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Abstract Reduction of the perioperative cardiovascular risk with pharmacological interventions plays a prominent role in routine anesthesia practice. For example, perioperative beta-blockade is well established in anesthesiological treatment of patients. There is a growing body of evidence supporting the cardioprotective effects of volatile anesthetics known as anesthetic-induced preconditioning. There are numerous and complex data from animal studies. The mechanisms of anesthetic-induced preconditioning have been extensively studied but have still not been clearly identified. Initial clinical data show the cardioprotective effects of volatile agents by looking at parameters of myocardial function and laboratory values and therefore, the question of the relevance of these data for routine clinical practice has been raised. This review gives a summary of the currently available data focusing on the mechanisms of anesthesiological preconditioning and clinical studies. [ABSTRACT FROM AUTHOR]

Background: A vaccine (HB-101) consisting of 2 nonreplicating lymphocytic choriomeningitis virus (LCMV) vectors expressing the human cytomegalovirus antigens glycoprotein B (gB) and the 65-kD phosphoprotein (pp65), respectively, is in development to prevent cytomegalovirus infection., Methods: HB-101 was tested in cytomegalovirus-naive, healthy adults in a randomized, double-blind, placebo-controlled, dose-escalation Phase I trial. Fifty-four subjects received low, medium, or high dose of HB-101 or placebo by intramuscular administration at Month 0, 1, and 3. Safety and immunogenicity were the respective primary and secondary endpoints. Subjects were followed for 12 months after the initial immunization., Results: Vaccination was associated with transient mild to moderate adverse events. HB-101 administration induced dose-dependent gB- and pp65-specific cellular responses, dominated by pp65-specific CD8 T cells, a high fraction of which were polyfunctional. Two administrations were sufficient to elicit dose-dependent gB-binding and cytomegalovirus-neutralizing antibodies (Abs). Cytomegalovirus-specific immune responses were boosted after each administration. Only 1 of 42 vaccine recipients mounted a transient LCMV vector-neutralizing Ab response., Conclusions: HB-101 was well tolerated and induced cytomegalovirus-specific polyfunctional CD8 T-cell and neutralizing Ab responses in the majority of subjects. Lack of vector-neutralizing Ab responses should facilitate booster vaccinations. These results justify further clinical evaluation of this vaccine candidate., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Study Objective: To investigate the influence of duration of deep hypothermic circulatory arrest (DHCA) on recovery of the bispectral index (BIS)., Design: Prospective cohort study., Setting: Operating room of university teaching hospital., Patients: 30 adult, ASA physical status III and IV patients scheduled for cardiac surgery with extracorporeal circulation (ECC) and DHCA., Interventions: There were no study-specific interventions undertaken with the study patients., Measurements: After induction of anesthesia, propofol and sufentanil were used for maintenance. Duration until BIS values reached indices of 10, 20, and 30 after DHCA was measured. DeltaBIS was defined as the difference between BIS before the start of ECC and after DHCA at the same nasopharyngeal body temperature. Data are means + or - SD (ranges)., Main Results: Duration of DHCA was 24 + or - 15 min (8-71 min). The deepest nasopharyngeal temperature was 20.1 + or - 2.7 degrees C at the end of DHCA. BIS reduction was 1.8/ degrees C. At the end of DHCA, BIS was 2 + or - 6 and at the end of ECC, BIS was 33 + or - 11. Duration until BIS reached a value of 10 (BIS10) was 23 + or - 21 min (0-83 min); until BIS reached 20 (BIS20): 36 + or - 36 min (0-140 min); and until BIS reached 30 (BIS30): 43 + or - 29 min (1-130 min). Regression analysis between duration of DHCA and BIS10 was R = 0.76; BIS20: R = 0.67; and BIS30: R = 0.54., Conclusion: Deep hypothermia influences BIS linearly. In addition, there appears to be a reasonable correlation between recovery of BIS values and duration of DHCA., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background and Objective: Epidural blockade in major abdominal surgery bears the potential to increase gastrointestinal perfusion and thus to improve patient outcome. The aim of this study was to assess the differential influence of thoracic and lumbar epidural anaesthesia and analgesia (EAA) on blood lactate levels and central venous oxygen saturation (ScvO2) as parameters of global oxygen supply/demand ratio, as well as on the plasma disappearance rate of indocyanine green (PDR(ICG)), a noninvasive method to evaluate liver perfusion., Methods: We enrolled 17 patients receiving thoracic and 17 patients receiving lumbar EAA in addition to general anaesthesia for major abdominal surgery. Lactate, ScvO2 and PDR(ICG) were measured postoperatively on the ICU. Subsequently, epidural application of local anaesthetics was started with a bolus of bupivacaine 0.25% (thoracic 10 ml, lumbar 12 ml) followed by continuous infusion of bupivacaine (thoracic 8 ml h(-1) 0.175%, lumbar 10 ml h(-1) 0.125%) and fentanyl (2 microg ml(-1)). Central venous pressure was maintained by titrated volume replacement. Lactate, ScvO2 and PDR(ICG) were measured again after 2 h., Results: In both the groups, the mean arterial pressure and heart rate as well as lactate levels and ScvO2 did not change significantly. Although there was a slight but not significant decrease of PDR(ICG) in patients with lumbar EAA (from 25.9 +/- 7.68 to 23.2 +/- 5.90; NS), thoracic EAA resulted in a significant increase of PDR(ICG) (from 21.3 +/- 5.13 to 24.0 +/- 6.66; P < 0.05) for the group mean, but with substantial variability in individual patients in the lumbar EAA group., Conclusion: Liver perfusion was increased with thoracic but not lumbar EAA after major abdominal surgery in most patients. PDR(ICG) allows assessment of individual changes of liver blood flow due to therapeutic intervention, for example, EAA.

Background: Sepsis may lead to the suppression of stimulated cytokine release after Gram-negative stimuli, correlating with a fatal outcome. Treatment of sepsis includes adequate therapy with antibiotics. The aim of this study was to investigate the role of antibiotics in the modulation of the lipopolysaccharide (LPS)-stimulated cytokine response of human monocytes., Methods: In this ex vivo, in vitro study, whole blood samples were taken from 10 healthy volunteers, stimulated with LPS in the presence or absence of various antibiotics (penicillin, amoxicillin, cefuroxime, ceftazidime, cefotaxime, piperacillin/tazobactam, imipenem/cilastatin, gentamicin, netilmicin, ciprofloxacin, vancomycin) and cultured for 24 h. Thereafter, tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) were measured in the supernatants by enzyme-linked immunosorbent assay (ELISA). Furthermore, CD14 and HLA-DR expression on monocytes was assessed using flow cytometry., Results: All cephalosporins decreased LPS-stimulated IL-10 release. Cefuroxime and cefotaxime also decreased the expression density of the LPS recognition molecule CD14 on monocytes. An increase in LPS-stimulated IL-10 release was observed with vancomycin. A suppression of LPS-stimulated TNF-alpha and IL-10 release was observed in the presence of ciprofloxacin., Conclusion: These results indicate a modulation of the expression density of CD14 on monocytes, together with a shift from a balanced to an inflammatory cytokine release pattern, by cefuroxime and cefotaxime. Vancomycin changes the response to an anti-inflammatory release pattern. After ciprofloxacin, a profound unresponsiveness of immune-competent cells to LPS stimulation is observed. Because of the critical role of a balanced innate immune response, these data may be of importance for the selection of antibiotics in septic patients.

Background: Vocal cord injuries, postoperative hoarseness, and sore throat are common complications after general anesthesia. One-lung ventilation can be achieved via two techniques: double-lumen endotracheal tube or endobronchial blocker such as the Arndt blocker. The current study was designed to assess the impact of these techniques for one-lung ventilation on the incidence and severity of postoperative hoarseness, vocal cord lesions, and sore throat., Methods: In this prospective trial, 60 patients were randomly assigned to two groups. One-lung ventilation was achieved with either an endobronchial blocker (blocker group) or a double-lumen-tube (double-lumen group). Postoperative hoarseness and sore throat were assessed at 24, 48, and 72 h after surgery. Bronchial injuries and vocal cord lesions were examined by bronchoscopy immediately after surgery., Results: In 56 included patients, postoperative hoarseness occurred significantly more frequently in the double-lumen group compared with the blocker group: 44% versus 17%, respectively (P = 0.046). Similar findings were observed for vocal cord lesions: 44% versus 17%, respectively (P = 0.046). The incidence of bronchial injuries was comparable between groups (P = 0.540). Cumulative number of days with hoarseness and sore throat were significantly increased in the double-lumen group compared with the blocker group (P < 0.01). No major complications such as bronchial ruptures were observed., Conclusions: Clinicians should be aware of an increased incidence of minor airway injuries that may impair patient satisfaction when using a double-lumen tube instead of an endobronchial blocker for one-lung ventilation.

Background: In the present investigation we compared the consumption of desflurane (DES) and isoflurane (ISO) using a standardized minimal-flow protocol with a forced reduction of the fresh gas flow (FGF)., Methods: 54 adult women were examined. After induction of anaesthesia a forced reduction of the FGF was started: 5 min 0.5 l/min O(2) + 1 l/min N(2)O, 10 min 0.5 l/min O(2) + 0.5 l/min N(2)O; finally 0.3 l/min O(2) + 0.2 l/min N(2)O up to the end of surgery. The consumption of DES/ISO was determined with a precision balance., Results: In the DES group the uptake was around 0.3 vol-%, i.e. less than 8% of the target 2/3 MAC value was taken up. For ISO the uptake was around 0.25 vol-%, i.e. the uptake was approximately 30% of the target 2/3-MAC value. The DES consumption was after 60 min 17.0+/-1.1 g, 120 min--27.3+/-1.8 g and 180 min--36.5+/-1.7 g. ISO consumption was significantly lower: 7.6+/-0.8 g, 12.4+/-1.7 g and 15.5+/-1.6 g. The use of DES yielded higher costs, i.e. 2.28 EUR for 60 min, 3.63 EUR for 120 min and 4.97 EUR for 180 min. The consumption of the inhaled anaesthetics can be calculated as: DES (g)=4.84+0.184 x duration (min) (R(2)=0.981), ISO (g)=2.049+0.0826 x duration (R(2)=0.979). The costs are: DES (EUR)=0.85+0.0323 x duration (min); ISO (EUR)=0.19+0.0077 x duration (min)., Conclusion: With a forced reduction of the FGF the DES consumption is still higher.

Autoregressive modeling with exogenous input of middle-latency auditory evoked potentials (A-Line AEP index, AAI) has been developed for monitoring depth of anesthesia. We investigated the prediction of recovery and dose-response relationship of desflurane and AAI or bispectral index (BIS) values. Twenty adult men scheduled for radical prostatectomy were recruited. To minimize opioid effects, analgesia was provided by a concurrent epidural in addition to the general anesthetic. Electrodes for AAI and BIS monitoring and a headphone for auditory stimuli were applied. Propofol and remifentanil were used for anesthetic induction. Maintenance of anesthesia was with desflurane only. For comparison to AAI and BIS monitor parameters, pharmacokinetic models for desflurane and propofol distribution and effect-site concentrations were used to predict clinical end-points (Prediction probability P(K)). Patients opened their eyes at an AAI value of 47 +/- 20 and a BIS value of 77 +/- 14 (mean +/- sd), and the prediction probability for eye opening was P(K) = 0.81 for AAI, P(K) = 0.89 for BIS, and P(K) = 0.91 for desflurane effect-site concentration. The opening of eyes was best predicted by the calculated desflurane effect-site concentration. The relationship between predicted desflurane effect-site concentration versus AAI and BIS was calculated by nonlinear regression analysis (r = 0.75 for AAI and r = 0.80 for BIS). The correlation between BIS and clinical end-points of anesthesia or the desflurane effect-compartment concentration is better than for the AAI.

Reduction of the perioperative cardiovascular risk with pharmacological interventions plays a prominent role in routine anesthesia practice. For example, perioperative beta-blockade is well established in anesthesiological treatment of patients. There is a growing body of evidence supporting the cardioprotective effects of volatile anesthetics known as anesthetic-induced preconditioning. There are numerous and complex data from animal studies. The mechanisms of anesthetic-induced preconditioning have been extensively studied but have still not been clearly identified. Initial clinical data show the cardioprotective effects of volatile agents by looking at parameters of myocardial function and laboratory values and therefore, the question of the relevance of these data for routine clinical practice has been raised. This review gives a summary of the currently available data focusing on the mechanisms of anesthesiological preconditioning and clinical studies.

Introduction: We investigated gender differences of drug consumption and recovery times for propofol-remifentanil anaesthesia., Methods: Adult patients scheduled for minor orthopaedic surgery were randomised to receive a propofol-remifentanil anaesthesia controlled either by EEG monitoring (Narcotrend or BIS) or solely by clinical parameters. Anaesthesia was induced with remifentanil 0.4 microg/kg/min and a propofol target-controlled infusion (TCI) at 3.5 microg/ml. After intubation remifentanil was reduced to 0.2 microg/kg/min whereas propofol TCI was adjusted according to clinical parameters or to the following EEG target values: during maintenance to "D(0)" (Narcotrend) or "50" (BIS), 15 min before the end of surgery to "C(1)" (Narcotrend) or "60" (BIS). Recovery times were recorded and average normalised propofol consumption was calculated from induction and maintenance doses., Results: A total of 60 male and 60 female patients completed the study. Gender differences were observed for recovery times (with standard practice) and for propofol consumption (with BIS monitoring). In the standard protocol group, propofol consumption was nearly identical for male and female patients whereas recovery times were significantly longer in the male group. In both EEG-guided groups propofol consumption was less for male patients while recovery times were slightly longer. In the group of female patients higher propofol TCI concentrations had to be used to reach the same BIS or Narcotrend values., Conclusion: With propofol-remifentanil anaesthesia, gender has impact on recovery times and propofol consumption. If the same amounts of propofol are applied, males awake later, with BIS or Narcotrend monitoring males receive less propofol for comparable EEG effects.

Unlabelled: A common side effect associated with succinylcholine is postoperative myalgia. The pathogenesis of this myalgia is still unclear; inflammation has been suggested but without convincing evidence. We designed the present study to investigate whether an inflammatory reaction contributes to this myalgia. The incidence and severity of succinylcholine-associated myalgia was determined in 64 patients pretreated with saline or dexamethasone before succinylcholine (n = 32 for each). Incidence and severity of myalgia did not differ significantly between the two groups: 15 patients in the dexamethasone group complained of myalgia compared with 18 patients in the saline group, and severe myalgia was reported by five patients and three patients, respectively (not significant). At 48 h after surgery, 12 patients in both groups still suffered from myalgia (not significant). In addition, interleukin-6 (IL-6) as an early marker of inflammation was assessed in a subgroup of 10 patients pretreated with saline. We found an increase of IL-6 for only three patients, but only one patient reported myalgia; no relationship between myalgia and the increase of IL-6 was found. In conclusion, there is no evidence for an inflammatory origin of succinylcholine-associated myalgia., Implications: Administration of dexamethasone before succinylcholine was not effective in decreasing the incidence or the severity of succinylcholine-induced postoperative myalgia. Furthermore, there was no significant relationship between postoperative myalgia and time course of interleukin-6 concentrations, a marker of inflammation. Pretreatment with dexamethasone is not justified to prevent postoperative myalgia after succinylcholine.

Background: Cardiopulmonary bypass (CPB) induces a systemic inflammatory reaction. Microcirculation-dependent alteration of the gut mucosal barrier with subsequent translocation of endotoxins is a postulated mechanism for this inflammatory response. This study was designed to elucidate whether two different approaches to modulate splanchnic perfusion may influence systemic inflammation to CPB., Methods: We examined 40 patients scheduled for elective coronary bypass surgery in a prospective, randomized study. One group (DPX) received dopexamine (1 micro g. kg-1. min-1) continuously after induction of anesthesia until 18 h after CPB. The control group (CON) received equal volumes of NaCl 0.9% in a time-matched fashion. In a third group (EPI) a continuous epidural infusion of bupivacaine 0.25% [(body height (cm) - 100). 10-1=ml.h-1] was administered for the whole study period. Procalcitonin (PCT), tumor necrosis factor (TNF-alpha), soluble TNF receptor, human soluble intercellular adhesion molecule-1, C-reactive protein (CRP) and leukocyte count were measured as parameters of inflammation., Results: All parameters significantly increased following CPB. Increases of PCT, TNF-alpha and leukocyte count were significantly attenuated in the DPX and EPI groups at different time points. However, neither splanchnic blood flow nor oxygen delivery and consumption were different when compared with the CON-group., Conclusion: These results do suggest that mechanisms other than an improved splanchnic blood flow by DPX and EPI treatment have to be considered for the anti-inflammatory effects.

Background: Various anesthetics have been suggested to interfere with the immune system. The ability of leukocytes to express surface receptors and mediators is fundamental to a successful host defense. Therefore, the effects of intravenous anesthetics on cytokine release by leukocytes and expression of surface molecules known to modulate this response were determined., Methods: Concentration-dependent effects of thiopentone, etomidate, propofol, ketamine, midazolam, and fentanyl on spontaneous and endotoxin (lipopolysaccharide; 1 microg/ml)-stimulated cytokine release were studied in whole blood from volunteers (n = 6) cultured for 25 h. In addition, expression of the lipopolysaccharide-recognition molecule CD14 and the major histocompatibility complex class II molecule human leukocyte locus A system-DR (HLA-DR) on monocytes were assessed using flow cytometry., Results: All anesthetics studied elicited only minor effects on spontaneous cytokine release even at pharmacologic concentrations. However, expression density of CD14 was reduced in the presence of thiopentone, etomidate, and propofol, whereas HLA-DR was unaffected. Lipopolysaccharide-stimulated tumor necrosis factor response was inhibited by thiopentone (12.8% [median]; 7.6-18.8 [25-75 percentile]) of control, and ketamine (46.4% [median]; 44.4-56.4 [25-75 percentile]), at pharmacologic concentrations, whereas it was augmented even in the presence of low concentrations of propofol (172.3% [median]; 120.5-200.7 [25-75 percentile]). Ketamine additionally decreased the concentration of interleukin (IL)-1beta (14.8% [median]; 12.0-18.0 [25-75 percentile]). Release of IL-1 receptor antagonist (IL-1ra) was inhibited by thiopentone, etomidate, and propofol, whereas the same anesthetics increased IL-10 concentration simultaneously. Midazolam and fentanyl did not alter the concentrations of any cytokine., Conclusions: These results suggest a complex modulation of the cytokine response by the studied anesthetics in cultured whole blood. Although effects on spontaneous cytokine release by leukocytes were negligible, some anesthetics affected their ability to respond to lipopolysaccharide.