Liposomal Bupivacaine for Peripheral Nerve Blockade: A Randomized, Controlled, Crossover, Triple-blinded Pharmacodynamic Study in Volunteers.

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.

Geo-economic variations in epidemiology, ventilation management and outcome of patients receiving intraoperative ventilation during general anesthesia- posthoc analysis of an observational study in 29 countries.

BACKGROUND: The aim of this analysis is to determine geo-economic variations in epidemiology, ventilator settings and outcome in patients receiving general anesthesia for surgery. METHODS: Posthoc analysis of a worldwide study in 29 countries. Lower and upper middle-income countries (LMIC and UMIC), and high-income countries (HIC) were compared. The coprimary endpoint was the risk for and incidence of postoperative pulmonary complications (PPC); secondary endpoints were intraoperative ventilator settings, intraoperative complications, hospital stay and mortality. RESULTS: Of 9864 patients, 4% originated from LMIC, 11% from UMIC and 85% from HIC. The ARISCAT score was 17.5 [15.0-26.0] in LMIC, 16.0 [3.0-27.0] in UMIC and 15.0 [3.0-26.0] in HIC (P = .003). The incidence of PPC was 9.0% in LMIC, 3.2% in UMIC and 2.5% in HIC (P < .001). Median tidal volume in ml kg- 1 predicted bodyweight (PBW) was 8.6 [7.7-9.7] in LMIC, 8.4 [7.6-9.5] in UMIC and 8.1 [7.2-9.1] in HIC (P < .001). Median positive end-expiratory pressure in cmH2O was 3.3 [2.0-5.0]) in LMIC, 4.0 [3.0-5.0] in UMIC and 5.0 [3.0-5.0] in HIC (P < .001). Median driving pressure in cmH2O was 14.0 [11.5-18.0] in LMIC, 13.5 [11.0-16.0] in UMIC and 12.0 [10.0-15.0] in HIC (P < .001). Median fraction of inspired oxygen in % was 75 [50-80] in LMIC, 50 [50-63] in UMIC and 53 [45-70] in HIC (P < .001). Intraoperative complications occurred in 25.9% in LMIC, in 18.7% in UMIC and in 37.1% in HIC (P < .001). Hospital mortality was 0.0% in LMIC, 1.3% in UMIC and 0.6% in HIC (P = .009). CONCLUSION: The risk for and incidence of PPC is higher in LMIC than in UMIC and HIC. Ventilation management could be improved in LMIC and UMIC. TRIAL REGISTRATION: Clinicaltrials.gov , identifier: NCT01601223.

A prospective observational study on the feasibility of subumbilical laparoscopic procedures under epidural anesthesia in sedated spontaneously breathing infants with a natural airway.

BACKGROUND: Laparoscopic procedures are usually performed under general anesthesia with a secured airway including endotracheal intubation or supraglottic airways. AIMS: This is a prospective study of the feasibility of subumbilical laparoscopic procedures under epidural anesthesia in sedated, spontaneous breathing infants with a natural airway. METHODS: We consecutively enrolled 20 children <3 years old with nonpalpable testes scheduled for diagnostic laparoscopy with or without an ensuing orchidopexy, inguinal revision, or Fowler-Stephens maneuver. Inhalational induction for venous access was followed by sedation with propofol and ultrasound-guided single-shot epidural anesthesia via the caudal or thoracolumbar approach using 1.0 or 0.5 ml kg-1 ropivacaine 0.38%, respectively. The primary outcome measure was block success, defined as no increase in heart rate by >15% or other indicators of pain upon skin incision. RESULTS: Of the 20 children (median age: 10 months; IQR: 8.3-12), 17 (85%) were anesthetized through a caudal and 3 (15%) through a direct thoracolumbar epidural, 18 (90%) underwent a surgical procedure and 2 (10%) diagnostic laparoscopy only. Five patients (25%) received block augmentation using an intravenous bolus of fentanyl (median dose: 0.9 µg kg-1 ; IQR: 0.8-0.95) after the initial prick test and before skin incision. There was no additional need for systemic pain therapy in the operating theater or recovery room. No events of respiratory failure or aspiration were observed. CONCLUSIONS: In experienced hands, given our success rate of 100%, epidural anesthesia performed in sedated spontaneously breathing infants with a natural airway can be an alternative strategy for subumbilical laparoscopic procedures.

The Association of Intraoperative driving pressure with postoperative pulmonary complications in open versus closed abdominal surgery patients - a posthoc propensity score-weighted cohort analysis of the LAS VEGAS study.

BACKGROUND: It is uncertain whether the association of the intraoperative driving pressure (ΔP) with postoperative pulmonary complications (PPCs) depends on the surgical approach during abdominal surgery. Our primary objective was to determine and compare the association of time-weighted average ΔP (ΔPTW) with PPCs. We also tested the association of ΔPTW with intraoperative adverse events. METHODS: Posthoc retrospective propensity score-weighted cohort analysis of patients undergoing open or closed abdominal surgery in the 'Local ASsessment of Ventilatory management during General Anaesthesia for Surgery' (LAS VEGAS) study, that included patients in 146 hospitals across 29 countries. The primary endpoint was a composite of PPCs. The secondary endpoint was a composite of intraoperative adverse events. RESULTS: The analysis included 1128 and 906 patients undergoing open or closed abdominal surgery, respectively. The PPC rate was 5%. ΔP was lower in open abdominal surgery patients, but ΔPTW was not different between groups. The association of ΔPTW with PPCs was significant in both groups and had a higher risk ratio in closed compared to open abdominal surgery patients (1.11 [95%CI 1.10 to 1.20], P <  0.001 versus 1.05 [95%CI 1.05 to 1.05], P <  0.001; risk difference 0.05 [95%CI 0.04 to 0.06], P <  0.001). The association of ΔPTW with intraoperative adverse events was also significant in both groups but had higher odds ratio in closed compared to open abdominal surgery patients (1.13 [95%CI 1.12- to 1.14], P <  0.001 versus 1.07 [95%CI 1.05 to 1.10], P <  0.001; risk difference 0.05 [95%CI 0.030.07], P <  0.001). CONCLUSIONS: ΔP is associated with PPC and intraoperative adverse events in abdominal surgery, both in open and closed abdominal surgery. TRIAL REGISTRATION: LAS VEGAS was registered at clinicaltrials.gov (trial identifier NCT01601223 ).

Epidural versus general anesthesia for open pyloromyotomy in infants: A retrospective observational study.

BACKGROUND: Thoracic epidural anesthesia for open infantile hypertrophic pyloric stenosis surgery is a controversial issue in the presence of little comparative data. AIMS: To compare this approach to general anesthesia for desaturation events (≤90% oxygen saturation) and absolute values of minimal oxygen saturation, minimal heart frequency, operating-room occupancy time, and durations of surgery in a retrospective study design. METHODS: Data were retrieved for patients with infantile hypertrophic pyloric stenosis managed by thoracic epidurals under sedation or general anesthesia with rapid sequence induction between 01/2007 and 12/2017. Oxygen saturation and heart rate were analyzed over eight 5-minutes intervals relative to the start of anesthesia / sedation (four-time intervals) and before discharge of the patient from the operating room (four-time intervals). Fisher's exact tests and mixed model two-way analysis of variance for repeated measures were employed for intergroup comparisons. RESULTS: The epidural and general anesthesia groups included 69 and 32 evaluable infants, respectively. Patients managed under epidural anesthesia had cumulatively higher minimimal mean (SD) oxygen saturation values (98.2 [2.6] % versus 96.6 [5.2] %, p < 0.001) and lower minimal mean (SD) heart rate values (127.9 [15.0] beats per minute versus 140.7 [17.2] beats per minute, p < 0.001) over time. Similarly, the frequency of desaturation events (defined as ≤90% oxygen saturation) was significantly lower for these patients during the period of 5 minutes after induction of sedation or general anesthesia (odds ratio 7.4 [2.1-25.9]; p = 0.001) and during the subsequent period of five minutes (odds ratio 6.2 [1.1-33.9]; p = 0.031). One case of prolonged respiratory weaning was observed in the general anesthesia group. The mean (SD) operating-room occupancy was 61.9 (16.6) minutes for the epidural anesthesia group versus 73.3 (22.2) minutes for the general anesthesia group (p = 0.005) as a result of shorter emergence from sedation. CONCLUSIONS: In our series, maintaining spontaneous breathing with minimal airway manipulation in patients undergoing open repair of hypertrophic pyloric stenosis under single-shot epidural anesthesia resulted in fewer desaturation events ≤90% than general anesthesia. In addition, this approach seems to result in shorter turnover times in the operating room.

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study.

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients. OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference. DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries. MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation. RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT. CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223.

The effects of preoperative moderate to severe anaemia on length of hospital stay: A propensity score-matched analysis in non-cardiac surgery patients.

BACKGROUND: Anaemia is frequently recorded during preoperative screening and has been suggested to affect outcomes after surgery negatively. OBJECTIVES: The objectives were to assess the frequency of moderate to severe anaemia and its association with length of hospital stay. DESIGN: Post hoc analysis of the international observational prospective 'Local ASsessment of VEntilatory management during General Anaesthesia for Surgery' (LAS VEGAS) study. PATIENTS AND SETTING: The current analysis included adult patients requiring general anaesthesia for non-cardiac surgery. Preoperative anaemia was defined as a haemoglobin concentration of 11 g dl-1 or lower, thus including moderate and severe anaemia according to World Health Organisation criteria. MAIN OUTCOME MEASURES: The primary outcome was length of hospital stay. Secondary outcomes included hospital mortality, intra-operative adverse events and postoperative pulmonary complications (PPCs). RESULTS: Haemoglobin concentrations were available for 8264 of 9864 patients. Preoperative moderate to severe anaemia was present in 7.7% of patients. Multivariable analysis showed that preoperative moderate to severe anaemia was associated with an increased length of hospital stay with a mean difference of 1.3 ((95% CI 0.8 to 1.8) days; P < .001). In the propensity-matched analysis, this association remained present, median 4.0 [IQR 1.0 to 5.0] vs. 2.0 [IQR 0.0 to 5.0] days, P = .001. Multivariable analysis showed an increased in-hospital mortality (OR 2.9 (95% CI 1.1 to 7.5); P  = .029), and higher incidences of intra-operative hypotension (36.3 vs. 25.3%; P < .001) and PPCs (17.1 vs. 10.5%; P = .001) in moderately to severely anaemic patients. However, this was not confirmed in the propensity score-matched analysis. CONCLUSIONS: In this international cohort of non-cardiac surgical patients, preoperative moderate to severe anaemia was associated with a longer duration of hospital stay but not increased intra-operative complications, PPCs or in-hospital mortality. TRIAL REGISTRATION: The LAS VEGAS study was registered at Clinicaltrials.gov, NCT01601223.

Brainwave entrainment to minimise sedative drug doses in paediatric surgery: a randomised controlled trial.

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-1vs 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.

Intraoperative ventilator settings and their association with postoperative pulmonary complications in neurosurgical patients: post-hoc analysis of LAS VEGAS study.

BACKGROUND: Limited information is available regarding intraoperative ventilator settings and the incidence of postoperative pulmonary complications (PPCs) in patients undergoing neurosurgical procedures. The aim of this post-hoc analysis of the 'Multicentre Local ASsessment of VEntilatory management during General Anaesthesia for Surgery' (LAS VEGAS) study was to examine the ventilator settings of patients undergoing neurosurgical procedures, and to explore the association between perioperative variables and the development of PPCs in neurosurgical patients. METHODS: Post-hoc analysis of LAS VEGAS study, restricted to patients undergoing neurosurgery. Patients were stratified into groups based on the type of surgery (brain and spine), the occurrence of PPCs and the assess respiratory risk in surgical patients in Catalonia (ARISCAT) score risk for PPCs. RESULTS: Seven hundred eighty-four patients were included in the analysis; 408 patients (52%) underwent spine surgery and 376 patients (48%) brain surgery. Median tidal volume (VT) was 8 ml [Interquartile Range, IQR = 7.3-9] per predicted body weight; median positive end-expiratory pressure (PEEP) was 5 [3 to 5] cmH20. Planned recruitment manoeuvres were used in the 6.9% of patients. No differences in ventilator settings were found among the sub-groups. PPCs occurred in 81 patients (10.3%). Duration of anaesthesia (odds ratio, 1.295 [95% confidence interval 1.067 to 1.572]; p = 0.009) and higher age for the brain group (odds ratio, 0.000 [0.000 to 0.189]; p = 0.031), but not intraoperative ventilator settings were independently associated with development of PPCs. CONCLUSIONS: Neurosurgical patients are ventilated with low VT and low PEEP, while recruitment manoeuvres are seldom applied. Intraoperative ventilator settings are not associated with PPCs.

The LAS VEGAS risk score for prediction of postoperative pulmonary complications: An observational study.

BACKGROUND: Currently used pre-operative prediction scores for postoperative pulmonary complications (PPCs) use patient data and expected surgery characteristics exclusively. However, intra-operative events are also associated with the development of PPCs. OBJECTIVE: We aimed to develop a new prediction score for PPCs that uses both pre-operative and intra-operative data. DESIGN: This is a secondary analysis of the LAS VEGAS study, a large international, multicentre, prospective study. SETTINGS: A total of 146 hospitals across 29 countries. PATIENTS: Adult patients requiring intra-operative ventilation during general anaesthesia for surgery. INTERVENTIONS: The cohort was randomly divided into a development subsample to construct a predictive model, and a subsample for validation. MAIN OUTCOME MEASURES: Prediction performance of developed models for PPCs. RESULTS: Of the 6063 patients analysed, 10.9% developed at least one PPC. Regression modelling identified 13 independent risk factors for PPCs: six patient characteristics [higher age, higher American Society of Anesthesiology (ASA) physical score, pre-operative anaemia, pre-operative lower SpO2 and a history of active cancer or obstructive sleep apnoea], two procedure-related features (urgent or emergency surgery and surgery lasting ≥ 1 h), and five intra-operative events [use of an airway other than a supraglottic device, the use of intravenous anaesthetic agents along with volatile agents (balanced anaesthesia), intra-operative desaturation, higher levels of positive end-expiratory pressures > 3 cmH2O and use of vasopressors]. The area under the receiver operating characteristic curve of the LAS VEGAS risk score for prediction of PPCs was 0.78 [95% confidence interval (95% CI), 0.76 to 0.80] for the development subsample and 0.72 (95% CI, 0.69 to 0.76) for the validation subsample. CONCLUSION: The LAS VEGAS risk score including 13 peri-operative characteristics has a moderate discriminative ability for prediction of PPCs. External validation is needed before use in clinical practice. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, number NCT01601223.

Platelets Toll-like receptor-4 in Crohns disease.

BACKGROUND: Platelets are activated in Crohn's disease (CD) and interplay with leukocytes. Engagement of Toll-like receptor-4 (TLR-4), which is expressed in human platelets, may be involved in crosstalks between platelets and leukocytes leading to their mutual activation for host defense. MATERIALS AND METHODS: Human neutrophil peptides (HNPs), lipoprotein binding peptides, and sCD14 were determined by enzyme-linked immunosorbent assays in 42 patients with active CD, in 43 patients with CD in remission, and in 30 healthy individuals. Neutrophil-platelet aggregates and binding of the TLR-4 monoclonal antibody to platelets were determined by flow cytometry. RESULTS: Levels of HNPs were higher in patients with CD than in controls (P = 0.0003 vs. active CD and P = 0.01 vs. CD in remission). Likewise, neutrophils with adhering platelets were higher in patients with active CD than in controls (P = 0.004). Binding of the TLR-4 antibody in patients with active CD was similar to that in controls, while patients in remission had significantly higher binding capacities (P = 0.59 and P = 0.003). Incubation of plasma from patients with active disease or patients in remission with platelets from healthy controls confirmed lower binding of the TLR-4 antibody in the presence of plasma from active diseased patients compared to controls (P = 0.039), possibly due to high levels of lipopolysaccharides, as suggested by high levels of sCD14 and lipoprotein binding protein. CONCLUSION: Our study indicates involvement of platelet TLR-4 in enhancing the secretion of antimicrobial peptides from neutrophils. While platelet aggregation can be due to a variety of mechanisms in inflammatory disease, the mutual activation of platelets and neutrophils may augment host defense.

Protective versus Conventional Ventilation for Surgery: A Systematic Review and Individual Patient Data Meta-analysis.

BACKGROUND: Recent studies show that intraoperative mechanical ventilation using low tidal volumes (VT) can prevent postoperative pulmonary complications (PPCs). The aim of this individual patient data meta-analysis is to evaluate the individual associations between VT size and positive end-expiratory pressure (PEEP) level and occurrence of PPC. METHODS: Randomized controlled trials comparing protective ventilation (low VT with or without high levels of PEEP) and conventional ventilation (high VT with low PEEP) in patients undergoing general surgery. The primary outcome was development of PPC. Predefined prognostic factors were tested using multivariate logistic regression. RESULTS: Fifteen randomized controlled trials were included (2,127 patients). There were 97 cases of PPC in 1,118 patients (8.7%) assigned to protective ventilation and 148 cases in 1,009 patients (14.7%) assigned to conventional ventilation (adjusted relative risk, 0.64; 95% CI, 0.46 to 0.88; P < 0.01). There were 85 cases of PPC in 957 patients (8.9%) assigned to ventilation with low VT and high PEEP levels and 63 cases in 525 patients (12%) assigned to ventilation with low VT and low PEEP levels (adjusted relative risk, 0.93; 95% CI, 0.64 to 1.37; P = 0.72). A dose-response relationship was found between the appearance of PPC and VT size (R2 = 0.39) but not between the appearance of PPC and PEEP level (R2 = 0.08). CONCLUSIONS: These data support the beneficial effects of ventilation with use of low VT in patients undergoing surgery. Further trials are necessary to define the role of intraoperative higher PEEP to prevent PPC during nonopen abdominal surgery.

Iron deficiency alters megakaryopoiesis and platelet phenotype independent of thrombopoietin.

Iron deficiency is a common cause of reactive thrombocytosis, however, the exact pathways have not been revealed. Here we aimed to study the mechanisms behind iron deficiency-induced thrombocytosis. Within few weeks, iron-depleted diet caused iron deficiency in young Sprague-Dawley rats, as reflected by a drop in hemoglobin, mean corpuscular volume, hepatic iron content and hepcidin mRNA in the liver. Thrombocytosis established in parallel. Moreover, platelets produced in iron deficient animals displayed a higher mean platelet volume and increased aggregation. Bone marrow studies revealed subtle alterations that are suggestive of expansion of megakaryocyte progenitors, an increase in megakaryocyte ploidy and accelerated megakaryocyte differentiation. Iron deficiency did not alter the production of hematopoietic growth factors such as thrombopoietin, interleukin 6 or interleukin 11. Megakaryocytic cell lines grown in iron-depleted conditions exhibited reduced proliferation but increased ploidy and cell size. Our data suggest that iron deficiency increases megakaryopoietic differentiation and alters platelet phenotype without changes in megakaryocyte growth factors, specifically TPO. Iron deficiency-induced thrombocytosis may have evolved to maintain or increase the coagulation capacity in conditions with chronic bleeding.

The impact of biological sex in peripheral nerve blockade: A prospective pharmacodynamic, pharmacokinetic and morphometric study in volunteers.

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.

Upgraded ESRF BM29 beamline for SAXS on macromolecules in solution.

Small-angle X-ray scattering (SAXS) measurements of proteins in solution are becoming increasingly popular with biochemists and structural biologists owing to the presence of dedicated high-throughput beamlines at synchrotron sources. As part of the ESRF Upgrade program a dedicated instrument for performing SAXS from biological macromolecules in solution (BioSAXS) has been installed at the renovated BM29 location. The optics hutch has been equipped with new optical components of which the two principal elements are a fixed-exit double multilayer monochromator and a 1.1 m-long toroidal mirror. These new dedicated optics give improved beam characteristics (compared with the previous set-up on ID14-3) regarding the energy tunability, flux and focusing at the detector plane leading to reduced parasitic scattering and an extended s-range. User experiments on the beamline have been successfully carried out since June 2012. A description of the new BioSAXS beamline and the set-up characteristics are presented together with examples of obtained data.

Ultrasound-Guided Dorsal Penile Nerve Block in Children: An Anatomical-Based Observational Study of a New Anesthesia Technique.

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.

Sex differences in pediatric caudal epidural anesthesia under sedation without primary airway instrumentation.

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.

Perioperative sedation requirements of infants aged 0 to 3 months subjected to lower-body surgery under caudal blockade: a randomized controlled trial.

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.

Ad-hoc preoperative management and respiratory events in pediatric anesthesia during the first COVID-19 lockdown-an observational cohort study.

BACKGROUND: Early pre-anesthetic management for surgery is aimed at identifying risk factors, which notably in children are mostly airway related. The first COVID-19 lockdown opened a unique 'window of opportunity' to study what impact an ad-hoc management strategy would bring to bear on intraoperative respiratory events. METHODS: In this observational cohort study we included all patients with an American Society of Anesthesiology (ASA) Physical Status of I or II, aged 0 to ≤18 years, who underwent elective surgery at our center during the first national COVID-19 lockdown (March 15th to May 31st, 2020) and all analogue cases during the same calendar period of 2017-2019. The primary outcome parameter was a drop in peripheral oxygen saturation (SpO2) below 90% during anesthesia management. The study is completed and registered with the German Clinical Trials Register, DRKS00024128. RESULTS: Given 125 of 796 evaluable cases during the early 2020 lockdown, significant differences over the years did not emerge for the primary outcome or event counts (p>0.05). Events were exceedingly rare even under general anesthesia (n = 3) and non-existent under regional anesthesia (apart from block failures: n = 4). Regression analysis for SpO2 events <90% yielded no significant difference for ad-hoc vs standard preoperative management (p = 0.367) but more events based on younger patients (p = 0.007), endotracheal intubation (p = 0.007), and bronchopulmonary procedures (p = 0.001). CONCLUSIONS: Early assessment may not add to the safety of pediatric anesthesia. As a potential caveat for other centers, the high rate of anesthesia without airway manipulation at our center may contribute to our low rate of respiratory events.