Corrigendum: The functional trajectory in frail compared with non-frail critically ill patients during the hospital stay.

[This corrects the article DOI: 10.3389/fmed.2021.748812.].

Hemoadsorption in the critically ill-Final results of the International CytoSorb Registry.

The aim of the current paper is to summarize the results of the International CytoSorb Registry. Data were collected on patients of the intensive care unit. The primary endpoint was actual in-hospital mortality compared to the mortality predicted by APACHE II score. The main secondary endpoints were SOFA scores, inflammatory biomarkers and overall evaluation of the general condition. 1434 patients were enrolled. Indications for hemoadsorption were sepsis/septic shock (N = 936); cardiac surgery perioperatively (N = 172); cardiac surgery postoperatively (N = 67) and "other" reasons (N = 259). APACHE-II-predicted mortality was 62.0±24.8%, whereas observed hospital mortality was 50.1%. Overall SOFA scores did not change but cardiovascular and pulmonary SOFA scores decreased by 0.4 [-0.5;-0.3] and -0.2 [-0.3;-0.2] points, respectively. Serum procalcitonin and C-reactive protein levels showed significant reduction: -15.4 [-19.6;-11.17] ng/mL; -17,52 [-70;44] mg/L, respectively. In the septic cohort PCT and IL-6 also showed significant reduction: -18.2 [-23.6;-12.8] ng/mL; -2.6 [-3.0;-2.2] pg/mL, respectively. Evaluation of the overall effect: minimal improvement (22%), much improvement (22%) and very much improvement (10%), no change observed (30%) and deterioration (4%). There was no significant difference in the primary outcome of mortality, but there were improvements in cardiovascular and pulmonary SOFA scores and a reduction in PCT, CRP and IL-6 levels. Trial registration: ClinicalTrials.gov Identifier: NCT02312024 (retrospectively registered).

Hemoadsorption in 'Liver Indication'-Analysis of 109 Patients' Data from the CytoSorb International Registry.

BACKGROUND: Our aim is to report the results of the 'liver indication' subset of patients in the CytoSorb International Registry. METHODS: Structured data were recorded. Treatment characteristics and changes from T1 (start of hemoadsorption) to T2 (termination) were evaluated with a special focus on bilirubin, C-reactive protein, procalcitonin, interleukin-6, platelet levels, SOFA scores, mortality, and subjective assessment by the attending physicians. RESULTS: Until January 2021, from the total 1434 patients, 109 (age: 49.2 ± 17.1 years, 57.8% males) received treatment for hyperbilirubinemia. APACHE II-predicted mortality was 49.6 ± 26.8%. In the study, 91% of patients were alive at the termination of hemoadsorption and improvement was observed by the physicians in 75 cases. Overall, 65 (59.6%) patients died in the hospital, and 60 (55.0%) died in the ICU. Patients received a median of two treatments for a median of 43 h (interquartile range: 24-72 h) in total. Serum bilirubin levels reduced significantly to -4.6 (95% CI: -6.329 to -2.8) mg/dL. Thrombocytopenia was reported in four patients as an adverse event. CONCLUSIONS: We report the largest case series on hemoadsorption for 'liver indication' from the CytoSorb International Registry. The finding of significant bilirubin removal observed in our study could have substantial impact in designing and executing further studies on the effects of hemoadsorption in liver dysfunction, which are certainly warranted.

The Functional Trajectory in Frail Compared With Non-frail Critically Ill Patients During the Hospital Stay.

Background: Long-term outcome is determined not only by the acute critical illness but increasingly by the reduced functional reserve of pre-existing frailty. The patients with frailty currently account for one-third of the critically ill, resulting in higher mortality. There is evidence of how frailty affects the intrahospital functional trajectory of critically ill patients since prehospital status is often missing. Methods: In this prospective single-center cohort study at two interdisciplinary intensive care units (ICUs) at a university hospital in Germany, the frailty was assessed using the Clinical Frailty Scale (CFS) in the adult patients with critical illness with an ICU stay >24 h. The functional status was assessed using the sum of the subdomains "Mobility" and "Transfer" of the Barthel Index (MTB) at three time points (pre-hospital, ICU discharge, and hospital discharge). Results: We included 1,172 patients with a median age of 75 years, of which 290 patients (25%) were frail. In a propensity score-matched cohort, the probability of MTB deterioration till hospital discharge did not differ in the patients with frailty (odds ratio (OR) 1.3 [95% CI 0.8-1.9], p = 0.301), confirmed in several sensitivity analyses in all the patients and survivors only. Conclusion: The patients with frailty have a reduced functional status. Their intrahospital functional trajectory, however, was not worse than those in non-frail patients, suggesting a rehabilitation potential of function in critically ill patients with frailty.

Association of Troponin T levels and functional outcome 3 months after subarachnoid hemorrhage.

TroponinT levels are frequently elevated after subarachnoid hemorrhage (SAH). However, their clinical impact on long term outcomes still remains unclear. This study evaluates the association of TroponinT and functional outcomes 3 months after SAH. Data were obtained in the frame of a randomized controlled trial exploring the association of Goal-directed hemodynamic therapy and outcomes after SAH (NCT01832389). TroponinT was measured daily for the first 14 days after admission or until discharge from the ICU. Outcome was assessed using Glasgow Outcome Scale (GOS) 3 months after discharge. Logistic regression was used to explore the association between initial TroponinT values stratified by tertiles and admission as well as outcome parameters. TroponinT measurements were analyzed in 105 patients. TroponinT values at admission were associated with outcome assessed by GOS in a univariate analysis. TroponinT was not predictive of vasospasm or delayed cerebral ischemia, but an association with pulmonary and cardiac complications was observed. After adjustment for age, history of arterial hypertension and World Federation of Neurosurgical Societies (WFNS) grade, TroponinT levels at admission were not independently associated with worse outcome (GOS 1-3) or death at 3 months. In summary, TroponinT levels at admission are associated with 3 months-GOS but have limited ability to independently predict outcome after SAH.

Algorithm-guided goal-directed haemodynamic therapy does not improve renal function after major abdominal surgery compared to good standard clinical care: a prospective randomised trial.

BACKGROUND: Acute kidney injury is a common complication after major surgery. In this study, we investigated whether an algorithm-guided goal-directed haemodynamic therapy (GDT) can improve renal outcome compared to good standard clinical care. METHODS: A total of 180 patients undergoing major abdominal surgery were prospectively and randomly assigned to one of two groups: in the GDT group, patients were treated with a GDT algorithm using transpulmonary thermodilution while standard care was applied to the control patients. Change in creatinine was studied as the primary end point, postoperative complications as well as 1-year mortality as secondary outcomes. Haemodynamics in GDT and control patients were compared calculating goal-achievement rates. RESULTS: Postoperative change in creatinine (18 ± 39 µmol/l (control) vs. 16 ± 42 µmol/l (GDT); mean difference (95 % confidence interval) 1.6 µmol/l (-10 to 13 µmol/l)) was comparable between the GDT and the control group. Postoperative complications and mortality during hospital stay and after 1 year were not influenced by the use of a GDT algorithm. Achievement rates of haemodynamic goals were not higher in the GDT group compared to the already high (>80 %) rates in the control group. Multivariate regression analysis revealed intraoperative hypotension (MAP < 70 mmHg) and postoperative hypovolaemia (GEDI < 640 ml/m(2)) as risk factors for postoperative renal impairment. CONCLUSIONS: In this study, GDT was not superior to standard clinical care in order to avoid renal failure after major abdominal surgery. The reason for this finding is most likely the high achievement rate of haemodynamic goals in the control group, which cannot be improved by the GDT algorithm. TRIAL REGISTRATION: Clinicaltrials.gov; NCT01035541; registered 17 December 2009.

The German Validation Study of the Surgical Intensive Care Unit Optimal Mobility Score.

PURPOSE: Immobilization of critically ill patients leads to muscle weakness, which translates to increased costs of care and long-term functional disability. We tested the validity of a German Surgical Intensive Care Unit (ICU) Optimal Mobilization Score (SOMS) in 2 different cohorts (neurocritical and nonneurocritical care patients). MATERIALS AND METHODS: Physical therapists estimated the patients' mobilization capacity by using the German version of the SOMS the morning after admission. We tested the prognostic value of the prediction for ICU and hospital length of stay (LOS) as well as for mortality, and built a model to account for other known predictors of these outcomes in the 2 cohorts. RESULTS: A total of 128 patients were included in the analysis, 48 of these were neurocritical care patients. The SOMS predicted mortality and ICU and hospital LOS. Neurocritical care patients stayed significantly longer in the ICU (median 12 vs 4 days, P < .001) and in the hospital (25 vs 17 days, P = .02). The SOMS predicted ICU and hospital LOS. It predicted mortality only in nonneurocritical patients. CONCLUSIONS: The German SOMS assessed by physical therapists on the day after ICU admission predicts ICU and hospital LOS, and mortality. Our data suggest that the association between early mobilization and mortality is more complex in neurocritical care patients.

Overwhelming Postsplenectomy Infection: A Prospective Multicenter Cohort Study.

BACKGROUND: Recent population-based cohort studies have questioned the role of pneumococci as the most frequent pathogen causing severe infection in patients after splenectomy. The aim of the study was to define the causative pathogens and clinical presentation of patients with overwhelming postsplenectomy infection (OPSI). METHODS: In a prospective cohort study in 173 German intensive care units, we searched for patients with and without asplenia and community-acquired severe sepsis/septic shock. Clinical and laboratory variables and survival of patients were assessed. RESULTS: Fifty-two patients with severe sepsis or septic shock with asplenia and 52 without asplenia were included. OPSI patients more often had a history of malignancy (38% vs 17%; P = .016) and had a lower body mass index (24 kg/m(2) vs 28 kg/m(2); P = .004). Streptococcus pneumoniae was detected more frequently in OPSI patients (42% vs 12% without asplenia; P < .001) and more frequently manifested as bloodstream infection (31% vs 6%; P = .002). Gram-negative infection was similar in both groups (12% vs 19%; P = .157). Pneumococcal vaccine coverage of OPSI patients was low overall (42% vs 8% among patients without asplenia; P < .001). Purpura fulminans was a frequent complication, developing in 19% of OPSI patients vs 5% of patients without asplenia (P = .038). The interval between splenectomy and OPSI was 6 years (range, 1 month-50 years). On multivariable Poisson regression, asplenia was the only predictive variable independently associated with pneumococcal sepsis (adjusted relative risk, 2.53 [95% confidence interval, 1.06-6.08]). CONCLUSIONS: Pneumococcal infections remain the most important cause of severe sepsis and septic shock following splenectomy.

Effects of isoflurane-induced anaesthesia on cognitive performance in a mouse model of Alzheimer's disease: A randomised trial in transgenic APP23 mice.

BACKGROUND: Results from in-vitro experiments suggest that inhalational anaesthetics may have a detrimental effect on the course and incidence of Alzheimer's disease. However, case-control studies in humans show no negative impact of anaesthetics on the course of Alzheimer's disease. OBJECTIVE: To test the hypothesis that 2 h of general anaesthesia with 1 MAC isoflurane changes learning abilities of young and old transgenic Alzheimer's mice (APP23 mice). DESIGN: Randomised controlled double-blinded study in mice. SETTING: Animal laboratory and operating theatre in the Klinik für Anästhesiologie, Technische Universität München, Germany ANIMALS: Ninety-six male mice divided in four groups: young (4 months) APP23 mice and corresponding wild-type mice; old (14 to 16 months) APP23 and corresponding wild-type mice. INTERVENTION: Mice were either anaesthetised for 2 h with 1 MAC isoflurane or sham-anaesthetised ('isoflurane' or 'control'). MAIN OUTCOME MEASURES: Learning and locomotor activity during the following 8 days using the modified Hole Board Test for mice. Results are median (interquartile range) and median difference (95% confidence interval). RESULTS: Young mice, [1.0 (1.3)] as assessed by the number of omission errors, learned better than old [1.8 (1.8); age: P = 0.004, median difference 0.5 (0.2 to 1.0)]. Anaesthetised animals [0.8 (1.5)] learned better than controls [1.6 (1.7); anaesthesia: P = 0.010, median difference 0.5 (0.1 to 0.9)]. This was accompanied by higher locomotor activity in young compared to old mice as assessed by number of line crossings per minute [10 (5) min(-1) vs. 7 (3) min(-1), P < 0.001, median difference 3 (2 to 4) min(-1)]. Anaesthesia and genotype Alzheimer's disease had no impact on locomotor activity. CONCLUSION: Isoflurane may have protective, rather than detrimental, effects on cognition in Alzheimer's disease.

Cognitive deficits after systemic induction of inducible nitric oxide synthase: a randomised trial in rats.

BACKGROUND: Nitric oxide acts as an important neurotransmitter as well as a sepsis mediator. During sepsis, high levels of nitric oxide, produced by the inducible form of the nitric oxide synthase (iNOS), may lead to disturbances concerning these conflicting roles and cause septic encephalopathy. To evaluate this theory, we aimed at first, to demonstrate cognitive dysfunction in a rat model based on systemic iNOS induction; second, to elucidate molecular mechanisms; and third, to prevent cognitive deficits in our sepsis model. METHODS: We used a rat systemic inflammation model that is based on the induction of iNOS by heat-killed Corynebacterium parvum in different doses (30 or 60 mg kg). NO2/NO3 plasma levels were measured to prove iNOS induction. Cognitive performance was investigated. In brain tissue, NOS protein and NOS activity were determined. To prevent cognitive deficits, two groups of rats received L-N-(1-Iminoethyl)-lysine (L-NIL), a specific iNOS inhibitor in the drinking water. RESULTS: The rats[Combining Acute Accent] cognitive performance, that is, short-term memory as well as long-term memory was impaired in C. parvum rats with a peak at the third day after injection in the 60 mg kg group. At the same day, neuronal NOS (nNOS)-protein content in the prefrontal cortex was reduced in C. parvum rats. nNOS activity was also reduced in C. parvum rats. The cognitive deficit in short-term memory could be prevented by L-NIL. CONCLUSION: We demonstrate early, reversible cognitive deficits in a rat model of systemic inflammation with increased systemic iNOS activity. As systemic inhibition of iNOS activity prevented rats from the deficit in short-term memory, an involvement of systemic iNOS induction in this deficit is likely. Whether the reduced nNOS-protein expression and nNOS activity are connected to systemic iNOS induction, however, remains unclear.

Nitric oxide is not a mediator of inflammation-induced resistance to atracurium.

Resistance to atracurium as a result of increased drug binding to alpha1-acid glycoprotein is associated with increased inducible nitric oxide synthase activity and increased nitric oxide levels in plasma. We investigated if the inhibition of inducible nitric oxide synthase and suppression of nitric oxide can reverse the resistance to atracurium. As a model of alpha1-acid glycoprotein and nitric oxide increase, 84 male Sprague-Dawley rats received an IV injection of either 60 mg/kg Corynebacterium parvum (CP) or saline (control). The 2 groups (CP/Control) were further divided into subgroups, receiving the selective inducible nitric oxide synthase inhibitor, N-Iminolysine, via drinking water at different concentrations. On day 4 post-CP injection, the pharmacodynamics of atracurium were determined. Plasma concentrations of nitric oxide, atracurium, and alpha1-acid glycoprotein were measured and acetylcholine receptor numbers were quantified. In the CP groups, N-Iminolysine suppressed nitric oxide levels in a dose-dependent manner. Resistance to atracurium persisted. alpha1-acid glycoprotein serum levels remained increased in all CP groups with no differences in acetylcholine receptor expression. Our results suggest that the mechanism leading to increased expression of alpha1-acid glycoprotein and consecutive increased protein binding of atracurium is not mediated by inducible nitric oxide synthase induction and nitric oxide expression.