Direct Cytotoxic and Indirect, Immune-Mediated Effects of Local Anesthetics Against Cancer

Local anesthetics are frequently employed during surgery in order to control peri- and postoperative pain. Retrospective studies have revealed an unexpected correlation between increased long-term survival and the use of local anesthetics during oncological surgery. This effect of local anesthetics might rely on direct cytotoxic effects on malignant cells or on indirect, immune-mediated effects. It is tempting to speculate, yet needs to be formally proven, that the combination of local anesthetics with oncological surgery and conventional anticancer therapy would offer an opportunity to control residual cancer cells. This review summarizes findings from fundamental research together with clinical data on the use of local anesthetics as anticancer standalone drugs or their combination with conventional treatments. We suggest that a better comprehension of the anticancer effects of local anesthetics at the preclinical and clinical levels may broadly improve the surgical treatment of cancer.

Effects of auriculopalpebral nerve block on ocular parameters in dogs

The objective of this study was to compare the effects of two local anesthetics used on auriculopalpebral block on eyelid akinesia, tear production, intraocular pressure (IOP) and tear break-up time (TBUT) in conscious dogs. A blind, randomized, prospective study was conducted to determine the effects of auriculopalpebral block using ropivacaine 0.75% and bupivacaine 0.5% in 12 healthy non-brachycephalic dogs (24 eyes). Threat response and eyelid reflex tests, Schirmer tear test (STT), IOP and tear break-up time were conducted before blockage and at 30, 60, 120, 240 and 360 minutes after application. A difference was observed between the values found at 30, 60, 120 and 240 minutes compared to baseline for threat response and eyelid reflex tests in the two groups evaluated, proving eyelid akinesia after blockages. No difference was found for STT, IOP and TBUT between baseline values and post-anesthesia times or between groups. It was possible to conclude that ropivacaine and bupivacaine on auriculopalpebral block in conscious dogs promoted eyelid akinesia for at least 240 minutes, not altering ocular physiological parameters of tear production, intraocular pressure, and tear break-up time after blockages.

Two cases of late-onset cardiovascular toxicities after a single injection of local anesthetics during supraclavicular brachial plexus block - A report of two cases -

Background: Local anesthetics systemic toxicity (LAST) is a grave complication of regional anesthesia that usually occurs immediately after local anesthetics injection. Here, we report on rare late-onset toxicity cases after supraclavicular brachial plexus blocks.Case: Two patients underwent surgery for radius fractures. We used lidocaine 100 mg and ropivacaine 150 mg for blocking and infused dexmedetomidine for intraoperative sedation. The 63-year-old male patient’s blood pressure dropped to 87/60 mmHg after 3 h 15 min after blocking. Ventricular fibrillation occurred 10 min later. After five defibrillations, electrocardiography showed ventricular tachycardia that was normalized through one cardioversion. The 54-year-old female patient’s heart rate decreased to 35 beats/min 2 h 30 min after blocking. Her vital signs returned to normal after administering atropine, ephedrine, epinephrine, and lipid emulsion.Conclusions: Physicians should remember that LAST may occur long after local anesthetic injection and be aware of factors that may adversely affect the course of LAST.

Three Studies Evaluating the Potential for Lidocaine, Bupivacaine or Procaine to Reduce Pain-Related Behaviors following Ring Castration and/or Tail Docking in Lambs

The use of local anesthesia at the time of ring castration and tail docking can improve lamb welfare. However, few local anesthetics are registered for sheep, and data on their duration of effect is limited. Three studies were conducted to evaluate the efficacy of procaine (P), lidocaine (L), and bupivacaine (B) in terms of observed alleviation of behavioral responses to castration and/or tail docking in 10-min blocks in the first 60 min post-treatment. In each study, comparisons were made between two groups of lambs castrated and/or tail docked with rubber rings and either receiving the agent using the NUMNUTS® instrument (N) or receiving no anesthetic agent (RR). Acute pain behavior was lower in NL (n = 28) than RRL (n = 15) males in the first 10 min post-procedure (p < 0.05); lower in NB (n = 16) than RRB (n = 16) males in periods 10–20 min (0.05 < p < 0.01), 20–30 min (p < 0.05) and 40–50 min (0.05 < p < 0.01); lower in NB (n = 16) than RRB (n = 16) females between 20 and 40 min post-procedure (0.05 < p < 0.01); lower in NP (n = 8) than RRP (n = 7) males in period 10–20 min (0.05 < p < 0.01), and lower in NP (n = 9) than RRP (n = 9) females in periods 0–10 min (0.05 < p < 0.01), and 10–40 min (p < 0.05). Benefits were modest, and the effects of procaine appear to last longer than lidocaine, while bupivacaine is slower to take effect than either procaine or lidocaine but may provide longer-lasting pain relief. The duration of action of local anesthetics is short in sheep, and detailed behavioral evaluations are required in the first hour post-procedure to establish efficacy.

Adverse reactions of local anesthetics

The article explains the adverse reactions of local anesthetics, in particular one of them, called the toxicity of local anesthetics. It has been shown that for the development of systemic toxicity of local anesthetics, higher doses of the latter are required in comparison with those recommended in the instructions. It is proposed in the regulatory documents to replace the term 'toxicity of local anesthetics' with the term 'side effects of local anesthetics'

Mechanisms of Cancer Inhibition by Local Anesthetics

The use of local anesthetics during surgical treatment of cancer patients is an important part of perioperative analgesia. In recent years, it has been showed that local anesthetics can directly or indirectly affect the progression of tumors. In vitro and in vivo studies have demonstrated that local anesthetics reduced cancer recurrence. The etiology of this effect is likely multifactorial. Numerous mechanisms were proposed based on the local anesthetic used and the type of cancer. Mechanisms center on NaV1.5 channels, Ras homolog gene family member A, cell cycle, endothelial growth factor receptor, calcium Influx, microRNA and mitochondrial, in combination with hyperthermia and transient receptor potential melastatin 7 channels. Local anesthetics significantly decrease the proliferation of cancers, including ovarian, breast, prostate, thyroid, colon, glioma, and histiocytic lymphoma cell cancers, by activating cell death signaling and decreasing survival pathways. We also summarized clinical evidence and randomized trial data to confirm that local anesthetics inhibited tumor progression.

Effect of the use of dexmedetomidine as a local anesthetic adjuvant to bupivacaine 0.125% in epidural labor analgesia: randomized controlled study

Background Multiple methods exist for the management of pain during normal labor. Epidural analgesia has been reported to be an effective method in that perspective. The current study was conducted to evaluate the efficacy of dexmedetomidine as an adjuvant to local anesthetics in epidural analgesia for pregnant females presented for normal delivery. Sixty pregnant females were included in this prospective randomized study, and they were divided into two equal groups: control group which received bupivacaine alone and dexmedetomidine group that received bupivacaine with dexmedetomidine. The primary outcome was the onset of analgesia, while the secondary outcomes included the duration of analgesia, hemodynamic changes, labor progress, neonatal outcomes, and maternal complications. Results Dexmedetomidine group was associated with earlier onset of analgesia (P ˂ 0.001), prolonged duration (P ˂ 0.001), and lower need for top-up doses (P ˂ 0.001) compared to control group. Also, sedation and maternal satisfaction were significantly better in the same group (P = 0.001, 0.025; respectively). Labor progress parameters and neonatal outcomes were comparable between the two groups. Dexmedetomidine group has lower heart rate and mean arterial blood pressure compared to the control group. Despite of dexmedetomidine group had higher incidence of hypotension and bradycardia, it was statistically insignificant when compared to control group. Conclusions Dexmedetomidine is a reliable and an effective adjuvant to the local anesthetics in epidural analgesia during normal delivery as it resulted in earlier onset and significant prolongation of the analgesic time with decrease in the top-up doses intake. Trial registration Pan African Clinical Trial Registry (PACTR201710002664704). Register on 3 October 2017.

Effects of Local Anesthetics With Vasoconstrictors on Dental Pulp Blood Flow and Oxygen Tension

Objective: The aim of this study was to investigate the changes in pulpal blood flow (PBF) and pulpal oxygen tension (PpulpO2) after injecting local anesthetics with vasoconstrictors. Methods: Under general anesthesia, male Japanese White rabbits were injected with 0.6 mL of 2% lidocaine with 1:80,000 epinephrine (LE) or 3% propitocaine (prilocaine) with 0.03 IU felypressin (PF) at the apical area of the lower incisor. Results: Relative to baseline, PBF and PpulpO2 significantly decreased 5 minutes after LE or PF injection as compared with saline. The decrease in PBF was significantly lower in the LE group than in the PF group. Although the LE group had a larger decrease in PpulpO2 relative to baseline than the PF group did, that difference was not significant. PBF and PpulpO2 recovered to baseline faster in the PF group than in the LE group. Conclusion: The injection of local anesthetic solutions containing vasoconstrictors (LE or PF) transiently caused significant decreases in PBF that resulted in significant decreases in PpulpO2. The recovery of PpulpO2 was faster than PBF regardless of the vasoconstrictor used.

A guide to regional analgesia for Total Knee Arthroplasty

Regional analgesia has been introduced successfully into the postoperative pain management after total knee arthroplasty, reducing pain scores, opioid use and adverse effects. Combination of regional analgesia techniques is associated with better pain management and lower side effects than single regional techniques. Adductor canal block provides good analgesia and considerably lower detrimental effect in muscular strength than femoral nerve block, enhancing surgical recovery. Infiltration techniques may have equivalent analgesic effect than epidural analgesia and peripheral nerve blocks, however there should be awareness of dose dependent toxicity. Novel long-acting local anesthetics role for regional analgesia is still to be determined, and will require larger randomized trials to support its advantage over traditional local anesthetics. Cite this article: EFORT Open Rev 2021;6:1181-1192. DOI: 10.1302/2058-5241.6.210045