Search

Aims: Cerebral complications after cardiac arrest (CA) remain a major problem worldwide. The aim was to test the effects of sodium-ß-hydroxybutyrate (SBHB) infusion on brain injury in a clinically relevant swine model of CA., Results: CA was electrically induced in 20 adult swine. After 10 min, cardiopulmonary resuscitation was performed for 5 min. After return of spontaneous circulation (ROSC), the animals were randomly assigned to receive an infusion of balanced crystalloid (controls, n = 11) or SBHB (theoretical osmolarity 1189 mOsm/l, n = 8) for 12 h. Multimodal neurological and cardiovascular monitoring were implemented in all animals. Nineteen of the 20 animals achieved ROSC. Blood sodium concentrations, osmolarity and circulating KBs were higher in the treated animals than in the controls. SBHB infusion was associated with significantly lower plasma biomarkers of brain injury at 6 (glial fibrillary acid protein, GFAP and neuron specific enolase, NSE) and 12 h (neurofilament light chain, NFL, GFAP and NSE) compared to controls. The amplitude of the stereoelectroencephalograph (sEEG) increased in treated animals after ROSC compared to controls. Cerebral glucose uptake was lower in treated animals., Conclusions: In this experimental model, SBHB infusion after resuscitated CA was associated with reduced circulating markers of cerebral injury and increased sEEG amplitude., (© 2024. The Author(s).)

Background: This study aimed to explore the characteristics of abnormal regional resting-state functional magnetic resonance imaging (rs-fMRI) activity in comatose patients in the early period after cardiac arrest (CA), and to investigate their relationships with neurological outcomes. We also explored the correlations between jugular venous oxygen saturation (SjvO2) and rs-fMRI activity in resuscitated comatose patients. We also examined the relationship between the amplitude of the N20-baseline and the rs-fMRI activity within the intracranial conduction pathway of somatosensory evoked potentials (SSEPs)., Methods: Between January 2021 and January 2024, eligible post-resuscitated patients were screened to undergo fMRI examination. The amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) of rs-fMRI blood oxygenation level-dependent (BOLD) signals were used to characterize regional neural activity. Neurological outcomes were evaluated using the Glasgow-Pittsburgh cerebral performance category (CPC) scale at 3 months after CA., Results: In total, 20 healthy controls and 31 post-resuscitated patients were enrolled in this study. The rs-fMRI activity of resuscitated patients revealed complex changes, characterized by increased activity in some local brain regions and reduced activity in others compared to healthy controls (P < 0.05). However, the mean ALFF values of the whole brain were significantly greater in CA patients (P = 0.011). Among the clusters of abnormal rs-fMRI activity, the cluster values of ALFF in the left middle temporal gyrus and inferior temporal gyrus and the cluster values of ReHo in the right precentral gyrus, superior frontal gyrus and middle frontal gyrus were strongly correlated with the CPC score (P < 0.001). There was a strong correlation between the mean ALFF and SjvO2 in CA patients (r = 0.910, P < 0.001). The SSEP N20-baseline amplitudes in CA patients were negatively correlated with thalamic rs-fMRI activity (all P < 0.001)., Conclusions: This study revealed that abnormal rs-fMRI BOLD signals in resuscitated patients showed complex changes, characterized by increased activity in some local brain regions and reduced activity in others. Abnormal BOLD signals were associated with neurological outcomes in resuscitated patients. The mean ALFF values of the whole brain were closely related to SjvO2 levels, and changes in the thalamic BOLD signals correlated with the N20-baseline amplitudes of SSEP responses., Trial Registration: NCT05966389 (Registered July 27, 2023)., (© 2024. The Author(s).)

Purpose: To evaluate the potential association between early dysnatremia and 6-month functional outcome after cardiac arrest., Methods: We pooled data from four randomised clinical trials in post-cardiac-arrest patients admitted to the ICU with coma after stable return of spontaneous circulation (ROSC). Admission natremia was categorised as normal (135-145 mmol/L), low, or high. We analysed associations between natremia category and Cerebral Performance Category (CPC) 1 or 2 at 6 months, with and without adjustment on the modified Cardiac Arrest Hospital Prognosis Score (mCAHP)., Results: We included 1163 patients (581 from HYPERION, 352 from TTH48, 120 from COMACARE, and 110 from Xe-HYPOTHECA) with a mean age of 63 ± 13 years and a predominance of males (72.5%). A cardiac cause was identified in 63.6% of cases. Median time from collapse to ROSC was 20 [15-29] minutes. Overall, mean natremia on ICU admission was 137.5 ± 4.7 mmol/L; 211 (18.6%) and 31 (2.7%) patients had hyponatremia and hypernatremia, respectively. By univariate analysis, CPC 1 or 2 at 6 months was significantly less common in the group with hyponatremia (50/211 [24%] vs. 363/893 [41%]; P = 0.001); the mCAHP-adjusted odds ratio was 0.45 (95%CI 0.26-0.79, p = 0.005). The number of patients with hypernatremia was too small for a meaningful multivariable analysis., Conclusions: Early hyponatremia was common in patients with ROSC after cardiac arrest and was associated with a poorer 6-month functional outcome. The mechanisms underlying this association remain to be elucidated in order to determine whether interventions targeting hyponatremia are worth investigating. Registration ClinicalTrial.gov, NCT01994772, November 2013, 21., (© 2023. The Author(s).)

Introduction: Though early hypotension after pediatric in-hospital cardiac arrest (IHCA) is associated with inferior outcomes, ideal post-arrest blood pressure (BP) targets have not been established. We aimed to leverage prospectively collected BP data to explore the association of post-arrest BP thresholds with outcomes. We hypothesized that post-arrest systolic and diastolic BP thresholds would be higher than the currently recommended post-cardiopulmonary resuscitation BP targets and would be associated with higher rates of survival to hospital discharge., Methods: We performed a secondary analysis of prospectively collected BP data from the first 24 h following return of circulation from index IHCA events enrolled in the ICU-RESUScitation trial (NCT02837497). The lowest documented systolic BP (SBP) and diastolic BP (DBP) were percentile-adjusted for age, height and sex. Receiver operator characteristic curves and cubic spline analyses controlling for illness category and presence of pre-arrest hypotension were generated exploring the association of lowest post-arrest SBP and DBP with survival to hospital discharge and survival to hospital discharge with favorable neurologic outcome (Pediatric Cerebral Performance Category of 1-3 or no change from baseline). Optimal cutoffs for post-arrest BP thresholds were based on analysis of receiver operator characteristic curves and spline curves. Logistic regression models accounting for illness category and pre-arrest hypotension examined the associations of these thresholds with outcomes., Results: Among 693 index events with 0-6 h post-arrest BP data, identified thresholds were: SBP > 10th percentile and DBP > 50th percentile for age, sex and height. Fifty-one percent (n = 352) of subjects had lowest SBP above threshold and 50% (n = 346) had lowest DBP above threshold. SBP and DBP above thresholds were each associated with survival to hospital discharge (SBP: aRR 1.21 [95% CI 1.10, 1.33]; DBP: aRR 1.23 [1.12, 1.34]) and survival to hospital discharge with favorable neurologic outcome (SBP: aRR 1.22 [1.10, 1.35]; DBP: aRR 1.27 [1.15, 1.40]) (all p < 0.001)., Conclusions: Following pediatric IHCA, subjects had higher rates of survival to hospital discharge and survival to hospital discharge with favorable neurologic outcome when BP targets above a threshold of SBP > 10th percentile for age and DBP > 50th percentile for age during the first 6 h post-arrest., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Prognosis after resuscitation from cardiac arrest (CA) remains poor, with high morbidity and mortality as a result of extensive cardiac and brain injury and lack of effective treatments. Hypertonic sodium lactate (HSL) may be beneficial after CA by buffering severe metabolic acidosis, increasing brain perfusion and cardiac performance, reducing cerebral swelling, and serving as an alternative energetic cellular substrate. The aim of this study was to test the effects of HSL infusion on brain and cardiac injury in an experimental model of CA., Methods: After a 10-min electrically induced CA followed by 5 min of cardiopulmonary resuscitation maneuvers, adult swine (n = 35) were randomly assigned to receive either balanced crystalloid (controls, n = 11) or HSL infusion started during cardiopulmonary resuscitation (CPR, Intra-arrest, n = 12) or after return of spontaneous circulation (Post-ROSC, n = 11) for the subsequent 12 h. In all animals, extensive multimodal neurological and cardiovascular monitoring was implemented. All animals were treated with targeted temperature management at 34 °C., Results: Thirty-four of the 35 (97.1%) animals achieved ROSC; one animal in the Intra-arrest group died before completing the observation period. Arterial pH, lactate and sodium concentrations, and plasma osmolarity were higher in HSL-treated animals than in controls (p < 0.001), whereas potassium concentrations were lower (p = 0.004). Intra-arrest and Post-ROSC HSL infusion improved hemodynamic status compared to controls, as shown by reduced vasopressor requirements to maintain a mean arterial pressure target > 65 mmHg (p = 0.005 for interaction; p = 0.01 for groups). Moreover, plasma troponin I and glial fibrillary acid protein (GFAP) concentrations were lower in HSL-treated groups at several time-points than in controls., Conclusions: In this experimental CA model, HSL infusion was associated with reduced vasopressor requirements and decreased plasma concentrations of measured biomarkers of cardiac and cerebral injury., (© 2023. The Author(s).)

Background: Post-cardiac arrest, outcomes for most patients are poor, regardless of setting. Many patients who do achieve spontaneous return of circulation require vasopressor therapy to maintain organ perfusion. There is some evidence to support the use of corticosteroids in cardiac arrest., Research Question: Assess the efficacy and safety of corticosteroids in patients following in- and out-of-hospital cardiac arrest., Study Design and Methods: We searched databases CINAHL, EMBASE, LILACS, MEDLINE, Web of Science, CENTRAL, ClinicalTrails.gov, and ICTRP. We included randomized controlled trials (RCTs) that examined the efficacy and safety of corticosteroids, as compared to placebo or usual care in patients post-cardiac arrest. We pooled estimates of effect size using random effects meta-analysis and report relative risk (RR) with 95% confidence intervals (CIs). We assessed risk of bias (ROB) for the included trials using the modified Cochrane ROB tool and rated the certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation methodology., Results: We included 8 RCTs (n = 2213 patients). Corticosteroids administered post-cardiac arrest had an uncertain effect on mortality measured at the longest point of follow-up (RR 0.96, 95% CI 0.90-1.02, very low certainty, required information size not met using trial sequential analysis). Corticosteroids probably increase return of spontaneous circulation (ROSC) (RR 1.32, 95% CI 1.18-1.47, moderate certainty) and may increase the likelihood of survival with good functional outcome (RR 1.49, 95% CI 0.87-2.54, low certainty). Corticosteroids may decrease the risk of ventilator associated pneumonia (RR 0.76, 95% CI 0.46-1.09, low certainty), may increase renal failure (RR 1.29, 95% CI 0.84-1.99, low certainty), and have an uncertain effect on bleeding (RR 2.04, 95% CI 0.53-7.84, very low certainty) and peritonitis (RR 10.54, 95% CI 2.99-37.19, very low certainty)., Conclusions: In patients during or after cardiac arrest, corticosteroids have an uncertain effect on mortality but probably increase ROSC and may increase the likelihood of survival with good functional outcome at hospital discharge. Corticosteroids may decrease ventilator associated pneumonia, may increase renal failure, and have an uncertain effect on bleeding and peritonitis. However, the pooled evidence examining these outcomes was sparse and imprecision contributed to low or very low certainty of evidence., (© 2023. The Author(s).)

Cardiac arrest (CA) is a major cause of morbidity and mortality frequently associated with neurological and systemic involvement. Supportive therapeutic strategies such as mechanical ventilation, hemodynamic settings, and temperature management have been implemented in the last decade in post-CA patients, aiming at protecting both the brain and the lungs and preventing systemic complications. A lung-protective ventilator strategy is currently the standard of care among critically ill patients since it demonstrated beneficial effects on mortality, ventilator-free days, and other clinical outcomes. The role of protective and personalized mechanical ventilation setting in patients without acute respiratory distress syndrome and after CA is becoming more evident. The individual effect of different parameters of lung-protective ventilation, including mechanical power as well as the optimal oxygen and carbon dioxide targets, on clinical outcomes is a matter of debate in post-CA patients. The management of hemodynamics and temperature in post-CA patients represents critical steps for obtaining clinical improvement. The aim of this review is to summarize and discuss current evidence on how to optimize mechanical ventilation in post-CA patients. We will provide ten tips and key insights to apply a lung-protective ventilator strategy in post-CA patients, considering the interplay between the lungs and other systems and organs, including the brain., (© 2022. The Author(s).)

Purpose: Veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) can be used to restore organ perfusion in patients with cardiogenic shock until native heart recovery occurs. It may be challenging, however, to determine when patients can be weaned successfully from ECMO-surviving without requiring further mechanical support or heart transplant. We aimed to systematically review the medical literature to determine the biomarkers, hemodynamic and echocardiographic parameters associated with successful weaning of VA-ECMO in adults with cardiogenic shock and to present an evidence-based weaning algorithm incorporating key findings., Method: We systematically searched PubMed, Embase, ProQuest, Google Scholars, Web of Science and the Grey literature for pertinent original research reports. We excluded studies limited to extracorporeal cardiopulmonary resuscitation (ECPR) as the neurological prognosis may significantly alter the decision-making process surrounding the device removal in this patient population. Studies with a mixed population of VA-ECMO for cardiogenic shock or cardiac arrest were included. We excluded studies limited to patients in which ECMO was only used as a bridge to VAD or heart transplant, as such patients are, by definition, never "successfully weaned." We used the Risk of Bias Assessment tool for Non-Randomized Studies. The study was registered on the International prospective register of systematic reviews (PROSPERO CRD42020178641)., Results: We screened 14,578 records and included 47 that met our pre-specified criteria. Signs of lower initial severity of shock and myocardial injury, early recovery of systemic perfusion, left and right ventricular recovery, hemodynamic and echocardiographic stability during flow reduction trial and/or pump-controlled retrograde trial off predicted successful weaning. The most widely used parameter was the left ventricular outflow tract velocity time integral, an indicator of stroke volume. Most studies had a moderate or high risk of bias. Heterogeneity in methods, timing, and conditions of measurements precluded any meta-analysis., Conclusions: In adult patients on VA-ECMO for cardiogenic shock, multiple biomarkers, hemodynamic and echocardiographic parameters may be used to track resolution of systemic hypoperfusion and myocardial recovery in order to identify patients that can be successfully weaned., (© 2022. The Author(s).)

Most of the patients who die after cardiac arrest do so because of hypoxic-ischemic brain injury (HIBI). Experimental evidence shows that temperature control targeted at hypothermia mitigates HIBI. In 2002, one randomized trial and one quasi-randomized trial showed that temperature control targeted at 32-34 °C improved neurological outcome and mortality in patients who are comatose after cardiac arrest. However, following the publication of these trials, other studies have questioned the neuroprotective effects of hypothermia. In 2021, the largest study conducted so far on temperature control (the TTM-2 trial) including 1900 adults comatose after resuscitation showed no effect of temperature control targeted at 33 °C compared with normothermia or fever control. A systematic review of 32 trials published between 2001 and 2021 concluded that temperature control with a target of 32-34 °C compared with fever prevention did not result in an improvement in survival (RR 1.08; 95% CI 0.89-1.30) or favorable functional outcome (RR 1.21; 95% CI 0.91-1.61) at 90-180 days after resuscitation. There was substantial heterogeneity across the trials, and the certainty of the evidence was low. Based on these results, the International Liaison Committee on Resuscitation currently recommends monitoring core temperature and actively preventing fever (37.7 °C) for at least 72 h in patients who are comatose after resuscitation from cardiac arrest. Future studies are needed to identify potential patient subgroups who may benefit from temperature control aimed at hypothermia. There are no trials comparing normothermia or fever control with no temperature control after cardiac arrest., (© 2022. The Author(s).)

During refractory cardiogenic shock and cardiac arrest, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used to restore a circulatory output. However, it also impacts significantly arterial oxygenation. Recent guidelines of the Extracorporeal Life Support Organization (ELSO) recommend targeting postoxygenator partial pressure of oxygen (P POST O 2 ) around 150 mmHg. In this narrative review, we intend to summarize the rationale and evidence for this P POST O 2 target recommendation. Because this is the most used configuration, we focus on peripheral VA-ECMO. To date, clinicians do not know how to set the sweep gas oxygen fraction (F S O 2 ). Because of the oxygenator's performance, arterial hyperoxemia is common during VA-ECMO support. Interpretation of oxygenation is complex in this setting because of the dual circulation phenomenon, depending on both the native cardiac output and the VA-ECMO blood flow. Such dual circulation results in dual oxygenation, with heterogeneous oxygen partial pressure (PO 2 ) along the aorta, and heterogeneous oxygenation between organs, depending on the mixing zone location. Data regarding oxygenation during VA-ECMO are scarce, but several observational studies have reported an association between hyperoxemia and mortality, especially after refractory cardiac arrest. While hyperoxemia should be avoided, there are also more and more studies in non-ECMO patients suggesting the harm of a too restrictive oxygenation strategy. Finally, setting F S O 2 to target strict normoxemia is challenging because continuous monitoring of postoxygenator oxygen saturation is not widely available. The threshold of P POST O 2 around 150 mmHg is supported by limited evidence but aims at respecting a safe margin, avoiding both hypoxemia and severe hyperoxemia., (© 2022. The Author(s).)

Purpose: To assess the performance of the post-cardiac arrest (CA) prognostication strategy algorithm recommended by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) in 2020., Methods: This was a retrospective analysis of the Korean Hypothermia Network Prospective Registry 1.0. Unconscious patients without confounders at day 4 (72-96 h) after return of spontaneous circulation (ROSC) were included. The association between the prognostic factors included in the prognostication strategy algorithm, except status myoclonus and the neurological outcome, was investigated, and finally, the prognostic performance of the prognostication strategy algorithm was evaluated. Poor outcome was defined as cerebral performance categories 3-5 at 6 months after ROSC., Results: A total of 660 patients were included in the final analysis. Of those, 108 (16.4%) patients had a good neurological outcome at 6 months after CA. The 2020 ERC/ESICM prognostication strategy algorithm identified patients with poor neurological outcome with 60.2% sensitivity (95% CI 55.9-64.4) and 100% specificity (95% CI 93.9-100) among patients who were unconscious or had a GCS&#95;M score ≤ 3 and with 58.2% sensitivity (95% CI 53.9-62.3) and 100% specificity (95% CI 96.6-100) among unconscious patients. When two prognostic factors were combined, any combination of prognostic factors had a false positive rate (FPR) of 0 (95% CI 0-5.6 for combination of no PR/CR and poor CT, 0-30.8 for combination of No SSEP N20 and NSE 60)., Conclusion: The 2020 ERC/ESICM prognostication strategy algorithm predicted poor outcome without an FPR and with sensitivities of 58.2-60.2%. Any combinations of two predictors recommended by ERC/ESICM showed 0% of FPR., (© 2022. The Author(s).)

Background: We assessed the prognostic accuracy of the standardized electroencephalography (EEG) patterns ("highly malignant," "malignant," and "benign") according to the EEG timing (early vs. late) and investigated the EEG features to enhance the predictive power for poor neurologic outcome at 1 month after cardiac arrest., Methods: This prospective, multicenter, observational, cohort study using data from Korean Hypothermia Network prospective registry included adult patients with out-of-hospital cardiac arrest (OHCA) treated with targeted temperature management (TTM) and underwent standard EEG within 7 days after cardiac arrest from 14 university-affiliated teaching hospitals in South Korea between October 2015 and December 2018. Early EEG was defined as EEG performed within 72 h after cardiac arrest. The primary outcome was poor neurological outcome (Cerebral Performance Category score 3-5) at 1 month., Results: Among 489 comatose OHCA survivors with a median EEG time of 46.6 h, the "highly malignant" pattern (40.7%) was most prevalent, followed by the "benign" (33.9%) and "malignant" (25.4%) patterns. All patients with the highly malignant EEG pattern had poor neurologic outcomes, with 100% specificity in both groups but 59.3% and 56.1% sensitivity in the early and late EEG groups, respectively. However, for patients with "malignant" patterns, 84.8% sensitivity, 77.0% specificity, and 89.5% positive predictive value for poor neurologic outcome were observed. Only 3.5% (9/256) of patients with background EEG frequency of predominant delta waves or undetermined had good neurologic survival. The combination of "highly malignant" or "malignant" EEG pattern with background frequency of delta waves or undetermined increased specificity and positive predictive value, respectively, to up to 98.0% and 98.7%., Conclusions: The "highly malignant" patterns predicted poor neurologic outcome with a high specificity regardless of EEG measurement time. The assessment of predominant background frequency in addition to EEG patterns can increase the prognostic value of OHCA survivors. Trial registration KORHN-PRO, NCT02827422 . Registered 11 September 2016-Retrospectively registered., (© 2021. The Author(s).)

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 (TO x ) generated by the moving correlation coefficient between cerebral tissue oxygenation measured by NIRS and MAP was used as a dynamic index of CVR with TO x  > 0 indicating impaired reactivity and TO x  > 0.3 used to delineate the lower and upper MAP bounds for disrupted CVR. TO x 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 TO x 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 TO x , 76 patients (70%) had impaired CVR and among these, chronic hypertension was more common (58% vs. 31%, p = 0.002). Integrated TO x 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 < 0.05). NfL concentrations were higher in patients with impaired CVR compared to those with intact CVR (43 IQR [15-650] vs 20 IQR [13-199] pg/ml, 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 ., (© 2021. The Author(s).)

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 ., (© 2021. Skrifvars et al.)

Background: In-hospital cardiac arrest (IHCA) is a major adverse event with a high mortality rate if not treated appropriately. Extracorporeal cardiopulmonary resuscitation (ECPR), as adjunct to conventional cardiopulmonary resuscitation (CCPR), is a promising technique for IHCA treatment. Evidence pertaining to neurological outcomes after ECPR is still scarce., Methods: We performed a comprehensive systematic search of all studies up to December 20, 2019. Our primary outcome was neurological outcome after ECPR at any moment after hospital discharge, defined by the Cerebral Performance Category (CPC) score. A score of 1 or 2 was defined as favourable outcome. Our secondary outcome was post-discharge mortality. A fixed-effects meta-analysis was performed., Results: Our search yielded 1215 results, of which 19 studies were included in this systematic review. The average survival rate was 30% (95% CI 28-33%, I 2  = 0%, p = 0.24). In the surviving patients, the pooled percentage of favourable neurological outcome was 84% (95% CI 80-88%, I 2  = 24%, p = 0.90)., Conclusion: ECPR as treatment for in-hospital cardiac arrest is associated with a large proportion of patients with good neurological outcome. The large proportion of favourable outcome could potentially be explained by the selection of patients for treatment using ECPR. Moreover, survival is higher than described in the conventional CPR literature. As indications for ECPR might extend to older or more fragile patient populations in the future, research should focus on increasing survival, while maintaining optimal neurological outcome.

Objectives: To re-evaluate the role of median nerve somatosensory evoked potentials (SSEPs) and bilateral loss of the N20 cortical wave as a predictor of unfavorable outcome in comatose patients following cardiac arrest (CA) in the therapeutic hypothermia (TH) era., Methods: Review the results and conclusions drawn from isolated case reports and small series of comatose patients following CA in which the bilateral absence of N20 response has been associated with recovery, and evaluate the proposal that SSEP can no longer be considered a reliable and accurate predictor of unfavorable neurologic outcome., Results: There are many methodological limitations in those patients reported in the literature with severe post anoxic encephalopathy who recover despite having lost their N20 cortical potential. These limitations include lack of sufficient clinical and neurologic data, severe core body hypothermia, specifics of electrophysiologic testing, technical issues such as background noise artifacts, flawed interpretations sometimes related to interobserver inconsistency, and the extreme variability in interpretation and quality of SSEP analysis among different clinicians and hospitals., Conclusions: The absence of the SSEP N20 cortical wave remains one of the most reliable early prognostic tools for identifying unfavorable neurologic outcome in the evaluation of patients with severe anoxic-ischemic encephalopathy whether or not they have been treated with TH. When confounding factors are eliminated the false positive rate (FPR) approaches zero.

Background: We hypothesized that the absence of P25 and the N20-P25 amplitude in somatosensory evoked potentials (SSEPs) have higher sensitivity than the absence of N20 for poor neurological outcomes, and we evaluated the ability of SSEPs to predict long-term outcomes using pattern and amplitude analyses., Methods: Using prospectively collected therapeutic hypothermia registry data, we evaluated whether cortical SSEPs contained a negative or positive short-latency wave (N20 or P25). The N20-P25 amplitude was defined as the largest difference in amplitude between the N20 and P25 peaks. A good or poor outcome was defined as a Glasgow-Pittsburgh Cerebral Performance Category (CPC) score of 1-2 or 3-5, respectively, 6 months after cardiac arrest., Results: A total of 192 SSEP recordings were included. In all patients with a good outcome (n = 51), both N20 and P25 were present. Compared to the absence of N20, the absence of N20-P25 component improved the sensitivity for predicting a poor outcome from 30.5% (95% confidence interval [CI], 23.0-38.8%) to 71.6% (95% CI, 63.4-78.9%), while maintaining a specificity of 100% (93.0-100.0%). Using an amplitude < 0.64 μV, i.e., the lowest N20-P25 amplitude in the good outcome group, as the threshold, the sensitivity for predicting a poor neurological outcome was 74.5% (95% CI, 66.5-81.4%). Using the highest N20-P25 amplitude in the CPC 4 group (2.31 μV) as the threshold for predicting a good outcome, the sensitivity and specificity were 52.9% (95% CI, 38.5-67.1%) and 96.5% (95% CI, 91.9-98.8%), respectively. The predictive performance of the N20-P25 amplitude was good, with an area under the receiver operating characteristic curve (AUC) of 0.94 (95% CI, 0.90-0.97). The absence of N20 was statistically inferior regarding outcome prediction (p < 0.05), and amplitude analysis yielded significantly higher AUC values than did the pattern analysis (p < 0.05)., Conclusions: The simple pattern analysis of whether the N20-P25 component was present had a sensitivity comparable to that of the N20-P25 amplitude for predicting a poor outcome. Amplitude analysis was also capable of predicting a good outcome.

Background: Organ dysfunction is common after cardiac arrest and associated with worse short-term outcome, but its impact on long-term outcome and treatment costs is unknown., Methods: We used nationwide registry data from the intensive care units (ICU) of the five Finnish university hospitals to evaluate the association of 24-h extracerebral Sequential Organ Failure Assessment (24h-EC-SOFA) score with 1-year survival and healthcare-associated costs after cardiac arrest. We included adult cardiac arrest patients treated in the participating ICUs between January 1, 2003, and December 31, 2013. We acquired the confirmed date of death from the Finnish Population Register Centre database and gross 1-year healthcare-associated costs from the hospital billing records and the database of the Finnish Social Insurance Institution., Results: A total of 5814 patients were included in the study, and 2401 were alive 1 year after cardiac arrest. Median (interquartile range (IQR)) 24h-EC-SOFA score was 6 (5-8) in 1-year survivors and 7 (5-10) in non-survivors. In multivariate regression analysis, adjusting for age and prior independency in self-care, the 24h-EC-SOFA score had an odds ratio (OR) of 1.16 (95% confidence interval (CI) 1.14-1.18) per point for 1-year mortality. Median (IQR) healthcare-associated costs in the year after cardiac arrest were €47,000 (€28,000-75,000) in 1-year survivors and €12,000 (€6600-25,000) in non-survivors. In a multivariate linear regression model adjusting for age and prior independency in self-care, an increase of one point in the 24h-EC-SOFA score was associated with an increase of €170 (95% CI €150-190) in the cost per day alive in the year after cardiac arrest. In the same model, an increase of one point in the 24h-EC-SOFA score was associated with an increase of €4400 (95% CI €3300-5500) in the total healthcare-associated costs in 1-year survivors., Conclusions: Extracerebral organ dysfunction is associated with long-term outcome and gross healthcare-associated costs of ICU-treated cardiac arrest patients. It should be considered when assessing interventions to improve outcomes and optimize the use of resources in these patients.

Background: Cardiorespiratory arrest can result in a spectrum of hypoxic ischemic brain injury leading to global hypoperfusion and brain death (BD). Because up to 40% of patients with BD are viable organ donors, avoiding delayed diagnosis of this condition is critical. High b-value diffusion weighted imaging (DWI) measures primarily molecular self-diffusion; however, low b-values are sensitive to perfusion. We investigated the feasibility of low b-value DWI in discriminating the global hypoperfusion of BD and hypoxic ischemic encephalopathy (HIE)., Methods: We retrospectively reviewed cardiorespiratory arrest subjects with a diagnosis of HIE or BD. Inclusion criteria included brain DWI acquired at both low (50 s/mm 2 ) and high (1000-2000 s/mm 2 ) b-values. Automated segmentation was used to determine mean b50 apparent diffusion coefficient (ADC) values in gray and white matter regions. Normal subjects with DWI at both values were used as age- and sex-matched controls., Results: We evaluated 64 patients (45 with cardiorespiratory arrest and 19 normal). Cardiorespiratory arrest patients with BD had markedly lower mean b50 ADC in gray matter regions compared with HIE (0.70 ± 0.18 vs. 1.95 ± 0.25 × 10 -3  mm 2 /s, p < 0.001) and normal subjects (vs. 1.79 ± 0.12 × 10 -3  mm 2 /s, p < 0.001). HIE had higher mean b50 ADC compared with normal (1.95 ± 0.25 vs. 1.79 ± 0.12 × 10 -3  mm 2 /s, p = 0.016). There was wide separation of gray matter ADC values in BD subjects compared with age matched normal and HIE subjects. White matter values were also markedly decreased in the BD population, although they were less predictive than gray matter., Conclusion: Low b-value DWI is promising for the discrimination of HIE with maintained perfusion and brain death in cardiorespiratory arrest.

Hypoxic-ischaemic brain injury (HIBI) is the main cause of death in patients who are comatose after resuscitation from cardiac arrest. A poor neurological outcome-defined as death from neurological cause, persistent vegetative state, or severe neurological disability-can be predicted in these patients by assessing the severity of HIBI. The most commonly used indicators of severe HIBI include bilateral absence of corneal and pupillary reflexes, bilateral absence of N 2 O waves of short-latency somatosensory evoked potentials, high blood concentrations of neuron specific enolase, unfavourable patterns on electroencephalogram, and signs of diffuse HIBI on computed tomography or magnetic resonance imaging of the brain. Current guidelines recommend performing prognostication no earlier than 72 h after return of spontaneous circulation in all comatose patients with an absent or extensor motor response to pain, after having excluded confounders such as residual sedation that may interfere with clinical examination. A multimodal approach combining multiple prognostication tests is recommended so that the risk of a falsely pessimistic prediction is minimised.

Secondary injury is a major determinant of outcome in hypoxic ischemic brain injury (HIBI) after cardiac arrest and may be mitigated by optimizing cerebral oxygen delivery (CDO 2 ). CDO 2 is determined by cerebral blood flow (CBF), which is dependent upon mean arterial pressure (MAP). In health, CBF remains constant over the MAP range through cerebral autoregulation. In HIBI, the zone of intact cerebral autoregulation is narrowed and varies for each patient. Maintaining MAP within the intact autoregulation zone may mitigate ischemia, hyperemia and secondary injury. The optimal MAP in individual patients can be determined using real time autoregulation monitoring techniques.

Background: Ischemia/reperfusion injury (I/R) is an important pathophysiology of post-cardiac arrest syndrome (PCAS) against multiple organ dysfunction and mortality. The inflammatory response in PCAS causes systemic I/R. The purpose of this study was to demonstrate the pathophysiology of systemic I/R for secondary brain damage using the biomarkers high-mobility group box 1 (HMGB1), neuron-specific enolase (NSE), and interleukin-6 (IL-6)., Methods: This study was designed as a single-institution prospective observational study. Subjects were observed for 90 days, and neurological outcome was classified according to the Glasgow-Pittsburgh Cerebral Performance Categories Scale (CPC). Serum HMGB1, NSE, and IL-6 were evaluated for variability, correlation with each biomarker, or the Sequential Organ Function Assessment (SOFA) score and CPC at return of spontaneous circulation at 0, 24, 48, and 168 h., Results: A total of 128 patients were enrolled in this study. Initial HMGB1 correlated with CPC (ρ = 0.27, p = 0.036) and SOFA score (ρ = 0.33, p < 0.001). The early phase of HMGB1 (0-24 h), all phases of IL-6, and the delayed phase of NSE (24-168 h) manifested poor neurological outcome. HMGB1 showed a significant correlation with NSE (ρ = 0.29, p = 0.002 at 0 h; ρ = 0.42, p < 0.001 at 24 h) and IL-6 (ρ = 0.36, p < 0.001 at 24 h)., Conclusions: Serum HMGB1 for first 24 h after cardiac arrest was significantly correlated with SOFA score, NSE, and IL-6. This result suggests that systemic I/R may contribute to secondary brain aggravation. It is expected that research on HMGB1 focused on systemic I/R will help prevent aggravating neurological outcomes.

Background: We recently showed that electroencephalography (EEG) patterns within the first 24 hours robustly contribute to multimodal prediction of poor or good neurological outcome of comatose patients after cardiac arrest. Here, we confirm these results and present a cost-minimization analysis. Early prognosis contributes to communication between doctors and family, and may prevent inappropriate treatment., Methods: A prospective cohort study including 430 subsequent comatose patients after cardiac arrest was conducted at intensive care units of two teaching hospitals. Continuous EEG was started within 12 hours after cardiac arrest and continued up to 3 days. EEG patterns were visually classified as unfavorable (isoelectric, low-voltage, or burst suppression with identical bursts) or favorable (continuous patterns) at 12 and 24 hours after cardiac arrest. Outcome at 6 months was classified as good (cerebral performance category (CPC) 1 or 2) or poor (CPC 3, 4, or 5). Predictive values of EEG measures and cost-consequences from a hospital perspective were investigated, assuming EEG-based decision- making about withdrawal of life-sustaining treatment in the case of a poor predicted outcome., Results: Poor outcome occurred in 197 patients (51% of those included in the analyses). Unfavorable EEG patterns at 24 hours predicted a poor outcome with specificity of 100% (95% CI 98-100%) and sensitivity of 29% (95% CI 22-36%). Favorable patterns at 12 hours predicted good outcome with specificity of 88% (95% CI 81-93%) and sensitivity of 51% (95% CI 42-60%). Treatment withdrawal based on an unfavorable EEG pattern at 24 hours resulted in a reduced mean ICU length of stay without increased mortality in the long term. This gave small cost reductions, depending on the timing of withdrawal., Conclusions: Early EEG contributes to reliable prediction of good or poor outcome of postanoxic coma and may lead to reduced length of ICU stay. In turn, this may bring small cost reductions.

Hypoxic ischemic brain injury (HIBI) after cardiac arrest (CA) is a leading cause of mortality and long-term neurologic disability in survivors. The pathophysiology of HIBI encompasses a heterogeneous cascade that culminates in secondary brain injury and neuronal cell death. This begins with primary injury to the brain caused by the immediate cessation of cerebral blood flow following CA. Thereafter, the secondary injury of HIBI takes place in the hours and days following the initial CA and reperfusion. Among factors that may be implicated in this secondary injury include reperfusion injury, microcirculatory dysfunction, impaired cerebral autoregulation, hypoxemia, hyperoxia, hyperthermia, fluctuations in arterial carbon dioxide, and concomitant anemia.Clarifying the underlying pathophysiology of HIBI is imperative and has been the focus of considerable research to identify therapeutic targets. Most notably, targeted temperature management has been studied rigorously in preventing secondary injury after HIBI and is associated with improved outcome compared with hyperthermia. Recent advances point to important roles of anemia, carbon dioxide perturbations, hypoxemia, hyperoxia, and cerebral edema as contributing to secondary injury after HIBI and adverse outcomes. Furthermore, breakthroughs in the individualization of perfusion targets for patients with HIBI using cerebral autoregulation monitoring represent an attractive area of future work with therapeutic implications.We provide an in-depth review of the pathophysiology of HIBI to critically evaluate current approaches for the early treatment of HIBI secondary to CA. Potential therapeutic targets and future research directions are summarized.

Introduction: Early prediction of a good outcome in comatose patients after cardiac arrest still remains an unsolved problem. The main aim of the present study was to examine the accuracy of middle-latency SSEP triggered by a painful electrical stimulation on median nerves to predict a favorable outcome., Methods: No- and low-flow times, pupillary reflex, Glasgow motor score and biochemical data were evaluated at ICU admission. The following were considered within 72 h of cardiac arrest: highest creatinine value, hyperthermia occurrence, EEG, SSEP at low- (10 mA) and high-intensity (50 mA) stimulation, and blood pressure reactivity to 50 mA. Intensive care treatments were also considered. Data were compared to survival, consciousness recovery and 6-month CPC (Cerebral Performance Category)., Results: Pupillary reflex and EEG were statistically significant in predicting survival; the absence of blood pressure reactivity seems to predict brain death within 7 days of cardiac arrest. Middle- and short-latency SSEP were statistically significant in predicting consciousness recovery, and middle-latency SSEP was statistically significant in predicting 6-month CPC outcome. The prognostic capability of 50 mA middle-latency-SSEP was demonstrated to occur earlier than that of EEG reactivity., Conclusions: Neurophysiological evaluation constitutes the key to early information about the neurological prognostication of postanoxic coma. In particular, the presence of 50 mA middle-latency SSEP seems to be an early and reliable predictor of good neurological outcome, and its absence constitutes a marker of poor prognosis. Moreover, the absence 50 mA blood pressure reactivity seems to identify patients evolving towards the brain death.

Introduction: There is a sex difference in the risk of ischemic acute kidney injury (AKI), and estrogen mediates the protective effect of female sex. We previously demonstrated that preprocedural chronic restoration of physiologic estrogen to ovariectomized female mice ameliorated AKI after cardiac arrest and cardiopulmonary resuscitation (CA/CPR). In the present study, we hypothesized that male mice and aged female mice would benefit from estrogen administration after CA/CPR. We tested the effect of estrogen in a clinically relevant manner by administrating it after CA/CPR., Methods: CA/CPR was performed in young (10-15 weeks), middle-aged (43-48 weeks), and aged (78-87 weeks) C57BL/6 male and female mice. Mice received intravenous 17β-estradiol or vehicle 15 min after resuscitation. Serum chemistries and unbiased stereological assessment of renal injury were completed 24 h after CA. Regional renal cortical blood flow was measured by a laser Doppler, and renal levels of estrogen receptor alpha (ERα) and G protein-coupled estrogen receptor (GPER) were evaluated with immunoblotting., Results: Post-arrest estrogen administration reduced injury in young males without significant changes in renal blood flow (percentage reduction compared with vehicle: serum urea nitrogen, 30 %; serum creatinine (sCr), 41 %; volume of necrotic tubules (VNT), 31 %; P < 0.05). In contrast, estrogen did not affect any outcomes in young females. In aged mice, estrogen significantly reduced sCr (80 %) and VNT (73 %) in males and VNT (51 %) in females. Serum estrogen levels in aged female mice after CA/CPR were the same as levels in male mice. With age, renal ERα was upregulated in females., Conclusions: Estrogen administration after resuscitation from CA ameliorates renal injury in young males and aged mice in both sexes. Because injury was small, young females were not affected. The protective effect of exogenous estrogen may be detectable with loss of endogenous estrogen in aged females and could be mediated by differences in renal ERs. Post-arrest estrogen administration is renoprotective in a sex- and age-dependent manner.

Introduction: Previous studies evaluating whether subsequent conversion to shockable rhythms in patients who had initially non-shockable rhythms was associated with altered clinical outcome reported inconsistent results. Therefore, we hypothesized that subsequent shock delivery by emergency medical service (EMS) providers altered clinical outcomes in patients with initially non-shockable rhythms., Methods: We tested for an association between subsequent shock delivery in EMS resuscitation and clinical outcomes in patients with initially non-shockable rhythms (n = 11,481) through a survey of patients after out-of-hospital cardiac arrest in the Kanto region (SOS-KANTO) 2012 study cohort, Japan. The primary investigated outcome was 1-month survival with favorable neurological functions. The secondary outcome variable was the presence of subsequent shock delivery. We further evaluated the association of interval from initiation of cardiopulmonary resuscitation to shock with clinical outcomes., Results: In the univariate analysis of initially non-shockable rhythms, patients who received subsequent shock delivery had significantly increased frequency of return of spontaneous circulation, 24-hour survival, 1-month survival, and favorable neurological outcomes compared to the subsequent not shocked group (P < 0.0001). In the multivariate logistic regression analysis, subsequent shock was significantly associated with favorable neurological outcomes (vs. not shocked; adjusted P = 0.0020, odds ratio, 2.78; 95% confidence interval, 1.45-5.30). Younger age, witnessed arrest, initial pulseless electrical activity rhythms, and cardiac etiology were significantly associated with the presence of subsequent shock in patients with initially non-shockable rhythms., Conclusions: In this study of cardiac arrest patients with initially non-shockable rhythms, patients who received early defibrillation by EMS providers had increased 1-month favorable neurological outcomes.

Introduction: The aim of this study was to evaluate the incidence and determinants of AKI in a large cohort of cardiac arrest patients., Methods: We reviewed all patients admitted, for at least 48 hours, to our Dept. of Intensive Care after CA between January 2008 and October 2012. AKI was defined as oligo-anuria (daily urine output <0.5 ml/kg/h) and/or an increase in serum creatinine (≥0.3 mg/dl from admission value within 48 hours or a 1.5 time from baseline level). Demographics, comorbidities, CA details, and ICU interventions were recorded. Neurological outcome was assessed at 3 months using the Cerebral Performance Category scale (CPC 1-2 = favorable outcome; 3-5 = poor outcome)., Results: A total of 199 patients were included, 85 (43%) of whom developed AKI during the ICU stay. Independent predictors of AKI development were older age, chronic renal disease, higher dose of epinephrine, in-hospital CA, presence of shock during the ICU stay, a low creatinine clearance (CrCl) on admission and a high cumulative fluid balance at 48 hours. Patients with AKI had higher hospital mortality (55/85 vs. 57/114, p = 0.04), but AKI was not an independent predictor of poor 3-month neurological outcome., Conclusions: AKI occurred in more than 40% of patients after CA. These patients had more severe hemodynamic impairment and needed more aggressive ICU therapy; however the development of AKI did not influence neurological recovery.

Introduction: Post-cardiac arrest patients are often exposed to 100% oxygen during cardiopulmonary resuscitation and the early post-arrest period. It is unclear whether this contributes to development of pulmonary dysfunction or other patient outcomes., Methods: We performed a retrospective cohort study including post-arrest patients who survived and were mechanically ventilated at least 24 hours after return of spontaneous circulation. Our primary exposure of interest was inspired oxygen, which we operationalized by calculating the area under the curve of the fraction of inspired oxygen (FiO₂AUC) for each patient over 24 hours. We collected baseline demographic, cardiovascular, pulmonary and cardiac arrest-specific covariates. Our main outcomes were change in the respiratory subscale of the Sequential Organ Failure Assessment score (SOFA-R) and change in dynamic pulmonary compliance from baseline to 48 hours. Secondary outcomes were survival to hospital discharge and Cerebral Performance Category at discharge., Results: We included 170 patients. The first partial pressure of arterial oxygen (PaO₂):FiO₂ ratio was 241 ± 137, and 85% of patients had pulmonary failure and 55% had cardiovascular failure at presentation. Higher FiO₂AUC was not associated with change in SOFA-R score or dynamic pulmonary compliance from baseline to 48 hours. However, higher FiO₂AUC was associated with decreased survival to hospital discharge and worse neurological outcomes. This was driven by a 50% decrease in survival in the highest quartile of FiO₂AUC compared to other quartiles (odds ratio for survival in the highest quartile compared to the lowest three quartiles 0.32 (95% confidence interval 0.13 to 0.79), P = 0.003)., Conclusions: Higher exposure to inhaled oxygen in the first 24 hours after cardiac arrest was not associated with deterioration in gas exchange or pulmonary compliance after cardiac arrest, but was associated with decreased survival and worse neurological outcomes.

The prognosis of patients who are admitted in a comatose state following successful resuscitation after cardiac arrest remains uncertain. Although the introduction of therapeutic hypothermia (TH) and improvements in post-resuscitation care have significantly increased the number of patients who are discharged home with minimal brain damage, short-term assessment of neurological outcome remains a challenge. The need for early and accurate prognostic predictors is crucial, especially since sedation and TH may alter the neurological examination and delay the recovery of motor response for several days. The development of additional tools, including electrophysiological examinations (electroencephalography and somatosensory evoked potentials), neuroimaging and chemical biomarkers, may help to evaluate the extent of brain injury in these patients. Given the extensive literature existing on this topic and the confounding effects of TH on the strength of these tools in outcome prognostication after cardiac arrest, the aim of this narrative review is to provide a practical approach to post-anoxic brain injury when TH is used. We also discuss when and how these tools could be combined with the neurological examination in a multimodal approach to improve outcome prediction in this population.

There has been a dramatic change in hospital care of cardiac arrest survivors in recent years, including the use of target temperature management (hypothermia). Clinical signs of recovery or deterioration, which previously could be observed, are now concealed by sedation, analgesia, and muscle paralysis. Seizures are common after cardiac arrest, but few centers can offer high-quality electroencephalography (EEG) monitoring around the clock. This is due primarily to its complexity and lack of resources but also to uncertainty regarding the clinical value of monitoring EEG and of treating post-ischemic electrographic seizures. Thanks to technical advances in recent years, EEG monitoring has become more available. Large amounts of EEG data can be linked within a hospital or between neighboring hospitals for expert opinion. Continuous EEG (cEEG) monitoring provides dynamic information and can be used to assess the evolution of EEG patterns and to detect seizures. cEEG can be made more simple by reducing the number of electrodes and by adding trend analysis to the original EEG curves. In our version of simplified cEEG, we combine a reduced montage, displaying two channels of the original EEG, with amplitude-integrated EEG trend curves (aEEG). This is a convenient method to monitor cerebral function in comatose patients after cardiac arrest but has yet to be validated against the gold standard, a multichannel cEEG. We recently proposed a simplified system for interpreting EEG rhythms after cardiac arrest, defining four major EEG patterns. In this topical review, we will discuss cEEG to monitor brain function after cardiac arrest in general and how a simplified cEEG, with a reduced number of electrodes and trend analysis, may facilitate and improve care.

Introduction: Ischemia/reperfusion after cardiopulmonary resuscitation (CPR) induces systemic inflammatory response and activation of endothelium and coagulation, resulting in a post-cardiac arrest syndrome. We analysed circulating (annexin V+) microparticles and their conjugates in resuscitated patients., Methods: 36 patients after successful resuscitation, 20 control patients with stable cardiac disease and 15 healthy subjects were included prospectively. Two blood samples were drawn, one immediately and one 24 hours after return of spontaneous circulation (ROSC) to detect (annexin V+) monocyte-derived microparticles (MMPs) or procoagulant (annexin V+) platelet-derived microparticles (PMPs) and conjugates of endothelial-derived (annexin V+) microparticles (EMPs) with monocytes (EMP-MC) or platelets (EMP-PC). Measurements were performed by flow cytometric analysis. Additionally, the effect of isolated microparticles on cultured endothelial cells was assessed by ELISA., Results: MMPs were significantly elevated immediately after ROSC compared to the cardiological control group (control; p < 0.01) and healthy subjects (healthy; p < 0.05) and persisted to be elevated in the following 24 hours after CPR (p < 0.05 vs. control and healthy, respectively). Procoagulant PMPs increased within the first 24 hours after ROSC (p < 0.01 vs. control and p < 0.005 vs. healthy). Conjugates of EMP with monocytes and platelets were both significantly elevated immediately after CPR (EMP-MC: p < 0.05 vs. control and p < 0.05 vs. healthy; EMP-PC: p < 0.05 vs. control and p < 0.05 vs. healthy), while only EMP-MC showed persisting high levels within 24 hours after CPR (p < 0.05 vs. control and p < 0.01 vs. healthy). MMP levels of ≥ 1.0/μL 24 hours after CPR predicted adverse outcome at 20 days (p < 0.05). Furthermore, isolated microparticles circulating in CPR patients early after ROSC led to enhanced endothelial apoptosis ex vivo compared to those of the healthy controls (p < 0.005)., Conclusions: Resuscitated patients show substantially increased levels of different (annexin V+) microparticles and their conjugates immediately and 24 hours after cardiopulmonary resuscitation, suggesting an early onset of inflammation, an ongoing endothelial activation and a procoagulatory state. Additionally, microparticles of CPR patients may contribute to endothelial apoptosis. These results point to an involvement of microparticles in the development of the post-cardiac arrest syndrome.

Introduction: Neuron specific enolase (NSE) has been proven effective in predicting neurological outcome after cardiac arrest with a current cut off recommendation of 33 microg/l. However, most of the corresponding studies were conducted before the introduction of mild therapeutic hypothermia (MTH). Therefore we conducted a study investigating the association between NSE and neurological outcome in patients treated with MTH., Methods: In this prospective observational cohort study the data of patients after cardiac arrest receiving MTH (n = 97) were consecutively collected and compared with a retrospective non-hypothermia (NH) group (n = 133). Serum NSE was measured 72 hours after admission to ICU. Neurological outcome was classified according to the Pittsburgh cerebral performance category (CPC 1 to 5) at ICU discharge., Results: NSE serum levels were significantly lower under MTH compared to NH in univariate analysis. However, in a linear regression model NSE was affected significantly by time to return of spontaneous circulation (ROSC) and ventricular fibrillation rhythm but not by MTH. The model for neurological outcome identified NSE, NSE*MTH (interaction) as well as time to ROSC as significant predictors. Receiver Operating Characteristic (ROC) analysis revealed a higher cutoff value for unfavourable outcome (CPC 3 to 5) with a specificity of 100% in the hypothermia group (78.9 microg/l) compared to the NH group (26.9 microg/l)., Conclusions: Recommended cutoff levels for NSE 72 hours after ROSC do not reliably predict poor neurological outcome in cardiac arrest patients treated with MTH. Prospective multicentre trials are required to re-evaluate NSE cutoff values for the prediction of neurological outcome in patients treated with MTH.

Background: Temperature management is used with increased frequency as a tool to mitigate neurological injury. Although frequently used, little is known about the optimal cooling methods for inducing and maintaining controlled normo- and hypothermia in the intensive care unit (ICU). In this study we compared the efficacy of several commercially available cooling devices for temperature management in ICU patients with various types of neurological injury., Methods: Fifty adult ICU patients with an indication for controlled mild hypothermia or strict normothermia were prospectively enrolled. Ten patients in each group were assigned in consecutive order to conventional cooling (that is, rapid infusion of 30 ml/kg cold fluids, ice and/or coldpacks), cooling with water circulating blankets, air circulating blankets, water circulating gel-coated pads and an intravascular heat exchange system. In all patients the speed of cooling (expressed as degrees C/h) was measured. After the target temperature was reached, we measured the percentage of time the patient's temperature was 0.2 degrees C below or above the target range. Rates of temperature decline over time were analyzed with one-way analysis of variance. Differences between groups were analyzed with one-way analysis of variance, with Bonferroni correction for multiple comparisons. A p < 0.05 was considered statistically significant., Results: Temperature decline was significantly higher with the water-circulating blankets (1.33 +/- 0.63 degrees C/h), gel-pads (1.04 +/- 0.14 degrees C/h) and intravascular cooling (1.46 +/- 0.42 degrees C/h) compared to conventional cooling (0.31 +/- 0.23 degrees C/h) and the air-circulating blankets (0.18 +/- 0.2 degrees C/h) (p < 0.01). After the target temperature was reached, the intravascular cooling device was 11.2 +/- 18.7% of the time out of range, which was significantly less compared to all other methods., Conclusion: Cooling with water-circulating blankets, gel-pads and intravascular cooling is more efficient compared to conventional cooling and air-circulating blankets. The intravascular cooling system is most reliable to maintain a stable temperature.

Neurologic disability is a feared outcome of resuscitation from cardiac arrest. The study by Rech and colleagues in the previous issue of Critical Care describes the use of neuron-specific enolase to inform an early prognosis in patients who survived in-hospital cardiac arrest. In their study 'none of the patients had a DNR order and there was no limitation of life support.' As a result, 10% of patients remained in a vegetative state at 6 months, a higher percentage than in other recent studies. The existence of a population of patients in which all are fully supported without withholding care or withdrawal of care may represent an important research opportunity. High neuron-specific enolase levels have been reported in patients that awoke and seem to occur in studies with a higher percentage of patients in a vegetative state at follow-up (more uniform support). If a comprehensive set of clinical, electrophysiological, biochemical and imaging measures could be obtained in a uniform manner in a cohort of patients without limitations in care, a more objective set of comprehensive prognostic indicators could be obtained. A focused international consortium is called for.

Metabolic acidosis is a common finding after cardiac arrest. Until recently this acidosis was mainly attributed to lactate. The physico-chemical approach to acid-base balance permits the detection of previously unmeasured ions. These ions have been shown to affect the acid-base status of patients.