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Adrenaline improves regional cerebral blood flow, cerebral oxygenation and cerebral metabolism during CPR in a porcine cardiac arrest model using low-flow extracorporeal support
The effects of adrenaline on cerebral blood vessels during cardiopulmonary resuscitation (CPR) are not well understood. We developed an extracorporeal CPR model that maintains constant low systemic blood flow while allowing adrenaline-associated effects on cerebral vasculature to be assessed at different mean arterial pressure (MAP) levels independently of the effects on systemic blood flow.
Methods
After eight minutes of cardiac arrest, low-flow extracorporeal life support (ECLS) (30 ml/kg/min) was started in fourteen pigs. After ten minutes, continuous adrenaline administration was started to achieve MAP values of 40 (n = 7) or 60 mmHg (n = 7). Measurements included intracranial pressure (ICP), cerebral perfusion pressure (CePP), laser-Doppler-derived regional cerebral blood flow (CBF), cerebral regional oxygen saturation (rSO2), brain tissue oxygen tension (PbtO2) and extracellular cerebral metabolites assessed by cerebral microdialysis.
Results
During ECLS without adrenaline, regional CBF increased by only 5% (25th to 75th percentile: −3 to 14; p = 0.2642) and PbtO2 by 6% (0–15; p = 0.0073) despite a significant increase in MAP to 28 mmHg (25–30; p < 0.0001) and CePP to 10 mmHg (8–13; p < 0.0001). Accordingly, cerebral microdialysis parameters showed a profound hypoxic-ischemic pattern. Adrenaline administration significantly improved regional CBF to 29 ± 14% (p = 0.0098) and 61 ± 25% (p < 0.001) and PbtO2 to 15 ± 11% and 130 ± 82% (both p < 0.001) of baseline in the MAP 40 mmHg and MAP 60 mmHg groups, respectively. Importantly, MAP of 60 mmHg was associated with metabolic improvement.
Conclusion
This study shows that adrenaline administration during constant low systemic blood flow increases CePP, regional CBF, cerebral oxygenation and cerebral metabolism.
Administration of adrenaline during cardiopulmonary resuscitation (CPR) is primarily intended to increase coronary perfusion pressure and thereby coronary blood flow, which is closely associated with the return of spontaneous circulation (ROSC).
Equally important, adrenaline is thought to maintain minimal cerebral perfusion pressure (CePP) in order to prevent hypoxic-ischaemic brain damage, especially in the case of prolonged resuscitation. However, despite decades of use, there is still much doubt whether adrenaline improves or worsens the neurological outcome of cardiac arrest (CA) patients.
Evaluation of pre-hospital administration of adrenaline (epinephrine) by emergency medical services for patients with out of hospital cardiac arrest in Japan: controlled propensity matched retrospective cohort study.
Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry.
indicating that our understanding of adrenaline-associated effects on cerebral haemodynamics during CPR is rather limited. While CePP consistently increases following adrenaline administration, cerebral blood flow (CBF) improves in some studies and deteriorates in others due to disproportionate vasoconstriction.
Study of the effects of epinephrine on cerebral oxygenation and metabolism during cardiac arrest and resuscitation by hyperspectral near-infrared spectroscopy.
Undoubtedly, a certain degree of systemic vasoconstriction to increase perfusion pressure is necessary to allow organ blood flow; too much concomitant cerebral vasoconstriction, however, may have negative effects on brain perfusion.
The aim of the present study was to investigate the effect of adrenaline-triggered vasoconstriction on CBF and cerebral oxygen delivery during CPR and to evaluate whether these effects change in a dose-dependent manner. For this purpose, we used low-flow extracorporeal life support (ECLS) in a swine CA model providing a constant 30 ml/kg/min systemic blood flow to simulate basic life support (BLS). Subsequently, mean arterial pressure (MAP) was increased to 40 and 60 mmHg by continuous infusion of adrenaline to investigate the pressure-related effects of adrenaline on regional cerebral perfusion, cerebral oxygenation and cerebral metabolism.
Methods
This study was approved by the Institutional Animal Care and Use Committee of the University of Innsbruck and the Austrian Ministry of Science, Research and Economy (Protocol number: BMWFW-66.011/0121-V/3b/2018). It was conducted at the experimental research unit of the Department of Anaesthesiology and Intensive Care Medicine of the Medical University of Innsbruck in compliance with EU regulations for animal experimentation (Directive 2010/63/EU of the European Parliament and the European Council).
Animal preparation
Fourteen domestic pigs, weighing 37 ± 4 kg, were used. Sedation was achieved with azaperone [4 mg/kg intramuscular (IM); Jansen, Vienna, Austria], atropine (0.01 mg/kg IM), ketamine (30 mg/kg IM) and propofol [1 mg/kg intravenous (IV)]. After intubation during spontaneous ventilation, the pigs were curarized with rocuronium (1 mg/kg IV) and ventilated volume-controlled (Julian, Draeger, Lübeck, Germany) with 21% inspiratory oxygen. The tidal volume was set at 10 ml/kg body weight, the positive end-expiratory pressure at 5 mmHg and the ventilation rate was adjusted to maintain normocapnia (35–45 mmHg). Anaesthesia was maintained with propofol (6–8 mg/kg/h IV) and remifentanil (0.2–0.3 µg/kg/min IV) as previously described.
Elo-Mel isoton (Fresenius Kabi, Graz, Austria) was infused at 10 ml/kg/h IV to maintain normovolaemia.
Before starting invasive instrumentation 1.5 g IV cefuroxime was administered to prevent septic complications. Next, the scalp and galea aponeurotica were removed on the left hemisphere and two burr holes were drilled in the frontal cranial bone. Through one burr hole an intracranial pressure probe (Neurovent-P, Raumedic AG, Helmbrechts, Germany), a brain tissue oxygen catheter (LICOX, Sanova Pharma GmbH, Vienna, Austria) and a cerebral microdialysis (CMD) catheter (CMA-71, M Dialysis, Stockholm, Sweden) were inserted into the white matter of the frontal lobe. The flow rate of the CMD perfusion fluid (Perfusion Fluid CNS, M Dialysis, Stockholm, Sweden) was adjusted to 2.0 µl/min and samples were analysed with an Iscusflex device (M Dialysis, Stockholm, Sweden). Through the other burr hole a laser-Doppler flow probe (Periflux System 4000, PERIMED AB, Järfälla, Sweden) was fixed on the cortical surface. Then, a near-infrared spectroscopy (NIRS) optode (INVOSTM System, Somanetics Inc., Troy, MI, USA) was affixed to the scalp over the right hemisphere.
Next, a Swan-Ganz catheter (Edwards Lifesciences, Irvine, CA, USA) was inserted in the pulmonary artery via an 8.5 Fr internal jugular vein catheter (Arrow, Reading, PA, USA). A 6.0 Fr arterial catheter (Arrow, Reading, PA, USA) was inserted in the lower abdominal aorta via the left femoral artery. Intravascular catheters were attached to pressure transducers (Xtrans, Codan, Forstinning, Germany) and calibrated at the level of the right atrium, which in supine position corresponds to the level of the meatus acusticus externus.
Prior to cardiopulmonary bypass (CPB) cannulation, intravenous heparin (600 IU/kg IV) was given to prevent thrombus formation. A 15 Fr cannula (Bio-Medicus, Medtronic, Minneapolis, MN, USA) was placed in the right femoral artery and a 17 Fr cannula (Bio-Medicus, Medtronic, Minneapolis, MN, USA) in the left femoral vein. The CPB circuit included a centrifugal pump (Revolution Pump 5, Sorin Group, Limassol, Cyprus), a membrane oxygenator (A.L.ONE, Eurosets, Medolla, Italy) and a heat exchanger. Non-heparin-bonded polyvinyl chloride tubing was used and the priming was done with crystalloid solution (Elo-Mel isoton, Fresenius Kabi, Graz, Austria).
Standard surface electrocardiogram and haemodynamic and respiratory variables were continuously recorded (Datex-Ohmeda AS/3, GE Healthcare, Buckinghamshire, Great Britain) and simultaneously imported with the aid of specific software (Datex-Ohmeda S/5 collect, GE Healthcare, Buckinghamshire, Great Britain). Blood gases were analyzed with a blood gas analyzer (ABL800 Flex®; Radiometer, Brønshøj, Denmark).
Study protocol
After a stabilisation period following instrumentation, baseline values for haemodynamic, cerebral perfusion, oxygenation and metabolism parameters were recorded and blood gases taken. Ventricular fibrillation (VF) was induced by applying a 50-Hz, 60 V alternating current via two subcutaneous needle electrodes. Ventilation and intravenous anaesthesia were discontinued at this point. After eight minutes of untreated CA, low-flow ECLS was started with a constant flow rate of 30 ml/kg/min as previously reported.
After ten minutes of ECLS pigs were randomized to a study group. Continuous adrenaline administration was commenced and titrated to a target MAP of 40 mmHg (Group 1) or 60 mmHg (Group 2). After 20 minutes of ECLS with adrenaline support the animals were euthanized.
Measurement parameters
MAP, ICP and rSO2 were recorded at ten second intervals, while PbtO2 values were registered every minute. Perfusion units (PU) were monitored continuously and averaged over a 30-second time period at baseline, after eight minutes of CA and after 1, 5, 10, 11, 15, 20, 25 and 30 minutes of ECLS. CMD samples as well as arterial blood gases were obtained at baseline, after eight minutes of CA and after 5, 10, 15, 20, 25 and 30 minutes of ECLS. CPP was calculated as the difference between MAP and ICP.
Statistical analysis
Statistical analyses were performed using R, version 4.0.0. Continuous data are presented as median (25th to 75th percentile) and categorical variables as frequencies (%). Effect size and precision with estimated median differences (ED) between groups are shown for continuous data with 95% confidence interval (CI). All statistical assessments were two-sided, a significance level of 5% was used. The Wilcoxon rank sum test was applied to assess differences between groups. The course of continuously measured parameters is illustrated for each animal complemented by the mean course per group. Differences in time series are assessed using a linear mixed-effects model with random intercepts for animals as well as time points and the group as fixed effect. Effect size is given by the difference in mean between groups, with 95% CIs.
Results
The protocol was completed in all 14 animals. Baseline characteristics including blood gas values are presented in Fig. 1, Fig. 2, Fig. 3 and Table 1, Table 2.
Fig. 1Shown are the mean courses of mean arterial pressure (MAP), intracranial pressure (ICP), and cerebral perfusion pressure (CePP) for all animals during CA and ECSL alone (solid black) and for animals in the MAP 40 mmHg (solid blue) and the MAP 60 mmHg group (dashed red) during ECLS with adrenaline administration, complemented by the individual curves of each animal. CA denotes cardiac arrest and ECLS extracorporeal life support.
Fig. 2Shown are the mean courses of cerebral regional perfusion units (PU), cerebral regional oxygen saturation (rSO2) and brain tissue oxygen tension (PbtO2) for all animals during CA and ECSL alone (solid black) and for animals in the MAP 40 mmHg (solid blue) and the MAP 60 mmHg group (dashed red) during ECLS with adrenaline administration, complemented by the individual curves of each animal. CA denotes cardiac arrest and ECLS extracorporeal life support.
Fig. 3Values for the lactate-to-pyruvate ratio (L/P ratio) of all animals (n = 14) during extracorporeal life support (ECLS) before adrenaline administration are shown as grey bars and during ECLS with adrenaline administration as blue (MAP 40 mmHg group, n = 7) or red (MAP 60 mmHg group, n = 7) bars. Data are presented as medians (25th to 75th percentile). * indicates a significant change compared to the end of ECLS before adrenaline administration.
Table 1Blood gas and cerebral microdialysis parameters of all animals at baseline, end of cardiac arrest (CA) and after ten minutes of extracorporeal life support (ECLS) prior to adrenaline administration. Data are presented as medians (25th to 75th percentile) with estimated differences (ED) assessed by Wilcoxon Rank Sum Test. Hba denotes haemoglobin in arterial blood; paO2 and paCO2 partial pressure of oxygen and carbon dioxide in arterial blood; SaO2 and ScvO2 arterial and cerebral venous oxygen saturation; Laca and Laccv lactate in arterial and in cerebral venous blood; CMD cerebral microdialysis; L/P ratio lactate-to-pyruvate ratio.
Table 2Blood gas and cerebral microdialysis parameters of MAP 40 mmHg and MAP 60 mmHg animals during extracorporeal life support (ECLS) with adrenaline administration. Presented are the results from the linear mixed-effects models as means with standard deviation (SD) and estimated mean difference between groups. Hba denotes haemoglobin in arterial blood; paO2 and paCO2 partial pressure of oxygen and carbon dioxide in arterial blood; SaO2 and ScvO2 arterial and cerebral venous oxygen saturation; Laca and Laccv lactate in arterial and in cerebral venous blood; CMD cerebral microdialysis; L/P ratio lactate-to-pyruvate ratio.
Mean arterial, intracranial and cerebral perfusion pressure
With induction of CA, MAP decreased to hydrostatic pressure (p < 0.0001), while ICP initially increased (p < 0.0001) returning to baseline values until the end of CA. Accordingly, calculated CePP was always negative (corresponding to 0 mmHg) during untreated CA in all animals (Fig. 1). With commencement of low-flow ECLS, MAP increased to 28 mmHg (25th to 75th percentile: 25–30 mmHg; p < 0.0001) and CePP to 10 mmHg (8–13 mmHg; p < 0.0001), while ICP did not change (p = 0.1647). After starting adrenaline administration, the respective target MAP was reached after two minutes
in both groups (p = 0.2908), leading to mean CePP values of 24 mmHg in the MAP 40 mmHg group and 41 mmHg in the MAP 60 mmHg group. The estimated difference between groups was statistically significant [ED 17 mmHg with 95% CI [10 to 24]; p < 0.001]. MAP values were maintained unchanged until the end of the protocol, with pigs in the MAP 40 mmHg and the MAP 60 mmHg group receiving 12 ± 6 µg/kg/min and 47 ± 40 µg/kg/min adrenaline, respectively.
Laser-Doppler derived regional CBF: Perfusion units (PU)
With induction of CA, PU rapidly decreased to 10% (3–17; p < 0.0001) of baseline and did not change during ten minutes of ECLS prior to adrenaline administration [ED 5% (-3 to 14) p = 0.2642] (Fig. 2). With adrenaline administration PU increased to 29 ± 14% (p = 0.0098) of baseline in the MAP 40 mmHg group and to 61 ± 25% (p < 0.001) of baseline in the MAP 60 mmHg group. The ED of 32 [1–63] between groups was not significant (p = 0.0662).
Cerebral oxygenation: Regional oxygen saturation in brain tissue (rSO2) and partial pressure of oxygen in brain tissue (PbtO2)
With induction of CA, baseline rSO2 decreased from 52% [50–56] to 15% (15–15; p < 0.0001) and increased to 28% (23–33, p < 0.0001) after ten minutes of ECLS. After starting adrenaline administration, rSO2 decreased within one minute in all animals [ED 6% (1–7); p = 0.0059]. rSO2 remained low in both groups until the end of the experiment with no group difference [ED 0.1% (-8.8 to 9.0); p = 0.9839] (Fig. 2).
At baseline, the animals had a PbtO2 of 7.0 mmHg (5.9–10.1). After induction of CA, PbtO2 dropped to 0% (0–0; p < 0.0001) of baseline and increased to 6% (0–15; p = 0.0073) after ten minutes of ECLS in all animals. Adrenaline administration increased PbtO2 to 15 ± 11% (p < 0.001) in the MAP 40 mmHg group and to 130 ± 82% (p < 0.001) in the MAP 60 mmHg group, resulting in a significant group difference (p = 0.0362) (Fig. 2).
Cerebral metabolism parameters
Baseline lactate to pyruvate ratio (L/P ratio) in all animals increased from 30 (13–38) to 307 (229–445; p < 0.0001) during CA and ten minutes of ECLS (Table 1). With adrenaline administration, the L/P ratio significantly decreased to 183 (70–350; p = 0.0061) until the end of the experiment in all animals. On a group level, only the decrease in the MAP 60 mmHg group was significant (p = 0.0111) (Fig. 3). Cerebral glucose significantly decreased in all animals from 0.55 mM (0.32–0.72) to 0.1 mM (0.06–0.1; p < 0.0001) during CA and ten minutes of ECLS and significantly increased [ED 0.1 (0–0.2); p = 0.0423] after commencement of adrenaline administration until the end of the experiment. Mean values of cerebral metabolic parameters during 20 minutes of ECLS with adrenaline administration did not significantly differ between groups (Table 2).
Discussion
In this study, we observed that PbtO2 and NIRS values increased during low-flow ECLS whereas laser-Doppler derived regional CBF did not compared with no-flow cardiac arrest. After commencement of adrenaline administration targeting a MAP of 40 or 60 mmHg, regional CBF and PbtO2 increased and NIRS values decreased. Cerebral metabolism deteriorated during low-flow ECLS and significantly improved with adrenaline administration in the MAP 60 mmHg group.
During the first ten minutes of low-flow ECLS prior to adrenaline administration, MAP and CePP significantly increased and reached levels reported in previous experimental studies on BLS.
Increased cortical cerebral blood flow with LUCAS; a new device for mechanical chest compressions compared to standard external compressions during experimental cardiopulmonary resuscitation.
Comparison of a 10-breaths-per-minute versus a 2-breaths-per-minute strategy during cardiopulmonary resuscitation in a porcine model of cardiac arrest.
The effect of 50% compared to 100% inspired oxygen fraction on brain oxygenation and post cardiac arrest mitochondrial function in experimental cardiac arrest.
This increase in perfusion pressures, however, did not translate to a clinically relevant improvement in regional CBF (+5%) and cerebral oxygenation (+6%), resulting in a severe hypoxic pattern of extracellular cerebral metabolic parameters.
This observation may be explained by the fact that CePP values remained relatively low and presumably always below a certain critical threshold considered necessary to maintain organ blood flow, the so-called critical closing pressure.
This is supported by previous work that showed that a minimum CePP of between 25 and 35 mmHg is required to preserve CBF and cerebral energy supply during experimental CPR.
Effect of arrest time and cerebral perfusion pressure during cardiopulmonary resuscitation on cerebral blood flow, metabolism, adenosine triphosphate recovery, and pH in dogs.
CePP values below the critical closing pressure may also be responsible for the fact that even high-quality BLS was not able to generate a measurable improvement in cerebral oxygen supply and cerebral metabolism in several previous experimental studies.
Comparison of a 10-breaths-per-minute versus a 2-breaths-per-minute strategy during cardiopulmonary resuscitation in a porcine model of cardiac arrest.
The administration of adrenaline, on the other hand, targeting a MAP of 40 or 60 mmHg while maintaining unchanged low systemic blood flow, resulted in a significant improvement in regional CBF and cerebral oxygenation as demonstrated by an increase in PUs and PbtO2. The literature contains conflicting reports regarding the effect of adrenaline on microvascular CBF and/or cerebral oxygenation during low-flow situations such as CPR. Ristagno et al. observed reduced microvascular CBF after a single bolus of adrenaline compared to vasopressin or placebo when using orthogonal polarization spectral imaging.
In contrast to our study, microvascular CBF was investigated in the early postresuscitation phase and not during CPR. In addition, Ristagno et al. used considerably shorter arrest and resuscitation times, which may have limited the severity of vasoplegia. High circulating adrenaline levels immediately after achieving ROSC may actually negatively affect cerebral microcirculation, although it is known that a complex microvascular flow pattern with areas of no, low or even increased flow may be present simultaneously in early cerebral reperfusion.
In accordance with our results, more recent studies using various NIRS technologies observed an improvement in CBF and cerebral oxygenation after bolus administration of adrenaline during experimental CPR.
Study of the effects of epinephrine on cerebral oxygenation and metabolism during cardiac arrest and resuscitation by hyperspectral near-infrared spectroscopy.
Study of the effects of epinephrine on cerebral oxygenation and metabolism during cardiac arrest and resuscitation by hyperspectral near-infrared spectroscopy.
commercially available NIRS devices do not necessarily reflect the complex cerebral perfusion and oxygenation conditions during CPR. In fact, NIRS values significantly decreased after adrenaline administration in our study indicating impaired cerebral perfusion and/or oxygenation, whereas regional CBF and PbtO2 actually significantly improved. Several experimental studies found similar results during both resuscitation and spontaneous circulation following vasopressor administration suggesting that cerebral NIRS measurements may be confounded by signals originating from extracerebral tissues, e.g. as a result of vasopressor-induced cutaneous vasoconstriction.
The influence of norepinephrine and phenylephrine on cerebral perfusion and oxygenation during propofol-remifentanil and propofol-remifentanil-dexmedetomidine anaesthesia in piglets.
. Two recent experimental studies support our hypothesis. By comparing standard and hemodynamically directed CPR using titrated adrenaline, they demonstrated that higher perfusion pressures are associated with improved cerebral oxygen delivery and even better neurological outcomes.
Whether cerebral autoregulation is already compromised during cardiac arrest and its pathophysiological significance requires further investigation.
Furthermore, CMD revealed that the increase in perfusion pressures following adrenaline resulted in improved cerebral metabolism. Assessment of cerebral metabolism by extracellular cerebral metabolites, e.g. lactate, pyruvate and glucose, is well established in neurocritical care.
The cerebral lactate to pyruvate (L/P) ratio is a recognized marker of the redox status of the cell allowing differentiation between aerobic and anaerobic metabolism.
Both in clinical and experimental CPR studies an elevated L/P ratio has been shown to characterize brain metabolic distress, whereas a decrease in a formerly elevated L/P ratio indicated recovery of oxygen-dependent energy metabolism.
Association of brain metabolites with blood lactate and glucose levels with respect to neurological outcomes after out-of-hospital cardiac arrest: a preliminary microdialysis study.
Microdialysis assessment of cerebral perfusion during cardiac arrest, extracorporeal life support and cardiopulmonary resuscitation in rats - a pilot trial.
In our study the L/P ratio progressively increased during ECLS prior to adrenaline administration reflecting ongoing cerebral ischemia. With commencement of adrenaline administration the L/P ratio significantly decreased in the MAP 60 mmHg group. Although cerebral metabolites did not completely normalize, the simultaneous decrease in L/P ratio and the increase in cerebral glucose indicates improved oxygen and substrate delivery to the brain and recovery of cerebral metabolism.
Taken together, adrenaline administration increased not only CePP but also regional CBF and cerebral oxygen supply, thereby limiting hypoxic-ischemic brain damage during CPR. It is important to mention that we administered adrenaline continuously in order to reliably detect adrenaline-associated effects on CBF and cerebral oxygenation. Bolus administration of adrenaline, as recommended during clinical CPR, was found to be unsuitable for this purpose due to its short duration of action.
Study of the effects of epinephrine on cerebral oxygenation and metabolism during cardiac arrest and resuscitation by hyperspectral near-infrared spectroscopy.
Interestingly, there was high variability in the response to adrenaline with widely varying infusion rates required to maintain the target MAP. This observation has been documented previously and confirms that individualised administration of adrenaline during CPR may be indicated with appropriate monitoring.
Further research is needed to investigate the influence of adrenaline on cerebral haemodynamics during CPR.
This study has several limitations. Blood flow during ECLS is different from that generated by external chest compression. Therefore, our results may not be completely transferable to clinical CPR. However, ECLS settings (30% of calculated cardiac output) were chosen as close as possible to conditions prevailing during BLS as previously described.
Due to a high degree of standardization, the use of ECLS allowed pressure-related effects of adrenaline on cerebral blood flow, oxygenation and metabolism to be investigated independently of variations in systemic blood flow and arterial partial pressure of oxygen and carbon dioxide. Second, brain metabolic data revealed considerable interindividual variability. Although our experiment was strongly protocolized, individual changes in this extreme pathophysiological condition may still occur. Furthermore, we used a relatively high flow rate (2 µl/min) for CMD to increase temporal resolution. Although perfusion speed influences the recovery of extracellular metabolites, hampering comparison of absolute values between experiments, the L/P ratio should generally remain stable and maintain its validity.
The results of this ECLS model demonstrate that adrenaline administration improves CePP, regional CBF, cerebral oxygenation and cerebral metabolism. Our results cast doubt on the widely accepted assumption that adrenaline negatively impacts regional CBF and cerebral oxygenation during low-flow states such as CPR. Further studies are needed to clarify whether CPR aiming at specific hemodynamic target values can improve cerebral oxygen delivery during CPR.
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
We thank Mr. Peter Hamm as well as our perfusionists Mr. Anton Jeller and Mr. Michael Lindner for their excellent technical support.
References
Paradis N.A.
Martin G.B.
Rivers E.P.
et al.
Coronary perfusion pressure and the return of spontaneous circulation in human cardiopulmonary resuscitation.
Evaluation of pre-hospital administration of adrenaline (epinephrine) by emergency medical services for patients with out of hospital cardiac arrest in Japan: controlled propensity matched retrospective cohort study.
Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry.
Study of the effects of epinephrine on cerebral oxygenation and metabolism during cardiac arrest and resuscitation by hyperspectral near-infrared spectroscopy.
Increased cortical cerebral blood flow with LUCAS; a new device for mechanical chest compressions compared to standard external compressions during experimental cardiopulmonary resuscitation.
Comparison of a 10-breaths-per-minute versus a 2-breaths-per-minute strategy during cardiopulmonary resuscitation in a porcine model of cardiac arrest.
The effect of 50% compared to 100% inspired oxygen fraction on brain oxygenation and post cardiac arrest mitochondrial function in experimental cardiac arrest.
Effect of arrest time and cerebral perfusion pressure during cardiopulmonary resuscitation on cerebral blood flow, metabolism, adenosine triphosphate recovery, and pH in dogs.
The influence of norepinephrine and phenylephrine on cerebral perfusion and oxygenation during propofol-remifentanil and propofol-remifentanil-dexmedetomidine anaesthesia in piglets.
Association of brain metabolites with blood lactate and glucose levels with respect to neurological outcomes after out-of-hospital cardiac arrest: a preliminary microdialysis study.
Microdialysis assessment of cerebral perfusion during cardiac arrest, extracorporeal life support and cardiopulmonary resuscitation in rats - a pilot trial.
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