Increase of urinary TIMP-2 and IGFBP7 as potential predictor of acute kidney injury requiring renal replacement therapy and patients' outcome following complex endovascular and open thoracic abdominal aortic aneurysm surgery - a prospective observational study.

Background: Acute kidney injury (AKI) as complication after open and endovascular repair of thoracoabdominal aortic aneurysm (TAAA) is one major predictor of mortality and postoperative complications. We evaluated tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) as combined early biomarker for AKI detection and predictor of patients' outcome. Patients and methods: Between 2014 and 2015, 52 patients have been enrolled in this observational study, of whom 29 (55.8%) underwent elective open repair and 23 (44.2%) endovascular repair. TIMP2 × IGFBP7 were measured until 48 hours after admission on intensive-care unit (ICU) and were analyzed regarding their predictive ability for AKI (defined according to the KDIGO criteria) requiring temporary renal replacement therapy (RRT) and 90-day mortality using ROC curves. Results: Mean patient age was 64.5 years (Min: 43, Max: 85), endovascular treated patients were older (p <0.0001). 40.4% (n = 21) developed AKI, and 21.2% (n = 11) required renal replacement therapy. In-hospital and total mortality rates were 7.7% (n = 4) and 9.6% (n = 5), respectively. At no time a significant difference in TIMP2 × IGFB7 levels between patients undergoing open or endovascular surgery was observed. The predictive quality of the TIMP2 × IGFBP7 value on ICU admission was sound regarding AKI requiring temporary renal replacement therapy (sensitivity: 55.56% [38.1-72.1%], specificity: 90.91% [58.7-99.8%] with an area under the curve [AUC]: 0.694 [0.543-0.820]). Mean follow-up was 13.2 months (Min: 2, Max: 20), regarding the 90-day mortality, the predictive property of the TIMP2 × IGFBP7 value was not sufficient (sensitivity: 80% [28.4-99.5%], specificity: 52.38% [36.4-68%], and AUC: 0.607 [0.454-0.746]). Conclusions: TIMP2 × IGFBP7 level measured 6-12 hrs postoperatively may be useful as an early detectable biomarker for AKI requiring temporary renal replacement therapy. It seems not suited to predict patients' outcome following complex thoracoabdominal aortic surgery, regardless if performed by open or endovascular repair.

Inguinal hernia repair in preterm neonates: is there evidence that spinal or general anaesthesia is the better option regarding intraoperative and postoperative complications? A systematic review and meta-analysis.

OBJECTIVES: Whether spinal anaesthesia (SA) reduces intraoperative and postoperative complications compared with general anaesthesia (GA) was investigated. DESIGN: The meta-analysis was structured based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Databases (PubMed, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science) were searched, and four randomised controlled trials (RCTs) and two retrospective cohort studies were included. A random-effects model with pooled risk ratios and mean differences with 95% CIs were used. Statistical heterogeneity was evaluated using the I2 statistic. Quality assessment of the studies was performed by assessing the risk of bias according to the Cochrane and GRADE methodology. SETTING: Publications from January 1990 to November 2018 were included. PARTICIPANTS AND INTERVENTIONS: Our study selection captured information from studies focusing on neonates born before the 37th gestational week who were scheduled for an inguinal hernia repair operation under either SA or GA. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measures were apnoea, postoperative ventilation and method failure rates according to predefined eligibility criteria. The duration of surgery, desaturation events <80%, hospital stay duration and postoperative bradycardia were secondary outcomes. RESULTS: We found significantly fewer events for the outcomes 'any episode of apnoea' and 'mechanical ventilation postoperatively' in the SA group. Bradycardias were significantly less common in the SA group. In total, 7.5% of the SA group were converted to GA. The duration of surgery was significantly shorter in the SA group. No significant differences were found in the outcome measures 'postoperative oxygen supplementation', 'prolonged apnoea', 'postoperative oxygen desaturation <80%' and 'hospital stay'. CONCLUSIONS: We consider SA a convenient alternative for hernia repair in preterm infants, providing more safety regarding postoperative apnoea. To the best of our knowledge, this is the first meta-analysis to include studies exclusively comparing SA versus GA. More high-quality RCTs are needed. TRIAL REGISTRATION NUMBER: CRD42016048683.

Oxidation-Reduction Potential in Patients undergoing Transcatheter or Surgical Aortic Valve Replacement.

BACKGROUND: Aortic valve stenosis has gained increasingly more importance due to its high prevalence in elderly people. More than two decades ago, transcatheter aortic valve replacement emerged for patients who were denied surgery, and its noninferiority has been demonstrated in numerous studies. Oxidative stress has generated great interest because of its sensitivity to cell damage and the possibility of offering early hints of clinical outcomes. The aim of the present study was to investigate whether there is a significant difference between transcatheter (TAVR) or surgical aortic valve replacement (SAVR) in terms of the changes in oxidation-reduction potential (ORP) and antioxidant capacity. Therefore, we investigated perioperative oxidative stress levels and their influence on clinical outcomes. METHODS: A total of 72 patients (50% TAVR versus 50% SAVR) were included in the present study. Static oxidation-reduction potential (sORP) and antioxidant capacity were measured using the RedoxSys™ Diagnostic System (Luoxis Diagnostics, USA) in serum samples drawn before and after surgery, as well as on the first postoperative day. In addition, clinical data were obtained to evaluate the clinical outcome of each case. RESULTS: TAVR patients had higher preoperative sORP levels compared to the SAVR patients and more severe comorbidities. Unlike the TAVR cohort, patients in the SAVR group showed a significant difference in sORP from the pre- to postoperative levels. Capacity demonstrated higher preoperative levels in the SAVR cohort and also a greater difference postoperatively compared to the TAVR cohort. Regression analysis revealed a significant correlation between pre- and postoperative capacity levels (r = -0.9931, p < 0.0001), providing a method of predicting postoperative capacity levels by knowing the preoperative levels. According to the multivariable analysis, both sORP and antioxidant capacity are dependent on time point, baseline value, and type of surgery, with the largest variations observed for time effect and surgery method. CONCLUSION: A high preoperative sORP level correlated to more severe illness in the TAVR patients. As the TAVR patients did not show significant differences in their preoperative levels, we assume that there was a smaller production of oxidative agents during TAVR due to the less invasive nature of the procedure. Baseline values and development of antioxidant capacity values strengthen this hypothesis. The significant correlation of pre- and postoperative capacity levels might allow high risk patients to be detected more easily and might provide more adequate and individualized therapy preoperatively. This trial is registered with clinicaltrials.gov, identifier: NCT 02488876.

Macrophage Migration Inhibitory Factor Predicts Outcome in Complex Aortic Surgery.

The perioperative inflammatory response is associated with outcome after complex aortic repair. Macrophage migration inhibitory factor (MIF) shows protective effects in ischemia-reperfusion (IR), but also adverse pro-inflammatory effects in acute inflammation, potentially leading to adverse outcome, which should be investigated in this trial. This prospective study enrolled 52 patients, of whom 29 (55.7%) underwent open repair (OR) and 23 (44.3%) underwent endovascular repair (ER) between 2014 and 2015. MIF serum levels were measured until 72 h post-operatively. We used linear mixed models and ROC analysis to analyze the MIF time-course and its diagnostic ability. Compared to ER, OR induced higher MIF release perioperatively; at 12 h after ICU admission, MIF levels were similar between groups. MIF course was significantly influenced by baseline MIF level (P = 0.0016) and acute physiology and chronic health evaluation (APACHE) II score (P = 0.0005). MIF level at 24 h after ICU admission showed good diagnostic value regarding patient survival [sensitivity, 80.0% (28.4-99.5%); specificity, 51.2% (35.1-67.1%); AUC, 0.688 (0.534-0.816)] and discharge modality [sensitivity, 87.5% (47.3-99.7%); specificity, 73.7% (56.9-86.6%), AUC, 0.789 (0.644-0.896)]. Increased perioperative MIF-levels are related to an increased risk of adverse outcome in complex aortic surgery and may represent a biomarker for risk stratification in complex aortic surgery.

Tissue oxygen saturation as an early indicator of delayed lactate clearance after cardiac surgery: a prospective observational study.

BACKGROUND: In this observational study near infrared spectroscopy (NIRS) was evaluated as a non-invasive monitor of impaired tissue oxygenation (StO2) after cardiac surgery. StO2, cardiac output, mixed venous oxygen saturation and mean arterial pressure were compared with lactate clearance as established measure for sufficient tissue perfusion and oxygen metabolism. METHODS: Forty patients after cardiac surgery (24 aortocoronary bypass grafting, 5 heart valve, 3 ascending aorta and 8 combined procedures) were monitored until postoperative day 1 with NIRS of the thenar muscle (InSpectra™ StO2-monitor, Hutchinson Technology), a pulmonary-artery catheter and intermittent blood gas analyses for the assessment of lactate clearance. RESULTS: StO2 was reduced 4 h after surgery (75 ± 6 %), but recovered at day 1 (84 ± 5 %), while lactate concentration remained increased. Using uni- and multivariate regression analysis, minimum StO2 (r = 0.46, p <0.01) and cardiac index (r = 0.40, p <0.05) correlated with lactate clearance at day 1, while minimum mixed venous saturation and mean arterial pressure did not. In a receiver-operating characteristics (ROC) analysis, minimum StO2 (with a threshold of 75 %) predicted a lactate clearance <10 % at day 1 with an area under the ROC-curve of 0.83, a sensitivity of 78 % and a specificity of 88 %. In the subgroup with StO2 <75 %, troponin and creatine kinase MB were significantly increased at day 1. CONCLUSIONS: StO2 below 75 % in the first hours after surgery was a better early indicator of persistent impaired lactate clearance at day 1 than cardiac index, mixed venous oxygen saturation or mean arterial pressure.

Xenon triggers pro-inflammatory effects and suppresses the anti-inflammatory response compared to sevoflurane in patients undergoing cardiac surgery.

INTRODUCTION: Cardiac surgery encompasses various stimuli that trigger pro-inflammatory mediators, reactive oxygen species and mobilization of leucocytes. The aim of this study was to evaluate the effect of xenon on the inflammatory response during cardiac surgery. METHODS: This randomized trial enrolled 30 patients who underwent elective on-pump coronary-artery bypass grafting in balanced anaesthesia of either xenon or sevoflurane. For this secondary analysis, blood samples were drawn prior to the operation, intra-operatively and on the first post-operative day to measure the pro- and anti-inflammatory cytokines interleukin-6 (IL-6), interleukin-8/C-X-C motif ligand 8 (IL-8/CXCL8), and interleukin-10 (IL-10). Chemokines such as C-X-C motif ligand 12/ stromal cell-derived factor-1α (CXCL12/SDF-1α) and macrophage migration inhibitory factor (MIF) were measured to characterize xenon's perioperative inflammatory profile and its impact on migration of peripheral blood mononuclear cells (PBMC). RESULTS: Xenon enhanced the postoperative increase of IL-6 compared to sevoflurane (Xenon: 90.7 versus sevoflurane: 33.7 pg/ml; p = 0.035) and attenuated the increase of IL-10 (Xenon: 127.9 versus sevoflurane: 548.3 pg/ml; p = 0.028). Both groups demonstrated a comparable intraoperative increase of oxidative stress (intra-OP: p = 0.29; post-OP: p = 0.65). While both groups showed an intraoperative increase of the cardioprotective mediators MIF and CXCL12/SDF-1α, only MIF levels decreased in the xenon group on the first postoperative day (50.0 ng/ml compared to 23.3 ng/ml; p = 0.012), whereas it remained elevated after sevoflurane anaesthesia (58.3 ng/ml to 53.6 ng/ml). Effects of patients' serum on chemotactic migration of peripheral mononuclear blood cells taken from healthy volunteers indicated a tendency towards enhanced migration after sevoflurane anaesthesia (p = 0.07). CONCLUSIONS: Compared to sevoflurane, balanced xenon anaesthesia triggers pro-inflammatory effects and suppresses the anti-inflammatory response in cardiac surgery patients even though the clinical significance remains unknown. TRIAL REGISTRATION: This clinical trial was approved by the European Medicines Agency (EudraCT-number: 2010-023942-63) and at ClinicalTrials.gov ( NCT01285271 ; first received: January 24, 2011).

The importance of intraoperative selenium blood levels on organ dysfunction in patients undergoing off-pump cardiac surgery: a randomised controlled trial.

INTRODUCTION: Cardiac surgery is accompanied by an increase of oxidative stress, a significantly reduced antioxidant (AOX) capacity, postoperative inflammation, all of which may promote the development of organ dysfunction and an increase in mortality. Selenium is an essential co-factor of various antioxidant enzymes. We hypothesized a less pronounced decrease of circulating selenium levels in patients undergoing off-pump coronary artery bypass (OPCAB) surgery due to less intraoperative oxidative stress. METHODS: In this prospective randomised, interventional trial, 40 patients scheduled for elective coronary artery bypass grafting were randomly assigned to undergo either on-pump or OPCAB-surgery, if both techniques were feasible for the single patient. Clinical data, myocardial damage assessed by myocard specific creatine kinase isoenzyme (CK-MB), circulating whole blood levels of selenium, oxidative stress assessed by asymmetric dimethylarginine (ADMA) levels, antioxidant capacity determined by glutathionperoxidase (GPx) levels and perioperative inflammation represented by interleukin-6 (IL-6) levels were measured at predefined perioperative time points. RESULTS: At end of surgery, both groups showed a comparable decrease of circulating selenium concentrations. Likewise, levels of oxidative stress and IL-6 were comparable in both groups. Selenium levels correlated with antioxidant capacity (GPx: r = 0.720; p<0.001) and showed a negative correlation to myocardial damage (CK-MB: r =  -0.571, p<0.001). Low postoperative selenium levels had a high predictive value for the occurrence of any postoperative complication. CONCLUSIONS: OPCAB surgery is not associated with less oxidative stress and a better preservation of the circulating selenium pool than on-pump surgery. Low postoperative selenium levels are predictive for the development of complications. TRIAL REGISTRATION: ClinicalTrials.gov NCT01409057.

Safety and pitfalls in frozen elephant trunk implantation.

The frozen elephant trunk (FET) procedure, or open stent grafting, is a tool for the combined open and endovascular treatment via a median sternotomy of extensive aortic disease involving both aortic arch and descending thoracic aorta. The technique aims to stabilize the maximum extent of the thoracic aorta in one step, with the goal of either rendering a secondary intervention to the downstream aorta unnecessary or producing an easy landing zone for secondary thoracic endovascular aortic repair (TEVAR) or open surgery. Even though large case series have reported good results, we still have no conclusive evidence as to which patients and what kind of pathologies benefit from this technique. The surgical sequences described for total arch replacement with the FET procedure are just as varied as the associated devices and indications. This article focuses on important perioperative and surgical aspects, as well as potential complications during FET procedures.

Xenon consumption during general surgery: a retrospective observational study.

BACKGROUND: High costs still limits the widespread use of xenon in the clinical practice. Therefore, we evaluated xenon consumption of different delivery modes during general surgery. METHODS: A total of 48 patients that underwent general surgery with balanced xenon anaesthesia were retrospectively analysed according to the mode of xenon delivery during maintenance phase (ECO mode, AUTO mode or MANUAL mode). RESULTS: Xenon consumption was highest during the wash-in phase (9.4 ± 2.1l) and further decreased throughout maintenance of anaesthesia. Comparison of different xenon delivery modes revealed significant reduced xenon consumption during ECO mode (18.5 ± 3.7L (ECO) vs. 24.7 ± 11.5L (AUTO) vs. 29.6 ± 14.3L (MANUAL); p = 0.033). No differences could be detected with regard to anaesthetic depth, oxygenation or performance of anaesthesia. CONCLUSION: The closed-circuit respirator Felix Dual offers effective reduction of xenon consumption during general surgery when ECO mode is used.

Thoracic stent graft sizing for frozen elephant trunk repair in acute type A dissection.

OBJECTIVE: Although stenting of the descending aorta simultaneously with proximal aortic repair has become an accepted part of the therapy for acute type A dissection, no general recommendations have been accepted regarding the choice of diameter and length of the stent grafts. The present study explored the safety and effectiveness of sizing the stent graft of the hybrid prosthesis in relation to the total aortic diameter and extending the landing zone to the level of the T10-T12 vertebrae. METHODS: The frozen elephant trunk procedure was performed on 32 patients with acute type A aortic dissection. The stent graft size was chosen according to the total aortic diameter measured on contrast-enhanced computed tomography scans. The stent graft was inserted with the distal landing zone at the level of vertebrae T10-T12. All patients underwent computed tomography or magnetic resonance angiography before discharge; 8 patients underwent subsequent endovascular stent extension. RESULTS: The 30-day survival was 100%, with 3.1% (1/32) overall mortality at 17 ± 4 months (range, 1-33) of follow-up. The postoperative complications included pneumonia in 5, pulmonary embolism in 3, sepsis in 1, and permanent recurrent laryngeal nerve damage in 1 patient. No ischemic brain or spinal cord injury occurred. During follow-up, no endoleaks or false lumen patency developed. CONCLUSIONS: Sizing the stent graft of the hybrid prosthesis according to the total aortic diameter and choosing a distal landing zone between vertebrae T10 and T12 is safe, with low midterm mortality and morbidity. It allows an extensive repair of the dissected aorta with early definite occlusion of the false lumen and prepares for potential endovascular extension of the graft.

Selenium blood concentrations in patients undergoing elective cardiac surgery and receiving perioperative sodium selenite.

OBJECTIVES: We recently reported that cardiac surgical patients in our institution exhibited low selenium blood levels preoperatively, which were further aggravated during surgery and independently associated with the development of postoperative multiorgan failure. Low circulating selenium levels result in a decreased antioxidant capacity. Both can be treated effectively by sodium-selenite administration. Little is known about the kinetics of exogenously administered sodium-selenite during acute perioperative oxidative stress. The aim of this study was to assess the effects of perioperative high-dose sodium-selenite administration on selenium blood concentrations in cardiac surgical patients. METHODS: One hundred four cardiac surgical patients were enrolled in this prospective observational trial. Patients received an intravenous bolus of 2000 µg selenium after an induction of anesthesia and 1000 µg selenium every day further during their intensive care unit (ICU) stay. Selenium blood levels were measured at regular intervals. RESULTS: Preoperative sodium-selenite administration increased selenium blood concentrations to normal values on ICU admission, but failed to prevent a significant decrease of circulating selenium on the first postoperative day. During the further ICU stay, selenium blood levels were normalized by the administration strategy and did not exceed the German reference range. No acute selenium-specific side effects occurred. When matching the participating patients to a historical control group without sodium-selenite administration, the chosen strategy was associated with a decrease in SAPS II (23 ± 7 versus 29 ± 8, P = 0.005) and SOFA scores (4 ± 3 versus 7 ± 2, P = 0.007) on the first postoperative day, but was unable to improve the postoperative outcome in patients staying >1 d in ICU. CONCLUSIONS: Despite preemptive high-dose sodium-selenite administration, cardiac surgical patients experienced a significant decrease in circulating selenium levels on the first postoperative day.

Early cognitive function, recovery and well-being after sevoflurane and xenon anaesthesia in the elderly: a double-blinded randomized controlled trial.

BACKGROUND: The postoperative cognitive function is impaired in elderly patients after general anaesthesia. The fast recovery after xenon anaesthesia was hypothesized to be advantageous in this scenario. We compared early postoperative cognitive function after xenon and sevoflurane anaesthesia in this study. METHODS: The study was approved by the local ethics committee and written informed consent was obtained from each patient. Patients aged 65-75 years (ASA I-III) scheduled for elective surgery (duration 60-180 min) were enrolled. Investigators performing cognitive testing and patients were blinded towards allocation to either xenon or sevoflurane anaesthesia. Baseline assessment of cognitive function was carried out 12-24 h before the operation. The results were compared to follow-up tests 6-12 and 66-72 h after surgery. Primary outcome parameter was the subtest "Alertness" of the computerized Test of Attentional Performance (TAP). Secondary outcome parameters included further subtests of the TAP, several Paper-Pencil-Tests, emergence times from anaesthesia, modified Aldrete scores and patients' well-being. RESULTS: 40 patients were randomized and equally allocated to both groups. No significant differences were found in the TAP or the Paper-Pencil-Tests at 6-12 and 66-72 h after the operation. All emergence times were faster after xenon anaesthesia. The modified Aldrete scores were significantly higher during the first hour in the xenon group. No difference in well-being could be detected between both groups. CONCLUSIONS: The results show no difference in the incidence of postoperative cognitive dysfunction (POCD) after xenon or sevoflurane anaesthesia. Emergence from general anaesthesia was faster in the xenon group.

The use of the Airtraq® optical laryngoscope for routine tracheal intubation in high-risk cardio-surgical patients.

BACKGROUND: The Airtraq® optical laryngoscope (Prodol Ltd., Vizcaya, Spain) is a novel disposable device facilitating tracheal intubation in routine and difficult airway patients. No data investigating routine tracheal intubation using the Airtaq® in patients at a high cardiac risk are available at present. Purpose of this study was to investigate the feasibility and hemodynamic implications of tracheal intubation with the Aitraq® optical laryngoscope, in high-risk cardio-surgical patients. METHODS: 123 consecutive ASA III patients undergoing elective coronary artery bypass grafting were routinely intubated with the Airtraq® laryngoscope. Induction of anesthesia was standardized according to our institutional protocol. All tracheal intubations were performed by six anesthetists trained in the use of the Airtraq® prior. RESULTS: Overall success rate was 100% (n = 123). All but five patients trachea could be intubated in the first attempt (95,9%). 5 patients were intubated in a 2nd (n = 4) or 3rd (n = 1) attempt. Mean intubation time was 24.3 s (range 16-128 s). Heart rate, arterial blood pressure and SpO2 were not significantly altered. Minor complications were observed in 6 patients (4,8%), i.e. two lesions of the lips and four minor superficial mucosal bleedings. Intubation duration (p = 0.62) and number of attempts (p = 0.26) were independent from BMI and Mallampati score. CONCLUSION: Tracheal intubation with the Airtraq® optical laryngoscope was feasible, save and easy to perform in high-risk patients undergoing cardiac surgery. In all patients, a sufficient view on the vocal cords could be obtained, independent from BMI and preoperative Mallampati score. TRIAL REGISTRATION: DRKS 00003230.

The intraoperative decrease of selenium is associated with the postoperative development of multiorgan dysfunction in cardiac surgical patients.

OBJECTIVE: The trace elements selenium, copper, and zinc are essential for maintaining the oxidative balance. A depletion of antioxidative trace elements has been observed in critically ill patients and is associated with the development of multiorgan dysfunction and an increased mortality. Cardiac surgery using cardiopulmonary bypass provokes ischemia-reperfusion-mediated oxidative stress. We hypothesized that an intraoperative decrease of circulating trace elements may be involved in this response. DESIGN: Prospective observational clinical study. SETTING: University hospital cardiothoracic operation theater and intensive care unit. PATIENTS: Sixty patients (age 65 ± 14 yrs) undergoing cardiac surgery with the use of cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Whole blood concentrations of selenium, copper, and zinc were measured after induction of anesthesia and 1 hr after admission to the intensive care unit. All patients were separated in a priori defined subgroups according to the development of no organ failure, single organ failure, and ≥ 2 organ failures in the postoperative period. RESULTS: Fifty patients exhibited a significant selenium deficiency already before surgery, whereas copper and zinc concentrations were within the reference range. In all patients, blood levels of selenium, copper, and zinc were significantly reduced after end of surgery when compared to preoperative values (selenium: 89.05 ± 12.65 to 70.84 ± 10.46 µg/L; zinc: 5.15 ± 0.68 to 4.19 ± 0.73 mg/L; copper: 0.86 ± 0.15 to 0.65 ± 0.14 mg/L; p < .001). During their intensive care unit stay, 17 patients were free from any organ failure, while 31 patients developed single-organ failure and 12 patients multiple organ failure. Multilogistic regression analysis showed that selenium concentrations at end of surgery were independently associated with the postoperative occurrence of multiorgan failure (p = .0026, odds ratio 0.8479, 95% confidence interval 0.7617 to 0.9440). CONCLUSIONS: Cardiac surgery using cardiopulmonary bypass resulted in a profound intraoperative decrease of whole blood levels of antioxidant trace elements. Low selenium concentrations at end of surgery were an independent predictor for the postoperative development of multiorgan failure.

Case study of hepatic radiofrequency ablation causing a systemic inflammatory response under total intravenous anesthesia.

OBJECTIVE: To investigate the effects of hepatic radiofrequency ablation (RFA) in patients with malignant liver disease with respect to inflammation activation and stress response. MATERIALS AND METHODS: In an observational trial, we investigated the physiologic parameters of 17 patients (20 interventions) who underwent percutaneous RFA under general anesthesia after applying total intravenous anesthesia. TNFα, IL-6, IL-8, IL-10, adrenaline and noradrenaline, liver enzymes, lactate and creatine kinase were determined pre-interventionally after induction of anesthesia (T1), 90 minutes after initiation of RFA (T2), immediately after the conclusion of the procedure (T3), and 24 hours after the procedure (T4). RESULTS: A significant increase in body temperature (p < 0.001), and mean arterial pressure (p = 0.001) were measured intraoperatively (T2) and the day after the procedure (T4). Increased levels of IL-6 were measured at T3 and T4 (p = 0.001). IL-10 increased immediately after the procedure (T3; p = 0.007). IL-6 levels correlated well with the total energy applied (r = 0.837). Significant increases in the levels of adrenaline and noradrenaline were present at T3 and T4 (p < 0.001). The RFA-induced destruction of hepatic tissue was associated with increased levels of AST, ALT, GLDH and LDH. CONCLUSION: Percutaneous RFA of hepatic malignancies causes an inflammatory and endocrine activation, similar to the systemic inflammatory response syndrome. These effects have to be taken in account when dealing with patients susceptible to sepsis or multi-organ failure.

Influence of temperature on the positive inotropic effect of levosimendan, dobutamine and milrinone.

BACKGROUND AND OBJECTIVE: Patients in cardiac surgery and critically ill patients often demonstrate either hypothermia or fever. In addition, owing to heart failure, they frequently require inotropic support. The relative effectiveness of modern inotropic agents at various temperatures has not yet been evaluated. Therefore, we investigated the influence of levosimendan, dobutamine and milrinone on the contractile response of myocardial trabeculae at various temperatures. METHODS: A total of 120 guinea pig ventricular trabeculae were placed in oxygenated 4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid (HEPES) buffer, stimulated at a frequency of 1.3 Hz and randomly assigned to a temperature of 31 degrees C, 34 degrees C, 37 degrees C or 40 degrees C. Concentrations of all substances were increased stepwise from 10(-9) to 10(-5) mol l(-1) (milrinone up to 10(-4) mol l(-1)). Maximum developed force, time to peak tension, Tsystolic(50%) and Tdiastolic(50%) were continuously recorded. RESULTS: All agents showed a dose-dependent positive inotropic effect (P < 0.0001 for all). Levosimendan acted at every temperature as a positive inotrope (P = 0.0643). Dobutamine-related inotropy showed a clear trend towards temperature dependence, although statistical evaluation did not prove this (P = 0.0624). Milrinone-related inotropy was abolished at 31 degrees C and 34 degrees C, and temperature dependence was significant (P < 0.0001). Hypothermia induced a positive inotropic effect. CONCLUSION: Our results suggest no modulation of levosimendan-induced inotropy under the experimental temperatures tested. This observation is possibly due to its Ca2+-sensitizing mechanism, which might not be influenced by temperature-related changes in intracellular Ca2+ levels. In contrast, the inotropic effect of cyclic AMP-coupled dobutamine and milrinone is suppressed under hypothermia-related interaction with intracellular Ca2+ homeostasis. Hence, levosimendan might prove to be the preferred inotropic drug in hypothermic patients.

Selective left ventricular adriamycin-induced cardiomyopathy in the pig.

OBJECTIVE: The aim of this study was the development of an experimental cardiomyopathy induced with Adriamycin (Pharmacia & Upjohn, Erlangen, Germany) with selective toxic damage of the left ventricular myocardium that avoided an ischemic component. METHODS: An intracoronary catheter was implanted directly into the left main stem in pigs and connected to a percutaneous access port that was used for repetitive Adriamycin administration (3-5 x 25 mg weekly over a 1-hour period). Hemodynamic and echocardiographic variables were measured before Adriamycin administration, 1 week after, and at 4 weeks. Thereafter, all hearts were autopsied for detailed histologic examination. Statistical analysis was done by an analysis of variance for multiple parameters. RESULTS: All pigs had normal baseline cardiac function. Measurements after Adriamycin administration and 4 weeks later demonstrated a continued increase of the central venous pressure, pulmonary artery pressure, pulmonary wedge pressure, and pulmonary vascular resistance, whereas cardiac output, stroke volume index, and left ventricular stroke work index decreased. These results were supported by the echocardiographic data depicting an increase of left ventricular diameters and volumes, accompanied by a decrease of intraventricular and left ventricular posterior wall thickness as well as left ventricular ejection fraction. Right ventricular volumes and function did not change during the trial. The histologic examination of the hearts revealed a selective toxic damage of the left ventricular myocardium with multifocal necroses and advanced tissue reorganization. CONCLUSION: This animal model creates a selective left ventricular damage that avoids ischemic damage of the myocardium. Both aspects can improve research on Adriamycin-induced cardiomyopathy, especially preventive or therapeutic strategies.