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:

The past two decades have seen remarkable progress in pediatric regional anesthesia. Significant efforts have been made to develop central and peripheral techniques that are both practicable and reliable, with increasing success and very low complication rates driving a growing appreciation for this subspecialty. Regional anesthesia can be used to optimize perioperative pain control, to avoid mechanical ventilation, and to take advantage of favorable immunomodulatory and gastrointestinal side effects in children. Implementing a broad spectrum of these techniques will require specialized knowledge of anatomic structures, experience to select appropriate techniques for specific surgical procedures, and considerable hand skills to execute these techniques. This review has been written to summarize state-of-the-art information about all relevant aspects of pediatric regional anesthesia and to provide a practical approach to how regional anesthesia in children can be implemented in daily clinical practice.

Addition of nonopioid analgesic drugs reduces pain and opioid requirements in acute low back pain. In noncancer chronic low back pain (CLBP), the efficacy of a combined regimen to reduce breakthrough pain has not been proven so far. Evaluation of the effects of intravenous (i.v.) nonopioid analgesic drugs on pain intensity and lumbar mobility in CLBP patients on chronic opioid therapy. Randomised, placebo-controlled, double blinded, crossover study. Vienna General Hospital, Austria, from December 2002 to May 2004. Thirty-six adults with CLBP on chronic opioid therapy. Inclusion criteria are as follows: American Society of Anesthesiologists' physical status less than 3, visual analogue scale (VAS) more than 4 and no known allergy to any of the used drugs. After written informed consent and VAS assessment, any oral nonopioid analgesic drug (NSAIDs, metamizol, paracetamol) was replaced by placebo 10 days before the first test infusion as a washout period. Coanalgesics (anticonvulsants, antidepressants) were maintained. Each patient received randomly four i.v. test infusions of diclofenac 75 mg (and orphenadrine 30 mg), parecoxib 40 mg, paracetamol 1 g and isotonic saline. A washout time of 72 h was allowed between each infusion. Primary outcome was as follows: VAS pain intensity (0 to 100 mm) at inclusion, before and within 30 min after infusion. Secondary outcomes were as follows: Roland-Morris questionnaire, McGill pain questionnaire and a test panel of physical functioning for spinal mobility, muscular endurance, balance and coordination. The differences in means of the above assessments among the groups were analysed. We found an improvement in VAS from the day of inclusion to the day of each appointment. We observed no improvement in pain intensity (VAS) or in any of the physical functioning tests immediately before versus after administration of the four i.v. drugs. Reductions in sensory, affective and cognitive dimensions of the McGill pain questionnaire were statistically significant in the diclofenac group. A trend of McGill pain questionnaire improvement existed in the other groups. The present data show that the anticipation of an i.v. infusion of nonopioid analgesic drug improves VAS significantly, probably through expectation-related mechanisms. However, single dose i.v. infusions of nonopioid analgesic drugs fail to improve pain intensity and spinal mobility in CLBP patients on chronic opioid treatment, even immediately after the infusion.

Accurate temperature measurement is crucial for the perioperative management of pediatric patients, and non-invasive thermometry is necessary when invasive methods are infeasible. A prospective observational study was conducted on 57 patients undergoing elective surgery. Temperatures were measured using a dual-sensor heat-flux (DHF) thermometer (Tcore™) and a rectal temperature probe (TRec), and the agreement between the two measurements was assessed. The DHF measurements showed a bias of +0.413 °C compared with those of the TRec. The limits of agreement were broader than the pre-defined ±0.5 °C range (−0.741 °C and +1.567 °C). Although the DHF sensors tended to overestimate the core temperature compared to the rectal measurements, an error grid analysis demonstrated that 95.81% of the DHF measurements would not have led to a wrong clinical decision, e.g., warming or cooling when not necessary. In conclusion, the low number of measurements that would have led to incorrect decisions suggests that the DHF sensor can be considered an option for continuous temperature measurement when more invasive methods are infeasible.

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.