Post-cardiac Arrest Research Articles

Therapeutic Hypothermia Following Cardiopulmonary Arrest: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

The risk-benefit profile of therapeutic hypothermia is controversial with several randomized controlled trials providing conflicting results. The purpose of this systematic review and meta-analysis was to determine if therapeutic hypothermia provides beneficial neurologic outcomes relative to adverse effects. MEDLINE and EMBASE databases were searched for randomized controlled trials of post-cardiac arrest patients comparing therapeutic hypothermia (~33 degrees Celsius) to normothermia or the standard of care (36 - 38 degrees Celsius). Data were collected using the Covidence systematic review software. Statistical analysis was performed by Review Manager software. Risk of bias, sensitivity, and heterogeneity were analyzed using the Cochran's Collaboration tool, trial sequential analysis (TSA) software, and I2 statistic respectively. A total of 1825 studies were screened and 5 studies (n=3614) were included. No significant differences existed between the hypothermia group and normothermia for favorable neurologic outcome (risk ratio [RR] 1.17, 95% confidence interval [CI] 0.97 to 1.41) or all-cause mortality (RR 0.97, 95% CI 0.89 to 1.05). When compared to normothermia, the hypothermia group had greater risk of adverse effects (RR 1.16, 95% CI 1.04 to 1.28), which was driven by the onset of arrhythmias. Subgroup analyses revealed that therapeutic hypothermia provided greater neurologic benefit in trials with a higher percentage of subjects with shockable rhythms (RR 0.73, 95% CI 0.6 to 0.88). Trial sequential analysis revealed statistical futility for therapeutic hypothermia and favorable neurologic outcome, mortality, and adverse effects. Therapeutic hypothermia does not provide consistent benefit in neurologic outcome or mortality in the general cardiac arrest population. Patients with shockable rhythms may show favorable neurologic outcome with therapeutic hypothermia and further investigation in this population is warranted. Any potential benefit associated with therapeutic hypothermia must be weighed against the increased risk of adverse effects, particularly the onset of arrhythmias.

Optimal Timing of Targeted Temperature Management for Post-Cardiac Arrest Syndrome: Is Sooner Better?

Targeted temperature management (TTM) is often considered to improve post-cardiac arrest patients' outcomes. However, the optimal timing to initiate cooling remained uncertain. This retrospective analysis enrolled all non-traumatic post-cardiac arrest adult patients with either out-of-hospital cardiac arrest (OHCA) or in-hospital cardiac arrest (IHCA) who received TTM from July 2015 to July 2021 at our hospital. The values of time delay before TTM and time to target temperature were divided into three periods according to optimal cut-off values identified using receiver operating characteristic curve analysis. A total of 177 patients were enrolled. A shorter time delay before TTM (pre-induction time) was associated with a lower survival chance at 28 days (32.00% vs. 54.00%, p = 0.0279). Patients with a longer cooling induction time (>440 minis) had better neurological outcomes (1.58% vs. 1.05%; p = 0.001) and survival at 28 days (58.06% vs. 29.25%; p = 0.006). After COX regression analysis, the influence of pre-induction time on survival became insignificant, but patients who cooled slowest still had a better chance of survival at 28 days. In conclusion, a shorter delay before TTM was not associated with better clinical outcomes. However, patients who took longer to reach the target temperature had better hospital survival and neurological outcomes than those who were cooled more rapidly. A further prospective study was warranted to evaluate the appropriate time window of TTM.

OMICRON AS A CARDIOVASCULAR MANIFESTATION: A RARE PRESENTATION AND MANAGEMENT AT TERTIARY CANCER CARE CENTER WITH LIMITED RESOURCES

Severe Acute Respiratory Distress Syndrome Coronavirus 2 (SARS CoV-2) and its new variant Omicron was propelling the surge in Coronavirus Disease (COVID-19) in India and the world over. COVID-19 is associated with various extrapulmonary manifestations leading to acute coronary syndrome (ACS) in many patients. In our case report, a 55-year-old male with carcinoma soft palate on neo-adjuvant chemotherapy and radiotherapy came to our hospital emergency in an unconscious state. Cardiopulmonary resuscitation was initiated in the emergency suite, he was revived and shifted to the critical care unit for post cardiac arrest management. Patient was hemodynamically unstable and started on vasopressor support, electrocardiogram showed ischemic changes in anterolateral leads with cardiac enzyme troponin-T was positive. A diagnosis of ACS was made and managed appropriately. The patient got stabilized over a few hours, reverse transcriptase-polymerase chain reaction (RT-PCR) test was positive for novel COVID-19. Since our institute is a L2 setting hospital with limited resources, he was shifted to a higher centre for effective COVID-19 management. ACS is a deadly manifestation in COVID-19 patients. Cancer patients are immuno-compromised with a propensity for the hypercoagulable state due to the disease itself. We suggest that Omicron a new variant of concern leading to COVID-19 with cancer burden can aggravate extrapulmonary manifestation in a vulnerable population. We should be extra careful in the management of these patients.

Escherichia coli-induced inflammatory responses are temperature-dependent in human whole blood ex vivo

Systemic inflammatory conditions are often associated with hypothermia or hyperthermia. Therapeutic hypothermia is used in post-cardiac arrest and some other acute diseases. There is a need for more knowledge concerning the effect of various temperatures on the acute inflammatory response. The complement system plays a crucial role in initiating the inflammatory response. We hypothesized that temperatures above and below the physiologic 37 °C affect complement activation and cytokine production ex vivo. Lepirudin-anticoagulated human whole blood from 10 healthy donors was incubated in the presence or absence of Escherichia coli at different temperatures (4 °C, 12 °C, 20 °C, 33 °C, 37 °C, 39 °C, and 41 °C). Complement activation was assessed by the terminal C5b-9 complement complex (TCC) and the alternative convertase C3bBbP using ELISA. Cytokines were measured using a 27-plex assay. Granulocyte and monocyte activation was evaluated by CD11b surface expression using flow cytometry. A consistent increase in complement activation was observed with rising temperature, reaching a maximum at 41 °C, both in the absence (C3bBbP p < 0.05) and presence (C3bBbP p < 0.05 and TCC p < 0.05) of E. coli. Temperature alone did not affect cytokine production, whereas incubation with E. coli significantly increased cytokine levels of IL-1β, IL-2, IL-6, IL-8, IFN-γ, and TNF at temperatures > 20 °C. Maximum increase occurred at 39 °C. However, a consistent decrease was observed at 41 °C, significant for IL-1β (p = 0.003). Granulocyte CD11b displayed the same temperature-dependent pattern as cytokines, with a corresponding increase in endothelial cell apoptosis and necrosis. Thus, blood temperature differentially determines the degree of complement activation and cytokine release.

Efficacy of inhaled hydrogen on neurological outcome following brain ischaemia during post-cardiac arrest care (HYBRID II): a multi-centre, randomised, double-blind, placebo-controlled trial

Inhaled molecular hydrogen gas (H2) has been shown to improve outcomes in animal models of cardiac arrest (CA). H2 inhalation is safe and feasible in patients after CA. We investigated whether inhaled H2 would improve outcomes after out-of-hospital CA (OHCA). HYBRID II is a prospective, multicentre, randomised, double-blind, placebo-controlled trial performed at 15 hospitals in Japan, between February 1, 2017, and September 30, 2021. Patients aged 20-80 years with coma following cardiogenic OHCA were randomly assigned (1:1) using blinded gas cylinders to receive supplementary oxygen with 2% H2 or oxygen (control) for 18h. The primary outcome was the proportion of patients with a 90-day Cerebral Performance Category (CPC) of 1 or 2 assessed in a full-analysis set. Secondary outcomes included the 90-day score on a modified Rankin scale (mRS) and survival. HYBRID II was registered with the University Hospital Medical Information Network (registration number: UMIN000019820) and re-registered with the Japan Registry for Clinical Trials (registration number: jRCTs031180352). The trial was terminated prematurely because of the restrictions imposed on enrolment during the COVID-19 pandemic. Between February 1, 2017, and September 30, 2021, 429 patients were screened for eligibility, of whom 73 were randomly assigned to H2 (n=39) or control (n=34) groups. The primary outcome, i.e., a CPC of 1 or 2at 90 days, was achieved in 22 (56%) and 13 (39%) patients in the H2 and control groups (relative risk compared with the control group, 0.72; 95% CI, 0.46-1.13; P=0.15), respectively. Regarding the secondary outcomes, median mRS was 1 (IQR: 0-5) and 5 (1-6) in the H2 and control groups, respectively (P=0.01). An mRS score of 0 was achieved in 18 (46%) and 7 (21%) patients in the H2 and control groups, respectively (P=0.03). The 90-day survival rate was 85% (33/39) and 61% (20/33) in the H2 and control groups, respectively (P=0.02). The increase in participants with good neurological outcomes following post-OHCA H2 inhalation in a selected population of patients was not statistically significant. However, the secondary outcomes suggest that H2 inhalation may increase 90-day survival without neurological deficits. Taiyo Nippon Sanso Corporation. For the Japanese translation of the abstract see Supplementary Materials section.

Long-term function, quality of life and healthcare utilization among survivors of pediatric out-of-hospital cardiac arrest

BackgroundSurvival following pediatric out-of-hospital cardiac arrest (OHCA) has improved over the past 2 decades but data on survivors’ long-term outcomes are limited. We aimed to evaluate long-term outcomes in pediatric OHCA survivors more than one year after cardiac arrest. MethodsOHCA survivors <18 years old who received post-cardiac arrest care in the PICU at a single center between 2008–2018 were included. Parents of patients <18 years and patients ≥18 years at least one year after cardiac arrest completed a telephone interview. We assessed neurologic outcome (Pediatric Cerebral Performance Category [PCPC]), activities of daily living (Pediatric Glasgow Outcomes Scale-Extended, Functional Status Scale (FSS)), HRQL (Pediatric Quality of Life Core and Family Impact Modules), and healthcare utilization. Unfavorable neurologic outcome was defined as PCPC > 1 or worsening from pre-arrest baseline to discharge. FindingsForty four patients were evaluable. Follow-up occurred at a median of 5.6 years [IQR 4.4, 8.9] post-arrest. Median age at arrest was 5.3 [1.3,12.6] years; median CPR duration was 5 [1.5, 7] minutes. Survivors with unfavorable outcome at discharge had worse FSS Sensory and Motor Function scores and higher rates of rehabilitation service utilization. Parents of survivors with unfavorable outcome reported greater disruption to family functioning. Healthcare utilization and educational support requirements were common among all survivors. ConclusionsSurvivors of pediatric OHCA with unfavorable outcome at discharge have more impaired function multiple years post-arrest. Survivors with favorable outcome may experience impairments and significant healthcare needs not fully captured by the PCPC at hospital discharge.

Prognostic Association Between Frailty and Post-Arrest Health Outcomes in Patients Receiving Home Care: A Population-Based Retrospective Cohort Study

AimTo evaluate the association between frailty and post-cardiac arrest survival, functional decline, and cognitive decline, among patients receiving home care. MethodsFrailty was measured using the Clinical Frailty Scale (CFS) and a valid frailty index. We used multivariable logistic regression to measure the association between frailty and post-arrest outcomes after adjusting for age, sex, and arrest setting. Functional independence and cognitive performance were measured using the interRAI ADL Long-Form and Cognitive Performance Scale, respectively. We conducted sub-group analytics of in-hospital and out-of-hospital arrests. ResultsOur cohort consisted of 7,901 home care clients; most patients arrested out-of-hospital (55.4%) and were 75 years or older (66.3%). Most were classified as frail (94.2%) with a CFS score of 5 or greater. The 30-day survival rate was higher for in-hospital (26.6%) than out-of-hospital cardiac arrests (5.2%). Most patients who survived to discharge had declines in post-arrest functional independence (65.8%) and cognitive performance (46.5%). A one-point increase in the CFS decreased the odds of 30-day survival by 8% (aOR = 0.92; 95%CI = 0.87–0.97). A 0.1 unit increase in the frailty index reduced the odds of 30-day survival by 9% (aOR = 0.91; 95%CI = 0.86–0.96). The frailty index was associated with declines in functional independence (OR = 1.16; 95%CI = 1.02–1.31) and cognitive performance (OR = 1.24; 95%CI = 1.09–1.42), while the CFS was not. ConclusionFrailty is associated with cardiac arrest survival and post-arrest cognitive and functional status in patients receiving home care. Post-cardiac arrest cognitive and functional status are best predicted using more comprehensive frailty indices.

Novel serum biomarkers for predicting neurological outcomes in postcardiac arrest patients treated with targeted temperature management

ObjectiveTo determine the clinical feasibility of novel serum biomarkers in out-of-hospital cardiac arrest (OHCA) patients treated with target temperature management (TTM).MethodsThis study was a prospective observational study conducted on OHCA patients who underwent TTM. We measured conventional biomarkers, neuron‑specific enolase and S100 calcium-binding protein (S-100B), as well as novel biomarkers, including tau protein, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase-L1 (UCH-L1), at 0, 24, 48, and 72 h after the return of spontaneous circulation identified by SIMOA immunoassay. The primary outcome was poor neurological outcome at 6 months after OHCA.ResultsA total of 100 patients were included in this study from August 2018 to May 2020. Among the included patients, 46 patients had good neurologic outcomes at 6 months after OHCA. All conventional and novel serum biomarkers had the ability to discriminate between the good and poor neurological outcome groups (p < 0.001). The area under the curves of the novel serum biomarkers were highest at 72 h after cardiac arrest (CA) (0.906 for Tau, 0.946 for NFL, 0.875 for GFAP, and 0.935 for UCH-L1). The NFL at 72 h after CA had the highest sensitivity (77.1%, 95% CI 59.9–89.6) in predicting poor neurological outcomes while maintaining 100% specificity.ConclusionNovel serum biomarkers reliably predicted poor neurological outcomes for patients with OHCA treated with TTM when life-sustaining therapy was not withdrawn. Cutoffs from two large existing studies (TTM and COMACARE substudy) were externally validated in our study. The predictive power of the novel biomarkers was the highest at 72 h after CA.

One-Year Review in Cardiac Arrest: The 2022 Randomized Controlled Trials.

Cardiac arrest, one of the leading causes of death, accounts for numerous clinical studies published each year. This review summarizes the findings of all the randomized controlled clinical trials (RCT) on cardiac arrest published in the year 2022. The RCTs are presented according to the following categories: out-of- and in-hospital cardiac arrest (OHCA, IHCA) and post-cardiac arrest care. Interestingly, more than 80% of the RCTs encompassed advanced life support and post-cardiac arrest care, while no studies focused on the treatment of IHCA, except for one that, however, explored the temperature control after resuscitation in this population. Surprisingly, 9 out of 11 RCTs led to neutral results demonstrating equivalency between the newly tested interventions compared to current practice. One trial was negative, showing that oxygen titration in the immediate pre-hospital post-resuscitation period decreased survival compared to a more liberal approach. One RCT was positive and introduced new defibrillation strategies for refractory cardiac arrest. Overall, data from the 2022 RCTs discussed here provide a solid basis to generate new hypotheses to be tested in future clinical studies.

Artificial Intelligence in Resuscitation: A Scoping Review.

Cardiac arrest is a significant cause of premature mortality and severe disability. Despite the death rate steadily decreasing over the previous decade, only 22% of survivors achieve good clinical status and only 25% of patients survive until their discharge from the hospital. The objective of this scoping review was to review relevant AI modalities and the main potential applications of AI in resuscitation. We conducted the literature search for related studies in PubMed, EMBASE, and Google Scholar. We included peer-reviewed publications and articles in the press, pooling and characterizing the data by their model types, goals, and benefits. After identifying 268 original studies, we chose 59 original studies (reporting 1,817,419 patients) to include in the qualitative synthesis. AI-based methods appear to be superior to traditional methods in achieving high-level performance. AI might be useful in predicting cardiac arrest, heart rhythm disorders, and post-cardiac arrest outcomes, as well as in the delivery of drone-delivered defibrillators and notification of dispatchers. AI-powered technologies could be valuable assistants to continuously track patient conditions. Healthcare professionals should assist in the research and development of AI-powered technologies as well as their implementation into clinical practice.

The Effect of Early Application of Synthetic Peptides 19-2.5 and 19-4LF to Improve Survival and Neurological Outcome in a Mouse Model of Cardiac Arrest and Resuscitation

The synthetic antimicrobial peptides (sAMPs) Pep19-2.5 and Pep19-4LF have been shown in vitro and in vivo to reduce the release of pro-inflammatory cytokines, leading to the suppression of inflammation and immunomodulation. We hypothesized that intervention with Pep19-2.5 and Pep19-4LF immediately after cardiac arrest and resuscitation (CA-CPR) might attenuate immediate systemic inflammation, survival, and long-term outcomes in a standardized mouse model of CA-CPR. Long-term outcomes up to 28 days were assessed between a control group (saline) and two peptide intervention groups. Primarily, survival as well as neurological and cognitive parameters were assessed. In addition, systemic inflammatory molecules and specific biomarkers were analyzed in plasma as well as in brain tissue. Treatment with sAMPs did not provide any short- or long-term benefits for either survival or neurological outcomes, and no significant benefit on inflammation in the CA-CPR animal model. While no difference was found in the plasma analysis of early cytokines between the intervention groups four hours after resuscitation, a significant increase in UCH-L1, a biomarker of neuronal damage and blood-brain barrier rupture, was measured in the Pep19-4LF-treated group. The theoretical benefit of both sAMPs tested here for the treatment of post-cardiac arrest syndrome could not be proven.

Neuroprognostication after cardiac arrest: what the cardiologist should know.

Two aspects are a key to mastering prognostication of comatose cardiac arrest survivors: a detailed knowledge about the clinical trajectories of consciousness recovery (or lack thereof) and the ability to correctly interpret the results of multimodal investigations, which include clinical examination, electroencephalography, neuroimaging, evoked potentials, and blood biomarkers. While the very good and the very poor ends of the clinical spectrum typically do not pose diagnostic challenges, the intermediate 'grey zone' of post-cardiac arrest encephalopathy requires cautious interpretation of the available information and sufficiently long clinical observation. Late recovery of coma patients with initially ambiguous diagnostic results is increasingly reported, as are unresponsive patients with various forms of residual consciousness, including so-called cognitive motor dissociation, rendering prognostication of post-anoxic coma highly complex. The aim of this paper is to provide busy clinicians with a high-yield, concise overview of neuroprognostication after cardiac arrest, emphasizing notable developments in the field since 2020.

Outcome in Children Admitted to the First PICU in Malawi.

Dedicated PICUs are slowly starting to emerge in sub-Saharan Africa. Establishing these units can be challenging as there is little data from this region to inform which populations and approaches should be prioritized. This study describes the characteristics and outcome of patients admitted to the first PICU in Malawi, with the aim to identify factors associated with increased mortality. Review of a prospectively constructed PICU database. Univariate analysis was used to assess associations between demographic, clinical and laboratory factors, and mortality. Univariate associations ( p < 0.1) for mortality were entered in two multivariable models. A recently opened PICU in a public tertiary government hospital in Blantyre, Malawi. Children admitted to PICU between August 1, 2017, and July 31, 2019. None. Of 531 included PICU admissions, 149 children died (28.1%). Mortality was higher in neonates (88/167; 52.7%) than older children (61/364; 16.8%; p ≤ 0.001). On univariate analysis, gastroschisis, trachea-esophageal fistula, and sepsis had higher PICU mortality, while Wilms tumor, other neoplasms, vocal cord papilloma, and foreign body aspiration had higher survival rates compared with other conditions. On multivariable analysis, neonatal age (adjusted odds ratio [AOR], 4.0; 95% CI, 2.0-8.3), decreased mental state (AOR, 5.8; 95 CI, 2.4-13.8), post-cardiac arrest (AOR, 2.0; 95% CI, 1.0-8.0), severe hypotension (AOR, 6.3; 95% CI, 2.0-19.1), lactate greater than 5 mmol/L (AOR, 4.2; 95% CI, 1.5-11.2), pH less than 7.2 (AOR, 3.1; 95% CI, 1.2-8.0), and platelets less than 150 × 10 9 /L (AOR, 2.4; 95% CI, 1.1-5.2) were associated with increased mortality. In the first PICU in Malawi, mortality was relatively high, especially in neonates. Surgical neonates and septic patients were identified as highly vulnerable, which stresses the importance of improvement of PICU care bundles for these groups. Several clinical and laboratory variables were associated with mortality in older children. In neonates, severe hypotension was the only clinical variable associated with increased mortality besides blood gas parameters. This stresses the importance of basic laboratory tests, especially in neonates. These data contribute to evidence-based approaches establishing and improving future PICUs in sub-Saharan Africa.

ANTERIOR THALAMIC ISCHAEMIC STROKE SECONDARY TO CARDIOPULMONARY ARREST.

Ischaemic anterior thalamic lesions are rare and can present with disturbances of behaviour and memory. We describe a patient with post-cardiac arrest thalamic stroke. A 63-year-old man presented with cardiac arrest, was resuscitated after receiving life support, and showed no lesions on computed tomography. Three days later, he presented with short-term memory disturbance and disorientation, with a de novo anterior thalamic lesion. The anterior thalamic nucleus, supplied by the posterior communicating artery, is part of the Papez circuit and has a role in modulating behaviour and memory. An anterior thalamic syndrome presents with no sensory-motor deficits. Anterior thalamic stroke is a rare condition and can present with disturbances of short-term memory and behaviour; it usually does not include any motor or sensory deficits.Thalamic stroke can occur due to global hypoxia, such as during cardiopulmonary arrest.

Bio-physiological susceptibility of the brain, heart, and lungs to systemic ischemia reperfusion and hyperoxia-induced injury in post-cardiac arrest rats

Cardiac arrest (CA) patients suffer from systemic ischemia–reperfusion (IR) injury leading to multiple organ failure; however, few studies have focused on tissue-specific pathophysiological responses to IR-induced oxidative stress. Herein, we investigated biological and physiological parameters of the brain and heart, and we particularly focused on the lung dysfunction that has not been well studied to date. We aimed to understand tissue-specific susceptibility to oxidative stress and tested how oxygen concentrations in the post-resuscitation setting would affect outcomes. Rats were resuscitated from 10 min of asphyxia CA. Mechanical ventilation was initiated at the beginning of cardiopulmonary resuscitation. We examined animals with or without CA, and those were further divided into the animals exposed to 100% oxygen (CA_Hypero) or those with 30% oxygen (CA_Normo) for 2 h after resuscitation. Biological and physiological parameters of the brain, heart, and lungs were assessed. The brain and lung functions were decreased after CA and resuscitation indicated by worse modified neurological score as compared to baseline (222 ± 33 vs. 500 ± 0, P < 0.05), and decreased PaO2 (20 min after resuscitation: 113 ± 9 vs. baseline: 128 ± 9 mmHg, P < 0.05) and increased airway pressure (2 h: 10.3 ± 0.3 vs. baseline: 8.1 ± 0.2 mmHg, P < 0.001), whereas the heart function measured by echocardiography did not show significant differences compared before and after CA (ejection fraction, 24 h: 77.9 ± 3.3% vs. baseline: 82.2 ± 1.9%, P = 0.2886; fractional shortening, 24 h: 42.9 ± 3.1% vs. baseline: 45.7 ± 1.9%, P = 0.4658). Likewise, increases of superoxide production in the brain and lungs were remarkable, while those in the heart were moderate. mRNA gene expression analysis revealed that CA_Hypero group had increases in Il1b as compared to CA_Normo group significantly in the brain (P < 0.01) and lungs (P < 0.001) but not the heart (P = 0.4848). Similarly, hyperoxia-induced increases in other inflammatory and apoptotic mRNA gene expression were observed in the brain, whereas no differences were found in the heart. Upon systemic IR injury initiated by asphyxia CA, hyperoxia-induced injury exacerbated inflammation/apoptosis signals in the brain and lungs but might not affect the heart. Hyperoxia following asphyxia CA is more damaging to the brain and lungs but not the heart.

SHock-INduced Endotheliopathy (SHINE): A mechanistic justification for viscoelastography-guided resuscitation of traumatic and non-traumatic shock.

Irrespective of the reason for hypoperfusion, hypocoagulable and/or hyperfibrinolytic hemostatic aberrancies afflict up to one-quarter of critically ill patients in shock. Intensivists and traumatologists have embraced the concept of SHock-INduced Endotheliopathy (SHINE) as a foundational derangement in progressive shock wherein sympatho-adrenal activation may cause systemic endothelial injury. The pro-thrombotic endothelium lends to micro-thrombosis, enacting a cycle of worsening perfusion and increasing catecholamines, endothelial injury, de-endothelialization, and multiple organ failure. The hypocoagulable/hyperfibrinolytic hemostatic phenotype is thought to be driven by endothelial release of anti-thrombogenic mediators to the bloodstream and perivascular sympathetic nerve release of tissue plasminogen activator directly into the microvasculature. In the shock state, this hemostatic phenotype may be a counterbalancing, yet maladaptive, attempt to restore blood flow against a systemically pro-thrombotic endothelium and increased blood viscosity. We therefore review endothelial physiology with emphasis on glycocalyx function, unique biomarkers, and coagulofibrinolytic mediators, setting the stage for understanding the pathophysiology and hemostatic phenotypes of SHINE in various etiologies of shock. We propose that the hyperfibrinolytic phenotype is exemplified in progressive shock whether related to trauma-induced coagulopathy, sepsis-induced coagulopathy, or post-cardiac arrest syndrome-associated coagulopathy. Regardless of the initial insult, SHINE appears to be a catecholamine-driven entity which early in the disease course may manifest as hyper- or hypocoagulopathic and hyper- or hypofibrinolytic hemostatic imbalance. Moreover, these hemostatic derangements may rapidly evolve along the thrombohemorrhagic spectrum depending on the etiology, timing, and methods of resuscitation. Given the intricate hemochemical makeup and changes during these shock states, macroscopic whole blood tests of coagulative kinetics and clot strength serve as clinically useful and simple means for hemostasis phenotyping. We suggest that viscoelastic hemostatic assays such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are currently the most applicable clinical tools for assaying global hemostatic function-including fibrinolysis-to enable dynamic resuscitation with blood products and hemostatic adjuncts for those patients with thrombotic and/or hemorrhagic complications in shock states.

Myoclonus in comatose patients with electrographic status epilepticus after cardiac arrest: Corresponding EEG patterns, effects of treatment and outcomes

ObjectiveTo clarify the significance of any form of myoclonus in comatose patients after cardiac arrest with rhythmic and periodic EEG patterns (RPPs) by analyzing associations between myoclonus and EEG pattern, response to anti-seizure medication and neurological outcome. DesignPost hoc analysis of the prospective randomized Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resuscitation (TELSTAR) trial. SettingEleven ICUs in the Netherlands and Belgium. PatientsOne hundred and fifty-seven adult comatose post-cardiac arrest patients with RPPs on continuous EEG monitoring. InterventionsAnti-seizure medication vs no anti-seizure medication in addition to standard care. Measurements and Main ResultsOf 157 patients, 98 (63%) had myoclonus at inclusion. Myoclonus was not associated with one specific RPP type. However, myoclonus was associated with a smaller probability of a continuous EEG background pattern (48% in patients with vs 75% without myoclonus, odds ratio (OR) 0.31; 95% confidence interval (CI) 0.16–0.64) and earlier onset of RPPs (24% vs 9% within 24 hours after cardiac arrest, OR 3.86;95% CI 1.64–9.11). Myoclonus was associated with poor outcome at three months, but not invariably so (poor neurological outcome in 96% vs 82%, p = 0.004). Anti-seizure medication did not improve outcome, regardless of myoclonus presence (6% good outcome in the intervention group vs 2% in the control group, OR 0.33; 95% CI 0.03–3.32). ConclusionsMyoclonus in comatose patients after cardiac arrest with RPPs is associated with poor outcome and discontinuous or suppressed EEG. However, presence of myoclonus does not interact with the effects of anti-seizure medication and cannot predict a poor outcome without false positives.

Predicting neurological outcome after cardiac arrest by combining computational parameters extracted from standard and deviant responses from auditory evoked potentials.

Despite multimodal assessment (clinical examination, biology, brain MRI, electroencephalography, somatosensory evoked potentials, mismatch negativity at auditory evoked potentials), coma prognostic evaluation remains challenging. We present here a method to predict the return to consciousness and good neurological outcome based on classification of auditory evoked potentials obtained during an oddball paradigm. Data from event-related potentials (ERPs) were recorded noninvasively using four surface electroencephalography (EEG) electrodes in a cohort of 29 post-cardiac arrest comatose patients (between day 3 and day 6 following admission). We extracted retrospectively several EEG features (standard deviation and similarity for standard auditory stimulations and number of extrema and oscillations for deviant auditory stimulations) from the time responses in a window of few hundreds of milliseconds. The responses to the standard and the deviant auditory stimulations were thus considered independently. By combining these features, based on machine learning, we built a two-dimensional map to evaluate possible group clustering. Analysis in two-dimensions of the present data revealed two separated clusters of patients with good versus bad neurological outcome. When favoring the highest specificity of our mathematical algorithms (0.91), we found a sensitivity of 0.83 and an accuracy of 0.90, maintained when calculation was performed using data from only one central electrode. Using Gaussian, K-neighborhood and SVM classifiers, we could predict the neurological outcome of post-anoxic comatose patients, the validity of the method being tested by a cross-validation procedure. Moreover, the same results were obtained with one single electrode (Cz). statistics of standard and deviant responses considered separately provide complementary and confirmatory predictions of the outcome of anoxic comatose patients, better assessed when combining these features on a two-dimensional statistical map. The benefit of this method compared to classical EEG and ERP predictors should be tested in a large prospective cohort. If validated, this method could provide an alternative tool to intensivists, to better evaluate neurological outcome and improve patient management, without neurophysiologist assistance.

Diaphragmatic rupture and massive pneumoperitoneum after cardiopulmonary resuscitation

Introduction:Although cardiopulmonary resuscitation is an emergency life‐saving procedure, the intervention itself can cause major and often fatal injuries, with diaphragmatic rupture being very rare. This report describes a patient who experienced bilateral pneumothoraces, left diaphragmatic rupture, and pneumoperitoneum after extended cardiopulmonary resuscitation.Case presentation:A 90‐year‐old woman experienced a cardiac arrest. Spontaneous circulation was restored after 49 min of cardiopulmonary resuscitation performed by a bystander, emergency medical service providers, and emergency department staff. Imaging showed bilateral pneumothoraces, left diaphragmatic rupture, and massive pneumoperitoneum. The patient's guardian refused to permit surgery for the diaphragmatic rupture, and the patient died despite chest and abdominal decompression and post‐cardiac arrest care.Discussion and conclusion:Procedures to restore spontaneous circulation in patients experiencing cardiac arrest may result in fatal cardiopulmonary resuscitation–related injuries. Clinicians providing post‐cardiac arrest care should plan management for these iatrogenic injuries.

Opportunities and barriers to translating the hibernation phenotype for neurocritical care.

Targeted temperature management (TTM) is standard of care for neonatal hypoxic ischemic encephalopathy (HIE). Prevention of fever, not excluding cooling core body temperature to 33°C, is standard of care for brain injury post cardiac arrest. Although TTM is beneficial, HIE and cardiac arrest still carry significant risk of death and severe disability. Mammalian hibernation is a gold standard of neuroprotective metabolic suppression, that if better understood might make TTM more accessible, improve efficacy of TTM and identify adjunctive therapies to protect and regenerate neurons after hypoxic ischemia brain injury. Hibernating species tolerate cerebral ischemia/reperfusion better than humans and better than other models of cerebral ischemia tolerance. Such tolerance limits risk of transitions into and out of hibernation torpor and suggests that a barrier to translate hibernation torpor may be human vulnerability to these transitions. At the same time, understanding how hibernating mammals protect their brains is an opportunity to identify adjunctive therapies for TTM. Here we summarize what is known about the hemodynamics of hibernation and how the hibernating brain resists injury to identify opportunities to translate these mechanisms for neurocritical care.