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INTRODUCTION: The aim of the EuReCa ONE study was to determine the incidence, process, and outcome for out of hospital cardiac arrest (OHCA) throughout Europe.METHODS: This was an international, pr ...

Objectives Regional anesthesia for patients undergoing carotid endarterectomy is associated with improved intraoperative hemodynamic stability compared with general anesthesia. The authors hypothesized that the reported advantages might be related to attenuated ipsilateral baroreflex control of blood pressure, caused by chemical denervation of the carotid bulb baroreceptor nerve fibers. Design A prospective cohort study. Setting Single-center university hospital. Participants The study included 46 patients undergoing carotid endarterectomy using superficial cervical block. Interventions A noninvasive computational periprocedural measurement of baroreceptor sensitivity was performed in all patients. Two groups were formed, depending on the patients’ subjective response to surgical stimulation regarding the necessity of additional intraoperative local anesthesia (LA) administration on the carotid bulb. Group A (block alone) included 23 patients who required no additional anesthesia, and group B (block + LA) consisted of 23 patients who required additional anesthesia. Measurements and Main Results Baroreceptor sensitivity showed no significant change after application of the block in both groups (group A: median [IQR], 5.19 [3.07-8.54] v 4.96 [3.1-9.07]; p = 0.20) (group B: median [IQR], 4.47 [3.36-8.09] v 4.53 [3.29-8.01]; p = 0.55). There was a significant decrease in baroreceptor sensitivity in group B after intraoperative LA administration (median [IQR], 4.53 [3.29-8.01] v 3.31 [2.26-7.31]; p = 0.04). Conclusions Standard superficial cervical plexus block did not impair local baroreceptor function, and, therefore, it was not related to improved cerebral perfusion in awake patients undergoing carotid endarterectomy. However, direct infiltration of the carotid bulb was associated with the expected attenuation of baroreflex sensitivity.

Animal studies and pathophysiological considerations suggest that therapeutic hypothermia after cardiopulmonary resuscitation is the more effective the earlier it is induced. Therefore this study is sought to examine whether pharmacological facilitated hypothermia by administration of 5'-adenosine monophosphate (AMP) is neuroprotective in a rat model of cardiac arrest (CA) and resuscitation.Sixty-one rats were subjected to CA. After 6 min of ventricular fibrillation advanced cardiac life support was started. After successful return of spontaneous circulation (ROSC, n=40), animals were randomized either to placebo group (n=14) or AMP group (800 mg/kg body weight, n=14). Animals were kept at an ambient temperature of 18°C for 12 h after ROSC and core body temperature was measured using a telemetry temperature probe. Neuronal damage was analyzed by counting Nissl-positive (i.e. viable) neurons and TUNEL-positive (i.e. apoptotic) cells in coronal brain sections 7 days after ROSC. Functional status evaluated on days 1, 3 and 7 after ROSC by a tape removal test.Time until core body temperature dropped to34.0°C was 31 min [28; 45] in AMP-treated animals and 125 min [90; 180] in the control group (p=0.003). Survival until 7 days after ROSC was comparable in both groups. Also number of Nissl-positive cells (AMP: 1 [1; 7] vs. placebo: 2 [1; 3] per 100 pixel; p=0.66) and TUNEL-positive cells (AMP: 56 [44; 72] vs. placebo: 53 [41; 67] per 100 pixel; p=0.70) did not differ. Neither did AMP affect functional neurological outcome up to 7 days after ROSC. Mean arterial pressure 20 min after ROSC was 49 [45; 55] mmHg in the AMP group in comparison to 91 [83; 95] mmHg in the control group (p0.001).Although application of AMP reduced the time to reach a core body temperature of34°C neither survival was improved nor neuronal damage attenuated. Reason for this is probably induction of marked hypotension as an adverse reaction to AMP treatment.

Post-resuscitation myocardial dysfunction is an important cause of death in the intensive care unit after initially successful cardiopulmonary resuscitation (CPR) of pre-hospital cardiac arrest (CA) patients. Volatile anaesthetics reduce ischaemic-reperfusion injury in regional ischaemia in beating hearts. This effect, called anaesthetic-induced pre- or postconditioning, can be shown when the volatile anaesthetic is given either before regional ischaemia or in the reperfusion phase. However, up to now, little data exist for volatile anaesthetics after global ischaemia due to CA. Therefore, the goal of this study was to clarify whether Sevoflurane improves post-resuscitation myocardial dysfunction after CA in rats. Following institutional approval by the Governmental Animal Care Committee, 144 male Wistar rats (341±19g) were randomized either to a control group or to one of the 9 interventional groups receiving 0.25 MAC, 0.5 MAC or 1 MAC of Sevoflurane for 5min either before resuscitation (SBR), during resuscitation (SDR) or after resuscitation (SAR). After 6min of electrically induced ventricular fibrillation CPR was performed. Before CA (baseline) as well as 1h and 24h after restoration of spontaneous circulation (ROSC), continuous measurement of ejection fraction (EF), and preload adjusted maximum power (PAMP) as primary outcome parameters and end systolic pressure (ESP), end diastolic volume (EDV) and maximal slope of systolic pressure increment (dP/dtmax) as secondary outcome parameters was performed using a conductance catheter. EF was improved in all Sevoflurane treated groups 1h after ROSC in comparison to control, except for the 0.25 MAC SDR and 0.25 MAC SAR group (0.25 MAC SBR: 38±8, p=0.02; 0.5 MAC SBR: 39±7, p=0.04; 1 MAC SBR: 40±6, p=0.007; 0.5 MAC SDR: 38±7, p=0.02; 1 MAC SDR: 40±6, p=0.006; 0.5 MAC SAR: 39±6, p=0.01; 1 MAC SAR: 39±6, p=0.002, vs. 30±7%). Twenty-four hours after ROSC, EF was higher than control in all interventional groups (p0.05 for all groups). EF recovered to baseline values 24h after ROSC in all SBR and SAR groups. PAMP was improved in comparison to control (4.6±3.0mW/μl(2)) 24h after ROSC in 0.5 MAC SBR (9.4±6.9mW/μl(2), p=0.04), 1 MAC SBR (8.9±4.4mW/μl(2), p=0.04), 1 MAC SDR (8.0±5.7mW/μl(2), p=0.04), and 1 MAC SAR (7.3±3.5mW/μl(2), p=0.04). ESP, EDV, and dP/dtmax was not different from control 1h as well as 24h after ROSC with the exception of 1 MAC SDR with a reduced ESP 1h after ROSC (89±16 vs. 103±22mmHg, p=0.04). Sevoflurane treatment did not affect survival rate. This animal study of CA and resuscitation provides the hypothesis that pharmacological pre- or postconditioning with the volatile anaesthetic Sevoflurane - administered before CA, during resuscitation or after ROSC - results in an improved myocardial inotropy 24h after ROSC. Sevoflurane treatment seems to improve EF even in the early phase of reperfusion 1h after ROSC. Therefore further targeted studies on the optimal dose and time point of administration of Sevoflurane in cardiopulmonary resuscitation seem to be worthwhile (Institutional protocol number: 35-9185.81/G-24/08).

Aim of the study Therapeutic hypothermia improves outcome after cardiac arrest. Dopamine D 2 agonists and serotonin 5-HT 1A agonists lower body temperature by decreasing the set-point. We investigated the effect of these drugs on temperature and cerebral recovery of rats after cardiac arrest. Methods Male Wistar-Han rats were subjected to 6min of cardiac arrest due to ventricular fibrillation. Following restoration of circulation, 1mg quinpirole, 1mg 8-OH-DPAT or vehicle were injected subcutaneously. Body temperature was monitored for 48h. One additional group was kept normothermic. Animals were neurologically tested by a tape removal test. After 7 days, histology of hippocampal CA-1 sector was analysed with Nissl and TUNEL staining. Results Rats became spontaneously hypothermic after cardiac arrest. Induction of hypothermia was facilitated by both quinpirole (−0.033±0.008°C/min) and 8-OH-DPAT (−0.029±0.010°C/min) when compared to vehicle (−0.020±0.005°C/min). Total ‘dose' of hypothermia (area under the curve) was not different. All animals showed a neurological deficit, which improved with time; after 7 days, test results of the normothermic group (30 [11–88]s) still tended to be worse than those of the hypothermic groups (vehicle 8 [6–14]s, quinpirole 9 [4–17]s, 8-OH-DPAT 10 [8–22]s). There were no clear differences in Nissl or TUNEL histology after 7 days. Conclusion Both quinpirole and 8-OH-DPAT led to faster induction of hypothermia. However, the outcome was not different from spontaneous hypothermia, probably because the total ‘dose' of hypothermia was not influenced.

Subject Recent data demonstrated potent neuroprotective effects of growth hormones such as granulocyte colony-stimulating factor (G-CSF) after focal cerebral ischaemia. In order to assess possible effects of intracerebroventricular application of G-CSF on cerebral recovery after cardiac arrest (CA) in rats, neurological testing and histological analyses were performed. Interventions After 6min of electrically induced CA, rats were resuscitated (CPR) and divided into two groups (G-CSF vs. placebo) with two different reperfusion times (7 and 14 days). G-CSF (3.84μg) or placebo was applied 30min after restoration of spontaneous circulation (ROSC). At 24h, 3, 7, 10 and 14 days, behavioural neurological testing was done (tape removal test, TRT). Neuronal degeneration of the hippocampal CA-1 sector was analyzed by TUNEL- and Nissl-staining. Results Before CA all animals passed the TRT (G-CSF 7 [4–12] s, placebo 9 [6–10] s). After ROSC both groups showed a clear neurological deficit (24h: G-CSF and placebo 180 [180–180] s), that improved with ongoing reperfusion times, without reaching baseline values (14 days: G-CSF 25 [21–59] s, placebo 34 [14–175] s). Survival rates did not differ between the groups. All animals showed massive neurodegeneration histologically without any differences between the groups 7 days after CA (TUNEL-positive: G-CSF 63.2 [53.8–72.1], placebo 72.6 [66.6–82.7]; Nissl-positive: G-CSF 2.5 [1.8–3.4], placebo 2.8 [2.0–5.1]). At 14 days, TUNEL-staining revealed no differences (G-CSF 45.2 [35.0–60.0], placebo 56.0 [37.6–63.4]), while G-CSF treatment led to fewer Nissl-positive neurons (G-CSF 1.5 [1.2–2.2], placebo 3.1 [2.1–4.2]; p =0.011). Conclusions Despite promising experimental data concerning focal cerebral ischaemia, in this model of 6min of normothermic CA no beneficial effects of G-CSF application could be demonstrated by behavioural testing and histological analyses of the hippocampal CA-1 sector.

This study evaluated the time course of caspase activation in selectively vulnerable brain areas (hippocampus, nucleus reticularis thalami (NRT), cortex and striatum) following cardiopulmonary resuscitation (CPR) after global cerebral ischemia due to cardiac arrest (CA) in rats. Caspases are well known to play a crucial role in the apoptotic cascade and inflammatory syndromes and, therefore, represent potential therapeutic postischemic targets. Given the delayed neurodegeneration following CA, it is highly important to study the time course of caspase activation in regard to therapeutic interventions after CA. To assess caspase activity, in situ staining was applied to detect general caspase activity at 6h, 3d and 7d and caspase-3 activity at 3d after return of spontaneous circulation (ROSC). For detection of neuronal apoptosis, TUNEL staining was applied at 7d after ROSC. Distinct patterns of early caspase activation were observed at 6h and 3d in the NRT and striatum and of late activation at 7d in the hippocampal CA-1 sector. General caspase and caspase-3 activity correlated strongly at 3d after ROSC in all areas studied. At 7d, the TUNEL-positive neuron counts in the hippocampal CA-1 sector correlated strongly with caspase activation. In conclusion, general caspase and caspase-3 activity after 6 min of CA and the delayed occurrence of TUNEL-positive neurons strongly indicate that neuronal degeneration after CA is at least strongly associated with apoptosis. Therefore, postischemic antiapoptotic interventions might offer potential future therapeutic opportunities global cerebral ischemia due to CA.

Summary Background The response of the human body to cardiac arrest (CA) and cardiopulmonary resuscitation is characterised by excessive coagulation, inadequate endogenous anti-coagulation and fibrinolysis as well as an inflammatory syndrome that closely resembles the immunological profile observed in patients with sepsis. Recombinant human activated protein C (rhAPC) has been found to be protective in severe sepsis and in animal models of stroke and spinal cord injury. In the present study, we evaluated the effects of rhAPC on neurological outcome after CA in rats. Methods After 6min of CA and subsequent cardiopulmonary resuscitation, male Wistar rats were randomized into 3 treatment groups: high dose rhAPC (2mg/kg bolus and 0.1mg/(kgh) for 6h), low dose rhAPC (0.5mg/kg and 0.025mg/(kgh) for 6h), and placebo ( n =12 per treatment and reperfusion time). Neurological outcome was determined using a tape removal test and a composite neurological deficit score (NDS). As secondary measurements, we evaluated overall and neuronal survival, hippocampal caspase activity and inflammatory markers. Results No difference between groups was found with the NDS. The tape removal test showed only a transitory improvement in the low dose group at 3 d after CA ( P =0.041). No significant differences were observed for secondary measurements. Conclusion A clear and lasting effect of rhAPC on neurological outcome or inflammation after CA could not be shown in this study but the detailed analysis of the postresuscitation syndrome given here builds a firm basis for further research.

Summary Background After transient global cerebral ischaemia, selectively vulnerable areas of the brain show delayed neuronal degeneration. Recent data have demonstrated potent neuroprotective effects of the application of growth hormones like erythropoietin (EPO) after focal cerebral ischaemia. In order to assess possible effects of the application of EPO on cerebral recovery after cardiac arrest in rats, the vulnerable hippocampal CA-1 sector was investigated. Methods Thirty male Wistar rats were randomised into two groups (EPO versus placebo; n =15 per group). Cardiac arrest was induced by ventricular fibrillation during general anaesthesia. After 6min of global cerebral ischaemia, animals were resuscitated by external chest compressions combined with defibrillation. Investigator blinded bolus application of EPO (5000IE/kg bodyweight) and placebo was performed at three different time points, respectively: 5min before cardiac arrest (i.v.; intravenously), 24h (i.p.; intraperitoneally) and 72h (i.p.) after ischaemia. At 24h, 72h and 7days, animals were tested according to a neurological deficit score. After 7days of reperfusion, coronal brain sections were analysed by TUNEL- and Nissl-staining. A caspase activity assay was done to determine antiapoptotic properties of EPO. Statistical analyses were done using ANOVA. Results Neurological deficit scoring did not show differences between the groups. However, in all groups typical delayed neuronal degeneration could be found in the CA-1 sector. There was no difference in neuronal survival between the groups (viable neurons EPO (median [interquartile range]): 15.5 [10.1–21.3]; placebo: 16.8 [7.7–26.3]). Results from TUNEL-staining revealed no differences in the amount of apoptotic cell death between the groups (EPO: 71.2 [58.1–81.8]; placebo: 73.4 [67.8–78.2]). Caspase activity assays demonstrated a strong expression of general caspase activity as well as caspase-3 activity in the CA-1 sector and the nucleus reticularis thalami, without any differences between both groups. Conclusion Despite the well known neuroprotective properties of EPO in ischaemia induced neuronal degeneration, this study could not reveal any beneficial effects of EPO after global cerebral ischaemia due to cardiac arrest in rats.