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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).)