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.

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.

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.

Pharmacological inhibition of pleckstrin homology domain leucine-rich repeat protein phosphatase is neuroprotective: differential effects on astrocytes.

Pleckstrin homology domain and leucine-rich repeat protein phosphatase 1 (PHLPP1) inhibits protein kinase B (AKT) survival signaling in neurons. Small molecule pan-PHLPP inhibitors (selective for PHLPP1 and PHLPP2) may offer a translatable method to induce AKT neuroprotection. We tested several recently discovered PHLPP inhibitors (NSC117079 and NSC45586; benzoic acid, 5-[2-[4-[2-(2,4-diamino-5-methylphenyl)diazenyl]phenyl]diazenyl]-2-hydroxy-,sodium salt.) in rat cortical neurons and astrocytes and compared the biochemical response of these agents with short hairpin RNA (shRNA)-mediated PHLPP1 knockdown (KD). In neurons, both PHLPP1 KD and experimental PHLPP inhibitors activated AKT and ameliorated staurosporine (STS)-induced cell death. Unexpectedly, in astrocytes, both inhibitors blocked AKT activation, and NSC117079 reduced viability. Only PHLPP2 KD mimicked PHLPP inhibitors on astrocyte biochemistry. This suggests that these inhibitors could have possible detrimental effects on astrocytes by blocking novel PHLPP2-mediated prosurvival signaling mechanisms. Finally, because PHLPP1 levels are reportedly high in the hippocampus (a region prone to ischemic death), we characterized hippocampal changes in PHLPP and several AKT targeting prodeath phosphatases after cardiac arrest (CA)-induced brain injury. PHLPP1 levels increased in rat brains subjected to CA. None of the other AKT inhibitory phosphatases increased after global ischemia (i.e., PHLPP2, PTEN, PP2A, and PP1). Selective PHLPP1 inhibition (such as by shRNA KD) activates AKT survival signaling in neurons and astrocytes. Nonspecific PHLPP inhibition (by NSC117079 and NSC45586) only activates AKT in neurons. Taken together, these results suggest that selective PHLPP1 inhibitors should be developed and may yield optimal strategies to protect injured hippocampal neurons and astrocytes-namely from global brain ischemia.

Cardiac arrest caused by acute intoxication-insight from a registry.

INTRODUCTION: The aim of the study was to evaluate the epidemiology and outcome after cardiac arrest caused by intoxication. METHODS: A retrospective analysis of 1991 to 2010 medical record of patients experiencing cardiac arrest caused by self-inflicted, intentional intoxication was performed. The setting was an emergency department of a tertiary care university hospital. The primary end point was the presentation of epidemiologic data in relation to favorable neurologic outcome, defined as cerebral performance categories 1 or 2 and 180-day survival. Furthermore, the patients were subdivided into a single-substance and polysubstance group, depending on the substances causing the intoxication. RESULTS: Of 3644 patients admitted to our department, 99 (2.7%) with a median age of 26 (interquartile range, 19-42) years (37% female) were included. Cardiac arrest was witnessed in 62 cases (63%). Eleven patients (11%) received basic life support by bystanders, and 11 (11%) had a shockable rhythm in the initial electrocardiogram. The combined end point "good survival" was achieved by 34 patients (34%). Cardiac arrest occurred out of hospital in 73 patients (74%) and in-hospital in 26 patients (26%). A single substance causing the intoxication was found in 56 patients (56%). Opiates were the leading substance, with 25 patients (25%) using them. CONCLUSION: Cardiac arrest caused by intoxication is found predominately in young patients. Overall, favorable neurologic survival was achieved in 34%. Opiate-related cardiac arrest was associated with poor survival and a high incidence of neurologic deficits.

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.

Mild therapeutic hypothermia improves outcomes compared with normothermia in cardiac-arrest patients--a retrospective chart review.

OBJECTIVE: Studies showing the effectiveness of therapeutic hypothermia (32-34°C) in postcardiac arrest patients have been criticized because of patients with elevated body temperature (>37.5°C) in the noncooled control group. Thus, the effects of spontaneous normothermia (<37.5°C) compared with mild therapeutic hypothermia were studied. DESIGN: Retrospective chart review from 1991 to 2010. PATIENTS: Witnessed out-of-hospital arrest, presumed to be of cardiac origin, aged 18 to 80 yrs and with a Glassgow Coma Scale score of <8 at admission. INTERVENTIONS: Patients with sustained restoration of spontaneous circulation who did not receive therapeutic hypothermia and never exceeded 37.5°C during the 36 hrs postcardiac arrest were compared with patients who received mild therapeutic hypothermia. MEASUREMENTS AND MAIN RESULTS: The primary end point was a favorable neurological outcome, defined as Cerebral Performance Categories 1 or 2; the secondary end point was overall survival to 180 days. Significantly more patients in the hypothermia group had Cerebral Performance Categories 1 or 2 (hypothermia: 256 of 467 [55%] vs. normothermia: 69 of 165 [42%]) and survived for >180 days (hypothermia: 315 of 467 [67%] vs. normothermia: 79 of 165 [48%]). The propensity score adjusted risk ratio for good neurological outcome of patients undergoing hypothermia treatment was 1.37 (confidence interval 1.09-1.72, p≤.01) and for dying within 180 days was 0.57 (confidence interval 0.44-0.73, p≤.01) compared to normothermia. CONCLUSIONS: Therapeutic hypothermia is associated with significantly improved neurological outcome and 180-day survival compared to spontaneous normothermia in cardiac-arrest patients.

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.

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.

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.

Temperature monitored on the cuff surface of an endotracheal tube reflects body temperature.

OBJECTIVE: When treating patients with cardiac arrest with mild therapeutic hypothermia, a reliable and easy-to-use temperature probe is desirable. This study was conducted to investigate the accuracy and safety of tracheal temperature as a measurement of body temperature. DESIGN: Observational cohort study. SETTING: Emergency department of a tertiary care university hospital. PATIENTS: Patients successfully resuscitated from cardiac arrest intended for mild hypothermia therapy. INTERVENTIONS: Intubation was performed with a newly developed endotracheal tube that contains a temperature sensor inside the cuff surface. During the cooling, mild hypothermia maintenance, and rewarming phases, the temperature was recorded minute by minute. These data were compared with the temperature assessed by esophageal and blood temperature probes. Thereafter, tracheoscopy was performed to evaluate the condition of the tracheal mucosa. MEASUREMENTS AND MAIN RESULTS: Approximately 2000 measurements per temperature sensor per patient were recorded in 21 patients. The mean bias between the blood temperature and the tracheal temperature was -0.16 degrees C (limits of agreement: -0.36 degrees C to 0.04 degrees C). The mean bias between the esophageal and tracheal temperatures was -0.22 degrees C (limits of agreement: -0.49 degrees C to 0.07 degrees C). Agreement between temperature probes investigated by the Bland-Altman method showed a mean bias of less than -(1/4) degrees C, and time lags assessed graphically by hysteresis plots were negligible. No clinically relevant injury to the tracheal mucosa was detected. CONCLUSION: Temperature monitoring at the cuff surface of an endotracheal tube is safe and provides accurate and reliable data in all phases of therapeutically induced mild hypothermia after cardiac arrest.

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.

Pronounced platelet hyperfunction in patients with cardiac arrest achieving restoration of spontaneous circulation.

OBJECTIVE: Markers of platelet activation are increased in patients undergoing cardiopulmonary resuscitation. Hyperfunctional platelets may contribute to impairment of microcirculatory function and overall poor outcome despite restoration of spontaneous circulation (ROSC). Patients with myocardial infarction have hyperfunctional platelets, which predict the degree of myocardial necrosis. Thus, we hypothesized that platelets may be even more activated in patients whose myocardial infarction leads to cardiac arrest and compared them with patients whose cardiac arrest was due to a noncardiac origin. DESIGN: Prospective observational study. SETTING: Emergency department of a tertiary care hospital. PATIENTS: One hundred four patients with witnessed cardiac arrest who achieved ROSC. INTERVENTIONS: Blood sampling. MEASUREMENTS AND MAIN RESULTS: We assessed collagen adenosine diphosphate closure time with the platelet function analyzer-100, and measured plasma levels of von Willebrand factor: ristocetin cofactor activity levels by turbidometry. Independent physicians diagnosed the origin of cardiac arrest. The majority of cardiac arrests were caused by myocardial ischemia. Invariably, collagen adenosine diphosphate closure time values (55 seconds; 95% confidence interval: 52-58 seconds) were much shorter in these patients compared with patients with other causes of cardiac arrest (110 seconds; 95% confidence interval: 84-135 seconds, p < 0.001). von Willebrand factor: ristocetin cofactor activity plasma levels were more than three-fold above normal values in both groups. CONCLUSIONS: Patients with myocardial ischemia-triggered cardiac arrest had the highest degree of platelet hyperfunction under high shear rates, which was not solely due to increased von Willebrand factor. Future trials are necessary to clarify whether rapid, more aggressive antiplatelet therapy improves outcome after cardiac arrest.

Effect of cooling after human cardiac arrest on myocardial infarct size.

AIMS: The Hypothermia after Cardiac Arrest (HACA) trial assessed whether mild therapeutic hypothermia improved the rate of good neurological recovery in patients after ventricular fibrillation cardiac arrest of presumed cardiac origin. We evaluated the impact of hypothermia on myocardial injury. METHODS: Re-analysis of a HACA trial subset for our department (cooling, n=55; controls, n=56). Plasma levels of CK, CKMB and ST-scores were used as a measure of infarct size. RESULTS: Area under the curve (AUC) for CK was 28,786U/l x 24 h (IQR 5646-44,998) in the cooling group and 20,373U/l x 24 h (IQR 8211-30,801) for controls (p=0.40), for CKMB AUC was 1691U/l x 24 h (IQR 724-3330) and 1187U/l x 24 h (IQR 490-2469), respectively (p=0.18). The ST score was -40% (IQR [-55]-[+16]) in the cooling group (n=23) and -22% (IQR [-84]-[+33]) for controls (n=24) (p=0.76). When the cooling group was stratified into early (< or =8h) and longer (>8h) time to target temperature, the early group displayed a significantly lower CK 7340U/l x 24 h (IQR 3921-33,753) vs. 38,986U/l x 24 h (IQR 23,945-57,514, p=0.007) and a lower CKMB. CONCLUSION: Cooling after successful resuscitation for ventricular fibrillation cardiac arrest did not influence infarct size. Cautious interpretation of the subgroup analysis may indicate a favourable trend for early cooling.

Head and neck cooling after cardiac arrest results in lower jugular bulb than esophageal temperature.

PURPOSE: To determine whether during the initial phase of head and neck cooling, jugular bulb temperature (Tjb; which may reflect brain temperature) is lower than esophageal temperature (Tes). BASIC PROCEDURES: To compare Tes and Tjb, patients received head or head and neck cooling after cardiac arrest. MAIN FINDINGS: The first series with head cooling (n = 5; mean age 54 with a range of 41-62 years; 1 female and 4 males; mean body weight 80 kg with a range of 70-85 kg) showed a mean difference of 0.22 degrees C (95% CI, -1.14 to 0.70; P = .55; limits of agreement, -3.17 to 2.73) between Tes and Tjb over 12 hours. For the second series, with head and neck cooling (n = 6, mean age 65 with a range of 56-76 years; 3 females and 3 males; mean body weight 75 kg with a range of 65-91 kg), Tjb was lower than Tes with a difference of 0.60 degrees C (95% CI, 0.22 to 0.99; P = .01; limits of agreement, -3.10 to 4.30). During the first 3 hours, Tjb decreased faster than Tes (1.1 degrees C/h [95% CI, 0.4 to 1.8; P < .01]). PRINCIPAL CONCLUSION: During the initial phase of therapeutic hypothermia, Tjb seems to be lower than Tes.

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.

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.

Thoracic-impedance changes measured via defibrillator pads can monitor signs of circulation.

AIMS: To investigate the potential for finding an alternative for the 'pulse check' during CPR, we studied the use of thoracic impedance measured via the defibrillator pads for circulation assessment during CPR. MATERIALS AND METHODS: Transthoracic impedance, ECG and arterial pressures were recorded on 69 patients with a resulting data set of 434 segments. The circulatory-related impedance waveform was first isolated manually and features characterising its shape were suggested. RESULTS: The features were correlated with corresponding blood pressure measurements, where a low, but significant, correlation coefficient (0.3) was found. By dividing the data set in groups of sufficient and insufficient circulation and using a neural network, we found that trends in features of the impedance waveform showed a discriminative potential for the two groups. Our classifier achieved a sensitivity of 90% for recognising insufficient circulation with a specificity of 82%. CONCLUSIONS: We have shown that the circulation-related information found in the impedance signal may be used for circulatory assessment, especially the recognition of restoration of spontaneous circulation after cardiac arrest.

Cold infusions alone are effective for induction of therapeutic hypothermia but do not keep patients cool after cardiac arrest.

AIM OF THE STUDY: Cold infusions have proved to be effective for induction of therapeutic hypothermia after cardiac arrest but so far have not been used for hypothermia maintenance. This study investigates if hypothermia can be induced and maintained by repetitive infusions of cold fluids and muscle relaxants. MATERIAL AND METHODS: Patients were eligible, if they had a cardiac arrest of presumed cardiac origin and no clinical signs of pulmonary oedema or severely reduced left ventricular function. Rocuronium (0.5 mg/kg bolus, 0.5 mg/kg/h for maintenance) and crystalloids (30 ml/kg/30 min for induction, 10 ml/kg every 6h for 24h maintenance) were administered via large bore peripheral venous cannulae. If patients failed to reach 33+/-1 degrees C bladder temperature within 60 min, endovascular cooling was applied. RESULTS: Twenty patients with a mean age of 57 (+/-15) years and mean body mass index of 27 (+/-4)kg/m(2) were included (14 males). Mean temperature at initiation of cooling (median 27 (IQR 16; 87)min after admission) was 35.4 (+/-0.9) degrees C. In 13 patients (65%) the target temperature was reached within 60 min, 7 patients (35%) failed to reach the target temperature. Maintaining the target temperature was possible in three (15%) patients and no adverse events were observed. CONCLUSION: Cold infusions are effective for induction of hypothermia after cardiac arrest, but for maintenance additional cooling techniques are necessary in most cases.