Stephan Marsch

Inflammation and Long-Term Mortality After Non–ST Elevation Acute Coronary Syndrome Treated With a Very Early Invasive Strategy in 1042 Consecutive Patients

Background—This study sought to evaluate the predictive value of C-reactive protein (CRP) on long-term mortality in non–ST-elevation acute coronary syndromes (NSTACS) that were treated with a very early aggressive revascularization strategy. Methods and Results—We conducted a prospective cohort study in 1042 consecutive patients with NSTACS who were undergoing coronary angiography and subsequent coronary stenting of the culprit lesion as the primary revascularization strategy within 24 hours. Levels of CRP were determined on admission. The patients were followed for a mean of 20 months. In-hospital mortality was significantly higher in patients with a CRP>10 mg/L (3.7% versus 1.2% with CRP<3 mg/L and versus 0.8% with CRP of 3 to 10 mg/L; relative risk for CRP>10 mg/L compared with CRP≤10 mg/L was 4.2, 95% confidence interval [CI] was 1.6 to 11.0;P =0.004). The increase in mortality in patients with CRP>10 mg/L persisted during follow-up. Long-term mortality was 3.4% with CRP<3 mg/L, 4.4% with CRP between 3 and 10 mg/L, and 12.7% with CRP>10 mg/L (relative risk for CRP>10 mg/L compared with CRP≤10 mg/L, 0.8; 95% CI, 2.3 to 6.2;P <0.001). In addition, Kaplan-Meier survival analysis demonstrated a significantly reduced survival at 4 years in patients with a CRP>10 mg/L (78% versus 88% for a CRP of 3 to 10 mg/L and versus 92% for CRP<3 mg/L;P <0.001 by log-rank). In a multivariate analysis, CRP was an independent predictor of long-term mortality. Patients with a CRP>10 mg/L had >4 times the risk of death (odds ratio, 4.1; 95% CI, 2.3 to 7.2). Conclusion—CRP is a strong independent predictor of short and long-term mortality after NSTACS that are treated with very early revascularization.

Anesthetic drugs in status epilepticus: Risk or rescue? A 6-year cohort study

Objective: To evaluate the risks of continuously administered IV anesthetic drugs (IVADs) on the outcome of adult patients with status epilepticus (SE). Methods: All intensive care unit patients with SE from 2005 to 2011 at a tertiary academic medical care center were included. Relative risks were calculated for the primary outcome measures of seizure control, Glasgow Outcome Scale score at discharge, and death. Poisson regression models were used to control for possible confounders and to assess effect modification. Results: Of 171 patients, 37% were treated with IVADs. Mortality was 18%. Patients with anesthetic drugs had more infections during SE (43% vs 11%; p < 0.0001) and a 2.9-fold relative risk for death (2.88; 95% confidence interval 1.45–5.73), independent of possible confounders (i.e., duration and severity of SE, nonanesthetic third-line antiepileptic drugs, and critical medical conditions) and without significant effect modification by different grades of SE severity and etiologies. As IVADs were used after first- and second-line drugs failed, there was a correlation between treatment-refractory SE and the use of IVADs, leading to insignificant results regarding the risk of IVADs and outcome after additional adjustment for refractory SE. Conclusion: Our findings heighten awareness regarding adverse effects of IVADs. Randomized controlled trials are needed to further clarify the association of IVADs with outcome in patients with SE. Classification of evidence: This study provides Class III evidence that patients with SE receiving IVADs have a higher proportion of infection and an increased risk of death as compared to patients not receiving IVADs.

Brief leadership instructions improve cardiopulmonary resuscitation in a high-fidelity simulation: A randomized controlled trial

Objective:The influence of teaching leadership on the performance of rescuers remains unknown. The aim of this study was to compare leadership instruction with a general technical instruction in a high-fidelity simulated cardiopulmonary resuscitation scenario. Design:Prospective, randomized, controlled superiority trial, Setting:Simulator Center of the University Hospital Basel in Switzerland. Subjects:Two-hundred thirty-seven volunteer medical students in teams of three. Intervention:During a baseline visit, the medical students participated in a video-taped simulated witnessed cardiac arrest. Participants were thereafter randomized to receive instructions focusing either on correct positions of arms and shoulders (technical instruction group) or on leadership and communication to enhance team coordination (leadership instruction group). A follow-up simulation was conducted after 4 mos. Measurements and Main Results:The primary outcome were the amount of hands-on time, defined as duration of uninterrupted cardiopulmonary resuscitation in the first 180 secs after the onset of the cardiac arrest (hands-on time). Secondary outcomes were time to start cardiopulmonary resuscitation, total leadership utterances, and technical skills. Outcomes were compared based on videotapes coded by two independent researchers. After a balanced performance at baseline, the leadership instruction group demonstrated a longer hands-on time (120 secs; interquartile range, 98–135 vs. 87 secs; interquartile range, 61–108; p < .001), a shorter median time to start cardiopulmonary resuscitation (44 secs; interquartile range, 32–62; vs. 67 secs; interquartile range, 43–79; p = .018), and had more leadership utterances (7; interquartile range, 4–10; vs. 5; interquartile range, 2–8; p = .02) in the follow-up visit. The rate of correct arm and shoulder positions was higher in teams with technical instruction (59%; 19 out of 32; vs. 23%; 7 out of 31; p = .003). Conclusions:Video-assisted leadership and technical instructions after a simulated cardiopulmonary resuscitation scenario showed sustained efficacy after a 4-mo duration. Leadership instructions were superior to technical instructions, with more leadership utterances and better overall cardiopulmonary resuscitation performance.

Teamwork and Leadership in Cardiopulmonary Resuscitation

Despite substantial efforts to make cardiopulmonary resuscitation (CPR) algorithms known to healthcare workers, the outcome of CPR has remained poor during the past decades. Resuscitation teams often deviate from algorithms of CPR. Emerging evidence suggests that in addition to technical skills of individual rescuers, human factors such as teamwork and leadership affect adherence to algorithms and hence the outcome of CPR. This review describes the state of the science linking team interactions to the performance of CPR. Because logistical barriers make controlled measurement of team interaction in the earliest moments of real-life resuscitations challenging, our review focuses mainly on high-fidelity human simulator studies. This technique allows in-depth investigation of complex human interactions using precise and reproducible methods. It also removes variability in the clinical parameters of resuscitation, thus letting researchers study human factors and team interactions without confounding by clinical variability from resuscitation to resuscitation. Research has shown that a prolonged process of team building and poor leadership behavior are associated with significant shortcomings in CPR. Teamwork and leadership training have been shown to improve subsequent team performance during resuscitation and have recently been included in guidelines for advanced life support courses. We propose that further studies on the effects of team interactions on performance of complex medical emergency interventions such as resuscitation are needed. Future efforts to better understand the influence of team factors (e.g., team member status, team hierarchy, handling of human errors), individual factors (e.g., sex differences, perceived stress), and external factors (e.g., equipment, algorithms, institutional characteristics) on team performance in resuscitation situations are critical to improve CPR performance and medical outcomes of patients.

Cell-Specific Integration of Artificial Organelles Based on Functionalized Polymer Vesicles

Cell organelles are subcellular structures characterized by specific functionalities. They often consist of membrane-delineated microcompartments with a unique set of enzymes. Here we report the design of synthetic organelles based on nanometer-sized polymer vesicles, show their introduction into cells in a target-specific fashion, document their intact biochemical functionality in the cellular environment, and study their intracellular trafficking. This novel paradigm of introducing polymer-based artificial organelles to specific target cells for expansion of their biochemical capabilities appears suited for biomedical applications such as enzyme replacement in genetic diseases or, more generically, to add a desired biochemical function to a cell.

Cerebral perfusion in sepsis-associated delirium.

IntroductionThe pathophysiology of sepsis-associated delirium is not completely understood and the data on cerebral perfusion in sepsis are conflicting. We tested the hypothesis that cerebral perfusion and selected serum markers of inflammation and delirium differ in septic patients with and without sepsis-associated delirium.MethodsWe investigated 23 adult patients with sepsis, severe sepsis, or septic shock with an extracranial focus of infection and no history of intracranial pathology. Patients were investigated after stabilisation within 48 hours after admission to the intensive care unit. Sepsis-associated delirium was diagnosed using the confusion assessment method for the intensive care unit. Mean arterial pressure (MAP), blood flow velocity (FV) in the middle cerebral artery using transcranial Doppler, and cerebral tissue oxygenation using near-infrared spectroscopy were monitored for 1 hour. An index of cerebrovascular autoregulation was calculated from MAP and FV data. C-reactive protein (CRP), interleukin-6 (IL-6), S-100β, and cortisol were measured during each data acquisition.ResultsData from 16 patients, of whom 12 had sepsis-associated delirium, were analysed. There were no significant correlations or associations between MAP, cerebral blood FV, or tissue oxygenation and sepsis-associated delirium. However, we found a significant association between sepsis-associated delirium and disturbed autoregulation (P = 0.015). IL-6 did not differ between patients with and without sepsis-associated delirium, but we found a significant association between elevated CRP (P = 0.008), S-100β (P = 0.029), and cortisol (P = 0.011) and sepsis-associated delirium. Elevated CRP was significantly correlated with disturbed autoregulation (Spearman rho = 0.62, P = 0.010).ConclusionIn this small group of patients, cerebral perfusion assessed with transcranial Doppler and near-infrared spectroscopy did not differ between patients with and without sepsis-associated delirium. However, the state of autoregulation differed between the two groups. This may be due to inflammation impeding cerebrovascular endothelial function. Further investigations defining the role of S-100β and cortisol in the diagnosis of sepsis-associated delirium are warranted.Trial registrationClinicalTrials.gov NCT00410111.

Intelligent nanomaterials for medicine: Carrier platforms and targeting strategies in the context of clinical application

UNLABELLED Nanomedical approaches are a major transforming factor in medical diagnosis and therapies. Based on important earlier work in the field of liposomal drug delivery and metallic nanomaterials, the last decade has brought a broad array of new and improved intelligent nanoscale platforms which are not only suited to deliver drugs and imaging agents but also to carry advanced functionality including internal and external stimuli-responsiveness in a highly targeted fashion to a diseased area. This review focuses on required properties and differences of basic delivery platforms in regard to deliver smart functionality, on building blocks suited to enhance tissue-, cell- and receptor-specific targeting and on nano-bio interaction. Further it discusses advantages and disadvantages of those platforms for future clinical application with regard to the subject of complement activation and hypersensitivity reactions in particular against polyethylene glycol (PEG) and possible functionalization with nanosize switches. FROM THE CLINICAL EDITOR This review focuses on the properties of platforms designed to deliver smart functionality, using appropriate building blocks to enhance tissue-, cell-, and receptor-specific targeting. The authors also discuss potential complications such as complement activation and hypersensitivity reactions, and possible functionalization with nanosize switches.

Intravenous levetiracetam: Treatment experience with the first 50 critically ill patients

Levetiracetam (LEV) is a broad-spectrum antiepileptic drug with no known interactions and a favorable profile of adverse events. These properties make it a good candidate for use in critically ill patients. An intravenous formulation of LEV was recently approved. The present study retrospectively assesses the safety and efficacy of LEV in the first 50 critically ill patients treated with intravenous LEV. Indications for use were seizure prophylaxis, acute symptomatic seizures, and all forms of status epilepticus. There were no major adverse effects, although less prominent changes may have been masked by the already severely compromised condition of these patients. Two patients (4%) had transiently lowered platelet counts (55,000 and 82,000, respectively). Efficacy, defined as cessation of seizure activity or prevention of its recurrence, was observed in 41 of 50 patients (82%). Antiepileptic treatment of critically ill patients with LEV seems to be effective and safe according to the data for this small cohort, but this observation warrants further prospective investigation in a larger number of patients.

Performance of first responders in simulated cardiac arrests

Objective:Survival of in-hospital cardiac arrests depends more on first responders than on cardiac arrest teams. The objective of this study was to determine the adherence to algorithms of cardiopulmonary resuscitation of first responders in simulated cardiac arrests in intensive care. A second objective was to assess the effect of the early vs. late availability of a physician on the performance of nurse-based teams acting as first responders. Design:Prospective study. Setting:Patient simulator in a tertiary level intensive care unit. Participants:A total of 20 teams consisting of three registered nurses and one resident each. Interventions:A simulated witnessed cardiac arrest due to ventricular fibrillation occurred in the presence of one nurse while the remaining two nurses could be called to help. Depending on the time of the residents’ arrival, teams were classified as “early” (median arrival 50 secs after the onset of the arrest) or “late” (median arrival 150 secs after the onset of the arrest). Measurements and Main Results:In all teams, the recognition of the arrest and the calling for help occurred in a timely fashion. However, a median of 85 secs (interquartile range [IQ], 130 secs) elapsed until the start of cardiac massage and 100 secs (IQ, 45 secs) to the first defibrillation. Once commenced, cardiac massage and mask ventilation were carried out during 61% (IQ, 33%) and 77% (IQ, 23%) of the possible time only. Delays and interruptions were generally not recalled by the participants. Compared with teams with late arriving residents, teams with early arriving residents administered more countershocks: 4.5 (IQ, 2) vs. 3.5 (IQ, 1.5; p = .026). Conclusions:First responders in intensive care often failed to build a team structure that ensured timely, effective, monitored, and ongoing team activity. The early availability of a physician increased the number of countershocks administered. Self-reporting is unsuitable to reliably assess the quality of cardiopulmonary resuscitation.

Mortality and recovery from refractory status epilepticus in the intensive care unit: A 7‐year observational study

Refractory status epilepticus (RSE) is a life‐threatening neurologic emergency with high mortality and morbidity. The aim of this study was to identify and quantify associations between clinical characteristics of adult RSE patients and outcome.