Pneumonia and septic pneumonic shock are the most common indications for long-term mechanical ventilation and prolonged weaning, independent of any comorbidities. Multidrug resistant (MDR) bacteria ...are emerging as a cause of pneumonia or occur as a consequence of antimicrobial therapy. The influence of MDR bacteria on outcomes in patients with prolonged weaning is unknown.
Patients treated in a specialized weaning unit of a university hospital between April 2013 and April 2016 were analyzed. Demographic data, clinical characteristics, length of stay (LOS) in the intensive care unit (ICU) and weaning unit, ventilator-free days and mortality rates were determined in prolonged weaning patients with versus without MDR bacteria (methicillin-resistant Staphylococcus aureus bacteria, MRSA; extended spectrum beta lactamase ESBL- and Gyrase-producing gram negative bacteria resistant to three of four antibiotic groups 3 MRGN; panresistant Pseudomonas aeruginosa and other carbapenemase-producing gram-negative bacteria resistant to all four antibiotic groups 4 MRGN). Weaning failure was defined as death or discharge with invasive ventilation.
Of 666 patients treated in the weaning unit, 430 fulfilled the inclusion criteria and were included in the analysis. A total of 107 patients had isolates of MDR bacteria suspected as causative pathogens identified during the treatment process. Patients with MDR bacteria had higher SAPS II values at ICU admission and a significantly longer ICU LOS. Four MRGN P. aeruginosa and Acinetobacter baumanii were the most common MDR bacteria identified. Patients with versus without MDR bacteria had significantly higher arterial carbon dioxide levels at the time of weaning admission and a significantly lower rate of successful weaning (23% vs 31%, p < 0.05). Mortality rate on the weaning unit was 12.4% with no difference between the two patient groups. There were no significant differences between patient groups in secondary infections and ventilator-free days.
In patients with pneumonia or septic pneumonic shock undergoing prolonged weaning, infection with MDR bacteria may influence the weaning success rate but does not appear to impact on patient survival.
Background: The COVID-19 pandemic represents an unprecedented global challenge and implicates a wide range of burden on medical professionals. Here, we evaluated the perception of the COVID-19 ...pandemic among medical professionals in Germany.
Methods: A total of n = 2827 medical professionals participated in an online survey between 27 March and 11 April.
Results: While most participants stated that Germany was well prepared and rated the measures taken by their employer as positive, subgroup analyses revealed decisive differences. The preventive measures were rated significantly worse by nurses compared to doctors (p < 0.001) and by participants from ambulatory healthcare centres compared to participants from maximum-care hospitals (p < 0.001). Importantly, shortage of protective medical equipment was reported more commonly in the ambulatory sector (p < 0.001) and in East German federal states (p = 0.004). Moreover, the majority of health care professionals (72.4%) reported significant restrictions of daily work routine. Finally, over 60% of medical professionals had concerns regarding their own health, which were more pronounced among female participants (p = 0.024).
Conclusion: This survey may indicate starting points on how medical professionals could be supported in carrying out their important activities during the ongoing and future healthcare challenges.
Purpose
Second-generation FloTrac software has been shown to reliably measure cardiac output (CO) in cardiac surgical patients. However, concerns have been raised regarding its accuracy in vasoplegic ...states. The aim of the present multicenter study was to investigate the accuracy of the third-generation software in patients with sepsis, particularly when total systemic vascular resistance (TSVR) is low.
Methods
Fifty-eight septic patients were included in this prospective observational study in four university-affiliated ICUs. Reference CO was measured by bolus pulmonary thermodilution (iCO) using 3–5 cold saline boluses. Simultaneously, CO was computed from the arterial pressure curve recorded on a computer using the second-generation (CO
G2
) and third-generation (CO
G3
) FloTrac software. CO was also measured by semi-continuous pulmonary thermodilution (CCO).
Results
A total of 401 simultaneous measurements of iCO, CO
G2
, CO
G3
, and CCO were recorded. The mean (95%CI) biases between CO
G2
and iCO, CO
G3
and iCO, and CCO and iCO were −10 (−15 to −5)% −0.8 (−1.1 to −0.4) L/min, 0 (−4 to 4)% 0 (−0.3 to 0.3) L/min, and 9 (6–13)% 0.7 (0.5–1.0) L/min, respectively. The percentage errors were 29 (20–37)% for CO
G2
, 30 (24–37)% for CO
G3
, and 28 (22–34)% for CCO. The difference between iCO and CO
G2
was significantly correlated with TSVR (
r
2
= 0.37,
p
< 0.0001). A very weak (
r
2
= 0.05) relationship was also observed for the difference between iCO and CO
G3
.
Conclusions
In patients with sepsis, the third-generation FloTrac software is more accurate, as precise, and less influenced by TSVR than the second-generation software.
Objective
The attitudes about the usage of artificial intelligence in healthcare are controversial. Unlike the perception of healthcare professionals, the attitudes of patients and their companions ...have been of less interest so far. In this study, we aimed to investigate the perception of artificial intelligence in healthcare among this highly relevant group along with the influence of digital affinity and sociodemographic factors.
Methods
We conducted a cross-sectional study using a paper-based questionnaire with patients and their companions at a German tertiary referral hospital from December 2019 to February 2020. The questionnaire consisted of three sections examining (a) the respondents’ technical affinity, (b) their perception of different aspects of artificial intelligence in healthcare and (c) sociodemographic characteristics.
Results
From a total of 452 participants, more than 90% already read or heard about artificial intelligence, but only 24% reported good or expert knowledge. Asked on their general perception, 53.18% of the respondents rated the use of artificial intelligence in medicine as positive or very positive, but only 4.77% negative or very negative. The respondents denied concerns about artificial intelligence, but strongly agreed that artificial intelligence must be controlled by a physician. Older patients, women, persons with lower education and technical affinity were more cautious on the healthcare-related artificial intelligence usage.
Conclusions
German patients and their companions are open towards the usage of artificial intelligence in healthcare. Although showing only a mediocre knowledge about artificial intelligence, a majority rated artificial intelligence in healthcare as positive. Particularly, patients insist that a physician supervises the artificial intelligence and keeps ultimate responsibility for diagnosis and therapy.
Background Although macrophage migration inhibitory factor ( MIF ) has been demonstrated to mediate cardioprotection in ischemia/reperfusion injury and antagonize fibrotic effects through its ...receptor, CD 74, the function of the soluble CD 74 receptor ectodomain ( sCD 74) and its interaction with circulating MIF have not been explored in cardiac disease. Methods and Results Cardiac fibroblasts were isolated from hearts of neonatal mice and differentiated into myofibroblasts. Co-treatment with recombinant MIF and sCD 74 induced cell death ( P<0.001), which was mediated by receptor-interacting serine/threonine-protein kinase ( RIP) 1/ RIP 3-dependent necroptosis ( P=0.0376). This effect was specific for cardiac fibroblasts and did not affect cardiomyocytes. Gene expression analyses using microarray and RT - qPCR technology revealed a 4-fold upregulation of several interferon-induced genes upon co-treatment of myofibroblasts with sCD 74 and MIF (Ifi44: P=0.011; Irg1: P=0.022; Clec4e: P=0.011). Furthermore, Western blot analysis confirmed the role of sCD 74 as a modulator of MIF signaling by diminishing MIF -mediated protein kinase B ( AKT) activation ( P=0.0197) and triggering p38 activation ( P=0.0641). We obtained evidence that sCD 74 inhibits MIF -mediated survival pathway through the C-X-C chemokine receptor 4/ AKT axis, enabling the induction of CD 74-dependent necroptotic processes in cardiac myofibroblasts. Preliminary clinical data revealed a lowered sCD 74/ MIF ratio in heart failure patients (17.47±10.09 versus 1.413±0.6244). Conclusions These findings suggest that treatment of cardiac myofibroblasts with sCD 74 and MIF induces necroptosis, offering new insights into the mechanism of myofibroblast depletion during scar maturation. Preliminary clinical data provided first evidence about a clinical relevance of the sCD 74/ MIF axis in heart failure, suggesting that these proteins may be a promising target to modulate cardiac remodeling and disease progression in heart failure.
Evidence-based infectious disease and intensive care management is more relevant than ever. Medical expertise in the two disciplines is often geographically limited to university institutions. In ...addition, the interconnection between inpatient and outpatient care is often insufficient (eg, no shared electronic health record and no digital transfer of patient findings).
This study aims to establish and evaluate a telemedical inpatient-outpatient network based on expert teleconsultations to increase treatment quality in intensive care medicine and infectious diseases.
We performed a multicenter, stepped-wedge cluster randomized trial (February 2017 to January 2020) to establish a telemedicine inpatient-outpatient network among university hospitals, hospitals, and outpatient physicians in North Rhine-Westphalia, Germany. Patients aged ≥18 years in the intensive care unit or consulting with a physician in the outpatient setting were eligible. We provided expert knowledge from intensivists and infectious disease specialists through advanced training courses and expert teleconsultations with 24/7/365 availability on demand respectively once per week to enhance treatment quality. The primary outcome was adherence to the 10 Choosing Wisely recommendations for infectious disease management. Guideline adherence was analyzed using binary logistic regression models.
Overall, 159,424 patients (10,585 inpatients and 148,839 outpatients) from 17 hospitals and 103 outpatient physicians were included. There was a significant increase in guideline adherence in the management of Staphylococcus aureus infections (odds ratio OR 4.00, 95% CI 1.83-9.20; P<.001) and in sepsis management in critically ill patients (OR 6.82, 95% CI 1.27-56.61; P=.04). There was a statistically nonsignificant decrease in sepsis-related mortality from 29% (19/66) in the control group to 23.8% (50/210) in the intervention group. Furthermore, the extension of treatment with prophylactic antibiotics after surgery was significantly less likely (OR 9.37, 95% CI 1.52-111.47; P=.04). Patients treated by outpatient physicians, who were regularly participating in expert teleconsultations, were also more likely to be treated according to guideline recommendations regarding antibiotic therapy for uncomplicated upper respiratory tract infections (OR 1.34, 95% CI 1.16-1.56; P<.001) and asymptomatic bacteriuria (OR 9.31, 95% CI 3.79-25.94; P<.001). For the other recommendations, we found no significant effects, or we had too few observations to generate models. The key limitations of our study include selection effects due to the applied on-site triage of patients as well as the limited possibilities to control for secular effects.
Telemedicine facilitates a direct round-the-clock interaction over broad distances between intensivists or infectious disease experts and physicians who care for patients in hospitals without ready access to these experts. Expert teleconsultations increase guideline adherence and treatment quality in infectious disease and intensive care management, creating added value for critically ill patients.
ClinicalTrials.gov NCT03137589; https://clinicaltrials.gov/ct2/show/NCT03137589.
Acute respiratory distress syndrome (ARDS) results in significant hypoxia, and ARDS is the central pathology of COVID-19. Inhaled prostacyclin has been proposed as a therapy for ARDS, but data ...regarding its role in this syndrome are unavailable. Therefore, we investigated whether inhaled prostacyclin would affect the oxygenation and survival of patients suffering from ARDS.
We performed a prospective randomized controlled single-blind multicenter trial across Germany. The trial was conducted from March 2019 with final follow-up on 12th of August 2021. Patients with moderate to severe ARDS were included and randomized to receive either inhaled prostacyclin (3 times/day for 5 days) or sodium chloride (Placebo). The primary outcome was the oxygenation index in the intervention and control groups on Day 5 of therapy. Secondary outcomes were mortality, secondary organ failure, disease severity and adverse events.
Of 707 patients approached 150 patients were randomized to receive inhaled prostacyclin (n = 73) or sodium chloride (n = 77). Data from 144 patients were analyzed. The baseline PaO
/FiO
ratio did not differ between groups. The primary analysis of the study was negative, and prostacyclin improved oxygenation by 20 mmHg more than Placebo (p = 0.17). Secondary analysis showed that the oxygenation was significantly improved in patients with ARDS who were COVID-19-positive (34 mmHg, p = 0.04). Mortality did not differ between groups. Secondary organ failure and adverse events were similar in the intervention and control groups.
The primary result of our study was negative. Our data suggest that inhaled prostacyclin might be beneficial treatment in patients with COVID-19 induced ARDS.
The study was approved by the Institutional Review Board of the Research Ethics Committee of the University of Tübingen (899/2018AMG1) and the corresponding ethical review boards of all participating centers. The trial was also approved by the Federal Institute for Drugs and Medical Devices (BfArM, EudraCT No. 2016003168-37) and registered at clinicaltrials.gov (NCT03111212) on April 6th 2017.
ABSTRACTAdrenomedullin is a vasoactive peptide that improves endothelial barrier function in sepsis, but may also cause hypotension and organ failure. Treatment with a non-neutralizing monoclonal ...anti-adrenomedullin antibody showed improvement in murine sepsis models. We tested the effects of the humanized monoclonal anti-adrenomedullin antibody Adrecizumab in a porcine two-hit model of hemorrhagic and septic shock.In this randomized, blinded study 12 German Landrace pigs were bled to half of baseline mean arterial pressure for 45 min. Sepsis was induced using an Escherichia coli clot placed into the abdominal cavity 6 h after hemorrhagic shock. Animals received either 2 mg/kg BW anti-adrenomedullin antibody or vehicle solution immediately after sepsis induction. After 4 h, resuscitation was initiated using balanced crystalloids and noradrenalin to maintain a central venous pressure of 8 to 12 mm Hg, a mean arterial pressure ≥ 65 mm Hg, and a ScvO2 ≥70% for another 8 h. Hemodynamic parameters, laboratory parameters, and kidney histology were assessed.The amount of volume resuscitation was significantly lower and significantly less animals developed a septic shock in the antibody-treated group, compared with the vehicle group. Kidney histology showed significantly lower granulocytes in both cortex and medulla in antibody-treated animals, while the remaining four kidney measures (serum creatinine and urine output and cortical and medullary injury in histopathology) did not reach the significance levels. After induction of sepsis, plasma adrenomedullin increased immediately in both the groups, but increased quicker and more pronounced in the antibody group.In this two-hit shock model, treatment with an anti-adrenomedullin antibody significantly increased plasma adrenomedullin levels, while significantly less animals developed septic shock and renal granulocyte extravasation was significantly reduced. Thus, therapy with Adrecizumab may provide benefit in sepsis, and clinical investigation of this drug candidate is warranted.
The aim of this work was to develop and evaluate the reinforcement learning algorithm VentAI, which is able to suggest a dynamically optimized mechanical ventilation regime for critically-ill ...patients. We built, validated and tested its performance on 11,943 events of volume-controlled mechanical ventilation derived from 61,532 distinct ICU admissions and tested it on an independent, secondary dataset (200,859 ICU stays; 25,086 mechanical ventilation events). A patient "data fingerprint" of 44 features was extracted as multidimensional time series in 4-hour time steps. We used a Markov decision process, including a reward system and a Q-learning approach, to find the optimized settings for positive end-expiratory pressure (PEEP), fraction of inspired oxygen (FiO
) and ideal body weight-adjusted tidal volume (Vt). The observed outcome was in-hospital or 90-day mortality. VentAI reached a significantly increased estimated performance return of 83.3 (primary dataset) and 84.1 (secondary dataset) compared to physicians' standard clinical care (51.1). The number of recommended action changes per mechanically ventilated patient constantly exceeded those of the clinicians. VentAI chose 202.9% more frequently ventilation regimes with lower Vt (5-7.5 mL/kg), but 50.8% less for regimes with higher Vt (7.5-10 mL/kg). VentAI recommended 29.3% more frequently PEEP levels of 5-7 cm H
O and 53.6% more frequently PEEP levels of 7-9 cmH
O. VentAI avoided high (>55%) FiO
values (59.8% decrease), while preferring the range of 50-55% (140.3% increase). In conclusion, VentAI provides reproducible high performance by dynamically choosing an optimized, individualized ventilation strategy and thus might be of benefit for critically ill patients.
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