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. 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. 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. 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.
Summary Aim The earliest initiation of mild hypothermia after resuscitation from cardiac arrest is crucial. This study aimed to evaluate the feasibility and safety of out-of-hospital surface cooling ...in such cases. Methods Cooling pads stored below 0 °C in the ambulance were applied as soon as possible after restoration of spontaneous circulation in the out-of-hospital setting. This continued in the emergency department until an oesophageal temperature of 34 °C was reached, when the pads were removed. A target temperature of 33 °C was maintained for 24 h. Results are given as median and interquartile range. Results From September 2006 to January 2007, 15 victims of cardiac arrest were included. Cooling was initiated at 12 (8.5–15) min after restoration of spontaneous circulation. Oesophageal temperatures decreased from 36.6 (36.2–36.6) °C to 33 °C within 70 (55–106) min. Hospital admission was at 45 (34–52) min, with oesophageal temperatures of 35.4 (34.6–35.9)°C; the target 33 °C was achieved 50 (29–82) min after admission. No skin lesions were observed. Conclusion Non-invasive surface cooling immediately after resuscitation from cardiac arrest, in the out-of-hospital setting, proved to be feasible, fast and safe. Whether early cooling will improve neurological outcome needs to be determined in future studies.
Abstract 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. 29 min; 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.
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;
<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.
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.
We examined the mechanism whereby early nitrite therapy is protective after resuscitation from asphyxial cardiac arrest. We found that nitrite rapidly crosses the blood–brain barrier and S‐nitrosates mitochondrial proteins with associated reductions in superoxide (O2−) and peroxide (H2O2) generation. Using pharmacologic inhibition studies in a neuronal oxygen glucose deprivation model, we demonstrated that nitrite‐mediated protection is dependent on nitric oxide (NO) formation and cysteine S‐nitrosation rather than the classical soluble guanylate cyclase (sGC) pathway.
Summary Aim of the study There is sufficient evidence that therapeutic hypothermia after non-traumatic cardiac arrest improves neurological outcome and reduces mortality. Many different invasive and ...non-invasive cooling devices are currently available. Our purpose was to show the efficacy, safety and feasibility using a non-invasive cooling device to control patient temperature within a range of 33–37 °C. Materials and methods A convenience sample of patients who have been resuscitated successfully from cardiac arrest and were intended for mild hypothermia therapy according to the guidelines and inclusion criteria were studied in a prospective observational case series at an emergency department of a tertiary care university hospital. The Medivance Arctic Sun System provides a new, non-invasive approach to reach a target temperature of 33 °C quickly, to maintain the target temperature for 24 h, and then to actively re-warm at 0.4 °C/h to normothermia. Cooling was applied using the Arctic Sun in 27 patients. Data are presented as median and the interquartile range (25, 75%). Results Median age was 58 (49.5, 70) years. Time from cooling start to target temperature was 137 (96, 168) min, cooling rate was 1.2 °C/h (0.8, 1.5), stability of target temperature during hypothermia maintenance phase was satisfactory at 33.0 °C (32.9, 33.1), and duration of re-warming was 428 (394, 452) min. Conclusion Using the Arctic Sun System in post-resuscitation care medicine for cooling cardiac arrest survivors is feasible and has proven to be highly effective in lowering patients’ temperature rapidly without inducing skin irritations.
Figure 2 – Graphical abstract (ambulance car pictographs by Lukas Huber, with kind permission).
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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.
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)diazenylphenyldiazenyl-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.
Abstract 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 24 h. 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.
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