Informing patients and providers of the likelihood of survival after in-hospital cardiac arrest (IHCA), neurologically intact or with minimal deficits, may be useful when discussing do-not-attempt-resuscitation orders.To develop a simple prearrest point score that can identify patients unlikely to survive IHCA, neurologically intact or with minimal deficits.The study included 51,240 inpatients experiencing an index episode of IHCA between January 1, 2007, and December 31, 2009, in 366 hospitals participating in the Get With the Guidelines-Resuscitation registry. Dividing data into training (44.4%), test (22.2%), and validation (33.4%) data sets, we used multivariate methods to select the best independent predictors of good neurologic outcome, created a series of candidate decision models, and used the test data set to select the model that best classified patients as having a very low (<1%), low (1%-3%), average (>3%-15%), or higher than average (>15%) likelihood of survival after in-hospital cardiopulmonary resuscitation for IHCA with good neurologic status. The final model was evaluated using the validation data set.Survival to discharge after in-hospital cardiopulmonary resuscitation for IHCA with good neurologic status (neurologically intact or with minimal deficits) based on a Cerebral Performance Category score of 1.The best performing model was a simple point score based on 13 prearrest variables. The C statistic was 0.78 when applied to the validation set. It identified the likelihood of a good outcome as very low in 9.4% of patients (good outcome in 0.9%), low in 18.9% (good outcome in 1.7%), average in 54.0% (good outcome in 9.4%), and above average in 17.7% (good outcome in 27.5%). Overall, the score can identify more than one-quarter of patients as having a low or very low likelihood of survival to discharge, neurologically intact or with minimal deficits after IHCA (good outcome in 1.4%).The Good Outcome Following Attempted Resuscitation (GO-FAR) scoring system identifies patients who are unlikely to benefit from a resuscitation attempt should they experience IHCA. This information can be used as part of a shared decision regarding do-not-attempt-resuscitation orders.

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

Prognostication of outcome after cardiac arrest (CA) is challenging. We assessed the prognostic value of daily blood levels of C-reactive protein (CRP), a cheap and widely available inflammatory biomarker, after CA.We reviewed the data of all patients admitted to our intensive care unit (ICU) after CA between January 2009 and December 2011 and who survived for at least 24h. We collected demographic data, CA characteristics (initial rhythm; location of arrest; time to return of spontaneous circulation [ROSC]), occurrence of infection, ICU survival and neurological outcome at three months (good=cerebral performance category [CPC] 1-2; poor=CPC 3-5). CRP levels were measured daily from admission to day 3.A total of 130 patients were admitted after successful resuscitation from CA and survived more than 24h; 76 patients (58%) developed an infection and overall mortality was 56%. CRP levels increased from admission to day 3. CRP levels were higher in in-hospital than in out-of-hospital CA, especially on admission and day 1 (44.1 vs. 2.1 mgL(-1) and 74.5 vs. 29.5 mgL(-1), respectively; p<0.001), and in patients with non-shockable than in those with shockable rhythms. In a logistic regression model, high CRP levels on admission were independently associated with poor neurological outcome at 3 months.CRP levels increase in the days following successful resuscitation of CA. Higher CRP levels in patients with in-hospital CA, non-shockable rhythms and infection, suggest a greater inflammatory response in these patients. High CRP levels on admission may identify patients at high-risk of poor outcome and could be a target for future therapies.Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The aim of the research was to assess whether concentrations of inflammatory markers in blood of patients after cardiac arrest (CA) are related to their clinical state and survival.Forty-six patients, aged 63 ±12 years, 21 of them after out-of-hospital CA and 25 after in-hospital CA, were enrolled in the study. Twenty-five patients survived and were discharged from hospital (CA-S); 21 died during hospitalization (CA-D). The clinical state of the patients was evaluated by the Glasgow Coma Scale (GCS) and the Acute Physiology and Chronic Health Evaluation II (APACHE II). On the day immediately after CA (day 1) and on the following day (day 2) the plasma concentration of high specific C-reactive protein (hs-CRP), tumour necrosis factor (TNF)-α, interleukin-10 and interleukin-6 (Ile-6) were measured.In CA-D patients, compared with CA-S, a significantly higher concentration of hs-CRP (on day 1, 19 ±5 vs. 15 ±4; on day 2, 21 ±3 vs. 16 ±5 mg/l, p < 0.001) and Ile-6 (on day 1, 24.9 ±19.8 vs. 9.2 ±11.3; on day 2, 24.2 ±19.7 vs. 6.9 ±6.8 IU/ml, p < 0.001) was found. The level of TNF-α was greater in CA-D on day 1 (0.42 ±0.75 vs. 0.18 ±0.21 IU/ml, p < 0.04). Concentrations of hs-CRP and Ile-6 were correlated with the scores of GCS and APACHE II. Using logistic regression analysis and ROC curves the prognostic value of hs-CRP and Ile-6 for survival was proven.Post-cardiac arrest immuno-inflammatory response, reflected mainly in elevated plasma concentration of hs-CRP and Ile-6, is not only correlated with patients' clinical state but also with prediction of survival.

Respiratory failure in patients with Guillain-Barré syndrome (GBS) can lead to serious complications and dysfunctions, emphasizing the importance of early detection. The C-reactive protein-to-albumin ratio (CAR) is emerging as a novel inflammatory marker for predicting neurological outcome. We aimed to identify the association of CAR with respiratory failure and short-term outcome in GBS patients.A total of 200 patients diagnosed with GBS were retrospectively analyzed. Data were collected from an electronic database. The associations of C-reactive protein (CRP), albumin, and CAR at admission with outcomes were evaluated by logistic regression analysis. Using receiver operating characteristic curves, we calculated the cutoff value for the CAR and compared its discriminatory power with that of C-reactive protein alone.Fifty-two (26%) patients showed poor short-term outcome, and 50 (25%) developed respiratory failure. CAR > 0.21 was an independent predictor of respiratory failure, and CAR > 0.19 was an independent predictor of poor short-term outcome. CAR showed a better predictive value than CRP alone. In addition, the c-index of the predictive nomogram for respiratory failure was higher when it included CAR (0.962) than when it did not (0.958). A similar result was observed for the predictive nomogram for poor short-term outcome (0.953 vs 0.947).CAR > 0.21, a novel inflammatory biomarker, is independently associated with the occurrence of respiratory failure in GBS patients, while CAR > 0.19 is independently associated with poor short-term outcome. CAR may help identify GBS patients at high risk of poor prognosis.© 2020. Fondazione Società Italiana di Neurologia.

It is now known that inflammation is involved in the pathophysiology of acute ischaemic stroke (AIS). It has been proven that CRP and albumin alone are useful in predicting a prognosis for stroke patients. A combination of these two parameters, namely the ratio of CRP to albumin (CAR), is believed to be a more accurate indicator of inflammatory status than CRP or albumin alone, and may be more valuable than either of them separately in predicting the prognosis of ıschaemic stroke patients. However, the role of CAR as a predictor of mortality in patients with AIS remains unclear.We retrospectively enrolled 260 patients who were referred to our clinic within the first 24 hours of symptom presentation and who were diagnosed with AIS between January 2015 and December 2018. The patient group was classified into two groups according to 90-day mortality. These groups were compared in terms of C-reactive protein, albumin, and CAR.The C-reactive protein and CAR values were higher, and the albumin level was lower, in non-surviving patients. The CAR value was also found to be a significant independent variable of 90-day mortality in patients with AIS (p < 0.001). The optimum cut-off value of CAR in predicting the 90-day mortality for patients with AIS was 0.50, with 64.1% sensitivity and 56.2% specificity.Our study demonstrated that a high CAR value is an independent predictor of 90-day mortality in patients with AIS.

Most survivors of cardiac arrest are comatose after resuscitation, and meaningful neurological recovery occurs in a small proportion of cases. Treatment can be lengthy, expensive, and often difficult for families and caregivers. Physical examination is potentially useful in this clinical scenario, and the information obtained may help physicians and families make accurate decisions about treatment and/or withdrawal of care.To determine the precision and accuracy of the clinical examination in predicting poor outcome in post-cardiac arrest coma.We searched MEDLINE for English-language articles (1966-2003) using the terms coma, cardiac arrest, prognosis, physical examination, sensitivity and specificity, and observer variation. Other sources came from bibliographies of retrieved articles and physical examination textbooks. Studies were included if they assessed the precision and accuracy of the clinical examination in prognosis of post-cardiac arrest coma in adults. Eleven studies, involving 1914 patients, met our inclusion criteria.Two authors independently reviewed each study to determine eligibility, abstract data, and classify methodological quality using predetermined criteria. Disagreement was resolved by consensus.Summary likelihood ratios (LRs) were calculated from random effects models. Five clinical signs were found to strongly predict death or poor neurological outcome: absent corneal reflexes at 24 hours (LR, 12.9; 95% confidence interval [CI], 2.0-68.7), absent pupillary response at 24 hours (LR, 10.2; 95% CI, 1.8-48.6), absent withdrawal response to pain at 24 hours (LR, 4.7; 95% CI, 2.2-9.8), no motor response at 24 hours (LR, 4.9; 95% CI, 1.6-13.0), and no motor response at 72 hours (LR, 9.2; 95% CI, 2.1-49.4). The proportion of individuals' dying or having a poor neurological outcome was calculated by pooling the outcome data from the 11 studies (n = 1914) and used as an estimate of the pretest probability of poor outcome. The random effects estimate of poor outcome was 77% (95% CI, 72%-80%). The highest LR increases the pretest probability of 77% to a posttest probability of 97% (95% CI, 87%-100%). No clinical findings were found to have LRs that strongly predicted good neurological outcome.Simple physical examination maneuvers strongly predict death or poor outcome in comatose survivors of cardiac arrest. The most useful signs occur at 24 hours after cardiac arrest, and earlier prognosis should not be made by clinical examination alone. These data provide prognostic information, rather than treatment recommendations, which must be made on an individual basis incorporating many other variables.

Ischemia-reperfusion injury forms the basis of tissue damage and cellular apoptosis in many pathologic and traumatic processes. The tissue damage follows a natural progression of cellular and metabolic events initiated by an ischemic episode. Ischemia causes intracellular/extracellular changes principally resulting in increased intracellular calcium, pH changes, and adenosine triphosphate depletion that end in cell death if the process is not interrupted. This interruption takes the form of reperfusion, characterized by a "flushing" of tissues with toxic metabolites, principally reactive oxygen species. The immediate effect is mitochondrial pore permeability, complement activation, cytochrome release, cytokine activation, inflammation, edema, neutrophil platelet adhesion, capillary plugging, and thrombosis. This sets the stage for the long recognized "no-reflow" phenomenon and progressive tissue death. Current recognition of cellular "cross-talk" and molecular events have introduced new logical strategies to sequentially combat the events occurring in relation to ischemia-reperfusion injury. These include mechanical preconditioning and pharmacological preconditioning and postconditioning strategies. It is likely that success in reversing or limiting tissue damage will be found in a sequential multitargeted approach using a combination of these strategies-clinical trials in this regard are sorely needed.

Cardiac arrest induces the cessation of cerebral blood flow, which can result in brain damage. The primary intervention to salvage the brain under such a pathological condition is to restore the cerebral blood flow to the ischemic region. Ischemia is defined as a reduction in blood flow to a level that is sufficient to alter normal cellular function. Brain tissue is highly sensitive to ischemia, such that even brief ischemic periods in neurons can initiate a complex sequence of events that may ultimately culminate in cell death. However, paradoxically, restoration of blood flow can cause additional damage and exacerbate the neurocognitive deficits in patients who suffered a brain ischemic event, which is a phenomenon referred to as "reperfusion injury." Transient brain ischemia following cardiac arrest results from the complex interplay of multiple pathways including excitotoxicity, acidotoxicity, ionic imbalance, peri-infarct depolarization, oxidative and nitrative stress, inflammation, and apoptosis. The pathophysiology of post-cardiac arrest brain injury involves a complex cascade of molecular events, most of which remain unknown. Many lines of evidence have shown that mitochondria suffer severe damage in response to ischemic injury. Mitochondrial dysfunction based on the mitochondrial permeability transition after reperfusion, particularly involving the calcineurin/immunophilin signal transduction pathway, appears to play a pivotal role in the induction of neuronal cell death. The aim of this article is to discuss the underlying pathophysiology of brain damage, which is a devastating pathological condition, and highlight the central signal transduction pathway involved in brain damage, which reveals potential targets for therapeutic intervention.

To investigate serial serum concentrations of procalcitonin (PCT) and C-reactive protein (CRP) in patients treated with mild hypothermia after cardiac arrest, and to study their association to severe infections, post cardiac arrest syndrome (PCAS) and long-term outcome.Serum samples from cardiac arrest patients treated with mild hypothermia were collected serially at admission, 2, 6, 12, 24, 36, 48 and 72 h after cardiac arrest. PCT and CRP concentrations were determined and tested for association with three definitions of infection, two surrogate markers of PCAS (circulation-SOFA and time to return of spontaneous circulation (ROSC)) and cerebral performance category (CPC) at six months.Eighty-four patients were included. PCT displayed an earlier release pattern than CRP with a significant increase within 2h, increasing further at 6h and onwards in patients with poor outcome. CRP increased later and continued to rise during the study period. PCT was strongly associated with circulation-SOFA and time to ROSC, and predicted a poor neurologic outcome with high accuracy (area under the receiver operating characteristic curve of 0.88, 0.86 and 0.87 at 12, 24 and 48 h respectively). No association of PCT or CRP to infection was observed.Our results suggest that PCT is released early after resuscitation following cardiac arrest, is associated with markers of PCAS but not with infection, and is an accurate predictor of poor outcome. Validation of these findings in larger studies is warranted.Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Out-of-hospital cardiac arrest (OHCA) is a public health concern, and many studies have been conducted on return of spontaneous circulation (ROSC) and its prognostic factors. Rotational thromboelastometry (ROTEM), a point-of-care testing (POCT) method, has been useful for predicting ROSC in patients with OHCA, but very few studies have focused on patients with non-shockable rhythm. We examined whether the parameters of POCT could predict ROSC in patients with OHCA and accompanying non-shockable rhythm.This is a single-center, retrospective observational study. Complete blood count, blood gas, and ROTEM POCT measurements were used. This study included patients with non-traumatic OHCA aged 18 years or older who were transported to the emergency department and evaluated using POCT between January 2013 and December 2021. The patients were divided into the ROSC and non-ROSC groups. Prehospital information and POCT parameters were compared using receiver operating characteristic (ROC) curve analysis, and further logistic regression analysis was performed.Sixty-seven and 135 patients were in the ROSC and non-ROSC groups, respectively. The ROC curves showed a high area under the curve (AUC) for K of 0.77 (95% confidence interval []: 0.71-0.83) and EXTEM amplitude 5 min after clotting time (A5) of 0.70 (95%: 0.62-0.77). The odds ratios for ROSC were as follows: female sex 3.67 (95%: 1.67-8.04); K 0.64 (95%: 0.48-0.84); and EXTEM A5 1.03 (95%: 1.01-1.06).In OHCA patients with non-shockable rhythm, K level and the ROTEM parameter EXTEM A5 may be useful in predicting ROSC.Copyright: © World Journal of Emergency Medicine.

Whether admission C-reactive protein (aCRP) concentrations are associated with neurological outcome after out-of-hospital cardiac arrest (OHCA) is controversial. Based on established kinetics of CRP, we hypothesized that aCRP may reflect the pre-arrest state of health and investigated associations with neurological outcome. Prospectively collected data from the Vienna Clinical Cardiac Arrest Registry of the Department of Emergency Medicine were analysed. Adults (≥ 18 years) who suffered a non-traumatic OHCA between January 2013 and December 2018, without return of spontaneous circulation or extracorporeal cardiopulmonary resuscitation therapy were eligible. The primary endpoint was a composite of unfavourable neurologic function or death (defined as Cerebral Performance Category 3-5) at 30 days. Associations of CRP levels drawn within 30 min of hospital admission were assessed using binary logistic regression. ACRP concentrations were overall low in our population (n = 832), but higher in the unfavourable outcome group [median: 0.44 (quartiles 0.15-1.44) mg/dL vs. 0.26 (0.11-0.62) mg/dL, p < 0.001]. The crude odds ratio for higher aCRP concentrations was 1.19 (95% CI 1.10-1.28, p < 0.001, per mg/dL) to have unfavourable neurological outcome. After multivariate adjustment for traditional prognostication markers the odds ratio of higher aCRP concentrations was 1.13 (95% CI 1.04-1.22, p = 0.002). Sensitivity of aCRP was low, but specificity for unfavourable neurological outcome was 90% for the cut-off at 1.5 mg/dL and 97.5% for 5 mg/dL CRP. In conclusion, high aCRP levels are associated with unfavourable neurological outcome at day 30 after OHCA.

C-reactive protein (CRP) is an acute-phase protein used clinically to diagnose infectious and inflammatory disease and monitor response to treatment. CRP measurement in the peri-operative period was audited and patterns of change analysed for elective general surgical patients.General surgical patients (201) admitted for elective general surgery over a 3-month period were considered for the study. CRP results pre- and postoperatively were recorded, and data on co-morbid conditions and surgical procedure were noted.CRP was requested pre-operatively on 84% of patients. A high CRP was more likely to be found in patients with co-morbidity. Postoperatively, CRP was requested during the first 3 days on 69% of patients. CRP peaked at postoperative days two or three, and then fell. In patients who had a high pre-operative CRP, the peak CRP was higher and occurred later, than those who had a normal pre-operative CRP.CRP requesting pre-operatively is common, but is not recommended in NICE guidelines. Postoperatively, CRP levels rise; as a result, its use as a tool to screen for infection is limited. CRP has a role in diagnosis of infection after the first three postoperative days and in monitoring response to treatment. Therefore, routine use of CRP measurements pre-operatively and in the first 2 or 3 days post-operatively is not recommended. A peri-operative CRP should only be requested if there is a clear clinical indication.

To determine molecular information about the antioxidant properties of human serum albumin, which is an important extracellular antioxidant. To obtain this information, we studied this function of the protein by using H2O2 as the representative reactive oxygen species and two recombinant mutants and ten genetic variants with single-residue mutations.The antioxidant capabilities of the isoforms were registered as their ability to diminish the H2O2-induced conversion of dihydrorhodamine 123 to rhodamine 123, which can emit fluorescence at 536 nm. Structural properties were examined by circular dichroism and SDS-PAGE.Cysteine residues are important for the antioxidant function, but their effect depends on their position in the protein, with Cys410 > Cys34 ~ Cys169 (when not involved in forming a disulfide bond). Likewise, the substitution of a glutamic acid at position 122 or 541, but not at 240 or 560, improves the antioxidant effect, perhaps by making the methionine residues in their vicinity, Met123 and Met548, respectively, more accessible for the oxidant. A lysine at position 505, but not at 82 or 570, decreases the oxidative effect. Finally, the mutations D269G and K276N had no effect. In certain cases, albumin acts as a sacrificial antioxidant, as in the case of the mutants C34S and, in particular, R410C and E505K.The information gained is of protein chemical relevance, but it may also be helpful in understanding the function of proteins that act as antioxidants in biological systems subjected to oxidative stress in conditions such as inflammation and aging.Copyright © 2015 Elsevier Inc. All rights reserved.

We aimed to evaluate the lactate/albumin ratio (LAR) to identify its significance as a prognostic marker for favorable neurologic outcome and survival in patients with return of spontaneous circulation after out-of-hospital cardiac arrest (OHCA). Based on the LAR and multiple parameters, we developed new nomograms and externally validated the tools.We conducted an observational study using a prospective, multicenter registry of out-of-cardiac arrest resuscitation provided by the Korean Cardiac Arrest Research Consortium registry from October 2015 to June 2017.A total of 524 patients were included in this study. An increased LAR was significantly associated with decreased favorable neurologic outcomes (odds ratio [OR] 0.787; 95% confidence interval [CI], 0.630-0.983; P = 0.035) and survival at discharge (OR 0.744; 95% CI, 0.638-0.867; P < 0.001). The areas under the curve (AUCs) for predicting neurologic outcome and survival to discharge using the LAR were 0.824 (P < 0.001) and 0.781 (P < 0.001), respectively. An LAR value of more than the optimal cutoff values of 2.82 and 3.62 could significantly improve prediction of decreased favorable neurologic outcome and survival to discharge, respectively. We constructed nomograms based on the multivariate logistic model. The model for predicting favorable neurologic outcomes and survival discharge had AUCs of 0.927 (P < 0.001) and 0.872 (P < 0.001), respectively.The prognostic performance of the LAR was superior to a single measurement of lactate for predicting favorable neurologic outcomes and survival to discharge after OHCA. The newly developed nomograms can provide rapid prediction of probability of clinical outcomes.

The optimal time to measure serum albumin concentration (SAC) to predict prognosis in cardiac arrest (CA) survivors has not been elucidated. We aimed to compare the relationships between time-related SAC, optic nerve sheath diameter (ONSD), intracranial pressure (ICP), and neurological prognosis in CA survivors.We undertook a retrospective study examining CA patients treated with target temperature management (TTM). ICP was measured using cerebrospinal fluid (CSF) pressure and ONSD was obtained before TTM. SAC was measured repeatedly at 4-6 h intervals from the hospital arrival time. We analysed CSF pressure, ONSD, and minimum SAC (MSAC) separately, or in combination, to predict poor neurological outcome.Of 83 patients enrolled, the good outcome group comprised 25 (34%) patients. MSAC at 24 h (MSAC24) had a higher area under the receiver operating characteristic curve (AUC) (0.687; 95% confidence interval (CI), 0.668-0.926) than other time points. CSF pressure showed a higher AUC (0.973; 95% CI, 0.911-0.996) than MSAC24 and ONSD (0.677; 95% CI, 0.565-0.776). In contrast to using MSAC24 and ONSD separately, the combination of both modalities resulted in a better AUC, thus improving the prediction of the neurological outcome (0.734; 95% CI, 0.626-0.825) and ICP (0.758; 95% CI, 0.651-0.845) after return of spontaneous circulation (ROSC) from CA.A higher ICP was strongly associated with and seemed predictive of poor outcome. Furthermore, the MSAC24/ONSD combination may be a useful predictor of high ICP and poor neurological outcome. Prospective studies should be conducted to confirm these results.Copyright © 2018 Elsevier B.V. All rights reserved.