[Ward-based clinical pharmacists in intensive care medicine: an economic evaluation]. / Stationsapotheker:innen in der Intensivmedizin: ökonomische Nutzenanalyse.

BACKGROUND: The positive impact of pharmaceutical care in improving medication safety is considered proven. Little is known about the economic benefit of clinical pharmaceutical services in Germany. OBJECTIVE: In 2020, a pilot project was started at the Ernst von Bergmann Hospital to introduce ward-based clinical pharmacists in intensive care medicine, also in order to determine the economic benefit of the medication management offered. METHODS: By a team of experienced intensive care physicians and clinical pharmacists on the basis of a consensus principle, each pharmaceutical intervention (PI) was assigned a probability score (Nesbit probability score) with which an adverse drug event (ADE) would have occurred. Assuming that each ADE results in an increased length of stay, the costs of intensive care treatment/day were used as potential savings. The model thereby combines the findings of two international publications to enable an economic analysis of pharmaceutical services. RESULTS: During the study period, 177 pharmaceutical interventions were evaluated and corresponding probability scores for the occurrence of ADE were determined. From this, annual savings of €â€¯80,000 through avoided costs were calculated. CONCLUSION: In this project, the economic benefit of pharmaceutical services in intensive care medicine was proven. Ward-based clinical pharmacists are now an integral part of the intensive care treatment team at the Ernst von Bergmann Hospital.

Establishment of an extracorporeal cardio-pulmonary resuscitation program in Berlin - outcomes of 254 patients with refractory circulatory arrest.

OBJECTIVE: Optimal management of out of hospital circulatory arrest (OHCA) remains challenging, in particular in patients who do not develop rapid return of spontaneous circulation (ROSC). Extracorporeal cardiopulmonary resuscitation (eCPR) can be a life-saving bridging procedure. However its requirements and feasibility of implementation in patients with OHCA, appropriate inclusion criteria and achievable outcomes remain poorly defined. DESIGN: Prospective cohort study. SETTING: Tertiary referral university hospital center. PATIENTS: Here we report on characteristics, course and outcomes on the first consecutive 254 patients admitted between August 2014 and December 2017. INTERVENTION: eCPR program for OHCA. MESUREMENTS AND MAIN RESULTS: A structured clinical pathway was designed and implemented as 24/7 eCPR service at the Charité in Berlin. In total, 254 patients were transferred with ongoing CPR, including automated chest compression, of which 30 showed or developed ROSC after admission. Following hospital admission predefined in- and exclusion criteria for eCPR were checked; in the remaining 224, 126 were considered as eligible for eCPR. State of the art postresuscitation therapy was applied and prognostication of neurological outcome was performed according to a standardized protocol. Eighteen patients survived, with a good neurological outcome (cerebral performance category (CPC) 1 or 2) in 15 patients. Compared to non-survivors survivors had significantly shorter time between collaps and start of eCPR (58 min (IQR 12-85) vs. 90 min (IQR 74-114), p = 0.01), lower lactate levels on admission (95 mg/dL (IQR 44-130) vs. 143 mg/dL (IQR 111-178), p <  0.05), and less severe acidosis on admission (pH 7.2 (IQR 7.15-7.4) vs. 7.0 (IQR6.9-7.2), p <  0.05). Binary logistic regression analysis identified latency to eCPR and low pH as independent predictors for mortality. CONCLUSION: An eCPR program can be life-saving for a subset of individuals with refractory circulatory arrest, with time to initiation of eCPR being a main determinant of survival.

Pre-hospital management of patients with chest pain and/or dyspnoea of cardiac origin. A position paper of the Acute Cardiovascular Care Association (ACCA) of the ESC.

Chest pain and acute dyspnoea are frequent causes of emergency medical services activation. The pre-hospital management of these conditions is heterogeneous across different regions of the world and Europe, as a consequence of the variety of emergency medical services and absence of specific practical guidelines. This position paper focuses on the practical aspects of the pre-hospital treatment on board and transfer of patients taken in charge by emergency medical services for chest pain and dyspnoea of suspected cardiac aetiology after the initial assessment and diagnostic work-up. The objective of the paper is to provide guidance, based on evidence, where available, or on experts' opinions, for all emergency medical services' health providers involved in the pre-hospital management of acute cardiovascular care.

Early clinical outcomes as a function of use of newer oral P2Y12 inhibitors versus clopidogrel in the EUROMAX trial.

Objective: To ascertain whether different oral P2Y12 inhibitors might affect rates of acute stent thrombosis and 30-day outcomes after primary percutaneous coronary intervention (pPCI). Methods: The European Ambulance Acute Coronary Syndrome Angiography (EUROMAX) randomised trial compared prehospital bivalirudin with heparin with optional glycoprotein IIb/IIIa inhibitor treatment in patients with ST-segment elevation myocardial infarction triaged to pPCI. Choice of P2Y12 inhibitor was at the investigator's discretion. In a prespecified analysis, we compared event rates with clopidogrel and newer oral P2Y12 inhibitors (prasugrel, ticagrelor). Rates of the primary outcome (acute stent thrombosis) were examined as a function of the P2Y12 inhibitor used for loading and 30-day outcomes (including major adverse cardiac events) as a function of the P2Y12 inhibitor used for maintenance therapy. Logistic regression was used to adjust for differences in baseline characteristics. Results: Prasugrel or ticagrelor was given as the loading P2Y12 inhibitor in 49% of 2198 patients and as a maintenance therapy in 59%. No differences were observed in rates of acute stent thrombosis for clopidogrel versus newer P2Y12 inhibitors (adjusted OR 0.50, 95% CI 0.13 to 1.85). After adjustment, no difference was observed in 30-day outcomes according to maintenance therapy except for protocol major (p=0.029) or minor (p=0.025) bleeding and Thrombolysis In Myocardial Infarction minor bleeding (p=0.002), which were less frequent in patients on clopidogrel. Consistent results were observed in the bivalirudin and heparin arms. Conclusions: The choice of prasugrel or ticagrelor over clopidogrel was not associated with differences in acute stent thrombosis or 30-day ischaemic outcomes after pPCI. Trial registration number: NCT01087723.

[Pre-hospital management of patients with chest pain and/or dyspnoea of cardiac origin.] / Gestione pre-ospedaliera dei pazienti con dolore toracico e/o dispnea di origine cardiacaPosition Paper Acute Cardiovascular Care Association (ACCA) della Società Europea di Cardiologia.

Chest pain and acute dyspnoea are frequent causes of emergency medical services activation. The pre-hospital management of these conditions is heterogeneous across different regions of the world and Europe, as a consequence of the variety of emergency medical services and absence of specific practical guidelines. This position paper focuses on the practical aspects of the pre-hospital treatment on board and transfer of patients taken in charge by emergency medical services for chest pain and dyspnoea of suspected cardiac aetiology after the initial assessment and diagnostic work-up. The objective of the paper is to provide guidance, based on evidence, where available, or on experts' opinions, for all emergency medical services' health providers involved in the pre-hospital management of acute cardiovascular care.

Bivalirudin is superior to heparins alone with bailout GP IIb/IIIa inhibitors in patients with ST-segment elevation myocardial infarction transported emergently for primary percutaneous coronary intervention: a pre-specified analysis from the EUROMAX trial.

AIMS: In the HORIZONS trial, in-hospital treatment with bivalirudin reduced bleeding and mortality in primary percutaneous coronary intervention (PCI) compared with heparin and routine glycoprotein IIb/IIIa inhibitors (GPI). It is unknown whether this advantage of bivalirudin is observed in comparison with heparins only with GPI used as bailout. METHODS AND RESULTS: In the EUROMAX study, 2198 patients with ST-segment elevation myocardial infarction (STEMI) were randomized during transport for primary PCI to bivalirudin or to heparins with optional GPI. Primary and principal outcome was the composites of death or non-CABG-related major bleeding at 30 days. This pre-specified analysis compared patients receiving bivalirudin (n = 1089) with those receiving heparins with routine upstream GPI (n = 649) and those receiving heparins only with GPI use restricted to bailout (n = 460). The primary outcome death and major bleeding occurred in 5.1% with bivalirudin, 7.6% with heparin plus routine GPI (HR 0.67 and 95% CI 0.46-0.97, P = 0.034), and 9.8% with heparins plus bailout GPI (HR 0.52 and 95% CI 0.35-0.75, P = 0.006). Following adjustment by logistic regression, bivalirudin was still associated with significantly lower rates of the primary outcome (odds ratio 0.53, 95% CI 0.33-0.87) and major bleeding (odds ratio 0.44, 95% CI 0.24-0.82) compared with heparins alone with bailout GPI. Rates of stent thrombosis were higher with bivalirudin (1.6 vs. 0.6 vs. 0.4%, P = 0.09 and 0.09). CONCLUSION: Bivalirudin, started during transport for primary PCI, reduces major bleeding compared with both patients treated with heparin only plus bailout GPI and patients treated with heparin and routine GPI, but increased stent thrombosis.

Bivalirudin started during emergency transport for primary PCI.

BACKGROUND: Bivalirudin, as compared with heparin and glycoprotein IIb/IIIa inhibitors, has been shown to reduce rates of bleeding and death in patients undergoing primary percutaneous coronary intervention (PCI). Whether these benefits persist in contemporary practice characterized by prehospital initiation of treatment, optional use of glycoprotein IIb/IIIa inhibitors and novel P2Y12 inhibitors, and radial-artery PCI access use is unknown. METHODS: We randomly assigned 2218 patients with ST-segment elevation myocardial infarction (STEMI) who were being transported for primary PCI to receive either bivalirudin or unfractionated or low-molecular-weight heparin with optional glycoprotein IIb/IIIa inhibitors (control group). The primary outcome at 30 days was a composite of death or major bleeding not associated with coronary-artery bypass grafting (CABG), and the principal secondary outcome was a composite of death, reinfarction, or non-CABG major bleeding. RESULTS: Bivalirudin, as compared with the control intervention, reduced the risk of the primary outcome (5.1% vs. 8.5%; relative risk, 0.60; 95% confidence interval [CI], 0.43 to 0.82; P=0.001) and the principal secondary outcome (6.6% vs. 9.2%; relative risk, 0.72; 95% CI, 0.54 to 0.96; P=0.02). Bivalirudin also reduced the risk of major bleeding (2.6% vs. 6.0%; relative risk, 0.43; 95% CI, 0.28 to 0.66; P<0.001). The risk of acute stent thrombosis was higher with bivalirudin (1.1% vs. 0.2%; relative risk, 6.11; 95% CI, 1.37 to 27.24; P=0.007). There was no significant difference in rates of death (2.9% vs. 3.1%) or reinfarction (1.7% vs. 0.9%). Results were consistent across subgroups of patients. CONCLUSIONS: Bivalirudin, started during transport for primary PCI, improved 30-day clinical outcomes with a reduction in major bleeding but with an increase in acute stent thrombosis. (Funded by the Medicines Company; EUROMAX ClinicalTrials.gov number, NCT01087723.).

Design and methods of European Ambulance Acute Coronary Syndrome Angiography Trial (EUROMAX): an international randomized open-label ambulance trial of bivalirudin versus standard-of-care anticoagulation in patients with acute ST-segment-elevation myocardial infarction transferred for primary percutaneous coronary intervention.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) triaged to primary percutaneous coronary intervention (PCI), anticoagulation often is initiated in the ambulance during transfer to a PCI site. In this prehospital setting, bivalirudin has not been compared with standard-of-care anticoagulation. In addition, it has not been tested in conjunction with the newer P2Y12 inhibitors prasugrel or ticagrelor. DESIGN: EUROMAX is a randomized, international, prospective, open-label ambulance trial comparing bivalirudin with standard-of-care anticoagulation with or without glycoprotein IIb/IIIa inhibitors in 2200 patients with STEMI and intended for primary percutaneous coronary intervention (PCI), presenting either via ambulance or to centers where PCI is not performed. Patients will receive either bivalirudin given as a 0.75 mg/kg bolus followed immediately by a 1.75-mg/kg per hour infusion for ≥30 minutes prior to primary PCI and continued for ≥4 hours after the end of the procedure at the reduced dose of 0.25 mg/kg per hour, or heparins at guideline-recommended doses, with or without routine or bailout glycoprotein IIb/IIIa inhibitor treatment according to local practice. The primary end point is the composite incidence of death or non-coronary-artery-bypass-graft related protocol major bleeding at 30 days by intention to treat. CONCLUSION: The EUROMAX trial will test whether bivalirudin started in the ambulance and continued for 4 hours after primary PCI improves clinical outcomes compared with guideline-recommended standard-of-care heparin-based regimens, and will also provide information on the combination of bivalirudin with prasugrel or ticagrelor.

Fate of patients with prehospital resuscitation for ST-elevation myocardial infarction and a high rate of early reperfusion therapy (results from the PREMIR [Prehospital Myocardial Infarction Registry]).

Patients with acute ST-segment elevation myocardial infarction (STEMI) needing prehospital cardiopulmonary resuscitation (CPR) have a very high adverse-event rate. However, little is known about the fate of these patients and predictors of mortality in the era of early reperfusion therapy. From March 2003 through December 2004, 2,317 patients with prehospital diagnosed STEMI were enrolled in the Prehospital Myocardial Infarction Registry. One hundred ninety patients (8.2%) underwent prehospital CPR and were included in our analysis. Overall 90% of patients were treated with early reperfusion therapy, 56.3% received prehospital thrombolysis and 1/2 of these patients received early percutaneous coronary intervention after thrombolysis, 28.4% of patients were treated with primary percutaneous coronary intervention, and 5.3% received in-hospital thrombolysis. Total mortality was 40.0%. The highest mortality was seen in patients with asystole (63%) or pulseless electric activity (64%). Independent predictors of mortality were need for endotracheal intubation and older age, whereas ventricular fibrillation as initial heart rhythm was associated with survival. In conclusion, in this large registry with prehospital diagnosed STEMI, incidence of prehospital CPR was about 8%. Even with a very high rate of early reperfusion therapy, in-hospital mortality was high. Especially in elderly patients with asystole as initial heart rhythm and with need for endotracheal intubation, prognosis is poor despite aggressive reperfusion therapy.

A rare case of neuroleptic malignant syndrome presenting with serious hyperthermia treated with a non-invasive cooling device: a case report.

INTRODUCTION: A rare side effect of antipsychotic medication is neuroleptic malignant syndrome, mainly characterized by hyperthermia, altered mental state, haemodynamic dysregulation, elevated serum creatine kinase and rigor. There may be multi-organ dysfunction including renal and hepatic failure as well as serious rhabdomyolysis, acute respiratory distress syndrome and disseminated intravascular coagulation. The prevalence of neuroleptic malignant syndrome is between 0.02% and 2.44% for patients taking neuroleptics and it is not necessary to fulfil all cardinal features characterizing the syndrome to be diagnosed with neuroleptic malignant syndrome. Because of other different life-threatening diseases matching the various clinical findings, the correct diagnosis can sometimes be hard to make. A special problem of intensive care treatment is the management of severe hyperthermia. Lowering of body temperature, however, may be a major clinical problem because hyperthermia in neuroleptic malignant syndrome is typically unresponsive to antipyretic agents while manual cooling proves difficult due to peripheral vasoconstriction. CASE PRESENTATION: A 22-year-old Caucasian man was admitted unconscious with a body temperature of 42 degrees C, elevated serum creatine phosphokinase, tachycardia and hypotonic blood pressure. In addition to intensive care standard therapy for coma and shock, a non-invasive cooling device (Arctic Sun 2000((R)), Medivance Inc., USA), originally designed to induce mild therapeutic hypothermia in patients after cardiopulmonary resuscitation, was used to lower body temperature. After successful treatment it became possible to obtain information from the patient about his recent ambulant treatment with Olanzapin (Zyprexa(R)) for schizophrenia. CONCLUSION: Numerous case reports have been published about patients who developed neuroleptic malignant syndrome due to Olanzapin (Zyprexa(R)) medication. Frequently hyperthermia has been observed in these cases with varying outcomes. In our case the only residual impairment for the patient is dysarthria with corresponding symmetric cerebellar pyramidal cell destruction demonstrated by increased signal intensity in T2-weighted magnetic resonance imaging, most likely caused by the excessive hyperthermia.

Reperfusion rate and inhospital mortality of patients with ST segment elevation myocardial infarction diagnosed already in the prehospital phase: results of the German Prehospital Myocardial Infarction Registry (PREMIR).

AIMS: We sought to evaluate the in-hospital fate of patients with ST segment elevation myocardial infarction (STEMI) diagnosed already in the prehospital phase by physican equipped ambulances. METHODS: A total of 2326 consecutive STEMI patients were included in PREMIR. For this analysis 218 patients with prehospital cardiopulmonary resuscitation were excluded. RESULTS: The median time between symptom onset and 12-lead ECG was 85 min. The median time intervals between the diagnostic 12-lead ECG and prehospital fibrinolysis were 10 min, until inhospital fibrinolysis 52 min and until primar PCI 86min, respectively. Reperfusion therapy with prehospital fibrinolysis (24%), inhospital fibrinolysis (13%) or primary PCI (45%) was performed in 82% of the patients. Inhospital mortality was 6.0% in patients with prehospital fibrinolysis (n = 504), 5.8% in patients with inhospital fibrinolysis (n = 278), 4.5% in patients with primary percutaneous coronary intervention (n = 962) and 16.2% in patients without early reperfusion therapy (n = 377), respectively. In the multivariate propensity score analysis comparing prehospital fibrinolysis and primary PCI we observed no significant difference in the odds for in-hospital mortality (odds ratio: 1.57, 95% CI: 0.94-2.63). The final discharge diagnosis was STEMI in 90% of the patients, in patients with prehospital fibrinolysis 95%. CONCLUSIONS: In patients with STEMI already diagnosed in the prehospital phase the ischemic time is short, accuracy of the diagnosis is high and reperfusion therapy is performed in over 82%. Inhospital mortality was not different between prehospital fibrinolysis and primary PCI.

Facilitated percutaneous coronary intervention (PCI) in patients with acute ST-elevation myocardial infarction: comparison of prehospital tirofiban versus fibrinolysis before direct PCI.

AIMS: Early start of treatment including coronary revascularization has been recognized as crucial variable in the outcome of acute ST-segment elevation myocardial infarction (STEMI). The lack of availability and the realisation that an optimum reperfusion strategy will need to incorporate mechanical reperfusion as part of that strategy has led to a great deal of interest in pharmacologic reperfusion combined with mechanical reperfusion or facilitated PCI. It is not clear whether GPIIb/IIIa-blockade or fibrinolysis better facilitates PCI. METHODS: We identified 138 patients who have been primarily treated by our mobile emergency care mobile from July 2001 until February 2003 with tirofiban or fibrinolysis. Seventy-nine patients had ST-elevation myocardial infarction (STEMI) and available angiograms within 24 h. RESULTS: Forty-four patients had tirofiban (TIRO; 60.6 S.D. 11.4 years, 64% male) and 35 patients underwent fibrinolysis (FIB; 31.4% tenecteplase, 54.3% reteplase, 11.4% alteplase, 2.9% streptokinase; 58.8 S.D. 12.2 years, 80% male). Data were analyzed with respect to TIMI-flow and corrected frame count (cTFC) before and after PCI, bleeding complications at 30 days and long-term follow up for major adverse events (median 288 days; MACE: Death, hospitalized re-infarction, intracranial hemorrhage). Catheter films were re-analyzed by an investigator blinded to the prehospital therapy. Time from onset of symptoms to first medical contact was 1.98 h in TIRO compared to 0.5 h in FIB (p<0.001) and time from first prehospital medical contact to catheter was 1.46 h in the TIRO compared to 2.85 h in the FIB group (p<0.001). TIMI 3-flow before PCI was observed in 20.5% of TIRO and 62.9% in FIB (p<0.001). After PCI TIMI 3-flow was achieved in 90.5% and 90.0%, respectively (p=n.s.). Final cTFC was 24 in TIRO and 29 in FIB (p=n.s.). Visible thrombi were detected in 30.2% in TIRO and 23.5% in FIB (p=n.s.). Major bleeding occurred in one TIRO patient (fatal lung bleeding after ultima ratio abciximab on top of tirofiban), 2 patients (4.5%) received transfusions. In FIB 2 intracerebral hemorrhages, 5 transfusions (14.3%) and 3 pulmonary bleedings during mandatory ventilation were observed. After 30 days 4.5% in TIRO and 22.9% in FIB had MACE (p=0.015). During long-term follow up the primary endpoint was observed in 4.5% of TIRO and 28.6% (p=0.003) of FIB. Two patients died in TIRO and 9 patients in FIB. CONCLUSIONS: We conclude that (1) prehospital start of tirofiban for facilitated PCI is safe and effective if administered by experienced emergency physicians; (2) routine fibrinolysis should be limited to areas where catheter based therapy is not available within 90 min and (3) fibrinolysis should be given for facilitated PCI in randomized trials only at the moment.

Inadvertent puncture of the thoracic duct during attempted central venous catheter placement.

We report a case of puncture of the thoracic duct during left subclavian vein catheterization on the intensive care unit. Computed tomography and measurement of the triglyceride levels in the aspirated fluid proved the inadvertent penetration of the guidewire into the thoracic duct. Early recognition of central line misplacement avoided serious complications. Inadvertent central venous catheter placement into the thoracic duct may have the potential complications of infusion mediastinum and chylothorax.