Genotype- and sex-specific changes in vital parameters during isoflurane anesthesia in a mouse model of Alzheimer’s disease

BackgroundThe prevalence of neurodegenerative diseases is increasing as is life expectancy with Alzheimer’s disease accounting for two-thirds of dementia cases globally. Whether general anesthesia and surgery worsen cognitive decline is still a matter of debate and most likely depending on the interplay of various influencing factors. In order to account for this complexity, Alzheimer’s disease animal models have been developed. The Tg2576 model of Alzheimer’s disease is a well-established mouse model exhibiting amyloidopathy and age-dependent sex-specific differences in Alzheimer’s disease symptomology. Yet, data on anesthesia in this mouse model is scarce and a systematic comparison of vital parameters during anesthesia with wild-type animals is missing. In order to investigate the safety of general anesthesia and changes in vital parameters during general anesthesia in Tg2576 mice, we did a secondary analysis of vital parameters collected during general anesthesia in aged Tg2576 mice.MethodsAfter governmental approval (General Administration of the Free State of Bavaria, file number: 55.2-1-54-2532-149-11) 60 mice at 10-12 months of age were exposed to isoflurane (1.6 Vol%) for 120 min, data of 58 mice was analyzed. During general anesthesia, heart rate, respiratory rate, temperature, isoflurane concentration and fraction of inspired oxygen were monitored and collected. Data were analyzed using univariate and multivariate linear mixed regression models.ResultsDuring general anesthesia, heart rate decreased in a sex-specific manner. Respiratory rate decreased and body temperature increased dependent on genotype. However, the changes were limited and all vital parameters stayed within physiological limits.ConclusionIsoflurane anesthesia in the Tg2576 mouse model is safe and does not seem to influence experimental results by interacting with vital parameters. The present study provides information on appropriate anesthesia in order to advance research on anesthesia and AD and could contribute to improving laboratory animal welfare

Surgical Intensive Care Unit Optimal Mobilisation Score (SOMS) trial: a protocol for an international, multicentre, randomised controlled trial focused on goal-directed early mobilisation of surgical ICU patients

Introduction: Immobilisation in the intensive care unit (ICU) leads to muscle weakness and is associated with increased costs and long-term functional disability. Previous studies showed early mobilisation of medical ICU patients improves clinical outcomes. The Surgical ICU Optimal Mobilisation Score (SOMS) trial aims to test whether a budget-neutral intervention to facilitate goal-directed early mobilisation in the surgical ICU improves participant mobilisation and associated clinical outcomes. Methods and analysis The SOMS trial is an international, multicentre, randomised clinical study being conducted in the USA and Europe. We are targeting 200 patients. The primary outcome is average daily SOMS level and key secondary outcomes are ICU length of stay until discharge readiness and ‘mini’ modified Functional Independence Measure (mmFIM) at hospital discharge. Additional secondary outcomes include quality of life assessed at 3 months after hospital discharge and global muscle strength at ICU discharge. Exploratory outcomes will include: ventilator-free days, ICU and hospital length of stay and 3-month mortality. We will explore genetic influences on the effectiveness of early mobilisation and centre-specific effects of early mobilisation on outcomes. Ethics and dissemination Following Institutional Review Board (IRB) approval in three institutions, we started study recruitment and plan to expand to additional centres in Germany and Italy. Safety monitoring will be the domain of the Data and Safety Monitoring Board (DSMB). The SOMS trial will also explore the feasibility of a transcontinental study on early mobilisation in the surgical ICU. Results: The results of this study, along with those of ancillary studies, will be made available in the form of manuscripts and presentations at national and international meetings. Registration This study has been registered at clinicaltrials.gov (NCT01363102)

Assessment of mobilization capacity in 10 different ICU scenarios by different professions

Background: Mobilization of intensive care patients is a multi-professional task. Aim of this study was to explore how different professions working at Intensive Care Units (ICU) estimate the mobility capacity using the ICU Mobility Score in 10 different scenarios. Methods: Ten fictitious patient-scenarios and guideline-related knowledge were assessed using an online survey. Critical care team members in German-speaking countries were invited to participate. All datasets including professional data and at least one scenario were analyzed. Kruskal Wallis test was used for the individual scenarios, while a linear mixed-model was used over all responses. Results: In total, 515 of 788 (65%) participants could be evaluated. Physicians (p = 0.001) and nurses (p = 0.002) selected a lower ICU Mobility Score (-0.7 95% CI -1.1 to -0.3 and -0.4 95% CI -0.7 to -0.2, respectively) than physical therapists, while other specialists did not (p = 0.81). Participants who classified themselves as experts or could define early mobilization in accordance to the "S2e guideline: positioning and early mobilisation in prophylaxis or therapy of pulmonary disorders" correctly selected higher mobilization levels (0.2 95% CI 0.0 to 0.4, p = 0.049 and 0.3 95% CI 0.1 to 0.5, p = 0.002, respectively). Conclusion: Different professions scored the mobilization capacity of patients differently, with nurses and physicians estimating significantly lower capacity than physical therapists. The exact knowledge of guidelines and recommendations, such as the definition of early mobilization, independently lead to a higher score. Interprofessional education, interprofessional rounds and mobilization activities could further enhance knowledge and practice of mobilization in the critical care team

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

Prehabilitation of elderly frail or pre-frail patients prior to elective surgery (PRAEP-GO): study protocol for a randomized, controlled, outcome assessor-blinded trial

Background: Frailty is expressed by a reduction in physical capacity, mobility, muscle strength, and endurance. (Pre-) frailty is present in up to 42% of the older surgical population, with an increased risk for peri- and postoperative complications. Consequently, these patients often suffer from a delayed or limited recovery, loss of autonomy and quality of life, and a decrease in functional and cognitive capacities. Since frailty is modifiable, prehabilitation may improve the physiological reserves of patients and reduce the care dependency 12 months after surgery. Methods: Patients >= 70 years old scheduled for elective surgery or intervention will be recruited in this multicenter, randomized controlled study, with a target of 1400 participants with an allocation ratio of 1:1. The intervention consists of (1) a shared decision-making process with the patient, relatives, and an interdisciplinary and interprofessional team and (2) a 3-week multimodal, individualized prehabilitation program including exercise therapy, nutritional intervention, mobility or balance training, and psychosocial interventions and medical assessment. The frequency of the supervised prehabilitation is 5 times/week for 3 weeks. The primary endpoint is defined as the level of care dependency 12 months after surgery or intervention. Discussion: Prehabilitation has been proven to be effective for different populations, including colorectal, transplant, and cardiac surgery patients. In contrast, evidence for prehabilitation in older, frail patients has not been clearly established. To the best of our knowledge, this is currently the largest prehabilitation study on older people with frailty undergoing general elective surgery

Neuromuscular blockade improves surgical conditions (NISCO).

We examined the impact of muscle relaxation on surgical conditions and patients' postoperative outcome during elective laparoscopic cholecystectomy under balanced anaesthesia.After approval and consent, 57 anaesthetized patients were randomly assigned to group no neuromuscular blockade (No NMB) and deep neuromuscular blockade (Deep NMB), i.e. no twitch response to train-of-four nerve stimulation. Laparoscopic cholecystectomy was performed using the 4-trocar technique with a CO2-pneumoperitoneum. Surgical conditions were assessed using a Visual Analogue Scale. Movement of diaphragm or abdominal muscles, inadequate visibility, or breathing and coughing against the ventilator were documented as events reflecting inadequate muscle relaxation. Independently, surgeons could request 0.3 mg/kg rocuronium to improve surgical conditions. Workflow variables were obtained as a surrogate of surgical conditions. Data are presented as mean (95 % confidence interval). The trial is registered at ClinicalTrials.gov (NCT00895778).While in 12 of 25 patients of group "No NMB" one or more adverse events impaired the surgical procedure (p < 0.001), only 1 of 25 patients of group "Deep NMB" showed an adverse event. Deep NMB resulted in an absolute risk reduction of 0.44 (0.23-0.65) and a number needed to treat of 2.3 (1.5-4.4), respectively. Surgeons requested 0.3 mg/kg rocuronium in 10 of 25 cases (40 %) of group "No NMB" only. This dose significantly improved surgical conditions by an average 62 of 100 possible points. All further variables did not differ between groups.Deep NMB ameliorates surgical conditions for laparoscopic cholecystectomy by improved visibility and reduction of involuntary movements