmol/l (p < .05) and stayed low. During rewarming, potassium concentrations increased, and magnesium and ionizes calcium concentration decreased (p < .05). Median 24-h diuresis results on days one and two were 2198 and 2048 ml respectively, and the electrolyte excretion mostly stayed low in the reference interval.CONCLUSIONS: Electrolytes mostly remained within the reference interval. A temporal change occurred in potassium, magnesium and calcium concentrations with TTM's different phases. No hypothermia effect on diuresis was detected, and urine excretion of electrolytes mostly stayed low.

The aim of these guidelines is to provide evidence based guidance for temperature control in adults who are comatose after resuscitation from either in-hospital or out-of-hospital cardiac arrest, regardless of the underlying cardiac rhythm. These guidelines replace the recommendations on temperature management after cardiac arrest included in the 2021 post-resuscitation care guidelines co-issued by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM). The guideline panel included thirteen international clinical experts who authored the 2021 ERC-ESICM guidelines and two methodologists who participated in the evidence review completed on behalf of the International Liaison Committee on Resuscitation (ILCOR) of whom ERC is a member society. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations. The panel provided suggestions on guideline implementation and identified priorities for future research. The certainty of evidence ranged from moderate to low. In patients who remain comatose after cardiac arrest, we recommend continuous monitoring of core temperature and actively preventing fever (defined as a temperature > 37.7 degrees C) for at least 72 hours. There was insufficient evidence to recommend for or against temperature control at 32-36 degrees C or early cooling after cardiac arrest. We recommend not actively rewarming comatose patients with mild hypothermia after return of spontaneous circulation (ROSC) to achieve normothermia. We recommend not using prehospital cooling with rapid infusion of large volumes of cold intravenous fluids immediately after ROSC.

Background Impaired cerebrovascular reactivity (CVR) is one feature of post cardiac arrest encephalopathy. We studied the incidence and features of CVR by near infrared spectroscopy (NIRS) and associations with outcome and biomarkers of brain injury. Methods A post-hoc analysis of 120 comatose OHCA patients continuously monitored with NIRS and randomised to low- or high-normal oxygen, carbon dioxide and mean arterial blood pressure (MAP) targets for 48 h. The tissue oximetry index (TOx) generated by the moving correlation coefficient between cerebral tissue oxygenation measured by NIRS and MAP was used as a dynamic index of CVR with TOx > 0 indicating impaired reactivity and TOx > 0.3 used to delineate the lower and upper MAP bounds for disrupted CVR. TOx was analysed in the 0–12, 12–24, 24–48 h time-periods and integrated over 0–48 h. The primary outcome was the association between TOx and six-month functional outcome dichotomised by the cerebral performance category (CPC1-2 good vs. 3–5 poor). Secondary outcomes included associations with MAP bounds for CVR and biomarkers of brain injury. Results In 108 patients with sufficient data to calculate TOx, 76 patients (70%) had impaired CVR and among these, chronic hypertension was more common (58% vs. 31%, p = 0.002). Integrated TOx for 0–48 h was higher in patients with poor outcome than in patients with good outcome (0.89 95% CI [− 1.17 to 2.94] vs. − 2.71 95% CI [− 4.16 to − 1.26], p = 0.05). Patients with poor outcomes had a decreased upper MAP bound of CVR over time (p = 0.001), including the high-normal oxygen (p = 0.002), carbon dioxide (p = 0.012) and MAP (p = 0.001) groups. The MAP range of maintained CVR was narrower in all time intervals and intervention groups (p p = 0.042). Conclusion Impaired CVR over 48 h was more common in patients with chronic hypertension and associated with poor outcome. Decreased upper MAP bound and a narrower MAP range for maintained CVR were associated with poor outcome and more severe brain injury assessed with NfL. Trial registration ClinicalTrials.gov, NCT02698917.

Background Temperature control with target temperature management (TTM) after cardiac arrest has been endorsed by expert societies and adopted in international clinical practice guidelines but recent evidence challenges the use of hypothermic TTM. Methods Systematic review and Bayesian meta-analysis of clinical trials on adult survivors from cardiac arrest undergoing TTM for at least 12 h comparing TTM versus no TTM or with a separation > 2 °C between intervention and control groups using the PubMed/MEDLINE, EMBASE, CENTRAL databases from inception to 1 September 2021 (PROSPERO CRD42021248140). All randomised and quasi-randomised controlled trials were considered. The risk ratio and 95% confidence interval for death (primary outcome) and unfavourable neurological recovery (secondary outcome) were captured using the original study definitions censored up to 180 days after cardiac arrest. Bias was assessed using the updated Cochrane risk-of-bias for randomised trials tool and certainty of evidence assessed using the Grading of Recommendation Assessment, Development and Evaluation methodology. A hierarchical robust Bayesian model-averaged meta-analysis was performed using both minimally informative and data-driven priors and reported by mean risk ratio (RR) and its 95% credible interval (95% CrI). Results In seven studies (three low bias, three intermediate bias, one high bias, very low to low certainty) recruiting 3792 patients the RR by TTM 32–34 °C was 0.95 [95% CrI 0.78—1.09] for death and RR 0.93 [95% CrI 0.84—1.02] for unfavourable neurological outcome. The posterior probability for no benefit (RR ≥ 1) by TTM 32–34 °C was 24% for death and 12% for unfavourable neurological outcome. The posterior probabilities for favourable treatment effects of TTM 32–34 °C were the highest for an absolute risk reduction of 2–4% for death (28–53% chance) and unfavourable neurological outcome (63–78% chance). Excluding four studies without active avoidance of fever in the control arm reduced the probability to achieve an absolute risk reduction > 2% for death or unfavourable neurological outcome to ≤ 50%. Conclusions The posterior probability distributions did not support the use of TTM at 32–34 °C compared to 36 °C also including active control of fever to reduce the risk of death and unfavourable neurological outcome at 90–180 days. Any likely benefit of hypothermic TTM is smaller than targeted in RCTs to date.

The EPO-TBI multi-national randomized controlled trial found that erythropoietin (EPO), when compared to placebo, did not affect 6-month neurological outcome, but reduced illness severity-adjusted mortality in patients with traumatic brain injury (TBI), making the cost-effectiveness of EPO in TBI uncertain. The current study uses patient-level data from the EPO-TBI trial to evaluate the cost-effectiveness of EPO in patients with moderate or severe TBI from the healthcare payers' perspective. We addressed the issue of transferability in multi-national trials by estimating costs and effects for specific geographical regions of the study (Australia/New Zealand, Europe, and Saudi Arabia). Unadjusted mean quality-adjusted life-years (QALYs; 95% confidence interval [CI]) at 6 months were 0.027 (0.020-0.034; p

Aim Studies suggest that hyperoxemia increases short-term mortality after cardiopulmonary resuscitation (CPR), but the effect of hyperoxemia on long-term outcomes is unclear. We determined the prevalence of early hyperoxemia after CPR and its association with long-term neurological outcome and mortality. Methods We analysed data from adult cardiac arrest patients treated after CPR in tertiary ICUs during 2005–2013. We retrieved data from the resuscitation and the first arterial blood sample collected after return of spontaneous circulation (ROSC) (severe hyperoxemia defined as PaO2 > 40 kPa and moderate as PaO2 16–40 kPa). We inspected two outcomes, neurological performance at one year after resuscitation according to the Cerebral Performance Category and one-year mortality. We used logistic regression to test associations between hyperoxemia and the outcome and interaction analyses to test the effect of hyperoxemia exposure on the outcomes in smaller subgroups. Results Of 1110 patients 11% had severe hyperoxemia, prevalence was 10% for out-of-hospital arrests, 13% for in-hospital arrests and 9% for in-ICU arrests. In total 585(53%) patients had an unfavourable neurological outcome. Compared to normoxemia, severe (Odds ratio [OR] 0.81, 95% confidence interval [CI] 0.50–1.30) and moderate hyperoxemia (OR 0.94 95%CI 0.69–1.27) did not associate with neurological outcome. Additionally, hyperoxemia had no association with mortality. In subgroup analyses there were no significant associations between severe hyperoxemia and outcomes regardless of cardiac arrest location, initial rhythm or time-to-ROSC. Conclusion We found no association between early post-arrest hyperoxemia and unfavourable outcome. Subgroup analysis found no differential effect depending on arrest location, initial rhythm or time-to-ROSC.

Background Several studies have suggested no change in the outcome of patients with traumatic brain injury (TBI) treated in intensive care units (ICUs). This is mainly due to the shift in TBI epidemiology toward older and sicker patients. In Finland, the share of the population aged 65 years and over has increased the most in Europe during the last decade. We aimed to assess changes in 12-month and hospital mortality of patients with TBI treated in the ICU in Finland. Methods We used a national benchmarking ICU database (Finnish Intensive Care Consortium) to study adult patients who had been treated for TBI in four tertiary ICUs in Finland during 2003–2019. We divided admission years into quartiles and used multivariable logistic regression analysis, adjusted for case-mix, to assess the association between admission year and mortality. Results A total of 4535 patients were included. Between 2003–2007 and 2016–2019, the patient median age increased from 54 to 62 years, the share of patients having significant comorbidity increased from 8 to 11%, and patients being dependent on help in activities of daily living increased from 7 to 15%. Unadjusted hospital and 12-month mortality decreased from 18 and 31% to 10% and 23%, respectively. After adjusting for case-mix, a reduction in odds of 12-month and hospital mortality was seen in patients with severe TBI, intracranial pressure monitored patients, and mechanically ventilated patients. Despite a reduction in hospital mortality, 12-month mortality remained unchanged in patients aged ≥ 70 years. Conclusion A change in the demographics of ICU-treated patients with TBI care is evident. The outcome of younger patients with severe TBI appears to improve, whereas long-term mortality of elderly patients with less severe TBI has not improved. This has ramifications for further efforts to improve TBI care, especially among the elderly.

Context Parent/family presence at pediatric resuscitations has been slow to become consistent practice in hospital settings and has not been universally implemented. A systematic review of the literature on family presence during pediatric and neonatal resuscitation has not been previously conducted. Objective To conduct a systematic review of the published evidence related to family presence during pediatric and neonatal resuscitation. Data sources Six major bibliographic databases was undertaken with defined search terms and including literature up to June 14, 2020. Study selection 3200 titles were retrieved in the initial search; 36 ultimately included for review. Data extraction Data was double extracted independently by two reviewers and confirmed with the review team. All eligible studies were either survey or interview-based and as such we turned to narrative systematic review methodology. Results The authors identified two key sets of findings: first, parents/family members want to be offered the option to be present for their child’s resuscitation. Secondly, health care provider attitudes varied widely (ranging from 15% to >85%), however, support for family presence increased with previous experience and level of seniority. Limitations English language only; lack of randomized control trials; quality of the publications. Conclusions Parents wish to be offered the opportunity to be present but opinions and perspectives on the family presence vary greatly among health care providers. This topic urgently needs high quality, comparative research to measure the actual impact of family presence on patient, family and staff outcomes. PROSPERO registration number CRD42020140363.

BackgroundPsychiatric sequelae after traumatic brain injury (TBI) are common and may impede recovery. We aimed to assess the occurrence and risk factors of post-injury psychotropic medication use in intensive care unit (ICU)-treated patients with TBI and its association with late mortality.MethodsWe conducted a retrospective multi-centre observational study using the Finnish Intensive Care Consortium database. We included adult TBI patients admitted in four university hospital ICUs during 2003–2013 that were alive at 1 year after injury. Patients were followed-up until end of 2016. We obtained data regarding psychotropic medication use through the national drug reimbursement database. We used multivariable logistic regression models to assess the association between TBI severity, treatment-related variables and the odds of psychotropic medication use and its association with late all-cause mortality (more than 1 year after TBI).ResultsOf 3061 patients, 2305 (75%) were alive at 1 year. Of these, 400 (17%) became new psychotropic medication users. The most common medication types were antidepressants (61%), antipsychotics (35%) and anxiolytics (26%). A higher Glasgow Coma Scale (GCS) score was associated with lower odds (OR 0.93, 95% CI 0.90–0.96) and a diffuse injury with midline shift was associated with higher odds (OR 3.4, 95% CI 1.3–9.0) of new psychotropic medication use. After adjusting for injury severity, new psychotropic medication use was associated with increased odds of late mortality (OR 1.19, 95% CI 1.19–2.17, median follow-up time 6.4 years).ConclusionsPsychotropic medication use is common in TBI survivors. Higher TBI severity is associated with increased odds of psychotropic medication use. New use of psychotropic medications after TBI was associated with increased odds of late mortality. Our results highlight the need for early identification of potential psychiatric sequelae and psychiatric evaluation in TBI survivors.

The European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) have collaborated to produce these post-resuscitation care guidelines for adults, which are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. The topics covered include the post-cardiac arrest syndrome, diagnosis of cause of cardiac arrest, control of oxygenation and ventilation, coronary reperfusion, haemodynamic monitoring and management, control of seizures, temperature control, general intensive care management, prognostication, long-term outcome, rehabilitation and organ donation. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06368-4.

BACKGROUND High oxygen levels may worsen cardiac arrest reperfusion injury. We determined the incidence of hyperoxia during and immediately after successful cardiopulmonary resuscitation and identified factors associated with intra-arrest cerebral oxygenation measured with near-infrared spectroscopy (NIRS). METHODS A prospective observational study of out-of-hospital cardiac arrest patients treated by a physician-staffed helicopter unit. Collected data included intra-arrest brain regional oxygen saturation (rSO2) with NIRS, invasive blood pressures, end-tidal CO2 (etCO2) and arterial blood gas samples. Moderate and severe hyperoxia were defined as arterial oxygen partial pressure (paO2) 20.0-39.9 and ≥40 kPa, respectively. Intra-arrest factors correlated with the NIRS value, rSO2, were assessed with the Spearman's correlation test. RESULTS Of 80 recruited patients, 73 (91%) patients had rSO2 recorded during CPR, and 46 had an intra-arrest paO2 analysed. ROSC was achieved in 28 patients, of whom 20 had paO2 analysed. Moderate hyperoxia was seen in one patient during CPR and in four patients (20%, 95% CI 7-42%) after ROSC. None had severe hyperoxia during CPR, and one patient (5%, 95% 0-25%) immediately after ROSC. The rSO2 during CPR was correlated with intra-arrest systolic (r = 0.28, p

Background Cardiac arrest (CA) is a leading cause of death worldwide. As population ages, the need for research focusing on CA in elderly increases. This study investigated treatment intensity, 12-month neurological outcome, mortality and healthcare-associated costs for patients aged over 75 years treated for CA in an intensive care unit (ICU) of a tertiary hospital. Methods This single-centre retrospective study included adult CA patients treated in a Finnish tertiary hospital’s ICU between 2005 and 2013. We stratified the study population into two age groups: $$\ge$$ ≥ 75 years. We compared interventions defined by the median daily therapeutic scoring system (TISS-76) between the age groups to find differences in treatment intensity. We calculated cost-effectiveness by dividing the total one-year healthcare-associated costs of all patients by the number of survivors with a favourable neurological outcome. Favourable outcome was defined as a cerebral performance category (CPC) of 1–2 at 12 months after cardiac arrest. Logistic regression analysis was used to identify independent associations between age group, mortality and neurological outcome. Results This study included a total of 1,285 patients, of which 212 (16 %) were $$\ge$$ ≥ 75 years of age. Treatment intensity was lower for the elderly compared to the younger group, with median TISS scores of 116 and 147, respectively (p p p p Conclusions The elderly ICU-treated CA patients in this study had worse neurological outcomes, higher mortality and lower cost-effectiveness than younger patients. Elderly received less intense treatment. Further efforts are needed to recognize the tools for assessing which elderly patients benefit from a more aggressive treatment approach in order to improve the cost-effectiveness of post-CA management.

Postcardiac arrest myocardial dysfunction (PCAMD) is a frequent complication faced during post-resuscitation care that adversely impacts survival and neurological outcome. Both mechanical and electrical factors contribute to the occurrence of PCAMD. Prearrest ventricular function, the cause of cardiac arrest, global ischemia, resuscitation factors, ischemia/reperfusion injury and post-resuscitation treatments contribute to the severity of PCMAD. the pathophysiology of PCAMD is complex and include myocytes energy failure, impaired contractility, cardiac edema, mitochondrial damage, activation of inflammatory pathways and the coagulation cascade, persistent ischemic injury and myocardial stiffness. Hypotension and low cardiac output with vasopressor/inotropes need are frequent after resuscitation. However, clinical, hemodynamic and laboratory signs of shock are frequently altered by cardiac arrest pathophysiology and post-resuscitation treatment, potentially being misleading and not fully reflecting the severity of postcardiac arrest syndrome. Even if validated criteria are lacking, an extensive hemodynamic evaluation is useful to define a "benign" and a "malign" form of myocardial dysfunction and circulatory shock, potentially having treatment and prognostic implications. cardiac output is frequently decreased after cardiac arrest, particularly in patients treated with target temperature management (TTM); however, it is not independently associated with outcome. sinus bradycardia during TTM seems independently associated with survival and good neurological outcome, representing a promising prognostic indicator. Higher mean arterial pressure (MAP) seems to be associated with improved survival and cerebral function after cardiac arrest; however, two recent randomized clinical trials failed to replicate these results. recommendations on hemodynamic optimization are relatively poor and are largely based on general principle of intensive care medicine. Skrifvars, MB (corresponding author), Univ Helsinki, Dept Anesthesiol Intens Care & Pain Med, Haartmaninkatu 4, Helsinki 00029, Finland. markus.skrifyars@hus.fi

Fibroblast growth factor (FGF) 21 is a marker associated with mitochondrial and cellular stress. Cardiac arrest causes mitochondrial stress, and we tested if FGF 21 would reflect the severity of hypoxia-reperfusion injury after cardiac arrest. We measured serum concentrations of FGF 21 in 112 patients on ICU admission and 24, 48 and 72 h after out-of-hospital cardiac arrest with shockable initial rhythm included in the COMACARE study (NCT02698917). All patients received targeted temperature management for 24 h. We defined 6-month cerebral performance category 1–2 as good and 3–5 as poor neurological outcome. We used samples from 40 non-critically ill emergency room patients as controls. We assessed group differences with the Mann Whitney U test and temporal differences with linear modeling with restricted maximum likelihood estimation. We used multivariate logistic regression to assess the independent predictive value of FGF 21 concentration for neurologic outcome. The median (inter-quartile range, IQR) FGF 21 concentration was 0.25 (0.094–0.91) ng/ml in controls, 0.79 (0.37–1.6) ng/ml in patients at ICU admission (P P P = 0.01), and their interaction (F 3.0, P = 0.03), on FGF 21 concentration. In multivariate logistic regression analysis, adjusting for relevant clinical covariates, higher average FGF 21 concentration during the first 72 h was independently associated with poor neurological outcome (odds ratio 1.60, 95% confidence interval 1.10–2.32). We conclude that post cardiac arrest patients experience cellular and mitochondrial stress, reflected as a systemic FGF 21 response. This response is higher with a more severe hypoxic injury but it is not exacerbated by hyperoxia.

Oxygen (O2) toxicity remains a concern, particularly to the lung. This is mainly related to excessive production of reactive oxygen species (ROS). Supplemental O2, i.e. inspiratory O2 concentrations (FIO2) > 0.21 may cause hyperoxaemia (i.e. arterial (a) PO2 > 100 mmHg) and, subsequently, hyperoxia (increased tissue O2 concentration), thereby enhancing ROS formation. Here, we review the pathophysiology of O2 toxicity and the potential harms of supplemental O2 in various ICU conditions. The current evidence base suggests that PaO2 > 300 mmHg (40 kPa) should be avoided, but it remains uncertain whether there is an “optimal level” which may vary for given clinical conditions. Since even moderately supra-physiological PaO2 may be associated with deleterious side effects, it seems advisable at present to titrate O2 to maintain PaO2 within the normal range, avoiding both hypoxaemia and excess hyperoxaemia.

BACKGROUND: No data are available on the quality of targeted temperature management (TTM) provided to out-of-hospital cardiac arrest (OHCA) patients and its association with outcome.METHODS: Post hoc analysis of the TTH48 study (NCT01689077), which compared the effects of prolonged TTM at 33 °C for 48 h to standard 24-h TTM on neurologic outcome. Admission temperature, speed of cooling, rewarming rates, precision (i.e. temperature variability), overcooling and overshooting as post-cooling fever (i.e. >38.0 °C) were collected. A specific score, ranging from 1 to 9, was computed to define the "quality of TTM".RESULTS: On a total of 352 patients, most had a moderate quality of TTM (n = 217; 62% - score 4-6), while 80 (23%) patients had a low quality of TTM (score 1-3) and only 52 (16%) a high quality of TTM (score 7-9). The proportion of patients with unfavorable neurological outcome (UO; Cerebral Performance Category of 3-5 at 6 months) was similar between the different quality of TTM groups (p = 0.90). Although a shorter time from arrest to target temperature and a lower proportion of time outside the target ranges in the TTM 48-h than in the TTM 24-h group, quality of TTM was similar between groups. Also, the proportion of patients with UO was similar between the different quality of TTM groups when TTM 48-h and TTM 24-h were compared.CONCLUSIONS: In this study, high quality of TTM was provided to a small proportion of patients. However, quality of TTM was not associated with patients' outcome.

Occult cerebral ischemia is one likely contributor to the development of hypoxic ischemic brain injury in patients after cardiac arrest. Local brain hypoxia may occur, irrespective of significant hypotension, especially if autoregulation of cerebral blood flow (CBF) is impaired. The regional brain saturation of oxygen (rSO2) may be estimated non-invasively, using near infrared spectroscopy (NIRS). The rSO2 also offers a surrogate measure of CBF and makes it possible to estimate the efficacy and limits of cerebrovascular autoregulation by calculating the moving correlation in the time domain between arterial pressure and rSO2. The advantage of NIRS is its easy implementation, providing continuous data. Studies have not, thus far, shown unequivocal associations between the rSO2 estimates of autoregulation and the magnitude of hypoxic ischemic brain injury or the clinical neurological outcome. With the use of invasive catheters inserted through a cranial burr hole, the partial pressure of oxygen in brain tissue (PbtO2) can be measured directly—as can intracranial pressure (ICP), local blood flow and markers of metabolism. Such catheters are commonly used in neurointensive care, but less so in the management of cardiac arrest patients. This is due to the risk of bleeding complications associated with anticoagulation and antiplatelet therapy, which is standard practice in cases where the cause of the arrest is myocardial ischemia. Pilot studies have shown promise—both for the use of PbtO2 and for its potentially superior precision over NIRS in detecting brain ischemia. The means available for treating cerebral ischemia include manipulating the arterial blood pressure with vasopressors, as well as modifying blood oxygen and carbon dioxide levels by adjusting ventilatory management. Thus far, no conclusive evidence exists supporting these interventions to alleviate hypoxic ischemic brain injury and improve outcome. One possible strategy is the adoption of a multimodal treatment strategy to detect and treat cerebral ischemia—similar to the management of patients with TBI.

Aim of the study: EEG slow wave activity (SWA) has shown prognostic potential in post-resuscitation care. In this prospective study, we investigated the accuracy of continuously measured early SWA for prediction of the outcome in comatose cardiac arrest (CA) survivors. Methods: We recorded EEG with a disposable self-adhesive frontal electrode and wireless device continuously starting from ICU admission until 48 h from return of spontaneous circulation (ROSC) in comatose CA survivors sedated with propofol. We determined SWA by offline calculation of C-Trend® Index describing SWA as a score ranging from 0 to 100. The functional outcome was defined based on Cerebral Performance Category (CPC) at 6 months after the CA to either good (CPC 1–2) or poor (CPC 3–5). Results: Outcome at six months was good in 67 of the 93 patients. During the first 12 h after ROSC, the median C-Trend Index value was 38.8 (interquartile range 28.0–56.1) in patients with good outcome and 6.49 (3.01–18.2) in those with poor outcome showing significant difference (p < 0.001) at every hour between the groups. The index values of the first 12 h predicted poor outcome with an area under curve of 0.86 (95% CI 0.61−0.99). With a cutoff value of 20, the sensitivity was 83.3% (69.6%–92.3%) and specificity 94.7% (83.4%–99.7%) for categorization of outcome. Conclusion: EEG SWA measured with C-Trend Index during propofol sedation offers a promising practical approach for early bedside evaluation of recovery of brain function and prediction of outcome after CA.

Purpose To provide clinical practice recommendations and generate a research agenda on mechanical ventilation and respiratory support in patients with acute brain injury (ABI). Methods An international consensus panel was convened including 29 clinician-scientists in intensive care medicine with expertise in acute respiratory failure, neurointensive care, or both, and two non-voting methodologists. The panel was divided into seven subgroups, each addressing a predefined clinical practice domain relevant to patients admitted to the intensive care unit (ICU) with ABI, defined as acute traumatic brain or cerebrovascular injury. The panel conducted systematic searches and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was used to evaluate evidence and formulate questions. A modified Delphi process was implemented with four rounds of voting in which panellists were asked to respond to questions (rounds 1–3) and then recommendation statements (final round). Strong recommendation, weak recommendation, or no recommendation were defined when > 85%, 75–85%, and

Purpose The coronavirus disease 2019 (COVID-19) poses major challenges to health-care systems worldwide. This pandemic demonstrates the importance of timely access to intensive care and, therefore, this study aims to explore the accessibility of intensive care beds in 14 European countries and its impact on the COVID-19 case fatality ratio (CFR). Methods We examined access to intensive care beds by deriving (1) a regional ratio of intensive care beds to 100,000 population capita (accessibility index, AI) and (2) the distance to the closest intensive care unit. The cross-sectional analysis was performed at a 5-by-5 km spatial resolution and results were summarized nationally for 14 European countries. The relationship between AI and CFR was analyzed at the regional level. Results We found national-level differences in the levels of access to intensive care beds. The AI was highest in Germany (AI = 35.3), followed by Estonia (AI = 33.5) and Austria (AI = 26.4), and lowest in Sweden (AI = 5) and Denmark (AI = 6.4). The average travel distance to the closest hospital was highest in Croatia (25.3 min by car) and lowest in Luxembourg (9.1 min). Subnational results illustrate that capacity was associated with population density and national-level inventories. The correlation analysis revealed a negative correlation of ICU accessibility and COVID-19 CFR (r = − 0.57; p

The effect of conservative versus liberal oxygen therapy on mortality rates in post cardiac arrest patients is uncertain.We undertook an individual patient data meta-analysis of patients randomised in clinical trials to conservative or liberal oxygen therapy after a cardiac arrest. The primary end point was mortality at last follow-up.Individual level patient data were obtained from seven randomised clinical trials with a total of 429 trial participants included. Four trials enrolled patients in the pre-hospital period. Of these, two provided protocol-directed oxygen therapy for 60 min, one provided it until the patient was handed over to the emergency department staff, and one provided it for a total of 72 h or until the patient was extubated. Three trials enrolled patients after intensive care unit (ICU) admission and generally continued protocolised oxygen therapy for a longer period, often until ICU discharge. A total of 90 of 221 patients (40.7%) assigned to conservative oxygen therapy and 103 of 206 patients (50%) assigned to liberal oxygen therapy had died by this last point of follow-up; absolute difference; odds ratio (OR) adjusted for study only; 0.67; 95% CI 0.45 to 0.99; P = 0.045; adjusted OR, 0.58; 95% CI 0.35 to 0.96; P = 0.04.Conservative oxygen therapy was associated with a statistically significant reduction in mortality at last follow-up compared to liberal oxygen therapy but the certainty of available evidence was low or very low due to bias, imprecision, and indirectness.CRD42019138931.

Correction: Volume: 156 Pages: 194-195 DOI: 10.1016/j.resuscitation.2020.05.028 Published: NOV 2020 Aim: To determine the type of airway devices used during in-hospital cardiac arrest (IHCA) resuscitation attempts. Methods: International multicentre retrospective observational study of in-patients aged over 18 years who received chest compressions for cardiac arrest from April 2016 to September 2018. Patients were identified from resuscitation registries and rapid response system databases. Data were collected through review of resuscitation records and hospital notes. Airway devices used during cardiac arrest were recorded as basic (adjuncts or bag-mask), or advanced, including supraglottic airway devices, tracheal tubes or tracheostomies. Descriptive statistics and multivariable regression modelling were used for data analysis. Results: The final analysis included 598 patients. No airway management occurred in 36 (6%), basic airway device use occurred at any time in 562 (94%), basic airway device use without an advanced airway device in 182 (30%), tracheal intubation in 301 (50%), supraglottic airway in 102 (17%), and tracheostomy in 1 (0.2%). There was significant variation in airway device use between centres. The intubation rate ranged between 21% and 90% while supraglottic airway use varied between 1% and 45%. The choice of tracheal intubation vs. supraglottic airway as the second advanced airway device was not associated with immediate survival from the resuscitation attempt (odds ratio 0.81; 95% confidence interval 0.35-1.8). Conclusion: There is wide variation in airway device use during resuscitation after IHCA. Only half of patients are intubated before return of spontaneous circulation and many are managed without an advanced airway. Further investigation is needed to determine optimal airway device management strategies during resuscitation following IHCA.

Background: Acute kidney injury (AKI) is common after cardiac arrest and targeted temperature management (TTM). The impact of different lengths of cooling on the development of AKI has not been well studied. In this study of patients included in a randomised controlled trial of TTM at 33 °C for 24 versus 48 h after cardiac arrest (TTH48 trial), we examined the influence of prolonged TTM on AKI and the incidence and factors associated with the development of AKI. We also examined the impact of AKI on survival. Methods: This study was a sub-study of the TTH48 trial, which included patients cooled to 33 ± 1 °C after out-of-hospital cardiac arrest for 24 versus 48 h. AKI was classified according to the KDIGO AKI criteria based on serum creatinine and urine output collected until ICU discharge for a maximum of seven days. Survival was followed for up to six months. The association of admission factors on AKI was analysed with multivariate analysis and the association of AKI on mortality was analysed with Cox regression using the time to AKI as a time-dependent covariate. Results: Of the 349 patients included in the study, 159 (45.5%) developed AKI. There was no significant difference in the incidence, severity or time to AKI between the 24- and 48-h groups. Serum creatinine values had significantly different trajectories for the two groups with a sharp rise occurring during rewarming. Age, time to return of spontaneous circulation, serum creatinine at admission and body mass index were independent predictors of AKI. Patients with AKI had a higher mortality than patients without AKI (hospital mortality 36.5% vs 12.5%, p < 0.001), but only AKI stages 2 and 3 were independently associated with mortality. Conclusions: We did not find any association between prolonged TTM at 33 °C and the risk of AKI during the first seven days in the ICU. AKI is prevalent after cardiac arrest and TTM and occurs in almost half of all ICU admitted patients and more commonly in the elderly, with an increasing BMI and longer arrest duration. AKI after cardiac arrest is an independent predictor of time to death.

To discuss recent findings relevant to optimizing blood pressure targets in adult, postcardiac arrest (PCA) patients and whether to tailor these based on specific patient, cardiac arrest or treatment characteristics.Observational data suggest that mean arterial pressure (MAP) below 65-75 mmHg in PCA patients is associated with worse outcome. A higher MAP could be beneficial in patients with chronic hypertension who more frequently have a right shift of the cerebral autoregulation curve. Two recent randomized pilot trials compared lower and higher MAP targets during PCA care and found no significant effect on biomarkers of neurological injury. The haemodynamic interventions in those studies did not use any cerebral perfusion endpoints beyond a static MAP targets during ICU stay. Individualized, dynamic MAP targets based on assessments of cerebral perfusion and tailored to the specifics of the patient, cardiac arrest circumstances and treatment responses may be more conducive to improved outcomes. Pilot data suggest that near infrared spectroscopy monitoring may be used to determine the cerebral autoregulatory capacity and an optimal MAP, but this approach is yet to be tested in clinical trials.Current evidence suggests targeting a MAP of at least 65-75 mmHg in PCA patients. Future studies should focus on whether certain patient groups could benefit from higher and dynamic MAP targets.

Objective Inhalation of noble and other gases after cardiac arrest (CA) might improve neurological and cardiac outcomes. This article discusses up-to-date information on this novel therapeutic intervention. Data sources CENTRAL, MEDLINE, online published abstracts from conference proceedings, clinical trial registry clinicaltrials.gov, and reference lists of relevant papers were systematically searched from January 1960 till March 2019. Study selection Preclinical and clinical studies, irrespective of their types or described outcomes, were included. Data extraction Abstract screening, study selection, and data extraction were performed by two independent authors. Due to the paucity of human trials, risk of bias assessment was not performed Data synthesis After screening 281 interventional studies, we included an overall of 27. Only, xenon, helium, hydrogen, and nitric oxide have been or are being studied on humans. Xenon, nitric oxide, and hydrogen show both neuroprotective and cardiotonic features, while argon and hydrogen sulfide seem neuroprotective, but not cardiotonic. Most gases have elicited neurohistological protection in preclinical studies; however, only hydrogen and hydrogen sulfide appeared to preserve CA1 sector of hippocampus, the most vulnerable area in the brain for hypoxia. Conclusion Inhalation of certain gases after CPR appears promising in mitigating neurological and cardiac damage and may become the next successful neuroprotective and cardiotonic interventions.

Background We studied the associations between ischemia and hypothermia duration, that is, the hypothermic to ischemic ratio (H/I ratio), with mortality in patients included in a trial on two durations of targeted temperature management (TTM) at 33 degrees C. Methods The TTH48 (NCT01689077) trial compared 24 and 48 hours of TTM in patients after cardiac arrest. We calculated the hypothermia time from return of spontaneous circulation (ROSC) until the patient reached 37 degrees C after TTM and the ischemic time from CA to ROSC. We compared continuous variables with the Mann-Whitney U test. Using COX regression, we studied the independent association of the logarithmically transformed H/I ratio and time to death as well as interaction between time to ROSC, hypothermia duration, and intervention group. We visualized the predictive ability of variables with receiver operating characteristic curve analysis. Results Of the 338 patients, 237 (70%) survived for 6 months. The H/I ratio was 155 (IQR 111-238) in survivors and 114 (IQR 80-169) in non-survivors (P