[The Role of the Anaesthesiologist in Liver Transplantation - Preoperative Evaluation]. / Die Rolle des Anästhesisten bei Lebertransplantationen ­ präoperative Evaluation.

Preoperative evaluation prior to listing for orthotopic liver transplantation (LT) requires a careful multidisciplinary approach with specialized teams including surgeons, hepatologists and anesthesiologists in order to improve short- and long-term clinical outcomes. Due to inadequate supply of donor organs and changing demographics, patients listed for LT have become older, sicker and share more comorbidities. As cardiovascular events are the leading cause for early mortality precise evaluation of risk factors is mandatory. This review focuses on the detection and management of coronary artery disease, cirrhotic cardiomyopathy, portopulmonary hypertension and hepatopulmonary syndrome in patients awaiting LT. Further insights are being given into scoring systems, patients with Acute-on-chronic-liver-failure (ACLF), frailty, NASH cirrhosis and into psychologic evaluation of patients with substance abuse.

Development of an Anticipatory Triage-Ranking Algorithm Using Dynamic Simulation of the Expected Time Course of Patients With Trauma: Modeling and Simulation Study.

BACKGROUND: In cases of terrorism, disasters, or mass casualty incidents, far-reaching life-and-death decisions about prioritizing patients are currently made using triage algorithms that focus solely on the patient's current health status rather than their prognosis, thus leaving a fatal gap of patients who are under- or overtriaged. OBJECTIVE: The aim of this proof-of-concept study is to demonstrate a novel approach for triage that no longer classifies patients into triage categories but ranks their urgency according to the anticipated survival time without intervention. Using this approach, we aim to improve the prioritization of casualties by respecting individual injury patterns and vital signs, survival likelihoods, and the availability of rescue resources. METHODS: We designed a mathematical model that allows dynamic simulation of the time course of a patient's vital parameters, depending on individual baseline vital signs and injury severity. The 2 variables were integrated using the well-established Revised Trauma Score (RTS) and the New Injury Severity Score (NISS). An artificial patient database of unique patients with trauma (N=82,277) was then generated and used for analysis of the time course modeling and triage classification. Comparative performance analysis of different triage algorithms was performed. In addition, we applied a sophisticated, state-of-the-art clustering method using the Gower distance to visualize patient cohorts at risk for mistriage. RESULTS: The proposed triage algorithm realistically modeled the time course of a patient's life, depending on injury severity and current vital parameters. Different casualties were ranked by their anticipated time course, reflecting their priority for treatment. Regarding the identification of patients at risk for mistriage, the model outperformed the Simple Triage And Rapid Treatment's triage algorithm but also exclusive stratification by the RTS or the NISS. Multidimensional analysis separated patients with similar patterns of injuries and vital parameters into clusters with different triage classifications. In this large-scale analysis, our algorithm confirmed the previously mentioned conclusions during simulation and descriptive analysis and underlined the significance of this novel approach to triage. CONCLUSIONS: The findings of this study suggest the feasibility and relevance of our model, which is unique in terms of its ranking system, prognosis outline, and time course anticipation. The proposed triage-ranking algorithm could offer an innovative triage method with a wide range of applications in prehospital, disaster, and emergency medicine, as well as simulation and research.

Caudal Block versus Wound Infiltration for Inguinal Procedures in Young Children: A Randomized Clinical Study.

INTRODUCTION: Inguinal procedures in children are frequent and typically performed in an outpatient setting. We aimed to analyze whether there is a difference in postoperative pain scores and setup time (start of anesthesia management to incision time) when comparing caudal block (CB) with local wound infiltration. MATERIALS AND METHODS: We enrolled pediatric outpatients scheduled for inguinal procedures. Patients were randomized to receive either preincision CBs or end-of-procedure local wound infiltration. Postoperative pain scores until 24 hours postoperatively and setup time were analyzed. RESULTS: Fifty-two patients were included in the study. Thirty patients received a CB, and 22 patients received local infiltration (LI). There was no significant difference in postoperative pain scores. Setup time was significantly higher in the CB group: median 22.5 minutes IQR (16-46 minutes) compared with 17 minutes in the LI group IQR (10-35 minutes), p-value of 0.0026. CONCLUSION: Both CB and LI result in good postoperative pain control after inguinal procedures in pediatric outpatients. Since LI is less time consuming and has lower risks for complications, we recommend this technique for inguinal procedures in pediatric outpatients. Our findings will need to be confirmed in larger cohorts, but we believe the evidence generated with this study has the potential to positively influence patient care, operating room efficiency, and costs.

Hemodynamic Instability during Surgery for Pheochromocytoma: A Retrospective Cohort Analysis.

BACKGROUND: Perioperative hemodynamic instability is one of the most common adverse events in patients undergoing adrenalectomy for pheochromocytoma. The aim of this study was to analyze the impact of perioperative severe hemodynamic instability. METHODS: We present a retrospective, single-center analysis in a major tertiary hospital of all consecutive patients undergoing elective adrenalectomy from 2005 to 2019 for pheochromocytoma. Severe perioperative hypertension and hypotension were evaluated, defined as changes in blood pressure larger than 30% of the preoperative patient-specific mean arterial pressure (MAP). RESULTS: Unilateral adrenalectomy was performed in 67 patients. Intraoperative episodes of hemodynamic instability occurred in 97% of all patients (n = 65), severe hypertension occurred in 24 patients (36%), and severe hypotensive episodes occurred in 62 patients (93%). Patients with more than five severe hypotensive episodes (n = 29) received higher preoperative alpha-adrenergic blockades (phenoxybenzamine 51 ± 50 mg d-1 vs. 29 ± 27 mg d-1; p = 0.023) and had a longer mean ICU stay (39.6 ± 41.5 h vs. 20.6 ± 19.1 h, p = 0.015). CONCLUSION: Intraoperative hypotensive, rather than hypertensive, episodes occurred during adrenalectomy. The occurrence of more than five hypotensive episodes correlated well with a significantly longer hospital stay and ICU time.

Allopregnanolone Enhances GABAergic Inhibition in Spinal Motor Networks.

The neurosteroid allopregnanolone (ALLO) causes unconsciousness by allosteric modulation of γ-aminobutyric acid type A (GABAA) receptors, but its actions on the spinal motor networks are unknown. We are therefore testing the hypothesis that ALLO attenuates the action potential firing of spinal interneurons and motoneurons predominantly via enhancing tonic, but not synaptic GABAergic inhibition. We used video microscopy to assess motoneuron-evoked muscle activity in organotypic slice cultures prepared from the spinal cord and muscle tissue. Furthermore, we monitored GABAA receptor-mediated currents by performing whole-cell voltage-clamp recordings. We found that ALLO (100 nM) reduced the action potential firing of spinal interneurons by 27% and that of α-motoneurons by 33%. The inhibitory effects of the combination of propofol (1 µM) and ALLO on motoneuron-induced muscle contractions were additive. Moreover, ALLO evoked a tonic, GABAA receptor-mediated current (amplitude: 41 pA), without increasing phasic GABAergic transmission. Since we previously showed that at a clinically relevant concentration of 1 µM propofol enhanced phasic, but not tonic GABAergic inhibition, we conclude that ALLO and propofol target distinct subpopulations of GABAA receptors. These findings provide first evidence that the combined application of ALLO and propofol may help to reduce intraoperative movements and undesired side effects that are frequently observed under total intravenous anesthesia.

Effects of awake caudal anesthesia on mean arterial blood pressure in very low birthweight infants.

BACKGROUND: Intraoperative blood pressure is a relevant variable for postoperative outcome in infants undergoing surgical procedures. It is therefore important to know whether the type of anesthesia has an impact on intraoperative blood pressure management in very low birth weight infants. Here, we retrospectively analyzed intraoperative blood pressure in very low birthweight infants receiving either awake caudal anesthesia without sedation, or caudal block in combination with general anesthesia, both for open inguinal hernia repair. METHODS: Ethical approval was provided by the University of Tuebingen Ethical Committee on 05/29/2018 with the project number 403/2018BO2. Patient records of infants admitted by the neonatologist (median age at birth 31.1 ± 3.5 weeks, median weight at birth 1240 ± 521 g) which were scheduled for inguinal hernia repair were retrospectively evaluated for the course of mean arterial blood pressure and perioperative interventions to stabilize blood pressure. A total of 42 patients were included, 16 patients (11 boys, 5 girls) received awake caudal anesthesia, 26 patients (22 boys, 4 girls) a combination of general anesthesia and caudal block. RESULTS: Approximately 3% of the measured mean arterial blood pressure values in the caudal anesthesia group were below a critical margin of 35 mmHg, in contrast to 47% in the combined anesthesia group (p < 0.001). Patients in the latter group showed a significantly larger drop of mean arterial blood pressure below 35 mmHg (4.7 ± 2.7 mmHg vs. 1.9 ± 1.6 mmHg; p < 0.005) and a significantly longer time of mean arterial blood pressure below 35 mmHg (25.6 ± 26.0 min vs. 0.9 ± 2.3 min; p < 0.001), although they received more volume and vasopressor boluses for stabilization (27 ± 14.8 ml vs. 10 ± 4.1 ml; p < 0.01 and 0.15 ± 0.06 ml vs. 0 ml of cafedrine/theoadrenaline; p < 0.001). CONCLUSIONS: The study indicates that the use of caudal block as stand alone procedure for inguinal hernia repair in very low birthweight infants might be advantageous in preventing critical blood pressure drops compared to a combination of caudal block with general anesthesia.

Impact of soman and acetylcholine on the effects of propofol in cultured cortical networks.

Patients intoxicated with organophosphorous compounds may need general anaesthesia to enable mechanical ventilation or for control of epileptiform seizures. It is well known that cholinergic overstimulation attenuates the efficacy of general anaesthetics to reduce spontaneous network activity in the cortex. However, it is not clear how propofol, the most frequently used intravenous anaesthetic today, is affected. Here, we investigated the effects of cholinergic overstimulation induced by soman and acetylcholine on the ability of propofol to depress spontaneous action potential activity in organotypic cortical slices measured by extracellular voltage recordings. Cholinergic overstimulation by co-application of soman and acetylcholine (10 µM each) did not reduce the relative inhibition of propofol (1.0 µM; mean normalized action potential firing rate 0.49 ± 0.06 of control condition, p < 0.001, Wilcoxon signed rank test) but clearly reduced its efficacy. Co-application of atropine (10 nM) did not improve the efficacy. Propofol preserved its relative inhibitory potential but did not produce a degree of neuronal depression which can be expected to assure hypnosis in humans. Since a combination with atropine did not improve its efficacy, an increase in dosage will probably be necessary when propofol is used in victims suffering from organophosphorous intoxication.

ECG changes after percutaneous edge-to-edge mitral valve repair.

BACKGROUND: Mitral regurgitation (MR) has a severe impact on hemodynamics and induces severe structural changes in the left atrium. Atrial remodeling is known to alter excitability and conduction in the atrium facilitating atrial fibrillation and atrial flutter. PMVR is a feasible and highly effective procedure to reduce MR in high-risk patients, which are likely to suffer from atrial rhythm disturbances. So far, electroanatomical changes after PMVR have not been studied. HYPOTHESIS: In the current study, we investigated changes in surface electrocardiograms (ECGs) of patients undergoing PMVR for reduction of MR. METHODS: We evaluated 104 surface ECGs from patients in sinus rhythm undergoing PMVR. P wave duration, P wave amplitude, PR interval, QRS duration, QRS axis, and QT interval were evaluated before and after PMVR and at follow-up. RESULTS: We found no changes in QRS duration, QRS axis, and QT interval after successful PMVR. However, P wave duration, amplitude, and PR interval were significantly decreased after reduction of MR through PMVR (P < .05, respectively). CONCLUSION: The data we provide offers insight into changes in atrial conduction after reduction of MR using PMVR in patients with sinus rhythm.

Comparison of safety and periprocedural complications of transfemoral aortic valve replacement under local anaesthesia: minimalist versus complete Heart Team.

AIMS: The aim of the study was to evaluate peri-interventional complications and in-hospital complications in different team settings when performing transfemoral aortic valve replacement (TAVR) under local anaesthesia. METHODS AND RESULTS: We performed TAVR under local anaesthesia with a minimalist Heart Team consisting of two interventional cardiologists, an echocardiographer and two cardiac catheterisation laboratory nurses. In August 2015, new guidelines for TAVR were issued by the National Federal Joint Committee. In accordance with these guidelines, we began to perform TAVR using a complete Heart Team, consisting of two interventional cardiologists, an echocardiographer, a cardiac surgeon, an anaesthesiologist, a cardiovascular perfusionist, two cardiac catheterisation laboratory nurses, a surgical nurse and an anaesthetist nurse. In this study, we retrospectively analysed periprocedural and in-hospital outcomes. Two hundred and ninety-two (55.1%) patients were treated by the minimalist Heart Team, whereas 238 (44.9%) were treated by the complete Heart Team. There were no significant differences in periprocedural (1.4% vs. 1.3%, p=1.0) and in-hospital mortality (4.8% vs. 5.0%, p=0.9) as well as in conversion to open heart (0.3% vs. 0.8%, p=0.59) or immediate vascular surgery (0.3% vs. 2.1%, p=0.1) for minimalist versus complete Heart Team, respectively. CONCLUSIONS: TAVR under local anaesthesia can be safely performed by a minimalist Heart Team. We did not observe any differences in fatal periprocedural complications and mortality when compared with those of a complete Heart Team.

Screening and evaluation of potential recipients and donors for living donor uterus transplantation: results from a single-center observational study.

OBJECTIVE: To report our experience with the screening and selection of potential recipients and living donors of our uterus transplantation (UTx) program. DESIGN: Part of an observational program. SETTING: University hospital. PATIENT(S): Patients with absolute uterine factor infertility (AUFI). INTERVENTION(S): Screening by e-mail and telephone, selection during surgical consultation, and preoperative investigations according to a multistep procedure for living donation. MAIN OUTCOME MEASURE(S): Age, cause of AUFI, exclusion reasons, and preoperative workup. RESULT(S): A total of 212 potential recipients expressed interest in participation. Among the 46 potential recipients and 49 directed donors were 4 potential recipients, each with 2 directed donors. Mean (range) age of potential recipients was 29.6 (19-41) years. Of the potential recipients, 39 (84.8%) had congenital AUFI and 7 (17.3%) had acquired AUFI. Ultimately, 15 potential recipients with 16 directed donors were selected for participation, with 1 potential recipient having 2 directed donors. Mean age of included potential recipients was 28.9 (22-35) years, and mean donor age was 51.3 (37-62) years. Fourteen potential recipients (93.3%) had congenital AUFI, and one potential recipient (6.7%) had undergone hysterectomy for obstetric complications. CONCLUSION(S): The number of potential candidates for UTx is not inconsiderable, with congenital AUFI being the leading cause of AUFI in our cohort. However, our findings highlight that large numbers of AUFI patients need to be screened, considering our exclusion rates were >50%, owing to ABO incompatibility, unavailability of a directed donor, and self-withdrawal. Moreover, meticulous preoperative screening, including in-depth psychological assessment, is mandatory to maximize living donor safety and UTx success.

Clinical and economical impact of the presence of an extended heart team throughout the balloon-expandable transcatheter aortic valve implantation procedure.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a standard therapy for aortic valve stenosis in patients at intermediate-to-high surgical risk. Previously, TAVI at our site was performed by a minimalist heart team (MHT), comprised of two interventional cardiologists, echocardiography staff and two cardiac catheterization laboratory nurses. After revision of German Federal Joint Committee (G-BA) guidelines in September 2015, the presence of an extended heart team (EHT; including a full cardiac surgical team) became mandatory throughout the TAVI procedure. We aimed to evaluate the impact of the EHT on clinical and economical outcomes. METHODS: Data was retrospectively extracted from the medical records of patients receiving an Edwards SAPIEN 3 valve at the University Hospital Tübingen, Germany, between 2014 and 2017 and matched with cost data from the national invoice system of hospitals (InEK). For comparison, patients were grouped according to whether they underwent TAVI with or without the EHT. RESULTS: Overall, data for 341 patients (MHT 233; EHT 118) were analysed. Baseline characteristics were largely similar between groups (mean age 81.0 years; 54.5% female), though EHT patients had a lower mean logEuroSCORE (17.5% vs. 19.8%; p = 0.011) and more prior PCI/stenting (39.0% vs. 26.9%; p = 0.022). The rate of immediate procedural death (1.7%) was comparable between groups, as was mortality at 30 days (4.2%). Overall, 1.2% of patients required conversion to surgery. The cost of the index hospitalisation (minus the prosthesis) was higher in the EHT condition (difference + €1604), largely driven by expenditure on physicians (difference + €581; p < 0.001), medical technicians (difference + €372; p < 0.001) and medical supplies (difference +€244; p = 0.001). CONCLUSION: At our site, the presence of an EHT throughout the TAVI procedure appears to substantially increase hospital expenditure without significantly improving patient outcomes. We suggest that TAVI by a minimalist HT with a surgical team on call in case of emergency may be sufficient.

Midazolam is effective to reduce cortical network activity in organotypic cultures during severe cholinergic overstimulation with soman.

Intoxication with organophosphorus compounds can result in life-threatening organ dysfunction and refractory seizures. Sedation or hypnosis is essential to facilitate mechanical ventilation and control seizure activity. The range of indications for midazolam includes both hypnosis and seizure control. Since benzodiazepines cause sedation and hypnosis by dampening neuronal activity of the cerebral cortex, we investigated the drug's effect on action potential firing of cortical neurons in brain slices. Extensive cholinergic overstimulation was induced by increasing acetylcholine levels and simultaneously treating the slices with soman to block acetylcholinesterase activity. At control conditions midazolam reduced discharge rates (median/95% confidence interval) from 8.8 (7.0-10.5) Hz (in the absence of midazolam) to 2.2 (1.4-2.9) Hz (10 µM midazolam) and 1.6 (0.9-2.2) Hz (20 µM midazolam). Without midazolam, cholinergic overstimulation significantly enhanced neuronal activity to 13.1 (11.0-15.2) Hz. Midazolam attenuated firing rates during cholinergic overstimulation to 6.5 (4.8-8.2) Hz (10 µM midazolam) and 4.1 (3.3-6.0) Hz (20 µM midazolam), respectively. Thus, high cholinergic tone attenuated the drug's efficacy only moderately. These results suggest that midazolam is worth being tested as a promising drug to induce sedation and hypnosis in patients suffering from severe organophosphorous intoxication.

Automated closed-loop management of body temperature using forced-air blankets: preliminary feasibility study in a porcine model.

BACKGROUND: Management of a patient's body temperature is an important aspect of care that should be addressed by targeted temperature management (TTM). Often, non-invasive methods like forced-air blankets are used. Especially in the operating room this management may be a subsidiary and repetitive task requiring constant observation of the patient's body temperature and adaption using the limited set of available settings. Thus, automation of TTM is a feasible target to improve patient outcome and reduce caregiver workload. METHODS: A Philips IntelliVue MP 50 patient monitor with an arterial PiCCO catheter system was used to measure patient blood temperature. Thermal management was performed with a 3M Bair Hugger 755 warming unit with forced air blankets. The warming unit was extended by a computer interface to allow for remote and automated control. A proposed closed-loop algorithm reads the measured temperature and performs automated control of the 3M Bair Hugger. Evaluation was performed in an experimental intensive care setting for animal studies. Two fully automated trials are compared with two manual and two uncontrolled trials in the same study setting using six female pigs for prolonged observation times of up to 90 hours in each trial. RESULTS: The developed system and proposed algorithm allow more precise temperature management by keeping a set target temperature within a range of ± 0.5 °C in 88% of the observation time and within a range of ± 1.0 °C at all times. The proposed algorithm yielded better performance than did manual control or uncontrolled trials. It was able to adapt to individual patient needs as it is more dynamic than look-up table approaches with fixed settings for various temperatures. CONCLUSIONS: Closed-loop TTM using non-invasive forced-air warming blankets was successfully tested in a porcine study with the proposed hardware interface and control algorithm. This automation can be beneficial for patient outcome and can reduce caregiver workload and patient risk in clinical settings. As temperature readings are most often available, existing devices like the 3M Bair Hugger can easily be expanded. However, even if clinical application is feasible, open questions regarding approval and certification of such automated systems within the current legal situation still need to be answered.