| 1. |
- Covaciu, Lucian, 1964-
(author)
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Intranasal Cooling for Cerebral Hypothermia Treatment
- 2010
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Doctoral thesis (other academic/artistic)abstract
- 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.
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| 2. |
- Lagedal, Rickard, 1981-
(author)
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Coronary angiography after out-of-hospital cardiac arrest
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Out-of-hospital cardiac arrest (OHCA) is a common cause of death with a survival rate of 10% in Sweden. The chance of survival depends on rapid recognition, high quality cardiopulmonary resuscitation and post-resuscitation care including searching and treating the cause of the arrest. Ischaemic cardiac disease including acute coronary artery occlusions is the most common cause of OHCA. Acute coronary artery lesions can be diagnosed and treated with coronary angiography and subsequent PCI. This thesis analyses various aspects of coronary angiography after OHCA. Paper I+II describes the rational, protocol and the results from the pilot phase (n=117) of a randomized multicentre clinical trial. We compared a strategy of immediate coronary angiography in patients successfully resuscitated after OHCA with a strategy without immediate coronary angiography. We did not reach the stipulated time of 120 minutes from first medical contact to angiography, but our study strategy was feasible. No major unexpected safety issues were reported. The main phase of the study could therefore be started with only minor changes from the pilot phase protocol. In a registry study of 1133 patients (Paper III) coronary angiographic findings were compared with ECG and comorbidities in unconscious patients after OHCA. In patients without ST-elevation, the rate of PCI attempts was higher in patients with ST-depression (47%) and in patients with ECG classified as “other findings” (45%) compared to patients with normal ECG (33%), OR 1.78 (CI 1.13-2.82) and OR 1.65 (CI 1.04-2.61), respectively. When analysing patients without ST-elevation, no difference in PCI rates were found between the comorbidity groups and neither between patients with shockable compared to non-shockable initial ECG rhythm. Paper IV is a registry study (n=3906) analysing the impact of patient income on the probability to receive early coronary angiography after OHCA. When dividing patients into income quarters and adjusting for confounders, increasing income was associated with higher rates of early coronary angiography. Thirty-six percent of patients in the highest income quarter received early angiography compared to fifteen percent in the lowest income quarter, OR 1.64 (1.27-2.11). Adding potential mediators to explain this finding gradually decreased the difference, and the main explanatory factor for this difference was that higher income is associated with higher rates of shockable ECG rhythm. 30-day survival was also higher in the highest income quarter compared to the lowest income group in the fully adjusted analysis, OR 1.51 (CI 1.22-1.89).
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| 3. |
- Nordmark, Johanna, 1968-
(author)
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Aspects of Induced Hypothermia following Cardiopulmonary Resuscitation : Cerebral and Cardiovascular Effects
- 2009
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Doctoral thesis (other academic/artistic)abstract
- Hypothermia treatment with cooling to a body temperature of 32-34°C has been shown to be an effective way of improving neurological outcome and survival in unconscious patients successfully resuscitated after cardiac arrest (CA). The method is used clinically but there are still many questions on the biological mechanisms and on how the treatment is best performed. This thesis focuses on cerebral and haemodynamic effects of hypothermia and rewarming. A porcine model of CA was used. To shorten time to reach target temperature, induction of hypothermia, by means of infusion of 4°C cold fluid, was started already during ongoing cardiopulmonary resuscitation. The temperature was satisfactorily reduced without obvious haemodynamic disturbances. Cerebral effects of hypothermia and rewarming were studied. Microdialysis monitoring showed signs of cerebral energy failure (increased lactate/pyruvate-ratio) and excitotoxicity (increased glutamate) immediately after CA. There was a risk of secondary energy failure that was reduced by hypothermia. Intracranial pressure (ICP) increased gradually after CA irrespectively of if hypothermia was used or not. There were no indications of increasing cerebral disturbances during rewarming. Haemodynamic effects of hypothermia treatment and rewarming were examined in a study of patients successfully resuscitated after CA. Hypothermia was induced by means of cold intravenous infusion. No negative effects on the cardiovascular system were revealed. There were indications of decreased intravascular volume in spite of a positive fluid balance. Cerebral microdialysis and ICP recording were performed in four patients. All patients had signs of energy failure and excitotoxicity following CA. ICP was only exceptionally above 20 mmHg. In contrast to the experimental study indications of increasing ischemia were seen during rewarming. Glycerol had a biphasic pattern, perhaps due to an overspill of metabolites from the general circulation. As most patients become extensively anti-coagulated following CA, intracranial monitoring is not suitable to be used in routine care.
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| 4. |
- Semenas, Egidijus
(author)
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Sex Differences in Cardiac and Cerebral Damage after Hypovolemic Cardiac Arrest
- 2011
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Doctoral thesis (other academic/artistic)abstract
- Resuscitation from haemorrhagic shock and the subsequent circulatory arrest remains a major clinical challenge in the care of trauma patients. Numerous experimental studies in sexually mature animals have shown a gender dimorphism in response to trauma and haemorrhagic shock. The first study was designed to evaluate sex differences in outcome after resuscitation from hypovolemic circulatory arrest. We intended to examine innate sex differences, and chose to study sexually immature animals. The study showed that cerebral cortical blood flow was greater, blood-brain-barrier was better preserved and neuronal injury was smaller in female as compared to male piglets. The second study demonstrated that female sex was associated with enhanced haemodynamic response, cardioprotection, and better survival. This cardioprotective effect was observed despite comparable estradiol and testosterone levels in male and female animals, indicating an innate gender-related cardioprotection. In both studies (I and II) female sex was associated with a smaller increase in the cerebral expression of inducible and neuronal nitric oxide synthase (iNOS and nNOS). Thus in the study III we tested the hypothesis that exogenously administered 17β-estradiol (E2) could improve neurological outcome by NOS modulation. The results showed that compared with the control group, animals in the E2 group exhibited a significantly smaller increase in nNOS and iNOS expression, a smaller blood-brain-barrier disruption and a mitigated neuronal injury. There was also a significant correlation between nNOS and iNOS levels and neuronal injury. A hypothesis if female-specific cardioprotection may be attributed to a smaller NOS activity was tested in study IV. The animals received methylene blue (MB) during CPR, but were otherwise treated according to the same protocol as studies I-II. The female-specific cardioprotection could be attributed to a smaller NOS activity, but NOS inhibition with MB did not improve survival or myocardial injury, although it abated the difference between the sexes.
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| 5. |
- Larsson, Ing-Marie, 1963-
(author)
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Post-Cardiac Arrest Care : Therapeutic Hypothermia, Patient Outcomes and Relatives’ Experiences
- 2014
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Doctoral thesis (other academic/artistic)abstract
- The overall aim of the thesis was to study post-resuscitation care of cardiac arrest (CA) patients with a focus on therapeutic hypothermia treatment, outcomes up to six months post-CA and relatives’ experiences during the hospital stay.In Paper I, the aim was to asses effectiveness of hypothermia treatment with cold, 4°C, intravenous crystalloid infusion combined with ice packs. In conclusion, the described cooling method was found to be useful for inducing and maintaining hypothermia, allowed good temperature control during rewarming and to be feasible in clinical practice.The aim in Paper II was to investigate biomarkers and the association of serum glial fibrillary acidic protein (GFAP) levels with outcome, and to compare GFAP with neuron-specific enolas (NSE) and S100B. The result showed increased GFAP levels in the poor outcome group, but did not show sufficient sensitivity to predict neurological outcome. Both NSE and S100B were shown to be better predictors. A combination of the investigated biomarkers did not increase the ability to predict neurological outcome.In Paper III, the aim was to investigate whether there were any changes in and correlations between anxiety, depression and health-related quality of life (HRQoL) over time, between hospital discharge and one and six months post-CA. There was improvement over time in HRQoL, but changes over time in anxiety and depression were not found. Physical problems seemed to affect HRQoL more than psychological problems. The results also indicate that the less anxiety and depression patients perceive, the better their HRQoL.In the fourth paper, the aim was to describe relatives’ experiences during the next of kin’s hospital stay after surviving a CA. The analysis resulted in three themes: The first period of chaos, Feeling secure in a difficult situation, and Living in a changed existence.In conclusion, the results of the thesis have helped to improve knowledge within the areas studied and reveal aspects that should be taken into account in the overall treatment of this group of patients. The thesis have also shown the importance of developing an overall view and establishing a chain of care from an individual’s CA until follow-up for both the patient and his/her relatives.
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| 6. |
- Lindgren, Erik
(author)
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Mechanical chest compressions and gender differences in out-of-hospital-cardiac-arrest
- 2016
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Licentiate thesis (other academic/artistic)abstract
- Paper I and II. Both early defibrillation and high quality chest compressions are affecting the chances of survival after cardiac arrest (CA). Manual chest compressions delivers only approximately 30% of normal cardiac output and is further deteriorating during transport. Mechanical chest compressions has in experimental studies delivered higher perfusion pressures, cerebral blood flow and end-tidal CO2 compared to manual CPR. Two pilot studies showed no difference in outcome compared to manual CPR. The LINC trial was the first large randomized trial testing the effectiveness and safety of mechanical chest compressions compared to manual CPR. The objectives were to determine whether CPR with mechanical chest compression and defibrillation during ongoing CPR, compared with CPR with manual chest compressions, according to guidelines, would improve 4-hour survival after out-of-hospital cardiac arrest (OHCA).
We could not identify any significant differences in outcome between the two groups.Paper III. Despite women having several adverse characteristics associated with bad outcome after CA, female gender is considered being an independent predictor for early survival. This is however no longer seen after the initial phase, when male survival is significantly higher. The reason for this difference is not known. This has previously been shown in register based studies. This is, to our best knowledge, the first analysis based on a population from a randomized controlled trial. We aimed to identify gender differences in survival after OHCA.
Female gender was an independent predictor for early survival, but this difference was no longer seen at hospital discharge or after 6 months.
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| 7. |
- Johansson, Jakob, 1968-
(author)
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Cardiopulmonary Resuscitation : Pharmacological Interventions for Augmentation of Cerebral Blood Flow
- 2004
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Doctoral thesis (other academic/artistic)abstract
- 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.
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| 8. |
- Lindgren, Erik, 1972-
(author)
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Cardiac Arrest – mechanical chest compressions, gender differences and coronary angiography
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Cardiac arrest is a major health problem with over 6000 cases of out-of-hospital cardiac arrest (OHCA) and 2500 cases of in-hospital cardiac arrest (IHCA) per year in Sweden. Survival are low. Many factors affect the chances of survival, including effective cardiopulmonary resuscitation and optimal post resuscitation care. These thesis involve these areas. Paper I+II describe a randomized clinical trial (n=2589). We compared a novel CPR algorithm with defibrillations during ongoing chest compressions delivered with a mechanical chest compression device and manual CPR according to guidelines. We found no difference in 4-hour survival, 23.6% with mechanical CPR and 23.7% with manual CPR. The vast majority of survivors in both groups had good neurological outcomes by 6 months. Paper III is a registry study (n=1498). We investigated impact of gender in performance and findings of early coronary angiography (CAG) and percutaneous coronary intervention (PCI), comorbidity and outcome among OHCA victims with an initially shockable rhythm. We found no difference between men and women in rates of ST-elevation/left bundle branch block (LBBB), 40% vs. 38% or rates of CAG, 45% vs. 40%. Among patients without ST-elevation/LBBB more men than women had CAG followed by PCI, 59% vs. 42% (P=0.03) and more advanced coronary artery disease. We found no association between gender and use of early CAG. Paper IV is a retrospective observational single centre study (n=423) of ICU treated victims of cardiac arrest. OHCA and IHCA were compared regarding comorbidity, characteristics of the arrest, treatment including CAG and CAG findings and outcome. OHCA patients had less preexisting comorbidity, lower rates of bystander CPR 71% vs 100% (p<0.001) and longer time to return of spontaneous circulation, 20 vs 10 minutes (p<0.001). OHCA patients more often had a shockable first rhythm, 47% vs 13% (p<0.001) and CA without any obvious non-cardiac origin, 77% vs 50% (p<0.001). OHCA patients more often underwent early CAG, 52% vs 25% (p<0.001) but no difference in rates of subsequent PCI or angiogram with at least one significant stenosis was seen. OHCA and IHCA did not differ in 30-days survival, 42% vs 41% or 1-year survival, 39% vs 33%
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| 9. |
- Mörtberg, Erik
(author)
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Assessment of the Cerebral Ischemic/Reperfusion Injury after Cardiac Arrest
- 2010
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Doctoral thesis (other academic/artistic)abstract
- The cerebral damage after cardiac arrest is thought to arise both from the ischemia during the cardiac arrest but also during reperfusion. It is the degree of cerebral damage which determines the outcome in patients. This thesis focuses on the cerebral damage after cardiac arrest. In two animal studies, positron emission tomography (PET) was used to measure cerebral blood flow, oxygen metabolism and oxygen extraction in the brain. After restoration of spontaneous circulation (ROSC) from five or ten minutes of cardiac arrest there was an immediate hyperperfusion, followed by a hypoperfusion which was most evident in the cortex. The oxygen metabolism decreased after ROSC with the lowest values in the cortex. The oxygen extraction was high at 60 minutes after ROSC, indicating an ischemic situation. After ten minutes of cardiac arrest, there was a hyperperfusion in the cerebellum. In 31 patients resuscitated after cardiac arrest and treated with hypothermia for 24 hours, blood samples were collected from admission until 108 hours after ROSC. The samples were analyzed for different biomarkers in order to test the predictive value of the biomarkers. The patients were assessed regarding their neurological outcome at discharge from the intensive care unit and after six months. Brain derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) was not associated with outcome. Neuron specific enolase (NSE) concentrations were higher among those with a poor outcome with a sensitivity of 57% and a specificity of 93% when sampled 96 hours after ROSC. S-100B was very accurate in predicting outcome; after 24 hours after ROSC it predicted a poor outcome with a sensitivity of 87% and a specificity of 100%. Tau protein predicted a poor outcome after 96 hours after ROSC with a sensitivity of 71% and a specificity of 93%.
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| 10. |
- Seilitz, Jenny, 1978-
(author)
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The gastrointestinal tract in cardiac anaesthesia and intensive care : Clinical and experimental studies
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Gastrointestinal (GI) complications after cardiac surgery have a substantial impact on outcome. The aims were to investigate the frequency of, and methods for detecting, GI dysfunction after cardiac surgery and its relation to outcome, and the impact of vasoactive drugs on the GI tract in experimental cardiogenic shock. Paper I investigated the intraabdominal metabolism, using intraperitoneal microdialysis, during and after routine cardiac surgery in six patients. The results imply that, even during a normal perioperative course, the GI tract may be subjected to a subclinical anaerobic state. In Paper II the impact of stepwise reductions of cardiac output (CO) on the metabolism and circulation in the GI tract was studied in anaesthetised pigs using cardiac tamponade (n=6) or partial inflation of a caval vein balloon (n=6). The two models had similar haemodynamic effects and the intraabdominal metabolism became increasingly anaerobic when the CO was reduced by 50%. In Paper III the caval vein balloon model was utilised to examine the GI effects of two inodilators (levosimendan and milrinone) and two vasoconstrictors (vasopressin and norepinephrine) at 40% CO reduction (n=7/group). Negligible splanchnic vasodilation by the inodilators in fixed low CO, and possible GI specific side effects of high dose vasopressors, were demonstrated. Paper IV included 501 cardiac surgery patients assessed using the Acute Gastrointestinal Injury (AGI) grade. Only 32.7% were asymptomatic during the first three postoperative days. At least GI dysfunction, i.e. AGI grade ≥2, developed in 2.2% and was associated with more complex surgeries and higher postoperative frequencies of GI complications and mortality. In Paper V a biomarker for enterocyte damage, intestinal fatty acid-binding protein (IFABP), was investigated in relation to AGI grade. The group with AGI ≥2 (n=11) was compared to a matched group without GI symptoms (n=22). An I-FABP concentration in the fourth quartile on day one was associated with higher frequencies of organ dysfunction and 365-day mortality. In conclusion, this thesis provides evidence for an association between intraoperative GI injury, postoperative GI dysfunction and manifest complications, and that the effects of inodilators and vasoconstrictors must be considered.
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