Effect of Lidocaine 2% Versus Bupivacaine 0.5% and 1 Versus 2 Dual Separate Injections on Onset and Duration of Ultrasound-Guided Wrist Blocks: A Blinded 2 × 2 Factorial Randomized Clinical Trial.

BACKGROUND: Local anesthetics are often selected or mixed to accomplish faster onset of anesthesia. However, with ultrasound guidance, local anesthetics are delivered with greater precision, which may shorten the onset time with all classes of local anesthetics. In this study, we compared onset time and duration of ultrasound-guided wrist blocks with a fast onset versus a longer lasting local anesthetic administered via single or dual (spatially separate) injections at the level of the midforearm. METHODS: In this randomized clinical trial, 36 subjects scheduled for carpal tunnel release were randomly assigned to receive ultrasound-guided median and ulnar nerve blocks with lidocaine 2% or bupivacaine 0.5% via single or dual injections (n = 9 in each group). Subjects fulfilled the study requirements. The main outcome variables were onset and duration of sensory blockade, which were tested separately in 2 (drug) × 2 (injection) analysis of variances (ANOVAs) with interaction terms. RESULTS: Sensory block onset time did not differ significantly between subjects given lidocaine 2% (9.2 ± 3.4 minutes) or bupivacaine 0.5% (9.5 ± 3.1 minutes) (P = .76; mean difference, -0.3 ± 1.1 minutes [95% confidence interval {CI}, -2.5 to 1.9]) or between the single- (9.6 ± 2.8 minutes) and dual- (9.1 ± 3.6 minutes) injection groups (P = .69; mean difference, -0.4 ± 1.1 minutes [95% CI, -1.8 to 2.6]). Sensory duration was longer for subjects in the bupivacaine 0.5% group (27.3 ± 11.6 hours) than for subjects in the lidocaine 2% group (8.4 ± 4.1 hours) (P < .001; 95% CI, 12.7-25.1). However, sensory duration in the single- (15.7 ± 12.5 hours) and dual- (19.4 ± 13.1 hours) injection groups did not differ significantly (P = .28; mean difference, -3.7 ± 4.3 hours [95% CI, -12.6 to 5.1]). CONCLUSIONS: No significant effect was found for onset time between lidocaine 2% and bupivacaine 0.5% used in ultrasound-guided wrist blocks. Dual injections did not shorten onset time. Since mean nerve block duration was longer with bupivacaine 0.5%, our results suggest that the selection of local anesthetic for the median and ulnar nerves at the level of the midforearm should be based on the desired duration of the block and not on its speed of onset.

Neurotoxicity of intraneural injection of bupivacaine liposome injectable suspension versus bupivacaine hydrochloride in a porcine model.

OBJECTIVE: To test whether neurotoxic effects of a bupivacaine liposome injectable suspension differ from those of a standard formulation of bupivacaine hydrochloride (HCl) after intraneural injection into the sciatic nerves in pigs. STUDY DESIGN: Prospective, randomized study. ANIMALS: Fifteen pigs, hybrids of Landrace and Large White. METHODS: After the National Ethics Committee approval, 15 pigs were randomly allocated to three groups (n = 5/group) to receive intraneural injections of 4 mL of 1.33% bupivacaine liposome injectable suspension, 0.5% bupivacaine HCl or normal saline. Serial neurologic examinations were conducted to detect sensory and motor response to noxious stimuli using a modified Thalhammer's scale at 2 hour intervals for the first 12 hours after injection and daily thereafter for 2 weeks. Fiber characteristics (density) of the harvested sciatic nerves were measured during histomorphometric analysis. Inflammatory response was studied using immunohistochemical analysis. Data were tested using analyses of variance; p values for paired comparisons were Bonferroni adjusted. RESULTS: Compared with bupivacaine HCl, bupivacaine liposome injectable suspension provided longer sensory (11.2 ± 1.8 hours versus 3.2 ± 1.1 hours, respectively, p < 0.0001) and motor (10.0 ± 2.0 hours versus 4.0 ± 1.4 hours respectively, p < 0.0001) blockade. Histomorphometric parameters were similar among the groups. No changes in axonal density or myelin structure indicative of injury to the sciatic nerves were observed in any of the groups. Number of immunopositive cells did not differ between the bupivacaine liposome injectable suspension (23 ± 6 cells per mm2) and the bupivacaine HCl groups (21 ± 4 cells per mm2), p > 0.90. CONCLUSIONS AND CLINICAL RELEVANCE: Intraneural injections of bupivacaine liposome injectable suspension or bupivacaine HCl in our porcine model did not result in evidence of neurotoxicity.

Effect of Bupivacaine Liposome Injectable Suspension on Sensory Blockade and Analgesia for Dupuytren Contracture Release.

Purpose: To study the efficacy of bupivacaine liposome injectable suspension in prolonging sensory blocks of the median and ulnar nerves for subjects with Dupuytren contracture release by collagenase injection. We hypothesized that combining liposome bupivacaine and bupivacaine hydrochloride would extend the duration of blocks without added complications. Methods: We randomized 32 subjects scheduled for Dupuytren contracture release with collagenase Clostridium histolyticum injections to receive forearm blocks of the median and ulnar nerves with a mixture of 5 mL liposome bupivacaine 1.33% plus 2.5 mL bupivacaine hydrochloride 0.5% per nerve (n = 16) or 7.5 mL bupivacaine hydrochloride 0.5% alone per nerve (n = 16). Sensory block and analgesia were assessed through the first posttreatment week. Results: Sensory block was nearly 4 times longer in subjects who received the liposome bupivacaine mixture compared with subjects who received bupivacaine hydrochloride alone. Most subjects (13 of 16) who received the liposome bupivacaine mixture had adequate analgesia for finger manipulation to rupture the cords, whereas most subjects (15 of 16) who received bupivacaine hydrochloride alone required additional anesthesia. Subjects in the liposome mixture group reported lower pain scores through the first 3 days after treatment. There were no serious side effects. Conclusions: Addition of liposome bupivacaine to forearm blocks for Dupuytren contracture release prolonged sensory block and improved pain scores without increasing side effects or impairing hand function. Supplemental lidocaine injections for the painful phases of Dupuytren contracture release with collagenase C histolyticum injections were not required by most subjects who received liposome bupivacaine. Type of study/level of evidence: Therapeutic I.

Distribution of Injectate and Sensory-Motor Blockade After Adductor Canal Block.

BACKGROUND: The analgesic efficacy reported for the adductor canal block may be related to the spread of local anesthetic outside the adductor canal. METHODS: Fifteen patients undergoing knee surgery received ultrasound-guided injections of local anesthetic at the level of the adductor hiatus. Sensory-motor block and spread of contrast solution were assessed. RESULTS: Sensation was rated as "markedly diminished" or "absent" in the saphenous nerve distribution and "slightly diminished" in the sciatic nerve territory without motor deficits. Contrast solution was found in the popliteal fossa. CONCLUSIONS: The spread of injectate to the popliteal fossa may contribute to the analgesic efficacy of adductor canal block.

Behavior During Tethered Kicking in Infants With Periventricular Brain Injury.

PURPOSE: To describe behavior of children with periventricular brain injury (PBI) in a tethered-kicking intervention. METHODS: Sixteen infants with PBI were randomly assigned to exercise or no-training in a longitudinal pilot study. Frequencies of leg movements and interlimb coordination were described from videos at 2 and 4 months' corrected age (CA). RESULTS: Eight of the 13 children (62%) with longitudinal data increased the frequency of leg movements while tethered to a mobile between 2 and 4 months' CA. Movement frequency was correlated with scores on the Test of Infant Motor Performance, but no differences between experimental groups were found. Children with typical development at 12 months' CA increased the proportion of leg movements that were synchronous between 2 and 4 months, as did a child with cerebral palsy in the experimental group. CONCLUSIONS: The tethered-kicking intervention facilitates movement in infants with PBI, but effects on development remain to be demonstrated.

The Disposition of Radiocontrast in the Interscalene Space in Healthy Volunteers.

BACKGROUND: We measured the spread of radiocontrast in the interscalene space after injection under low (<15 psi) and high (>20 psi) pressures. METHODS: Nine healthy volunteers received ultrasound-guided injections of 10 mL radio-opaque NaCl 0.9% in both interscalene spaces. Spread of injectate as assessed by computed tomography scan and discomfort on injection were recorded. RESULTS: Under both opening pressure conditions, injectate contacted 3 brachial plexus roots and spilled over the surface of the anterior and/or middle scalene muscles underneath the cervical fascia. CONCLUSIONS: Regardless of injection pressure, the interscalene space was filled with 10 mL of radiocontrast injectate.

Population pharmacokinetics of oral baclofen in pediatric patients with cerebral palsy.

OBJECTIVE: To characterize the population pharmacokinetics (PK) of oral baclofen and assess impact of patient-specific covariates in children with cerebral palsy (CP) in order to support its clinical use. SUBJECTS DESIGN: Children (2-17 years of age) with CP received a dose of titrated oral baclofen from 2.5 mg 3 times a day to a maximum tolerated dose of up to 20 mg 4 times a day. PK sampling followed titration of 10-12 weeks. Serial R- and S-baclofen plasma concentrations were measured for up to 16 hours in 49 subjects. Population PK modeling was performed using NONMEM 7.1 (ICON PLC; Ellicott City, Maryland). RESULTS: R- and S-baclofen showed identical concentration-time profiles. Both baclofen enantiomers exhibited linear and dose/kg-proportional PK, and no sex differences were observed. Average baclofen terminal half-life was 4.5 hours. A 2-compartment PK model with linear elimination and transit absorption steps adequately described concentration-time profiles of both baclofen enantiomers. The mean population estimate of apparent clearance/F was 0.273 L/h/kg with 33.4% inter-individual variability (IIV), and the apparent volume of distribution (Vss/F) was 1.16 L/kg with 43.9% IIV. Delayed absorption was expressed by a mean transit time of 0.389 hours with 83.7% IIV. Body weight, a possible genetic factor, and age were determinants of apparent clearance in these children. CONCLUSION: The PK of oral baclofen exhibited dose-proportionality and were adequately described by a 2-compartment model. Our population PK findings suggest that baclofen dosage can be based on body weight (2 mg/kg per day) and the current baclofen dose escalation strategy is appropriate in the treatment of children with CP older than 2 years of age.

The osteoarthritis knee model: psychophysical characteristics and putative outcomes.

UNLABELLED: The knee osteoarthritis (KOA) model is a convenient and coherent archetype that is frequently used in pharmaceutical trials of drugs with analgesic and/or anti-inflammatory properties; yet, little is known about its specific pathophysiology. The presumed chronic inflammatory etiology of osteoarthritis suggests that nociceptive processes and neurogenic inflammation predominate in this condition. However, most chronic pain conditions are associated with changes in peripheral and central processing. Recent data corroborate this as an important mechanism in KOA. We compared psychophysical characteristics (including thermal Quantitative Sensory Testing); thermal, mechanical, and functional wind-up; thermal and mechanical aftersensations; and pressure algometry of 37 subjects with KOA with 35 age- and sex-matched controls. A third of the KOA subjects demonstrated hypoesthesia to vibration and the 4.56 von Frey fiber, yet few showed allodynia in their worse knee. The majority of subjects had abnormalities to pinprick (41% were hyperalgesic and 27% were hypoesthetic). Compared to controls, the more painful knee was hypoesthetic to cold detection and had greater thermal wind-up, lower pressure-pain thresholds, thermal and mechanical aftersensations, and twice the pain ratings of controls after stair climb. Substantial intraindividual differences were found in KOA subjects and controls for mechanical wind-up and algometric thresholds. PERSPECTIVE: These results develop the KOA model and suggest mechanistic hypotheses. Certain of these tests may ultimately prove to be responsive, quasi-objective, and quantitative outcomes for research and lend empirical support to the notion of measurable sensitization in osteoarthritis.

Effects on motor development of kicking and stepping exercise in preterm infants with periventricular brain injury: a pilot study.

BACKGROUND: Preterm infants with periventricular brain injury (PBI) have a high incidence of atypical development and leg movements. OBJECTIVE: Determine whether kicking and treadmill stepping intervention beginning at 2 months corrected age (CA) in children with PBI improves motor function at 12 months CA when compared with control subjects. METHOD: In a multi-center pilot study for a controlled clinical trial, sixteen infants with PBI were randomly assigned to home exercise consisting of kicking and treadmill stepping or a no-training control condition. Development was assessed at 2, 4, 6, 10, and 12 months CA with the Alberta Infant Motor Scale (AIMS). At 12 months children were classified as normal, delayed, or with cerebral palsy (CP). RESULTS: At 12 months CA 3 of 7 (43%) of the exercise group children walked alone or with one hand held versus 1 of 9 (11%) in the control group (p=0.262), but no significant differences in AIMS scores were found at any age. Half of the subjects had CP or delay; the outcomes of these infants were not improved by exercise. Compliance with the home program was lower than requested and may have affected results. CONCLUSION: Although not statistically significant with a small sample size, self-produced kicking and treadmill exercise may lower age at walking in infants with normal development following PBI, but improvements of the protocol to increase and document compliance are needed before a larger study is implemented.

Measuring care and comfort in children with cerebral palsy: the care and comfort caregiver questionnaire.

OBJECTIVE: To evaluate the psychometric properties of the Care and Comfort Caregiver Questionnaire (CareQ), which was developed to measure the perceived effort of caregivers in providing care for children with moderate to severe cerebral palsy (CP). DESIGN: Cross-sectional data collection from a representative sample of a large racially/ethnically diverse geographic region. SETTING: Outpatient CP clinics at a metropolitan rehabilitation institution. PARTICIPANTS: A total of 100 primary caregivers of children with CP whose Gross Motor Function Classification System (GMFCS) levels were III-V. METHODS: The CareQ was administered to primary caregivers of children with CP. Internal consistency of the CareQ and its 3 domains (Personal Care, Positioning/Transfers, and Comfort) were evaluated with the Cronbach α. Construct validity of the CareQ was evaluated by its correlation with the Pediatric Functional Independence Measure (WeeFIM). Associations between CareQ scores and child and caregiver characteristics were assessed. RESULTS: Mean CareQ scores for children with GMFCS levels III, IV, and V were 30.6, 42.8, and 45.1, respectively (P < .01). The Cronbach α was 0.90 for total CareQ and 0.93, 0.80, and 0.82 for its Personal Care, Positioning/Transfers, and Comfort domains, respectively. Total CareQ and WeeFIM scores were negatively correlated (r = -.22; P = .03). Total CareQ scores were positively correlated with the child's age (r = .38; P < .01) and with body weight (r =.37; P < .01); however, no caregiver characteristics were associated with CareQ scores. CONCLUSIONS: The CareQ is a concise and internally consistent measure of difficulty of care as perceived by caregivers of children whose GMFCS levels were III-V. Further investigation should include assessment of responsiveness of the CareQ to changes in the child's functional status over time and/or with rehabilitation interventions.

Association of apolipoprotein E genotype and cerebral palsy in children.

OBJECTIVES: We tested the hypotheses that apolipoprotein E genotype, in particular carriage of the epsilon4 allele, is more likely to be associated with cerebral palsy and that children with more severe neurologic impairment are more likely to carry this allele. METHODS: In this cross-sectional study, 209 children with cerebral palsy were matched with healthy control subjects according to gender and race. Diagnosis of cerebral palsy was confirmed through physician consultation, medical chart review, and parent interview. Apolipoprotein E genotyping was performed with DNA obtained with buccal swabs. Severity of motor impairment was rated by physical therapists, and occipitofrontal circumference was measured. RESULTS: Compared with gender- and race-matched control subjects, overall risk for cerebral palsy was elevated 3.4-fold among children carrying an epsilon4 allele and was particularly elevated for children with quadriplegia/triplegia. This finding was independent of birth weight. Carriage of the epsilon4 allele was also associated with increased severity of cerebral palsy and with a trend toward increased likelihood for microcephaly. Moreover, children carrying an epsilon2 allele were at greater risk for cerebral palsy. CONCLUSIONS: These data implicate the apolipoprotein E epsilon4 and epsilon2 genotypes as susceptibility factors in determining neurologic outcomes after perinatal brain injury. Additional studies are warranted to establish the role of apolipoprotein E in specific pathogenetic pathways leading to cerebral palsy or poor neurologic outcomes after perinatal brain injury.

Abruptly attenuated terminal ictal pattern in pediatrics.

PURPOSE: We examined the ictal discharges at the end of pediatric seizures and categorized the various patterns. One particular pattern, termed "abruptly attenuated termination" was studied in detail. METHODS: Ictal segments captured on video-EEG monitoring during a 26-month interval were analyzed for a variety of ictal termination patterns, including one that we rigorously defined as abruptly attenuated termination pattern (AAT). We studied the associations between AAT and the other ictal EEG and clinical features. RESULTS: AAT was noted in 16 of 200 (8%) pediatric seizures. All 16 were immediately preceded by repetitive spikes or spike-waves. The presence of AAT also correlated with ictal spread pattern, initial ictal pattern, laterality of onset, seizure duration, age, and epilepsy etiology. AAT is more often noted in children older than 6 months and in children with idiopathic or cryptogenic forms of epilepsy. CONCLUSIONS: The minority of pediatric seizures recorded in a tertiary epilepsy monitoring unit end with diffuse, synchronized abrupt attenuation. AAT probably is the result of an active process that is developmentally related. It appears to require some degree of mature and intact neurophysiology and may involve the thalamocortical circuit.

The effectiveness of video technology as an adjunct to teach and evaluate epidural anesthesia performance skills.

BACKGROUND: Although video review has been used in teaching, it has not been reported for use as an adjunct to teaching anesthesiology residents. The purpose of the prospective, randomized, blinded study was to determine whether teaching with video review improves epidural anesthesia skills of anesthesiology residents. METHODS: Twenty-two second-year (CA-2) anesthesiology residents beginning their first obstetric anesthesia rotation were assigned to video or non-video groups. All residents were filmed daily as they placed epidural analgesia. Residents assigned to the video group reviewed their tapes twice a week with an attending anesthesiologist, whereas residents assigned to the non-video group never saw their films. Four experienced attending anesthesiologists independently judged videotapes taken on days 1, 15, and 30 and scored the residents for "overall" skill (range of summed overall grades, 0-40), as well as on 13 predetermined criteria. RESULTS: As determined by kappa coefficients, interrater reliability was high among the judges (k = 0.7-0.8). Residents in the video group improved to a greater degree than residents in the non-video group. On day 1, the median overall grades for the video and non-video groups were 21 and 12, respectively. By day 15, the corresponding grades had increased to 32 and 24, respectively (P < 0.01). However, overall median grades continued to improve between days 15 and 30 in the video group only (P < 0.01). CONCLUSIONS: Review of resident videotapes resulted in greater improvement in overall and predetermined performance criteria. In addition, video review was helpful in identifying skills that were inadequately learned, thus allowing for specific teaching in those areas.