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Background: Dural puncture, paraesthesia and vascular puncture are the most common complications of epidural catheter insertion. Their association with variation in midline needle insertion depth is unknown., Objective: This study evaluated the risk of dural and vascular punctures and the unwanted events paraesthesia and multiple skin punctures related to midline needle insertion depth., Material and Methods: A total of 14,503 epidural catheter insertions including lumbar (L1-L5; n = 5367), low thoracic (T7-T12, n = 8234) and upper thoracic (T1-T6, n = 902) insertions, were extracted from the German Network for Regional Anaesthesia registry between 2007 and 2015. The primary outcomes were compared with logistic regression and adjusted (adj) for confounders to determine the risk of complications/events. Results are presented as odds ratios (OR, [95% confidence interval])., Main Results: Midline insertion depth depended on body mass index, sex, and spinal level. After adjusting for confounders increased puncture depth (cm) remained an independent risk factor for vascular puncture (adjOR 1.27 [1.09-1.47], p = 0.002) and multiple skin punctures (adjOR 1.25 [1.21-1.29], p < 0.001). In contrast, dural punctures occurred at significantly shallower depths (adjOR 0.73 [0.60-0.89], p = 0.002). Paraesthesia was unrelated to insertion depth. Body mass index and sex had no influence on paraesthesia, dural and vascular punctures. Thoracic epidural insertion was associated with a lower risk of vascular puncture than at lumbar sites (adjOR 0.39 [0.18-0.84], p = 0.02)., Conclusion: Variation in midline insertion depth is an independent risk factor for epidural complications; however, variability precludes use of depth as a reliable guide to insertion in individual patients.

Background: Ultrasound, nerve stimulation, and their combination are all considered acceptable ways to guide peripheral nerve blocks. Which approach is most effective and associated with the fewest complications is unknown. We therefore used a large registry to analyze whether there are differences in vascular punctures, multiple skin punctures, and unintended paresthesia., Methods: Twenty-six thousand seven hundred and thirty-three cases were extracted from the 25-center German Network for Regional Anesthesia registry between 2007 and 2016 and grouped into ultrasound-guided puncture (n = 10,380), ultrasound combined with nerve stimulation (n=8173), and nerve stimulation alone (n = 8180). The primary outcomes of vascular puncture, multiple skin punctures, and unintended paresthesia during insertion were compared with conditional logistic regression after 1:1:1 propensity score matching. Results are presented as odds ratios and 95% CIs., Results: Propensity matching successfully paired 2508 patients with ultrasound alone (24% of 10,380 patients), 2508 patients with a combination of ultrasound/nerve stimulation (31% of 8173 patients), and 2508 patients with nerve stimulation alone (31% of 8180 patients). After matching, no variable was imbalanced (standardized differences <0.1). Compared with ultrasound guidance alone, the odds of multiple skin punctures (2.2 [1.7-2.8]; P < .001) and vascular puncture (2.7 [1.6-4.5]; P < .001) were higher with nerve stimulation alone, and the odds for unintended paresthesia were lower with nerve stimulation alone (0.3 [0.1-0.7]; P = .03). The combined use of ultrasound/nerve stimulation showed higher odds of multiple skin punctures (1.5 [1.2-1.9]; P = .001) and lower odds of unintended paresthesia (0.4 [0.2-0.8]; P = .007) compared with ultrasound alone. Comparing the combined use of ultrasound/nerve stimulation with ultrasound alone, the odds for vascular puncture (1.3 [0.7-2.2]; P = .4) did not differ significantly. Systemic toxicity of local anesthetics was not observed in any patient with ultrasound guidance alone, in 1 patient with the combined use of ultrasound and nerve stimulation, and in 1 patient with nerve stimulation alone., Conclusions: Use of ultrasound alone reduced the odds of vascular and multiple skin punctures. However, the sole use of ultrasound increases the odds of paresthesia.

Cellulose acetates can be homogeneously transferred with (3-isocyanatopropyl) triethoxysilane, yielding the corresponding carbamates containing reactive ethoxysilane moieties. The products obtained under different conditions are characterized by liquid and solid-state NMR spectroscopy. A slight hydrolysis in products of high Si-content occurs, which strongly affects the solubility of the polymers. The soluble products can be shaped and crosslinked, forming siloxane and silanol polymer network. By incorporating tetraethoxysilane as inorganic precursor, novel silanized film can be prepared and are studied by scanning electron microscopy., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background and Objectives: Psoas blocks are an alternative to femoral nerve blocks and have the potential advantage of blocking the entire lumbar plexus. However, the psoas muscle is located deeply, making psoas blocks more difficult than femoral blocks. In contrast, while femoral blocks are generally easy to perform, the inguinal region is prone to infection. We thus tested the hypothesis that psoas blocks are associated with more insertion-related complications than femoral blocks but have fewer catheter-related infections., Methods: We extracted 22,434 surgical cases from the German Network for Regional Anesthesia registry (2007-2014) and grouped cases as psoas (n = 7593) and femoral (n = 14,841) blocks. Insertion-related complications (including single-shot blocks and catheter) and infectious complications (including only catheter) in each group were compared with χ tests. The groups were compared with multivariable logistic models, adjusted for potential confounding factors., Results: After adjustment for potential confounding factors, psoas blocks were associated with more complications than femoral blocks including vascular puncture 6.3% versus 1.1%, with an adjusted odds ratio (aOR) of 3.6 (95% confidence interval [CI], 2.9-4.6; P < 0.001), and multiple skin punctures 12.6% versus 7.7%, with an aOR of 2.6 (95% CI, 2.1-3.3; P <0.001). Psoas blocks were also associated with fewer catheter-related infections: 0.3% versus 0.9% (aOR of 0.4; 95% CI, 0.2-0.8; P = 0.016), and with improved patient satisfaction (mean ± SD 0- to 10-point scale score, 9.6 ± 1.2 vs 8.4 ± 2.9; P < 0.001). Results from a propensity-matched sensitivity analysis were similar., Conclusions: Psoas blocks are associated with more insertion-related complications but fewer infectious complications., Clinical Trial Registration: ID NCT02846610.

Purpose: To demonstrate the feasibility of complete target immobilization by means of high-frequency jet ventilation (HFJV); and to show that the saving of planning target volume (PTV) on the stereotactic body radiation therapy (SBRT) under HFJV, compared with SBRT with respiratory motion, can be predicted with reliable accuracy by computed tomography (CT) scans at peak inspiration phase., Methods and Materials: A comparison regarding different methods for defining the PTV was carried out in 22 patients with tumors that clearly moved with respiration. A movement span of the gross tumor volume (GTV) was defined by fusing respiration-correlated CT scans. The PTV enclosed the GTV positions with a safety margin throughout the breathing cycle. To create a PTV from CT scans acquired under HFJV, the same margins were drawn around the immobilized target. In addition, peak inspiration phase CT images (PIP-CTs) were used to approximate a target immobilized by HFJV., Results: The resulting HFJV-PTVs were between 11.6% and 45.4% smaller than the baseline values calculated as respiration-correlated CT-PTVs (median volume reduction, 25.4%). Tentative planning by means of PIP-CT PTVs predicted that in 19 of 22 patients, use of HFJV would lead to a reduction in volume of >or=20%. Using this threshold yielded a positive predictive value of 0.89, as well as a sensitivity of 0.94 and a specificity of 0.5., Conclusions: In all patients, SBRT under HFJV provided a reliable immobilization of the GTVs and achieved a reduction in PTVs, regardless of patient compliance. Tentative planning facilitated the selection of patients who could better undergo radiation in respiratory standstill, both with greater accuracy and lung protection., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

With reference to radiosurgery of the liver, we describe techniques designed to solve the methodological problem of striking targets subject to respiratory motion with the necessary precision. Implanting a gold marker in the vicinity of the liver tumor was the first step in ensuring the reproducibility of the isocenter's position. An 18-karat gold rod measuring 1.9 x 3 mm was implanted approximately 2 cm from the edge of the tumor as this was displayed in the spiral, thin-slice CT with contrast media. Both the implantation of the marker and the required, CT-controlled biopsy of the liver tumor can be achieved simultaneously with the same puncture needle. The efficiency of high-frequency jet ventilation (HFJV) in neutralizing the targeted organ's respiratory motion during stereotactic single-dose irradiation was evaluated. The procedure was carried out on ten patients without any complications. In the time between treatment planning and irradiation (3 days), no significant marker migration was observable. In all cases, the gold marker (volume: 7.5 mm(3)) was readily observable in the treatment beam using portal imaging. HFJV provided reliable immobilization. The liver motion in each anesthetized patient was limited to under 3.0 mm in all directions. Thus, the correct field settings and target reproducibility were able to be analyzed and documented during the irradiation. The combination of marker and HFJV enables the determination of stereotactic coordinates directly related to the liver itself and, in this way, stereotactic radiation treatment of liver tumors is freed from the uncertainties involved in orientation to bony landmarks, in respiratory motion, and in changes of position in the stereotactic body frame. The method is feasible and can improve the accuracy of stereotactic body radiation therapy.

Introduction: The aim of this study was to investigate efficacy and tolerability of propofol, remifentanil and cisatracurium or mivacurium in routine anesthetic practice., Patients and Methods: A total of 6,161 patients scheduled for abdominal or orthopedic surgery were included in this open multicenter phase IV study. Perioperative hemodynamics as well as induction, recovery and discharge times, anesthetics, frequency of PONV and side-effects were studied., Results: Quality of induction and maintenance of anesthesia were evaluated by anesthesiologists to be good or very good in 88%. 86% of the patients assessed anesthesia as good or very good. Adverse events were reported for 28 patients (0.45%), with hypotension and bradycardia being most frequent. Recovery was evaluated by anesthesiologists to be good or very good in 88%, surgeons and nursing staff assessed the TIVA as good or very good in 90%. Most frequent postoperative complaints were pain (16.7%), nausea (6.1%), shivering (3.1%) and vomiting (0.7%)., Conclusions: The study showed that total intravenous anesthesia using propofol, remifentanil and cisatracurium or mivacurium is safe, tolerable and effective and has a high degree of acceptance.

Unlabelled: Sodium channel blockers are approved for IV administration in the treatment of neuropathic pain states. Preclinical studies have suggested antihyperalgesic effects on the peripheral and central nervous system. Our objective in this study was to determine the time course of the analgesic and antihyperalgesic mechanisms of perioperative lidocaine administration. Forty patients undergoing major abdominal surgery participated in this randomized and double-blinded study. Twenty patients received lidocaine 2% (bolus injection of 1.5 mg/kg in 10 min followed by an IV infusion of 1.5 mg. kg(-1). h(-1)), and 20 patients received saline placebo. The infusion started 30 min before skin incision and was stopped 1 h after the end of surgery. Lidocaine blood concentrations were measured. Postoperative pain ratings (numeric rating scale of 0-10) and morphine consumption (patient-controlled analgesia) were assessed up to 72 h after surgery. Mean lidocaine levels during surgery were 1.9 +/- 0.7 microg/mL. Patient-controlled analgesia with morphine produced good postoperative analgesia (numeric rating scale at rest,

Background and Objective: Knowledge of the pharmacodynamic interaction between remifentanil and propofol is important to permit optimal dosage strategies. We studied this pharmacodynamic interaction using the median power frequency of the processed electroencephalogram as a control parameter for feedback-controlled dosing of propofol., Methods: Twenty-one patients were given total intravenous anaesthesia with remifentanil and propofol. During three target-controlled infusion regimens, the target concentrations of remifentanil (5, 10, 15 ng mL(-1)) and propofol dosing were automatically adjusted to keep the median power frequency in the range 2 +/- 0.5 Hz. In each patient and during each remifentanil target concentration, four arterial propofol/remifentanil concentration pairs were measured. The type of interaction was tested using the relative distance from the line of additivity and the isobole was modelled using Bernstein splines., Results: The results from 13 patients were used for data analysis. The measured remifentanil concentrations during the three targets were (mean +/- SD): 3.6 +/- 0.9, 8.1 +/- 2.5 and 12.4 +/- 2.8 ng mL(-1). The corresponding propofol concentrations were 2.64 +/- 0.86, 2.13 +/- 0.58 and 2.09 +/- 0.58 microg mL(-1). The data were best described with an additive type of interaction and the isobole was estimated using: ((c)Remifentanil/64.2 ng mL(-1)) + ((c)Propofol/2.61 microg mL(-1)) = 1., Conclusions: Within the studied concentration range, remifentanil and propofol showed an additive type of pharmacodynamic interaction on the electroencephalogram.

Background and Objective: For total intravenous anaesthesia an opioid is often combined with a hypnotic. A supra-additive interaction has been reported for clinical signs such as loss of consciousness or loss of the eyelash reflex. This study investigated the type of interaction of alfentanil and propofol on the electroencephalogram., Methods: Twenty patients scheduled for abdominal surgery were enrolled in the study. Anaesthesia was induced and maintained with alfentanil and propofol. Each patient received a target-controlled infusion of alfentanil. Three target concentrations of 150, 225 and 300 ng mL(-1) were applied to each patient in random order. Propofol was added to the alfentanil infusion by a feedback system. The set point was the range of 1.5-2.5 Hz median frequency of the electroencephalogram. Four arterial blood samples were taken within the last 20 min of each period. The mean drug concentrations were used to determine the type of interaction and an isobole was estimated by fitting Bernstein spline functions to the data., Results: In 17 patients, all three alfentanil target concentrations could be administered. The test for supra-additivity as well as the isobole construction resulted in an additive type of interaction. The line of additivity cA/cA0 + cP/cP0 = 1 was best fitted for the values (standard deviation) cA0 = 1240 (51)ng mL(-1) and cP0 = 5.21 (0.36) microg mL(-1)., Conclusions: The type of interaction between alfentanil and propofol on the electroencephalogram in the investigated dose range is additive. This gives the freedom and need to select the appropriate dosing ratio of alfentanil and propofol by other considerations.

In a double-blind randomized study, the incidence and severity of postoperative nausea and vomiting was investigated with a new formulation of etomidate (Etomidate-(R)Lipuro, B. Braun Melsungen AG, Germany) compared with propofol for induction of a balanced anaesthesia with isoflurane/fentanyl in air. The incidence and intensity of nausea was examined by use of a visual analogue scale (VAS; 0-100 mm) at 1, 2, between 6 and 8, and 24 h postoperatively. One-hundred-and-sixty-four patients undergoing orthopedic procedures were studied. For etomidate vs. propofol, 14.6% vs. 14.2% male and 26.8% vs. 27.5% female patients were nauseated during the first two postoperative hours. The median rating for nausea remained below 5 mm at any time in both groups, i.e. the intensity of nausea was very low. The incidence of vomiting was higher in women receiving etomidate (26.8% vs. 10%). We conclude that etomidate does not increase nausea during the early postoperative period.

Objective: We investigated the pharmacologic properties of midazolam with special regard to age using the electroencephalogram (EEG) as a measure of the hypnotic-sedative effect., Methods: Nine younger (24 to 28 years) and nine elderly (67 to 81 years) male volunteers received midazolam by a computer-controlled device. Two infusion cycles with linearly increasing target plasma levels (slope, 40 ng/mL/min for the younger subjects; 20 ng/mL/min for the elderly subjects) were administered until defined end points were attained (median EEG frequency <4 Hz and loss of responsiveness to acoustic stimuli). An EEG was recorded to quantitate the hypnotic effect, relating the median frequency of the power spectrum to the plasma level by a sigmoid Emax model, including an effect compartment. Pharmacokinetic data were derived from arterial blood samples with use of a three-compartment model., Results: The total doses needed to reach the defined end points were 71+/-9 mg and 35+/-6 mg for the younger and elderly subjects, respectively (P < .001). Pharmacokinetic parameters were similar in both groups (clearance, 399+/-91 and 388+/-97 mL/min; steady-state volume of distribution, 85+/-22 and 104 +/-11 L in young and elderly subjects, respectively). Pharmacodynamic data showed a large difference in half-maximum concentration (EC50; young subjects, 522+/-236 ng/mL; elderly subjects, 223+/-56 ng/mL; P < .05), a steep concentration-response curve, and distinct hysteresis. We found much interindividual variability in the plasma concentrations necessary to achieve the clinical end points, regardless of age., Conclusions: These results suggest that the lower doses needed to reach sedation in the elderly subjects were attributable to a 50% decrease in EC50, not to changes in pharmacokinetics.

An intravenous bolus dose of 0.75 mg Kg-1 eltanolone emulsion was administered to 18 unpremedicated ASA I or II patients. In addition to clinical observation and haemodynamic monitoring, EEG power spectrum and median frequency were recorded. Venous blood was collected to establish a concentration-effect relation using the median frequency as a pharmacodynamic parameter for hypnotic effect, and with analysis of data with the sigmoidal Emax model. Emax was determined as the maximal decrease of the median frequency caused by the CNS depressant effect of eltanolone. The results of seven of 15 patients with complete serum and EEG analysis could be described by a sigmoidal curve. The calculated IC50, the serum concentration producing 50% inhibition of Emax, was 0.57 micrograms mL-1. Median frequency occasionally decreased independently of eltanolone serum concentration in seven patients because interference by natural sleep was not prevented before induction or during awakening by setting continuous stimulations. In relation to the peak serum concentration, the decrease in median frequency occurred late in one patient. Nevertheless, the present study provides a preliminary estimation of the IC50 of eltanolone. From the clinical point of view, eltanolone showed satisfactory induction characteristics which warrant further evaluation.

Changes in the EEG power spectrum were studied in 50 patients (ASA status I or II), receiving either 2 mg.kg-1 of racemic ketamine or 1 mg.kg-1 of S-(+) ketamine in a randomized and double-blind manner after prior administration of 0.1 mg.kg-1 of midazolam. The patients receiving intramuscular premedication with midazolam about 45 minutes prior to induction of anaesthesia showed, in a deliberately quiet environment and mostly in the early morning, a delta dominated EEG (56% delta power) with a reduced alpha peak (17% alpha power) and an average median of 4 Hz as the baseline findings of the EEG power spectrum. The intravenous administration of midazolam led to activation of the lower beta range (13-18 Hz) and the subsequent injection of ketamine caused an increase in activity in the fast beta range (21-30 Hz), both being accompanied by a reduction of delta power from 56% to 40%. Correspondingly, an increase in the median frequency was noted. Causing nearly the same changes in EEG, S-(+) ketamine was confirmed to be twice as potent as racemic ketamine.

In a randomized, double-blind study, we have examined the stereoselective disposition and pharmacodynamic characteristics of ketamine in surgical patients after i.v. administration of S(+)-ketamine 1 mg/kg body weight (25 patients) or racemic ketamine 2 mg/kg body weight (25 patients). S(+)-Ketamine was not inverted to R(-)-ketamine. After racemate administration we observed statistically significant (P < 0.01) smaller clearance and volume of distribution for R(-)-ketamine compared with S(+)-ketamine. In contrast, the pharmacokinetic variables of S(+)-ketamine were not significantly different between treatment groups. Systolic and diastolic arterial pressure and heart rate increased significantly (P < 0.005) in both groups. At 1, 3 and 15 min after S(+)-ketamine administration, significantly greater increase in systolic and diastolic pressures were observed compared with the racemate group. There was no correlation between the changes in haemodynamic variables and plasma catecholamine concentrations, which remained unaffected after administration of the medications.

Since the 1940s several preclinical investigations have demonstrated the anaesthetic activity of a series of structurally related pregnanes without notable endocrine action. One of the most active of these is pregnanolone (3-alpha-hydroxy-5-beta-pregnane-20-one), which is a naturally occurring metabolite of progesterone. Pregnanolone is not soluble in water, which has prevented its use for clinical research. In 1987, however, a stable oil-in-water emulsion of eltanolone that could be used for i.v. administration in man was introduced by KABI Pharmacia, Stockholm, Sweden. METHODS. In an open study the dose of eltanolone that induces anaesthesia in 50% of the patients (AD50) was estimated according to the "up and down method" of Dixon and Massey. Respiratory and cardiovascular effects were evaluated as well as the reliability of eltanolone emulsion. The study was conducted in accordance with the Declaration of Helsinki and started after the approval of the local Medical Ethics Review Committee. In all, 31 patients of ASA risk categories I and II (male or female with non child-bearing potential) were included in the study after written informed consent had been obtained. All patients were premedicated with 5 mg midazolam i.m. about 30 min before the injection of eltanolone. Eltanolone emulsion was given i.v., usually on the back of the hand, over 20 s. In connection with the injection of eltanolone every patient was asked whether he or she felt any pain or discomfort at the injection site. As suggested by results in volunteers in a previous study the starting dose was 0.5 mg/kg body weight. Cessation of counting and loss of eyelash reflex were used as indicators of efficacy in the induction of anaesthesia. If these criteria were achieved within 120 s after the start of injection (responder) the dose for the next patient was decreased by 15%, if not (non-responder), the next patient received the same dose plus 15% (up to 1.01 mg/kg body weight). Heart rate and oxygen saturation were recorded continuously (Sirecust 404; Nellcor) from 1 min before to 10 min after the start of injection, and blood pressure was measured noninvasively 1 min before induction and then at 1, 2, 3, 5, 8 and 10 min from the start of the eltanolone injection (Sirecust 888). If oxygen saturation fell to 85% oxygen was applied by way of the face mask and the patients were ventilated if necessary. Respiratory disturbances, time to and duration of apnoea were recorded, as were involuntary movements or increase in muscle tone. Usually intubation was carried out at the end of the 10-min observation period using thiopentone, vecuronium and suxamethonium. If a patient did not fall asleep or awoke prematurely, intubation was performed in the same way and from this point pharmacodynamic parameters were no longer evaluated for the study. RESULTS. The AD50 was 0.33 mg/kg body weight, and the 95% confidence interval, 0.30-0.36 mg/kg body weight. The eltanolone dose varied from 0.25 to 0.5 mg/kg body weight. Induction was successful in 17 (of 31) patients according to the eyelash reflex as criterion and in 28 according to cessation of counting. Above 0.38 mg/kg body weight efficacy variables were achieved in all patients, while below 0.29 mg/kg body weight eyelash reflex was not lost in any patient. The mean time to loss of consciousness (cessation of counting) in the responder group was 48 +/- 12 s after the start of injection and loss of eyelash reflex was recorded after 94 +/- 13 s. In the nonresponder group eyelash reflex persisted over 120 s in all patients and counting stopped on average after 72 +/- 23 s. Three patients in this group also did not stop counting (dose: 0.29 mg/kg body weight). Blood pressure remained stable in all patients but 1 throughout the observation period. In 1 patient there was an alarming rise in blood pressure from 160/90 mmHg before to 200/100 mmHg 3 min after the injection.(ABSTRACT TRUNCATED AT 400 WORDS)