Ultralong peripheral nerve block by lidocaine:prilocaine 1:1 mixture in a lipid depot formulation: comparison of in vitro, in vivo, and effect kinetics

BACKGROUND: The aim of this study was to develop stable and easily injectable lipid depot preparations of local anesthetics in which the drug concentration can be varied according to desired duration of action. METHODS: The formulations contained a 2.0, 5.0, 10, 20, 40, 60, 80, or 100% eutectic mixture of lidocaine and prilocaine base in medium-chain triglyceride. Duration of sciatic nerve block and local neurotoxicity was investigated in rats with 2.0% lidocaine:prilocaine HCl solution and 99.5% ethanol as controls. The rate of release of local anesthetic from the site of administration and the possibility to predict in vivo depot characteristics from in vitro release data were investigated for the 20 and 60% formulations. RESULTS: The duration of sensory sciatic block was prolonged 3 times with the 20% formulation and approximately 180 times with the 60% formulation, in comparison with the 2% aqueous solution. With the 80 and 100% formulations, all animals still showed nerve block after 2 weeks. The in vivo release of local anesthetic could be approximately predicted from in vitro data for the 20% but not for the 60% formulation. The formulations of 60% or greater and ethanol showed neurotoxic effects. CONCLUSIONS: The pharmaceutical properties of these formulations compare favorably with those of other depot preparations. The high-percentage ones showed the longest duration of action yet reported for sciatic nerve block in rats. The possibility of using a high-concentration local anesthetic depot formulation as an alternative to ethanol or phenol for long-term nerve blocks in chronic pain merits further investigation.     

Ultralong Peripheral Nerve Block by Lidocaine:Prilocaine 1:1 Mixture in a Lipid Depot Formulation: Comparison of In Vitro, In Vivo, and Effect Kinetics

Background: The aim of this study was to develop stable and easily injectable lipid depot preparations of local anesthetics in which the drug concentration can be varied according to desired duration of action.

Methods: The formulations contained a 2.0, 5.0, 10, 20, 40, 60, 80, or 100% eutectic mixture of lidocaine and prilocaine base in medium-chain triglyceride. Duration of sciatic nerve block and local neurotoxicity was investigated in rats with 2.0% lidocaine:prilocaine HCl solution and 99.5% ethanol as controls. The rate of release of local anesthetic from the site of administration and the possibility to predict in vivo depot characteristics from in vitro release data were investigated for the 20 and 60% formulations.

Results: The duration of sensory sciatic block was prolonged 3 times with the 20% formulation and approximately 180 times with the 60% formulation, in comparison with the 2% aqueous solution. With the 80 and 100% formulations, all animals still showed nerve block after 2 weeks. The in vivo release of local anesthetic could be approximately predicted from in vitro data for the 20% but not for the 60% formulation. The formulations of 60% or greater and ethanol showed neurotoxic effects.     

Fentanyl does not improve the nerve block characteristics of axillary brachial plexus anaesthesia performed with ropivacaine

BACKGROUND: The aim of this prospective, randomized, double-blind study was to evaluate the effects of adding 1 microg. kg-1 fentanyl to ropivacaine 7.5 mg. ml-1 for axillary brachial plexus anaesthesia. METHODS: With Ethics Committee approval and written consent, 30 ASA physical status I-II in-patients, scheduled for orthopaedic hand procedures were randomly allocated to receive axillary brachial plexus block with 20 ml of either ropivacaine 7.5 mg. ml-1 (n=15) or ropivacaine 7.5 mg. ml-1+1 microg. ml-1 fentanyl (n=15). Nerve blocks were placed using a nerve stimulator with the multiple injection technique. A blinded observer recorded the time to onset of surgical block (loss of pinprick sensation in the innervation areas of the hand (C6-C8) with concomitant inability to flex the wrist against gravity and move the fingers when squeezing the hand) and first request for pain medication after surgery. RESULTS: No differences in demography, degree of sedation or peripheral oxygen saturation were observed between the two groups. Median (range) time required to achieve readiness for surgery was 15 min (5-36 min) with ropivacaine alone and 15 min (5-40 min) with the ropivacaine-fentanyl mixture. No differences in the intraoperative quality of nerve block were reported between the two groups. Four patients receiving ropivacaine plain and two patients receiving the ropivacaine-fentanyl mixture did not require analgesics during the first 24 h after surgery (P=0.62). The degree of pain experienced at first analgesic request in those patients asking for pain medication, as well as median consumption of postoperative analgesics, were similar in the two groups. First postoperative analgesic request was made at 11 h (25th-75th percentiles: 9.1-14 h) in patients receiving ropivacaine alone and at 11.8 h (25th-75th percentiles: 9.8-15 h) in patients receiving the ropivacaine-fentanyl mixture (P=0.99). CONCLUSION: The addition of fentanyl 1 microg. ml-1 to ropivacaine 7.5 mg. ml-1 does not improve the nerve block characteristics of axillary brachial plexus anaesthesia for orthopaedic procedures involving the hand.     

A comparison of two approaches to sciatic nerve block

This study compared the posterior and popliteal fossa approaches for sciatic nerve block. Patients scheduled to undergo foot surgery were allocated randomly into one of two groups: group A (n = 20) received sciatic nerve block via the posterior approach and group B (n = 20) received a block using the popliteal fossa approach. All blocks were performed with the aid of a peripheral nerve stimulator and alkalinised 0.5% bupivacaine with 1 in 200,000 adrenaline was injected in a dose of 2 mg.kg-1. Nineteen of 20 blocks in group A were successful compared with nine of 20 in group B (p less than 0.01). There was no significant difference between the groups in respect of time to onset or duration of block. Patients in group B reported less discomfort during performance of the sciatic nerve block but required supplementary nerve blocks more frequently. We recommend the use of the posterior approach for sciatic nerve block.     

Peribulbar anaesthesia: a double-blind comparison of three local anaesthetic solutions

A prospective, randomised, double-blinded study comparing three agents for peribulbar anaesthesia is reported. Sixty patients undergoing extracapsular cataract extraction under local anaesthesia were randomly allocated to receive peribulbar anaesthesia with lignocaine 2% with adrenaline; prilocaine 3% with felypressin 0.03 IU.ml-1 or 2% lignocaine and 0.5% bupivacaine in a ratio of 1:1, using a standardised two-injection technique. The pain of injection, time of onset of the block and the operating conditions at the start and finish of surgery were assessed. Peribulbar anaesthesia using lignocaine 2% was significantly more painful than the other solutions. The onset of anaesthesia adequate for surgery was similar in all three groups. Prilocaine 3% with felypressin was associated with the greatest number of blocks providing total akinesia of the eye. Inadequate duration of anaesthesia was seen in only one case; the solution used for this block was 2% lignocaine.     

Sciatic nerve palsy following uneventful sciatic nerve block

We describe the loss of function in the sciatic nerve after an uneventful sciatic nerve block using 25 ml of lignocaine 1% with adrenaline 1 in 200 000 in a patient receiving β blocker drugs. Lack of pain on injection and complete regeneration of the nerve after 12 months in a patient with severe peripheral vascular disease led us to postulate ischaemic nerve damage as a mechanism of injury. Adrenaline-induced unopposed α-mediated vasoconstriction in a β-blocked patient is suggested as a possible mechanism of peripheral nerve injury worthy of further investigation.     

The effects of ornipressin and adrenaline on lignocaine nerve blocks

An electrophysiological method measuring nerve conduction following the electrical stimulation of a sciatic nerve branch in anaesthetised rats was used to evaluate under strictly controlled conditions the effects of 1:100,000 adrenaline and of 0.03 IU X ml-1 ornipressin on the speed of onset, depth and duration of lignocaine anaesthesia. It was shown that compared with plain lignocaine, lignocaine with ornipressin produced shorter onset of anaesthesia and improved its depth and duration. Adding adrenaline to lignocaine merely extended its duration of action. Ornipressin, therefore, even at low concentration, can be considered as a viable alternative vasoconstrictor to adrenaline, the use of which is undesirable in some categories of patients.     

Regional anaesthesia for surgery of the forearm and hand

Eighty patients who presented for surgery of the forearm or hand were allocated randomly to one of two groups. In Group A, surgery was performed under supraclavicular brachial plexus block only; a mixture of equal parts of prilocaine 1% and bupivacaine 0.5% without adrenaline was used. In Group B, supraclavicular brachial plexus block was performed using prilocaine 1% alone, but in addition discrete nerve blocks were performed at elbow level using 0.5% bupivacaine without adrenaline. Patients in Group B had a significantly shorter duration of unwanted postoperative motor blockade and a significantly longer duration of postoperative analgesia (p less than 0.005).     

Local anesthetics in lipid-depot formulations--neurotoxicity in relation to duration of effect in a rat model

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the possible local neurotoxicity of a number of lipid-depot formulations of local anesthetics in relation to their duration of action in sciatic-nerve block. METHODS: Formulations that contain 2%, 4%, 8%, 16%, 32%, or 64% of a mixture of bupivacaine and lidocaine base 4:1 in medium-chain triglyceride were prepared and evaluated, together with 0.5%, 1.0%, and 2.0% bupivacaine HCl solutions, bupivacaine 4.2% or 7.0% in medium-chain triglyceride, and 20% lidocaine base in a polar lipid vehicle. The duration of sensory and motor sciatic-nerve block was determined in rats. A week later, the sciatic nerves were dissected and removed for histopathologic examination by light microscopy. RESULTS: The duration of sensory and motor-nerve block was prolonged almost 4 times with the 32% and 13 times with the 64% bupivacaine:lidocaine formulation, in comparison to the 0.5% aqueous solution. The 64% formulation was applied by injection and also placed directly on the nerve with similar results. Slight to moderate signs of neurotoxicity were only found after administration of the 64% formulation. CONCLUSIONS: The findings suggest that depot formulations of local anesthetics with advantageous pharmaceutical and pharmacologic properties can be prepared by use of bupivacaine as the active component and natural lipids as carriers. A favorable balance between effects and toxicity may conceivably be obtained. After supplemental testing in more sensitive models for toxicity, such formulations could be candidates for clinical trials.     

Local anaesthetic adjuncts for peripheral regional anaesthesia: a narrative review

Moderate-to-severe postoperative pain persists for longer than the duration of single-shot peripheral nerve blocks and hence continues to be a problem even with the routine use of regional anaesthesia techniques. The administration of local anaesthetic adjuncts, defined as the concomitant intravenous or perineural injection of one or more pharmacological agents, is an attractive and technically simple strategy to potentially extend the benefits of peripheral nerve blockade beyond the conventional maximum of 8–14 hours. Historical local anaesthetic adjuncts include perineural adrenaline that has been demonstrated to increase the mean duration of analgesia by as little as just over 1 hour. Of the novel local anaesthetic adjuncts, dexmedetomidine and dexamethasone have best demonstrated the capacity to considerably improve the duration of blocks. Perineural dexmedetomidine and dexamethasone increase the mean duration of analgesia by up to 6 hour and 8 hour, respectively, when combined with long-acting local anaesthetics. The evidence for the safety of these local anaesthetic adjuncts continues to accumulate, although the findings of a neurotoxic effect with perineural dexmedetomidine during in-vitro studies are conflicting. Neither perineural dexmedetomidine nor dexamethasone fulfils all the criteria of the ideal local anaesthetic adjunct. Dexmedetomidine is limited by side-effects such as bradycardia, hypotension and sedation, and dexamethasone slightly increases glycaemia. In view of the concerns related to localised nerve and muscle injury and the lack of consistent evidence for the superiority of the perineural vs. systemic route of administration, we recommend the off-label use of systemic dexamethasone as a local anaesthetic adjunct in a dose of 0.1–0.2 mg.kg⁻¹ for all patients undergoing surgery associated with significant postoperative pain.     

地塞米松对0·5%罗哌卡因腰丛-坐骨神经联合阻滞作用的影响

目的评价地塞米松给药方式对0.5%罗哌卡因腰丛-坐骨神经联合阻滞(CLPSNB)作用时效的影响。方法60例神经刺激器定位CLPSNB患者随机分为三组,每组20例。A组,0.5%罗哌卡因45ml加地塞米松10mg行神经阻滞,同时静脉注射生理盐水(NS);B组,0.5%罗哌卡因45ml加NS2ml行神经阻滞,同时静脉注射地塞米松10mg;C组,0.5%罗哌卡因45ml加NS2ml神经阻滞,同时静脉注射NS2ml。结果感觉、运动阻滞持续时间A组[(15.2±3.3)h、(12.6±2.8)h]显著长于B组[(10.1±2.1)h、(7.9±1.6)h]和C组[(10.4±2.5)h、(7.6±2.3)h](P0.05)。结论地塞米松可以通过局部作用机制延长0.5%罗哌卡因CLPSNB持续时间。     

Dexamethasone as an adjuvant for peripheral nerve blockade: a randomised,triple-blinded crossover study in volunteers

Background

The efficacy of dexamethasone in extending the duration of local anaesthetic block is uncertain. In a randomised controlled triple blind crossover study in volunteers, we tested the hypothesis that neither i.v. nor perineurally administered dexamethasone prolongs the sensory block achieved with ropivacaine.

Effects of pH and buffer capacity modulation on the analgesic efficacy of lignocaine and pethidine solutions

Background. Objectives were to study the effects of variations in the pH and the buffer capacity of solutions of lignocaine or pethidine on their analgesic efficacy in peripheral nerve block. Methods. Infraorbital nerve blocks (IONB) were induced in rats during light pentobarbitone anaesthesia employing 0.2 ml of test solutions containing 10 mg · ml^-1 of lignocaine or pethidine dissolved in normal saline, 50 mmol and 150 mmol tris-hydroxymethylaminomethane (THAM) hydrochloride (THAM · HCI) of pH 4.8 and 4.5, respectively, or 100 mmol THAM-THAM · HCI of pH 7.4. The pH of solutions in saline was varied from 3.0 to 9.3 by adding HCI or NaHCO₃. The analgesic efficacy is expressed as the interval from injection to elicitation of a minimal response to electric stimulation at various intensities (threshold intensities) within the blocked area (IONB 3 to 10), and in terms of the area under the curve (AUC, threshold intensities vs. time). Results. When dissolved in saline, pH 7.4, pethidine exerted more pronounced effects than lignocaine [AUC by 3.5 times (P<0.001), IONB 3 to 10 by 2.7 (P<0.05) to 3.6 (P< 0.001) times]. Variations of the pH of solutions did not affect their analgesic efficacy. Lignocaine exerted more pronounced local analgesic effects when mixed with 150 mmol THAM · HCI than when mixed with saline (pH 7.4), but manifested even more pronounced effects when dissolved in THAM+THAM · HCI [AUC by 3.7 times (P<0.001), IONB 3 to 10 by 2.7 (P0.01) to 3.8 (P<0.001) times]. When dissolved in THAM+THAM · HCI, the analgesic efficacy of pethidine increased by 2.0 to 2.8 times (P<0.001), as compared to a solution in saline at the same pH. Conclusions. It is concluded that variations in the pH of solutions of lignocaine or pethidine in saline does not affect the analgesic efficacy of the drugs, presumably due to the low buffer capacity of the medium, whereas when dissolved in THAM+THAM · HCI · their effect is enhanced.     

Postoperative analgesia after triple nerve block for fractured neck of femur

Fifty patients with fractured neck of femur that required surgical correction with either a compression screw or pin and plate device were randomly allocated to receive one of two anaesthetic techniques, general anaesthesia combined with either opioid supplementation or triple nerve block (three in one block) with subcostal nerve block. The nerve blocks significantly reduced the quantity of opioid administered after operation; 48% of these patients required no additional analgesia in the first 24 hours. Plasma prilocaine levels in these patients were well below the toxic threshold, and peak absorption occurred 20 minutes after the injection. No untoward sequelae were associated with the nerve blocks.     

Prolonged Regional Nerve Blockade: Injectable Biodegradable Bupivacaine/Polyester Microspheres

Background: Biodegradable microspheres are a useful method of drug delivery because they are both injectable and biodegradable, eliminating the need for surgical implantation or removal. Previous work has characterized implantable preparations of local anesthetics in polymer pellets for prolonged regional anesthesia. In this article, the authors characterize injectable suspensions of bupivacaine-polymer microspheres and examine whether they can produce prolonged blockade of the sciatic nerve in rats.

Methods: Microspheres were prepared using polylactic-co-glycolic acid polymers loaded with 75% w/w bupivacaine by a solvent evaporation method. Bupivacaine release from microspheres was determined in vitro by ultraviolet spectroscopy and scintillation counting. Sensory and motor blockade of the rat sciatic nerve were assessed in vivo after injection of microsphere suspensions.

Results: Depending on the type of microspheres, the dose, and the additive used, mean duration of sciatic nerve block ranged from 10 h to 5.5 days. Incorporation of 0.05% w/w dexamethasone into the microspheres resulted in significant prolongation of block (up to 13-fold), and only preparations that contained dexamethasone produced blocks lasting beyond 1 day. Bupivacaine was released in a controlled manner in vitro. Dexamethasone does not substantially slow bupivacaine release from microspheres in vitro.     

The effect of oral dexamethasone on duration of analgesia after upper limb surgery under infraclavicular brachial plexus block: a randomised controlled trial

The effects of oral dexamethasone on peripheral nerve blocks have not been investigated. We randomly allocated adults scheduled for forearm or hand surgery to oral placebo (n = 61), dexamethasone 12 mg (n = 61) or dexamethasone 24 mg (n = 57) about 45 min before lateral infraclavicular block. Mean (SD) time until first pain after block were: 841 (327) min; 1171 (318) min; and 1256 (395) min, respectively. Mean (98.3%CI) differences in time until first postoperative pain for dexamethasone 24 mg vs. placebo and vs. dexamethasone 12 mg were: 412 (248–577) min, p < 0.001; and 85 (-78 to 249) min, p = 0.21, respectively. Mean (98.3%CI) difference in time until first postoperative pain for dexamethasone 12 mg vs. placebo was 330 (186–474) min, p < 0.001. Both 24 mg and 12 mg of oral dexamethasone increased the time until first postoperative pain compared with placebo in patients having upper limb surgery under infraclavicular brachial plexus block.     

Nerve blocks at the wrist for carpal tunnel release revisited: the use of sensory-nerve and motor-nerve stimulation techniques

BACKGROUND AND OBJECTIVES: Because the median nerve at the wrist has mainly sensory endings, the aim of this study was to assess the response of the median nerve to nerve stimulation at the wrist and to evaluate the quality of median nerve block. A control group of patients who received blinded injections was analyzed and compared post hoc. METHODS: One hundred and eleven patients scheduled for ambulatory endoscopic carpal-tunnel release performed under median and ulnar nerve blocks at the wrist were prospectively studied. The blocks were performed with a nerve stimulator. Nerve-stimulation techniques were explained to the patient before the block was performed. The patient was trained to inform the anesthetist of their perception of an electrical paresthesia that was synchronized to the nerve stimulator. The anesthetist recorded the first response of the patient to nerve stimulation: sensory (S), sensory-motor (SM), or motor response (M). When the minimal stimulating current was obtained, an equal volume of 4 mL of 1.5% mepivacaine was injected on median and ulnar nerves. If necessary, a lateral subcutaneous injection of 2 mL of 1.5% mepivacaine was administered at the wrist crease in the musculocutaneous nerve area. Thirty-five patients who received blinded local anesthetics injections were included post hoc. Quality of anesthesia was compared between groups. RESULTS: Responses included 89 S (80.2%), 18 SM (16.2%), and 4 M (3.71%). No differences occurred in time to perform the block, minimal current intensity, and efficacy. More punctures were necessary in the M group compared with the S group and the control group (P < .05). The onset time of sensory blocks increased significantly in control-group patients (P < .05), but the duration of the nerve-block procedure decreased in comparison with the M group. Respectively, 10% and 20% of patients experienced mild or severe pain in the nerve-stimulation group and control group. At 20 minutes, the block was complete for the median and ulnar nerves in 96.4% and 85% of the nerve-stimulation patients and control patients (P < .05). Two patients in the control group experienced painful mechanical paresthesia. Neither permanent nor transient nerve injuries were observed during or after the nerve block or surgery. CONCLUSION: This study describes how infrequently an initial motor response is identified when a nerve stimulator is used on the median nerve at the wrist. A very high success rate of median and ulnar nerve block at the wrist is obtained by use of sensory or sensory-motor-nerve stimulation and less than 10 mL of anesthetic solution.     

Alkalinisation of bupivacaine for sciatic nerve blockade

This double-blind study investigates the effect of pH adjustment of bupivacaine 0.5% with adrenaline 1:200,000 on block latency, duration of analgesia and systemic absorption of local anaesthetic after sciatic nerve blockade. Twenty-four adult patients were randomly allocated into one of two groups: Group A (n = 12) received bupivacaine with adrenaline 1:200,000 (pH 3.9) 2 mg/kg, while Group B (n = 12) received alkalinised bupivacaine with adrenaline 1:200,000 (pH 6.4) 2 mg/kg. Increasing the pH of the local anaesthetic solution significantly reduced block latency from 25 minutes in Group A to 12.5 minutes in Group B (p less than 0.001) and prolonged the duration of useful analgesia from 14.1 hours to 18.3 hours (p less than 0.001). There was no significant difference in plasma bupivacaine levels between the two groups. The results indicate that alkalinisation of bupivacaine reduces time to onset and prolongs the duration of useful analgesia when used for sciatic nerve blockade, without significantly increasing systemic absorption.     

A comparison of 1% ropivacaine with a mixture of 0.75% bupivacaine and 2% lignocaine for peribulbar anaesthesia

In a single centre, randomised, double-blind study, 54 patients underwent intraocular surgery under peribulbar anaesthesia with either ropivacaine 1% or a mixture of bupivacaine 0.75% and lignocaine 2%, both with hyaluronidase 7.5 iu.ml-1. There were no significant differences in volume of anaesthetic required, time to onset of block, peri-operative pain scores or frequency of adverse events between the ropivacaine group and the lignocaine and bupivacaine group.     

Ultrasound-guided umbilical nerve block in children: a brief description of a new approach

BACKGROUND: The most popular peripheral nerve blocks used in umbilical hernia repair are rectus sheath block and paraumbilical block. However, multiple anatomic variations have been described and some complications may occur. Ultrasonographic guidance of peripheral nerve blocks has reduced the number of complications and improved the quality of blocks. This case series describes a new ultrasound-guided puncture technique of the 10th intercostal nerve in pediatric umbilical surgery. METHODS: Ten children (age range: 2-5 years) scheduled for umbilical hernia repair were included. Following the induction of general anesthesia, the ultrasonographic anatomy of the umbilical region was studied with a 10-MHz linear probe. An ultrasound-guided peripheral block of the 10th intercostal nerve in the lateral edge of both rectus abdominis muscles (RMs) was performed (total of 20 punctures). Surgical conditions, intraoperative hemodynamic parameters, and postoperative analgesia by means of the modified CHEOPS scale were evaluated. RESULTS: Umbilical anatomy was clearly identified by ultrasound in all cases. The epigastric vessels were identified--above the umbilicus--within the depth of the muscular mass of the RM. The spread of local anesthetic was ultrasound-controlled in all cases. However, the intercostal nerve could not be visualized. All blocks were effective during the surgery. Postoperative analgesia was only required in two children in the second postoperative hour. There were no complications. CONCLUSIONS: Ultrasound guidance enables performance of an effective umbilical block in the lateral edge of RM. Further studies should be carried on to visualize the intercostal nerve and to compare this technique with the classical ones.