La thèse « Arrêt cardiaque réfractaire aux traitements pharmacologiques: quelle solution proposer pour améliorer la circulation systémique et cérébrale? » a montré que l'amélioration de la fonction circulatoire peut être obtenue à plusieurs étapes de la prise en charge de l'arrêt cardiaque. La première étude du travail, sous la forme d'une étude expérimentale à double randomisation, a montré que l'assistance circulatoire type extracorporeal life support ECLS apporte un bénéfice sur la mortalité dans la prise en charge de l'arrêt cardiaque réfractaire chez le cochon, et que l'adrénaline administrée en intraveineux lors de la résuscitation prolongée n'améliore pas la survie des animaux. La deuxième étude a montré que la canulation pour l'ECLS peut être réalisée rapidement par voie percutanée à l'aide d'un repérage échographique et en utilisant des guides rigides en salle de cathétérisme cardiaque chez les patients en arrêt cardiaque réfractaire, permettant l'initiation de l'ECLS dans des centres dotés de salle de cathétérisme sans chirurgie cardiovasculaire. La troisième étude a retrouvé que l'état de choc et le pH artériel<7,11 sont des critères pronostiques identifiant les patients qui, après un arrêt cardiaque, présentent une reprise d'une circulation spontanée mais sont à risque de décéder d'insuffisance circulatoire réfractaire au traitement par catécholamines. La quatrième étude à montré que la stabilisation de la fonction circulatoire par l'ECLS peut être suivie par une meilleure récupération de la fonction ventriculaire gauche en modulant la postcharge, par un dispositif pulsatile diminuant le débit de l'ECLS lors de la systole cardiaque. Enfin, l'optimisation de la circulation cérébrale nécessite en plus de l'optimisation de la circulation systémique, le contrôle de l'interaction entre la pression en gaz carbonique et le débit sanguin cérébral qui est amélioré par une normalisation de la pression en gaz carbonique en stratégie pH-stat. Cette stratégie mesure la pression en gaz carbonique à la température réelle du patient au lieu de la température de référence 37° comme dans la stratégie alpha-stat. L’ensemble de ces résultats, pouvant être appliqués à différentes étapes de la prise en charge d'un patient présentant un arrêt cardiaque, pourraient permettre l'amélioration du pronostic des patients. / The doctoral dissertation « Cardiac arrest refractory to pharmacological treatments : what solution to propose to improve systemic and cerebral circulation ? » showed that circulatory function improvement can be achieved at several stages of the management of cardiac arrest patients. The first study of the dissertation, a double randomization experimental study, showed that extracorporeal life support - ECLS type circulatory assistance improves mortality in refractory cardiac arrest in pigs, and intravenous administration of epinephrine during prolonged resuscitation does not improve survival.The second study showed that cannulation for ECLS can be performed rapidly by the percutaneous technique using echography guidance and stiff wires in the catheterization laboratory in refractory cardiac arrest patients allowing for ECLS initiation in centres with catheterization laboratories but without cardiovascular surgery.The third study found that circulatory shock and arterial pH<7.11 are prognostic criteria identifying patients who, after a cardiac arrest, have return of spontaneous circulation but are at risk of death from circulatory failure refractory to catecholamine treatment.The fourth study showed that hemodynamic stabilization by ECLS can be followed by a better recovery of the left ventricular function by modulating afterload using a pulsatile device lowering ECLS output during systole.Finally, optimization of the cerebral circulation requires besides optimization of the systemic circulation, the control of the interaction between carbon dioxyde partial pressure and cerebral circulatory output, which is improved by normalizing carbon dioxyde partial pressure in pH-stat strategy. This strategy measures partial pressure of carbon dioxyde at the real temperature of the patients instead of the theoretical 37° reference temperature as in alpha-stat strategy.All these results can be applied at different stages of the management of cardiac arrest patients and may improve their prognosis.

The adult and pediatric healthcare providers at a New England medical center attended simulation training for responding to cardiac arrests that incorporated the current American Heart Association (AHA) evidence-based standards. The purpose of this concurrent mixed method program evaluation was to compare the adult code blue and pediatric team training programs to the AHA's standards and identify if the staff learned the necessary skills to care for patients in cardiac arrest. The conceptual models used for the study were Crisis Resource Management and the transfer of learning model. The study sample was 660 adult and 269 pediatric healthcare providers who participated in both programs between 2012 and 2015. The research questions explored how the adult and pediatric programs compared, if they provided staff with necessary skills to care for cardiac arrests using current standards, and the staff perceptions of program effectiveness and barriers encountered. The data were collected using evaluation and observation forms and needs-assessment surveys. A chi square analysis identified differences between the programs on staff preparedness and transfer of knowledge into practice. The coding of the qualitative data identified themes from the participants' perceptions on program design. Results prompted a program and curriculum redesign to include multiple opportunities to allow staff to learn and practice skills for low volume high acuity situations. The study promotes social change by giving healthcare providers opportunities to translate evidence-based training into clinical practice. The ability to function effectively as a team in a crisis improves patient outcome and potentially reduces mortality and morbidity within the institution and community. Simulation education also improves staff confidence in performance of low volume and high acuity situations.

<p>Cardiac arrest results in immediate interruption of blood flow. The primary goal of cardiopulmonary resuscitation (CPR) is to re-establish blood flow and hence oxygen delivery to the vital organs. This thesis describes different pharmacological interventions aimed at increasing cerebral blood flow during CPR and after restoration of spontaneous circulation (ROSC).</p><p>In a porcine model of cardiac arrest, continuous infusion of adrenaline generated higher cortical cerebral blood flow during CPR as compared to bolus administration of adrenaline. While bolus doses resulted in temporary peaks in cerebral blood flow, continuous infusion led to a sustained increase in this flow.</p><p>Administration of vasopressin resulted in higher cortical cerebral blood flow and a lower cerebral oxygen extraction ratio as compared to continuous infusion of adrenaline during CPR. In addition, vasopressin generated higher coronary perfusion pressure during CPR and increased the likelihood of achieving ROSC.</p><p>Parameters of coagulation and inflammation were measured after successful resuscitation from cardiac arrest. Immediately after ROSC, thrombin-antithrombin complex, a marker of thrombin generation, was elevated and eicosanoid levels were increased, indicating activation of coagulation and inflammation after ROSC. The thrombin generation was accompanied by a reduction in antithrombin. In addition, there was substantial haemoconcentration in the initial period after ROSC.</p><p>By administration of antithrombin during CPR, supraphysiological levels of antithrombin were achieved. However, antithrombin administration did not increase cerebral circulation or reduce reperfusion injury, as measured by cortical cerebral blood flow, cerebral oxygen extraction and levels of eicosanoids, after ROSC. </p><p>In a clinical study, the adrenaline dose interval was found to be longer than recommended in the majority of cases of cardiac arrest. Thus, the adherence to recommended guidelines regarding the adrenaline dose interval seems to be poor. </p>

Cardiac arrest results in immediate interruption of blood flow. The primary goal of cardiopulmonary resuscitation (CPR) is to re-establish blood flow and hence oxygen delivery to the vital organs. This thesis describes different pharmacological interventions aimed at increasing cerebral blood flow during CPR and after restoration of spontaneous circulation (ROSC). In a porcine model of cardiac arrest, continuous infusion of adrenaline generated higher cortical cerebral blood flow during CPR as compared to bolus administration of adrenaline. While bolus doses resulted in temporary peaks in cerebral blood flow, continuous infusion led to a sustained increase in this flow. Administration of vasopressin resulted in higher cortical cerebral blood flow and a lower cerebral oxygen extraction ratio as compared to continuous infusion of adrenaline during CPR. In addition, vasopressin generated higher coronary perfusion pressure during CPR and increased the likelihood of achieving ROSC. Parameters of coagulation and inflammation were measured after successful resuscitation from cardiac arrest. Immediately after ROSC, thrombin-antithrombin complex, a marker of thrombin generation, was elevated and eicosanoid levels were increased, indicating activation of coagulation and inflammation after ROSC. The thrombin generation was accompanied by a reduction in antithrombin. In addition, there was substantial haemoconcentration in the initial period after ROSC. By administration of antithrombin during CPR, supraphysiological levels of antithrombin were achieved. However, antithrombin administration did not increase cerebral circulation or reduce reperfusion injury, as measured by cortical cerebral blood flow, cerebral oxygen extraction and levels of eicosanoids, after ROSC. In a clinical study, the adrenaline dose interval was found to be longer than recommended in the majority of cases of cardiac arrest. Thus, the adherence to recommended guidelines regarding the adrenaline dose interval seems to be poor.

Although survival rates are increasing, brain injury continues to be a leading cause of death after cardiac arrest (CA). Permanent brain damage after CA is determined by limited tolerance to ischemia from CA and cardiopulmonary resuscitation (CPR), as well as the unique cerebral response to reperfusion after return of spontaneous circulation (ROSC). A major pathway leading to neurotoxic cascade and neuronal injury after CA involves the increased presence of reactive oxygen and nitrogen species generated during ischemia and reperfusion. The magnitude of cerebral oxidative injury induced by free radicals increased with the duration of CA (Paper I). Nitric oxide (NO), a free radical responsible for the formation of reactive nitrogen species, is increased during global ischemia from CA and reperfusion (Paper IV). Hypothetically, the administration of a drug that counteracts the overproduction of NO and also acts as a scavenger of oxygen free radicals might be warranted in order to reduce the damage caused by nitrosative and oxidative stress. For these purposes we used methylene blue (MB), an old dye that has been used in medicine for almost half a century, and an experimental pig model of 20 min of ventricular fibrillation (VF) to reflect a clinical scenario of ischemia/reperfusion injury. Administration of MB added to a hypertonic-hyperoncotic solution (MBHSD) that was started during CPR and continued for 50 min after ROSC increased short-term survival by decreasing myocardial damage, as well as cerebral peroxidation and inflammatory injury (Paper II). Immunostaining of cerebral tissue collected at different time points after CA and ROSC (Paper IV) provided experimental evidence that cortical blood-brain barrier (BBB) disruption begins as early as  during the initial phase of untreated as well as treated CA. The results indicated that MB administration reduced the neurologic injury and BBB disruption considerably, but did not reverse the ongoing detrimental processes. The demonstrated positive effects of MB were related to a decrease of nitrite/nitrate tissue content, and thus to a decrease of excess NO due to the MB inhibitory effects on NOS isoforms. A mixture of MB in hypertonic sodium lactate (MBL) was investigated to facilitate administration of MB in “the field.” Based on findings that MBL cardio- and neuroprotective properties were similar to those of MBHSD, there is reason to believe that the use of MBL might be extended during ongoing CPR and after ROSC (Paper III). It would therefore make sense to try using MB as a pharmacological neuroprotectant during or after clinical CPR in order to expand the temporal therapeutic window before other measures for neuroprotection such as hypothermia are available.

The controlled lowering of core body temperature to 32°C to 34°C is defined as therapeutic hypothermia (TH). Therapeutic hypothermia has been shown to improve neurological outcome and survival in unconscious patients successfully resuscitated after cardiac arrest. Brain temperature is important for cerebral protection therefore methods for primarily cooling the brain have also been explored. This thesis focuses on the likelihood that intranasal cooling can induce, maintain and control cerebral hypothermia. The method uses bilaterally introduced intranasal balloons circulated with cold saline. Selective brain cooling induced with this method was effectively accomplished in pigs with normal circulation while no major disturbances in systemic circulation or physiological variables were recorded. The temperature gradients between brain and body could be maintained for at least six hours. Intranasal balloon catheters were used for therapeutic hypothermia initiation and maintenance during and after successful resuscitation in pigs. Temperature reduction was also obtained by combined intranasal cooling and intravenous ice-cold fluids with possible additional benefits in terms of physiologic stability after cardiac arrest. Rewarming was possible via the intranasal balloons. In these studies brain temperature was recorded invasively by temperature probes inserted in the brain. The fast changes in pig’s brain temperature could also be tracked by a non-invasive method. High-spatial resolution magnetic resonance spectroscopic imaging (MRSI) without internal reference showed a good association with direct invasive temperature monitoring. In addition the mapping of temperature changes during brain cooling was also possible. In awake and unsedated volunteers subjected to intranasal cooling brain temperature changes were followed by two MR techniques. Brain cooling was shown by the previously calibrated high-spatial resolution MRSI and by the phase-mapping method. Intranasal cooling reduced body temperature slightly. The volunteers remained alert during cooling, the physiological parameters stable, and no shivering was reported.

The overall aim of this thesis was to study the influence of physical activity on health. Risks and benefits of physical activity is of particular interest since there is a global trend of less physical activity among youths and adults. In order to investigate this aim we used a database from a large cross country ski race, Vasaloppet, with participants with a wide age range, and with both elite athletes and ordinary people who exercise and promote their health. The most serious risk of strenuous exercise is sudden death and it is challenging to identify preventive effects of major endemic diseases. Using epidemiological methodology we studied 200 000 Vasaloppet skiers and compared them with the general population. Based on personal identification numbers we added data from Swedish national personal and health registers, clinical registers as the cancer register, Swedeheart, or Swedish stroke register, and socioeconomic information from Statistics Sweden. In the Vasaloppet database we collected data on age, gender, finish time and number of races during the period 1989 to 2010. We evaluated risk of death during the race in two papers (I,II). During 90 years of annual races, cardiac arrest occurred in 20 skiers, of which five survived. The death rate is in average two per 100 000 skiers. We also studied the association with cancer incidence (paper III). The overall reduction of cancer was modest among skiers compared with the general population, but for cancers related to lifestyle the risks were markedly lower. We investigated the risk for recurrent myocardial infarction and found a 30% reduction among skiers (paper IV). In paper V we showed that skiers with a first stroke have a lower incidence of all-cause death. The skiers had a higher frequency of atrial fibrillation but had less severe stroke and no increased risk of recurrent stroke. Thus our data suggest that a lifestyle with a high level of physical activity may work as a protection after a cardiovascular event. Summary: The short excess mortality in endurance physical activity is by far outweighed by the long term protective effect of exercise in cardiovascular diseases and cancer.

The first paper examines the value of a statistical life (VSL) for out-of-hospital cardiac arrest (OHCA) victims. We found VSL values to be higher for OHCA victims than for people who die in road traffic accidents and a lower-bound estimate of VSL for OHCA would be in the range of 20 to 30 million Swedish crowns (SEK). The second paper concerns hypothetical bias in contingent valuation (CV) studies. We investigate the link between the determinants and empirical treatment of uncertainty through certainty calibration and find that the higher the confidence of the respondents the more we can trust that stated WTP is correlated to actual WTP. The third paper investigates the performance of two communication aids (a flexible community analogy and an array of dots) in valuing mortality risk reductions for OHCA. The results do not support the prediction of expected utility theory, i.e. that WTP for a mortality risk reduction increases with the amount of risk reduction (weak scope sensitivity), for any of the communication aids. The fourth paper presents a cost-benefit analysis to evaluate the effects of dual dispatch defibrillation by ambulance and fire services in the County of Stockholm. The intervention had positive economic effects, yielding a benefit-cost ratio of 36, a cost per quality-adjusted life-year (QALY) of € 13 000 and the cost per saved life was € 60 000. The fifth paper explores how different response times from OHCA to defibrillation affect patients’ survival rates by using geographic information systems (GIS). The model predicted a baseline survival rate of 3.9% and reducing the ambulance response time by 1 minute increased survival to 4.6%. The sixth paper analyzes demographic determinants of incident experience and risk perception, and the relationship between the two, for eight different risk domains. Males and highly educated respondents perceive their risks lower than what is expected compared to actual incident experience.

Abstract Background Todays guidelines for advanced CPR emphasize chest compressions with good quality and early defibrillation. Prehospital CPR performed by ambulance crew, an automated external defibrillator (AED) is used. The AED analyzes the heart rhythm and the performer is following the advice to chock the heart or not, given by the AED. During on-going CPR there are sequences when no chest compression is performed known as hands-off time. Hands-off time includes the time for the AED to analyze the heart rhythm and the time when advice is given to the crew. Studies show that prolonged hands-off time has a negative impact on survival after a sudden cardiac arrest. Purpose The purpose with this study was to look into if the hands-off time could decrease with use of manual mode on the defibrillator by the ambulance crew. The crew had to analyze, make a decision to chock or not, charge the defibrillator and give the chock if appropriate. Furthermore, the crews’ knowledge in analyzing heart rhythms that can be defibrillate was investigated.  Method A quasi-experimental method was used. 38 participants, all ambulance crew, were included in the study. The participants were randomized into two groups. One group performed CPR with an AED, the second group used the manual mode on the defibrillator. The study data were processed in SPSS. Results The time preceding the first defibrillation was significant shorter in the group using manual mode. There was no difference in total hands-off time between the two groups. All heart rhythms were interpreted right and all defibrillation were done correctly. Conclusions Time from establish cardiac arrest to first defibrillation was significant shorter in manual mode. Furthermore, all heart rhythms were interpreted right and all defibrillation were done correctly. Time from first defibrillation to start of chest compressions was equal in the two groups. There were no significant differences in hands-off time between the two groups.   Keyword: ambulance, cardiac arrest, automatic external defibrillator, manual defibrillator, manual rhythm analyze, hands-off time

I Sverige drabbas cirka 3000 patienter årligen av plötsligt hjärtstopp på sjukhus. Ett plötsligt hjärtstopp är en av de mest stressfyllda situationerna som sjukvårdspersonal utsätts för på sjukhus. Tidigare forskning har främst inriktat sig på medicinska och biofysiska aspekter vid återupplivning i samband med plötsligt hjärtstopp. De subjektiva upplevelserna för dem som utför hjärt-lungräddning och deras känslor är sällan beskrivna. Syftet var att beskriva anestesisjuksköterskans upplevelser av att delta vid plötsligt hjärtstopp på sjukhus. Datainsamlingen genomfördes dels genom intervju med en fokusgrupp med fem informanter och dels genom två individuella djupintervjuer. Dataanalysen genomfördes systematiskt enligt Graneheim &amp; Lundmans kvalitativa innehållsanalys. Resultatet utmynnade i tre kategorier med respektive subkategorier. Kategorierna som framkom var; Den givna rollen, Teamarbete och Reflektioner relaterade till hjärtstopp. Den givna rollen upplevdes både trygg, kravfylld och tillfredsställande. Ett tydligt ledarskap och en god kommunikation beskrevs som viktiga aspekter för att skapa riktning, mål och samarbete i teamet. De upplevde behov av feedback och debriefing fyllde en viktig funktion. Uppsatsen kan ligga till grund för ett framtida förbättringsarbete, diskussionsunderlag och uppföljning av plötsligt hjärtstopp. Ytterligare forskning inom området och över professionsgränserna är önskvärt. / In Sweden every year about 3000 patients are affected by sudden cardiac arrest in a hospital setting. Sudden cardiac arrest is one of the most stressful situations for hospital staff to handle. Earlier research has mainly focused on the medical and biophysical aspects of cardiac resuscitation. The subjective experience and feelings of those performing the resuscitation are seldom described. The aim of the study was to describe the nurse an esthetists’ experience of participation in sudden cardiac arrest resuscitation in a hospital setting. Data collection was done through focus group interviews involving five participants and indepth interviews with two participants. Data analysis was systematically performed according to Graneheim &amp; Lundmans qualitative content analysis. The result showed three categories with respective subcategories. The following categories emerged: The given role, Teamwork and Reflection related to cardiac arrest. The given role was perceived as safe, satisfying and filled with demands. A defined leadership and good communication were described as important factors in ensuring clear direction, goals and teamwork.          The participants experienced a need for feedback and felt debriefing was of the utmost importance. This study can lead to future areas of improvement including further discussion and follow up of sudden cardiac arrest in hospital settings. Further research in this area and across professional borders is needed.