Mathematische Modelle zur Prognose und Differentialdiagnose der Sepsis anhand eines SIRS-Algorithmus und Routineparameter der Intensivstation

Im Beobachtungszeitraum von April 2006 bis Oktober 2011 wurden Daten zu 13.548 Intensivpatienten in der elektronischen Patientenakte aufgezeichnet. Daraus wurden 256 Polytraumapatienten, darunter 85 Sepsisfälle, durch einen automatisierten Auswahlschritt, gefolgt von manueller, ärztlicher Validierung identifiziert und für diese auch gegebenenfalls der Zeitpunkt ihrer Sepsis bestimmt. Die klinischen SIRS-Kriterien wurden für die Anwendung bei Intensivpatienten durch die Berücksichtigung einer maschinellen Unterstützung der Beatmung sowie Kreislaufunterstützung durch Katecholamine erweitert und in einen Algorithmus übersetzt. Mit dessen Hilfe konnte für jede Minute des Patientenaufenthaltes die Anzahl der erfüllten SIRS-Kriterien bestimmt werden. Diese wurden nachfolgend auf verschiedene Weise zusammengefasst und als SIRS-Parameter in logistischen und bedingten logistischen Regressionsmodellen auf ihren Zusammenhang mit der Sepsis hin analysiert. Zusätzlich wurden die SIRS-Kriterien anhand von drei Deskriptoren als dynamische Parameter für relevante Zeitabschnitte im Behandlungsverlauf zusammengefasst. Dies geschah unter Berücksichtigung der Veränderung der Zahl der SIRS-Kriterien in einer gegebenen Minute im Vergleich zur vorhergehenden Minute. Als SIRS-Deskriptoren eines Intervalls wurden (1) der Durchschnitt der erfüllten SIRS-Kriterien als durchschnittliches λ, (2) die Anzahl der Veränderungen in der Anzahl der SIRS-Kriterien von einer Minute zur nächsten als C und (3) die Differenz der Anzahl der SIRS-Kriterien in der letzten und der ersten Minute des Intervalls als Trend Δ definiert. Für die Vorhersage der Sepsis wurden Sepsisfälle mit allen übrigen Patienten der Polytraumakohorte verglichen, dazu wurden die SIRS-Deskriptoren der ersten 24 Stunden nach Aufnahme untersucht und ihre Eignung zur Sepsisidentifikation mit dem klassischen SIRS verglichen. Zur Erkennung von Sepsisfällen zum Zeitpunkt ihrer Diagnosestellung (Differentialdiagnose) wurden diese im Rahmen einer eingebetteten Fall-Kontroll-Studie mit 10.995 sepsisfreien Kontrollintervallen gleicher Behandlungsdauer gematcht. In Fällen und Kontrollen wurden die SIRS-Deskriptoren des 24-Stunden Intervalls vor Sepsisdiagnose bzw. vor dem für das Matching herangezogenen Zeitpunkt verglichen. Für die multivariable Modellierung wurden neben SIRS-Parametern weitere 59 Parameter als mögliche Sepsisrisikofaktoren aus der elektronischen Datenbasis definiert, für die zunächst univariable Analysen durchgeführt wurden. Die multivariable Modellentwicklung erfolgte mit Hilfe von automatisierten Selektionsmethoden (Stepwise- und Forward-Methode), die auf alle Parameter und vorausgewählte Parametergruppen angewendet wurden. Für die Sepsisvorhersage mit SIRS-Deskriptoren wurde logistische Regression, für die Differentialdiagnose der Sepsis mit SIRS-Deskriptoren wurde auch bedingte logistische Regression angewendet. Die Daten der elektronischen Patientenakte der operativen Intensivstation der Universitätsmedizin Mannheim erlaubten eine erfolgreiche Umsetzung der klinischen SIRS-Kriterien mit einem Algorithmus. Mit Hilfe des Algorithmus wurde eine durchschnittliche Prävalenz des konventionellen SIRS (≥2 Kriterien) auf der Intensivstation der UMM von 43,3% bestimmt. Von 256 Polytraumapatienten entwickelten 85 (33,2%) eine Sepsis. Das konventionelle SIRS mit mindestens ≥1 Minute hatte eine Sensitivität von 91% und eine Spezifität von 19%, während ein SIRS-Kriteriendurchschnitt (durchschnittliches λ) von 1,72 eine Sensitivität von 51% und eine Spezifität von 77% zur Vorhersage der Sepsis hatte. Für die Sepsisdiagnose konnten, im Vergleich zum konventionellen SIRS, das eine Sensitivität von 99% und eine Spezifität von nur 31% aufwies, eine Sensitivität von 82% und eine Spezifität von 71% mit einer Kombination aus durchschnittlichem λ und dem Trend Δ erreicht werden. Das multivariable Modell, das statistisch und klinisch am besten für die Sepsisvorhersage geeignet war, enthielt 11 Parameter: neben der Anzahl der Minuten mit mehr als 2 erfüllten SIRS-Kriterien (SIRS-Zeit) den SAPSII, Thrombozyten, Kreatinin, Hb, Hkt, ISS, Ramsay-Skala, Vorerkrankungen der Atemwege und des Herz-Kreislauf Systems, sowie Diabetes. Das Modell erreichte eine AUC von 0,856. Das am besten zur Differentialdiagnose geeignete Modell beinhaltete 9 Parameter: den SIRS-Kriteriendurchschnitt (SIRS-Niveau) 8-4 Stunden vor Sepsisdiagnose, Temperatur, Laktat, Transfusion von Erythrozytenkonzentraten, Produkt aus AMV x pCO2, FiO2, Katecholamingabe, GCS und AIS Schädel. Es wies eine AUC von 0,864 auf. In dieser Arbeit wurde der Nutzen von Routinedaten für klinisch relevante, medizinische Fragestellungen aus der Intensivmedizin anhand einer umfassenden, komplexen Datenbasis gezeigt. Dies konnte insbesondere durch Entwicklung eines SIRS-Algorithmus dargestellt werden. Durch Umsetzung in einen dynamischen Parameter konnte für SIRS bei Polytraumapatienten eine Verbesserung der Spezifität für die Vorhersage der Sepsis, für die Differentialdiagnose eine Sensitivität und Spezifität erreicht werden, die mit etablierten Biomarkern konkurrieren kann. Auch für die multivariable Modellierung spielten mittels des SIRS-Algorithmus definierte Parameter eine wichtige Rolle für die Vorhersage und Differentialdiagnose der Sepsis bei Patienten nach erlittenem Polytrauma

Is antibacterial treatment intensity lower in elderly patients? A retrospective cohort study in a German surgical intensive care unit

Background: Demographic change concurrent with medical progress leads to an increasing number of elderly patients in intensive care units (ICUs). Antibacterial treatment is an important, often life-saving, aspect of intensive care but burdened by the associated antimicrobial resistance risk. Elderly patients are simultaneously at greater risk of infections and may be more restrictively treated because, generally, treatment intensity declines with age. We therefore described utilization of antibacterials in ICU patients older and younger than 80 years and examined differences in the intensity of antibacterial therapy between both groups. Methods: We analysed 17,464 valid admissions from the electronic patient data management system of our surgical ICU from April 2006 – October 2013. Antibacterial treatment rates were defined as days of treatment (exposed patient days) relative to patient days of ICU stay and calculated for old and young patients. Rates were compared in zero-inflated Poisson regression models adjusted for patients’ sex, mean SAPS II- and TISS-scores, and calendar years yielding adjusted rate ratios (aRRs). Rate ratios exceeding 1 represent higher rates in old patients reflecting greater treatment intensity in old compared to younger patients. Results: Observed antibacterial treatment rates were lower in patients 80 years and older compared to younger patients (30.97 and 39.73 exposed patient days per 100 patient days in the ICU, respectively). No difference in treatment intensity, however, was found from zero-inflated Poisson regression models permitting more adequate consideration of patient days with low treatment probability: for all antibacterials the adjusted rate ratio (aRR) was 1.02 (95%CI: 0.98–1.07). Treatment intensities were higher in elderly patients for penicillins (aRR 1.37 (95%CI: 1.26–1.48)), cephalosporins (aRR 1.20 (95%CI: 1.09–1.31)), carbapenems (aRR 1.35 (95%CI: 1.20–1.50)), fluoroquinolones (aRR 1.17 (95%CI: 1.05–1.30), and imidazoles (aRR 1.34 (95%CI: 1.23–1.46)). Conclusions: Elderly patients were generally less likely to be treated with antibacterials. This observation, however, did not persist in patients with comparable treatment probability. In these, antibacterial treatment intensity did not differ between younger and older ICU patients, for some antibacterial classes treatment intensity was even higher in the latter. Patient-level covariates are instrumental for a nuanced evaluation of age-effects in antibacterial treatment in the ICU

Concomitant mitral regurgitation in patients with low-gradient aortic stenosis: an analysis from the German Aortic Valve Registry

Background: Patients with severe aortic stenosis (AS) frequently presented mitral regurgitation (MR), which may interfere with the standard echocardiographic measurements of mean pressure gradient (MPG), flow velocity, and aortic valve area (AVA). Aims: Herein we investigated the prevalence and severity of MR in patients with severe AS and its role on the accuracy of the standard echocardiographic parameters of AS quantification. Methods: Of all patients with severe AS undergoing transcatheter or surgical aortic valve replacement enrolled in the German Aortic Registry from 2011 to 2017, 119,641 were included in this study. The population was divided based on the values of left ventricular ejection fraction ([LVEF] > 50%, LVEF 31-50%, and LVEF <= 30%] and AVA (0.80 to <= 1.00 cm(2), 0.60 to < 0.80 cm(2), 0.40 to < 0.60 cm(2), and 0.20 to < 0.40 cm(2)). Results: Overall, 77,890 (65%) patients with mild to-moderate and 4262 (4%) with severe MR were compared with 37,489 (31%) patients without MR. Patients with mild-to-moderate and severe MR presented significantly lower mPG (Delta mPG [95%CI] - 1.694 mmHg [- 2.123 to - 1.265], p 50%: AVA 0.80 to 1.00 cm(2); LVEF 31-50%: AVA 0.60 to 0.80 cm(2)). Conclusions: In patients with severe AS, concomitant MR is common, contributes to the onset of a low-gradient AS pattern, and affects the diagnostic accuracy of flow-dependent AVA measurements. In this setting, a multimodality, AVA-centric approach should be implemented

Percutaneous Thermal Ablation Therapy of Hepatocellular Carcinoma (HCC): Microwave Ablation (MWA) versus Laser-Induced Thermotherapy (LITT)

The purpose of this study is to compare the efficacy and safety of microwave ablation (MWA) versus laser-induced thermotherapy (LITT) as a local treatment for hepatocellular carcinoma (HCC,) with regard to therapy response, survival rates, and complication rates as measurable outcomes. This retrospective study included 250 patients (52 females and 198 males; mean age: 66 ± 10 years) with 435 tumors that were treated by MWA and 53 patients (12 females and 41 males; mean age: 67.5 ± 8 years) with 75 tumors that were treated by LITT. Tumor response was evaluated using CEMRI (contrast-enhanced magnetic resonance imaging). Overall, 445 MWA sessions and 76 LITT sessions were performed. The rate of local tumor progression (LTP) and the rate of intrahepatic distant recurrence (IDR) were 6% (15/250) and 46% (115/250) in the MWA-group and 3.8% (2/53) and 64.2% (34/53) in the LITT-group, respectively. The 1-, 3-, and 5-year overall survival (OS) rates calculated from the date of diagnosis were 94.3%, 65.4%, and 49.1% in the MWA-group and 96.2%, 54.7%, and 30.2% in the LITT-group, respectively (p-value: 0.002). The 1-, 2-, and 3-year disease-free survival (DFS) rates were 45.9%, 30.6%, and 24.8% in the MWA-group and 54.7%, 30.2%, and 17% in the LITT-group, respectively (p-value: 0.719). Initial complete ablation rate was 97.7% (425/435) in the MWA-group and 98.7% (74/75) in the LITT-group (p-value > 0.99). The overall complication rate was 2.9% (13/445) in the MWA-group and 7.9% (6/76) in the LITT-group (p-value: 0.045). Based on the results, MWA and LITT thermal ablation techniques are well-tolerated, effective, and safe for the local treatment of HCC. However, MWA is recommended over LITT for the treatment of HCC, since the patients in the MWA-group had higher survival rates

Association of mortality and early tracheostomy in patients with COVID-19: a retrospective analysis

COVID-19 adds to the complexity of optimal timing for tracheostomy. Over the course of this pandemic, and expanded knowledge of the disease, many centers have changed their operating procedures and performed an early tracheostomy. We studied the data on early and delayed tracheostomy regarding patient outcome such as mortality. We performed a retrospective analysis of all tracheostomies at our institution in patients diagnosed with COVID-19 from March 2020 to June 2021. Time from intubation to tracheostomy and mortality of early (≤ 10 days) vs. late (> 10 days) tracheostomy were the primary objectives of this study. We used mixed cox-regression models to calculate the effect of distinct variables on events. We studied 117 tracheostomies. Intubation to tracheostomy shortened significantly (Spearman’s correlation coefficient; rho = − 0.44, p ≤ 0.001) during the course of this pandemic. Early tracheostomy was associated with a significant increase in mortality in uni- and multivariate analysis (Hazard ratio 1.83, 95% CI 1.07–3.17, p = 0.029). The timing of tracheostomy in COVID-19 patients has a potentially critical impact on mortality. The timing of tracheostomy has changed during this pandemic tending to be performed earlier. Future prospective research is necessary to substantiate these results

Heat generation at the implant–bone interface by insertion of ceramic and titanium implants

Purpose: The aim of this study is to record material- and surface-dependent heat dissipation during the process of inserting implants into native animal bone. Materials and Methods: Implants made of titanium and zirconium that were identical in macrodesign were inserted under controlled conditions into a bovine rib tempered to 37 °C. The resulting surface temperature was measured on two bone windows by an infrared camera. The results of the six experimental groups, ceramic machined (1), sandblasted (2), and sandblasted and acid-etched surfaces (3) versus titanium implants with the corresponding surfaces (4, 5, and 6) were statistically tested. Results: The average temperature increase, 3 mm subcrestally at ceramic implants, differed with high statistical significance (p = 7.163 × 10−9, resulting from group-adjusted linear mixed-effects model) from titanium. The surface texture of ceramic implants shows a statistical difference between group 3 (15.44 ± 3.63 °C) and group 1 (19.94 ± 3.28 °C) or group 2 (19.39 ± 5.73 °C) surfaces. Within the titanium implants, the temperature changes were similar for all surfaces. Conclusion: Within the limits of an in vitro study, the high temperature rises at ceramic versus titanium implants should be limited by a very slow insertion velocity

Associated Factors of High Sedative Requirements within Patients with Moderate to Severe COVID-19 ARDS

The coronavirus pandemic continues to challenge global healthcare. Severely affected patients are often in need of high doses of analgesics and sedatives. The latter was studied in critically ill coronavirus disease 2019 (COVID-19) patients in this prospective monocentric analysis. COVID-19 acute respiratory distress syndrome (ARDS) patients admitted between 1 April and 1 December 2020 were enrolled in the study. A statistical analysis of impeded sedation using mixed-effect linear regression models was performed. Overall, 114 patients were enrolled, requiring unusual high levels of sedatives. During 67.9% of the observation period, a combination of sedatives was required in addition to continuous analgesia. During ARDS therapy, 85.1% (n = 97) underwent prone positioning. Veno-venous extracorporeal membrane oxygenation (vv-ECMO) was required in 20.2% (n = 23) of all patients. vv-ECMO patients showed significantly higher sedation needs (p &lt; 0.001). Patients with hepatic (p = 0.01) or renal (p = 0.01) dysfunction showed significantly lower sedation requirements. Except for patient age (p = 0.01), we could not find any significant influence of pre-existing conditions. Age, vv-ECMO therapy and additional organ failure could be demonstrated as factors influencing sedation needs. Young patients and those receiving vv-ECMO usually require increased sedation for intensive care therapy. However, further studies are needed to elucidate the causes and mechanisms of impeded sedation

Electroencephalogram-Based Evaluation of Impaired Sedation in Patients with Moderate to Severe COVID-19 ARDS

The sedation management of patients with severe COVID-19 is challenging. Processed electroencephalography (pEEG) has already been used for sedation management before COVID-19 in critical care, but its applicability in COVID-19 has not yet been investigated. We performed this prospective observational study to evaluate whether the patient sedation index (PSI) obtained via pEEG may adequately reflect sedation in ventilated COVID-19 patients. Statistical analysis was performed by linear regression analysis with mixed effects. We included data from 49 consecutive patients. None of the patients received neuromuscular blocking agents by the time of the measurement. The mean value of the PSI was 20 (&plusmn;23). The suppression rate was determined to be 14% (&plusmn;24%). A deep sedation equivalent to the Richmond Agitation and Sedation Scale of &minus;3 to &minus;4 (correlation expected PSI 25&ndash;50) in bedside examination was noted in 79.4% of the recordings. Linear regression analysis revealed a significant correlation between the sedative dosages of propofol, midazolam, clonidine, and sufentanil (p &lt; 0.01) and the sedation index. Our results showed a distinct discrepancy between the RASS and the determined PSI. However, it remains unclear to what extent any discrepancy is due to the electrophysiological effects of neuroinflammation in terms of pEEG alteration, to the misinterpretation of spinal or vegetative reflexes during bedside evaluation, or to other causes

Detecting Sepsis in Patients with Severe Subarachnoid Hemorrhage during Critical Care

Introduction: Sepsis and septic shock continue to have a very high mortality rate. Therefore, the last consensus-based sepsis guideline introduced the sepsis related organ failure assessment (SOFA) score to ensure a rapid diagnosis and treatment of sepsis. In neurosurgical patients, especially those patients with subarachnoid hemorrhage (SAH), there are considerable difficulties in interpreting the SOFA score. Therefore, our study was designed to evaluate the applicability of the SOFA for critical care patients with subarachnoid hemorrhage. Methods: Our retrospective monocentric study was registered (NCT05246969) and approved by the local ethics committee (# 211/18). Patients admitted to the Department of Neurosurgery at the Frankfurt University Hospital were enrolled during the study period. Results: We included 57 patients with 85 sepsis episodes of which 141 patients had SOFA score-positive results and 243 SIRS positive detections. We failed to detect a correlation between the clinical diagnosis of sepsis and positive SOFA or SIRS scores. Moreover, a significant proportion of sepsis that was incorrectly detected via the SOFA score could be attributed to cerebral vasospasms (p &lt; 0.01) or a decrease in Glasgow Coma Scale (p &lt; 0.01). Similarly, a positive SIRS score was often not attributed to a septic episode (49.0%). Discussion: Regardless of the fact that SAH is a rare disease, the relevance of sepsis detection should be given special attention in light of the long duration of therapy and sepsis prevalence. Among the six modules represented by the SOFA score, two highly modules were practically eliminated. However, to enable early diagnosis of sepsis, the investigator&rsquo;s clinical views and synopsis of various scores and laboratory parameters should be highlighted. Conclusions: In special patient populations, such as in critically ill SAH patients, the SOFA score can be limited regarding its applicability. In particular, it is very important to differentiate between CVS and sepsis

Impact of the Covid-19 pandemic on melanoma and non-melanoma skin cancer inpatient treatment in Germany – a nationwide analysis

Background: SARS-CoV-2 has massively changed the care situation in hospitals worldwide. Although tumour care should not be affected, initial reports from European countries were suggestive for a decrease in skin cancer during the first pandemic wave and only limited data are available thereafter. Objectives: The aim of this study was to investigate skin cancer cases and surgeries in a nationwide inpatient dataset in Germany. Methods: Comparative analyses were performed in a prepandemic (18 March 2019 until 17 March 2020) and a pandemic cohort (18 March 2020 until 17 March 2021). Cases were identified and analysed using the WHO international classification of diseases codes (ICDs) and process key codes (OPSs). Results: Comparing the first year of the pandemic with the same period 1 year before, a persistent decrease of 14% in skin cancer cases (n = 19 063) was observed. The largest decrease of 24% was seen in non-invasive in situ tumours (n = 1665), followed by non-melanoma skin cancer (NMSC) with a decrease of 16% (n = 15 310) and malignant melanoma (MM) with a reduction of 7% (n = 2088). Subgroup analysis showed significant differences in the distribution of sex, age, hospital carrier type and hospital volume. There was a decrease of 17% in surgical procedures (n = 22 548), which was more pronounced in minor surgical procedures with a decrease of 24.6% compared to extended skin surgery including micrographic surgery with a decrease of 15.9%. Conclusions: Hospital admissions and surgical procedures decreased persistently since the beginning of the pandemic in Germany for skin cancer patients. The higher decrease in NMSC cases compared to MM might reflect a prioritization effect. Further evidence from tumour registries is needed to investigate the consequences of the therapy delay and identify the upcoming challenges in skin cancer care