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The haemodynamic implications of epidural anaesthesia in children are poorly documented. We report macro- and micro-haemodynamic data from an observational study of 25 children ranging from neonates to six-years old, who underwent surgery conducted with a specific combination of monitoring systems. We analysed 90 min of study-related monitoring after epidural catheterisation, with skin incision taking place after around 30 min. We recorded macrohaemodynamic parameters (monitored using LiDCOrapid) including heart rate, mean arterial pressure, cardiac output, stroke volume, systemic vascular resistance and stroke volume variation. Microhaemodynamic parameters (monitored using Invos™) included cerebral and peri-renal oxygenation. Based on the entire 90 min of study-related monitoring, we found significant increases in cardiac output (p = 0.009), stroke volume (p = 0.006) and stroke volume variation (p = 0.008), as well as decreases in systemic vascular resistance (p = 0.007) around 30 min after epidural blockade. There were no significant changes in heart rate, arterial pressure and cerebral or peri-renal oxygenation during these 90 min. Considering that the microhaemodynamic parameters were not affected by the macrohaemodynamic changes, we conclude that autoregulation of the brain and the kidneys was maintained in children under epidural anaesthesia. [ABSTRACT FROM AUTHOR]

Previous results in volunteers have indicated the effective dose in 99% of subjects ( ED99) of local anaesthetic volume to be 0.10 ml.mm−2 of cross-sectional nerve area for sciatic nerve blockade. The objective of this prospective, randomised, double-blind study was to investigate the ED99 of local anaesthetic for ultrasound-guided sciatic nerve blockade in patients undergoing foot surgery, according to Dixon's up-and-down method and probit analysis. A starting volume of 0.20 ml local anaesthetic per mm2 cross-sectional nerve area was used. If surgical anaesthesia was judged to be adequate, the volume of local anaesthetic for the next case was reduced by 0.02 ml.mm−2, until the first block failed. Thereafter, the volume of local anaesthetic was increased by 0.02 ml.mm−2. The ED99 volume of local anaesthetic for ultrasound-guided sciatic nerve blockade was calculated to be 0.15 ml.mm−2 cross-sectional nerve area, which is higher than the previously evaluated ED99 volume in volunteers. [ABSTRACT FROM AUTHOR]

Previous results in volunteers have indicated the effective dose in 99% of subjects ( ED99) of local anaesthetic volume to be 0.10 ml.mm−2 of cross-sectional nerve area for sciatic nerve blockade. The objective of this prospective, randomised, double-blind study was to investigate the ED99 of local anaesthetic for ultrasound-guided sciatic nerve blockade in patients undergoing foot surgery, according to Dixon's up-and-down method and probit analysis. A starting volume of 0.20 ml local anaesthetic per mm2 cross-sectional nerve area was used. If surgical anaesthesia was judged to be adequate, the volume of local anaesthetic for the next case was reduced by 0.02 ml.mm−2, until the first block failed. Thereafter, the volume of local anaesthetic was increased by 0.02 ml.mm−2. The ED99 volume of local anaesthetic for ultrasound-guided sciatic nerve blockade was calculated to be 0.15 ml.mm−2 cross-sectional nerve area, which is higher than the previously evaluated ED99 volume in volunteers. [ABSTRACT FROM AUTHOR]

Background: Little is known about the pharmacodynamic characteristics of liposomal bupivacaine. Hypothesizing that they would not identify pharmacodynamic differences from plain bupivacaine during the initial period after administration, but would find better long-term pharmacodynamic characteristics, the authors designed a randomized, controlled, triple-blinded, single-center study in volunteers., Methods: Volunteers aged 18 to 55 yr (body mass index, 18 to 35 kg/m2) received two ulnar nerve blocks under ultrasound guidance. Using a crossover design with a washout phase of 36 days or more, one block was performed with liposomal and one with plain bupivacaine. Which came first was determined by randomization. Sensory data were collected by pinprick testing and motor data by thumb adduction, either way in comparison with the contralateral arm. Endpoints included success, time to onset, and duration of blockade. Residual efficacy was assessed by the volunteers keeping a diary. Statistical analysis included Wilcoxon signed-rank and exact McNemar's tests, as well as a generalized estimation equation model., Results: Successful sensory blockade was noted in 8 of 25 volunteers (32%) after liposomal and in 25 of 25 (100%) after plain bupivacaine (P < 0.0001). Significant differences emerged for time to onset, defined as 0% response to pinpricking in four of five hypothenar supply areas (P < 0.0001), and for time from onset to 80% or 20% in one of five areas (P < 0.001; P < 0.001). Carryover effects due to the randomized sequencing were unlikely (estimate, -0.6286; sequence effect, 0.8772; P = 0.474). Self-assessment greater than 3.5 days did reveal, for liposomal bupivacaine only, intermittent but unpredictable episodes of residual sensory blockade., Conclusions: The results show that liposomal bupivacaine is not a suitable "sole" drug for intraoperative regional anesthesia. Findings of its limited long-term efficacy add to existing evidence that a moderate effect, at best, should be expected on postoperative pain therapy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc., on behalf of the American Society of Anesthesiologists.)

Study Objective: The impact of biological sex in peripheral regional anaesthesia is largely unknown. We therefore designed a prospective study in volunteers to investigate the impact of biological sex on pharmacodynamic, pharmacokinetic and morphometric characteristics for peripheral nerve blockade., Methods: The initial study plan was powered to include 90 volunteers to find a difference of 35 min in duration of sensory block (primary outcome variable) with 80% power and alpha error at 5%. After discussions in ethical review, a pilot study of 2 x 12 volunteers from each sex were studied. Female and male volunteers received ultrasound guided nerve blockade with 3.0 mL ropivacaine 7.5 mg mL-1. Sensory duration of blockade, as the primary outcome, was evaluated by pinprick testing. Secondary outcomes were sensory onset time of blockade, pharmacokinetic characteristics and the visibility of ulnar nerves using ultrasound. Analyses included Mann-Whitney U-statistics with P<0.05 (two-sided) as significant., Results: After 24 participants, the median (IQR) duration of sensory blockade was 450 (420; 503) min in women and 480 (450; 510) min in men (P = 0.49). Sensory onset time of blockade, and ultrasound visibility of nerves were also similar between the study groups. The total drug exposure across time (AUC0-infinity) was significantly higher in women (P = 0.017). After a the planned power re-analysis after these 24 study paticipants, which suggested that > 400 subjects would be required with 80% power and alpha error of 5% to find significance for the primary outcome parameter for marginal differences, we terminated the study at this point., Conclusions: We did not detect significant differences between female and male study participants in terms of pharmacodynamic and morphometric characteristics after ultrasound guided ulnar nerve blocks. Women did show significantly greater pharmacokinetic ropivacaine exposures. The results of this study indicate that peripheral regional block pharmacodynamic characteristics are independent of the biological sex, whereas pharmacokinetic parameters are sex-dependent., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zadrazil et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Dorsal penile nerve block stands out as one of the commonly employed regional anesthetic techniques in children. Despite the large body of experience, failure rates are still significant. We included 20 children (median (SD) age of 73 (31) months) scheduled for circumcision without general anesthesia and secondary airway manipulation in a consecutive case series. Under ultrasound guidance and utilizing an in-plane needle guidance technique, the dorsal penile nerve block was administered with slight sedation, and spontaneous respiration was maintained in all cases. To investigate the underlying anatomy for dorsal penile nerve blockade, we dissected three cadavers. The primary study endpoint was the success rate of surgical blockade, meaning that the surgical procedure could be performed without additional general anesthesia and invasive airway management. The secondary endpoint was the requirement of analgesics until discharge from the post-anesthesia care unit. The primary endpoint was successfully met in all patients according to our strict definition without additional general anesthesia or airway manipulation. In addition, no child received analgesics until discharge from the recovery room. The anatomical investigation clarified the specific anatomy as baseline knowledge for an ultrasound-guided dorsal penile nerve blockade and enabled successful performance in 20 consecutive children where penile surgery was possible in light sedation without additional airway manipulation.

Study Objective: To identify sex differences associated with caudal epidurals, the most commonly used technique of pediatric regional anesthesia, based on individually validated data of ultrasound-guided blocks performed between 04/2014 and 12/2020., Methods: Prospectively collected and individually validated data of a cohort of children aged between 0-15 years was analyzed in a retrospective observational study. We included pediatric surgeries involving a primary plan of caudal epidural anesthesia under sedation (without airway instrumentation) and a contingency plan of general anesthesia. Sex-specific rates were analyzed for overall failure of the primary anesthesia plan, for residual pain, for block-related technical complications and for critical respiratory events. We used Fisher´s exact tests and multivariable logistic regressions were used to evaluate sex-specific associations., Results: Data from 487 girls and 2060 boys ≤15 years old (ASA status 1 to 4) were analyzed. The primary-anesthesia-plan failure rate was 5.5% (95%CI 3.8%-7.8%) (N = 27/487) among girls and 4.7% (95%CI 3.9%-5.7%) (N = 97/2060) among boys (p = 0.41). Residual pain was the main cause of failure, with rates of 4.5% (95%CI 2.9-6.6%) (N = 22/487) among girls and 3.0% (95%CI 2.3-3.8%) (N = 61/2060) among boys (p = 0.089). Block-related technical complications were seen at rates of 0.8% (95%CI 0.3%-1.9%) (N = 4/487) among girls vs 2.5% (95%CI 0.5-2.7%) (N = 51/2060) among boys and, hence, significantly more often among male patients (p = 0.023). Male sex was significantly associated with higher odds (adjusted OR: 3.18; 95% CI: 1.12-9; p = 0.029) for such technical complications regardless of age, ASA status, gestational week at birth or puncture attempts. Critical respiratory events occurred at a 1.7% (95%CI 1.2%-2.3%) rate (N = 35/2060) twice as high among boys as 0.8% (95%CI 0.3%-1.9%) (N = 4/487) among girls (p = 0.21)., Conclusions: While the the primary-anesthesia-plan failure rate was equal for girls and boys, technical complications and respiratory events are more likely to occur in boys., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Opfermann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

ADV6209, a new formulation of midazolam with the addition of γ-cyclodextrin for oral use, has recently been licensed as the first pediatric sedative in the European Union. We compared the clinical efficacy of ADV6209 to the standard formulation of midazolam in premedication to reduce anxiety in children before anesthesia induction in a randomized, double-blinded controlled trial. Eighty children (ASA I/II; age: 2-8 years) scheduled for elective surgery were randomized to receive 0.25 mg kg -1 of either conventional midazolam or ADV6209. Assessment tools included the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF) as well as scores for oral acceptance of the premedication and facemask acceptance during inhalational anesthesia induction. Mann-Whitney U and Pearson's chi-square tests were used for comparisons of outcome parameters. The primary outcome parameter of the study (mYPAS-SF anxiety score 30 min after the drug administration) did not reveal any significant intergroup difference between the ADV6209 group and the conventional midazolam group. Both drugs revealed their efficacy in reducing anxiety and in providing adequate sedation. The premedication dose was accepted by all children in the ADV6209 but rejected by 15% in the conventional midazolam group ( p = 0.037). Acceptance of facemask placement was not found to differ significantly. No adverse events related to the study medications were noted. ADV6209 was better orally accepted than the conventional midazolam preparation and proved its efficacy in reducing preoperative anxiety. This clinically interesting preparation may alleviate the premedication process of 2-8 year-old children and obviates off-label drug use.

Background and Objective: In microdose studies, drug pharmacokinetics is measured in humans after administration of subtherapeutic doses. While previous microdose studies focused primarily on plasma pharmacokinetics, we set out to evaluate the feasibility of microdosing for a pharmacokinetic assessment in subcutaneous tissue and epithelial lining fluid., Methods: Healthy subjects received a single intravenous bolus injection of a microdose of [ 14 C]ciprofloxacin (1.1 µg, 7 kBq) with (cohort A, n = 9) or without (cohort B, n = 9) a prior intravenous infusion of a therapeutic dose of unlabeled ciprofloxacin (400 mg). Microdialysis and bronchoalveolar lavage were applied for determination of subcutaneous and intrapulmonary drug concentrations. Microdose [ 14 C]ciprofloxacin was quantified by accelerator mass spectrometry and therapeutic-dose ciprofloxacin by liquid chromatography-tandem mass spectrometry., Results: The pharmacokinetics of therapeutic-dose ciprofloxacin (cohort A) in plasma, subcutaneous tissue, and epithelial lining fluid was in accordance with previous data. In plasma and subcutaneous tissue, the dose-adjusted area under the concentration-time curve of microdose ciprofloxacin was similar in cohorts A and B and within an 0.8-fold to 1.1-fold range of the area under the concentration-time curve of therapeutic-dose ciprofloxacin. Penetration of microdose ciprofloxacin into subcutaneous tissue was similar in cohorts A and B and comparable to that of therapeutic-dose ciprofloxacin with subcutaneous tissue-to-plasma area under the concentration-time curve ratios of 0.44, 0.44, and 0.38, respectively. Penetration of microdose ciprofloxacin into epithelial lining fluid was highly variable and failed to predict the epithelial lining fluid penetration of therapeutic-dose ciprofloxacin., Conclusions: Our study confirms the feasibility of microdosing for pharmacokinetic measurements in plasma and subcutaneous tissue. Microdosing combined with microdialysis is a potentially useful tool in clinical antimicrobial drug development, but its applicability for the assessment of pulmonary pharmacokinetics with bronchoalveolar lavage requires further studies., Clinical Trial Registration: ClinicalTrials.gov NCT03177720 (registered 6 June, 2017)., (© 2022. The Author(s).)

Purpose: Feasibility, reliability, and safety assessment of transcranial motor evoked potentials (MEPs) in infants less than 12 months of age., Methods: A total of 22 patients with a mean age of 33 (range 13-49) weeks that underwent neurosurgery for tethered cord were investigated. Data from intraoperative MEPs, anesthesia protocols, and clinical records were reviewed. Anesthesia during surgery was maintained by total intravenous anesthesia (TIVA)., Results: MEPs were present in all patients for the upper extremities and in 21 out of 22 infants for the lower extremities. Mean baseline stimulation intensity was 101 ± 20 mA. If MEPs were present at the end of surgery, no new motor deficit occurred. In the only case of MEP loss, preoperative paresis was present, and high baseline intensity thresholds were needed. MEP monitoring did not lead to any complications. TIVA was maintained with an average propofol infusion rate of 123.5 ± 38.2 µg/kg/min and 0.46 ± 0.17 µg/kg/min for remifentanil., Conclusion: In spinal cord release surgery, the use of intraoperative MEP monitoring is indicated regardless of the patient's age. We could demonstrate the feasibility and safety of MEP monitoring in infants if an adequate anesthetic regimen is applied. More data is needed to verify whether an irreversible loss of robust MEPs leads to motor deficits in this young age group., (© 2021. The Author(s).)

Background: It remains unclear how much sedation is required for subumbilical surgery under caudal blockade, and sedatives may carry a poorly understood risk of late sequelae in infants. We designed a randomized controlled study to evaluate total propofol consumption and perioperative sedation quality with the avoidance of continuous perioperative sedation in infants undergoing surgery under caudal anesthesia., Methods: Thirty-two infants (age: 0-3 months) were randomized to one of two groups in which perioperative administration of propofol was provided either "as needed" or by continuous infusion (5 mg kg -1 h -1 ). After induction of anesthesia via a facemask with sevoflurane, a venous access was established and 1 mL kg -1 of ropivacaine 0.35% was injected for caudal anesthesia. Intraoperative stress was assessed by repeated recording comfort behavioral scale scores and heart rates., Results: Significantly (P=0.0001) less propofol was administered in the as-needed group (0.7±1.4 mg/kg) than in the continuous-infusion group (3.0±1.6 mg/kg). This difference was not reflected in different requirements of additional intraoperative sedation (0.5±0.8 mg/kg in 5 versus 0.6±1.0 mg/kg in four cases; P=0.76)., Conclusions: As needed propofol administration offers no disadvantage in terms of intraoperative sedation, but significant dose reductions can be achieved by avoiding continuous propofol infusion.

Background: Pregnancy and pain of different origins is an unfavorable combination that presents all practitioners with special challenges. Pain negatively affects the homeostasis of humans. Patient compliance and in-depth knowledge of the fetotoxicity and teratogenicity of the substances are necessary to maintain a balance between therapy for the mother and safety of the unborn child., Objectives: Experts from various disciplines who are entrusted with the care of pregnant patients with pain have come together to develop drug and nondrug therapy concepts with the aim of providing adequate analgesia for pregnant pain patients., Materials and Methods: Relevant questions were formulated by experts and subjected to a literature search. Combined with further national and international recommendations, treatment concepts were developed and discussed in an interdisciplinary manner. Core statements were then drawn up and given recommendation grades., Results: Depending on the trimester, paracetamol, ibuprofen, diclofenac, metamizole, and opioids can be administered carefully in the event of pain; special care is required with nonsteroidal anti-inflammatory drugs (NSAIDs ) in the last trimester. COX‑2 inhibitors are not recommended. For neuropathic pain, amitriptyline, duloxetine, and venlafaxine are considered safe. Non-pharmacological treatment concepts are also available, namely transcutaneous electrical nerve stimulation (TENS therapy), kinesio tapes, and acupuncture. Lymphatic drainage is recommended in cases of edema, if not caused by preeclampsia., Conclusions: A deliberated concept for pain therapy during pregnancy should be initiated with a non-pharmacological intervention and, if necessary, supplemented with pharmacological agents., (© 2021. The Author(s).)

Background: Anaesthetic drugs may cause neuroapoptosis in children and are routinely used off-label in specific age groups. Techniques that reduce anaesthetic drug dose requirements in children may thus enhance the safety of paediatric sedation or anaesthesia. Brainwave entrainment, notably in the form of auditory binaural beats, has been shown to have sedative effects in adults. We evaluated the influence of brainwave entrainment on propofol dose requirements for sedation in children., Methods: We randomised 49 boys scheduled for sub-umbilical surgery under caudal blockade to an entrainment or a control group. Small differences in pitch were applied to each ear to create binaural beats, supplemented by synchronous visual stimuli, within the electroencephalographic frequency bands seen during relaxation and (rapid eye movement/non-rapid eye movement) sleep. After establishment of caudal block, propofol infusion was started at 5 mg kg -1 h -1 . Intraoperatively, the infusion rate was adjusted every 5 min depending on the sedation state judged by the bispectral index (BIS). The infusion rate was decreased by 1 mg kg -1 h -1 if BIS was <70, and was increased if BIS was >70, heart rate increased by 20%, or if there were other signs of inadequate sedation., Results: Mean propofol infusion rates were 3.0 (95% confidence interval [CI]: 2.4-3.6) mg kg -1 h -1 vs 4.2 (95% CI: 3.6-4.8) mg kg -1 h -1 in the entrainment and control groups, respectively (P<0.01). BIS values were similar in the two groups., Conclusions: Brainwave entrainment effectively reduced the propofol infusion rates required for sedation in children undergoing surgery with regional anaesthesia. Further studies are needed to investigate the possibility of phasing out propofol infusions completely during longer surgical procedures and optimising the settings of brainwave stimulation., Clinical Trial Registration: DRKS00005064., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Reducing preoperative anxiety is important as inadequate preoperative management can potentially give rise to behavioral problems in the postoperative course, leading to incalculable quantitative and qualitative handicaps later in life. We compared preanesthetic administration of midazolam to a psychological strategy of walking the children through the operating room and playfully demonstrating anesthesia equipment., Methods: Of 60 children initially randomized, 43 were ultimately evaluated along with their parents. Anxiety was assessed over defined times (T1-T5) using psychometric instruments., Results: Primary outcome parameter: change in mean visual analogue scales (VAS) score before anesthesia (T1) to immediately before its induction (T3) in the pediatric patients. This change was significantly different (P=0.045) with a higher decrease of anxiety in the psychology group (mean - 0.13, 95% confidence interval -2.82 to -0.075) compared to the medication group (mean 1.39, 95% confidence interval 0.12 to 3.01). Secondary outcome parameters, State-Trait Anxiety Inventory (STAI): despite no significant intergroup difference in trait anxiety, state anxiety increased significantly in the medication but not in the psychology group (both true of children and parents). Modified Yale Preoperative Anxiety Scale (m-YPAS): the only significant decreases in parameters (for vocalization and emotional expressivity) were seen in the psychology group, and all parameters confirmed the finding of significantly greater anxiety in the medication group than in the psychology group at T3., Conclusions: All psychometric instruments used in this study indicated that our psychological strategy of preanesthesia preparation was capable of successfully reducing anxiety in paediatric patients and their parents.

Arterial hypotension during cesarean delivery under spinal anesthesia can cause maternal and fetal adverse effects. Therefore, current guidelines recommend the continuous and preferably prophylactic use of vasopressors, emphasizing the use of alpha-agonists, such as phenylephrine. Besides a left lateral uterine displacement either an intravenous colloid preloading or a crystalloid co-loading is recommended. The blood pressure goal is to maintain a systolic arterial blood pressure of at least 90% of the initial baseline value and to avoid a drop to less than 80% of this baseline. To achieve this goal a prophylactic continuous phenylephrine infusion with an adjustable flow rate is recommended. It is advised to start with an initial dose of 25-50 µg/min, initiated immediately following the intrathecal injection of the local anesthetic and titrated according to the vital parameters. Parturients with cardiac diseases should be preoperatively evaluated following individual hemodynamic goals.

Background: Perioperative normovolemia is a major determinant of tissue oxygen availability and postoperative outcome. Thus, adequate volume replacement therapy remains an essential part of perioperative management. Nevertheless, volume optimization in overweight and obese surgical patients with alterations in cardiovascular function, peripheral perfusion, and body composition remains challenging. We, therefore, tested the hypothesis that Body Mass Index (BMI) correlates with fluid requirements during goal-directed management. Furthermore, we evaluated subcutaneous tissue oxygen tension (PsqO2) as an indicator of intravascular volume status and peripheral perfusion., Methods: Ninety women, undergoing open gynecologic surgery, were assigned to three groups according to their BMI, (lean: BMI 18.5 to 24.9 kg/m2, overweight: BMI 25 to 29.9 kg/m2, obese: BMI>30 kg/m2). Esophageal Doppler monitoring guided intraoperative crystalloid administration. Tissue oxygen tension was measured with a polarographic electrode in the subcutaneous tissue of the upper arm and served as a secondary outcome parameter., Results: BMI and fluid requirements did not correlate (r=0.093, P=0.384). Total amounts of administered crystalloids were comparable. Lean patients received 2223±1811 mL in total, while overweight patients received 1866±1261 mL. Obese patients required 2416±1143 mL of total crystalloids (P=0.327). Intra- and postoperative PsqO2 did not differ significantly (97.3 vs. 86.8 vs. 79.6 mmHg, P=0.06 and 74.5 vs. 83 vs. 81.5 mmHg, P=0.63, respectively)., Conclusions: BMI did not affect intraoperative fluid requirements. Doppler-guided intravascular volume optimization was associated with well-maintained subcutaneous tissue oxygen availability in all BMI groups.

Background: The efficacy of dexamethasone in extending the duration of local anaesthetic block is uncertain. In a randomised controlled triple blind crossover study in volunteers, we tested the hypothesis that neither i.v. nor perineurally administered dexamethasone prolongs the sensory block achieved with ropivacaine., Methods: Ultrasound-guided ulnar nerve blocks (ropivacaine 0.75% wt/vol, 3 ml, with saline 1 ml with or without dexamethasone 4 mg) were performed on three occasions in 24 male volunteers along with an i.v. injection of saline 1 ml with or without dexamethasone 4 mg. The combinations of saline and dexamethasone were as follows: control group, perineural and i.v. saline; perineural group, perineural dexamethasone and i.v. saline; i.v. group, perineural saline and i.v. dexamethasone. Sensory block was measured using a VAS in response to pinprick testing. The duration of sensory block was the primary outcome and time to onset of sensory block the secondary outcome., Results: All 24 subjects completed the trial. The median [inter-quartile range (IQR)] duration of sensory block was 6.87 (5.85-7.62) h in the control group, 7.37 (5.78-7.93) h in the perineural group and 7.37 (6.10-7.97) h in the i.v. group (P=0.61). There was also no significant difference in block onset time between the three groups., Conclusion: Dexamethasone 4 mg has no clinically relevant effect on the duration of sensory block provided by ropivacaine applied to the ulnar nerve., Clinical Trial Registration: DRKS, 00014604; EudraCT, 2018-001221-98., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Purpose: In 2014, FDA released a warning for prescription of doripenem for ventilator-associated bacterial pneumonia due to unsatisfactory clinical cure rates. The present study explores if the observed lack of efficacy might be explained by insufficient target site pharmacokinetics in intensive care patients after two different infusion schemes., Methods: Plasma and bronchoalveolar lavage sampling was performed in 16 intubated patients with pneumonia receiving doripenem either as 1-h or as 4-h infusion. Doripenem concentrations were measured at steady state in plasma over 8 h, bronchoalvoelar lavage was performed in each patient once either after 0 h, 2 h, 4 h or 6 h., Results: In plasma, mean values of C max , T max and AUC 0-8 were 16.87 mg/L, 0.69 h and 52.98 mg/L × h after 1 h of infusion, and 12.94 mg/L, 3.21 h and 70.64 mg/L × h after 4 h of infusion, respectively. While the later t max in plasma was with delay mirrored in the lung, for ELF, much lower concentrations were observed (C max , T max and AUC 0-8 after 1-h infusion of 4.6 mg/L, 2 h and 15.3 mg/L × h and after 4-h infusion 6.9 mg/L, 4 h and 14.8 mg/L × h)., Conclusion: The difference in plasma pharmacokinetics after 1-h and 4-h infusion reflects in the concentration versus time profile in the lung, but concentration at the target site was not only considerably lower but also subject to high inter-individual variability. We hypothesise that insufficient concentrations at the target site might have contributed to the previously described lack of clinical efficacy and confirmed the demand for assessment of target site pharmacokinetics in larger patient collectives.

Background: Caudal blockade, although an important technique of pediatric regional anesthesia, is rarely used in children heavier than 30 kg. This reservation is due to anatomical concerns and lack of pharmacokinetic data. We therefore set out to evaluate, in pediatric patients weighing 30-50 kg, the feasibility of ultrasound-guided caudal blockade and the pharmacokinetics of caudally administered ropivacaine., Methods: Twenty consecutive children were included. General anesthesia was used to ensure a secured airway. For the caudal punctures, we applied the same clinical standards as in smaller children, administering ropivacaine 3.1 mg·ml -1 for a volume of 1 ml·kg -1 via ultrasound guidance. Pharmacokinetic analysis was based on total plasma ropivacaine levels and included maximum concentration (C max ), time to C max (t max ), terminal elimination half-life, area under the concentration-time curve for the 4-h sampling period, apparent total body clearance, and apparent volume of distribution., Results: In all 19 cases of successful puncture, we identified the relevant anatomical structures (sacral cornua, sacral hiatus, dura mater) and verified correct administration of the local anesthetic by visualizing its cranial spread. Surgical blockade was successful in 18 of 20 cases (90%; one puncture was technically not possible and one child received intraoperatively 50 μg fentanyl). The pharmacokinetic profile of the administered ropivacaine 3.1 mg·ml -1 indicated plasma levels within safe ranges in pediatric patients weighing 30-50 kg., Conclusions: Based on our pharmacodynamic and pharmacokinetic results, we suggest that the body weight of 50 kg it is feasible to perform effective and safe caudal blockade in children up to 50 kg body weight., (© 2016 John Wiley & Sons Ltd.)

Background: Previous data have indicated the efficacy of dexmedetomidine as an additive to peripheral regional anaesthesia. There are no pharmacodynamic data regarding the addition of dexmedetomidine to local anaesthetics for perineural administration., Objective: The objective of this study is to assess the dose-dependency of dexmedetomidine when injected with ropivacaine for peripheral nerve blockade., Design: A randomised, triple-blind, controlled study in volunteers., Setting: Department of Clinical Pharmacology, Medical University of Vienna., Participants: Twenty-four volunteers., Interventions: All volunteers received an ulnar nerve block with 22.5 mg ropivacaine alone (R), or mixed with 50 (RD50), 100 (RD100) or 150 μg (RD150) dexmedetomidine., Main Outcome Measures: The primary outcome was the duration of complete sensory block to pinprick and time to complete recovery of pinprick. Secondary outcomes included block success and onset time, motor block, haemodynamic parameters and sedation level., Results: There was a significant dose-dependent (P < 0.0001) increase in the mean duration (SD) of sensory block with dexmedetomidine: R: 8.7 (1.5) h, RD50: 16.4 (4.0) h, RD100: 20.4 (2.8) h and group RD150: 21.2 (1.7) h. Sedation was also enhanced in a dose-dependent (P < 0.001) manner. Two volunteers each receiving 150 μg dexmedetomidine had postblock paraesthesia for 72 h., Conclusion: Dexmedetomidine mixed with ropivacaine produces a dose-dependent prolongation of sensory block and clinically relevant dose-dependent sedation. Dexmedetomidine 100 μg may represent a balance between efficacy and sedation.

Background: Adult meta-analysis has identified dexmedetomidine as a potentially useful adjunct to prolong the duration of peripheral nerve blocks. However, no data exist regarding the adjuvant use of dexmedetomidine in the setting of pediatric peripheral nerve blocks., Methods: Using a prospective, randomized, double-blind design, children (1½-8 years, ASA 1-2) scheduled for outpatient inguinal hernia repair were randomized to receive either an ultrasound-guided ilioinguinal/iliohypogastric nerve block (IINB) with plain ropivacaine 0.197% (Group LA; n = 21) or ropivacaine 0.197% with adjunct dexmedetomidine 0.3 μg·kg(-1) (Group LAD; n = 22). The primary endpoint of the study was time to first postoperative administration of supplemental analgesia (FPASA) triggered by a pain score ≥4 (CHIPPS or NRS scale). Intention-to-treat (ITT) analysis was decided as the primary statistical analysis of the data., Results: The median time to FPASA was prolonged by 88% following the use of adjunct dexmedetomidine (4.0 and 7.6 h in group LA and LAD, respectively) (P = 0.0717). Patients in Group LA displayed a significantly higher number of patients with a CHIPPS score ≥4 in the PACU (7 vs 0; P = 0.0029) as well as a higher incidence of PAED (4 vs 0; P = 0.0485) when compared to patients in Group LAD. No adverse events were recorded in any of the study groups., Conclusions: The use of dexmedetomidine as an adjunct to an IINB resulted in reduced incidences of CHIPPS pain scores ≥4 and PAED scores of ≥11 during early recovery following pediatric inguinal hernia repair. In addition, the use of adjunct dexmedetomidine was associated with a prolongation of the period to first supplemental analgesia demand. The results of the present exploratory study must be viewed as preliminary and need further validation by future larger sized studies and/or meta-analysis., (© 2015 John Wiley & Sons Ltd.)

Background: The relation between the pattern of local anaesthetic (LA) spread and the quality of peripheral nerve block is unclear., Methods: Twenty-one volunteers were randomized to receive a median nerve block with intended circumferential or intended non-circumferential spread of LA. Different predetermined volumes and needle placement techniques were used to produce the different patterns of LA spread. Volumetric, multiplanar 3D ultrasound imaging was performed to evaluate the pattern and extent of LA spread. Sensory block was assessed at predetermined intervals., Results: Complete circumferential spread of LA was achieved in only 67% of cases in the intended circumferential study group and in 33% of cases in the intended non-circumferential group. Block success was similar (90%) and independent of whether circumferential or non-circumferential spread of the LA was achieved. All block failures (n=4) occurred in the intended non-circumferential group with low volumes of LA. The onset of sensory block (independent of group allocation) was faster with circumferential spread of LA [median (IQR) onset time, 15 (8; 20) min] compared with non-circumferential spread of LA [median (IQR) onset time, 20 (15; 30) min]. More LA was used for circumferential blocks [median (IQR) volume of LA 2.8 (1.3; 3.6) vs 1.3 (1.1; 2.4) ml]., Conclusions: Even under optimal conditions, it was not possible to achieve circumferential spread of LA in all intended cases. The success of median nerve block seems to be independent of the pattern of LA spread., Clinical Trial Registration: DRKS 00003826., (© The Author [2014]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: This study was designed to examine the spread of local anesthetic (LA) via magnetic resonance imaging after a standardized ultrasound-guided thoracic paravertebral blockade., Methods: Ten volunteers were enrolled in the study. We performed ultrasound-guided single-shot paravertebral blocks with 20 ml mepivacaine 1% at the thoracic six level at both sides on two consecutive days. After each paravertebral blockade, a magnetic resonance imaging investigation was performed to investigate the three-dimensional spread of the LA. In addition, sensory spread of blockade was evaluated via pinprick testing., Results: The median (interquartile range) cranial and caudal distribution of the LA relative to the thoracic six puncture level was 1.0 (2.5) and 3.0 (0.75) [=4.0 vertebral levels] for the left and 0.5 (1.0) and 3.0 (0.75) [=3.5 vertebral levels] for the right side. Accordingly, the LA distributed more caudally than cranially. The median (interquartile range) number of sensory dermatomes which were affected by the thoracic paravertebral blockade was 9.8 (6.5) for the left and 10.7 (8.8) for the right side. The sensory distribution of thoracic paravertebral blockade was significantly larger compared with the spread of LA., Conclusions: Although the spread of LA was reproducible, the anesthetic effect was unpredictable, even with a standardized ultrasound-guided technique in volunteers. While it can be assumed that approximately 4 vertebral levels are covered by 20 ml LA, the somatic distribution of the thoracic paravertebral blockade remains unpredictable. In a significant percentage, the LA distributes into the epidural space, prevertebral, or to the contralateral side.