Pharmacokinetics Of Local Anesthetics Research Articles

Pharmacokinetics in regional anesthesia.

Pharmacokinetics of local anesthetics are one of the main determinants of success and safety of regional anesthesia and comprise local and systemic distribution phases. This review aims to summarize the latest research findings on this topic in the context of various regional blocks performed for different surgeries and patient populations. Research into local kinetics and systemic absorption of local anesthetics has chiefly been focused on novel fascial plane blocks, especially the erector spinae plane block, as these are increasingly adopted for regional anesthesia and pain management. As their clinical efficacy is very dependent on injection of large volumes of local anesthetic, doses over typically recommended limits are often administered. Fascial plane blocks are the regional anesthesia techniques in need of the most pharmacokinetic characterization, not only to better understand their complex mechanisms of action but also to avoid harm from excessive doses of local anesthetics. Further mapping of risk factors for systemic toxicity from administration in different block sites is crucial. Extremes of age and pregnancy are vulnerable patient populations but in whom regional anesthesia, including novel techniques, has been performed with few complications.

Onset times and duration of analgesic effect of various concentrations of local anesthetic solutions in standardized volume used for brachial plexus blocks

Visualization of the nerve structures of brachial plexus allows anesthesiologists to use a lower dose of local anesthetics. The content of this low dose is not unequivocal, consequently, the pharmacokinetics of local anesthetics used by various authors are difficult to compare. In this study, the onset times and duration of the analgesic effect of local anesthetic mixture solutions used for brachial plexus blocks are investigated and the quality of anesthesia is compared. 85 unpremedicated American Society of Anesthesiologist physical status I-III, 19-83-year-old patients scheduled for upper limb trauma surgery are assigned to four groups for the axillary-supraclavicular block with lidocaine 1% and bupivacaine 0,5% 1:1 mixture (Group LB) or bupivacaine 0.33% (Group BS) or lidocaine 0,66% (Group LS) or bupivacaine 0.5% and lidocaine 1% 2:1 mixture (Group BL). 0.4 ml/kg was administered to the four groups. The onset time was significantly shorter in the lidocaine group (LS 13.0 ± 1.02) than in the other study groups (LB 16.64 ± 0.89; BS 17.21 ± 0.74; BL 16.92 ± 0.51 min ±SEM, p = 0.002). No differences were observed in the onset times between LB, BS, and BL groups (p > 0.05). Statistical differences were found in the duration of local anesthetics between LB (392.9 ± 20.4), BS (546.4 ± 14.9), LS (172.85 ± 7.8), and BL (458.7 ± 11.9 min ±SEM, p = 0.001). Lidocaine does not shorten the onset times, but significantly decreases the duration of action of bupivacaine when used in mixture solutions. Lidocaine exhibits a good quality of block in the applied dose, while other solutions have excellent quality. Bupivacaine without lidocaine has the longest duration of action to achieve the longest postoperative analgesia.

Child and regional anesthesia - What for? Where? And how?

Regional anesthesia is experiencing a renaissance, which is certainly due to the possibility of an effective blockade of nociceptive impulsion from the surgery area, minimum pharmacological load during combined anesthesia, appropriate perioperative anesthesia and implementation of the equipment defining neuronal structure in routine practice. However, for the safe use of these techniques in pediatric practice, it is necessary to know the age-related anatomical and physiological characteristics of the child, the pharmacokinetics of local anesthetics and principles of their use. These issues are the focus of this review of the literature.

Current advances in intermittent epidural bolus for labor analgesia

Background In the recent years, intermittent epidural bolus(IEB) for labor analgesia is drawing increasing concern as a new method of administration. Objective The aim of this article is to address the role of IEB in labor analgesia. Content This article reviews the pharmacokinetics of local anesthetics, the degree of analgesia and motor blockage, as well as the effects of IEB on labor outcomes. Trend IEB may be widely accepted as an effective method of administration in labor analgesia through intense research and expanding procedural experience. Key words: Analgesia, obstetric; Anaesthetic techniques, epidural

Plasma Ropivacaine Concentrations After Ultrasound-Guided Rectus Sheath Block in Patients Undergoing Lower Abdominal Surgery

A rectus sheath block can provide postoperative analgesia for midline incisions. However, information regarding the pharmacokinetics of local anesthetics used in this block is lacking. In this study, we detail the time course of ropivacaine concentrations after this block. Thirty-nine patients undergoing elective lower abdominal surgery were assigned to 3 groups receiving rectus sheath block with 20 mL of different concentrations of ropivacaine. Peak plasma concentrations were dose dependent, and there were no significant differences in the times to peak plasma concentrations. The present data also suggested a slower absorption kinetics profile for ropivacaine after rectus sheath block than other compartment blocks.

Optimization of Spinal Anesthesia in Surgery of Intervertebral Disks

The paper gives the data of preoperative evaluation of autonomous nervous system tone and its correction, pharmacokinetics of local anesthetics in the subarachnoidal space, as well as the optimization of a procedure for spinal anesthesia in patients operated on for lumbosacral radiculitis.

Pharmacokinetics of local anaesthetics in infants and children.

Amide local anaesthetics used for regional anaesthesia in paediatric patients are potent sodium channel blockers with marked stereospecificity, which consistently influences their action, especially their toxic action on the heart. At toxic concentrations, they induce severe arrhythmias with the potential for cardiac arrest. These agents are all bound to serum proteins, mainly to alpha(1)-acid glycoprotein (AAG), but also to human serum albumin. Protein binding ranges from 65% (lidocaine) to more than 95% (bupivacaine, ropivacaine). Because AAG is a major acute phase protein, its concentration rapidly increases when inflammatory processes develop, particularly during the postoperative period. Neonates and infants have a lower AAG concentration in serum as compared with adults; therefore, their free fraction of local anaesthetics is increased accordingly. This has important clinical implications since, at least at steady state, the toxic effects of local anaesthetics are directly related to the free (unbound) drug concentration. After injection into the epidural space, absorption into the bloodstream follows a biphasic process. The buffering properties of the epidural space are important and prevent a rapid rise in concentration. In infants and children, the epidural space seems to protect patients in a similar manner. Moreover, it has been observed that the peak plasma concentration (C(max)) of ropivacaine is delayed in infants and children when compared with adults. The time to C(max) decreases from 90-120 minutes in infants aged less than 6 months to 30 minutes in children aged more than 8 years. This delay in C(max) may also be related to the lower clearance observed in younger patients. Local anaesthetics are metabolised by cytochrome P450 (CYP). The main CYP isoforms involved are CYP3A4 for lidocaine and bupivacaine and CYP1A2 for ropivacaine. CYP3A4 is not mature at birth but is partly replaced by CYP3A7. The intrinsic clearance of bupivacaine is only one-third of that in adults at 1 month of age, and two-thirds at 6 months. CYP1A2 is not fully mature before the age of 3 years. Indeed, the clearance of ropivacaine does not reach its maximum before the age of 5 years. However, at birth this clearance is not as low as expected, and ropivacaine may be used even in younger patients.

Pharmacokinetics of ropivacaine in uremic and nonuremic patients after axillary brachial plexus block.

Reports on the efficacy and pharmacokinetics of local anesthetics in uremic patients have been controversial. Our study involved 29 uremic and 28 nonuremic patients. We performed axillary block with ropivacaine 300 mg (50 mL). Venous blood samples were drawn for 24 h for assay of total and unbound plasma ropivacaine, 3-hydroxyropivacaine, pipecoloxylidide (PPX), and serum alpha(1)-acid glycoprotein (AAG). Block quality was similar in both groups. No toxicity occurred. Plasma clearance of ropivacaine was smaller and the area under the concentration-time curve of ropivacaine, 3-hydroxyropivacaine, and PPX larger in the uremic patients. The plasma concentration of PPX increased until 24 h in uremic patients whose AAG concentrations were also larger throughout the study. The free fraction of ropivacaine in plasma was smaller in the uremic group when measured 60 min and 12 h after the block, but the unbound concentration of ropivacaine was larger in the uremic group at 12 h. Enhanced absorption of ropivacaine into circulation, increased binding to AAG, and probably reduced urinary excretion of the metabolites lead to larger total plasma concentrations of ropivacaine and its main metabolites in uremic patients.

Recent advances in the pharmacokinetics of local anaesthetics. Long-acting amide enantiomers and continuous infusions.

The most widely used long-acting amide local anaesthetic is bupivacaine, a racemic mixture of 2 stereoisomers. However, there is evidence that the use of single enantiomer compounds offers advantages over racemic agents. Ropivacaine, the recently introduced propyl homologue of bupivacaine, is a pure S-(-)-enantiomer. It is associated with a reduced incidence of both cardiovascular and central nervous system toxicity, a concern with racemic bupivacaine, in preclinical studies. The relevant pharmacokinetic differences include a lower lipid solubility, a slightly higher plasma clearance and shorter elimination half-life (t 1/2 beta) compared with racemic bupivacaine, with a similar degree of plasma protein binding. More recently levobupivacaine, the pure S-(-)-enantiomer of bupivacaine, has been produced. Stereoselective differences have been observed between the 2 enantiomers and the racemic mixture, with levobupivacaine exhibiting a slightly higher degree of plasma protein binding, a lower volume of distribution, a higher plasma clearance, and a shorter t 1/2 beta than the R-(+)-enantiomer. In common with ropivacaine, levobupivacaine has been shown to have a reduced incidence of toxicity in comparison the R-(+)-enantiomer in preclinical studies, explained in part by a reduced affinity to both brain and myocardial tissue. Racemic bupivacaine is increasingly administered by continuous infusion to provide prolonged postoperative analgesia. The pharmacokinetic profile of the drug administered in this manner has only recently been elucidated and indicates a slow rise in total plasma concentration with increasing duration of infusion, mitigated by changes in plasma protein concentrations during the postoperative period. This appears to be the predominant reason why complications related to systemic toxicity are rarely observed with this technique. However, continuous administration of individual enantiomers may potentially serve as a safer option in the future.

Plasma concentrations of bupivacaine after lumbar sympathetic block.

To determine the pharmacokinetics of local anesthetics after lumbar sympathetic blocks, total and free (unbound) plasma concentrations of bupivacaine in venous blood samples were measured in 12 patients using a high-performance liquid chromatography (HPLC) technique. Administration of 30 mL of plain bupivacaine 0.175%, via two needles, resulted in a maximum total plasma concentration of 0.2-1.0 mg/L (mean 0.49 mg/L). These maximum concentrations were reached 10-45 min after the injection (mean 24 min). There were no clinical signs of central nervous system (CNS) toxicity attributable to local anesthetics. All patients showed hemodynamic stability after the blocks. We conclude that the absorption of local anesthetics after lumbar sympathetic blocks is slow compared to stellate ganglion or intercostal blocks, and does not result in toxic plasma concentrations. These blocks might well be performed in outpatients.

Pharmacokinetics and pharmacodynamics of medullar agents: a. Local anaesthetics

In considering the pharmacokinetics of local anaesthetics, both the systemic absorption and systemic disposition are of importance. Systemic absorption of local anaesthetics limits the duration of nerve block and is of concern in view of systemic toxicity. Initial absorption rates are higher after epidural than after subarachnoid injection, whereas the slower, secondary absorption rates are similar. Amide-type local anaesthetics undergo extensive tissue distribution. Volumes of distribution vary from approximately 60 to nearly 200 litres. Elimination occurs almost exclusively by biotransformation. Amide-type agents are predominantly metabolized in the liver. Total body clearances vary from 0.6 to 2.4 litres/min. Ester-type agents are hydrolysed in the liver and in blood, ensuring very fast elimination. Blood or plasma concentrations after single epidural injections vary with the local anaesthetic and the dose. Addition of adrenaline to local anaesthetic solutions reduces the peak plasma concentrations. Long-term continuous epidural infusions for postoperative pain relief may result in significant accumulation, reflecting increases in plasma protein binding. Plasma concentrations after subarachnoid administration are very low, so the risk of systemic toxicity is very small. The main factors determining the onset, quality and duration of epidural neural blockade are the local anaesthetic employed and its physicochemical properties. Onset in the caudad segments is usually faster, and spread of analgesia is higher in older patients. Addition of adrenaline prolongs the duration. Ongoing clinical studies show that ropivacaine is an effective long-acting local anaesthetic when given epidurally. Bupivacaine has frequently been used, either as a glucose-free or hyperbaric solution, for spinal anaesthesia. Glucose-free bupivacaine solutions provide long-lasting motor blockade, but appear to provide an unpredictable spread of analgesia. Advancing age has been shown to be associated with a prolonged duration of analgesia with glucose-free bupivacaine solutions and a greater spread of analgesia with hyperbaric bupivacaine solutions.

局所麻酔薬の動態

局所麻酔薬の動態