Background. Delirium following cardiac surgery is a relevant complication in the majority of elderly patients but its prediction is challenging. Cardiopulmonary bypass, essential for many interventions in cardiac surgery, is responsible for a severe inflammatory response leading to neuroinflammation and subsequent delirium. Neurofilament light protein (NfL) and tau protein (tau) are specific biomarkers to detect neuroaxonal injury as well as glial fibrillary acidic protein (GFAP), a marker of astrocytic activation. Methods. We thought to examine the perioperative course of these markers in a case series of each three cardiac surgery patients under off-pump cardiac arterial bypass without evolving delirium (OPCAB-NDEL), patients with a procedure under cardio-pulmonary bypass (CPB) without delirium (CPB-NDEL) and delirium after a CPB procedure (CPB-DEL). Delirium was diagnosed by the Confusion Assessment Method for the ICU and chart reviews. Results. We observed increased preoperative levels of tau in patients with later delirium, whereas values of NfL and GFAP did not differ. In the postoperative course, all biomarkers increased multi-fold. NfL levels sharply increased in patients with CPB reaching the highest levels in the CPB-DEL group. Conclusion. Tau and NfL might be of benefit to identify patients in cardiac surgery at risk for delirium and to detect patients with the postoperative emergence of delirium.

Qualitative assessment by the Heckmatt scale (HS) and quantitative greyscale analysis of muscle echogenicity were compared for their value in detecting intensive care unit-acquired weakness (ICU-AW). We performed muscle ultrasound (MUS) of eight skeletal muscles on day 3 and day 10 after ICU admission. We calculated the global mean greyscale score (MGS), the global mean z-score (MZS) and the global mean Heckmatt score (MHS). Longitudinal outcome was defined by the modified Rankin scale (mRS) and Barthel index (BI) after 100 days. In total, 652 ultrasound pictures from 38 critically ill patients (18 with and 20 without ICU-AW) and 10 controls were analyzed. Patients with ICU-AW had a higher MHS on day 10 compared to patients without ICU-AW (2.6 (0.4) vs. 2.2 (0.4), p = 0.006). The MHS was superior to ROC analysis (cut-off: 2.2, AUC: 0.79, p = 0.003, sensitivity 86%, specificity 60%) in detecting ICU-AW compared to MGS and MZS on day 10. The MHS correlated with the Medical Research Council sum score (MRC-SS) (r = −0.45, p = 0.004), the mRS (r = 0.45; p = 0.007) and BI (r = −0.38, p = 0.04) on day 100. Qualitative MUS analysis seems superior to quantitative greyscale analysis of muscle echogenicity for the detection of ICU-AW.

Cholinergic neurotransmission has a pivotal function in the caudate-putamen, and is highly associated with the pathophysiology of Parkinson's disease. Here, we investigated long-term changes in the densities of the muscarinic receptor subtypes M1, M2, M3 (mAchRs) and the nicotinic receptor subtype α4β2 (nAchRs) in the striatum of the 6-OHDA-induced hemiparkinsonian (hemi-PD) rat model using quantitative in vitro receptor autoradiography. Hemi-PD rats exhibited an ipsilateral decrease in striatal mAchR densities between 6 and 16%. Moreover, a massive and constant decrease in striatal nAchR density by 57% was found. A second goal of the study was to disclose receptor-related mechanisms for the positive motor effect of intrastriatally injected Botulinum neurotoxin-A (BoNT-A) in hemi-PD rats in the apomorphine rotation test. Therefore, the effect of intrastriatally injected BoNT-A in control and hemi-PD rats on mAchR and nAchR densities was analyzed and compared to control animals or vehicle-injected hemi-PD rats. BoNT-A administration slightly reduced interhemispheric differences of mAchR and nAchR densities in hemi-PD rats. Importantly, the BoNT-A effect on striatal nAchRs significantly correlated with behavioral testing after apomorphine application. This study gives novel insights of 6-OHDA-induced effects on striatal mAchR and nAchR densities, and partly explains the therapeutic effect of BoNT-A in hemi-PD rats on a cellular level.

Zusammenfassung Hintergrund Die „Intensive Care Unit-Acquired Weakness“ (ICU-AW) ist eine der häufigsten Ursachen für eine neuromuskuläre Dysfunktion in der Intensivmedizin. Gegenwärtig fehlen evidenzbasierte Empfehlungen zur Diagnostik, zum Monitoring und zu therapeutischen Maßnahmen. Ziel der Arbeit Die Erfassung des derzeitigen Vorgehens bei Diagnostik, Monitoring und präventiven und therapeutischen Ansätzen bei der ICU-AW auf deutschen Intensivstationen. Material und Methoden Onlinebefragung von 448 Mitgliedern des Wissenschaftlichen Arbeitskreises Intensivmedizin (WAKI) und des Wissenschaftlichen Arbeitskreises Neuroanästhesie (WAKNA). Ergebnisse Insgesamt wurden 68/448 (15,2 %) Fragebogen ausgewertet. Bei 13,4 % (9/67) der Befragten existiert ein strukturiertes diagnostisches Vorgehen zur Detektion der ICU-AW. Für Screening (60/68; 88,2 %) und Verlaufsbeurteilung (57/65; 87,7 %) wird die klinische Untersuchung präferiert. Etablierte Scores, wie der „Medical Research Council sum score“ (MRC-SS) spielen für Screening und Verlaufskontrolle der ICU-AW eine untergeordnete Rolle (7/68; 10,3 % und 7/65; 10,8 %). Mobilisation (45/68; 66,2 %) und Sedativareduktion (38/68; 55,9 %) stellen die häufigsten präventiven und therapeutischen Ansätze dar. Ein Mangel an Physiotherapeuten (64/68; 94,1 %) und Pflegekräften (57/68; 83,8 %) wird als Hauptdefizit bei der Versorgung von Patienten mit ICU-AW identifiziert. Insgesamt 91,2 % (62/68) der Befragten befürworten die Erstellung evidenzbasierter Empfehlungen zur Diagnostik, zum Monitoring und zu therapeutischen Ansätzen bei ICU-AW. Diskussion Ein einheitliches Konzept für Diagnostik, Monitoring, Prävention und Therapie der ICU-AW auf deutschen Intensivstationen fehlt weitgehend. Innovative diagnostische Ansätze könnten in Zukunft helfen, Patienten mit einem hohem Risiko für eine ICU-AW frühzeitig zu detektieren, präventive Maßnahmen einzuleiten sowie wertvolle prognostische Informationen zu gewinnen.

Mitochondria are key structures providing most of the energy needed to maintain homeostasis. They are the main source of adenosine triphosphate (ATP), participate in glucose, lipid and amino acid metabolism, store calcium and are integral components in various intracellular signaling cascades. However, due to their crucial role in cellular integrity, mitochondrial damage and dysregulation in the context of critical illness can severely impair organ function, leading to energetic crisis and organ failure. Skeletal muscle tissue is rich in mitochondria and, therefore, particularly vulnerable to mitochondrial dysfunction. Intensive care unit-acquired weakness (ICUAW) and critical illness myopathy (CIM) are phenomena of generalized weakness and atrophying skeletal muscle wasting, including preferential myosin breakdown in critical illness, which has also been linked to mitochondrial failure. Hence, imbalanced mitochondrial dynamics, dysregulation of the respiratory chain complexes, alterations in gene expression, disturbed signal transduction as well as impaired nutrient utilization have been proposed as underlying mechanisms. This narrative review aims to highlight the current known molecular mechanisms immanent in mitochondrial dysfunction of patients suffering from ICUAW and CIM, as well as to discuss possible implications for muscle phenotype, function and therapeutic approaches.