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. Editor’s Perspective: What We Already Know about This Topic: What This Article Tells Us That Is New:

We have recently described a bi-directional bulk flow of cerebrospinal fluid (CSF) (coined ‘the CSF rebound mechanism’) after the use of high-volume caudal block in infants, which may explain the secondary longitudinal spread of the block. If important the initial cephalad transfer of CSF should be of such a magnitude that it would cause a transient reduction in cerebral blood flow (CBF) and cerebral oxygenation. The primary aim of this observational study was to delineate the magnitude of the reduction of CBF velocity (CBFV) associated with high-volume caudal block in infants. Ultrasound Doppler measurements of CBFV in the middle cerebral artery and also haemodynamic parameters and cerebral regional oxygenation (C_RSO₂) were followed during 5 min after the initial caudal injection (1.5 ml kg⁻¹, ropivacaine 0.2%) in 12 infants <3 months of age. The caudal injection was associated with immediate and major reductions in CBFV indicating a concomitant reduction in CBF. A significant reduction of cerebral regional oxygenation C_RSO₂ was also observed. Systemic haemodynamic parameters were unchanged during the observation period. High-volume caudal block causes a biphasic change in CBFV and was also found to affect cerebral oxygenation. Our findings lend further support to ‘the CSF rebound mechanism’ for secondary spread of high-volume caudal block.

Zusammenfassung: Hintergrund: Schwangerschaft und Schmerzen unterschiedlicher Herkunft sind eine ungünstige Kombination, die alle BehandlerInnen vor besondere Herausforderungen stellt. Schmerzen beeinflussen die Homöostase des Menschen negativ. Compliance der Patientin und fundiertes Wissen über Fetotoxizität und Teratogenität von Analgetika sind nötig, um die Balance zwischen Therapie der Mutter und Sicherheit des Ungeborenen zu wahren. Ziel der Arbeit: ExpertInnen verschiedener Disziplinen, die mit der Betreuung von schwangeren Schmerzpatientinnen betraut sind, haben sich zusammengeschlossen, um medikamentöse und nichtmedikamentöse Therapiekonzepte zu erstellen, mit dem Ziel, eine suffiziente Analgesie von schwangeren Schmerzpatientinnen zu ermöglichen. Material und Methode: Relevante Fragestellungen wurden durch ExpertInnen formuliert und einer Literatursuche unterzogen. Kombiniert mit weiteren nationalen und internationalen Empfehlungen wurden Behandlungskonzepte entwickelt, interdisziplinär diskutiert und im Anschluss Kernaussagen erstellt, die mit Empfehlungsgraden abgestuft wurden. Ergebnisse: Abhängig vom Trimenon können bei Schmerzen Paracetamol, Ibuprofen, Diclofenac, Metamizol und Opioide wohlüberlegt verabreicht werden, besondere Vorsicht ist bei nichtsteroidalen Antirheumatika (NSAR) im letzten Trimenon geboten. COX-2-Hemmer werden nicht empfohlen. Bei neuropathischen Schmerzen gelten Amitriptylin, Duloxetin, Venlafaxin als sicher. Bei starker Migräne kann Sumatriptan zum Einsatz kommen. Nichtmedikamentöse Therapien wie transkutane elektrische Nervenstimulation (TENS-Therapie), Kinesio-Tapes und Akupunktur gelten als sicher. Lymphdrainagen werden bei Ödemen empfohlen, sofern sie nicht durch eine Präeklampsie bedingt sind. Schlussfolgerung: Die Therapie sollte mit einer nichtmedikamentösen Behandlung beginnen und eskalierend in einer Kombination aus medikamentösen und nichtmedikamentösen Konzepten enden.

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.

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.