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In the last two decades, safety concerns about general anesthesia (GA) arose from studies documenting brain cell death in various pharmacological conditions and animal models. Nowadays, a thorough characterization of sevoflurane-induced apoptosis in the entire neonatal mouse brain would help identify and further focus on underlying mechanisms. We performed whole-brain mapping of sevoflurane-induced apoptosis in post-natal day (P) 7 mice using tissue clearing and immunohistochemistry. We found an anatomically heterogenous increase in cleaved-caspase-3 staining. The use of a novel P7 brain atlas showed that the neocortex was the most affected area, followed by the striatum and the metencephalon. Histological characterization in cortical slices determined that post-mitotic neurons were the most affected cell type and followed inter- and intracortical gradients with maximal apoptosis in the superficial layers of the posterodorsal cortex. The unbiased anatomical mapping used here allowed us to confirm sevoflurane-induced apoptosis in the perinatal period, neocortical involvement, and indicated striatal and metencephalic damage while suggesting moderate hippocampal one. The identification of neocortical gradients is consistent with a maturity-dependent mechanism. Further research could then focus on the interference of sevoflurane with neuronal migration and survival during development.

We tested the hypothesis that pressure-support ventilation (PSV) allows a reduction in emergence time and laryngeal mask airway (LMA) removal time after general anesthesia compared to volume-controlled mechanical ventilation (CMV). Because spontaneous breathing (SB) is often used with LMA under general anesthesia, patients were allocated randomly to three groups (CMV, SB and PSV). Thirty-six consecutive ASA I-II patients scheduled for knee arthroscopic surgery under general anesthesia with a LMA and breathing throughout the ventilator circuit were included. Hemodynamic and ventilatory variables were recorded before and 10-min after general anesthesia-induction, at the surgical incision, at the end of anaesthetic drugs infusion and when the patient was totally awake (which defines emergence time). LMA removal time, drug consumption were recorded at the end of the surgical procedure. Leak fraction around the LMA was also evaluated. LMA removal time was significantly higher in the CMV-group (18 ± 6 min) compared to both SB (8 ± 4 min) and PSV (7 ± 4 min, P < 0.05) groups as well as for emergence time: CMV-group (32 ± 12 min), SB (17 ± 7 min) and PSV (13 ± 6 min, P < 0.05) groups. Total propofol consumption was significantly lower in the PSV-group (610 ± 180 mg) than in both CMV (852 ± 330 mg) and SB (734 ± 246 mg, P < 0.05) groups. Air leaks around the LMA was significantly higher in the CMV-group than in the SB and PSV groups (16% vs 3% and 7%, all P<0.05). In conclusion, in knee arthroscopic surgery, in comparison to CMV, PSV use during general anesthesia in unparalyzed patients decreases LMA removal time, propofol consumption and leaks around LMA while improving ventilatory variables without adverse effects. Controlled-Trials.com ISRCTN17382426.

BackgroundThe sensory innervation of the lower jaw mainly depends on the third root of the trigeminal nerve, the mandibular nerve (V3). The aim of this single-center, prospective, randomized, double-blind, placebo-controlled study was to evaluate the effectiveness of bilateral V3 block for postoperative analgesia management in mandibular osteotomies.Methods107 patients undergoing mandibular surgery (75 scheduled osteotomies and 32 mandible fractures) were randomized in two groups. A bilateral V3 block was performed in each group, either with ropivacaine 0.75% (block group, n=50) or with a placebo (placebo group, n=57). A postoperative multimodal analgesia was equally provided to both groups. The primary outcome was the cumulative morphine consumption at 24 hours. Secondary outcomes were the occurrence of severe pain and the incidence of postoperative nausea and vomiting (PONV) in the first 24 hours. Data were analyzed on an intention-to-treat basis.ResultsThe cumulative morphine consumption at 24 hours was significantly lower in the block group (median 8.0 mg (IQR 2.0–21.3) vs 12.0 mg (IQR 8.0–22.0), p=0.03), as well as the incidence of severe pain during the 24 hours of follow-up (4.0% vs 22.8%, p<0.01). The mandibular block had no impact on the incidence of PONV.ConclusionBilateral V3 block for mandibular osteotomies is an effective opioid-sparing procedure. It provided better postoperative analgesia in the first 24 hours, and it did not affect PONV incidence.Trial registration number NCT02618993.

Introduction Perioperative continuous peripheral nerve blocks (CPNB) are increasingly being used in children. Only one previous study has reported adverse events of CPNB in a high number of pediatric cases. We evaluated the indications, block efficacy, and adverse events related to CPNB in children. Methods All CPNBs that were performed in children for postoperative analgesia over a 5-year period at the Montpellier University Hospital in France were included in this study. The first bolus dose and the continuous doses of local anesthetic were not standardized. In the postoperative period, demographic data, quality of analgesia, amount of rescue analgesic medication, child/parent satisfaction, and adverse events were recorded in our Departmental Regional Anesthesia registry. Results A total of 339 catheters were evaluated in 292 children ASA physical status I to III. The median age was 8 yr (0.6–17 yr) and the median weight was 28 kg (7–116 kg). The main surgical indications were hip, femoral, or tibial osteotomies (44.5%) and club foot repair (27.4%). The local anesthetics used were either bupivacaine or ropivacaine. The mean volume of the local anesthetic bolus dose was 0.49 ± 0.16 mL · kg −1 , and the mean regimen of local anesthetic continuous infusion was 0.11 ± 0.04 mL · kg −1  · hr −1 . The median duration of CPNB was 61.6 hr (range 0–264 hr). Pain relief, which was evaluated with the children at rest, was considered optimal in the majority of patients throughout the study period. The Children and Infants Postoperative Pain Scale (CHIPPS) was used in children age 0–6 yr and the Visual Analog Pain Scale (VAS) was used in children 7 yr and older. There were no major adverse events. There were 211 minor adverse events recorded in 153 CPNBs (45.1%). The most frequently reported complication (20.1%) involved mechanical problems with the catheter, followed by nausea and vomiting (14.7%). Conclusion CPNBs are indicated after orthopedic surgery in children. Our results demonstrate that CPNBs are feasible in the pediatric setting, and in skilled hands, they promote prolonged analgesia in the majority of patients without major adverse events. The most common minor adverse events are catheter-related mechanical problems and postoperative nausea and vomiting.

Background Septorhinoplasty is a traumatic procedure that is associated with epistaxis and postoperative pain. The primary objective of this randomized double-blind controlled trial was to determine whether intranasal 5% lidocaine plus naphazoline decreases postoperative pain and lessens the use of rescue analgesics. Methods After induction of general anesthesia and laryngeal topical anesthesia with 5% lidocaine, 28 adult patients, scheduled to undergo septorhinoplasty, were randomly assigned to one of two groups, either topical intranasal saline 20 ml (control group) or intranasal 5% lidocaine plus naphazoline solution 0.2 mg ml −1 (lidocaine group). The perioperative dose of sufentanil, the mean end-tidal concentration of isoflurane, and surgeon satisfaction with the operative field were recorded. In the lidocaine group, plasma lidocaine concentrations were sampled 15, 20, 25, 35, 45, and 55 min after induction of anesthesia. Visual analogue scale pain scores were recorded 30, 60, 90, and 120 min after the patients arrived in the postanesthesia care unit and 24 h after surgery. Consumption of morphine rescue analgesia and the occurrence of any side effects were recorded at the end of the 24-h study period. Results The intranasal lidocaine-naphazoline application decreased isoflurane requirements [median values: 0.8% (0.7–1.5) vs. 1.2% (0.9–1.8), respectively; P  = 0.04] and enhanced surgical conditions. Patients in the lidocaine group experienced less postoperative pain than the control group [1 h after surgery: median values of visual analogue scale: 0 (0–20) vs. 50 (30–80), respectively; P  = 0.001], and they required fewer doses of subcutaneous morphine. Total plasma concentrations of lidocaine remained below 4 μg ml −1 throughout the study period. Conclusions Intranasal lidocaine plus naphazoline is a simple and efficient technique for decreasing intra- and postoperative pain and for lessening rescue analgesic requirements in the postoperative period after septorhinoplasty. Toxic plasma concentrations of lidocaine were not reached.

Purpose Bupivacaine-induced myotoxicity is associated with mitochondrial bioenergetic alterations. The impact of the duration of bupivacaine treatment on mitochondrial energy production remains undetermined. Here, we assessed, in vivo , the alteration of mitochondrial metabolism following different durations of bupivacaine exposure (40, 56, or 112 hr) that correspond to 5, 7, or 14 repeated injections of 0.25% bupivacaine, respectively. Methods Rats were divided randomly into seven different groups: one control group (no catheter); three groups with normal saline injections (1 mL·kg −1 ) every eight hours via a femoral nerve catheter for 40, 56, and 112 hr, respectively; and three groups with 0.25% bupivacaine injections (1 mL·kg −1 ) every eight hours via a femoral nerve catheter for 40, 56, and 112 hr. Psoas and gracilis muscle samples located within the bupivacaine infusion-diffusion space were investigated. To estimate mitochondrial respiratory capacity, the protein content of the mitochondrial respiratory chain apparatus was evaluated by measuring citrate synthase activity. To measure mitochondrial respiratory function, adenosine diphosphate-stimulated oxygen consumption was measured by polarography in saponin-skinned muscle fibres using glutamate-malate or succinate as energy substrates. Results In psoas and gracilis muscles, saline solution had no effect on the two mitochondrial parameters. Bupivacaine induced a significant decrease in the citrate synthase activity in psoas (r 2  = 0.74; P  < 0.001) and gracilis muscle (r 2  = 0.52; P  < 0.001), and there was a significant decrease in the adenosine diphosphate-stimulated oxygen consumption using glutamate or succinate as substrates in both muscles ( P  < 0.001). Conclusions The severity of bupivacaine-induced myotoxicity is closely linked to the duration of bupivacaine exposure in the muscle fibres located close to the catheter tip.

Short reports have noted that percutaneous prelocation is helpful in determining the anatomic course of a peripheral nerve, and, thereby, may serve as a guide for block needle insertion. We prospectively studied percutaneous electrode guidance to assist axillary brachial plexus blocks. In 131 consecutive patients, the tip of an insulated needle emitting 5 mA was placed on the skin above and below the axillary artery to obtain a hand motor response characteristic of the median, ulnar, and radial nerves in succession. The current was reduced until all movement had ceased. The needle was then inserted toward the nerve to be blocked, decreasing the intensity from 2 mA to 0.5 mA, so that the same selected motor response was still obtained. The length of the needle inserted was noted, and 1.5% lidocaine was injected. Pain verbal analogic score (VAS) values were noted during both procedures. Complete sensory blockade was evaluated at 30 min. Rates of successful percutaneous electrode guidance were 94.6% for the median nerve, 89.4% for the radial nerve, 88.5% for the ulnar nerve, and 85.5% for all 3 nerves together. A significant correlation was found between the lowest percutaneous current applied and the depth of the nerve stimulated at 0.5 mA. Pain VAS values were significantly lower during percutaneous stimulation than during needle insertion ( P < .05). Sensory block for all 3 nerves was noted in 92% of patients. Percutaneous electrode guidance using the insulated needle enabled clinicians to locate the terminal branches of the plexus in the axilla and appreciate their depth. This method could, therefore, minimize patient discomfort and perhaps the risk of nerve trauma.