Application, tolerance and safety of fondaparinux therapy in a German hospital: a prospective single-centre experience.

INTRODUCTION The pentasaccharide fondaparinux is widely approved for prophylaxis and treatment of thromboembolic diseases and therapy of acute coronary syndrome. It is also used off-label in patients with acute, suspected or antecedent heparin-induced thrombocytopenia (HIT). The aim of this prospective observational cohort study was to document fondaparinux' prescription practice, tolerance and therapy safety in a representative mixed German single-centre patient cohort. PATIENTS AND METHODS Between 09/2008 - 04/2009, 231 consecutive patients treated with fondaparinux were enrolled. Medical data were obtained from patient's records. The patients were clinically screened for thrombosis (Wells score), sequelae of HIT (4T's score), and bleeding complications (ISTH-criteria) and subjected to further assessment (i.e. sonography, HIT-diagnostics), if necessary. The mortality rate was assessed 30 days after therapy start. RESULTS Overall, 153/231 patients had a prophylactic, 74/231 patients a therapeutic, and 4/231 patients a successive prophylactic/therapeutic indication. In 11/231 patients fondaparinux was used due to suspected/antecedent HIT, in 5/231 patients due to a previous cutaneous delayed-type hypersensitivity to heparins. Other indications were rare. Three new/progressive thromboses were detected. No cases of HIT, major bleedings, or fatalities occurred. CONCLUSIONS Fondaparinux was well tolerated and was safe in prophylaxis and therapy; prescriptions mostly followed the current approval guidelines and were rarely related to HIT-associated indications (<5% of prescriptions), which is in contrast to previous study results in the U.S. (>94% of prescriptions were HIT-associated). A trend towards an individualised fondaparinux use based on the compound's inherent properties and the patients' risk profiles, i.e., antecedent HIT, bone fractures, heparin allergy, was observed.

Synchronous carotid and coronary bypass surgery using minimal extracorporeal circulation does not increase the risk of in-hospital stroke compared to isolated carotid endarterectomy under general anaesthesia

Gebiet: Chirurgie Abstract: Introduction: Carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) could be approached in a combined or a staged fashion. Some crucial studies have shown no significant difference in peri-operative stroke and death rate in combined versus staged CEA/CABG. At present conventional extracorporeal circulation (CECC) is regarded as the gold standard for performing on-pump coronary artery bypass grafting. On contrary, the use of minimized extracorporeal circulation (MECC) for CABG diminishes hemodilution, blood-air contact, foreign surface contact and inflammatory response. At the same time, general anaesthesia (GA) is a potential risk factor for higher perioperative stroke rate after isolated CEA, not only for the ipsilateral but also for the contralateral side especially in case of contralateral high-grade stenosis or occlusion. The aim of the study was to analyze if synchronous CEA/CABG using MECC (CEA/CABG group) allows reducing the perioperative stroke risk to the level of isolated CEA performed under GA (CEA-GA group). – Methods: A retrospective analysis of all patients who underwent CEA at our institution between January 2005 and December 2012 was performed. We compared outcomes between all patients undergoing CEA/CABG to all isolated CEA-GA during the same time period. The CEA/CABG group was additionally compared to a reference group consisting of patients undergoing isolated CEA in local anaesthesia. Primary outcome was in-hospital stroke. – Results: A total of 367 CEAs were performed, from which 46 patients were excluded having either off-pump CABG or other cardiac surgery procedures than CABG combined with CEA. Out of 321 patients, 74 were in the CEA/CABG and 64 in the CEA-GA group. There was a significantly higher rate of symptomatic stenoses among patients in the CEA-GA group (p<0.002). Three (4.1%) strokes in the CEA/CABG group were registered, two ipsilateral (2.7%) and one contralateral (1.4%) to the operated side. In the CEA-GA group 2 ipsilateral strokes (3.1%) occurred. No difference was noticed between the groups (p=1.000). One patient with stroke in each group had a symptomatic stenosis preoperatively. – Conclusions: Outcome with regard to mortality and neurologic injury is very good in both -patients undergoing CEA alone as well as patients undergoing synchronous CEA and CABG using the MECC system. Although the CEA/CABG group showed slightly increased risk of stroke, it can be considered as combined treatment in particular clinical situations.

Cardiovascular disease in Switzerland - health care, mortality and geographical pattern

SUMMARY Switzerland is facing an aging population and a growing amount of patients with chronic diseases. It is crucial to display health care processes and pathways, to identify inequalities and obstacles, and to point out possibilities for improvements of the Swiss health care system (e.g. increase efficiency). The introductory part of the thesis presents a brief description of the Swiss health care system, health services research and regional variation as well as an introduction of CVD and its epidemiological key figures, aetiology and treatments. This is followed by the description of the utilized methods and data, and the objectives of this thesis. The subsequent sections present the four articles included in this thesis. The first article focuses on a small area analysis on regional variation of avoidable hospitalisations in Switzerland including density of primary care physicians and specialists, rurality and hospital supply factors as explanatory variables in the analysis. Lower rates of avoidable hospitalisations were found in areas with very high supply of primary care physicians, increased avoidable hospitalisation rates in areas with more specialists and in areas with higher proportion of rural residents. The second article aims to examine whether emergency patients with acute ST-segment elevation myocardial infarction were adequately treated, i.e. according to the treatment guidelines, in Switzerland. Results show that older and female patients were less likely to receive revascularization which suggests that the treatment guidelines may not be uniformly applied in Switzerland. Similar to the first article, also in the third article a small area analysis was performed but this time investigating regional variation in costs at the end of life. Strongest associations of cost was found with cause of death, age and language region of the decedents. The strong spatial variation of costs could only partly be explained by the included covariates. Article four aims to examine the relationship of distance to different hospital types and mortality from AMI or stroke. We found that AMI mortality in the Swiss population 30 and older and stroke mortality in those 65 and above increased with distance to central and university hospitals, while adjusting for sociodemographic and economic characteristics of the population. The presentation of the four articles is followed by a discussion, which summarizes the main findings and the strengths and limitations of the presented articles. The thesis concludes with a discussion about the challenges for policy, practice and future research.

Plasma Heme Oxygenase-1 in Patients Resuscitated from out-of-Hospital Cardiac Arrest

Heme oxygenase-1 (HO-1) is an enzyme induced by hypoxia and reperfusion injury, and is associated with organ dysfunction in critically ill patients. Patients resuscitated from out-of-hospital cardiac arrest (OHCA) are subjected to hypoxemia, brain injury, and organ dysfunction. Accordingly, we studied HO-1 among these patients. A total of 143 OHCA patients resuscitated from a shockable initial rhythm and admitted to an ICU were included, with plasma HO-1 measured at ICU admission and at 24 h. We analyzed the associations between plasma HO-1 and time to return of spontaneous circulation (ROSC), 90-day mortality, and 12-month Cerebral Performance Category (CPC). HO-1 plasma concentrations were higher after OHCA compared with controls. HO-1 concentrations at admission and on day 1 associated with ROSC (P = 0.002 to P = 0.003). Admission and day 1 HO-1 plasma concentrations were higher in 90-day non-survivors than in survivors (P = 0.017, 0.026). In addition, poor neurological outcome (CPC 3-5) was associated with higher HO-1 plasma levels at admission (P = 0.024). Admission plasma HO-1 levels had an AUC of 0.623 to predict 90-day mortality and an AUC of 0.611 to predict CPC 3 to 5. In conclusion, we found that higher HO-1 plasma levels are associated with longer ROSC and poor long-term outcome.

NT-proBNP in patients with out-of-hospital cardiac arrest: Results from the FINNRESUSCI Study

AIM To assess whether the established cardiovascular biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP) provides prognostic information in patients with out-of-hospital cardiac arrest due to ventricular tachycardia or fibrillation (OHCA-VT/VF). METHODS We measured NT-proBNP levels in 155 patients with OHCA-VT/VF enrolled into a prospective multicenter observational study in 21 ICUs in Finland. Blood samples were drawn <6h of OHCA-VT/VF and later after 24h, 48h, and 96h. The end-points were mortality and neurological outcome classified according to Cerebral Performance Category (CPC) after one year. NT-proBNP levels were compared to high-sensitivity troponin T (hs-TnT) levels and established risk scores. RESULTS NT-proBNP levels were higher in non-survivors compared to survivors on study inclusion (median 1003 [quartile (Q) 1-3 502-2457] vs. 527 [179-1284]ng/L, p=0.001) and after 24h (1913 [1012-4573] vs. 1080 [519-2210]ng/L, p<0.001). NT-proBNP levels increased from baseline to 96h after ICU admission (p<0.001). NT-proBNP levels were significantly correlated to hs-TnT levels after 24h (rho=0.27, p=0.001), but not to hs-TnT levels on study inclusion (rho=0.05, p=0.67). NT-proBNP levels at all time points were associated with clinical outcome, but only NT-proBNP levels after 24h predicted mortality and poor neurological outcome, defined as CPC 3-5, in models that adjusted for SAPS II and SOFA scores. hs-TnT levels did not add prognostic information to NT-proBNP measurements alone. CONCLUSION NT-proBNP levels at 24h improved risk assessment for poor outcome after one year on top of established risk indices, while hs-TnT measurements did not further add to risk prediction.

Time-differentiated target temperature management after out-of-hospital cardiac arrest: a multicentre, randomised, parallel-group, assessor-blinded clinical trial (the TTH48 trial): study protocol for a randomised controlled trial

BACKGROUND The application of therapeutic hypothermia (TH) for 12 to 24 hours following out-of-hospital cardiac arrest (OHCA) has been associated with decreased mortality and improved neurological function. However, the optimal duration of cooling is not known. We aimed to investigate whether targeted temperature management (TTM) at 33 ± 1 °C for 48 hours compared to 24 hours results in a better long-term neurological outcome. METHODS The TTH48 trial is an investigator-initiated pragmatic international trial in which patients resuscitated from OHCA are randomised to TTM at 33 ± 1 °C for either 24 or 48 hours. Inclusion criteria are: age older than 17 and below 80 years; presumed cardiac origin of arrest; and Glasgow Coma Score (GCS) <8, on admission. The primary outcome is neurological outcome at 6 months using the Cerebral Performance Category score (CPC) by an assessor blinded to treatment allocation and dichotomised to good (CPC 1-2) or poor (CPC 3-5) outcome. Secondary outcomes are: 6-month mortality, incidence of infection, bleeding and organ failure and CPC at hospital discharge, at day 28 and at day 90 following OHCA. Assuming that 50 % of the patients treated for 24 hours will have a poor outcome at 6 months, a study including 350 patients (175/arm) will have 80 % power (with a significance level of 5 %) to detect an absolute 15 % difference in primary outcome between treatment groups. A safety interim analysis was performed after the inclusion of 175 patients. DISCUSSION This is the first randomised trial to investigate the effect of the duration of TTM at 33 ± 1 °C in adult OHCA patients. We anticipate that the results of this trial will add significant knowledge regarding the management of cooling procedures in OHCA patients. TRIAL REGISTRATION NCT01689077.