[Anesthesia for organ transplant patients]. / Anästhesie bei organtransplantierten Patient:innen.

Organ transplant patients who must undergo nontransplant surgical interventions can be challenging for the anesthesiologists in charge. On the one hand, it is important to carefully monitor the graft function in the perioperative period with respect to the occurrence of a possible rejection reaction. On the other hand, the ongoing immunosuppression may have to be adapted to the perioperative requirements in terms of the active substance and the route of administration, the resulting increased risk of infection and possible side effects (e.g., myelosuppression, nephrotoxicity and impairment of wound healing) must be included in the perioperative treatment concept. Furthermore, possible persistent comorbidities of the underlying disease and physiological peculiarities as a result of the organ transplantation must be taken into account. Support can be obtained from the expertise of the respective transplantation center.

Intraoperative suggestions to prevent postoperative delirium in patients undergoing transaortic valvular replacement: a randomized placebo-controlled trial.

BACKGROUND: Postoperative delirium (POD) is a serious complication following anaesthesia and surgery and significantly influences postoperative outcome especially in the elderly population. Intraoperative music and positive suggestions influence postoperative outcomes by attenuating analgesic demand and increasing patient satisfaction. AIMS: Here, we examined the effect of intraoperative music and positive suggestions on the development of POD in aged patients undergoing transcatheter aortic valve replacement (TAVR) procedure under general anaesthesia. METHODS: For this randomized placebo-controlled study, eligible patients without cognitive deficit, indicated by a MMSE < 10 points, were anesthetized using remifentanil and sevoflurane. Anaesthetic depth was guide with bispectral index. An audiotape with positive suggestions was applied from a MP3 player via headphones. POD, pain and PONV was assessed. CAM-ICU and Nu-DESC were done twice daily for the first 5 days. RESULTS: Of 140 patients 118 patients could be analysed (57 male, 80.6 ± 5.1 years). POD was diagnosed in 16 patients (12.7%). POD was significantly more often observed in male (12, 21.1%) than in female (4, 6.6%, p = 0.02) and in patients with a low MMSE (23.6 ± 4.5 vs. 26.8 ± 2.8, p = 0.001). Anaesthetic depth did not influence the incidence of POD. Intraoperative music and suggestions did not affect the rate of POD, pain, analgesic requirement or PONV. DISCUSSION: In patients undergoing TAVR male sex and low MMSE scoring are associated with an increase in POD. CONCLUSIONS: Intraoperative music and positive suggestions do not influence the incidence of POD in this patient group. STUDY REGISTRATION: DRKS: 00024444, start of registration: 4.02.202, final registration: 17.09.2021.

[Anaesthesia and Perioperative Management for Patients with Parkinson's Disease]. / Anästhesie und perioperative Betreuung bei Patienten mit Morbus Parkinson.

Idiopathic Parkinson's syndrome is associated with the loss of dopaminergic cells. It is defined by the presence of akinesia together with one of the cardinal symptoms: rigor, tremor, or postural instability. As the perioperative management of these patients can be challenging and they have an increased perioperative risk, every anaesthesiologist should know some special features. If a patient with Parkinson's disease does not receive the required amount of dopa, akinetic crisis may occur. Moreover, the administration of dopamine-antagonistic drugs can trigger a malignant neuroleptic syndrome. These are life-threatening clinical pictures that require intensive medical treatment. Therefore, patients with Parkinson's disease should be enabled to keep the period without the intake of the specific medication as short as possible. General anaesthesia should be performed with short acting anaesthetics and a regional anaesthesia might be beneficial. Besides, all dopamine antagonists sometimes used for prophylaxis or therapy of delirium or PONV (haloperidol, metoclopramide) are contraindicated. Alternatives are short-acting benzodiazepines, atypical neuroleptics and domperidone.

Predictors of portal vein complications after pediatric liver transplantation: A German center experience.

BACKGROUND: Portal vein complications (PVCs) after pediatric liver transplantation (LT) are sometimes asymptomatic, especially in the early phase, and can threaten both the graft and patient's survival. Therefore, the purpose of this study is to analyze the risk factors for portal vein thrombosis (PVT) and portal vein stenosis (PVS) after pediatric LT. METHODS: All pediatric patients (n = 115) who underwent primary LT at Regensburg University Hospital between January 2010 and April 2017 were included in this study. The pre-, intra-, and postoperative parameters of all patients were retrospectively reviewed and risk factors for both PVT and PVS were analyzed. RESULTS: Of the 115 patients, living donor LT was performed on 57 (49.5%) patients, and biliary atresia was the primary diagnosis in 65 patients (56%). After pediatric LT, 9% of patients developed PVT, and 16.5% developed PVS. Patient weight ≤7 kg [odds ratio (OR) 9.35, 95% confidence interval (CI) 1.03-84.9, p = .04] and GRWR >3% (OR 15.4, 95% CI 1.98-129.5, p = .01) were the independent risk factors for the development of PVT and PVS, respectively upon multivariate analysis. The overall patient survival rates at 1, 3, and 5 years were 91%, 90%, and 89%, respectively, and there was no difference in patient survival among those with and without PVCs. CONCLUSIONS: Pediatric patients with body weight <7 kg and/or receiving a graft with GRWR >3% may develop PVCs and so require certain surgical modifications, close follow-up, and prophylactic anticoagulant therapy following transplant.

[The role of the the transplant coordinator]. / Rolle des Transplantationsbeauftragten.

All hospitals that are defined as organ donation hospitals according to the Social Act V (SGB V), are legally bound to employ a transplant coordinator (TxB). The field of activities of the TxB includes not only the identification of donors, the diagnosis of irreversible loss of brain function, donor evaluation and organ protection but also the support of the complete organ donation process. The TxB is responsible for the establishment of in-house hospital standards as well as the organization of advanced and continuing education and is the contact person for all aspects of organ donation. Furthermore, the TxB acts as a link between the coordination center (German Organ Procurement Organization) and the allocation organisation (Eurotransplant). The activities are subject to the Transplantation Act and its implementation statutes; however, the TxB also needs corresponding knowledge of the various guidelines on organ donation and transplantation. Finally, the TxB is also responsible for the quality assurance of the organ donation process.

Cell Salvage During Liver Transplantation for Hepatocellular Carcinoma: A Retrospective Analysis of Tumor Recurrence Following Irradiation of the Salvaged Blood.

BACKGROUND: Orthotopic liver transplantation (OLT) is the treatment option for early-stage hepatocellular carcinoma (HCC). OLT is often associated with high blood loss, requiring blood transfusion. Retransfusion of autologous blood is a key part of blood conservation. There are, however, concerns that the retransfusion of salvaged blood might cause the spread of cancer cells and induce metastasis. Irradiation of salvaged blood before retransfusion eliminates viable cancer cells. Here, we analyzed the incidence of tumor recurrence in patients with HCC undergoing OLT who received irradiated cell-salvaged blood during transplant surgery. METHODS: We retrospectively analyzed patients undergoing OLT for HCC between 2002 and 2018 at our center. We compared the tumour recurrence in patients who received no retransfusion of autologous blood with patients who received autologous blood with or without preceding irradiation of the blood. RESULTS: Fifty-one (40 male, 11 female) patients were included in the analysis; 10 patients developed tumor recurrence within a time period of 2.45 ± 2.0 years. Statistical analysis revealed that there was no significant difference in tumor recurrence between patients who received autologous blood with or without irradiation. CONCLUSION: Intraoperative transfusion of cell-salvaged blood did not increase tumor recurrence rates. Cell salvage should be used in liver transplantation of HCC patients as part of a blood conservation strategy. The effect of blood irradiation on tumor recurrence could not be definitively evaluated.

ECMO in COVID-19-prolonged therapy needed? A retrospective analysis of outcome and prognostic factors.

BACKGROUND: The role of venovenous extracorporeal membrane oxygenation (VV ECMO) in patients with COVID-19-induced acute respiratory distress syndrome (ARDS) still remains unclear. Our aim was to investigate the clinical course and outcome of those patients and to identify factors associated with the need for prolonged ECMO therapy. METHODS: A retrospective single-center study on patients with VV ECMO for COVID-19-associated ARDS was performed. Baseline characteristics, ventilatory and ECMO parameters, and laboratory and virological results were evaluated over time. Six months follow-up was assessed. RESULTS: Eleven of 16 patients (68.8%) survived to 6 months follow-up with four patients requiring short-term (<28 days) and seven requiring prolonged (⩾28 days) ECMO support. Lung compliance before ECMO was higher in the prolonged than in the short-term group (28.1 (28.8-32.1) ml/cmH2O vs 18.7 (17.7-25.0) ml/cmH2O, p = 0.030). Mechanical ventilation before ECMO was longer (19 (16-23) days vs 5 (5-9) days, p = 0.002) and SOFA score was higher (12.0 (10.5-17.0) vs 10.0 (9.0-10.0), p = 0.002) in non-survivors compared to survivors. Low viral load during the first days on ECMO tended to indicate worse outcomes. Seroconversion against SARS-CoV-2 occurred in all patients, but did not affect outcome. CONCLUSIONS: VV ECMO support for COVID-19-induced ARDS is justified if initiated early and at an experienced ECMO center. Prolonged ECMO therapy might be required in those patients. Although no relevant predictive factors for the duration of ECMO support were found, the decision to stop therapy should not be made dependent of the length of ECMO treatment.

Definition, reasons, and risk factors for mortality of patients listed for liver transplantation - a single-center study.

BACKGROUND: In Germany, following the principle "sickest first", patients awaiting liver transplantation (LTPL) are often transplanted with high MELD score and run the risk that they can no longer be transplanted, getting "too sick for transplant". METHODS: In a retrospective single-center study, we analyzed the mortality of adult patients on the waiting list for LTPL during the years 2014 to 2017. To stratify risk factors, we compared characteristics of deceased and transplanted patients. RESULTS: The main reasons for mortality were sepsis (42.9 %), malignancy (24.3 %) and bleeding (10.0 %). Risk factors for mortality (OR, univariate logistic regression, p < 0.05) were acute on chronic liver failure (ACLF), loss of E-MELD, sepsis, pneumonia, proof of pathogens, candidemia, stay at ICU, multiple organ failure and mechanical ventilation. Multivariate analysis revealed pneumonia (p < 0.001) and high MELD (p = 0.031) as risk factors. Transplantation was more likely in patients with E-MELD. We suggest a Waiting List Mortality Index for Transplantation (WMIT), by dividing deceased patients to transplanted patients to assess mortality. Average WMIT in our cohort was 0.65. CONCLUSIONS: Mortality on the waiting list is mainly determined by pneumonia and infections in high-MELD patients. Therefore, patients with ACLF after infections should be prioritized for LTPL. A WMIT might suitably represent waiting list mortality.

Acute Kidney Injury and Renal Regional Oxygen Saturation During Pediatric Liver Transplantation.

BACKGROUND Kidney injury is a complication among children undergoing liver transplantation (pLTx). Cystatin C serum concentration seems to be superior to creatinine-based determination of kidney injury in adults and children. Near-infrared spectroscopy (NIRS) technology provides non-invasive and real-time measurement of renal tissue oxygenation. Here, we compared renal tissue oximetry (rSrO2) with conventional diagnostic criteria cystatin C and creatinine concentration in children undergoing pLTx. MATERIAL AND METHODS rSrO2 was measured intraoperatively in children undergoing pLTx over the left kidney, and was statistically compared with pre- and postoperative serum creatinine and cystatin C concentrations. RESULTS rSrO2 was affected by hemoglobin concentration, bilirubin concentration, and FiO2. Statistical analysis demonstrated that rSrO2 was significantly reduced in children with preoperative pathologic increased cystatin C concentrations compared to children without (63.7±4.3 vs. 53.4±4.9, p<0.05). We did not detect a significant difference in rSrO2 between children who developed postoperative renal impairment, either determined by increased postoperative cystatin C concentration, creatinine concentration, or the pRIFLE criteria. Intraoperative increase or decrease in rSrO2 did not predict the development of postoperative kidney injury. CONCLUSIONS In children with liver failure undergoing pLTx, a preoperative decrease in rSrO2 indicates compromised renal function. However, intraoperative rSrO2 is not predictive of postoperative kidney injury.

Shortening of the twitch stabilization period by tetanic stimulation in acceleromyography in infants, children and young adults (STSTS-Study): a prospective randomised, controlled trial.

Acceleromyography is characterised by an increase of the twitch response T1 (first twitch of the train-of-four [TOF]) during first 30 min of monitoring known as the staircase phenomenon. In adults the staircase phenomenon can be avoided by tetanic prestimulation. This study examined, if tetanic prestimulation eliminates the staircase phenomenon in children. After written informed consent, the neuromuscular function of 80 children, 10 in each age group (< 6 months, 6-12 months, 12-24 months, 2-3 years, 3-6 years, 6-12 years, 12-18 years, and ≥ 18 years) was measured on both arms simultaneously over 30 min under general anaesthesia. The ulnaris nerve was stimulated using the TOF technique every 15 s. The twitch response (T1, TOF ratio [TOFR]) was measured by acceleromyography. Before calibration, tetanic prestimmulation (50 Hz for 5 s) was administered to one randomly selected arm. The effect of tetanic prestimulation and age was analysed using general linear models based on the normalized T1 and TOFRs of both arms. Tetanic prestimulation significantly affected T1 values avoiding the staircase phenomenon (p < 0.0001). After 5.8 min [1.0-17.2 min] the normalized T1 values increased to 117% [102-147%] without prestimulation (p < 0.0001) independent of the age group (p = 0.539). The normalized TOFR was stable throughout the observation period of 30 min 100% [95-107%]. Infants (> 12 weeks), children, and young adults (< 18 years) develop similar characteristics of the staircase phenomenon than adults. Tetanic prestimulation prevents the staircase phenomenon in these age groups. The stability of the TOFR reading confirms its value to monitor neuromuscular function over time.Registration: The study was registered as NCT02552875 on Clinical Trials.gov on July 29, 2014.

Effects of Volatile Anesthetics on Proliferation and Viability of SW480 Colon Cancer Cells In Vitro.

BACKGROUND/AIM: For patients undergoing cancer surgery, the risk for cancer progression is enhanced during the perioperative period. To what extent the type of anesthetic can affect the metastatic process and finally the outcome of patients with cancer is under debate. For this reason, the aim of this study was to investigate the effects of the volatile anesthetics sevoflurane and desflurane on colon cancer cells in vitro. MATERIALS AND METHODS: SW480 colon carcinoma cells were exposed for 3 or 6 h to sevoflurane (1 or 2.5 vol%) or desflurane (6 or 12 vol%). Cell cycle distribution was analyzed by flow cytometry after a 24-72 h recovery and apoptosis was detected by annexin V staining after a 0-48 h recovery. Viability was tested by measuring ATP content after 0 and 24 h recovery. RESULTS: Treatment with sevoflurane or desflurane caused no or only slight changes in cell-cycle distribution and apoptosis rate. Desflurane at 12vol% significantly reduced cell viability by 17±25% and 11±22% after 3 and 6 h incubation and 24 h recovery, respectively, while 2.5 vol% sevoflurane slightly increased viability. CONCLUSION: At clinically relevant concentrations, sevoflurane and desflurane had only slight effects on SW480 colon cancer cells in vitro.

Anaesthesia-related complications and side-effects in TAVI: a retrospective study in Germany.

OBJECTIVES: This study was performed to analyse anaesthesia-related complications and side effects in patients undergoing transcatheter aortic valve implantation (TAVI) under general anaesthesia. DESIGN: Retrospective study. SETTING: The study was performed as a single-centre study in a hospital of tertiary care in Germany. PARTICIPANTS: All 853 patients, who underwent TAVI at the Universitätsklinikum Regensburg between January 2009 and July 2015, were included. 52.5% were female patients. PRIMARY AND SECONDARY OUTCOME MEASURES: We gathered information, such as recent illness, vital parameters and medication administered during the intervention and postoperatively for 12 hours. We analysed all anaesthesia-related complications and anaesthesia-related side effects that occurred during the intervention and entire hospital stay. RESULTS: We analysed all 853 TAVI procedures. The mean patient age was 79 ± 6 years. In 99.5% of cases, we used volatile-based anaesthesia. 2.8% (n=24; transfemoral (TF): n=19 [3.8%]; transapical (TA): n=5 [1.4%]) of all cases suffered from anaesthesia-related complications. 819 (TF: n=447; TA: n=372) anaesthesia-related side effects occurred in 586 (68.7%, TF: n=325 [64.2%], TA: n=261 [75.2%]) patients. Neither the complications nor the side effects had any serious consequences. Intraoperative hypothermia in 44% of cases (TF: n=202 [39.9%]; TA: n=173 [49.9%]) and postoperative nausea and vomiting in 27% (n=232; TF: n=131 [25.9%], TA: n=101 [29.1%]) of cases were the most common anaesthesia-related side effects. CONCLUSION: In this study, serious anaesthesia-related complications were rarely seen, and non-critical anaesthesia-related side effects could have been avoided through consistent prophylaxis and management. Therefore, despite their high anaesthetic risk, general anaesthesia is justifiable in patients who underwent TAVI.

Ischemia-related vascular complications of percutaneously initiated venoarterial extracorporeal membrane oxygenation: Indication setting, risk factors, manifestation and outcome.

PURPOSE: Venoarterial (VA) ECMO is widely accepted as salvage therapy for cardio-respiratory or cardiac failure. Vascular complications from cannulation are common and potentially life-threatening. Here, we retrospectively analyzed vascular complications following VA ECMO therapy. MATERIAL AND METHODS: Patients treated with VA ECMO via femoral cannulation from 2010 to 2016 were enrolled. Patient factors, indication and procedure were retrieved from our hospital database and statistically analyzed. RESULTS: 223 patients were enrolled. Survival rate was 43, 0%. Ischemic vascular complications were seen in 43, 9%. Main manifestation (82, 7%) was stenosis or occlusion of the femoral (common and superficial) or the external iliacal artery. Embolus or dissection occurred in 4, 1%. 32, 7% patients with ischemia required surgical intervention with 24,5% suffering from compartment syndrome. An antegrade perfusion catheter was established in 50% of the patients. Patients receiving VA ECMO for extracorporeal cardiopulmonary resuscitation had the lowest ischemic rates with 28,6%. Multiple regression analysis identified only the underlying indication and the size of the cannula as significant risk factor for vascular complications. Survival rates to hospital discharge were 37,3% and 47,2% in patients with and without ischemic complications. CONCLUSIONS: Cannula size and indication setting are the most important factors for the development of ischemic complications following VA ECMO.

The positive allosteric modulation of GABAA receptors mRNA in immature hippocampal rat neurons by midazolam affects receptor expression and induces apoptosis.

Background: Numerous experimental studies show that anesthetics are potentially toxic to the immature brain. Even though benzodiazepines are widely used in pediatric anesthesia and intensive care medicine, only a few studies examine the effects of these drugs on immature neurons. Methods: Hippocampal neuronal cell cultures of embryonic Wistar rats (15 days in culture) were incubated with midazolam 100 or 300 nM for either 30 min or 4 h. The time course of the mRNA expression of the glutamate receptors subunits NR1, NR2A and NR2B of the NMDA receptor, the GluA-1 and A-2 subunits of the AMPA receptor as well as the alpha 1 subunit of the GABAA receptor were examined by PCR. Apoptosis was detected using Western blot analysis for BAX, Bcl-2 and Caspase-3. Results: Midazolam at 100 and 300 nM applied for 30 min and 100 nM for 4 h affected glutamate receptor and GABAA receptor subunit expression. However, these effects were reversible within 72 h following washout. When 300 nM midazolam was applied for 4 h a significant increase in the NR 1 and NR 2A mRNA subunit expression could be detected. The increase in NR 2B receptor subunit expression as well as the GluA1 subunit expression was not reversible within 72 h following washout. This increase in mRNA glutamate receptor subunit expression was associated with a significant increase in neuronal apoptosis. Conclusion: In immature neurons midazolam altered GABA and glutamate mRNA receptor subunit expression. Prolonged increase in midazolam-induced glutamate receptor expression was associated with apoptosis.

Acetaminophen and Metamizole Induce Apoptosis in HT 29 and SW 480 Colon Carcinoma Cell Lines In Vitro.

BACKGROUND/AIM: The perioperative phase is supposed to be a period with high vulnerability for cancer dissemination. Acetaminophen and metamizole are common analgesics administered during this phase. We investigated the effect of acetaminophen, metamizole and 4-methylaminoantipyrine (MAA) on proliferation and apoptosis of colon carcinoma cell lines (SW 480 and HT 29). MATERIALS AND METHODS: Proliferation was detected by cell proliferation ELISA BrdU, and apoptosis by Annexin V staining. Cytochrome c and caspase 3, 8 and 9 expression levels were detected by western blot. RESULTS: Acetaminophen, metamizole or MAA caused slight changes in proliferation. Acetaminophen, metamizole or the combination increased apoptosis in both cell lines. All agents decreased caspase 3 and 8 expression in SW480. Acetaminophen decreased caspase 9 expression in both cell lines. CONCLUSION: In clinically relevant doses, acetaminophen and/or metamizole induce apoptosis in both colon cancer cell lines. Both mitochondrial and death receptor pathways might be involved in acetaminophen-induced apoptosis.

Effect of Hydroxyethyl Starch Solution on Incidence of Acute Kidney Injury in Patients Suffering from Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The application of third-generation hydroxyethyl starch (HES) solutions in critically ill patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) was often part of the treatment of delayed cerebral ischemia (DCI). However, there is increasing evidence showing a correlation between the application of HES and the incidence of acute kidney injury (AKI). METHODS: In a single-center retrospective analysis including 81 patients without a preexisting renal disorder suffering from aSAH who had received higher volumes of 6 % HES 130/0.4 due to standard treatment of DCI, the incidence of AKI during intensive care unit (ICU) stay was recorded using AKIN criteria. Furthermore, the course of serum creatinine after discharge from ICU was observed. RESULTS: 6 % HES 130/0.4 was given over a period of 12.9 ± 7.1 days resulting in a cumulative dose of 12543.2 ± 7743.6 mL. Four patients (4.9 %) fulfilled AKIN criteria stage 1 during ICU stay. In two of these patients, serum creatinine was within normal range again on day of discharge. Five patients showed elevated levels of serum creatinine within 1 to 22 months after hospitalization. A correlation between the amount of HES given and the incidence of AKI could not be found. CONCLUSION: The application of 6 % HES 130/0.4 did not lead to an elevated incidence of AKI in patients without an elevated baseline serum creatinine. However, there is still a lack of high-level evidence as prospective randomized trials are missing yet.

[Organ replacement therapy - extracorporeal liver assist devices]. / Organersatzverfahren - Leberunterstützungsverfahren.

Liver failure is a disease with a high mortality rate. Often liver transplantation is the sole therapeutic option. On the one hand, liver support systems probably support the liver to allow regeneration, on the other hand they are an option to bridge for transplantation. This article gives an overview on the clinically used liver assist devices (molecular adsorbent recirculating system [MARS], Prometheus system, single-pass albumin dialysis [SPAD], plasmapheresis) and discusses the applications in liver failure.

[Anesthesia with liver failure]. / Anästhesie bei Leberinsuffizienz.

Liver failure can be categorized into acute liver failure, chronic liver failure and acute decompensation of chronic liver failure, the so-called acute-on-chronic liver failure, the incidence of which has increased over the last few years. Liver failure leads to a variety of pathophysiological changes where the extent is dependent on the nature and duration of the liver disease. This includes restriction of synthesis and metabolism, such as coagulation defects. Especially chronic liver failure is associated with malfunction of extrahepatic organs, such as the cardiovascular system, the respiratory system and the kidneys. In addition to these pathophysiological alterations the Child-Turcotte-Pugh classification (CTP) and the model of end stage liver disease (MELD) are used for perioperative risk stratification.