Evaluation of a New Multiparameter Brain Probe for Simultaneous Measurement of Brain Tissue Oxygenation, Cerebral Blood Flow, Intracranial Pressure, and Brain Temperature in a Porcine Model.

BACKGROUND: A novel multiparameter brain sensor (MPBS) allows the simultaneous measurement of brain tissue oxygenation (ptiO2), cerebral blood flow (CBF), intracranial pressure (ICP), and brain temperature with a single catheter. This laboratory investigation evaluates the MPBS in an animal model in relation to established reference probes. METHODS: The study group consisted of 17 juvenile male pigs. Four MPBS and four reference probes were implanted per pig and compared simultaneously. The measured parameters were challenged by standardized provocations such as hyperoxia, dobutamine, and norepinephrine application, hypercapnia and hypoxia in combination with and without a controlled cortical impact (CCI) injury. Mean values over 2 min were collected for predefined time points and were analyzed using Bland-Altman plots. RESULTS: The protocol was successfully conducted in 15 pigs of which seven received CCI. ICP and ptiO2 were significantly influenced by the provocations. Subtraction of MPBS from reference values revealed a mean difference (limits of agreement) of 3.7 (- 20.5 to 27.9) mm Hg, - 2.9 (- 7.9 to 2.1) mm Hg, and 5.1 (- 134.7 to 145.0) % for ptiO2, ICP, and relative CBF, respectively. CONCLUSIONS: The MPBS is a promising measurement tool for multiparameter neuromonitoring. The conducted study demonstrates the in vivo functionality of the probe. Comparison with standard probes revealed a deviation which is mostly analogous to other multiparameter devices. However, further evaluation of the device is necessary before it can reliably be used for clinical decision making.

Quality indicators in intensive care medicine for Germany - fourth edition 2022.

The measurement of quality indicators supports quality improvement initiatives. The German Interdisciplinary Society of Intensive Care Medicine (DIVI) has published quality indicators for intensive care medicine for the fourth time now. After a scheduled evaluation after three years, changes in several indicators were made. Other indicators were not changed or only minimally. The focus remained strongly on relevant treatment processes like management of analgesia and sedation, mechanical ventilation and weaning, and infections in the ICU. Another focus was communication inside the ICU. The number of 10 indicators remained the same. The development method was more structured and transparency was increased by adding new features like evidence levels or author contribution and potential conflicts of interest. These quality indicators should be used in the peer review in intensive care, a method endorsed by the DIVI. Other forms of measurement and evaluation are also reasonable, for example in quality management. This fourth edition of the quality indicators will be updated in the future to reflect the recently published recommendations on the structure of intensive care units by the DIVI.

Multiparametric Monitoring of Early Pathophysiological Changes in a Porcine Model of Sequential Focal and Global Cerebral Ischemia.

OBJECTIVE: Large animal models of cerebral ischemia have the potential to increase the translational value of stroke research. This study aims to measure early changes of brain tissue oxygen pressure (ptiO2) and cerebral blood flow (CBF) to characterize a porcine model of sequential middle cerebral artery occlusion (MCAO) and common carotid artery occlusion (CCAO). METHODS: Eight juvenile German Landrace pigs received unilateral MCAO via a frontotemporal approach under continuous intraparenchymal multiparametric monitoring. Insufficient reduction (i.e., <50% in both ptiO2 and CBF) was followed by additional bilateral CCAO. Neurodegenerative changes were detected by Fluoro-Jade B (FJB) staining. RESULTS: Only 1 of 8 animals demonstrated a decrease of >50% in both ptiO2 and CBF after MCAO. Additional CCAO in 7 pigs led to a significant reduction of both ipsilateral and contralateral ptiO2 (P < 0.01) but not of CBF. There was no difference in ptiO2 and FJB positive area between hemispheres in this group. Measurement of ptiO2 correlated negatively with the FJB positive area (P < 0.05). CONCLUSIONS: Intraparenchymal multiparametric measurements of acute changes in ptiO2 and CBF were variable after MCAO. Bilateral CCAO led to a consistent decrease in ptiO2 and correlated with early degenerative histologic changes, but CBF did not. Real-time procedural ptiO2 monitoring could provide useful guidance in large animal ischemia models. Feasibility in the context of global cerebral hypoperfusion is demonstrated.

Decline in the number of patients with meningitis in German hospitals during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: In 2020, a wide range of hygiene measures was implemented to mitigate infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In consequence, pulmonary infections due to other respiratory pathogens also decreased. Here, we evaluated the number of bacterial and viral meningitis and encephalitis cases during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In a multicentre retrospective analysis of data from January 2016 until December 2020, numbers of patients diagnosed with bacterial meningitis and other types of CNS infections (such as viral meningitis and encephalitis) at 26 German hospitals were studied. Furthermore, the number of common meningitis-preceding ear-nose-throat infections (sinusitis, mastoiditis and otitis media) was evaluated. RESULTS: Compared to the previous years, the total number of patients diagnosed with pneumococcal meningitis was reduced (n = 64 patients/year in 2020 vs. n = 87 to 120 patients/year between 2016 and 2019, all p < 0.05). Additionally, the total number of patients diagnosed with otolaryngological infections was significantly lower (n = 1181 patients/year in 2020 vs. n = 1525 to 1754 patients/year between 2016 and 2019, all p < 0.001). We also observed a decline in viral meningitis and especially enterovirus meningitis (n = 25 patients/year in 2020 vs. n = 97 to 181 patients/year between 2016 and 2019, all p < 0.001). DISCUSSION: This multicentre retrospective analysis demonstrates a decline in the number of patients treated for viral and pneumococcal meningitis as well as otolaryngological infections in 2020 compared to previous years. Since the latter often precedes pneumococcal meningitis, this may point to the significance of the direct spread of pneumococci from an otolaryngological focus such as mastoiditis to the brain as one important pathophysiological route in the development of pneumococcal meningitis.

S2k guideline diagnosis and treatment of carbon monoxide poisoning.

Carbon monoxide (CO) can occur in numerous situations and ambient conditions, such as fire smoke, indoor fireplaces, silos containing large quantities of wood pellets, engine exhaust fumes, and when using hookahs. Symptoms of CO poisoning are nonspecific and can range from dizziness, headache, and angina pectoris to unconsciousness and death. This guideline presents the current state of knowledge and national recommendations on the diagnosis and treatment of patients with CO poisoning. The diagnosis of CO poisoning is based on clinical symptoms and proven or probable exposure to CO. Negative carboxyhemoglobin (COHb) levels should not rule out CO poisoning if the history and symptoms are consistent with this phenomenon. Reduced oxygen-carrying capacity, impairment of the cellular respiratory chain, and immunomodulatory processes may result in myocardial and central nervous tissue damage even after a reduction in COHb. If CO poisoning is suspected, 100% oxygen breathing should be immediately initiated in the prehospital setting. Clinical symptoms do not correlate with COHb elimination from the blood; therefore, COHb monitoring alone is unsuitable for treatment management. Especially in the absence of improvement despite treatment, a reevaluation for other possible differential diagnoses ought to be performed. Evidence regarding the benefit of hyperbaric oxygen therapy (HBOT) is scant and the subject of controversy due to the heterogeneity of studies. If required, HBOT should be initiated within 6 h. All patients with CO poisoning should be informed about the risk of delayed neurological sequelae (DNS).

Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study).

PURPOSE: The CIGMA study investigated a novel human polyclonal antibody preparation (trimodulin) containing ~ 23% immunoglobulin (Ig) M, ~ 21% IgA, and ~ 56% IgG as add-on therapy for patients with severe community-acquired pneumonia (sCAP). METHODS: In this double-blind, phase II study (NCT01420744), 160 patients with sCAP requiring invasive mechanical ventilation were randomized (1:1) to trimodulin (42 mg IgM/kg/day) or placebo for five consecutive days. Primary endpoint was ventilator-free days (VFDs). Secondary endpoints included 28-day all-cause and pneumonia-related mortality. Safety and tolerability were monitored. Exploratory post hoc analyses were performed in subsets stratified by baseline C-reactive protein (CRP; ≥ 70 mg/L) and/or IgM (≤ 0.8 g/L). RESULTS: Overall, there was no statistically significant difference in VFDs between trimodulin (mean 11.0, median 11 [n = 81]) and placebo (mean 9.6; median 8 [n = 79]; p = 0.173). Twenty-eight-day all-cause mortality was 22.2% vs. 27.8%, respectively (p = 0.465). Time to discharge from intensive care unit and mean duration of hospitalization were comparable between groups. Adverse-event incidences were comparable. Post hoc subset analyses, which included the majority of patients (58-78%), showed significant reductions in all-cause mortality (trimodulin vs. placebo) in patients with high CRP, low IgM, and high CRP/low IgM at baseline. CONCLUSIONS: No significant differences were found in VFDs and mortality between trimodulin and placebo groups. Post hoc analyses supported improved outcome regarding mortality with trimodulin in subsets of patients with elevated CRP, reduced IgM, or both. These findings warrant further investigation. TRIAL REGISTRATION: NCT01420744.

Quality indicators in intensive care medicine for Germany - third edition 2017.

Quality improvement in medicine is depending on measurement of relevant quality indicators. The quality indicators for intensive care medicine of the German Interdisciplinary Society of Intensive Care Medicine (DIVI) from the year 2013 underwent a scheduled evaluation after three years. There were major changes in several indicators but also some indicators were changed only minimally. The focus on treatment processes like ward rounds, management of analgesia and sedation, mechanical ventilation and weaning, as well as the number of 10 indicators were not changed. Most topics remained except for early mobilization which was introduced instead of hypothermia following resuscitation. Infection prevention was added as an outcome indicator. These quality indicators are used in the peer review in intensive care, a method endorsed by the DIVI. A validity period of three years is planned for the quality indicators.

Effect of a multifaceted educational intervention for anti-infectious measures on sepsis mortality: a cluster randomized trial.

PURPOSE: Guidelines recommend administering antibiotics within 1 h of sepsis recognition but this recommendation remains untested by randomized trials. This trial was set up to investigate whether survival is improved by reducing the time before initiation of antimicrobial therapy by means of a multifaceted intervention in compliance with guideline recommendations. METHODS: The MEDUSA study, a prospective multicenter cluster-randomized trial, was conducted from July 2011 to July 2013 in 40 German hospitals. Hospitals were randomly allocated to receive conventional continuous medical education (CME) measures (control group) or multifaceted interventions including local quality improvement teams, educational outreach, audit, feedback, and reminders. We included 4183 patients with severe sepsis or septic shock in an intention-to-treat analysis comparing the multifaceted intervention (n = 2596) with conventional CME (n = 1587). The primary outcome was 28-day mortality. RESULTS: The 28-day mortality was 35.1% (883 of 2596 patients) in the intervention group and 26.7% (403 of 1587 patients; p = 0.01) in the control group. The intervention was not a risk factor for mortality, since this difference was present from the beginning of the study and remained unaffected by the intervention. Median time to antimicrobial therapy was 1.5 h (interquartile range 0.1-4.9 h) in the intervention group and 2.0 h (0.4-5.9 h; p = 0.41) in the control group. The risk of death increased by 2% per hour delay of antimicrobial therapy and 1% per hour delay of source control, independent of group assignment. CONCLUSIONS: Delay in antimicrobial therapy and source control was associated with increased mortality but the multifaceted approach was unable to change time to antimicrobial therapy in this setting and did not affect survival.

Urosepsis--Etiology, Diagnosis, and Treatment.

BACKGROUND: Sepsis is among the most common causes of death in Germany. Urosepsis accounts for 9-31% of all cases and has a mortality of 20-40%, which is low compared with that of sepsis in general. As the population ages, the incidence of urosepsis is likely to rise. METHODS: Review of pertinent articles and guidelines retrieved by a selective search in PubMed. RESULTS: Enterobacteria and Gram-positive organisms are the pathogens that most commonly cause urosepsis. The diagnosis can and must be made early on the basis of the typical clinical features, altered vital signs, and laboratory abnormalities, so that timely treatment can be initiated. 80% of cases are due to obstructive uropathy. The diagnostic evaluation includes physical examination, blood cultures, urinalysis, procalcitonin measurement, and ultrasonography. In one study, each additional hour of delay in the treatment of urosepsis with antibiotics was found to lower the survival rate by 7.6%. Antibiotics should be chosen in consideration of local resistance patterns and the expected pathogen spectrum. CONCLUSION: Urologists, intensive care specialists, and microbiologists should all be involved in the interdisciplinary treatment of urosepsis. Patients' outcomes have improved recently, probably because of the frequent use of minimally invasive treatments to neutralize foci of infection. New biomarkers and new treatments still need to be validated in multicenter trials.

Hyperlactatemia is an independent predictor of mortality and denotes distinct subtypes of severe sepsis and septic shock.

PURPOSE: Current guidelines and most trials do not consider elevated lactate (Lac) serum concentrations when grading sepsis severity. We therefore assessed the association of different types of circulatory dysfunction regarding presence of hyperlactatemia and need for vasopressor support with clinical presentation and outcome of sepsis. METHODS: In a secondary analysis of a prospective observational multicenter cohort study, 988 patients with severe sepsis were investigated regarding vasopressor support, Lac levels, and outcome. RESULTS: Twenty-eight-day mortality regarding shock or hyperlactatemia was as follows: hyperlactatemia more than 2.5 mmol/L and septic shock (tissue dysoxic shock): 451 patients with a mortality of 44.8%; hyperlactatemia without vasopressor need (cryptic shock): 72 patients, mortality 35.3%; no hyperlactatemia with vasopressor need (vasoplegic shock): 331 patients, mortality 27.7%; and absence of hyperlactemia or overt shock (severe sepsis): 134 patients, mortality 14.2% (P < .001). These groups showed differences in source and origin of infection. The influence of hyperlactatemia on 28-day mortality (P < .001) (odds ratio 3.0, 95% confidence interval 2.1-4.1 for Lac >4 mmol/L) was independent of vasopressor support (P < .001) (odds ratio 2.0, 95% confidence interval 1.3-3.0 for norepinephrine >0.1 µg/kg per minute) in logistic regression. CONCLUSIONS: Hyperlactatemia increases risk of death independent of vasopressor need resulting in different phenotypes within the classic categories of severe sepsis and septic shock.

Description of the response of a new multi-parametric brain sensor to physiological and pathophysiological challenges in the cortex of juvenile pigs.

AIM: Monitoring of intracranial pressure (ICP), local cerebral blood flow (CBF) and oxygen is part of modern intensive critical care medicine. Preclinical evaluation of newly developed catheters that should monitor several parameters simultaneously is reported poorly in the literature. The goal of our study was (1) to evaluate a new multi-parametric sensor in brain tissue and (2) to establish a testing protocol using pathophysiological challenges that target measured parameters of the sensor and autoregulatory boundaries and could be used as preclinical standard protocol in future studies. MATERIAL AND METHODS: We describe data from 12 new multi-parametric brain sensors (MPBS) that were implanted into 3 porcine brains and combined measurement of brain tissue oxygenation (ptiO2), ICP, CBF and brain temperature for the first time. Pigs were treated with a period of hyperoxygenation, hypercapnia, hypoxia, dobutamine, and norepinephrine. RESULTS: None of the 12 MPBS failed. Our testing protocol induced standardized pathophysiological changes that were picked up by the new MPBS as significant alterations in brain ptiO2, ICP and CBF. The magnitude of changes was >20% in most tested MPBS. CONCLUSION: An experimental protocol with pre-defined end-points for O2, CO2, blood pressure and cardiac output should be standardized and reported if new sensors for multi-parametric brain monitoring are evaluated. The use of several sensors per brain of only a few animals is sufficient to determine functionality of new sensors in vivo as basis for a larger study with reference sensors and brain injury.