Prehospital emergency medicine research by additional teams on scene - Concepts and lessons learned.

While the initial minutes of acute emergencies significantly influence clinical outcomes, prehospital research often receives inadequate attention due to several challenges. Retrospective chart reviews carry the risk of incomplete and inaccurate data. Furthermore, prehospital intervention trials frequently encounter difficulties related to extensive training requirements, even during the planning phase. Consequently, we have implemented prospective research concepts involving additional paramedics and physicians directly at the scene during major emergency calls. Three concepts were used: (I) Paramedic field supervisor units, (II) a paramedic + physician field supervisor unit, (III) a special physician-based research car. This paper provides insights into our historical perspective, the current situation, and the lessons learned while overcoming certain barriers and using existing and novel facilitators. Our objective is to support other research groups with our experiences in their planning of upcoming prehospital trials.

Very long-term survivors of in-hospital and out-of-hospital cardiac arrest show considerable impairment of daily life.

BACKGROUND: Reliable data on long-term outcomes after cardiac arrest (CA) remain scarce. Identifying factors persistently impacting the quality of life after CA is crucial to improve long-term outcomes. METHODS: Adult in- and out-of-hospital CA patients surviving to hospital discharge between 1996 and 2015 were retrospectively included. We classified survivors in stages of survival time and assessed long-term survival and quality of life by contacting patients via a standardized telephone questionnaire including the modified Rankin Scale (mRS). RESULTS: Of 4,234 patients, 1,573 (37.2%) survived to hospital discharge. Among those, 693(44.1%) were alive at the time of the interview. We obtained interviews in 178 patients at a survival time of 7.8 (4.2-12.6) years. Younger age, female gender, and shorter duration of initial hospitalization and coma were associated with long-term survival. Conversely, higher median age at time of CA predicted poor outcome (mRS ≥ 3) and impaired quality of daily life. Around 25% declared being impaired in mobility, with female gender and higher age being predictors. Impairment in personal care and hygiene was stated in 11.8%, and activities of daily life such as shopping troubled 33.1%. Chronic pain impairing daily life was reported in 47.2% of cases, and lower socioeconomic status was suggestive of unfavourable outcome. CONCLUSION: Very long-term survivors showed considerable impairment of quality of life in terms of reduced mobility, self-care, or chronic pain. Higher age at time of CA and lower socioeconomic status showed worse outcomes. A more personalized screening of survivors for risk factors and long-term support are suggested.

Medical care at a mass gathering music festival : Retrospective study over 7 years (2011-2017).

BACKGROUND: Knowledge about longitudinal changes in epidemiological data at mass gathering events is sparse. The goal of this study was to determine and compare the type, severity and frequency of illnesses at a large music festival over 7 consecutive years (2011-2017). METHODS: Prospectively collected data from the rescue operation protocols of an Austrian music festival were retrieved and analyzed. Patient presentation rates (PPR) and transport to hospital rates (TTHR) were calculated and compared between years. Linear regression was used to investigate the association between (a) total number of visitors and number of patient presentations, and (b) environmental factors and temperature related medical emergencies. A descriptive analysis of pertinent medical logistics management was performed. RESULTS: The median (minimum to maximum) PPR and TTHR were 12.01 (9.33 in 2016 to 20.86 in 2011) and 0.57 (0.40 in 2017 to 1.06 in 2013) per 1000 visitors, respectively. In linear regression models, no significant associations were found between the number of visitors and either the total number of patient presentations, NACA 1-2 or NACA 3-5 classified emergencies. Environmental temperature had a significant impact on heat related patient presentations (p < 0.001). CONCLUSION: There were significant differences and a high variance in both PPR and TTHR over the years. Contrary to our expectations, the number of visitors did not predict the number of patient presentations. Ambient temperature was associated with the number of heat related emergencies but not with the number of cold related emergencies. Prevention strategies, such as the removal of insect nests, resulted in significantly fewer insect related emergencies.

Cardiac Arrest Induced by Asphyxia Versus Ventricular Fibrillation Elicits Comparable Early Changes in Cytokine Levels in the Rat Brain, Heart, and Serum.

Background Current postresuscitative care after cardiac arrest (CA) does not address the cause of CA. We previously reported that asphyxial CA (ACA) and ventricular fibrillation CA (VFCA) elicit unique injury signatures. We hypothesized that the early cytokine profiles of the serum, heart, and brain differ in response to ACA versus VFCA. Methods and Results Adult male rats were subjected to 10 minutes of either ACA or VFCA. Naives and shams (anesthesia and surgery without CA) served as controls (n=12/group). Asphyxiation produced an ≈4-minute period of progressive hypoxemia followed by a no-flow duration of ≈6±1 minute. Ventricular fibrillation immediately induced no flow. Return of spontaneous circulation was achieved earlier after ACA compared with VFCA (42±18 versus 105±22 seconds; P<0.001). Brain cytokines in naives were, in general, low or undetectable. Shams exhibited a modest effect on select cytokines. Both ACA and VFCA resulted in robust cytokine responses in serum, heart, and brain at 3 hours. Significant regional differences pinpointed the striatum as a key location of neuroinflammation. No significant differences in cytokines, neuron-specific enolase, S100b, and troponin T were observed across CA models. Conclusions Both models of CA resulted in marked systemic, heart, and brain cytokine responses, with similar degrees of change across the 2 CA insults. Changes in cytokine levels after CA were most pronounced in the striatum compared with other brain regions. These collective observations suggest that the amplitude of the changes in cytokine levels after ACA versus VFCA may not mediate the differences in secondary injuries between these 2 CA phenotypes.

The impact of a high-quality basic life support police-based first responder system on outcome after out-of-hospital cardiac arrest.

BACKGROUND: Laypersons' efforts to initiate basic life support (BLS) in witnessed Out-of-Hospital Cardiac Arrest (OHCA) remain comparably low within western society. Therefore, in order to shorten no-flow times in cardiac arrest, several police-based first responder systems equipped with automated external defibrillators (Pol-AED) were established in urban areas, which subsequently allow early BLS and AED administration by police officers. However, data on the quality of BLS and AED use in such a system and its impact on patient outcome remain scarce and inconclusive. METHODS: A total of 85 Pol-AED cases were randomly assigned to a gender, age and first rhythm matched non-Pol-AED control group (n = 170) in a 1:2 ratio. Data on quality of BLS were extracted via trans-thoracic impedance tracings of used AED devices. RESULTS: Comparing Pol-AED cases and the control group, we observed a similar compression rate per minute (p = 0.677) and compression ratio (p = 0.651), mirroring an overall high quality of BLS administered by police officers. Time to the first shock was significantly shorter in Pol-AED cases (6 minutes [IQR: 2-10] vs. 12 minutes [IQR: 8-17]; p<0.001). While Pol-AED was not associated with increased sustained return of spontaneous circulation (p = 0.564), a strong and independent impact on survival until hospital discharge (adj. OR: 1.85 [95%CI: 1.06-3.23; p = 0.030]) and a borderline significance for the association with favorable neurological outcome (adj. OR: 1.58 [95%CI: 0.96-2.89; p = 0.052) were observed. CONCLUSION: We were able to demonstrate an early start and a high quality of BLS and AED use in Pol-AED assessed OHCA cases. Moreover, the presence of Pol-AED care was associated with better patient survival and borderline significance for favorable neurological outcome.

Nitrite pharmacokinetics, safety and efficacy after experimental ventricular fibrillation cardiac arrest.

INTRODUCTION: Besides therapeutic hypothermia or targeted temperature management no novel therapies have been developed to improve outcomes of patients after cardiac arrest (CA). Recent studies suggest that nitrite reduces neurological damage after asphyxial CA. Nitrite is also implicated as a new mediator of remote post conditioning produced by tourniquet inflation-deflation, which is under active investigation in CA. However, little is known about brain penetration or pharmacokinetics (PK). Therefore, to define the optimal use of this agent, studies on the PK of nitrite in experimental ventricular fibrillation (VF) are needed. We tested the hypothesis that nitrite administered after resuscitation from VF is detectable in cerebrospinal fluid (CSF), brain and other organ tissues, produces no adverse hemodynamic effects, and improves neurologic outcome in rats. METHODS: After return of spontaneous circulation (ROSC) of 5 min untreated VF, adult male Sprague-Dawley rats were given intravenous nitrite (8 µM, 0.13 mg/kg) or placebo as a 5 min infusion beginning at 5 min after CA. Additionally, sham groups with and without nitrite treatment were also studied. Whole blood nitrite levels were serially measured. After 15 min, CSF, brain, heart and liver tissue were collected. In a second series, using a randomized and blinded treatment protocol, rats were treated with nitrite or placebo after arrest. Neurological deficit scoring (NDS) was performed daily and eight days after resuscitation, fear conditioning testing (FCT) and brain histology were assessed. RESULTS: In an initial series of experiments, rats (n = 21) were randomized to 4 groups: VF-CPR and nitrite therapy (n = 6), VF-CPR and placebo therapy (n = 5), sham (n = 5), or sham plus nitrite therapy (n = 5). Whole blood nitrite levels increased during drug infusion to 57.14 ±â€¯10.82 µM at 11 min post-resuscitation time (1 min after dose completion) in the VF nitrite group vs. 0.94 ±â€¯0.58 µM in the VF placebo group (p < 0.001). There was a significant difference between the treatment and placebo groups in nitrite levels in blood between 7.5 and 15 min after CPR start and between groups with respect to nitrite levels in CSF, brain, heart and liver. In a second series (n = 25 including 5 shams), 19 out of 20 animals survived until day 8. However, NDS, FCT and brain histology did not show any statistically significant difference between groups. CONCLUSIONS: Nitrite, administered early after ROSC from VF, was shown to cross the blood brain barrier after a 5 min VF cardiac arrest. We characterized the PK of intravenous nitrite administration after VF and were able to demonstrate nitrite safety in this feasibility study.

Growth differentiation factor-15 predicts poor survival after cardiac arrest.

BACKGROUND: Early prognostication in post-cardiac arrest (CA) patients remains challenging and biomarkers have evolved as helpful tools in risk assessment. The stress-response cytokine growth differentiation factor-15 (GDF-15) is dramatically up-regulated during various kinds of tissue injury and predicts outcome in many pathological conditions. We aimed to assess the predictive value of circulating GDF-15 in post-CA patients. METHODS: This prospective observational study included 128 consecutive patients (median age 60.3 years, 75.8% male) with return of spontaneous circulation after in- or out-of-hospital CA who were treated at a tertiary university hospital. GDF-15 serum levels were determined at admission. RESULTS: A total of 52 patients (40.6%) died during the 6-month follow-up. Median GDF-15 levels were significantly lower in survivors (1601 ng/L (interquartile range: 1114-2983 ng/L) than in non-survivors (3172 ng/L (1927-8340 ng/L); p < 0.001). GDF-15 levels were also significantly lower in patients with favourable neurological 6-month outcome (cerebral performance category (CPC) 1-2) than in those with poor neurological outcome (CPC 3-5; p < 0.001). GDF-15 significantly predicted 6-month mortality in univariate Cox regression analysis (hazard ratio (HR) per 1-standard deviation increase 1.76 [95% confidence interval (CI) 1.35-2.31; p < 0.001] and remained significant after multivariable adjustment (HR 1.57 [95% CI 1.19-2.07; p = 0.001]). Subgroup analysis revealed that the association between GDF-15 and 6-month outcome was present both in patients with in- and out-of-hospital CA. CONCLUSIONS: GDF-15 predicts poor survival and neurological outcome in post-CA patients. GDF-15 may reflect the extent of hypoxic injury to the brain and other organs and might help to improve early risk stratification after CA.

Aortic stenosis is an independent predictor for outcome in patients with in-hospital cardiac arrest.

BACKGROUND: Prognostic tools for decision-making whether to continue advanced life support or limit life sustaining interventions in In-Hospital Cardiac Arrest (IHCA), remain scarce and inconclusive. In this regard it seems intuitive that the presence of aortic stenosis (AS) impacts on both central and peripheral perfusion during resuscitative attempts and might worsen outcome. Therefore, we aimed to investigate the prognostic value of AS on outcome after IHCA. METHODS: Out of 11,641 patients presenting with acute coronary syndrome, a total of 151 patients were identified that received a standardized echocardiographic diagnostic immediately prior to an IHCA. Binary logistic regression analysis was used to elucidate the prognostic impact of AS on outcome. RESULTS: Within the entire study population, a total of 51 individuals with AS (mild: n = 19 [12.5%]; moderate: n = 11 [7.2%]; severe: n = 21 [13.8%]) were identified. We observed that 81% of patients with severe AS did not survive until hospital discharge. Additionally, the presence of AS showed a strong and independent inverse association with return of spontaneous circulation (adjusted odds ratio [OR] of 0.10 [95%CI:0.03-0.36], p < 0.001), survival (adj. OR of 0.14 [95%CI: 0.04-0.48]; p = 0.002) and favourable neurological outcome (OR of 0.16 [95%CI: 0.06-0.49]; p = 0.001). The observed prognostic impact remained stable irrespective of AS severity. CONCLUSION: AS proved to be a strong and independent predictor for mortality and poor outcome after IHCA. Therefore, the presence of AS mirrors an easily available predictive tool for risk stratification and decision-making.

Phenotyping Cardiac Arrest: Bench and Bedside Characterization of Brain and Heart Injury Based on Etiology.

OBJECTIVES: Cardiac arrest etiology may be an important source of between-patient heterogeneity, but the impact of etiology on organ injury is unknown. We tested the hypothesis that asphyxial cardiac arrest results in greater neurologic injury than cardiac etiology cardiac arrest (ventricular fibrillation cardiac arrest), whereas ventricular fibrillation cardiac arrest results in greater cardiovascular dysfunction after return of spontaneous circulation. DESIGN: Prospective observational human and randomized animal study. SETTING: University laboratory and ICUs. PATIENTS: Five-hundred forty-three cardiac arrest patients admitted to ICU. SUBJECTS: Seventy-five male Sprague-Dawley rats. INTERVENTIONS: We examined neurologic and cardiovascular injury in Isoflurane-anesthetized rat cardiac arrest models matched by ischemic time. Hemodynamic and neurologic outcomes were assessed after 5 minutes no flow asphyxial cardiac arrest or ventricular fibrillation cardiac arrest. Comparison was made to injury patterns observed after human asphyxial cardiac arrest or ventricular fibrillation cardiac arrest. MEASUREMENTS AND MAIN RESULTS: In rats, cardiac output (20 ± 10 vs 45 ± 9 mL/min) and pH were lower and lactate higher (9.5 ± 1.0 vs 6.4 ± 1.3 mmol/L) after return of spontaneous circulation from ventricular fibrillation cardiac arrest versus asphyxial cardiac arrest (all p < 0.01). Asphyxial cardiac arrest resulted in greater early neurologic deficits, 7-day neuronal loss, and reduced freezing time (memory) after conditioned fear (all p < 0.05). Brain antioxidant reserves were more depleted following asphyxial cardiac arrest. In adjusted analyses, human ventricular fibrillation cardiac arrest was associated with greater cardiovascular injury based on peak troponin (7.8 ng/mL [0.8-57 ng/mL] vs 0.3 ng/mL [0.0-1.5 ng/mL]) and ejection fraction by echocardiography (20% vs 55%; all p < 0.0001), whereas asphyxial cardiac arrest was associated with worse early neurologic injury and poor functional outcome at hospital discharge (n = 46 [18%] vs 102 [44%]; p < 0.0001). Most ventricular fibrillation cardiac arrest deaths (54%) were the result of cardiovascular instability, whereas most asphyxial cardiac arrest deaths (75%) resulted from neurologic injury (p < 0.0001). CONCLUSIONS: In transcending rat and human studies, we find a consistent phenotype of heart and brain injury after cardiac arrest based on etiology: ventricular fibrillation cardiac arrest produces worse cardiovascular dysfunction, whereas asphyxial cardiac arrest produces worsened neurologic injury associated with greater oxidative stress.

The impact of airway strategy on the patient outcome after out-of-hospital cardiac arrest: A propensity score matched analysis.

BACKGROUND: While guidelines mentioned supraglottic airway management in the case of out-of- hospital cardiac arrest, robust data of their impact on the patient outcome remain scare and results are inconclusive. METHODS: To assess the impact of the airway strategy on the patient outcome we prospectively enrolled 2224 individuals suffering cardiac arrest who were treated by the Viennese municipal emergency medical service. To control for potential confounders, propensity score matching was performed. Patients were matched in four groups with a 1:1:1:1 ratio ( n=210/group) according to bag-mask-valve, laryngeal tube, endotracheal intubation and secondary endotracheal intubation after primary laryngeal tube ventilation. RESULTS: The laryngeal tube subgroup showed the lowest 30-day survival rate among all tested devices ( p<0.001). However, in the case of endotracheal intubation after primary laryngeal tube ventilation, survival rates were comparable to the primary endotracheal tube subgroup. The use of a laryngeal tube was independently and directly associated with mortality with an adjusted odds ratio of 1.97 (confidence interval: 1.14-3.39; p=0.015). Additionally, patients receiving laryngeal tube ventilation showed the lowest rate of good neurological performance (6.7%; p<0.001) among subgroups. However, if patients received endotracheal intubation after initial laryngeal tube ventilation, the outcome proved to be significantly better (9.5%; p<0.001). CONCLUSION: We found that the use of a laryngeal tube for airway management in cardiac arrest was significantly associated with poor 30-day survival rates and unfavourable neurological outcome. A primary endotracheal airway management needs to be considered at the scene, or an earliest possible secondary endotracheal intubation during both pre-hospital and in-hospital post-return of spontaneous circulation critical care seems crucial and most beneficial for the patient outcome.

Mechanistic characterization of nitrite-mediated neuroprotection after experimental cardiac arrest.

Nitrite acts as an ischemic reservoir of nitric oxide (NO) and a potent S-nitrosating agent which reduced histologic brain injury after rat asphyxial cardiac arrest (ACA). The mechanism(s) of nitrite-mediated neuroprotection remain to be defined. We hypothesized that nitrite-mediated brain mitochondrial S-nitrosation accounts for neuroprotection by reducing reperfusion reactive oxygen species (ROS) generation. Nitrite (4 µmol) or placebo was infused IV after normothermic (37°C) ACA in randomized, blinded fashion with evaluation of neurologic function, survival, brain mitochondrial function, and ROS. Blood and CSF nitrite were quantified using reductive chemiluminescence and S-nitrosation by biotin switch. Direct neuroprotection was verified in vitro after 1 and 4 h neuronal oxygen glucose deprivation measuring neuronal death with inhibition studies to examine mechanism. Mitochondrial ROS generation was quantified by live neuronal imaging using mitoSOX. Nitrite significantly reduced neurologic disability after ACA. ROS generation was reduced in brain mitochondria from nitrite- versus placebo-treated rats after ACA with congruent preservation of brain ascorbate and reduction of ROS in brain sections using immuno-spin trapping. ATP generation was maintained with nitrite up to 24 h after ACA. Nitrite rapidly entered CSF and increased brain mitochondrial S-nitrosation. Nitrite reduced in vitro mitochondrial superoxide generation and improved survival of neurons after oxygen glucose deprivation. Protection was maintained with inhibition of soluble guanylate cyclase but lost with NO scavenging and ultraviolet irradiation. Nitrite therapy results in direct neuroprotection from ACA mediated by reductions in brain mitochondrial ROS in association with protein S-nitrosation. Neuroprotection is dependent on NO and S-nitrosothiol generation, not soluble guanylate cyclase.

Admission of out-of-hospital cardiac arrest victims to a high volume cardiac arrest center is linked to improved outcome.

AIM: Cardiac arrest centers have been associated with improved outcome for patients after cardiac arrest. Aim of this study was to investigate the effect on outcome depending on admission to high-, medium- or low volume centers. METHODS: Analysis from a prospective, multicenter registry for out of hospital cardiac arrest patients treated by the emergency medical service of Vienna, Austria. The frequency of cardiac arrest patients admitted per center/year (low <50; medium 50-100; high >100) was correlated to favorable outcome (30-day survival with cerebral performance category of 1 or 2). RESULTS: Out of 2238 patients (years 2013-2015) with emergency medical service resuscitation, 861 (32% female, age 64 (51;73) years) were admitted to 7 different centers. Favorable outcome was achieved in 267 patients (31%). Survivors were younger (58 vs. 66 years; p<0.001), showed shockable initial heart rhythm more frequently (72 vs. 35%; p<0.001), had shorter CPR durations (22 vs. 29min; p<0.001) and were more likely to be treated in a high frequency center (OR 1.6; CI: 1.2-2.1; p=0.001). In multivariate analysis, age below 65 years (OR 15; CI: 3.3-271.4; p=0.001), shockable initial heart rhythm (OR 10.1; CI: 2.4-42.6; p=0.002), immediate bystander or emergency medical service CPR (OR 11.2; CI: 1.4-93.3; p=0.025) and admission to a center with a frequency of >100 OHCA patients/year (OR 5.2; CI: 1.2-21.7; p=0.025) was associated with favorable outcome. CONCLUSIONS: High frequency of post-cardiac arrest treatment in a specialized center seems to be an independent predictor for favorable outcome in an unselected population of patients after out of hospital cardiac arrest.

Editor's Choice-Progress in the chain of survival and its impact on outcomes of patients admitted to a specialized high-volume cardiac arrest center during the past two decades.

AIM: Cardiac arrest (CA) is still associated with high mortality and morbidity. Data on the changes in management and outcomes over a long period of time are limited. Using data from a single emergency department (ED), we assessed changes over two decades. METHODS: In this single-center observational study, we prospectively included 4133 patients receiving cardiopulmonary resuscitation and being admitted to the ED of a tertiary care hospital between January 1992 and December 2012. RESULTS: There was a significant improvement in both 6-month survival rates (+10.8%; p < 0.001) and favorable neurological outcome (+4.7%; p < 0.001). While the number of witnessed CA cases decreased (-4.7%; p < 0.001) the proportion of patients receiving bystander basic life support increased (+8.3%; p < 0.001). The proportion of patients with initially shockable ECG rhythms remained unchanged, but cardiovascular causes of CA decreased (-9.6%; p < 0.001). Interestingly, the time from CA until ED admission increased (+0.1 hours; p = 0.024). The use of percutaneous coronary intervention and therapeutic hypothermia were significantly associated with survival. CONCLUSIONS: Outcomes of patients with CA treated at a specialized ED have improved significantly within the last 20 years. Improvements in every link in the chain of survival were noted.

Socioeconomic factors associated with outcome after cardiac arrest in patients under the age of 65.

AIM: In a prior study of seven North American cities Pittsburgh had the highest crude rate of cardiac arrest deaths in patients 18 to 64 years of age, particularly in neighborhoods with lower socioeconomic status (SES). We hypothesized that lower SES, associated poor health behaviors (e.g., illicit drug use) and pre-existing comorbid conditions (grouped as socioeconomic factors [SE factors]) could affect the type and severity of cardiac arrest, thus outcomes. METHODS: We retrospectively identified patients aged 18 to 64 years treated for in-hospital (IHCA) and out-of hospital arrest (OHCA) at two Pittsburgh hospitals between January 2010 and July 2012. We abstracted data on baseline demographics and arrest characteristics like place of residence, insurance and employment status. Favorable cerebral performance category [CPC] (1 or 2) was our primary outcome. We examined the associations between SE factors, cardiac arrest variables and outcome as well as post-resuscitation care. RESULTS: Among 415 subjects who met inclusion criteria, unfavorable CPC were more common in patients who were unemployed, had a history of drug abuse or hypertension. In OHCA, favorable CPC was more often associated with presentation with ventricular fibrillation/tachycardia (OR 3.53, 95% CI 1.43-8.74, p = 0.006) and less often associated with non-cardiovascular arrest etiology (OR 0.22, 95% CI 0.08-0.62, p = 0.004). We found strong associations between specific SE factors and arrest factors associated with outcome in OHCA patients only. Significant differences in post-resuscitation care existed based on injury severity, not on SES. CONCLUSIONS: SE factors strongly influence type and severity of OHCA but not IHCA resulting in an association with outcomes.

Quality of post arrest care does not differ by time of day at a specialized resuscitation center.

Previous studies suggest worse outcomes after out-of-hospital cardiac arrest (OHCA) at night. We analyzed whether patients admitted after nontraumatic OHCA to a resuscitation center received the same quality post arrest care at day and night and whether quality of care affected clinical outcomes. We analyzed data of OHCA patients with return of spontaneous circulation admitted to the Vienna general hospital emergency department between January 2006 and May 2013. Data reported include admission time (day defined from 8 AM to 4 PM based on staffing), time to initiation of hypothermia, and door-to-balloon time in patients with ST-elevation myocardial infarction. Survival and cognitive performance at 12 months were assessed. In this retrospective observational study, 1059 patients (74% males, n = 784) with a mean age of 58 ±â€Š16 years were analyzed. The vast majority was treated with induced hypothermia (77% of day vs. 79% of night admissions, P = 0.32) within 1 hour of admission (median time admission to cooling 27 (confidence interval [CI]: 10-60) vs. 23 (CI: 11-59) minutes day vs. night, P = 0.99). In 298 patients with ST-elevation myocardial infarction, median door-to-balloon time did not differ between day and night admissions (82 minutes, CI: 60 to 142 for day vs. 86 minutes, CI: 50 to 135 for night, P = 0.36). At 12 months, survival was recorded in 238 of 490 day and 275 of 569 night admissions (49% vs. 48%, P = 0.94%), and a good neurologic outcome was recorded in 210 of 490 day and 231 of 569 night admissions (43% vs. 41%, P = 0.46). Patients admitted to our department after OHCA were equally likely to receive timely high-quality postresuscitation care irrespective of time of day. Survival and good neurologic outcome at 12 months did not differ between day and night admissions. Our results may support the concept of specialized post arrest care centers.

Survivors of cardiac arrest with good neurological outcome show considerable impairments of memory functioning.

BACKGROUND: Deficits in cognitive function are a well-known dysfunction in survivors of cardiac arrest. However, data concerning memory function in this neurological vulnerable patient collective remain scarce and inconclusive. Therefore, we aimed to assess multiple aspects of retrospective and prospective memory performance in patients after cardiac arrest. METHODS: We prospectively enrolled 33 survivors of cardiac arrest, with cerebral performance categories (CPC) 1 and 2 and a control-group (n=33) matched in sex, age and educational-level. To assess retrospective and prospective memory performance we administrated 4 weeks after cardiac arrest the "Rey Adult Learning Test" (RAVLT), the "Digit-Span-Backwards Test", the "Logic-Memory Test" and the "Red-Pencil Test". RESULTS: Results indicate an impairment in immediate and delayed free recall, but not in recognition. However, the overall impairment in immediate recall was qualified by analyzing RAVLT performance, showing that patients were only impaired in trials 4 and 5 of the learning sequence. Moreover, working and prospective memory as well as prose recall were worse in cardiac arrest survivors. Cranial computed tomography was available in 61% of all patients (n=20) but there was no specific neurological damage detectable that could be linked to this cognitive impairment. CONCLUSION: Episodic long-term memory functioning appears to be particularly impaired after cardiac arrest. In contrast, short-term memory storage, even tested via free-call, seems not to be affected. Based on cranial computed tomography we suggest that global brain ischemia rather than focal brain lesions appear to underlie these effects.

Prehospital surface cooling is safe and can reduce time to target temperature after cardiac arrest.

PURPOSE: Mild therapeutic hypothermia proved to be beneficial when induced after cardiac arrest in humans. Prehospital cooling with i.v. fluids was associated with adverse side effects. Our primary objective was to compare time to target temperature of out-of hospital cardiac arrest patients cooled non-invasively either in the prehospital setting vs. the in-hospital (IH) setting, to assess surface-cooling safety profile and long term outcome. METHODS: In this retrospective, single center cohort study, a group of adult patients with restoration of spontaneous circulation (ROSC) after out-of hospital cardiac arrest were cooled with a surface cooling pad beginning either in the prehospital or IH setting for 24h. Time to target temperature (33.9°C), temperature on admission, time to admission after ROSC and outcome were compared. Also, rearrests and pulmonary edema were assessed. Neurologic outcome at 12 months was evaluated (Cerebral Performance Category, CPC 1-2, favorable outcome). RESULTS: Between September 2005 and February 2010, 56 prehospital cooled patients and 54 IH-cooled patients were treated. Target temperature was reached in 85 (66-117)min (prehospital) and in 135 (102-192)min (IH) after ROSC (p<0.001). After prehospital cooling, hospital admission temperature was 35.2 (34.2-35.8)°C, and in the IH-cooling patients initial temperature was 35.8 (35.2-36.3)°C (p=0.001). No difference in numbers of rearrests and pulmonary edema between groups was observed. In both groups, no skin lesions were observed. Favorable outcome was reached in 26.8% (prehospital) and in 37.0% (IH) of the patients (p=0.17). CONCLUSIONS: Using a non-invasive prehospital surface cooling method after cardiac arrest, target temperature can be reached faster without any major complications than starting cooling IH. The effect of early non-invasive cooling on long-term outcome remains to be determined in larger studies.

Regional TNFα mapping in the brain reveals the striatum as a neuroinflammatory target after ventricular fibrillation cardiac arrest in rats.

Cardiac arrest (CA) triggers neuroinflammation that could play a role in a delayed neuronal death. In our previously established rat model of ventricular fibrillation (VF) CA characterized by extensive neuronal death, we tested the hypothesis that individual brain regions have specific neuroinflammatory responses, as reflected by regional brain tissue levels of tumor necrosis factor (TNF)α and other cytokines. In a prospective study, rats were randomized to 6min (CA6), 8min (CA8) or 10min (CA10) of VF CA, or sham group. Cortex, striatum, hippocampus and cerebellum were evaluated for TNFα and interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-12 and interferon gamma at 3h, 6h or 14 d after CA by ELISA and Luminex. Immunohistochemistry was used to determine the cell source of TNFα. CA resulted in a selective TNFα response with significant regional and temporal differences. At 3h after CA, TNFα-levels increased in all regions depending on the duration of the insult. The most pronounced increase was observed in striatum that showed 20-fold increase in CA10 vs. sham, and 3-fold increase vs. CA6 or CA8 group, respectively (p<0.01). TNFα levels in striatum decreased between 3h and 6h, but increased in other regions between 3h and 14 d. TNFα levels remained twofold higher in CA6 vs. shams across brain regions at 14 d (p<0.01). In contrast to pronounced TNFα response, other cytokines showed only a minimal increase in CA6 and CA8 groups vs. sham in all brain regions with the exception that IL-1ß increased twofold in cerebellum and striatum (p<0.01). TNFα colocalized with neurons. In conclusion, CA produced a duration-dependent acute TNFα response, with dramatic increase in the striatum where TNFα colocalized with neurons. Increased TNFα levels persist for at least two weeks. This TNFα surge contrasts the lack of an acute increase in other cytokines in brain after CA. Given that striatum is a selectively vulnerable brain region, our data suggest possible role of neuronal TNFα in striatum after CA and identify therapeutic targets for future experiments. This study was approved by the University of Pittsburgh IACUC 1002340A-3.