A continuous peripheral nerve block (CPNB) consists of a percutaneously inserted catheter with its tip adjacent to a target nerve/plexus through which local anesthetic may be administered, providing ...a prolonged block that may be titrated to the desired effect. In the decades after its first report in 1946, a plethora of data relating to CPNB was published, much of which was examined in a 2011 Anesthesia & Analgesia article. The current update is an evidence-based review of the CPNB literature published in the interim. Novel insertion sites include the adductor canal, interpectoral, quadratus lumborum, lesser palatine, ulnar, superficial, and deep peroneal nerves. Noteworthy new indications include providing analgesia after traumatic rib/femur fracture, manipulation for adhesive capsulitis, and treating abdominal wall pain during pregnancy. The preponderance of recently published evidence suggests benefits nearly exclusively in favor of catheter insertion using ultrasound guidance compared with electrical stimulation, although little new data are available to help guide practitioners regarding the specifics of ultrasound-guided catheter insertion (eg, optimal needle-nerve orientation). After some previous suggestions that automated, repeated bolus doses could provide benefits over a basal infusion, there is a dearth of supporting data published in the past few years. An increasing number of disposable infusion pumps does now allow a similar ability to adjust basal rates, bolus volume, and lockout times compared with their electronic, programmable counterparts, and a promising area of research is communicating with and controlling pumps remotely via the Internet. Large, prospective studies now document the relatively few major complications during ambulatory CPNB, although randomized, controlled studies demonstrating an actual shortening of hospitalization duration are few. Recent evidence suggests that, compared with femoral infusion, adductor canal catheters both induce less quadriceps femoris weakness and improve mobilization/ambulation, although the relative analgesia afforded by each remains in dispute. Newly published data demonstrate that the incidence and/or severity of chronic, persistent postsurgical pain may, at times, be decreased with a short-term postoperative CPNB. Few new CPNB-related complications have been identified, although large, prospective trials provide additional data regarding the incidence of adverse events. Lastly, a number of novel, alternative analgesic modalities are under development/investigation. Four such techniques are described and contrasted with CPNB, including single-injection peripheral nerve blocks with newer adjuvants, liposome bupivacaine used in wound infiltration and peripheral nerve blocks, cryoanalgesia with cryoneurolysis, and percutaneous peripheral nerve stimulation.
Voltage-gated sodium channels play a vital role in nerve and muscle cells, enabling them to encode and transmit electrical signals. Currently, there exist several classes of drugs that aim to inhibit ...these channels for therapeutic purposes, including local anesthetics, antiepileptics and antiarrhythmics. However, sodium-channel-inhibiting drugs lack subtype specificity; instead, they inhibit all sodium channels in the human body. Improving understanding of the mechanisms of binding of existing nonselective drugs is important in providing insight into how subtype-selective drugs could be developed. This study used molecular dynamics simulations to investigate the binding of the antiepileptics carbamazepine and lamotrigine and the local anesthetic lidocaine in neutral and charged states to the recently resolved human Nav1.4 channel. Replica exchange solute tempering was used to enable greater sampling of each compound within the pore. It was found that all four compounds show similarities in their binding sites within the pore. However, the positions of the carbamazepine and lamotrigine did not occlude the center of the pore but preferentially bound to homologous domain DII and DIII. The charged and neutral forms of lidocaine positioned themselves more centrally in the pore, with more common interactions with DIV. The best localized binding site was for charged lidocaine, whose aromatic moiety interacted with Y1593, whereas the amine projected toward the selectivity filter. Comparisons with our previous simulations and published structures highlight potential differences between tonic and use-dependent block related to conformational changes occurring in the pore.
Caudal epidural blockade in children is one of the most widely administered techniques of regional anaesthesia. Recent clinical studies have answered major pharmacodynamic and pharmacokinetic ...questions, thus providing the scientific background for safe and effective blocks in daily clinical practice and demonstrating that patient selection can be expanded to range from extreme preterm births up to 50 kg of body weight. This narrative review discusses the main findings in the current literature with regard to patient selection (sub-umbilical vs mid-abdominal indications, contraindications, low-risk patients with spinal anomalies); anatomical considerations (access problems, age and body positioning, palpation for needle insertion); technical considerations (verification of needle position by ultrasound vs landmarks vs ‘whoosh’ or ‘swoosh’ testing); training and equipment requirements (learning curve, needle types, risk of tissue spreading); complications and safety (paediatric regional anaesthesia, caudal blocks); local anaesthetics (bupivacaine vs ropivacaine, risk of toxicity in children, management of toxic events); adjuvant drugs (clonidine, dexmedetomidine, opioids, ketamine); volume dosing (dermatomal reach, cranial rebound); caudally accessed lumbar or thoracic anaesthesia (contamination risk, verifying catheter placement); and postoperative pain. Caudal blocks are an efficient way to offer perioperative analgesia for painful sub-umbilical interventions. Performed on sedated children, they enable not only early ambulation, but also periprocedural haemodynamic stability and spontaneous breathing in patient groups at maximum risk of a difficult airway. These are important advantages over general anaesthesia, notably in preterm babies and in children with cardiopulmonary co-morbidities. Compared with other techniques of regional anaesthesia, a case for caudal blocks can still be made.
Intrathecal drug delivery is an efficient method to administer therapeutic molecules to the central nervous system. However, even with identical drug dosage and administration mode, the extent of ...drug distribution in vivo is highly variable and difficult to control. Different cerebrospinal fluid (CSF) pulsatility from patient to patient may lead to different drug distribution. Medical image-based computational fluid dynamics (miCFD) is used to construct a patient-specific model to quantify drug transport as a function of a spectrum of physiological CSF pulsations.
Magnetic resonance imaging (MRI) and CINE MRI were performed to capture the patient's central nervous system anatomy and CSF pulsatile flow velocities. An miCFD model was reconstructed from these MRIs and the patient's CSF flow velocities were computed. The effect of CSF pulsatility (frequency and stroke volume) was investigated for a bolus injection of a model drug at the L2 vertebral level. Drug distribution profiles along the entire spine were computed for different heart rates: 43, 60, and 120 bpm, and varied CSF stroke volumes: 1, 2, and 3 mL. To assess toxicity risk for patients with different physiological variables, therapeutic and toxic concentration thresholds for a common anesthetic were derived from experimental studies. Toxicity risk analysis was performed for an injection of a spinal anesthetic for patients with different heart rates and CSF stroke volumes.
Both heart rate and CSF stroke volume of the patient strongly influence drug distribution administered intrathecally. Doubling the heart rate (from 60 to 120 bpm) caused a 26.4% decrease in peak concentration in CSF after injection. Doubling the CSF stroke volume diminished the peak concentration after injection by 38.1%. Computations show that potentially toxic peak concentrations due to injection can be avoided by changing the infusion rate. Using slower infusion rates could avoid high peak concentrations in CSF while maintaining drug concentrations above the therapeutic threshold.
Our computations identify key variables for patient to patient variability in drug distribution in the spine observed clinically. The speed of drug transport is strongly affected by the frequency and magnitude of CSF pulsations. Toxicity risks associated with an injection can be reduced for a particular patient by adjusting the infusion variables with our rigorous miCFD model.
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Microemulsion is the preferred vehicle for local anesthetics; however, the toxicity and irritation associated with a quantity use of surfactants (S) and co-surfactants (CS), i.e., ...medium- or short-chain alcohols, restrict its commercial application. In this study, efforts have been made to enlarge the CS-free microemulsion area by mixing olive oil (OL) with α-linolenic acid (ALA) and linoleic acid (LA), and by using vitamin E succinate (VES) as an auxiliary oil. Through Box-Behnken design and the optimization of nondominated sorting genetic algorithm II, the optimal microemulsion formulation (ME0) with a large steady-state simultaneous permeation rate (Js) and skin retention was screened as 3.23% OL, 0.45% ALA, 1.81% LA, 0.91% VES, 13.60% S, 5% lidocaine and water. Three percent ethanol was screened as a permeability enhancer for the hydrogel of ME0, which showed a statistical increase in Js and skin retention through the abdominal skin of guinea pigs. The optimized formulation had desirable characterization, good stability and negligible irritation. The large Js and skin retention were well reflected in the pinprick test, wherein intensity of anesthetic effect and duration of action were increased significantly over the commercial cream. The developed CS-free microemulsion hydrogel with low S could be a promising strategy for the topical delivery of lidocaine.
Abdominal wall blocks rely on the spread of local anesthetic within musculofascial planes to anesthetize multiple small nerves or plexuses, rather than targeting specific nerve structures. ...Ultrasonography is primarily responsible for the widespread adoption of techniques including transversus abdominis plane and rectus sheath blocks, as well as the introduction of novel techniques such as quadratus lumborum and transversalis fascia blocks. These blocks are technically straightforward and relatively safe and reduce pain and opioid requirements in many clinical settings. The data supporting these outcomes, however, can be inconsistent because of heterogeneity of study design. The extent of sensory blockade is also somewhat variable, because it depends on the achieved spread of local anesthetic and the anatomical course of the nerves being targeted. The blocks mainly provide somatic analgesia and are best used as part of a multimodal analgesic regimen. This review summarizes the anatomical, sonographic, and technical aspects of the abdominal wall blocks in current use, examining the current evidence for the efficacy and safety of each.
Value in healthcare is reflected by patient-centered outcomes of care per health dollar expended. Although liposomal bupivacaine is more expensive, it has been shown to provide prolonged analgesia ...(up to 72 hours).
This study aimed to evaluate whether the addition of liposomal bupivacaine to standard bupivacaine could decrease opioid intake and improve pain control after laparotomy for gynecologic surgery compared with standard bupivacaine alone in an enhanced recovery after surgery pathway.
A prospective randomized controlled single-blinded trial of wound infiltration with liposomal bupivacaine plus 0.25% bupivacaine (study arm) vs 0.25% bupivacaine (control arm) was performed at a National Cancer Institute–designated tertiary referral cancer center. Participants were patients aged ≥18 years undergoing exploratory laparotomy for a gynecologic indication. All patients were treated on an enhanced recovery pathway including local wound infiltration before closure. In this study, 266 mg of liposomal bupivacaine (free base; equal to 300 mg bupivacaine HCL)+150 mg of bupivacaine mixed in the same syringe was used in the study arm, and 150 mg of bupivacaine was used in the control arm. The primary outcome was the proportion of patients who were opioid-free within 48 hours after surgery. Secondary outcomes included number of opioid-free days from postoperative day 0 to postoperative day 3, days to first opioid administration, morphine equivalent daily dose, and patient-reported outcomes collected with the MD Anderson Symptom Inventory. The MD Anderson Symptom Inventory was administered as a preoperative baseline, daily while hospitalized, and at least weekly for 8 weeks after discharge. All outcomes were prespecified before data collection.
In this study, 102 patients were evaluated. Among them, 16.7% of patients in the study arm received no opioids up to 48 hours compared with 14.8% in the control arm (P=.99). There were no significant differences in the amount of intraoperative opioids administered or days to first opioid use. There was no significant difference between the 2 arms in median cumulative morphine equivalent daily dose (21.3 study arm vs 33.8 control arm; P=.36) or between the groups in morphine equivalent daily dose per individual day. There were no significant differences in patient-reported pain or interference with walking between the 2 arms or other patient-reported outcomes.
Within an enhanced recovery after surgery pathway, adding liposomal bupivacaine to 0.25% bupivacaine wound infiltration did not decrease the proportion of patients who were opioid-free within 48 hours after surgery, did not decrease opioid intake, or did not improve patient’s self-reported pain and functional recovery compared with standard bupivacaine.
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The objective of the present study was to prepare and evaluate a ropivacaine-loaded microemulsion (ME) formulation and microemulsion-based Carbopol gel (ME-gel) for transdermal ...delivery. Pseudo-ternary phase diagrams and a simplex lattice experiment design were utilized to screen and optimize the ME formulation. In the process, drug solubility and particle size were inspected as dependent variables whilst Capryol® 90 (X1), Smix (X2, Labrasol®: absolute ethanol=1:2 w/w), water (X3) as independent variables. Following the optimization, the optimal ME formulation was comprised of 15% Capryol® 90, 53% Smix, and 32% water, respectively. Ropivacaine loaded ME appeared to be spherical under transmission electron microscope, and the average particle size was 58.79nm. The results of ex vivo permeation study showed that ropivacaine had a significant higher cumulative amount from ME than that from ME-gel. Histopathology study elucidated that the microstructure of skin surface was significantly changed by the treatment of ME formulation. Skin irritation study indicated that neither ME nor ME-gel caused any irritation responses. Both ME and ME-gel presented a remarkable analgesic activity on acetic acid-induced writhing in mice. In conclusion, ME could be a promising formulation for ropivacaine transdermally administration.
The dural puncture epidural (DPE) technique is associated with faster onset than the conventional epidural (EP) technique for labor analgesia. The programmed intermittent epidural bolus (PIEB) mode ...for maintaining labor analgesia allows for lower anesthetic drug consumption than the continuous epidural infusion (CEI) mode. Whether DPE technique with PIEB mode offers additional benefits for analgesia onset, local anesthetic drug consumption, and side effects versus EP or DPE techniques with CEI mode remains unclear.
Nulliparous women with a visual analog scale (VAS) pain score >50 mm and cervical dilation <5 cm were randomly assigned to receive EP + CEI, DPE + CEI, or DPE + PIEB for labor analgesia. A 25-gauge needle was used for dural puncture. Analgesia was initiated with 10 mL of 0.1% ropivacaine with 0.3 µg/mL of sufentanil and maintained with the same solution at 8 mL/h in all groups. A 5-mL patient-controlled epidural analgesia (PCEA) bolus was programmed with a 20-minute lockout. Breakthrough pain not amendable by PCEA was treated with provider boluses of 5 mL of 0.125% ropivacaine. The primary outcome was "time to adequate analgesia," defined as a VAS pain score ≤30 mm during 2 consecutive contractions, and was analyzed using Kaplan-Meier curves and a Cox proportional hazard model. Secondary outcomes included the VAS scores, ropivacaine consumption, sensory block level to ice, PCEA and provider boluses intervention, mode of delivery, duration of labor, Bromage scores, Apgar scores, occurrence of side effects, and maternal satisfaction with the anesthesia.
A total of 116 women were included (38 in the EP + CEI group, 40 in the DPE + CEI group, and 38 in the DPE + PIEB group). Adequate anesthesia was achieved faster in the DPE + CEI and DPE + PIEB groups than in the EP + CEI group (hazard ratio = 1.705; 95% confidence interval CI, 1.039-2.800; P = .015; and hazard ratio = 1.774; 95% CI, 1.070-2.941; P = .012, respectively). DPE technique with PIEB mode was associated with the fewest PCEA boluses and the lowest hourly ropivacaine consumption (both P < .001). There were no differences in the duration of labor, mode of delivery, Bromage scores, newborn Apgar scores, incidence of side effects, and maternal satisfaction scores among the groups.
The use of DPE technique for neuraxial analgesia was associated with faster onset than the use of the EP technique. DPE technique with PIEB mode achieved the greatest drug-sparing effect without increasing maternal or neonatal side effects.
Topical local anaesthetics provide effective analgesia for patients undergoing numerous superficial procedures, including repair of dermal lacerations. The need for cocaine in topical anaesthetic ...formulations has been questioned because of concern about adverse effects, thus novel preparations of cocaine-free anaesthetics have been developed. This review was originally published in 2011 and has been updated in 2017.
To assess whether benefits of non-invasive topical anaesthetic application occur at the expense of decreased analgesic efficacy. To compare the efficacy of various single-component or multi-component topical anaesthetic agents for repair of dermal lacerations. To determine the clinical necessity for topical application of the ester anaesthetic, cocaine.
For this updated review, we searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 11), Cumulative Index to Nursing and Allied Health Literature (CINAHL; 2010 to December 2016), Embase (2010 to December 2016) and MEDLINE (2010 to December 2016). We did not limit this search by language or format of publication. We contacted manufacturers, international scientific societies and researchers in the field. Weemailed selected journalsand reviewed meta-registers of ongoing trials. For the previous version of this review, we searched these databases to November 2010.
We included randomized controlled trials (RCTs) that evaluated the efficacy and safety of topical anaesthetics for repair of dermal laceration in adult and paediatric participants.
Two review authors independently assessed trial quality and extracted data. We contacted study authors for additional information when needed. We collected adverse event information from trial reports. We assessed methodological risk of bias for each included study and employed the GRADE approach to assess the overall quality of the evidence.
The present updated review included 25 RCTs involving 3278 participants. The small number of trials in each comparison group and the heterogeneity of outcome measures precluded quantitative analysis of data for all but one outcome: pain intensity. In two pooled studies, the mean self-reported visual analogue scale (VAS; 0 to 100 mm) score for topical prilocaine-phenylephrine (PP) was higher than the mean self-reported VAS (0 to 100 mm) score for topical tetracaine-epinephrine-cocaine (TAC) by 5.59 points (95% confidence interval (CI) 2.16 to 13.35). Most trials that compared infiltrated and topical anaesthetics were at high risk of bias, which is likely to have affected their results. Researchers found that several cocaine-free topical anaesthetics provided effective analgesic efficacy. However, data regarding the efficacy of each topical agent are based mostly on single comparisons in trials with unclear or high risk of bias. Mild, self-limited erythematous skin induration occurred in one of 1042 participants who had undergone application of TAC. Investigators reported no serious complications among any of the participants treated with cocaine-based or cocaine-free topical anaesthetics. The overall quality of the evidence according to the GRADE system is low owing to limitations in design and implementation, imprecision of results and high probability of publication bias (selective reporting of data). Additional well-designed RCTs with low risk of bias are necessary before definitive conclusions can be reached.
We have found two new studies published since the last version of this review was prepared. We have added these studies to those previously included and have conducted an updated analysis, which resulted in the same review conclusions as were presented previously.Mostly descriptive analysis indicates that topical anaesthetics may offer an efficacious, non-invasive means of providing analgesia before suturing of dermal lacerations. Use of cocaine-based topical anaesthetics might be hard to justify, given the availability of other effective topical anaesthetics without cocaine. However, the overall quality of the evidence according to the GRADE system is low owing to limitations in design and implementation, imprecision of results and high probability of publication bias (selective reporting of data). Additional well-designed RCTs with low risk of bias are necessary before definitive conclusions can be reached.
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