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- Lundin, Andreas, et al.
(författare)
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Drug therapy in cardiac arrest : a review of the literature
- 2016
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Ingår i: European heart journal. Cardiovascular pharmacotherapy. - : Oxford University Press (OUP). - 2055-6845 .- 2055-6837. ; 2:1, s. 54-75
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to review the literature on human studies of drug therapy in cardiac arrest during the last 25 years. In May 2015, a systematic literature search was performed in PubMed, Embase, the Cochrane Library, and CRD databases. Prospective interventional and observational studies evaluating a specified drug therapy in human cardiac arrest reporting a clinical endpoint [i.e. return of spontaneous circulation (ROSC) or survival] and published in English 1990 or later were included, whereas animal studies, case series and reports, studies of drug administration, drug pharmacology, non-specified drug therapies, preventive drug therapy, drug administration after ROSC, studies with primarily physiological endpoints, and studies of traumatic cardiac arrest were excluded. The literature search identified a total of 8936 articles. Eighty-eight articles met our inclusion criteria and were included in the review. We identified no human study in which drug therapy, compared with placebo, improved long-term survival. Regarding adrenaline and amiodarone, the drugs currently recommended in cardiac arrest, two prospective randomized placebo-controlled trials, were identified for adrenaline, and one for amiodarone, but they were all underpowered to detect differences in survival to hospital discharge. Of all reviewed studies, only one recent prospective study demonstrated improved neurological outcome with one therapy over another using a combination of vasopressin, steroids, and adrenaline as the intervention compared with standard adrenaline administration. The evidence base for drug therapy in cardiac arrest is scarce. However, many human studies on drug therapy in cardiac arrest have not been powered to identify differences in important clinical outcomes such as survival to hospital discharge and favourable neurological outcome. Efforts are needed to initiate large multicentre prospective randomized clinical trials to evaluate both currently recommended and future drug therapies.
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| 2. |
- Rysz, Susanne
(författare)
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Pathophysiology of critically ill covid-19 patients
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- With the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a new disease, COVID-19, challenged health care professionals and scientists. The angiotensin-converting enzyme type 2 (ACE2) was identified early in the pandemic as being the receptor used by SARS-CoV-2 for cell entrance. Since this discovery, a disruption of the renin-angiotensin-aldosterone system (RAAS) has been established as one of the main pathophysiological pathways for developing severe COVID-19. The RAAS is closely linked to cardiovascular health and a strict balance within the system is therefore crucial. The ACE2 is key to upholding this balance by keeping angiotensin II (ANG II) levels appropriate for the physiological demand. Any interference with ACE2-activity may result in increased unwanted ANG II effects such as hypertension, insulin resistance, thrombosis, and organ failure, all frequently seen during severe COVID-19. The overall aim of this thesis was to investigate the pathophysiological consequences of the viral interference with ACE2 and thus the RAAS, and its association with the clinical presentation of severe COVID-19. Study I: In this translational study, we induced a pharmacological RAAS imbalance in swine, either by infusing ANG II or/and blocking ACE2. This causes a pathophysiological state (including impaired lung perfusion, increased pulmonary artery pressure, decreased oxygenation, alveolar damage, and acute kidney injury) which shared several clinical and radiological features observed in severe COVID-19. Study II: In a retrospective observational study of 385 hospitalised SARS-CoV-2 positive patients, we investigated the association between chronic dysglycemia, diagnosed by analysis of available HbA1c, and SARS-CoV-2 associated respiratory failure. We found that prediabetes (OR 14.41 [95% CI 5.27-39.43]), unknown diabetes (OR 15.86 [95% CI 4.55-55.36]) and uncontrolled diabetes (OR 17.61 [95% CI 5.77-53.74]) were associated with an increased risk of respiratory failure, independent of age, sex, and BMI. Study III: In this retrospective observational study of 406 hospitalised patients, we investigated the dynamics of common plasma electrolytes and acid-base biomarkers in patients with severe COVID-19 and its association with the requirement for invasive ventilation and mortality. We found hyponatremia on admission in 53% of the studied population followed by the development of hypernatremia in 42% the patients within the first 2 weeks of hospitalisation. The development of hypernatremia was associated with a more severe course of COVID-19 and increased 30-day mortality (OR 3,94 [95% CI 2,27-6.85) Study IV: In this prospective observational study, we compared circulating concentrations of three main biomarkers of the RAAS (ANG II, ANG 1-7 and ACE2) and arginine vasopressin (copeptin) in 56 COVID-19 patients admitted to the intensive care unit. We found plasma concentration of ACE2 and copeptin to be low compared to healthy controls. These findings were not combined with low concentrations of ANG 1-7 or hypotension. We conclude that the interaction of SARS-CoV-2 with the RAAS may explain several of the clinical findings observed in COVID-19 patients. Patients with a pre-existing RAAS- imbalance may suffer from acute on chronic RAAS-activation with acceleration of several metabolic manifestations when infected with SARS-CoV-2. The complexity of RAAS and its impact on health and sickness needs to be further investigated, expanding the arsenal of tools for earlier identification of any developing imbalance within the system as well as intensifying treatment options to prevent disease progression. In summary, there are several findings in these studies indicating an association between an imbalanced RAAS and the development of severe COVID-19."
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| 3. |
- Rysz, Susanne, et al.
(författare)
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The effect of levosimendan on survival and cardiac performance in an ischemic cardiac arrest model - A blinded randomized placebo -controlled study in swine
- 2020
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 150, s. 113-120
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Tidskriftsartikel (refereegranskat)abstract
- Background: Survival after out-of-hospital cardiac arrest remains poor. Levosimendan could be a new intervention in this setting. Therefore, we conducted a blinded, placebo controlled randomized study investigating the effects of levosimendan on survival and cardiac performance in an ischemic cardiac arrest model in swine. Methods: Twenty-four anesthetised swines underwent experimentally-induced acute myocardial infarction and ventricular fibrillation. At the start of CPR, a bolus dose of levosimendan (12 μg kg-1) or placebo was given followed by a 24-h infusion (0.2 μg kg-1 min-1) after return of spontaneously circulation. Animals were evaluated by risk of death, post-resuscitation hemodynamics and infarction size by magnetic resonance imaging (MRI) up to 32 h post arrest. Results: Spontaneous circulation was restored in all (12/12) animals in the levosimendan group compared to two thirds (8/12) in the placebo group (P = 0.09). Protocol survival was higher for the levosimendan group (P = 0.02) with an estimated 88% lower risk of death compared to placebo (hazard ratio [95% confidence interval] 0.12 [0.01-0.96], P = 0.046). Cardiac output (CO) recovered 40% faster during the first hour of the intensive care period for the levosimendan group (difference 0.13 [0.01-0.26] L min-1P = 0.04). The placebo group required higher inotropic support during the intensive care period which masked an even bigger recovery in CO in the levosimendan group (58%). The MRI showed no difference in myocardial scar size or in myocardial area at risk. Conclusions: Levosimendan given intra-arrest and during the first 24-h of post-resuscitation care improved survival and cardiac performance in this ischemic cardiac arrest model. Institutional Protocol Number; KERIC 5.2.18-14933.
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