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.

Perioperative Risk Factors for Intensive Care Unit Readmissions and Mortality After Cardiac Surgery.

OBJECTIVE: The aim of this study was to identify perioperative risk factors associated with intensive care unit readmission and in-hospital death after cardiac surgery. DESIGN: Retrospective analysis using a multivariate regression model to identify independent risk factors for intensive care unit [ICU] readmission and in-hospital mortality. SETTING: The study was carried out in a single tertiary-care hospital. PARTICIPANTS: This was an analysis of 2,789 adult patients. INTERVENTIONS: All patients underwent cardiac surgery and were admitted to the intensive care unit perioperatively at the General Hospital Vienna. MEASUREMENTS AND MAIN RESULTS: Among the 2,789 patients included in the analysis, 167 (6%) were readmitted to the intensive care unit during the same hospital stay. Preoperative risk factors associated with ICU readmission included end-stage renal failure (odds ratio [OR] 2.80, 95% CI: 1.126-6.964), arrhythmia (OR 1.59, 95% CI: 1.019-2.480), chronic obstructive pulmonary disease (OR 1.51, 95% CI: 1.018-2.237), age >80 (OR 2.55, 95% CI: 1.189-5.466), and European System for Cardiac Operative Risk Evaluation II >8 (OR 1.40, 95% CI: 1.013-1.940). Readmitted patients were more likely to die than nonreadmitted patients (OR 5.3, 95% CI: 3.284-8.558). In-hospital mortality in readmitted patients was 19.2%, whereas that in the nonreadmitted study population was 5.1%. CONCLUSION: Preoperative risk assessment is crucial for identifying cardiac surgery patients at risk of ICU readmission and in-hospital death. The potentially modifiable risk factors pinpointed by this study call for the optimization of care before surgery and after ICU discharge.

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.

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.

Generic versus reference listed ropivacaine for peripheral nerve blockade: A randomised, triple-blinded, crossover, equivalence study in volunteers.

BACKGROUND: Generic drug preparations do not require the same degree of scrutiny as the originally licensed preparation before they can be approved for clinical use. The permitted tolerance limits for bioequivalent preparations might be associated with clinically relevant differences for drugs with a narrow therapeutic index, such as local anaesthetics. OBJECTIVE: We compared pharmacokinetic and pharmacodynamic characteristics of generic and reference listed or original preparations of ropivacaine. DESIGN: The current healthy volunteer study used a randomised, triple-blinded, cross-over equivalence design. SETTING: Tertiary university hospital, Medical University of Vienna. SUBJECTS: Healthy male volunteers (N=18) aged 18 to 60 years. INTERVENTIONS: A series of three ultrasound-guided ulnar nerve blocks separated by at least 6 days were carried out on each volunteer. Reference listed ropivacaine (NaropinTM) was used for two blocks and a generic preparation of ropivacaine was used for the other block. Sensory block onset and duration were evaluated using loss of pinprick sensation. MAIN OUTCOME MEASURES: Duration of sensory block was the primary outcome. Secondary outcomes included time-to-onset of sensory block, ropivacaine pharmacokinetics from venous blood samples and pH of the preparations. Equivalence was evaluated using the ratios of means and 90% confidence intervals (CIs) of log transformed data. RESULTS: Equivalence was demonstrated for the primary outcome measure, the duration of sensory block [original : generic ratio 1.01 (90% CI 0.87 to 1.16); P < 0.007] and all pharmacokinetic variables. Equivalence could not be concluded for time-to-onset of sensory block [reference : generic ratio 0.80 (90% CI 0.63 to 1.03); P = 0.27], although reproducibility of this variable using our experimental model was lower than for other variables. The generic preparation was significantly more alkaline [difference 0.06 pH units (95% CI 0.04 to 0.07); P < 0.0001]. CONCLUSION: Our finding of equivalence for sensory block duration and key pharmacokinetic variables between a generic and original preparation of ropivacaine is reassuring. The significant, but small, difference in pH is not clinically important. TRIAL REGISTRATION: EudraCT 2019-003148-61, German Clinical Trials Register (DRKS 00017750).

Brachial plexus block with ultrasound guidance for upper-limb trauma surgery in children: a retrospective cohort study of 565 cases.

BACKGROUND: Upper-limb trauma is a common indication for surgery in children, and general anaesthesia remains the method of choice for these procedures, even though suitable techniques of brachial plexus block are available and fast provision of regional anaesthesia offers a number of distinct advantages. METHODS: A retrospective analysis was performed of the data of a large cohort of children undergoing ultrasound-guided brachial plexus blocks during a 4-yr period at a major trauma centre with a catchment area of 3.5 million. A total of 565 cases were sourced from two independently operating patient documentation systems. Patient data were stratified into age groups with block success as the primary outcome parameter. The influence of age on the incidence of block failure was assessed with logistic regression. RESULTS: The block failure rate was 5.1%, starting at 1.2% in the youngest (0-3 yr), then continuously increasing up to 12.5% in the oldest (15-18 yr) but also smallest group. Age emerged as an independent predictor of block failure with an odds ratio of 1.115 and a 95% confidence interval of 1.014-1.226 (P=0.025). No complications were observed. CONCLUSIONS: In a cohort of children receiving real-world care, with regional blocks performed by a range of anaesthetists with different skill levels, a success rate of 94.9% for upper-limb blocks in children under various levels of sedation was observed. Upper-limb blocks can be performed with high probability of success and an excellent margin of safety; this particularly applies to small children. CLINICAL TRIAL REGISTRATION: NCT03842423.

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.

Risk factors for early bleeding complications after lung transplantation - a retrospective cohort study.

Risk factors for early bleeding complications after lung transplantation are not well described. Our aim was to evaluate coagulation test results and the use of extracorporeal membrane oxygenation as risk factors for bleeding after lung transplantation. We analyzed a single-center cohort of bilateral lung transplants between January 2009 and August 2015. Predictors of severe postoperative bleeding (bleeding requiring reoperation within 48 h of transplantation) were assessed using multivariable logistic regression. The effect of bleeding on survival was assessed using a Cox proportional-hazards model. Twenty-nine (4.5%) of 641 patients experienced severe postoperative bleeding. Postoperative fibrinogen levels (OR = 0.99, 95% CI 0.98-0.995, P = 0.001; per mg/dl increase) and pre- and postoperative use of extracorporeal membrane oxygenation (OR = 14.41% 95% CI 5.4-40.19, P < 0.001 and OR = 4.25, 95% CI 1.0-11.09, P = 0.002, respectively) were associated with an increased risk of severe postoperative bleeding. Severe postoperative bleeding was associated with decreased survival within 60 days after transplantation (adjusted HR = 5.73, 95% CI 2.52-13.02, P < 0.001). Low postoperative fibrinogen levels, and pre- and postoperative use of extracorporeal membrane oxygenation were risk factors for bleeding after lung transplantation.

Prognostic Impact of Persistent Thrombocytopenia During Extracorporeal Membrane Oxygenation: A Retrospective Analysis of Prospectively Collected Data From a Cohort of Patients With Left Ventricular Dysfunction After Cardiac Surgery.

OBJECTIVE: The prognostic impact of thrombocytopenia in patients supported by extracorporeal membrane oxygenation after cardiac surgery is uncertain. We investigated whether thrombocytopenia is independently predictive of poor outcome and describe the incidence and time course of thrombocytopenia in extracorporeal membrane oxygenation patients. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Cardiosurgical ICU at a tertiary referral center. PATIENTS: Three hundred adult patients supported with venoarterial extracorporeal membrane oxygenation for more than 24 hours because of refractory cardiogenic shock after heart surgery between January 2001 and December 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two-way analysis of variance was used to compare the time course of platelet count changes between survivors and nonsurvivors. Using multiple Cox regression with time-dependent covariates, we investigated the impact of platelet count on 90-day mortality. In nonsurvivors, the daily incidence of moderate (< 100 - 50 × 10/L), severe (49 - 20 × 10/L), and very severe (< 20 × 10/L) thrombocytopenia was 50%, 54%, and 7%, respectively. Platelet count had a biphasic temporal pattern with an initial decrease until day 4-5 after the initiation of extracorporeal membrane oxygenation. Although a significant recovery of the platelet count was observed in survivors, a recovery did not occur in nonsurvivors (p = 0.0001). After adjusting for suspected confounders, moderate, severe, and very severe thrombocytopenia were independently associated with 90-day mortality. The highest risk was associated with severe (hazard ratio, 5.9 [2.7-12.6]; p < 0.0001) and very severe thrombocytopenia (hazard ratio, 25.9 [10.7-62.9], p < 0.0001). CONCLUSION: Thrombocytopenia is an independent risk factor for poor outcome in extracorporeal membrane oxygenation patients after cardiac surgery, with persistent severe thrombocytopenia likely reflecting a high degree of physiologic imbalance.

Effect of hemoadsorption during cardiopulmonary bypass surgery - a blinded, randomized, controlled pilot study using a novel adsorbent.

BACKGROUND: Cardiopulmonary bypass (CPB) surgery initiates a systemic inflammatory response, which is associated with postoperative morbidity and mortality. Hemoadsorption (HA) of cytokines may suppress inflammatory responses and improve outcomes. We tested a new sorbent used for HA (CytoSorb™; CytoSorbents Europe GmbH, Berlin, Germany) installed in the CPB circuit on changes of pro- and anti-inflammatory cytokines levels, inflammation markers, and differences in patients' perioperative course. METHODS: In this first pilot trial, 37 blinded patients were undergoing elective CPB surgery at the Medical University of Vienna and were randomly assigned to HA (n = 19) or control group (n = 18). The primary outcome was differences of cytokine levels (IL-1ß, IL-6, IL-18, TNF-α, and IL-10) within the first five postoperative days. We also analyzed whether we can observe any differences in ex vivo lipopolysaccharide (LPS)-induced TNF-α production, a reduction of high-mobility box group 1 (HMGB1), or other inflammatory markers. Additionally, measurements for fluid components, blood products, catecholamine treatment, bioelectrical impedance analysis (BIA), and 30-day mortality were analyzed. RESULTS: We did not find differences in our primary outcome immediately following the HA treatment, although we observed differences for IL-10 24 hours after CPB (HA: median 0.3, interquartile range (IQR) 0-4.5; control: not traceable, P = 0.0347) and 48 hours after CPB (median 0, IQR 0-1.2 versus not traceable, P = 0.0185). We did not find any differences for IL-6 between both groups, and other cytokines were rarely expressed. We found differences in pretreatment levels of HMGB1 (HA: median 0, IQR 0-28.1; control: median 48.6, IQR 12.7-597.3, P = 0.02083) but no significant changes to post-treatment levels. No differences in inflammatory markers, fluid administration, blood substitution, catecholamines, BIA, or 30-day mortality were found. CONCLUSIONS: We did not find any reduction of the pro-inflammatory response in our patients and therefore no changes in their perioperative course. However, IL-10 showed a longer-lasting anti-inflammatory effect. The clinical impact of prolonged IL-10 needs further evaluation. We also observed strong inter-individual differences in cytokine levels; therefore, patients with an exaggerated inflammatory response to CPB need to be identified. The implementation of HA during CPB was feasible. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01879176, registration date: June 7, 2013.

Different Heparin Contents in Prothrombin Complex Concentrates May Impair Blood Clotting in Outpatients With Ventricular Assist Devices Receiving Phenprocoumon.

OBJECTIVES: Prothrombin complex concentrates (PCCs) are used to rapidly reverse anticoagulation by oral vitamin K antagonists. They differ in the content of clotting factors, endogenous anticoagulants, and heparin. The authors hypothesized that PCCs' specific heparin content may compromise the hemostatic effect. DESIGN: Prospective ex-vivo investigation. SETTING: University hospital. PARTICIPANTS: Venous blood samples were obtained from 8 patients with implanted ventricular assist devices who also were receiving phenprocoumon. INTERVENTIONS: Four different 4-factor PCCs were added to patient blood to attain a calculated increase in prothrombin time by 20%, 40%, and 60% greater than baseline in paired experiments. MEASUREMENTS AND MAIN RESULTS: Clotting was measured using thromboelastometry and endogenous thrombin potential. Two heparin-containing PCCs prolonged the clotting times in a concentration-dependent manner compared with baseline (p<0.01) and compared with PCCs containing significantly less or no heparin (p<0.01). The PCCs containing low or no heparin enhanced the area under the curve of thrombin generation and peak thrombin several fold relative to the heparin-containing PCCs (p<0.01). One of the PCCs containing heparin even decreased peak thrombin generation by ~90% compared with baseline (p<0.01). PCC with low or no heparin shortened the lag phase (p<0.01), whereas 1 heparin containing PCC prolonged the lag phase by 66% (p<0.01). CONCLUSIONS: Physicians should be aware of the differences in heparin contents. Extrapolation of results from one agent to other PCC preparations may be difficult. Patients with an implanted left ventricular assist device and anticoagulated with vitamin-K antagonists could benefit from the use of PCC with low heparin content when surgery or bleeding requires emergency reversal. Further clinical studies are warranted.

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.

Delayed volume resuscitation during initial management of ruptured abdominal aortic aneurysm.

OBJECTIVE: In acute traumatic bleeding, permissive arterial hypotension with delayed volume resuscitation is an established lifesaving concept as abridge to surgical control. This study investigated whether preoperatively administered volume also correlated inversely with survival after ruptured abdominal aortic aneurysm (rAAA). METHODS: This retrospective study analyzed prospectively collected and validated data of a consecutive cohort of patients with rAAAs (January 2001 to December 2010). Generally, fluid resuscitation was guided clinically by the patient's blood pressure and consciousness. All intravenous fluids (crystalloids, colloids, and blood products) administered before aortic clamping or endovascular sealing were abstracted from paramedic and anesthesia documentation and normalized to speed of administration (liters per hour). Logistic regression modeling, adjusted for suspected confounding covariates, was used to investigate whether total volume was independently associated with risk of death within 30 days of rAAA repair. RESULTS: A total of 248 patients with rAAAs were analyzed, of whom 237 (96%) underwent open repair. A median of 0.91 L of total volume per hour (interquartile range, 0.54-1.50 L/h) had been administered preoperatively to these patients. The postoperative 30-day mortality rate was 15.3% (38 deaths). The preoperative rate of fluid infusion correlated with 30-day mortality after adjustment for confounding factors, and the association persisted robustly through sensitivity analyses: each additional liter per hour increased the odds of perioperative death by 1.57-fold (95% confidence interval, 1.06-2.33; P = .026). CONCLUSIONS: Aggressive volume resuscitation of patients with rAAAs before proximal aortic control predicted an increased perioperative risk of death, which was independent of systolic blood pressure. Therefore, volume resuscitation should be delayed until surgical control of bleeding is achieved.

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.

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.

ADV6209 for Premedication in Pediatric Anesthesia: A Double-Blinded, Randomized Controlled Trial.

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.

Ultrasound-guided epidural anesthesia and sedation for open transvesical Cohen ureteric reimplantation surgery in 20 consecutive children: a prospective case series and proof-of-concept study.

BACKGROUND: Epidural anesthesia is usually combined with general anesthesia (GA) for children undergoing sub-umbilical surgery and GA in children is associated with a potential for respiratory events. Aiming to reduce airway manipulation and the use of GA drugs, we designed a study of transvesical Cohen ureteteric reimplantion under epidural anesthesia in sedated, spontaneously breathing children. METHODS: We enrolled 20 children (3-83 months, 6.3-25.0 kg) scheduled for open transvesical abdominal surgery with Pfannenstiel incision. Sedation was followed by ultrasound-guided epidural anesthesia. Increases in heart rate by >15% and or patient movements upon skin incision were rated as block deficiencies. Intubation equipment for advanced airway management was kept on standby. The primary study endpoint was successful blockade, meaning that no sequential airway management was required for the spontaneous breathing patients during surgery. Secondary endpoints included any use of fentanyl/propofol intraoperatively and of postoperative analgesics in the recovery room. RESULTS: All 20 blocks were successful, with no block deficiencies upon skin incision, no need for sequential airway management, and stable SpO2 levels (97-100%). Surgery took a median of 120.5 minutes (IQR: 89.3-136.5) and included one bolus of fentanyl in one patient 120 minutes into a protracted operation. No more systemic analgesia had to be provided in the recovery room. CONCLUSIONS: Sedation and epidural anesthesia emerged as a useful alternative to GA from our consecutive case series.

A Prospective Observational Study on Multiplate®-, ROTEM®- and Thrombin Generation Examinations Before and Early After Implantation of a Left Ventricular Assist Device (LVAD).

Background: Heart failure patients are frequently on coagulation-active medications before LVAD implantation and perioperative bleeding is a frequent complication after left ventricular assist device (LVAD) implantation. The role of point-of-care coagulation tests in assessing bleeding risk for LVAD implantation and the early postoperative time course of these tests is not well established. Methods: We prospectively enrolled 25 patients with terminal heart failure undergoing LVAD implantation. Study related TRAP-, ASPI- and ADP- tests of Multiplate® platelet aggregometry, ROTEM® rotational thromboelastometry (INTEM, EXTEM, FIBTEM), thrombin generation assay and conventional laboratory studies were measured at 11 predefined time-points during the first 21 postoperative days. We examined if preoperative TRAP-, ASPI-, ADP- and ROTEM values are correlated with estimated total blood loss (primary outcome parameter) during the first 21 days after LVAD implantation and compared the baseline values of these measurements between patients with a bleeding event to those without. We performed Spearman's correlation and non-parametric tests for paired and non-paired comparisons. Results: 7 out of 25 (28%) patients experienced a bleeding event of which 4 required surgical revision. Of the preoperatively performed measurements the TRAP test [Spearman's Rho (ρ) = -0.5, p = 0.01], INTEM CFT (ρ = 0.72, p < 0.001), INTEM alpha (-0.7, p < 0.001), EXTEM MCF (ρ = -0.63; p < 0.001), EXTEM alpha (ρ = -0.67; p < 0.001), FIBTEM MCF (ρ = -0.41; p = 0.042), Fibrinogen (Clauss) (ρ = -0.5; p = 0.011), Anti-thrombin activity (ρ = -0.49; p = 0.013) and platelet count (ρ = -0.42; p = 0.034) were significantly correlated to total blood loss. Patients undergoing a surgical bleeding revision had significantly reduced values in TRAP-[31.5 IQR (17.25-43.5U) vs. 69 IQR (52.5-87U); p = 0.004], ASPI-[16.5 IQR (5.5-35.7U) vs. 39 IQR (24.5-62.5U); p = 0.038], ADP-[30 IQR (22-69U) vs. 12.5 IQR (8.7-21.5U); p = 0.01], EXTEM MCF-[63 IQR (57.7-63.7) vs. 67 IQR (65-75.5); p = 0.019] and EXTEM alpha [74 IQR (68.75-74) vs. 79 IQR (78-80.5); p = 0.002] values before LVAD implantation. Conclusion: Multiplate® and ROTEM® measurements before LVAD implantation may identify LVAD candidates with platelet dysfunction and alterations of the primary hemostasis and could guide anesthetists and intensive care practitioners in bleeding risk stratification and in the perioperative clinical management.