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Background Delirium is a common complication in patients in Intensive Care Units (ICU). Interventions such as mobilization are effective in the prevention and treatment of delirium, although this is usually completed during the daytime. Aim The aim of this study was to assess the feasibility of mobilization in the evening to prevent and treat ICU patients from delirium by an additional mobility team over 2 weeks. Methods The design was a pilot, multi-centre, randomized, controlled trial in four mixed ICUs over a period of 2 weeks. The mobility team consisted of trained nurses and physiotherapists. Patients in the intervention group were mobilized onto the edge of the bed or more between 21.00 and 23.00. Patients in the control group received usual care. The primary outcome parameter was the feasibility of the study, measured as recruitment rate, delivery rate, and safety. Secondary outcomes were duration and incidence of delirium, mortality, duration of mechanical ventilation (MV), and hospital length of stay for 28 days follow-up, and power calculation for a full trial. Results Out of 185 patients present in the ICUs, 28.6% (n = 53) were eligible and could be recruited, of which 24.9% (n = 46, Intervention = 26, Control = 20) were included in the final analysis. In the intervention group, mobilization could be delivered in 75% (n = 54) of 72 possible occasions; mobilization-related safety events appeared in 16.7% (n = 9) without serious consequences. Secondary parameters were similar, with less delirium in the intervention group albeit not significant. With an association of Cramer's V = 0.237, a complete study reaching statistical significance would require at least 140 patients, last 6 weeks, and cost >30 000 €. Conclusions In a mixed ICU population, mobilization in the evening was feasible in one-quarter of patients with a low rate of safety events. Future trials seem to be feasible and worth conducting.

Objectives To describe the relationships between anticholinergic drug exposure, cholinesterase enzyme activity, inflammation, and the development of postoperative delirium in children. Design Single-center prospective cohort study. Setting Twenty-two bed PICU in a tertiary-care academic medical center in Germany. Patients A consecutive cohort of children admitted after major elective surgery. Interventions Children were screened for delirium bid over 5 consecutive postoperative days. Acetylcholinesterase and butyrylcholinesterase plasma activity levels were measured prior to surgery and once daily during the 5 day study period. Number of anticholinergic drugs and Anticholinergic Drug Scale score were calculated for each patient. Measurements and main results Ninety-three children (age range, 0-17 yr) were included. The number of anticholinergic drugs as well as the Anticholinergic Drug Scale score were significantly correlated with development of postoperative delirium, independently of disease severity. Baseline cholinesterase enzyme levels did not differ between patients who did and did not develop postoperative delirium. Butyrylcholinesterase levels, but not acetylcholinesterase levels, dropped by 33% postoperatively, independent of the presence of postoperative delirium. Postoperative butyrylcholinesterase levels were inversely related to number of anticholinergic drugs, Anticholinergic Drug Scale score, and C-reactive protein levels. Conclusions Anticholinergic drug exposure was related to development of postoperative delirium in this cohort, with demonstration of a dose-response relationship. As there are alternative options available for many of these medications, it may be reasonable to avoid anticholinergic exposure in the PICU whenever possible.

ZusammenfassungFür ein erfolgreiches PAD-Management ist eine validierte Erfassung von Schmerz, Agitation und Delir erforderlich. Eine Implementierung erfolgt allerdings nur schleppend. Warum das schneller gehen sollte und was dazu nötig ist, hat ein interaktives Kasuistik-Forum ergeben, bei dem Ärzte und Pflegende gleichermaßen vertreten waren.

Background Clinicians are commonly confronted with the differential diagnosis of altered mental status, impaired cognition and altered level of consciousness in hospitalized patients including those admitted to medical, geriatric, emergency, intensive and post-operative care units. Although delirium is the most common acute neuropsychiatric condition in the acute hospital setting this diagnosis is commonly delayed, made too late or missed altogether. Difficulties and importance of timely diagnosis The causes of delirious states are manifold. Both, direct damage to the brain tissue as well as encephalopathy as a result of other medical diseases, can be the cause of delirium. Depending on the predisposition delirious syndromes can be provoked by minor medical interventions. Clinical presentation is very variable, but remains largely independent of the triggering mechanisms. Purely catatonic, hypoactive, hyperactive and excitatory types as well as mixed forms can be distinguished.Immediate diagnosis of a delirious syndrome and rapid elucidation of its causes are keys for the implementation of curative therapy. There is a need to act fast because delirious phases are associated with significantly longer hospital stay and increased morbidity as a result of long-term cognitive deficits as well as increased mortality. As negative outcome is closely linked to the duration of a delirious episode, early diagnosis and rapid termination of the delirium constitute a significant positive predictor of outcome. In this respect, delirium represents an emergency, with or without concomitant cerebral or extracerebral symptoms.

Background & Aims: Transient elastography (TE) has routinely been implemented in the diagnosis and assessment of chronic liver disease. Little data are available in the post liver transplant (LTx) setting. Methods: Three months after LTx, we performed TE in 137 liver transplant recipients and investigated its predictive value upon further clinical outcome. The mean follow-up time for clinical outcome was 24 months. Results: Mean TE value was 10.6 kPa (± 6.3 kPa; range 2.8 – 29.9 kPa). There was a significant correlation between TE and aspartate aminotransferase (AST) (p=0.004), gamma-glutamyl transferase (GGT) (p=0.031) and bilirubin (p

Background: Multidrug-resistant (MDR) pathogens represent an emerging challenge in end-stage liver disease and in liver transplant recipients. Methods: We evaluated the impact of MDR bacteria upon clinical outcomes in patients with end-stage liver disease (n = 777) at the time of enrollment on the liver transplant (LTx) waiting list, after first LTx (n = 645), and after second LTx (n = 128). Results: Colonization/infection with MDR bacteria was present in 72/777 patients on the waiting list, in 98/645 patients at first LTx, and in 46/128 patients at second LTx. While on the LTx waiting list, the time until first hydropic decompensation (p = 0.021), hepatic encephalopathy (p < 0.001) and hepatorenal syndrome (p < 0.001) was reduced in the presence of MDR bacteria, which remained an independent risk factor of poor survival in multivariate analysis (p < 0.001). Following first and second liver transplant, MDR bacteria were associated with an increased risk of infection-related deaths (first LTx: p < 0.001; second LTx: p = 0.037) and reduced actuarial survival (first LTx: p < 0.001; second LTx: p = 0.046). Conclusions: We showed that MDR pathogens are associated with poor outcomes before, after first and after recurrent LTx.

Numerous extended donor criteria (EDC) have been identified in liver transplantation (LT), but different EDC have different impacts on graft and patient survival. This study aimed to identify major EDC (maEDC) that were best able to predict the outcome after LT and to examine the plausibility of an allocation algorithm based on these criteria. All consecutive LTs between 12/2006 and 03/2014 were included (n = 611). We analyzed the following EDC: donor age > 65 years, body mass index > 30, malignancy and drug abuse history, intensive care unit stay/ventilation > 7 days, aminotransferases > 3 times normal, serum bilirubin > 3 mg/dL, serum Na+ > 165 mmol/L, positive hepatitis serology, biopsy-proven macrovesicular steatosis (BPS) > 40%, and cold ischemia time (CIT) > 14 h. We analyzed hazard risk ratios of graft failure for each EDC and evaluated primary non-function (PNF). In addition, we analyzed 30-day, 90-day, 1-year, and 3-year graft survival. We established low- and high-risk graft (maEDC 0 vs. ≥ 1) and recipient (labMELD 40%, donor age > 65 years, and CIT > 14 h (all p 65 years, BPS > 40%, and CIT > 14 h are major EDC that decrease short and 3-year graft survival, and 3-year patient survival. An allocation algorithm based on maEDC and labMELD is therefore plausible.

To determine and quantify risk factors for postoperative pediatric delirium.Single-center prospective cohort study.Twenty-two bed PICU in a tertiary care academic medical center in Germany.All children admitted after major elective surgery (n = 93; 0-17 yr).After awakening, children were screened for delirium using the Cornell Assessment of Pediatric Delirium bid over a period of 5 days. Demographic and clinical data were collected from the initiation of general anesthesia.A total of 61 patients (66%) were delirious. Younger children developed delirium more frequently, and the symptoms were more pronounced. The number of preceding operations did not influence the risk of delirium. Total IV anesthesia had a lower risk than inhalational anesthesia (p0.05). Duration of anesthesia was similar in all groups. Patients with delirium had a longer duration of mechanical ventilation in the PICU (p0.001). Significant differences in cumulative doses of various medications (e.g., sedatives, analgesics, and anticholinergics) were noted between groups; these differences were independent of disease severity. Invasive catheters and respiratory devices (p0.01) as well as infections (p0.001) increased risk of delirium.A high prevalence of delirium was noted in the PICU, and several perioperative risk factors were identified. Our data may be a base for development of strategies to prevent and treat postoperative delirium in children.

Biliary strictures are an important cause of morbidity and mortality in primary hepatic disease and after liver transplantation (LT). We aimed to characterize inflammatory cytokines in biliary fluids in biliary strictures to investigate their immunological origin.We conducted a retrospective study on 72 patients with strictures after LT, eight patients with primary sclerosing cholangitis (PSC) and 15 patients with secondary sclerosing cholangitis (SSC). We measured cytokines interleukin (IL)-2, -4, -6, -10, -17, monocyte chemoattractant protein (MCP)-1, fibroblast growth factor (FGF)-2 and interferon (IFN)-γ as well as biochemical components such as protein and phospholipids in biliary fluid obtained from endoscopic retrograde cholangiography (ERC). Cell viability assays were performed on human cholangiocytes (H69) after being treated with IL-6, IL-4 and IFN-γ.Bile of patients with diffuse strictures after LT or due to SSC showed low values of all measured cytokines except for IL-6 levels, which were largely elevated in patients with diffuse strictures after LT. Patients high in biliary IL-6 showed an increase in profibrotic markers FGF-2 and MCP-1. In contrast, PSC bile was dominated by a Th1/Th17 profile with elevated IL-2, IL-17 and IFN-γ. In LT patients with biliary strictures, biliary IL-6 negatively predicted retransplantation-free survival after ERC.PSC patients showed a biliary Th1/Th17 cytokine profile, while SSC and diffuse strictures showed low values of cytokines except IL-6. In diffuse intrahepatic strictures after LT, biliary IL-6 is strongly associated with retransplantation-free survival after ERC.

Background : Delirium is a common complication in patients on Intensive Care Units (ICU). Caring interventions such as early mobilization are effective in prevention and treatment of delirium, but are recommended during daytime. It may be effective in the night, too. Method : The aim of this study was to prove the effect of mobilization in the evening to prevent or treat ICU patients from delirium. The design was a multicentric, randomized, controlled trial in 5 mixed ICUs over a period of 2 weeks with max. 28 days follow-up. Patients in the intervention group were mobilized onto the edge of the bed or more between 9:00 and 11:00 p.m. by an additional mobilization team, following safety criteria. Patients in the control group received usual care. Primary outcome parameter was the duration of a delirium. Secondary parameters were presence of delirium, mortality, duration of mechanical ventilation (MV) and stay, feasibility, and mobilization-related complications. Results : In summary, n=69 patients could be analysed (intervention n=36, control n=33). Due to limited resources, the trial was stopped and reached 62% of targeted sample size. Mobilization in the evening did not significantly reduce duration of existing delirium, delirium presence, length of MV or days in ICU and hospital for 28 days follow-up. In an unplanned post-hoc analysis, mobilization in the evening prevented patients from delirium in the first four days (6 (16.7%) vs. 13 (39.4%), p=0.032), with a number needed to treat of 5. The intervention was feasible in 71.7% of eligible patients, with 13.6% unwanted safety events. Conclusions : In a mixed ICU population, mobilization in the evening did not show a reduction in duration of delirium, MV or length of stay, but a reduction in the incidence of early onset delirium. Mobilization between 9:00 and 11:00 pm. by an interprofessional mobilization team may prevent patients from delirium. The intervention was feasible, safe, and accepted by most patients.

Clinicians are commonly confronted with the differential diagnosis of altered mental status, impaired cognition and altered level of consciousness in hospitalized patients including those admitted to medical, geriatric, emergency, intensive and post-operative care units. Although delirium is the most common acute neuropsychiatric condition in the acute hospital setting this diagnosis is commonly delayed, made too late or missed altogether.The causes of delirious states are manifold. Both, direct damage to the brain tissue as well as encephalopathy as a result of other medical diseases, can be the cause of delirium. Depending on the predisposition delirious syndromes can be provoked by minor medical interventions. Clinical presentation is very variable, but remains largely independent of the triggering mechanisms. Purely catatonic, hypoactive, hyperactive and excitatory types as well as mixed forms can be distinguished.Immediate diagnosis of a delirious syndrome and rapid elucidation of its causes are keys for the implementation of curative therapy. There is a need to act fast because delirious phases are associated with significantly longer hospital stay and increased morbidity as a result of long-term cognitive deficits as well as increased mortality. As negative outcome is closely linked to the duration of a delirious episode, early diagnosis and rapid termination of the delirium constitute a significant positive predictor of outcome. In this respect, delirium represents an emergency, with or without concomitant cerebral or extracerebral symptoms.

Indication for combined cardiac surgery and orthotopic liver transplantation is rare and patients are at high risks. Individual surgical strategy must be developed since a general standard of such procedure does not exist. We report the case of a 45-year-old woman who underwent simultaneously modified Bentall procedure and orthotopic liver transplantation. Underlying diseases were end-stage polycystic liver, aneurysm of the ascending aorta, and severe aortic regurgitation. To avoid prolonged bypass times, both teams worked simultaneously. During cardiac reperfusion, time inferior vena cava stayed ligated while the cyst liver was explanted.

Background/objectives: Solid pseudopapillary neoplasms of the pancreas (SPN) are rare tumors. For patients with unresectable liver metastases of SPN, no standard treatment has been defined so far. Here we report a case of a 40-year-old woman with SPN and metastases confirmed to the liver, and disease progression in the liver after primary tumor resection and chemotherapy with gemcitabine and cisplatin. Methods: Chemosaturation with percutaneous hepatic perfusions is a minimally invasive, repeatable regional therapy which delivers chemotherapy directly to the liver while limiting systemic toxicity. As an individual treatment approach, the patient was treated with chemosaturation with percutaneous hepatic perfusions of melphalan. Results: The procedure was performed twice within 8 weeks after which the liver metastases showed a marked reduction in size and vascularization (partial response). Grade 3 leukopenia after the second procedure was managed effectively with granulocyte colony-stimulating factor. No other toxicities were observed. Ten months after initiating treatment, the patient had a good performance status and remained stable. Conclusions: For SPN with unresectable liver metastases and progression despite systemic treatment, repeat chemosaturation with high-dose melphalan may also offer an effective regional treatment option. Copyright © 2014, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.

Delirium is a serious complication in patients in intensive care units. Previous surveys on delirium management in daily practice showed low adherence to published guidelines.To evaluate delirium management in nurses and physicians working in intensive care units in German-speaking countries and to identify related differences between nurses and physicians.The study used an open online survey with multiple-choice responses.An invitation for participation was spread via journals and electronic resources using a snowball system. Apart from recording socio-demographical characteristics, the survey collected data on delirium assessment, delirium-related processes, non-pharmacological prevention and treatment and barriers for implementation. Differences between nurses and physicians were tested by Fisher's exact test with sequential Bonferroni correction.The survey was conducted in autumn 2016, and 559 clinicians participated. More nurses than physicians reported screening for delirium. The majority of clinicians reported screening for delirium when this was suspected; more than 50% used validated instruments. Half of the clinicians had delirium-related structures implemented, such as two thirds reporting delirium-related processes. Most cited barriers were lack of time and missing knowledge about delirium and its assessment. With significant difference, physicians recommended more than nurses early removal of catheters and daily interprofessional goals for patients.In German-speaking countries, assessment of delirium needs further improvement, leading to accurate assessment. Delirium-related structures and processes appear to be implemented widely, with only a few differences between nurses and physicians.Nurses and physicians in this survey reported similar perceptions and attitudes towards management of delirium. Both professions need more knowledge and inter-professional training on when and how to use validated assessment instruments.

Objective Intensive care delirium is a substantial problem in adults. Intensive care delirium is increasingly recognized in pediatrics in parallel with the development of specific scoring systems for children. However, little is known about the fluctuating course of intensive care delirium in children after surgery and possible implications on diagnostic and therapeutic strategies. Design Patients that needed treatment in the PICU following elective surgery were screened for intensive care delirium with the Cornell Assessment of Pediatric Delirium. When the patients were awake (Richmond Agitation and Sedation Score > -3), two trained investigators conducted the Cornell Assessment of Pediatric Delirium twice daily for five consecutive days. Patients Ninety-three patients aged 0 to 17 years. Interventions Eight hundred forty-five assessments completed. Measurements and main results Of the 845 scores, 230 were consistent with delirium (27.2%). Sixty-one patients (65.5%) were diagnosed with intensive care delirium. Half of these patients (n = 30; 32.2%) had a short-lasting delirium that resolved within 24 hours, and half (n = 31; 33.3%) had delirium of longer duration. Delirium could be clearly distinguished from sedation by analysis of individual test items of the Cornell Assessment of Pediatric Delirium. Time spent delirious had a measurable effect on outcome variables, including hospital length of stay. Conclusion Most postoperative PICU patients develop intensive care delirium. Some have a short-lasting course, which underlines the need for early screening. Our findings support the view of delirium as a continuum of acute neurocognitive disorder. Further research is needed to investigate prophylactic and treatment approaches for intensive care delirium.

In the intensive care unit (ICU) we assessed the agreement between the delirium ratings of two independent delirium assessment methods: (a) the Confusion Assessment method for the ICU (CAM-ICU); and (b) the Intensive Care Delirium Screening Checklist (ICDSC). Prospective, descriptive cohort study. During a 6-month period, 174 patients (mean age 62.4 ± 13.0 years) admitted to the ICU after elective surgery or after an emergency were included and assessed with both delirium assessment systems by two trained independent investigators (research person and bedside nurses) during their ICU stay or for up to 7 days after ICU admission. Patients' clinical characteristics at ICU admission day were documented. After excluding permanently unconscious patients with ≤ –4 on the Richmond Agitation Sedations scale, delirium was identified in 71 of the 174 patients (41%). The patients who were included were tested in 374 paired but researcher-independent ratings of delirium by both scoring methods. The kappa coefficient determined over 7 days of ICU stay was 0.80 (CI 95%: 0.78–0.84; p

The Hepatic CHEMOSAT® Delivery System is an innovative medical device for the treatment of patients with unresectable primary liver tumors or unresectable hepatic metastases from solid organ malignancies. This system is used to perform chemosaturation percutaneous hepatic perfusion (CS-PHP), a procedure in which a high dose of the chemotherapeutic agent melphalan is delivered directly to the liver while limiting systemic exposure. In a clinical trial program, CS-PHP with melphalan significantly improved hepatic progression-free survival in patients with unresectable hepatic metastases from ocular or cutaneous melanoma. Clinically meaningful hepatic responses were also observed in patients with hepatocellular carcinoma or neuroendocrine tumors. Furthermore, the results of published studies and case reports demonstrated that CS-PHP with melphalan resulted in favorable tumor response rates in a range of tumor histologies (ocular or cutaneous melanoma, colorectal cancer, and hepatobiliary tumors). Analyses of the safety profile of CS-PHP revealed that the most common adverse effects were hematologic events (thrombocytopenia, anemia, and neutropenia), which were clinically manageable. Taken together, these findings indicate that CS-PHP is a promising locoregional therapy for patients with primary and secondary liver tumors and has a acceptable safety profile. Funding: Delcath Systems Inc., New York, NY, USA.

Introduction Delirium is a frequent complication after cardiac surgery. Although various risk factors for postoperative delirium have been identified, the relationship between nocturnal breathing disorders and delirium has not yet been elucidated. This study evaluated the relationship between sleep-disordered breathing (SDB) and postoperative delirium in cardiac surgery patients without a previous diagnosis of obstructive sleep apnea. Methods In this prospective cohort study, 92 patients undergoing elective cardiac surgery with extracorporeal circulation were evaluated for both SDB and postoperative delirium. Polygraphic recordings were used to calculate the apnea-hypopnea index (AHI; mean number of apneas and hypopneas per hour recorded) of all patients preoperatively. Delirium was assessed during the first four postoperative days using the Confusion Assessment Method. Clinical differences between individuals with and without postoperative delirium were determined with univariate analysis. The relationship between postoperative delirium and those covariates that were associated with delirium in univariate analysis was determined by a multivariate logistic regression model. Results The median overall preoperative AHI was 18.3 (interquartile range, 8.7 to 32.8). Delirium was diagnosed in 44 patients. The median AHI differed significantly between patients with and without postoperative delirium (28 versus 13; P = 0.001). A preoperative AHI of 19 or higher was associated with an almost sixfold increased risk of postoperative delirium (odds ratio, 6.4; 95% confidence interval, 2.6 to 15.4; P

Septic encephalopathy is associated with rapid deterioration of cortical functions. Using magnetic resonance imaging (MRI) we detected functional abnormalities in the hippocampal formation of patients with septic delirium. Hippocampal dysfunction was further investigated in an animal model for sepsis using lipopolysaccharide (LPS) injections to induce endotoxemia in rats, followed by electrophysiological recordings in brain slices. Endotoxemia induced a deficit in long term potentiation which was completely reversed by apamin, a blocker of small conductance calcium-activated potassium (SK) channels, and partly restored by treatment with physostigmine (eserine), an acetylcholinesterase inhibitor, or TBPB, a selective M1 muscarinic acetylcholine receptor agonist. These results suggest a novel role for SK channels in the etiology of endotoxemia and explain why boosting cholinergic function restores deficits in synaptic plasticity. Drugs which enhance cholinergic or M1 activity in the brain may prove beneficial in treatment of septic delirium in the intensive care unit. Electronic supplementary material The online version of this article (doi:10.1186/s40478-015-0245-8) contains supplementary material, which is available to authorized users.