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At least 19 recordsLinked to original sources
PubMed2026

Morbidity and mortality from local anesthetics: localized and systemic toxicity.

PURPOSE OF THE REVIEW: Local anesthetics remain vital to modern medicine, yet their narrow therapeutic window continues to result in complications. This review synthesizes recent literature to define the current landscape of local anesthetic-associated adverse events. RECENT FINDINGS: Perioperative mortality attributable to local anesthetics persists despite sustained safety initiatives and professional society recommendations. Pharmacovigilance and case data identify lidocaine (oropharyngeal, topical, and via local infiltration) as the predominant contributor to adverse outcomes, including death. Local anesthetic systemic toxicity remains an issue, with a recent shift in epidemiology: an increasing proportion of toxic events originates from surgeon- and proceduralist-administered analgesia. Anesthesiologist-controlled methods also cause toxicity via catheter-based delivery and nerve blocks in highly vascular regions. Localized toxicity in the form of high neuraxial contributes to morbidity, with recent reviews reinforcing known risk factors; whereas localized neurotoxicity appears less troublesome when managed appropriately. SUMMARY: The cumulative evidence identifies shifts in the patterns of systemic and localized toxicities. Bupivacaine-based peripheral nerve blocks no longer represent the principal cause of complications because of the advent of ultrasound guidance and lipid emulsion therapy. In contrast, high neuraxial techniques persist as a cause of morbidity, accompanied by intravenous/oropharyngeal lidocaine, proceduralist-administered local infiltration analgesia, and catheter-based delivery.

Humans↗
PubMed2026

Adductor Canal Block and Local Anesthetic Versus Local Anesthetic Alone in ACL Reconstruction: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Effective postoperative analgesia is crucial for early recovery after anterior cruciate ligament reconstruction (ACLR). Local infiltration analgesia (LIA) and adductor canal block (ACB) are common regional techniques, but their combined efficacy remains unclear. PURPOSE: To compare the effectiveness of LIA alone versus LIA combined with ACB in patients undergoing ACLR, with primary outcomes including postoperative opioid consumption and quadriceps function. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A double-blind randomized controlled trial enrolled 100 patients undergoing ACLR under general anesthesia. Patients were randomized into 2 groups: LIA + sham (saline injection) (n = 50) and LIA + ACB (n = 50). The primary outcome was postoperative opioid consumption in the first 24 hours. Secondary outcomes included visual analog scale (VAS) pain score, quadriceps function assessed by straight leg raise (SLR) at 3 hours, Quality of Recovery-15 (QoR-15) score, and Knee Injury and Osteoarthritis Outcome Score (KOOS) at 1 week. Statistical analysis was performed using t tests and chi-square tests with a P value <.05 considered significant. RESULTS: There was no significant difference in 24-hour opioid consumption between the LIA + ACB and LIA-only groups (P = .109). Similarly, VAS pain scores at 24 hours postoperatively showed no significant differences between the groups (P = .0804). Early functional recovery, assessed by SLR performance at 3 hours, was equivalent between groups (P = .6711). Additionally, QoR-15 scores on postoperative day 1 and KOOS values at 1 week demonstrated no significant differences (P = .6486 and P = .9054, respectively). Intraoperative opioid consumption was not different between the groups (P = .127). CONCLUSION: These findings indicate that the addition of ACB to LIA does not yield postoperative analgesic in ACLR. Consequently, LIA alone suffices for routine ACLR, potentially enabling clinicians to optimize perioperative workflows without incurring the additional time, financial burden, and resources associated with routine ACB administration. TRIAL REGISTRATION: ClinicalTrials.gov; NCT04721119.

Humans↗
PubMed1992

[Local anesthetics. CVII. Local anesthetic effects of phenylcarbamates--the effect of connecting chain modification].

The preceding study of the effect of the branching of the connecting chain by the metoxymethyl-, ethoxymethyl- and propoxymethyl group on the alpha carbon on local anaesthetic activity was a stimulus for the preparation of 16 drugs of the group of 1-ethoxyethoxymethyl-2-(1-pyrrolidinyl-), 2-piperidino- and 2-(1-perhydroazepinyl) ethyl esters of o-, m- and p-alkoxyphenylcarbamic acids. The discontinuation of the substituent on the alpha carbon of the connecting chain by another oxygen atom (introduction of an ethoxyethoxymethyl group) has a positive effect on surface and infiltration anaesthesia. Of the prepared agents, 2-piperidino- and 2-(1-perhydroazepinyl-) derivatives with a hexyl or heptyloxy group in the o-position of the benzene ring were most effective; they exceeded the standards cocaine and procaine more than one hundred times. p-Derivatives were least effective; in some cases their indices of effectiveness did not achieve the effectiveness of the standards in both surface and infiltration anaesthesia under study. Acute toxicity of all drugs lies within the range of the toxicities of the standards.

Anesthetics, Local↗
PubMed1976

Molecular mechanisms of nerve block by local anesthetics.

Local anesthetics block nerve conduction by preventing the increase in membrane permeability to sodium ions that normally leads to a nerve impulse. Among anesthetics containing tertiary amine groups, the cationic, protonated form appears to be more active than the neutral form. However, the neutral forms, as well as uncharged molecules like benzocaine and the aliphatic alcohols, also depress sodium permeability. Studies of single myelinated nerves and squid axons show no direct interaction between calcium ions and local anesthetics, thus disproving theories based on competition between these two agents. Likewise, hypotheses attributing local anesthesia to changes in electrical potentials at the membrane-water interface are disproven by the demonstrated potencies of electrically uncharged anesthetics. Hypotheses that propose that local anesthetics act by expanding the nerve membrane and causing a change in protein conformation that blocks sodium permeability are vague in conception and difficult to test experimentally. Evidence from voltage-clamp studies of single nerve fibers indicates that anesthetic molecules interact with the sodium channels directly, from the inner side of the nerve membrane. Anesthetics bind within sodium channels which have opened during membrane depolarization, preventing the normal sodium ion flux. Anesthetic molecules can dissociate from open channels, but not from channels that remain closed when the nerve is kept at rest. The "gating" properties that regulate the opening and closing of sodium channels are reversibly modified during anesthesia. Specifically, the inactivation function responds more slowly and requires more negative membrane potential changes to reach the same values as in unanesthetized nerves. A second, slow inactivation is observed following external application of tertiary amine anesthetics. The selective binding of anesthetics to open sodium channels provides a simple explanation for Wedenski inhibition, in which the block increases with the frequency of nerve impulses. When impulses occur at higher frequencies more sodium channels are open over a period of time comparable to the time necessary for the anesthetic binding reaction, thus more channels are blocked. In addition the changes of the inactivation function result in a longer refractory period and, thus, a decrease of impulse height at higher frequencies. Charged anesthetic molecules may bind in the pore of the sodium channel. Their binding can be modulated by the electrical field in the membrane. The channel has a higher affinity for larger anesthetic molecules, but this may result from their greater hydrophobicity as well as from their size. The binding site favors molecules that contain more polar linkages between the amine group and the aromatic residue. Binding of amine anesthetics is weakly stereospecific and, surprisingly, shows no absolute requirement for the terminal alkyl ammonium moiety present in most local anesthetics...

Action Potentials↗
PubMed1977

Neural blockade by local anesthetics.

Local anesthetics block nerve impulse propagation by occluding transmembrane sodium channels, so preventing depolarization. First, the uncharged lipid-soluble anesthetic base pentrates the membrane; then the positively charged cation binds to anionic components of the sodium channel's internal axoplasmic mouth. Though primarily a carrier, the base contributes to blockade by causing the membrane to swell, so pinching the sodium channels. Dissolved in water, local anesthetic salt crystals dissociate into anesthetic cation and base-proportional to the drug's fixed pKa and the tissue's variable pH. The cation-base concentration ration is critical to optimal neural blockade. If there is too little base, few anesthetic molecules will penetrate to the neural target; if too little cation, few sodium channels will be plugged.

Anesthetics, Local↗
PubMed1992

[Local anesthetics. 99. Synthesis and local anesthetic actions of alkoxyphenylcarbamates].

Within the framework of studying the influence of alterations of the connecting chain in the group of local anaesthetics a series of 24 compounds of 1-propoxymethyl-2-(1-pyrrolidinyl), 2-(1-piperidino)-, and 2-(1-perhydroazepinyl)-ethyl esters of o- and m-alkoxyphenylcarbamic acid were prepared. Studied compounds show a high index of relative local anaesthetic activity as compared to the standards cocaine and procaine, at a relatively low acute toxicity.

Anesthetics, Local↗
PubMed1976

The local anesthetic activity of saxitoxin alone and with vasoconstrictor and local anesthetic agents.

STX (saxitoxin), alone and with various vasoconstrictor and local anesthetic agents, was evaluated for its ability to produce topical anesthesia on the rabbit cornea, peripheral nerve block in the rat, and epidural anesthesia in the dog. High frequency and long duration of block can be attained if sufficiently high concentrations of STX are used, although latency is long and the doses used may produce systemic toxicity. Frequency of satisfactory blocks and mean duration of block can be increased and systemic toxicity reduced if STX is administered with a vasoconstrictor agent. Conventional local anesthetic agents also enhance the nerve blocking activity of STX. When appropriate concentrations of STX, vasoconstrictor and local anesthetic agents are used, systemic toxic effects are not manifested and the blocks produced exhibit the rapid onset and high frequency of block characteristic of the local anesthetic agent and the remarkably long duration of STX.

Anesthesia, Epidural↗
PubMed1975

[Relations between the physico-chemical properties, the chemical reactivity and the local-anesthetic activity/part 33: studies on the interactions of local-anesthetically active cinchocaine homologues with phospholipids (author's transl)].

The general part consists of a review on nerve stimulus mechanism as well as the nerve structure and the function of nerve membrane as the site of action of local anesthetics. Furthermore a possibility of interaction between local anesthetics and the membrane components especially phospholipids is discussed. These phospholipids show interesting properties with respect to ions as well as local-anesthetics, which allow us to suppose that they are important participants in nervous stimulus transmission. In the experimental part two methods are described. The first deals with the measurement of electrical resistance as function of time at cephalin and cholesterin impregnated filter membrane in solutions of cinchocain homologues. An increase in the resistance with the increase in concentration of test substances was observed. The same was the effect of increasing chain length in alkoxy group where after butoxy derivative, a deformation of membrane was observed. In the second method the drug binding capacity of cephalin dispersed in aqueous medium was measured. Here, too, the increase in the binding capacity with the increase in alkoxy chain was observed. The large difference in free binding energy between two subsequent homologues is explained as the effect of increase in van der Waals' forces and hydrophobic interactions on one hand, and a change in colloidal form of cephalin dispersion on the other hand.

Absorption↗
PubMedDate not supplied

Pleural permeability to local anesthetics--the influence of concentration, pH, and local anesthetic combinations.

The transpleural passage of lidocaine, bupivacaine-lidocaine mixtures, and of bupivacaine, with and without epinephrine, was studied in vitro using pleural from piglets. Our objective was to ascertain whether changing physical parameters of local anesthetics such as pH, concentration, and addition of epinephrine might influence the transfer. Rate of transfer is linearly related to concentration at a given pH, but raising the pH increases the rate for bupivacaine. No change in rate was detectable when the pH of lidocaine was increased or in the rate of transfer of bupivacaine when bupivacaine and lidocaine were mixed. The mixture did however facilitate lidocaine flux. Epinephrine [1:200,000] lowers the pH of the solution dramatically but does not statistically change the transpleural passage of bupivacaine. We conclude that the onset of interpleural blockade may be shortened by using more concentrated solutions of bupivacaine whose pH have been modified by the addition of alkali, by using the higher concentrations of lidocaine or by mixing lidocaine with bupivacaine.

Anesthetics, Local↗
PubMedDate not supplied

The local anesthetic activity of tetrodotoxin alone and in combination with vasoconstrictors and local anesthetics.

Tetrodotoxin (TTX), alone and in combination with various vasoconstrictors and local anesthetics, was evaluated for its ability to produce peripheral nerve blocks in the rat and central neural blocks in the cat and dog. High frequency and long duration of block can be attained if sufficiently high concentrations of TTX are used, although latency is long and high dosage may produce systemic toxicity. Frequency and mean duration of block can be increased and systemic toxicity reduced if TTX is administered with a vasoconstrictive agent. Conventional local anesthetics also enhance the nerve-blocking activity of TTX. When appropriate concentrations of TTX and local anesthetics are used, a high frequency of blocks characterized by short latency and long duration can be demonstrated. The studies present some indirect evidence that local anesthetics enhance TTX activity by reversibly increasing the permeability of various neural barriers to TTX.

Anesthesia, Epidural↗
PubMed1979

Etidocaine, a new local anesthetic.

Different local anesthetics have different physicochemical properties that result in different biological effects. Etidocaine (Duranest) is said to be a long-acting anesthetic with a rapid onset of action, properties that are particularly useful in busy office practices in which lengthy operative procedures are performed. Clinical testing confirmed that this anesthetic does, indeed, work in this manner, which makes it a good addition to the varieties of local anesthetics available.

Acetanilides↗