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Objective Experimental studies of head-up positioning (HUP) during cardiopulmonary resuscitation (CPR) have had some degree of conflicting published results. The current study aim was to analyze and reconcile those discrepancies in order to better clarify the effects of HUP CPR compared to conventional supine (SUP) CPR. Methods Three databases (PubMed, EMBASE and Cochrane Library) were searched comprehensively (from each respective database's inception to May 2021) for articles addressing HUP CPR. The primary outcome to be observed was cerebral perfusion pressure (CerPP), and secondary outcomes were mean intracranial pressure (ICP), mean arterial pressure (MAP), coronary perfusion pressure (CoPP) and frequencies of return of spontaneous circulation (ROSC). Results Seven key studies involving 131 animals were included for analysis. Compared to SUP CPR, CerPP (MD 10.37; 95% CI 7.11–13.64; p I2 = 58%) and CoPP (MD 7.56; 95% CI 1.84–13.27, p = 0.01; I2 = 75%) increased significantly with HUP CPR, while ICP (MD − 13.66; 95% CI − 18.6 to –8.71; p I2 = 96%) decreased significantly. Combining all study methodologies, there were no significant differences detected in MAP (MD − 1.63; 95% CI − 10.77–7.52; p = 0.73; I2 = 93%) or frequency of ROSC (RR 0.9; 95% CI 0.31–2.60; p = 0.84; I2 = 65%). However, in contrast to worse outcomes in studies using immediate elevation of the head in a reverse Trendelenburg position, study outcomes were significantly improved when HUP (head and chest only) was introduced in a steady, graduated manner following a brief period of basic CPR augmented by active compression–decompression (ACD) and impedance threshold (ITD) devices. Conclusion In experimental models, gradually elevating the head and chest following a brief interval of circulatory priming with ACD and ITD devices can enhance CoPP, lower ICP and improve CerPP significantly while maintaining MAP. This effect is immediate, remains sustained and is associated with improved outcomes.

Background Most deaths of comatose survivors of out-of-hospital sudden cardiac arrest result from withdrawal of life-sustaining treatment (WLST) decisions based on poor neurological prognostication and the family’s intention. Thus, accurate prognostication is crucial to avoid premature WLST decisions. However, targeted temperature management (TTM) with sedation or neuromuscular blockade against shivering significantly affects early prognostication. In this study, we investigated whether heart rate variability (HRV) analysis could prognosticate poor neurological outcome in comatose patients undergoing hypothermic TTM. Methods Between January 2015 and December 2017, adult patients with out-of-hospital sudden cardiac arrest, successfully resuscitated in the emergency department and admitted to the intensive care unit of the Niigata University in Japan, were prospectively included. All patients had an initial Glasgow Coma Scale motor score of 1 and received hypothermic TTM (at 34 °C). Twenty HRV-related variables (deceleration capacity; 4 time-, 3 geometric-, and 7 frequency-domain; and 5 complexity variables) were computed based on RR intervals between 0:00 and 8:00 am within 24 h after return of spontaneous circulation (ROSC). Based on Glasgow Outcome Scale (GOS) at 2 weeks after ROSC, patients were divided into good outcome (GOS 1–2) and poor outcome (GOS 3–5) groups. Results Seventy-six patients were recruited and allocated to the good (n = 22) or poor (n = 54) outcome groups. Of the 20 HRV-related variables, ln very-low frequency (ln VLF) power, detrended fluctuation analysis (DFA) (α1), and multiscale entropy (MSE) index significantly differed between the groups (p = 0.001), with a statistically significant odds ratio (OR) by univariate logistic regression analysis (p = 0.001). Multivariate logistic regression analysis of the 3 variables identified ln VLF power and DFA (α1) as significant predictors for poor outcome (OR = 0.436, p = 0.006 and OR = 0.709, p = 0.024, respectively). The area under the receiver operating characteristic curve for ln VLF power and DFA (α1) in predicting poor outcome was 0.84 and 0.82, respectively. In addition, the minimum value of ln VLF power or DFA (α1) for the good outcome group predicted poor outcome with sensitivity = 61% and specificity = 100%. Conclusions The present data indicate that HRV analysis could be useful for prognostication for comatose patients during hypothermic TTM.

Background The effect of renal replacement therapy (RRT) on the outcomes of severe acute kidney injury (AKI) after out-of-hospital cardiac arrest (OHCA) is uncertain. This study aimed to evaluate the association of RRT with 6-month mortality in patients with severe AKI treated with targeted temperature management (TTM) after OHCA. Methods This was a retrospective analysis of a prospectively collected multicentre observational cohort study that included adult OHCA patients treated with TTM across 22 hospitals in South Korea between October 2015 and December 2018. AKI was diagnosed using the Kidney Disease: Improving Global Outcomes criteria. The primary outcome was 6-month mortality and the secondary outcome was cerebral performance category (CPC) at 6 months. Multivariate Cox regression analysis was performed to define the role of RRT in stage 3 AKI. Results Among 10,426 patients with OHCA, 1373 were treated with TTM. After excluding those who died within 48 h of return of spontaneous circulation (ROSC) and those with pre-arrest chronic kidney disease, our study cohort comprised 1063 patients. AKI developed in 590 (55.5%) patients and 223 (21.0%) had stage 3 AKI. Among them, 115 (51.6%) were treated with RRT. The most common treatment modality among RRT patients was continuous renal replacement therapy (111 [96.5%]), followed by intermittent haemodialysis (4 [3.5%]). The distributions of CPC (1–5) at 6 months for the non-RRT vs. the RRT group were 3/108 (2.8%) vs. 12/115 (10.4%) for CPC 1, 0/108 (0.0%) vs. 1/115 (0.9%) for CPC 2, 1/108 (0.9%) vs. 3/115 (2.6%) for CPC 3, 6/108 (5.6%) vs. 6/115 (5.2%) for CPC 4, and 98/108 (90.7%) vs. 93/115 (80.9%) for CPC 5, respectively (P = 0.01). The RRT group had significantly lower 6-month mortality than the non-RRT group (93/115 [81%] vs. 98/108 [91%], P = 0.04). Multivariate Cox regression analyses showed that RRT was independently associated with a lower risk of death in patients with stage 3 AKI (hazard ratio, 0.569 [95% confidence interval, 0.377–0.857, P = 0.01]). Conclusion Dialysis interventions were independently associated with a lower risk of death in patients with stage 3 AKI treated with TTM after OHCA.

Background To quantitatively summarize the available epidemiological evidence on the survival rate of out-of-hospital cardiac arrest (OHCA) patients who received cardiopulmonary resuscitation (CPR). Methods We systematically searched the PubMed, Embase, and Web of Science databases, and the references of retrieved articles were manually reviewed to identify studies reporting the outcome of OHCA patients who received CPR. The overall incidence and outcome of OHCA were assessed using a random-effects meta-analysis. Results A total of 141 eligible studies were included in this meta-analysis. The pooled incidence of return of spontaneous circulation (ROSC) was 29.7% (95% CI 27.6–31.7%), the rate of survival to hospital admission was 22.0% (95% CI 20.7–23.4%), the rate of survival to hospital discharge was 8.8% (95% CI 8.2–9.4%), the pooled 1-month survival rate was 10.7% (95% CI 9.1–13.3%), and the 1-year survival rate was 7.7% (95% CI 5.8–9.5%). Subgroup analysis showed that survival to hospital discharge was more likely among OHCA patients whose cardiac arrest was witnessed by a bystander or emergency medical services (EMS) (10.5%; 95% CI 9.2–11.7%), who received bystander CPR (11.3%, 95% CI 9.3–13.2%), and who were living in Europe and North America (Europe 11.7%; 95% CI 10.5–13.0%; North America: 7.7%; 95% CI 6.9–8.6%). The survival to discharge (8.6% in 1976–1999 vs. 9.9% in 2010–2019), 1-month survival (8.0% in 2000–2009 vs. 13.3% in 2010–2019), and 1-year survival (8.0% in 2000–2009 vs. 13.3% in 2010–2019) rates of OHCA patients who underwent CPR significantly increased throughout the study period. The Egger’s test did not indicate evidence of publication bias for the outcomes of OHCA patients who underwent CPR. Conclusions The global survival rate of OHCA patients who received CPR has increased in the past 40 years. A higher survival rate post-OHCA is more likely among patients who receive bystander CPR and who live in Western countries.

Background: The prognosis in refractory out-of-hospital cardiac arrest (OHCA) with ongoing cardiopulmonary resuscitation (CPR) at hospital arrival is often considered dismal. The use of extracorporeal cardiopulmonary resuscitation (eCPR) for perfusion enhancement during resuscitation has shown variable results. We aimed to investigate outcome in refractory OHCA patients managed conservatively without use of eCPR. Methods: We included consecutive OHCA patients with refractory arrest or prehospital return of spontaneous circulation (ROSC) in the Copenhagen area in 2002-2011. Results: A total of 3992 OHCA patients with resuscitation attempts were included; in 2599, treatment was terminated prehospital, and 1393 (35%) were brought to the hospital either with ROSC (n = 1285, 92%) or with refractory OHCA (n = 108, 8%). Of patients brought in with refractory OHCA, 56 (52%) achieved ROSC in the emergency department. There were no differences between patients with refractory OHCA or prehospital ROSC with regard to age, sex, comorbidities, or etiology of OHCA. Time to emergency medical services (EMS) arrival was similar, whereas time to ROSC (when ROSC was achieved) was longer in refractory OHCA patients (EMS, 6 (5-9] vs. 7 [5-10] min, p = 0.8; ROSC, 15 [9-22] vs. 27 [20-41] min, p < 0.001). Independent factors associated with transport with refractory OHCA instead of prehospital termination of therapy were OHCA in public (OR, 3.6 [95% CI, 2.2-5.8]; p < 0.001), witnessed OHCA (OR, 3.7 [2.0-7.1]; p < 0.001), shockable rhythm (OR, 3.0 [1.9-4.7]; p < 0.001), younger age (OR, 1.2 [1.1-1.2]; p < 0.001), and later calendar year (OR, 1.4 [1.2-1.6]; p < 0.001). Thirty-day survival was 20% in patients with refractory OHCA compared with 42% in patients with prehospital ROSC (p < 0.001). Four of 28 refractory OHCA patients with duration of resuscitation > 60 min achieved ROSC. No difference in favorable neurological outcome in patients surviving to discharge was found (prehospital ROSC 84% vs. refractory OHCA 86%; p = 0.7). Conclusions: Survival after refractory OHCA with ongoing CPR at hospital arrival was significantly lower than among patients with prehospital ROSC. Despite a lower survival, the majority of survivors with both refractory OHCA and prehospital ROSC were discharged with a similar degree of favorable neurological outcome, indicating that continued efforts in spite of refractory OHCA are not in vain and may still lead to favorable outcome even without eCPR.

Background When an out-of-hospital cardiac arrest (OHCA) patient receives cardiopulmonary resuscitation (CPR) in the emergency department (ED), blood laboratory test results can be obtained by using point-of-care testing during CPR. In the present study, the relationship between blood laboratory test results during CPR and outcomes of OHCA patients was investigated. Methods This study was a multicenter retrospective analysis of prospective registered data that included 2716 OHCA patients. Data from the EDs of three university hospitals in different areas were collected from January 2009 to December 2014. Univariate and multivariable analyses were conducted to elucidate the factors associated with survival to discharge and neurological outcomes. A final analysis was conducted by including patients who had no prehospital return of spontaneous circulation and those who underwent rapid blood laboratory examination during CPR. Results Overall, 2229 OHCA patients were included in the final analysis. Among them, the rate of survival to discharge and a good Cerebral Performance Categories Scale score were 14% and 4.4%, respectively. The pH level was independently related to survival to hospital discharge (adjusted OR 6.287, 95% CI 2.601–15.197; p 8.5 mEq/L) during CPR. Conclusions Among the blood laboratory test results during CPR of OHCA patients, pH and potassium levels were observed as independent factors associated with survival to hospital discharge, and pH level was considered as an independent factor related to neurological recovery.

Background Venoarterial extracorporeal membrane oxygenation (VA-ECMO) support under extracorporeal cardiopulmonary resuscitation (eCPR) is the last option and may be offered to selected patients. Several factors predict outcome in these patients, including initial heart rhythm, comorbidities, and bystander cardiopulmonary resuscitation (CPR). We evaluated outcomes of all VA-ECMO patients treated within the last 5 years at our center in respect to low-flow duration during CPR. Methods We report retrospective registry data on all patients with eCPR treated at a university hospital between October 2010 and May 2016. Results A total of 133 patients (mean age 58.7 ± 2.6 years, Simplified Acute Physiology Score II score at admission 48.1 ± 3.4) were included in the analysis. The indication for eCPR was either in-hospital or out-of-hospital cardiac arrest without return of spontaneous circulation (n = 74 and 59, respectively). There was a significant difference in survival rates between groups (eCPR in-hospital cardiac arrest [IHCA] 18.9%, eCPR out-of-hospital cardiac arrest [OHCA] 8.5%; p

Background The benefits of early epinephrine administration in pediatric with nontraumatic out-of-hospital cardiac arrest (OHCA) have been reported; however, the effects in pediatric cases of traumatic OHCA are unclear. Since the volume-related pharmacokinetics of early epinephrine may differ obviously with and without hemorrhagic shock (HS), beneficial or harmful effects of nonselective epinephrine stimulation (alpha and beta agonists) may also be enhanced with early administration. In this study, we aimed to analyze the therapeutic effect of early epinephrine administration in pediatric cases of HS and non-HS traumatic OHCA. Methods This was a multicenter retrospective study (2003–2014). Children (aged ≤ 19 years) who experienced traumatic OHCA and were administered epinephrine for resuscitation were included. Children were classified into the HS (blood loss > 30% of total body fluid) and non-HS groups. The demographics, outcomes, postresuscitation hemodynamics (the first hour) after the sustained return of spontaneous circulation (ROSC), and survival durations were analyzed and correlated with the time to epinephrine administration (early 30 min) in the HS and non-HS groups. Cox regression analysis was used to adjust for risk factors of mortality. Results A total of 509 children were included. Most of them (n = 348, 68.4%) had HS OHCA. Early epinephrine administration was implemented in 131 (25.7%) children. In both the HS and non-HS groups, early epinephrine administration was associated with achieving sustained ROSC (both p p Conclusion Early epinephrine was significantly associated with achieving sustained ROSC in pediatric cases of HS and non-HS traumatic OHCA. For children with HS, early epinephrine administration was associated with both beneficial (increased cardiac output) and harmful effects (decreased urine output and metabolic acidosis) during the postresuscitation period. More importantly, early epinephrine was a risk factor associated with mortality in the HS group.

Objective Exposure to hyperoxemia and hypoxemia is common in out-of-hospital cardiac arrest (OHCA) patients following return of spontaneous circulation (ROSC), but its effects on neurological outcome are uncertain, and study results are inconsistent. Methods Exploratory post hoc substudy of the Target Temperature Management (TTM) trial, including 939 patients after OHCA with return of spontaneous circulation (ROSC). The association between serial arterial partial pressures of oxygen (PaO2) during 37 h following ROSC and neurological outcome at 6 months, evaluated by Cerebral Performance Category (CPC), dichotomized to good (CPC 1–2) and poor (CPC 3–5), was investigated. In our analyses, we tested the association of hyperoxemia and hypoxemia, time-weighted mean PaO2, maximum PaO2 difference, and gradually increasing PaO2 levels (13.3–53.3 kPa) with poor neurological outcome. A subsequent analysis investigated the association between PaO2 and a biomarker of brain injury, peak serum Tau levels. Results Eight hundred sixty-nine patients were eligible for analysis. Three hundred patients (35%) were exposed to hyperoxemia or hypoxemia at some time point after ROSC. Our analyses did not reveal a significant association between hyperoxemia, hypoxemia, time-weighted mean PaO2 exposure or maximum PaO2 difference and poor neurological outcome at 6-month follow-up after correction for co-variates (all analyses p = 0.146–0.847). We were not able to define a PaO2 level significantly associated with the onset of poor neurological outcome. Peak serum Tau levels at either 48 or 72 h after ROSC were not associated with PaO2. Conclusion Hyperoxemia or hypoxemia exposure occurred in one third of the patients during the first 37 h of hospitalization and was not significantly associated with poor neurological outcome after 6 months or with the peak s-Tau levels at either 48 or 72 h after ROSC. Electronic supplementary material The online version of this article (10.1186/s13054-019-2322-z) contains supplementary material, which is available to authorized users.

After cardiac arrest a combination of basic and advanced airway and ventilation techniques are used during cardiopulmonary resuscitation (CPR) and after a return of spontaneous circulation (ROSC). The optimal combination of airway techniques, oxygenation and ventilation is uncertain. Current guidelines are based predominantly on evidence from observational studies and expert consensus; recent and ongoing randomised controlled trials should provide further information. This narrative review describes the current evidence, including the relative roles of basic and advanced (supraglottic airways and tracheal intubation) airways, oxygenation and ventilation targets during CPR and after ROSC in adults. Current evidence supports a stepwise approach to airway management based on patient factors, rescuer skills and the stage of resuscitation. During CPR, rescuers should provide the maximum feasible inspired oxygen and use waveform capnography once an advanced airway is in place. After ROSC, rescuers should titrate inspired oxygen and ventilation to achieve normal oxygen and carbon dioxide targets.

Background Circulatory shock is a common syndrome with a high mortality and limited therapeutic options. Despite its discovery and use in clinical and experimental settings more than a half-century ago, angiotensin II (Ang II) has only been recently evaluated as a vasopressor in distributive shock. We examined existing literature for associations between Ang II and the resolution of circulatory shock. Methods We searched PubMed, MEDLINE, Ovid, and Embase to identify all English literature accounts of intravenous Ang II in humans for the treatment of shock (systolic blood pressure [SBP] ≤ 90 mmHg or a mean arterial pressure [MAP] ≤ 65 mmHg), and hand-searched the references of extracted papers for further studies meeting inclusion criteria. Of 3743 articles identified, 24 studies including 353 patients met inclusion criteria. Complete data existed for 276 patients. Extracted data included study type, publication year, demographics, type of shock, dosing of Ang II or other vasoactive medications, and changes in BP, lactate, and urine output. BP effects were grouped according to type of shock, with additional analyses completed for patients with absent blood pressure. Shock was distributive (n = 225), cardiogenic (n = 38), or from other causes (n = 90). Blood pressure as absent in 18 patients. Results For the 276 patients with complete data, MAP rose by 23.4% from 63.3 mmHg to 78.1 mmHg in response to Ang II (dose range: 15 ng/kg/min to 60 mcg/min). SBP rose by 125.2% from 56.9 mmHg to 128.2 mmHg (dose range: 0.2 mcg/min to a 1500 mcg bolus). A total of 271 patients with complete data were determined to exhibit a BP effect which was directly associated with Ang II. Subgroups (patients with cardiogenic, septic, and other types of shock) exhibited similar increases in BP. In patients with absent BP, deemed to be cardiac arrest, return of spontaneous circulation (ROSC) was achieved, and BP increased by an average of 107.3 mmHg in 11 of 18 patients. The remaining seven patients with cardiac arrest did not respond. Conclusions Intravenous Ang II is associated with increased BP in patients with cardiogenic, distributive, and unclassified shock. A role may exist for Ang II in restoring circulation in cardiac arrest. Electronic supplementary material The online version of this article (doi:10.1186/s13054-017-1896-6) contains supplementary material, which is available to authorized users.

Continuous electroencephalography (cEEG), interpreted by an experienced neurologist, has been reported to be useful in predicting neurological outcome in adult patients post cardiac arrest. Amplitude-integrated electroencephalography (aEEG) is a type of quantitative EEG and is easily interpreted by a non-neurologist. A few studies have shown the effectiveness of aEEG in prognostication among adult patients post cardiac arrest. In this study, we hypothesized that the pattern of aEEG after return of spontaneous circulation (ROSC) could successfully categorize patients post cardiac arrest according to their expected neurological outcome.We assessed the comatose survivors of out-of-hospital cardiac arrest who received targeted temperature management with midazolam-based sedation and were monitored with aEEG at our tertiary emergency care center from January 2013 to June 2017. We categorized the patients into categories 1 (C1) to 4 (C4). C1 included patients who regained continuous normal voltage (CNV) within 12 h post ROSC, C2 included those who recovered CNV 12-36 h post ROSC, C3 included those who did not recover CNV before 36 h post ROSC, and C4 included those who had burst suppression at any time post ROSC. We evaluated the outcomes of neurological function for each category at hospital discharge. A good outcome was defined as a cerebral performance category of 1 or 2.A total of 61 patients were assessed (median age, 60 years), among whom 42 (70%) had an initial shockable rhythm, and 52 (85%) had cardiac etiology. Of all 61 patients, 40 (66%) survived to hospital discharge and 27 (44%) had a good neurological outcome. Of 20 patients in C1, 19 (95%) had a good outcome, while the percentage dropped to 57% among C2 patients. No patients in C3 or C4 had a good outcome. Three patients could not be classified into any category.The pattern of aEEG during the early post-cardiac-arrest period can successfully categorize patients according to their neurological prognoses and could be used as a potential guide to customize post-cardiac-arrest care for each patient.

Background Evidence suggests that EMS-physician-guided cardiopulmonary resuscitation (CPR) in out-of-hospital cardiac arrest (OOHCA) may be associated with improved outcomes, yet randomized controlled trials are not available. The goal of this meta-analysis was to determine the association between EMS-physician- versus paramedic-guided CPR and survival after OOHCA. Methods and Results Studies that compared EMS-physician- versus paramedic-guided CPR in OOHCA published until June 2014 were systematically searched in MEDLINE, EMBASE and Cochrane databases. All studies were required to contain survival data. Data on study characteristics, methods, and as well as survival outcomes were extracted. A random-effects model was used for the meta-analysis due to a high degree of heterogeneity among the studies (I 2 = 44 %). Return of spontaneous circulation [ROSC], survival to hospital admission, and survival to hospital discharge were the outcome measures. Out of 3,385 potentially eligible studies, 14 met the inclusion criteria. In the pooled analysis (n = 126,829), EMS-physician-guided CPR was associated with significantly improved outcomes compared to paramedic-guided CPR: ROSC 36.2 % (95 % confidence interval [CI] 31.0 – 41.7 %) vs. 23.4 % (95 % CI 18.5 – 29.2 %) (pooled odds ratio [OR] 1.89, 95 % CI 1.36 – 2.63, p Conclusions This systematic review suggests that EMS-physician-guided CPR in out-of-hospital cardiac arrest is associated with improved survival outcomes.

Introduction The probability to achieve a return of spontaneous circulation (ROSC) after cardiac arrest can be improved by optimizing circulation during cardiopulomonary resuscitation using a percutaneous left ventricular assist device (iCPR). Inhaled nitric oxide may facilitate transpulmonary blood flow during iCPR and may therefore improve organ perfusion and outcome. Methods Ventricular fibrillation was electrically induced in 20 anesthetized male pigs. Animals were left untreated for 10 minutes before iCPR was attempted. Subjects received either 20 ppm of inhaled nitric oxide (iNO, n = 10) or 0 ppm iNO (Control, n = 10), simultaneously started with iCPR until 5 hours following ROSC. Animals were weaned from the respirator and followed up for five days using overall performance categories (OPC) and a spatial memory task. On day six, all animals were anesthetized again, and brains were harvested for neurohistopathologic evaluation. Results All animals in both groups achieved ROSC. Administration of iNO markedly increased iCPR flow during CPR (iNO: 1.81 ± 0.30 vs Control: 1.64 ± 0.51 L/min, p < 0.001), leading to significantly higher coronary perfusion pressure (CPP) during the 6 minutes of CPR (25 ± 13 vs 16 ± 6 mmHg, p = 0.002). iNO-treated animals showed significantly lower S-100 serum levels thirty minutes post ROSC (0.26 ± 0.09 vs 0.38 ± 0.15 ng/mL, p = 0.048), as well as lower blood glucose levels 120–360 minutes following ROSC. Lower S-100 serum levels were reflected by superior clinical outcome of iNO-treated animals as estimated with OPC (3 ± 2 vs. 5 ± 1, p = 0.036 on days 3 to 5). Three out of ten iNO-treated, but none of the Control animals were able to successfully participate in the spatial memory task. Neurohistopathological examination of vulnerable cerebral structures revealed a trend towards less cerebral lesions in neocortex, archicortex, and striatum in iNO-treated animals compared to Controls. Conclusions In pigs resuscitated with mechanically-assisted CPR from prolonged cardiac arrest, the administration of 20 ppm iNO during and following iCPR improved transpulmonary blood flow, leading to improved clinical neurological outcomes.

Duma and colleagues report that, in patients who achieved return of spontaneous circulation, prehospital use of epinephrine was consistently associated with a lower chance of survival, and this association showed a dose effect and persisted despite post-resuscitation interventions [1]. The accompanying editorial comment from Ewy [2] discusses the limitations and impact of this paper.

Introduction By maintaining sufficient cerebral blood flow and oxygenation, the goal of cardiopulmonary resuscitation (CPR) is to preserve the pre-arrest neurological state. To date, cerebral monitoring abilities during CPR have been limited. Therefore, we investigated the time-course of cerebral oxygen saturation values (rSO2) during advanced life support in out-of-hospital cardiac arrest. Our primary aim was to compare rSO2 values during advanced life support from patients with return of spontaneous circulation (ROSC) to patients who did not achieve ROSC. Methods We performed an observational study to measure rSO2 using Equanox™ (Nonin, Plymouth, MI) from the start of advanced life support in the pre-hospital setting. Results rSO2 of 49 consecutive out-of-hospital cardiac arrest patients were analyzed. The total increase from initial rSO2 value until two minutes before ROSC or end of advanced life support efforts was significantly larger in the group with ROSC 16% (9 to 36) compared to the patients without ROSC 10% (4 to 15) (P = 0.02). Mean rSO2 from the start of measurement until two minutes before ROSC or until termination of advanced life support was higher in patients with ROSC than in those without, namely 39% ± 7 and 31% ± 4 (P = 0.05) respectively. Conclusions During pre-hospital advanced life support, higher increases in rSO2 are observed in patients attaining ROSC, even before ROSC was clinically determined. Our findings suggest that rSO2 could be used in the future to guide patient tailored treatment during cardiac arrest and could therefore be a surrogate marker of the systemic oxygenation state of the patient.

Expanded abstract Citation Niklas Nielsen, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Åneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Køber L, Langørgen J, Lilja G, Møller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H. Targeted temperature management at 33 °C versus 36 °C after cardiac arrest. N Engl J Med. 2013;369:2197–206. doi:10.1056/NEJMoa1310519. Epub 2013 Nov 17. Pub Med PMID: 20089970. Background Brain ischemia and reperfusion injury leading to tissue degeneration and loss of neurological function following return of spontaneous circulation after cardiac arrest (CA) is a well-known entity. Two landmark trials in 2002 showed improved survival and neurological outcome of comatose survivors of out-of-hospital cardiac arrest (OHCA) of presumed cardiac origin when the patients were subjected to therapeutic hypothermia of 32 to 34 °C for 12 to 24 hours. However, the optimal target temperature for these cohorts is yet to be established and also it is not clear whether strict fever management and maintaining near normal body temperature are alone sufficient to improve the outcome. Methods Objective: The objective is to determine whether a hypothermic goal of a near-normal body temperature of 36 °C reduces all-cause mortality compared with a moderate hypothermia of 33 °C for the unconscious survivors of OHCA of presumed cardiac origin when subjected randomly to these different targeted temperatures. Design: A multicenter, international, open label, randomized controlled trial. Setting: Thirty-six ICUs in Europe and Australia participated in this study. Participants: Unconscious adults (older than 18 years of age) who survived (Glasgow coma scale less than 8) OHCA due to presumed cardiac origin with subsequent persistent return of spontaneous circulation (more than 20 minutes without chest compressions). Intervention: The above participant cohorts were randomized to targeted body temperature of either 33 °C or 36 °C for 36 hours after the CA with gradual rewarming of both groups to 37 °C (hourly increments of 0.5 °C) after the initial 28 hours. Body temperatures in both the groups were then maintained below 37.5 °C for 72 hours after the initial 36 hours. Outcomes: Primary outcome measure of all-cause mortality in both the groups at the end of the trial with the secondary outcome measure of all-cause mortality, composite neurological function as evaluated by cerebral performance category scale and modified ranking scale at the end of 180 days were studied. Results Out of the 939 participants, all-cause mortality at the end of the trial was 50 % in the 33 °C group (225 of 466 patients) compared with 48 % in the 36 °C group (235 of 473 patients); the hazard ratio with a temperature of 33 °C was 1.06 (95 % confidence interval (CI) 0.89 to 1.28, P = 0.51). At the end of 180 days, 54 % of patients in the 33 °C group versus 52 % in the 36 °C group had died or had poor neurological outcome according to cerebral performance category (risk ratio 1.02, 95 % CI 0.88 to 1.16, P = 0.78) but the modified ranking scale at the end of 180 days was unchanged (52 %) in both groups (risk ratio 1.01, 95 % CI 0.89 to 1.14, P = 0.87). Conclusions Maintaining targeted lower normothermia of 36 °C had similar outcomes compared with induced moderate hypothermia of 33 °C for unconscious survivors of OHCA of presumed cardiac cause.

Introduction Whole-body ischemia and reperfusion trigger a systemic inflammatory response. In this study, we analyzed the effect of temperature on the inflammatory response in patients treated with prolonged mild hypothermia after cardiac arrest. Methods Ten comatose patients with return of spontaneous circulation after pulseless electrical activity/asystole or prolonged ventricular fibrillation were treated with mild therapeutic hypothermia for 72 hours after admission to a tertiary care university hospital. At admission and at 12, 24, 36, 48, 72, 96 and 114 hours, the patients’ temperature was measured and blood samples were taken from the arterial catheter. Proinflammatory interleukin 6 (IL-6) and anti-inflammatory (IL-10) cytokines and chemokines (IL-8 and monocyte chemotactic protein 1), intercellular adhesion molecule 1 and complement activation products (C1r-C1s-C1inhibitor, C4bc, C3bPBb, C3bc and terminal complement complex) were measured. Changes over time were analyzed with the repeated measures test for nonparametric data. Dunn’s multiple comparisons test was used for comparison of individual time points. Results The median temperature at the start of the study was 34.3°C (33.4°C to 35.2°C) and was maintained between 32°C and 34°C for 72 hours. All patients were passively rewarmed after 72 hours, from (median (IQR)) 33.7°C (33.1°C to 33.9°C) at 72 hours to 38.0°C (37.5°C to 38.1°C) at 114 hours (P

Introduction Little is known about oxyhemoglobin (oxy-Hb) levels in the cerebral tissue during the development of anoxic and ischemic brain injury. We hypothesized that the estimated cerebral oxy-Hb level, a product of Hb and regional cerebral oxygen saturation (rSO2), determined at hospital arrival may reflect the level of neuroprotection in patients with post-cardiac arrest syndrome (PCAS). Methods The Japan Prediction of neurological Outcomes in patients with Post cardiac arrest (J-POP) registry is a prospective, multicenter, cohort study to test whether rSO2 predicts neurologic outcomes after out-of-hospital cardiac arrest (OHCA). This study assessed a subgroup of consecutive patients who fulfilled the J-POP registry criteria and successfully achieved return of spontaneous circulation (ROSC) from OHCA. The primary outcome measure was the neurologic status at 90 days. Results We analyzed data from 495 consecutive comatose survivors who were successfully resuscitated from OHCA, including 119 comatose patients with prehospital return of spontaneous circulation (ROSC; 24.0%) and 376 cardiac arrests at hospital arrival. In total, 75 patients (15.1%) presented with good neurologic outcomes. Univariate analysis revealed that the cerebral oxy-Hb levels were significantly higher in patients with good outcomes. Multivariate logistic regression using the backward-elimination method confirmed that the oxy-Hb level was a significant predictor of good neurologic outcomes (adjusted odds ratio, 1.27; 95% confidence interval (CI), 1.11 to 1.46). Analysis of the area under the receiver operating characteristic curve (AUC) revealed that an oxy-Hb cut-off of 5.5 provided optimal sensitivity and specificity for predicting good neurologic outcomes (AUC, 0.87; 95% CI, 0.83 to 0.91; sensitivity, 77.3%; specificity, 85.6%). The oxy-Hb level appeared to be an excellent prognostic indicator with significant advantages over rSO2 and base excess, according to AUC analysis. The significant trend for good neurologic outcomes was consistent, even in the subgroup of patients who achieved return of spontaneous circulation on hospital arrival (1st quartile, 0; 2nd quartile, 16.7%; 3rd quartile, 29.4%; 4th quartile, 53.3%; P

Introduction The aim of this study was to conduct a systematic review and meta-analysis for determining the effects of prehospital adrenaline administration on return of spontaneous circulation, hospital admission, survival to discharge and discharge with cerebral performance category 1 or 2 in out-of-hospital cardiac arrest patients. Methods MEDLINE and Scopus databases were searched to identify studies reported to March 2014. Study selection and data extraction were independently completed by two reviewers (PA and SR). The baseline characteristics of each study and number of events were extracted. Risk ratios (RR) and 95% confidence interval (CI) were estimated. Heterogeneity and publication bias were also explored. Results In total 15 studies were eligible and included in the study. Of 13 adult observational studies, four to eight studies were pooled for each outcome. These yielded a total sample size that ranged from 2,381 to 421,459. A random effects model suggested that patients receiving prehospital adrenaline were 2.89 times (95% CI: 2.36, 3.54) more likely to achieve prehospital return of spontaneous circulation than those not administered adrenaline. However, there were no significant effects on overall return of spontaneous circulation (RR = 0.93, 95% CI: 0.5, 1.74), admission (RR = 1.05, 95% CI: 0.80, 1.38) and survival to discharge (RR = 0.69, 95% CI: 0.48, 1.00). Conclusions Prehospital adrenaline administration may increase prehospital return of spontaneous circulation, but it does not improve overall rates of return of spontaneous circulation, hospital admission and survival to discharge. Electronic supplementary material The online version of this article (doi:10.1186/s13054-014-0463-7) contains supplementary material, which is available to authorized users.

Identification of prehospital prognostic factors in out-of-hospital cardiac arrests (OHCAs) with prehospital return of spontaneous circulation (ROSC) and establishment of a prediction model for survival with favorable neurological outcome may minimize the costs and save the medical resources. In this study, we developed a best model for predicting 1-month survival with favorable neurological outcome (defined as Glasgow-Pittsburgh cerebral performance category (CPC) scale = 1 or 2), using a logistic regression analysis.

Various criteria to terminate resuscitation have been reported. EMTs in Japan are not permitted to terminate resuscitation in the field. The aim of this study is to test the hypothesis that ECG rhythm response to basic CPR and its duration may predict hospital death.

A recent US multicentre study demonstrated an increased mortality in intensive care patients exposed to high arterial oxygen levels following return of spontaneous circulation (ROSC) after cardiac arrest [1]. We attempted to ascertain the incidence of hyperoxia and associated mortality in a similar cohort of patients in the UK.

Despite several large studies concerning out-of-hospital cardiac arrests in recent years, it is not clear whether their in-hospital counterparts have benefited from advances in resuscitation as well as post-resuscitation care.

Introduction: At hospital arrival, early prognostication for children after out-of-hospital cardiac arrest (OHCA) might help clinicians formulate strategies, particularly in the emergency department. In this study, we aimed to develop a simple and generally applicable bedside tool for predicting outcomes in children after cardiac arrest. Methods: We analyzed data of 5,379 children who had undergone OHCA. The data were extracted from a prospectively recorded, nationwide, Utstein-style Japanese database. The primary endpoint was survival with favorable neurological outcome (Cerebral Performance Category (CPC) scale categories 1 and 2) at 1 month after OHCA. We developed a decision tree prediction model by using data from a 2-year period (2008 to 2009, n= 3,693), and the data were validated using external data from 2010 (n= 1,686). Results: Recursive partitioning analysis for 11 predictors in the development cohort indicated that the best single predictor for CPC 1 and 2 at 1 month was the prehospital return of spontaneous circulation (ROSC). The next predictor for children with prehospital ROSC was an initial shockable rhythm. For children without prehospital ROSC, the next best predictor was a witnessed arrest. Use of a simple decision tree prediction model permitted stratification into four outcome prediction groups: good (prehospital ROSC and initial shockable rhythm), moderately good (prehospital ROSC and initial nonshockable rhythm), poor (prehospital non-ROSC and witnessed arrest) and very poor (prehospital non-ROSC and unwitnessed arrest). By using this model, we identified patient groups ranging from 0.2% to 66.2% for 1-month CPC 1 and 2 probabilities. The validated decision tree prediction model demonstrated a sensitivity of 69.7% (95% confidence interval (CI) = 58.7% to 78.9%), a specificity of 95.2% (95% CI = 94.1% to 96.2%) and an area under the receiver operating characteristic curve of 0.88 (95% CI = 0.87 to 0.90) for predicting 1-month CPC 1 and 2. Conclusions: With our decision tree prediction model using three prehospital variables (prehospital ROSC, initial shockable rhythm and witnessed arrest), children can be readily stratified into four groups after OHCA. This simple prediction model for evaluating children after OHCA may provide clinicians with a practical bedside tool for counseling families and making management decisions soon after patient arrival at the hospital.

Guidelines recommend to perform head computed tomography (CT) in nontraumatic cardiac arrest only if the patient remains unconscious after return of spontaneous circulation [1]. Nevertheless, in cardiac arrest due to neurological causes, head CT would dramatically change the therapeutic strategy in these patients [2]. The aim of this study is to present the experience of our ICU in nontraumatic out-of-hospital cardiac arrest (OHCA) patients and to demonstrate that neurological abnormalities can be the primary cause of cardiac arrest.

Introduction The 2010 cardiopulmonary resuscitation guidelines recommend emergency medical services (EMS) personnel consider prehospital termination-of-resuscitation (TOR) rules for out-of-hospital cardiac arrest (OHCA) following basic life support and/or advanced life support efforts in the field. However, the rate of implementation of international TOR rules is still low. Here, we aimed to develop and validate a new TOR rule for emergency department physicians to replace the international TOR rules for EMS personnel in the field. This rule aims to guide physicians in deciding whether to withhold further resuscitation attempts or terminate on-going resuscitation immediately after patient arrival. Methods We analyzed data prospectively collected in a nationwide Utstein-style Japanese database between 2005 and 2009, from 495,607 adult patients with OHCA. Patients were divided into development (n = 390,577) and validation (n = 105,030) groups. The main outcome measures were specificity, positive predictive value (PPV), and area under the receiver operating characteristic (ROC) curve for the newly developed TOR rule. Results We developed a new TOR rule that includes 3 criteria based on the results of multivariate logistic regression analysis for predicting a 1-month death after OHCA: no prehospital return of spontaneous circulation (adjusted odds ratio [OR], 25.8; 95% confidence interval [CI], 24.7–26.9), unshockable initial rhythm (adjusted OR, 2.76; 95% CI, 2.54–3.01), and unwitnessed by bystanders (adjusted OR, 2.18; 95% CI, 2.09–2.28). The specificity, PPV, and area under the ROC curve for this new TOR rule for predicting 1-month death in the validation group were 0.903 (95% CI, 0.894–0.911), 0.993 (95% CI, 0.992–0.993), and 0.874 (95% CI, 0.872–0.876), respectively. Conclusions We developed and validated a new TOR rule for emergency department physicians consisting of 3 prehospital variables (no prehospital ROSC, unshockable initial rhythm, and unwitnessed by bystanders) that is a >99% predictor of very poor outcome. However, the implementation of this new rule in other countries or EMS systems requires further validation studies.

During cardiopulmonary resuscitation (CPR) monitoring possibilities are limited. Parnia and colleagues investigated the feasibility and role of near-infrared spectroscopy (NIRS) during CPR in cardiac arrest patients (CA) [1]. NIRS could have a role in predicting return of spontaneous circulation (ROSC). Recently, the Equanox® with four wavelengths sensor was validated to provide absolute data on regional cerebral saturation [2]. We measured cerebral oxygenation (rSO2) during CPR with NIRS technology and analyzed the differences between initial cerebral saturations in patients achieving ROSC compared with patients without ROSC.

Introduction As emergency medical services (EMS) personnel in Japan are not allowed to perform termination of resuscitation in the field, most patients experiencing an out-of-hospital cardiac arrest (OHCA) are transported to hospitals without a prehospital return of spontaneous circulation (ROSC). As the crucial prehospital factors for outcomes are not clear in patients who had an OHCA without a prehospital ROSC, we aimed to determine the prehospital factors associated with 1-month favorable neurological outcomes (Cerebral Performance Category scale 1 or 2 (CPC 1–2)). Methods We analyzed the data of 398,121 adult OHCA patients without a prehospital ROSC from a prospectively recorded nationwide Utstein-style Japanese database from 2007 to 2010. The primary endpoint was 1-month CPC 1–2. Results The rate of 1-month CPC 1–2 was 0.49%. Multivariate logistic regression analysis indicated that the independent variables associated with CPC 1–2 were the following nine prehospital factors: (1) initial non-asystole rhythm (ventricular fibrillation (VF): adjusted odds ratio (aOR), 9.37; 95% confidence interval (CI), 7.71 to 11.4; pulseless ventricular tachycardia (VT): aOR, 8.50; 95% CI, 5.36 to 12.9; pulseless electrical activity (PEA): aOR, 2.75; 95% CI, 2.40 to 3.15), (2) age 2.0 in the regression model: initial non-asystole rhythm, age

Two international termination-of-resuscitation (TOR) rules for the emergency medical services (EMS) personnel have been proposed to identify nonsurvivors after out-of-hospital cardiac arrest (OHCA). The first is for use by responders providing basic life support (BLS) which includes three criteria: not witnessed by EMS personnel, no shocks are administered and no return of spontaneous circulation (ROSC). The other is for use by responders providing advanced life support (ALS) which adds two criteria: unwitnessed by a bystander and no bystander cardiopulmonary resuscitation. Simpler criteria as a universal TOR rule may be desirable for any level of EMS personnel. We performed this study to validate two TOR rules and a modified BLS TOR rule which includes three criteria: unwitnessed arrest, no shocks administered and no ROSC achieved before arrival at hospital for predicting refractory OHCAs.

Therapeutic hypothermia is largely used to protect the brain following return of spontaneous circulation (ROSC) after cardiac arrest (CA), but it is unclear whether we should start therapeutic hypothermia earlier, that is, before ROSC., Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

Induction of hypothermia is generally accepted to improve neurologic recovery of out-of-hospital cardiopulmonary arrest (CPA). Early prognostication of post-CPA patients is challenging. The aim of the present study was to evaluate the predictive factors for neurologic outcome in out-of-hospital cardiac arrest patients who returned their spontaneous circulation in a prehospital setting (PROSC) and underwent therapeutic hypothermia (TH).

Introduction It has been unclear if mechanical cardiopulmonary resuscitation (CPR) is a viable alternative to manual CPR. We aimed to compare resuscitation outcomes before and after switching from manual CPR to load-distributing band (LDB) CPR in a multi-center emergency department (ED) trial. Methods We conducted a phased, prospective cohort evaluation with intention-to-treat analysis of adults with non-traumatic cardiac arrest. At these two urban EDs, systems were changed from manual CPR to LDB-CPR. Primary outcome was survival to hospital discharge, with secondary outcome measures of return of spontaneous circulation, survival to hospital admission and neurological outcome at discharge. Results A total of 1,011 patients were included in the study, with 459 in the manual CPR phase (January 01, 2004, to August 24, 2007) and 552 patients in the LDB-CPR phase (August 16, 2007, to December 31, 2009). In the LDB phase, the LDB device was applied in 454 patients (82.3%). Patients in the manual CPR and LDB-CPR phases were comparable for mean age, gender and ethnicity. The mean duration from collapse to arrival at ED (min) for manual CPR and LDB-CPR phases was 34:03 (SD16:59) and 33:18 (SD14:57) respectively. The rate of survival to hospital discharge tended to be higher in the LDB-CPR phase (LDB 3.3% vs Manual 1.3%; adjusted OR, 1.42; 95% CI, 0.47, 4.29). There were more survivors in LDB group with cerebral performance category 1 (good) (Manual 1 vs LDB 12, P = 0.01). Overall performance category 1 (good) was Manual 1 vs LDB 10, P = 0.06. Conclusions A resuscitation strategy using LDB-CPR in an ED environment was associated with improved neurologically intact survival on discharge in adults with prolonged, non-traumatic cardiac arrest.

Introduction Extracorporeal membrane oxygenation (ECMO) is increasingly used in cardiac arrest (CA). Adequacy of carotid and coronary blood flows (CaBF, CoBF) and coronary perfusion pressure (CoPP) in ECMO treated CA is not well established. This study compares femoro-femoral (FF) to femoro-subclavian (FS) ECMO and intraaortic balloon counterpulsation (IABP) contribution based on CaBF, CoBF, CoPP, myocardial and brain oxygenation in experimental CA managed by ECMO. Methods In 11 female pigs (50.3 ± 3.4 kg), CA was randomly treated by FF versus FS ECMO ± IABP. Animals under general anesthesia had undergone 15 minutes of ventricular fibrillation (VF) with ECMO flow of 5 to 10 mL/kg/min simulating low-flow CA followed by continued VF with ECMO flow of 100 mL/kg/min. CaBF and CoBF were measured by a Doppler flow wire, cerebral and peripheral oxygenation by near infrared spectroscopy. CoPP, myocardial oxygen metabolism and resuscitability were determined. Results CaBF reached values > 80% of baseline in all regimens. CoBF > 80% was reached only by the FF ECMO, 90.0% (66.1, 98.6). Addition of IABP to FF ECMO decreased CoBF to 60.7% (55.1, 86.2) of baseline, P = 0.004. FS ECMO produced 70.0% (49.1, 113.2) of baseline CoBF, significantly lower than FF, P = 0.039. Addition of IABP to FS did not change the CoBF; however, it provided significantly higher flow, 76.7% (71.9, 111.2) of baseline, compared to FF + IABP, P = 0.026. Both brain and peripheral regional oxygen saturations decreased after induction of CA to 23% (15.0, 32.3) and 34% (23.5, 34.0), respectively, and normalized after ECMO institution. For brain saturations, all regimens reached values exceeding 80% of baseline, none of the comparisons between respective treatment approaches differed significantly. After a decline to 15 mmHg (9.5, 20.8) during CA, CoPP gradually rose with time to 68 mmHg (43.3, 84.0), P = 0 .003, with best recovery on FF ECMO. Resuscitability of the animals was high, both 5 and 60 minutes return of spontaneous circulation occured in eight animals (73%). Conclusions In a pig model of CA, both FF and FS ECMO assure adequate brain perfusion and oxygenation. FF ECMO offers better CoBF than FS ECMO. Addition of IABP to FF ECMO worsens CoBF. FF ECMO, more than FS ECMO, increases CoPP over time.

Introduction Cardiac arrest following trauma occurs infrequently compared with cardiac aetiology. Within the German Resuscitation Registry a traumatic cause is documented in about 3% of cardiac arrest patients. Regarding the national Trauma Registry, only a few of these trauma patients with cardiac arrest survive. The aim of the present study was to analyze the outcome of cardiopulmonary resuscitation (CPR) after traumatic cardiac arrest by combining data from two different large national registries in Germany. Methods This study includes 368 trauma patients (2.8%) out of 13,329 cardiac arrest patients registered within the Resuscitation Registry, whereby 3,673 patients with a cardiac cause and successful CPR served as a cardiac control group. We further analyzed a second group of 1,535 trauma patients with cardiac arrest and early CPR registered within the Trauma Registry, whereby a total of 25,366 trauma patients without any CPR attempts served as a trauma control group. The relative frequencies from each database were used to calculate relative percentages for patients with traumatic cardiac arrest in whom resuscitation was attempted. Results Within the Resuscitation Registry, cardiac arrest was present in 331 patients (89.9%) when the EMS personal arrived at the scene and in 37 patients (10.1%) when cardiac arrest occurred after arrival. Spontaneous circulation could be achieved in 107 patients (29.1%). A total of 101 (27.4%) were transferred to hospital, 95 of whom (25.8%) had return of spontaneous circulation (ROSC) on admission. According to the Trauma Registry, the overall hospital mortality rate for cardiac arrest patients following trauma was 73% (n = 593 of 814). About half of the patients who were admitted alive to hospital died within 24 hours, resulting in 13% survivors within 24 hours. 7% of the patients survived until hospital discharge, and only 2% of the patients had good neurological outcome. Conclusions Our present study encourages CPR attempts in cardiac arrest patients following severe trauma. When a manageable number of patients is present, the decision on whether to start CPR or not should be done liberally, using comparable criteria as in patients with cardiac etiology. In this respect, trauma management programs that restrict CPR attempts should not be encouraged.

Introduction In this study, we sought to examine whether pharmacological postconditioning with sevoflurane (SEVO) is neuro- and cardioprotective in a pig model of cardiopulmonary resuscitation. Methods Twenty-two pigs were subjected to cardiac arrest. After 8 minutes of ventricular fibrillation and 2 minutes of basic life support, advanced cardiac life support was started. After successful return of spontaneous circulation (N = 16), animals were randomized to either (1) propofol (CONTROL) anesthesia or (2) SEVO anesthesia for 4 hours. Neurological function was assessed 24 hours after return of spontaneous circulation. The effects on myocardial and cerebral damage, especially on inflammation, apoptosis and tissue remodeling, were studied using cellular and molecular approaches. Results Animals treated with SEVO had lower peak troponin T levels (median [IQR]) (CONTROL vs SEVO = 0.31 pg/mL [0.2 to 0.65] vs 0.14 pg/mL [0.09 to 0.25]; P < 0.05) and improved left ventricular systolic and diastolic function compared to the CONTROL group (P < 0.05). SEVO was associated with a reduction in myocardial IL-1β protein concentrations (0.16 pg/μg total protein [0.14 to 0.17] vs 0.12 pg/μg total protein [0.11 to 0.14]; P < 0.01), a reduction in apoptosis (increased procaspase-3 protein levels (0.94 arbitrary units [0.86 to 1.04] vs 1.18 arbitrary units [1.03 to 1.28]; P < 0.05), increased hypoxia-inducible factor (HIF)-1α protein expression (P < 0.05) and increased activity of matrix metalloproteinase 9 (P < 0.05). SEVO did not, however, affect neurological deficit score or cerebral cellular and molecular pathways. Conclusions SEVO reduced myocardial damage and dysfunction after cardiopulmonary resuscitation in the early postresuscitation period. The reduction was associated with a reduced rate of myocardial proinflammatory cytokine expression, apoptosis, increased HIF-1α expression and increased activity of matrix metalloproteinase 9. Early administration of SEVO may not, however, improve neurological recovery.

Cardiopulmonary resuscitation (CPR) guidelines published by the European Resuscitation Council are intended to improve survival of cardiac arrest by implementing medical practice based on scientific findings. This study investigated whether the introduction of the 2005 CPR guidelines, which mandated several fundamental practice changes, improved the rate of return of spontaneous circulation (ROSC) in a physician-staffed prehospital emergency medical system.

End-tidal carbon dioxide (CO2) correlates with cardiac output during cardiopulmonary resuscitation (CPR) in cardiac arrest patients. Increasing CO2 during CPR can also indicate the return of spontaneous circulation.

Introduction: Our purpose was to study whether the time to target temperature correlates with neurologic outcome in patients after cardiac arrest with restoration of spontaneous circulation treated with therapeutic mild hypothermia in an academic emergency department. Methods: Temperature data between April 1995 and June 2008 were collected from 588 patients and analyzed in a retrospective cohort study by observers blinded to outcome. The time needed to achieve an esophageal temperature of less than 34°C was recorded. Survival and neurological outcomes were determined within six months after cardiac arrest. Results: The median time from restoration of spontaneous circulation to reaching a temperature of less than 34°C was 209 minutes (interquartile range [IQR]: 130-302) in patients with favorable neurological outcomes compared to 158 min (IQR: 101-230) (P < 0.01) in patients with unfavorable neurological outcomes. The adjusted odds ratio for a favorable neurological outcome with a longer time to target temperature was 1.86 (95% CI 1.03 to 3.38, P = 0.04). Conclusions: In comatose cardiac arrest patients treated with therapeutic hypothermia after return of spontaneous circulation, a faster decline in body temperature to the 34°C target appears to predict an unfavorable neurologic outcome.

Introduction Partial pressure of end-tidal carbon dioxide (PetCO2) during cardiopulmonary resuscitation (CPR) correlates with cardiac output and consequently has a prognostic value in CPR. In our previous study we confirmed that initial PetCO2 value was significantly higher in asphyxial arrest than in ventricular fibrillation/pulseless ventricular tachycardia (VF/VT) cardiac arrest. In this study we sought to evaluate the pattern of PetCO2 changes in cardiac arrest caused by VF/VT and asphyxial cardiac arrest in patients who were resuscitated according to new 2005 guidelines. Methods The study included two cohorts of patients: cardiac arrest due to asphyxia with initial rhythm asystole or pulseless electrical activity (PEA), and cardiac arrest due to arrhythmia with initial rhythm VF or pulseless VT. PetCO2 was measured for both groups immediately after intubation and repeatedly every minute, both for patients with or without return of spontaneous circulation (ROSC). We compared the dynamic pattern of PetCO2 between groups. Results Between June 2006 and June 2009 resuscitation was attempted in 325 patients and in this study we included 51 patients with asphyxial cardiac arrest and 63 patients with VF/VT cardiac arrest. The initial values of PetCO2 were significantly higher in the group with asphyxial cardiac arrest (6.74 ± 4.22 kilopascals (kPa) versus 4.51 ± 2.47 kPa; P = 0.004). In the group with asphyxial cardiac arrest, the initial values of PetCO2 did not show a significant difference when we compared patients with and without ROSC (6.96 ± 3.63 kPa versus 5.77 ± 4.64 kPa; P = 0.313). We confirmed significantly higher initial PetCO2 values for those with ROSC in the group with primary cardiac arrest (4.62 ± 2.46 kPa versus 3.29 ± 1.76 kPa; P = 0.041). A significant difference in PetCO2 values for those with and without ROSC was achieved after five minutes of CPR in both groups. In all patients with ROSC the initial PetCO2 was again higher than 1.33 kPa. Conclusions The dynamic pattern of PetCO2 values during out-of-hospital CPR showed higher values of PetCO2 in the first two minutes of CPR in asphyxia, and a prognostic value of initial PetCO2 only in primary VF/VT cardiac arrest. A prognostic value of PetCO2 for ROSC was achieved after the fifth minute of CPR in both groups and remained present until final values. This difference seems to be a useful criterion in pre-hospital diagnostic procedures and attendance of cardiac arrest.

Introduction: Cardiac arrest is often fatal and can be extremely stressful to patients, even if spontaneous rhythm is returned. The purpose of this study was to analyze the hormonal response after return of spontaneous circulation (ROSC). Methods: This is a retrospective review of the chart and laboratory findings in a single medical facility. The patients admitted to the intensive care unit after successful resuscitation after out-of-hospital cardiac arrest were retrospectively identified and evaluated. Patients with hormonal diseases, patients who received cortisol treatment, those experiencing trauma, and pregnant women were excluded. Serum cortisol, adrenocorticotropic hormone (ACTH), and anti-diuretic hormone (ADH (vasopressin)) were analyzed and a corticotropin-stimulation test was performed. Mortality at one week and one month after admission, and neurologic outcome (cerebral performance category (CPC)) one month after admission were evaluated. Results: A total of 117 patients, including 84 males (71.8%), were evaluated in this study. One week and one month after admission, 87 (74.4%) and 65 patients (55.6%) survived, respectively. Relative adrenal insufficiency, and higher plasma ACTH and ADH levels were associated with shock-related mortality (P = 0.046, 0.005, and 0.037, respectively), and ACTH and ADH levels were also associated with late mortality (P = 0.002 and 0.004, respectively). Patients with relative adrenal insufficiency, ACTH ≧5 pg/mL, and ADH ≧30 pg/mL, had a two-fold increased risk of a poor outcome (shock-related mortality): (odds ratio (OR), 2.601 and 95% confidence interval (CI), 1.015 to 6.664; OR, 2.759 and 95% CI, 1.060 to 7.185; OR, 2.576 and 95% CI, 1.051 to 6.313, respectively). Thirty-five patients (29.9%) had a good CPC (1 to 2), and 82 patients (70.1%) had a bad CPC (3 to 5). Age ≧50 years and an ADH ≧30 pg/mL were associated with a bad CPC (OR, 4.564 and 95% CI, 1.794 to 11.612; OR, 6.568 and 95% CI, 1.918 to 22.483, respectively). Conclusions: The patients with relative adrenal insufficiency and higher blood levels of ACTH and ADH upon ROSC after cardiac arrest had a poor outcome. The effectiveness of administration of cortisol and ADH to patients upon ROSC after cardiac arrest is uncertain and additional studies are needed.

Introduction Neuron specific enolase (NSE) has been proven effective in predicting neurological outcome after cardiac arrest with a current cut off recommendation of 33 μg/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 μg/l) compared to the NH group (26.9 μg/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.

Introduction: The aim of the present study was to investigate the impact of the time interval from collapse to return of spontaneous circulation (CPA-ROSC) in cardiac arrest patients and the types of patients who will benefit from therapeutic hypothermia. Methods: Four hundred witnessed adult comatose survivors of out-of-hospital cardiac arrest of cardiac etiology were enrolled in the study. The favorable neurological outcome was defined as category 1 or 2 on the five-point Pittsburgh cerebral performance scale at the time of hospital discharge. A matching process based on the propensity score was performed to equalize potential prognostic factors in the hypothermia and normothermia groups, and to formulate a balanced 1:1 matched cohort study. Results: The rate of favorable neurological outcome was higher (P < 0.05) in the hypothermia group (n = 110) than in the normothermia group in patients with CPA-ROSC of 15 to 20 minutes (64% vs. 17%), 20 to 25 minutes (70% vs. 8%), 25 to 30 minutes (50% vs. 7%), 35 to 40 minutes (27% vs. 0%) and 40 to 45 minutes (29% vs. 2%). A similar association was observed in a propensity-matched cohort, but the differences were not significant. There was no significant difference in the rate of favorable neurological outcome between the hypothermia-matched group and the normothermia-matched group. In the patients whose CPA-ROSC was greater than 15 minutes, however, the rate of favorable neurological outcome was higher in the hypothermia-matched group than in the normothermia-matched group (27% vs. 4%, P < 0.001). In multivariate analysis, the CPA-ROSC was an independent predictor of favorable neurological outcome (every 1 minute: odds ratio = 0.89, 95% confidence interval = 0.85 to 0.92, P < 0.001). Conclusions: The CPA-ROSC is an independent predictor of neurological outcome. Therapeutic hypothermia is more beneficial in comatose survivors of cardiac arrest with CPA-ROSC greater than 15 minutes.

Introduction Knowledge about the influence of current neuroprotective interventions on prognostic markers after survival from cardiac arrest is lacking. This study aimed to investigate the effects of mild therapeutic hypothermia on the release of the astroglial protein S-100 after cardiopulmonary resuscitation (CPR) in survivors of out-of-hospital cardiac arrest. Methods This was a prospective, observational study performed during a two-year period, involving medical emergency services and five collaborating hospitals at the city of Aachen, Germany. Sixty-eight subjects were enrolled by the emergency physician on duty by taking blood samples after successful attempts at resuscitation with return of spontaneous circulation (ROSC), followed by samples at 6, 12, 24, 72 and 120 hours post ROSC by the appropriate intensive care unit staff. Depending on the decision of the attending physician, subjects were cooled down to 33°C (n = 37) for 24 hours or were held at 37°C (n = 31). Patients were tracked for estimating mortality and gross neurological outcome for 14 days. Results S-100 levels in patients not receiving mild therapeutic hypothermia (normothermia (NT)) showed equivalent numbers as compared with cooled patients (mild therapeutic hypothermia (MTH)) on baseline (NT = 1.38 μg/l versus MTH = 1.30 μg/l; P = 0.886). S-100 levels on baseline were significantly lower in patients with a good neurological outcome at 14 days after the event in comparison to their peers with adverse outcome (P = 0.014). Although the difference in S-100 levels of MTH patients with adverse or favourable neurological outcome reached statistical significance, it did not in NT patients. Conclusions Although the predictive power of S-100 levels were best on admission but not at later time points, MTH had no influence on S-100 serum levels in survivors of non-traumatic out-of-hospital cardiac arrest in the particular setting of this investigation.

Despite cardiac arrests accounting for 5.8% of admissions to intensive care, there is significant variation in the management and outcome of these patients in different units [1]. Randomised controlled trials have demonstrated that active cooling to 32 to 34°C for 12 to 24 hours after return of spontaneous circulation (ROSC) significantly improves the outcome of patients who have an out-of-hospital ventricular fibrillation arrest [2]. However there are a range of cooling techniques employed, and no trials have demonstrated that any particular system is superior [3].

Nasopharyngeal cooling during cardiopulmonary resuscitation has been shown to ease the resuscitation effort and to improve the resuscitation rate, survival and neurologic outcome in porcine models of both prolonged ventricular fibrillation and pulseless electrical activity arrest. The aim of this study was to determine whether nasopharyngeal cooling initiated during resuscitation improves the resuscitation rate (return of spontaneous circulation (ROSC)), survival and neurologic outcome.

Drug administration is an integral part of advanced life support (ALS). The coronary perfusion pressure (CorPP) during cardiopulmonary resuscitation (CPR) predicts the probability of return of spontaneous circulation, while the cerebral perfusion pressure (CPP) affects brain damage. Guidelines for cardiac arrest treatment recommend giving adrenaline (ADR) although there is no evidence showing long-term benefit from any medication. Vaso-pressin was probably the most effective alternative studied in both experimental and clinical trails. As vasopressin has never been available in Europe, we evaluated the effect of its synthetic analogue, terlipressin (TER), on vital organ perfusion in an animal model of ventricular fibrillation (VF) (Terlipressin in Cardiac Arrest (TERCA) study). The use of TER in VF has never been studied before.