Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by itsduration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants o...Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by itsduration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids(dexamethasone), anti-inflammatory agents(parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action(tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability(liposomal, microspheres and cyclodextrin systems) and further studies with other drugs(adenosine, neuromuscular blockers, dextrans).展开更多
The mechanisms of epidural-associated fever remain incompletely understood [1-3]. We propose that action of local anesthetic on TPRV1. The transient receptor potential cation channel subfamily V member 1 (TRPV1), also...The mechanisms of epidural-associated fever remain incompletely understood [1-3]. We propose that action of local anesthetic on TPRV1. The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor and the vanilloid receptor can explain this effect and explain mechanism of burning sensation on local anesthetic injected subcutaneously or intramuscular. Role of TRPV1 receptor was not discussed previously in Obstetric Anesthesia literature. Based on available data, we propose that Local Anesthetics work as agonist/antagonist on TPRV1 receptors. Antagonist action may cause hyperthermia through modifying thermoregulation [4], agonist action may cause hyperthermia thru release of IL-6 and other mediators of inflammation [5-10]. Agonist action may explain burning sensation on injection of Local Anesthetics. Burning sensation can be diminished by increasing pH of Local Anesthetic solution, because vanillin receptors are stimulated by acidification through lower pH [11,12].展开更多
Background: Procedures that require anesthesia of entire length of the arm should have combined Interscalene block (ISB) and Supraclavicular block (SCB) to ensure adequate block. However, dual block requires high dose...Background: Procedures that require anesthesia of entire length of the arm should have combined Interscalene block (ISB) and Supraclavicular block (SCB) to ensure adequate block. However, dual block requires high dose of local anesthetic (LA). We examined if Ultrasound (U/S) guided block helps to decrease the required volume of LA by visualizing trunks, so we only need injection of LA toward cervical nerve roots C5 and C6 aiming to block branches escaped from supraclavicular block. Patients and methods: Ninety-three patients were randomly allocated into one of three equal groups, each included 31 patients. All patients received SCB 20 ml (10 ml Bupivacaine 0.5% plus 10 ml lidocaine 2%) and ISB with different volumes of LA according to the group as follow: group A: 20 ml, group B: 15 ml, and group C: 10 ml. Result: No significant difference in onset of block (sensory and motor) and duration of block (motor only) between the three groups (P value > 0.05). The duration of sensory block was significantly longer in group A (760.65 ± 30.87 minutes) than in either group B (740.48 ± 21.15 minutes, P value P value P value P value P value P value < 0.001). Conclusion: A reduced volume of LA can be used in ultra sound guided ISB in combined with SCB to give satisfactory level of anesthesia to entire length of the arm, but the sensory block duration and duration of post-operative analgesia will be decreased significantly with decreasing the volume.展开更多
AIM : To systematically evaluate the effect of intraperitoneal local anesthetic on pain characteristics after laparoscopic cholecystectomy(LC).METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library. Randomized...AIM : To systematically evaluate the effect of intraperitoneal local anesthetic on pain characteristics after laparoscopic cholecystectomy(LC).METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library. Randomized controlled trials in English that compared the effect of intraperitoneal administration of local anesthetics on pain with that of placebo or nothing after elective LC under general anesthesia were included. The primary outcome variables analyzed were the combined scores of abdominal, visceral, parietal, and shoulder pain after LC at multiple time points. We also extracted pain scores at resting and dynamic states.RESULTS: We included 39 studies of 3045 patients in total. The administration of intraperitoneal local anesthetic reduced pain intensity in a resting state after laparoscopic cholecystectomy: abdominal [standardized mean difference(SMD) =-0.741; 95%CI:-1.001 to-0.48, P < 0.001]; visceral(SMD =-0.249; 95%CI:-0.493 to-0.006, P = 0.774); and shoulder(SMD =-0.273; 95%CI:-0.464 to-0.082, P = 0.097). Application of intraperitoneal local anesthetic significantly reduced the incidence of shoulder pain(RR = 0.437; 95%CI: 0.299 to 0.639, P < 0.001). There was no favorable effect on resting parietal or dynamic abdominal pain.CONCLUSION: Intraperitoneal local anesthetic as an analgesic adjuvant in patients undergoing laparoscopic cholecystectomy exhibited beneficial effects on postoperative abdominal, visceral, and shoulder pain in a resting state.展开更多
Aim: To study the features of local anesthetic solution spreading during sciatic nerve block in dependence on the anesthetic solution volume. Material and Methods: One hundred and sixty nine cases of sciatic nerve blo...Aim: To study the features of local anesthetic solution spreading during sciatic nerve block in dependence on the anesthetic solution volume. Material and Methods: One hundred and sixty nine cases of sciatic nerve blocks done under ultrasonic visualization control were analyzed. Sciatic nerve blocks were performed by lidocaine in volumes 30;25;20;15;12.5;10;7.5;6.5;5;4.5 ml. The cross-section area, equal to local anesthetic spreading, was determined;the extension of the anesthetic solution spreading along sciatic nerve was calculated. Results: The anesthetic agent solution spreads along sciatic nerve in proximal and distal direction, forming a kind of cylinder. The minimum volume of the local anesthetic, which covers sciatic nerve in the whole, is 5 ml. A rare (1.77%) variation of sciatic nerve structure was described, in which tibial and common peroneal nerves develop directly from the branches of sacral plexus. Conclusion: The decrease of the local anesthetic volume leads to reduction of its spreading distance and cross-section area. Ultrasonic visualization can provide for sciatic nerve anatomical peculiarities, which can have an effect on the block quality.展开更多
In order to examine whether repeated sciatic nerve blocks showed tachyphylaxis and continuity of sciatic nerve with spinal cord affected development of tachyphylaxis when assayed in vivo by duration of depression comp...In order to examine whether repeated sciatic nerve blocks showed tachyphylaxis and continuity of sciatic nerve with spinal cord affected development of tachyphylaxis when assayed in vivo by duration of depression compound action potentials (CAP), rats were anesthetized with halothane, ventilated, monitored and supported with stable hemodynamics and temperature. Posterior tibial nerve distally and sciatic nerve in thigh were exposed, placed on bipolar silver electrodes for stimulation and recording respectively. Three sequential sciatic nerve blocks were performed between these electrodes using 0.15 ml of 3 % chloroprocaine. Nine rats were chosen to observe the effects of repeated sciatic nerve blocks on CAP. In another 18 rats, a second investigator exposed the sciatic nerve near its origin at spinal cord and randomly performed nerve cut and sham (n=9), and closed the incision blinding the electrophysiologic investigator. The results showed that electrical stimulated tibial nerve induced sciatic nerve Aα/β, Aδ, C fiber mediated CAP waves. CAP amplitudes were remained stable during whole experimental procedure. CAP amplitudes were decreased completely with 3% chloroprocaine blocked sciatic nerve and recovered fully. The duration of CAP depression were reduced with repeated blocks. There were no selective blocked effects on Aα/β, Aδ, C fiber mediated CAP. With sciatic nerve cut proximally, there was no statistical significant tachyphylaxis with 3 % chloroprocaine repeated blocked sciatic nerve, and the duration of first and third blocked Aδ fiber mediated CAP was 108±20 and 92±14 min respectively (P>0.05). In normal rats the duration of first and third blocked Aδ fiber mediated CAP was 110±20 and 75±16 min respectively (P<0.05). It was suggested that tachyphylaxis to local anesthetics can occur in rats repeated blocked sciatic nerve when assayed in vivo by duration of depression CAP. The continuity of sciatic nerve with spinal cord is one of the important factors affecting the development of tachyphylaxis.展开更多
Posterior disc displacement of the temporomandibular joint is rare. We present a unique treatment method and magnetic resonance (MR) images of this condition. The patient was a 43-year-old male with a chief complaint ...Posterior disc displacement of the temporomandibular joint is rare. We present a unique treatment method and magnetic resonance (MR) images of this condition. The patient was a 43-year-old male with a chief complaint of abnormal occlusion. Regarding the present status, there was no occlusion on the right side. No temporomandibular joint pain, myalgia, or clicking were observed while mouth opening. On MR images, the posterior disc displacement without reduction on the right was observed and it was assumed that occlusal abnormality was due to this condition. We treated him with the following methods. After injection into the superior articular cavity with 2% lidocaine, a sodium hyaluronate preparation was injected followed by intermaxillary traction applied using rubber. The recovery of occlusion was confirmed in follow-up at 5 days after treatment. In the 13th days, the intermaxillary traction was removed. On MR images, the right disc condition was changed to anterior disc displacement with reduction. We consider our treatment methods are effective for this clinical condition.展开更多
<b>Introduction:</b> Local anesthetics (LAs) must be adsorbed to and permeate through membranes to reach their sites of action. The rates of these processes critically affect drug actions at the cellular l...<b>Introduction:</b> Local anesthetics (LAs) must be adsorbed to and permeate through membranes to reach their sites of action. The rates of these processes critically affect drug actions at the cellular level and also the <i>in vivo</i> pharmacokinetics of perineurally injected drugs. Therefore, we measured the adsorption equilibria and permeation kinetics of two LAs local anesthetics with markedly different hydrophobicities: tetracaine (TTC, P<sub>octanol:buffer</sub> = 3.6 × 10<sup>3</sup>) and procaine (PRO, P<sub>octanol:buffer</sub> = 8.1 × 10<sup>1</sup>), in unilamellar membranes of different composition and fluidity. <b>Methods:</b> Interactions with unilamellar vesicles made of dipalmitoylphosphatidylcholine (DPPC), at 23°C (solid gel state) or 45°C (liquid crystal state), without or with cholesterol (Chol), were investigated by a combination of fluorescence and stopped-flow techniques. Membrane adsorption was monitored by the LA’s fluorescence. Membrane permeation was monitored by the decrease of fluorescence intensity of intra-vesicular pyranine, when quenched by neighboring TTC or PRO. <b>Results:</b> Ionized TTC (TTCH<sup>+</sup>) and procaine (PROH<sup>+</sup>) adsorb to membranes more slowly and weakly than their neutral counterparts (time constant <i>τ</i> ~ 0.1 sec). Fluidizing of membranes, at the higher temperature (45°C) or by Chol inclusion, accelerated LA adsorption (faster than the mixing time of the stopped-flow device, 0.008 s). Permeation of protonated TTCH<sup>+</sup> through the solid gel DPPC membranes (23°C) occurred far more slowly than adsorption, (<i>τ</i> = 36.7 ± 0.7 s, n = 9), and 3 times slower than neutral TTC (<i>τ</i> = 10.9 ± 0.7 s, n = 9);neutral PRO permeated these membranes at the same rate as TTC. Inclusion of Chol with DPPC, disordering the fatty acyl tails of membrane phospholipids while crowding their polar headgroups, slowed permeation of TTC and of PRO to an even greater degree. <b>Conclusions:</b> Local anesthetic permeation through membranes is limited by the transport across the membrane core and not by the initial binding. Drug ionization greatly slows permeation, but greater hydrophobicity does not facilitate it. Lipid crowding caused by Chol, a normal membrane component, slows permeation by disorienting the LA bound at the surface.展开更多
目的比较临床常用的不同椎管内麻醉方式和局部麻醉药物用于择期剖宫产手术的麻醉效果和满意度,并观察其对剖宫产手术快速康复的影响。方法本研究为一项前瞻性研究,采用随机、对照、双盲的研究方法。选取2022年4月至10月于广州医科大学...目的比较临床常用的不同椎管内麻醉方式和局部麻醉药物用于择期剖宫产手术的麻醉效果和满意度,并观察其对剖宫产手术快速康复的影响。方法本研究为一项前瞻性研究,采用随机、对照、双盲的研究方法。选取2022年4月至10月于广州医科大学附属第三医院行剖宫产手术的150例产妇,美国麻醉医师协会(ASA)Ⅰ~Ⅱ级,年龄范围22~39岁,单胎足月孕产妇,无全身其他系统合并症,子宫下段横切口术式。采用随机数字表法分为腰硬联合麻醉罗哌卡因组(SR组)、硬膜外麻醉利多卡因组(EL组)和硬膜外麻醉甲哌卡因组(EM组),每组50例。SR组采用直入法经L3~4间隙行腰硬联合穿刺,在蛛网膜下腔应用等比重的0.5%罗哌卡因3 ml,EL组和EM组采用直入法经L2~3间隙行硬膜外穿刺,分别在硬膜外腔应用2%利多卡因和2%甲哌卡因,各12~15ml。3组硬膜外腔均留置硬膜外导管。观察3组产妇的麻醉效果(药物起效时间、药物剂量、药物达到的最高平面、新生儿血气结果)、麻醉满意度(产妇、外科医生和麻醉医生对麻醉效果的满意度),记录3组产妇的不良反应与快速康复相关的恢复指标(运动阻滞恢复和Bromage评分、术后镇痛的情况、首次下床活动、排气排尿以及出院的时间)情况。采用One way ANOVA、Kruskal-Wallis秩和检验进行统计分析。结果与SR组相比,EL和EM两组麻醉起效时间延长,药物用量增加。SR组低血压、恶心呕吐和术后尿潴留的发生率分别为34%(17/50)、24%(12/50)、14%(7/50),与EL组[14%(7/50)、4%(2/50)、2%(1/50)]和EM组[16%(8/50)、6%(3/50)、0]相比,差异均有统计学意义(均P<0.05)。SR、EL和EM组产妇的首次下床时间分别为(23.52±4.22)h、(18.30±3.80)h、(19.10±5.93)h,出院时间分别为(72.68±12.69)h、(65.28±19.88)h、(65.67±6.14)h,这说明在术后恢复指标上,EL、EM两组与SR组相比,具有一定的优势(均P<0.05)。3组麻醉满意度、新生儿血气结果、术后镇痛效果等比较,差异均无统计学意义(均P>0.05)。此外,EL和EM两组在麻醉效果和术后恢复指标中的差异均无统计学意义(均P>0.05)。结论与腰硬联合麻醉应用罗哌卡因相比,硬膜外麻醉采用利多卡因或甲哌卡因能够在不同程度上提高患者术后快速康复的效果,表现出现代加速康复理念的优越性。展开更多
文摘Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by itsduration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids(dexamethasone), anti-inflammatory agents(parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action(tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability(liposomal, microspheres and cyclodextrin systems) and further studies with other drugs(adenosine, neuromuscular blockers, dextrans).
文摘The mechanisms of epidural-associated fever remain incompletely understood [1-3]. We propose that action of local anesthetic on TPRV1. The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor and the vanilloid receptor can explain this effect and explain mechanism of burning sensation on local anesthetic injected subcutaneously or intramuscular. Role of TRPV1 receptor was not discussed previously in Obstetric Anesthesia literature. Based on available data, we propose that Local Anesthetics work as agonist/antagonist on TPRV1 receptors. Antagonist action may cause hyperthermia through modifying thermoregulation [4], agonist action may cause hyperthermia thru release of IL-6 and other mediators of inflammation [5-10]. Agonist action may explain burning sensation on injection of Local Anesthetics. Burning sensation can be diminished by increasing pH of Local Anesthetic solution, because vanillin receptors are stimulated by acidification through lower pH [11,12].
文摘Background: Procedures that require anesthesia of entire length of the arm should have combined Interscalene block (ISB) and Supraclavicular block (SCB) to ensure adequate block. However, dual block requires high dose of local anesthetic (LA). We examined if Ultrasound (U/S) guided block helps to decrease the required volume of LA by visualizing trunks, so we only need injection of LA toward cervical nerve roots C5 and C6 aiming to block branches escaped from supraclavicular block. Patients and methods: Ninety-three patients were randomly allocated into one of three equal groups, each included 31 patients. All patients received SCB 20 ml (10 ml Bupivacaine 0.5% plus 10 ml lidocaine 2%) and ISB with different volumes of LA according to the group as follow: group A: 20 ml, group B: 15 ml, and group C: 10 ml. Result: No significant difference in onset of block (sensory and motor) and duration of block (motor only) between the three groups (P value > 0.05). The duration of sensory block was significantly longer in group A (760.65 ± 30.87 minutes) than in either group B (740.48 ± 21.15 minutes, P value P value P value P value P value P value < 0.001). Conclusion: A reduced volume of LA can be used in ultra sound guided ISB in combined with SCB to give satisfactory level of anesthesia to entire length of the arm, but the sensory block duration and duration of post-operative analgesia will be decreased significantly with decreasing the volume.
文摘AIM : To systematically evaluate the effect of intraperitoneal local anesthetic on pain characteristics after laparoscopic cholecystectomy(LC).METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library. Randomized controlled trials in English that compared the effect of intraperitoneal administration of local anesthetics on pain with that of placebo or nothing after elective LC under general anesthesia were included. The primary outcome variables analyzed were the combined scores of abdominal, visceral, parietal, and shoulder pain after LC at multiple time points. We also extracted pain scores at resting and dynamic states.RESULTS: We included 39 studies of 3045 patients in total. The administration of intraperitoneal local anesthetic reduced pain intensity in a resting state after laparoscopic cholecystectomy: abdominal [standardized mean difference(SMD) =-0.741; 95%CI:-1.001 to-0.48, P < 0.001]; visceral(SMD =-0.249; 95%CI:-0.493 to-0.006, P = 0.774); and shoulder(SMD =-0.273; 95%CI:-0.464 to-0.082, P = 0.097). Application of intraperitoneal local anesthetic significantly reduced the incidence of shoulder pain(RR = 0.437; 95%CI: 0.299 to 0.639, P < 0.001). There was no favorable effect on resting parietal or dynamic abdominal pain.CONCLUSION: Intraperitoneal local anesthetic as an analgesic adjuvant in patients undergoing laparoscopic cholecystectomy exhibited beneficial effects on postoperative abdominal, visceral, and shoulder pain in a resting state.
文摘Aim: To study the features of local anesthetic solution spreading during sciatic nerve block in dependence on the anesthetic solution volume. Material and Methods: One hundred and sixty nine cases of sciatic nerve blocks done under ultrasonic visualization control were analyzed. Sciatic nerve blocks were performed by lidocaine in volumes 30;25;20;15;12.5;10;7.5;6.5;5;4.5 ml. The cross-section area, equal to local anesthetic spreading, was determined;the extension of the anesthetic solution spreading along sciatic nerve was calculated. Results: The anesthetic agent solution spreads along sciatic nerve in proximal and distal direction, forming a kind of cylinder. The minimum volume of the local anesthetic, which covers sciatic nerve in the whole, is 5 ml. A rare (1.77%) variation of sciatic nerve structure was described, in which tibial and common peroneal nerves develop directly from the branches of sacral plexus. Conclusion: The decrease of the local anesthetic volume leads to reduction of its spreading distance and cross-section area. Ultrasonic visualization can provide for sciatic nerve anatomical peculiarities, which can have an effect on the block quality.
文摘In order to examine whether repeated sciatic nerve blocks showed tachyphylaxis and continuity of sciatic nerve with spinal cord affected development of tachyphylaxis when assayed in vivo by duration of depression compound action potentials (CAP), rats were anesthetized with halothane, ventilated, monitored and supported with stable hemodynamics and temperature. Posterior tibial nerve distally and sciatic nerve in thigh were exposed, placed on bipolar silver electrodes for stimulation and recording respectively. Three sequential sciatic nerve blocks were performed between these electrodes using 0.15 ml of 3 % chloroprocaine. Nine rats were chosen to observe the effects of repeated sciatic nerve blocks on CAP. In another 18 rats, a second investigator exposed the sciatic nerve near its origin at spinal cord and randomly performed nerve cut and sham (n=9), and closed the incision blinding the electrophysiologic investigator. The results showed that electrical stimulated tibial nerve induced sciatic nerve Aα/β, Aδ, C fiber mediated CAP waves. CAP amplitudes were remained stable during whole experimental procedure. CAP amplitudes were decreased completely with 3% chloroprocaine blocked sciatic nerve and recovered fully. The duration of CAP depression were reduced with repeated blocks. There were no selective blocked effects on Aα/β, Aδ, C fiber mediated CAP. With sciatic nerve cut proximally, there was no statistical significant tachyphylaxis with 3 % chloroprocaine repeated blocked sciatic nerve, and the duration of first and third blocked Aδ fiber mediated CAP was 108±20 and 92±14 min respectively (P>0.05). In normal rats the duration of first and third blocked Aδ fiber mediated CAP was 110±20 and 75±16 min respectively (P<0.05). It was suggested that tachyphylaxis to local anesthetics can occur in rats repeated blocked sciatic nerve when assayed in vivo by duration of depression CAP. The continuity of sciatic nerve with spinal cord is one of the important factors affecting the development of tachyphylaxis.
文摘Posterior disc displacement of the temporomandibular joint is rare. We present a unique treatment method and magnetic resonance (MR) images of this condition. The patient was a 43-year-old male with a chief complaint of abnormal occlusion. Regarding the present status, there was no occlusion on the right side. No temporomandibular joint pain, myalgia, or clicking were observed while mouth opening. On MR images, the posterior disc displacement without reduction on the right was observed and it was assumed that occlusal abnormality was due to this condition. We treated him with the following methods. After injection into the superior articular cavity with 2% lidocaine, a sodium hyaluronate preparation was injected followed by intermaxillary traction applied using rubber. The recovery of occlusion was confirmed in follow-up at 5 days after treatment. In the 13th days, the intermaxillary traction was removed. On MR images, the right disc condition was changed to anterior disc displacement with reduction. We consider our treatment methods are effective for this clinical condition.
文摘<b>Introduction:</b> Local anesthetics (LAs) must be adsorbed to and permeate through membranes to reach their sites of action. The rates of these processes critically affect drug actions at the cellular level and also the <i>in vivo</i> pharmacokinetics of perineurally injected drugs. Therefore, we measured the adsorption equilibria and permeation kinetics of two LAs local anesthetics with markedly different hydrophobicities: tetracaine (TTC, P<sub>octanol:buffer</sub> = 3.6 × 10<sup>3</sup>) and procaine (PRO, P<sub>octanol:buffer</sub> = 8.1 × 10<sup>1</sup>), in unilamellar membranes of different composition and fluidity. <b>Methods:</b> Interactions with unilamellar vesicles made of dipalmitoylphosphatidylcholine (DPPC), at 23°C (solid gel state) or 45°C (liquid crystal state), without or with cholesterol (Chol), were investigated by a combination of fluorescence and stopped-flow techniques. Membrane adsorption was monitored by the LA’s fluorescence. Membrane permeation was monitored by the decrease of fluorescence intensity of intra-vesicular pyranine, when quenched by neighboring TTC or PRO. <b>Results:</b> Ionized TTC (TTCH<sup>+</sup>) and procaine (PROH<sup>+</sup>) adsorb to membranes more slowly and weakly than their neutral counterparts (time constant <i>τ</i> ~ 0.1 sec). Fluidizing of membranes, at the higher temperature (45°C) or by Chol inclusion, accelerated LA adsorption (faster than the mixing time of the stopped-flow device, 0.008 s). Permeation of protonated TTCH<sup>+</sup> through the solid gel DPPC membranes (23°C) occurred far more slowly than adsorption, (<i>τ</i> = 36.7 ± 0.7 s, n = 9), and 3 times slower than neutral TTC (<i>τ</i> = 10.9 ± 0.7 s, n = 9);neutral PRO permeated these membranes at the same rate as TTC. Inclusion of Chol with DPPC, disordering the fatty acyl tails of membrane phospholipids while crowding their polar headgroups, slowed permeation of TTC and of PRO to an even greater degree. <b>Conclusions:</b> Local anesthetic permeation through membranes is limited by the transport across the membrane core and not by the initial binding. Drug ionization greatly slows permeation, but greater hydrophobicity does not facilitate it. Lipid crowding caused by Chol, a normal membrane component, slows permeation by disorienting the LA bound at the surface.
文摘目的比较临床常用的不同椎管内麻醉方式和局部麻醉药物用于择期剖宫产手术的麻醉效果和满意度,并观察其对剖宫产手术快速康复的影响。方法本研究为一项前瞻性研究,采用随机、对照、双盲的研究方法。选取2022年4月至10月于广州医科大学附属第三医院行剖宫产手术的150例产妇,美国麻醉医师协会(ASA)Ⅰ~Ⅱ级,年龄范围22~39岁,单胎足月孕产妇,无全身其他系统合并症,子宫下段横切口术式。采用随机数字表法分为腰硬联合麻醉罗哌卡因组(SR组)、硬膜外麻醉利多卡因组(EL组)和硬膜外麻醉甲哌卡因组(EM组),每组50例。SR组采用直入法经L3~4间隙行腰硬联合穿刺,在蛛网膜下腔应用等比重的0.5%罗哌卡因3 ml,EL组和EM组采用直入法经L2~3间隙行硬膜外穿刺,分别在硬膜外腔应用2%利多卡因和2%甲哌卡因,各12~15ml。3组硬膜外腔均留置硬膜外导管。观察3组产妇的麻醉效果(药物起效时间、药物剂量、药物达到的最高平面、新生儿血气结果)、麻醉满意度(产妇、外科医生和麻醉医生对麻醉效果的满意度),记录3组产妇的不良反应与快速康复相关的恢复指标(运动阻滞恢复和Bromage评分、术后镇痛的情况、首次下床活动、排气排尿以及出院的时间)情况。采用One way ANOVA、Kruskal-Wallis秩和检验进行统计分析。结果与SR组相比,EL和EM两组麻醉起效时间延长,药物用量增加。SR组低血压、恶心呕吐和术后尿潴留的发生率分别为34%(17/50)、24%(12/50)、14%(7/50),与EL组[14%(7/50)、4%(2/50)、2%(1/50)]和EM组[16%(8/50)、6%(3/50)、0]相比,差异均有统计学意义(均P<0.05)。SR、EL和EM组产妇的首次下床时间分别为(23.52±4.22)h、(18.30±3.80)h、(19.10±5.93)h,出院时间分别为(72.68±12.69)h、(65.28±19.88)h、(65.67±6.14)h,这说明在术后恢复指标上,EL、EM两组与SR组相比,具有一定的优势(均P<0.05)。3组麻醉满意度、新生儿血气结果、术后镇痛效果等比较,差异均无统计学意义(均P>0.05)。此外,EL和EM两组在麻醉效果和术后恢复指标中的差异均无统计学意义(均P>0.05)。结论与腰硬联合麻醉应用罗哌卡因相比,硬膜外麻醉采用利多卡因或甲哌卡因能够在不同程度上提高患者术后快速康复的效果,表现出现代加速康复理念的优越性。