| 1. |
- Covaciu, Lucian, 1964-
(författare)
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Intranasal Cooling for Cerebral Hypothermia Treatment
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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. |
- Eiriksson, Kristinn, 1967-
(författare)
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Technical Aspects of Laparoscopic Liver Resection. An Experimental Study
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Various techniques are used to transect the liver. With increase in laparoscopic liver resections (LLR), it is of even more interest to develop surgical techniques to minimize bleeding and the risk for gas embolism during transection. Instrument like argon enhanced coagulator provides good hemostasis but increases the danger of gas embolism. The CO2 pneumoperitoneum that is routinely used in most types of laparoscopic surgery can be modified by the use of different gas pressure. It can be assumed that different pressure influences bleeding but also the risk for gas embolism.In presented porcine studies, three instrumental combinations have been studied. In study I sixteen piglets were randomized to LLR with either the cavitron ultrasonic aspirator (CUSA™) in combination with vessels sealing system (Ligasure™) or with CUSA™ and ultrascision scissors (Autosonix™), with the endpoints of intra-operative bleeding and gas embolism. In study IV sixteen piglets were randomized to LLR either with staple device (Endo-GIA™) or the Ligasure™ - CUSA™ combination with same primary endpoints and additionally secondary endpoints of effect on gas-exchange, systemic- and pulmonary hemodynamic.Focusing on intra-abdominal pressure (IAP) in study II, sixteen piglets were randomized to LLR with an IAP of either 8 or 16 mmHg. Primary endpoints were bleeding and gas embolism and secondary endpoints, effect on gas-exchange, systemic- and pulmonary hemodynamic.In study III effect of argon gas was tested during LLR. Sixteen piglets were randomized to either argon pneumoperitoneum or CO2 pneumoperitoneum. Primary endpoints were effect on gas-exchange, systemic- and pulmonary hemodynamic.In presented studies, we tested efficacy and safety of different techniques for LLR. CUSA™ can be used in combination with either Ligasure™ or Autosonix™. However, Ligasure™ reduces the amount of bleeding. The recent introduction of staplers seems promising with a further reduction in bleeding, gas embolism, and operating time. The IAP influences both the amount of bleeding as well as gas embolism. It seems reasonable to use a higher IAP to decrease bleeding with caution and with close monitoring for gas embolism. Argon gas embolism gives more extensive effect on gas-exchange and hemodynamic and should probably be avoided in this type of surgery.
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| 3. |
- Fors, Diddi
(författare)
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Gas Embolism in Laparoscopic Liver Surgery
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Laparoscopic liver surgery is complicated due to the structure of this organ with open sinusoids. A serious disadvantage is the risk of gas embolism (GE) due to CO2 pneumoperitoneum. CO2 can enter the vascular system through a wounded vein. A common opinion is that gas fluxes along a pressure gradient, e.g. CVP-intra abdominal pressure (IAP). The occurrence of GE could also be eased by entrainment, a ‘Venturi-like’ effect, due to cyclic differences in thoracic pressure and blood flow caused by mechanical ventilation at normal frequency.The aims of these studies were to survey, in a porcine model, the influence on respiratory and haemodynamic variables by GE, to determine at what frequency, severity and duration GE occurs during laparoscopic liver resection (LLR) and whether there are methods to influence the occurrence or severity of GE.Pulmonary and circulatory variables were monitored and measured as well as continuous blood gas monitoring. Transoesophageal echocardiogram was used to identify GE and, according to the amount of bubbles in the right outflow tract of the heart, GE was graded as 0, 1 and 2. Pneumoperitoneum was created by using CO2and IAP was set to 16 mm Hg.A single bolus dose of CO2 influenced respiratory and haemodynamic variables for at least 4 h. During LLR GE occurred in 65-70% of the animals, of which the more serious caused negative influence on cardiopulmonary variables.Elevated PEEP (15 cm H2O) increased CVP but GE occurred irrespective if CVP was lower than or exceeded IAP. In two last studies, a hepatic vein was cut and left open for 3 m before it was clipped. Interestingly, no signs of GE were seen despite an open vein and IAP > CVP in 8 of 20 animals. In the last study high frequency jet ventilation was used in order to minimise the risk of entrainment. The duration of GE was shortened.The occurrence of GE seemed to be influenced by several different factors. The physiological reaction of a GE is impossible to predict for a specific patient, and depends among other factors on comorbidity, and amount, site and entrance rate of GE.
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| 4. |
- Johansson, Jakob, 1968-
(författare)
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Cardiopulmonary Resuscitation : Pharmacological Interventions for Augmentation of Cerebral Blood Flow
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 5. |
- Lagedal, Rickard, 1981-
(författare)
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Coronary angiography after out-of-hospital cardiac arrest
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 6. |
- Larsson, Ing-Marie, 1963-
(författare)
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Post-Cardiac Arrest Care : Therapeutic Hypothermia, Patient Outcomes and Relatives’ Experiences
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 7. |
- Lindgren, Erik, 1972-
(författare)
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Cardiac Arrest – mechanical chest compressions, gender differences and coronary angiography
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 8. |
- Mörtberg, Erik
(författare)
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Assessment of the Cerebral Ischemic/Reperfusion Injury after Cardiac Arrest
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 9. |
- Nordmark, Johanna, 1968-
(författare)
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Aspects of Induced Hypothermia following Cardiopulmonary Resuscitation : Cerebral and Cardiovascular Effects
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 10. |
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