Perioperative intravenous lidocaine in thoracoscopic surgery for improved postoperative pain control: a randomized, placebo-controlled, double-blind, superiority trial.

Background: Pain, including associated pain management, remains a burden on patients after thoracic surgery. Our objective was to investigate whether perioperative intravenous administration of lidocaine reduces postoperative morphine consumption and pain intensity after video-assisted thoracoscopic surgery (VATS). Methods: In this double-blind, placebo-controlled superiority trial, patients undergoing VATS with a planned duration of ≤90 minutes were randomized within an intention-to-treat setting. Patients received either intravenous lidocaine or placebo as a bolus of 1.5 mg/kg 30 minutes before incision, followed by a continuous infusion of 3.0 mg/kg/hour until 2 hours after skin closure. Pain and morphine consumption were evaluated when resting and when coughing 1, 2, 4, 8, 16, 24, and 48 hours after skin closure and in a follow-up 14, 90, and 180 days postoperatively. Results: Twenty-eight patients were included in the lidocaine group, 24 in the placebo group. Patients' characteristics and preoperative pain scores were similar in both groups. When coughing, patients of the lidocaine group had less pain within 24 hours after skin closure than the placebo group (4.60±1.64 vs. 5.52±1.65; P=0.02). Morphine consumption was not statistically significantly lower in lidocaine group (18.22±12.87 vs. 21.26±9.39 mg; P=0.26). There were no significant differences between groups in secondary outcomes. Conclusions: Our results suggest that perioperative intravenous lidocaine administration reduces pain scores after VATS. The beneficial clinical effects are limited. Nevertheless, intravenous lidocaine may be helpful as part of a multimodal analgesia protocol or with patients in whom the use of other analgesics is contraindicated. Trial Registration: ClinicalTrials.gov NCT03677817.

Dexmedetomidine Prolongs Lidocaine Intravenous Regional Anesthesia in Rats by Blocking the Hyperpolarization-Activated Cation Current.

Purpose: Intravenous regional anesthesia (IVRA) using lidocaine provides effective localized analgesia but its duration is limited. The mechanism by which dexmedetomidine enhances lidocaine IVRA is unclear but may involve modulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Materials and Methods: Lidocaine IVRA with varying dexmedetomidine concentrations was performed in the tails of Sprague-Dawley rats. Tail-flick and tail-clamping tests assessed IVRA analgesia and anesthesia efficacy and duration. Contributions of α2 adrenergic receptors and HCN channels were evaluated by incorporating an α adrenergic receptor antagonist, the HCN channel inhibitor ZD7288, and the HCN channel agonist forskolin. Furthermore, whole-cell patch clamp electrophysiology quantified the effects of dexmedetomidine on HCN channels mediating hyperpolarization-activated cation current (Ih) in isolated dorsal root ganglion neurons. Results: Dexmedetomidine dose-dependently extended lidocaine IVRA duration and analgesia, unaffected by α2 receptor blockade. The HCN channel inhibitor ZD7288 also prolonged lidocaine IVRA effects, while the HCN channel activator forskolin shortened effects. In dorsal root ganglion neurons, dexmedetomidine concentration-dependently inhibited Ih amplitude and shifted the voltage-dependence of HCN channel activation. Conclusion: Dexmedetomidine prolongs lidocaine IVRA duration by directly inhibiting HCN channel activity, independent of α2 adrenergic receptor activation. This HCN channel inhibition represents a novel mechanism underlying the anesthetic and analgesic adjuvant effects of dexmedetomidine in IVRA.

Comparison of the Effects of Lidocaine and Amiodarone on Patients With Cardiac Arrest: A Systematic Review and Meta-Analysis.

The objective of this study was to compare the impact of amiodarone and lidocaine on survival and neurological outcomes following cardiac arrest. A systematic review of randomized controlled trials (RCTs) as well as cohort and cross-sectional trials was undertaken, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Potential relevant studies were searched in databases, including PubMed, Embase, Cochrane Library, and Web of Science, from the beginning of databases to February 15, 2024. Outcomes assessed in this study were survival to hospital discharge, survival to hospital admission or 24 hours, favorable neurological outcomes, and return of spontaneous circulation (ROSC). A total of seven studies (five observational and two RCTs) were included in this meta-analysis encompassing 19,081 patients with cardiac arrest. Pooled analysis showed no difference between amiodarone and lidocaine in terms of survival to hospital discharge (odds ratio (OR): 0.88, 95% confidence interval (CI): 0.75 to 1.04), ROSC (OR: 0.94, 95% CI: 0.84 to 1.05, p-value: 0.25), favorable neurological outcomes (OR: 0.88, 95% CI: 0.66 to 1.17, p-value: 0.38), and survival to 24 hours (OR: 0.82, 95% CI: 0.55 to 1.21, p-value: 0.31). While lidocaine demonstrated a slight survival advantage, the differences were statistically insignificant. Similarly, no significant variations were observed in ROSC incidence, neurological outcomes, or survival at 24 hours. These findings align with current guidelines but underscore the necessity for further rigorous RCTs to provide conclusive recommendations.

Anti-Proliferative Effects of Lidocaine as an Autophagy Inducer in Bladder Cancer via Intravesical Instillation: In Vitro and Xenograft Mouse Model Experiments.

Lidocaine exerts potential anti-tumor effects on various cancer cell lines, and its intravesical instillation is considered safer than intravenous administration for bladder cancer. However, the mechanisms underlying its anti-tumor effects have not been fully elucidated. Here, we aimed to elucidate the anti-tumor molecular mechanisms of lidocaine in bladder cancer cells and a xenograft model to substantiate the efficacy of its intravesical administration. We investigated the anti-proliferative and autophagyinducing activities of lidocaine in Nara Bladder Tumor No. 2 (NBT-II) rat bladder carcinoma cells using cell viability, flow cytometry, a wound healing assay, and western blotting. We also established a xenograft mouse model of bladder cancer, and cancer growth was examined using in vivo bioluminescence imaging. Lidocaine decreased cell viability, induced G0/G1 phase cell cycle arrest, and inhibited cell migration partially via glycogen synthase kinase (GSK) 3ß phosphorylation. Moreover, a combination of lidocaine and SB216763 (a GSK3ß inhibitor) suppressed autophagy-related protein expression. Bafilomycin-A1 with lidocaine significantly enhanced microtubule-associated protein 1A/1B-light chain (LC3B) expression; however, it decreased LC3B expression in combination with 3-methyladenine compared to lidocaine alone. In the xenograft mouse model, the bladder cancer volume was reduced by lidocaine. Overall, lidocaine exerts anti-proliferative effects on bladder cancer via an autophagy-inducing mechanism.

Evaluation of acceptance and preference of topical lidocaine application versus articaine injection anesthesia after nonsurgical periodontal treatment: A randomized clinical trial.

BACKGROUND: To compare acceptance and preference of topical lidocaine gel anesthesia with articaine injection anesthesia in patients with moderate periodontitis undergoing scaling and root debridement. METHODS: Ninety-one patients completed this randomized multicenter split-mouth controlled study and underwent two separate periodontal treatment sessions on different days, one with a topical intrapocket lidocaine gel application and the other with an articaine injection anesthesia in a different order depending on randomization. Parameters measured were the patients' preference for topical lidocaine gel anesthesia or injection anesthesia with articaine (primary efficacy criterion), their maximum and average pain, and their intensity of numbness as well as experience of side effects; the probing depth; and the dentists' preference and their evaluations of handling/application, onset and duration of anesthetic effect, and patient compliance. RESULTS: After having experienced both alternatives, 58.3% of the patients preferred the topical lidocaine gel instillation into the periodontal pockets. The safety profile of the lidocaine gel differed positively from the safety profile of articaine injection in type and frequency of adverse drug reactions. The dentists' acceptance and preference regarding either anesthetic method studied were balanced. CONCLUSIONS: Instillation of lidocaine gel into the periodontal pocket is a preferred alternative to injection anesthesia for most of the patients and an equivalent alternative for dentists in nonsurgical periodontal therapy.

Lidocaine patch as noninvasive alternative treatment option in children with anterior cutaneous nerve entrapment syndrome: A retrospective case series.

BACKGROUND: Chronic abdominal pain in children is occasionally caused by anterior cutaneous nerve entrapment syndrome (ACNES). Diagnosing and treating this typical peripheral abdominal wall neuropathy is challenging. Management usually starts with minimally invasive tender point injections. Nevertheless, these injections can be burdensome and might even be refused by children or their parents. However, a surgical neurectomy is far more invasive. Treatment with a Lidocaine 5% medicated patch is successfully used in a variety of peripheral neuropathies. AIMS: This single center retrospective case series aimed to evaluate the effectiveness and tolerability of lidocaine patches in children with ACNES. METHODS: Children aged under 18 diagnosed with ACNES who were treated with a 10 day lidocaine patch treatment between December 2021 and December 2022 were studied. Patient record files were used to collect treatment outcomes including pain reduction based on NRS and complications. RESULTS: Twelve of sixteen children (mean age 13 years; F:M ratio 3:1) diagnosed with ACNES started the lidocaine patch treatment. Two patients achieved a pain free status and remained pain free during a 4 and 7 months follow-up. A third child reported a lasting pain reduction, but discontinued treatment due to a temporary local skin rash. Five additional patients reported pain reduction only during application of the patch. The remaining four children experienced no pain relief. No adverse effects were reported. CONCLUSION: Lidocaine patches provides pain relief in a substantial portion of children with ACNES.

Acute Systemic Toxicity Caused by Topical Application of EMLA Cream on a Leg Ulcer: Case Report and Review of Literature.

INTRODUCTION: Systemic toxicity of eutectic mixture of local anesthetics (EMLA) cream is rare and is most commonly observed in children, for example, upon extensive application, and rarely occurs in adults with certain dispositions. CASE REPORT: We report the case of a 71-year-old man who developed methemoglobinemia and systemic intoxication upon topical application of EMLA cream for leg ulcer and stasis dermatitis prior to surgical debridement. Approximately 45 min after application, the patient was found to be in a somnolent state, was unable to articulate, and showed peripheral cyanosis. The blood concentration of methemoglobin (MetHb) was 15.1%, and therefore, a diagnosis of systemic toxicity of EMLA due to methemoglobinemia was established. After removal of the cream, oxygen was applied, and further observation revealed that the patient's condition rapidly improved without any residue. In the following, we also discuss literature related to systemic EMLA intoxication. CONCLUSION: EMLA cream may cause severe systemic toxicity even in adults under certain conditions, for example, when applied on damaged skin or in extensive amounts.

Using cryotherapy, EMLA (eutectic lidocaine/prilocaine) cream, or lidocaine spray to reduce pain during arteriovenous fistula puncture: A randomized controlled trial.

INTRODUCTION: In hemodialysis patients, pain associated with needle insertion into an arteriovenous fistula is a physical and psychological problem. The aim of this study was to assess the effectiveness of pre-puncture application of an ice pack, EMLA cream, or lidocaine spray to reduce pain associated with access puncture. METHODS: This was a multicenter study done in nine hemodialysis centers in Iraq. The study utilized a randomized, parallel-group design, in which patients being dialyzed using an arteriovenous access were allocated into one of four groups. Access puncture was preceded by nothing (control group), by use of ice pack cooling at the puncture site, by application of EMLA cream, or by application of lidocaine spray. Pain after access puncture was assessed during a single treatment for each patient. Pain was quantified using a Visual Analogue Scale. FINDINGS: A total of 1548 patients agreed to participate, and 1041 patients were included in the data analysis. Use of an ice pack, EMLA cream, or lidocaine spray each was associated with a lower pain score on access puncture compared with no pretreatment. The mean Visual Analogue Scores in the four groups were: 69.7 ± 15.7 in the controls, 39.8 ± 13.2 in the ice pack group, 45 ± 18.4 in the EMLA group, and 52.9 ± 15.2 in lidocaine group. Ranking of the pain severity scores suggested that ice pack use was associated with the least pain, followed by use of EMLA cream and use of lidocaine spray (severity score ranking, from lowest to highest, being 1.62, 2.18, and 2.63, respectively). DISCUSSION: Application of an ice pack prior to vascular access puncture is a fast and inexpensive technique to limit pain associated with this procedure.

Efficacy of ShotBlocker device versus vapocoolant spray for spinal needle pain relief during spinal anaesthesia in elective caesarean section - A randomised controlled trial.

Background and Aims: Apprehension of pain due to a spinal needle is often a cause of anxiety and refusal. ShotBlocker provides non-painful physical stimulation, inhibiting pain perception. The vapocoolant spray contains ethyl chloride vapours, rapidly raising the skin temperature and hampering the transmission of noxious stimuli. The present study compared the effectiveness of the ShotBlocker device and the vapocoolant spray in reducing spinal needle-associated pain in primigravida women undergoing elective lower-segment caesarean section (LSCS). Methods: We enroled 144 primigravida women undergoing elective LSCS and were randomised to Group SB (the ShotBlocker device was firmly pressed over the skin, and the spinal needle was inserted through its slit), Group V (the vapocoolant spray was applied at the puncture site before spinal needle insertion), and Group C (received local infiltration before spinal anaesthesia (SA)). The groups were compared for needle-associated pain and patient satisfaction using a 10-point visual analogue scale (VAS) and a 3-point Likert scale. Results: The mean (standard deviation) [95% confidence interval (CI)] VAS scores of Group SB 3.85 (0.74) [3.64, 4.07] and Group V 3.04 (0.74) [2.83, 3.26] were significantly lower than that of Group C 5.19 (0.92) [3.28, 3.62]). On the Likert scale, the maximum number of patients in the vapocoolant group (64.6%) responded satisfactorily, while in the control group, the majority (62.5%) of participants responded dissatisfied (P < 0.001). Conclusion: Both the ShotBlocker and vapocoolant spray reduce needle puncture-associated pain before SA in primigravida patients undergoing elective LSCS. However, the vapocoolant spray is more beneficial in reducing spinal needle-associated pain than the ShotBlocker device.

Effects of perioperative intravenous lidocaine and esketamine on the quality of recovery and emotional state of patients after thyroidectomy: A randomised, double-blind, controlled trial.

Background and Aims: Perioperative intravenous (IV) infusions of lidocaine and esketamine reduce postoperative pain, but there are few studies on the quality of recovery and patients' emotional states postoperatively. We aimed to explore the effects of perioperative IV lidocaine and esketamine on the quality of recovery and emotional state after thyroidectomy. Methods: In this randomised trial, 137 patients undergoing thyroidectomy were randomly assigned to three groups: a lidocaine group (Group L), an esketamine group (Group E) and a normal saline placebo group (Group C). The primary outcome was the Quality of Recovery 40 (QoR-40) on postoperative days (PODs) 1 and 2. The secondary outcomes included Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) scores on days 1 and 2 after surgery, pain scores, opioid consumption and incidence of postoperative nausea and vomiting (PONV). Statistical analysis was performed using the one-way analysis of variance (ANOVA), the Kruskal-Wallis and Chi-square tests. Results: The global QoR-40 scores in groups L and E on POD 1 and POD 2 were significantly higher than in group C (P < 0.001). The SAS and SDS scores on POD 1 and POD 2 in groups L and E were significantly lower than in group C (P < 0.05). There were statistically significant differences in Numerical Rating Scale (NRS) scores among the three groups at 1 h, 2 h, 6 h and 12 h (P < 0.05). Conclusion: Perioperative IV lidocaine and esketamine improve the quality of postoperative recovery and the emotional state of patients undergoing thyroidectomy.

Synergistic interaction of guanfacine or dexmedetomidine coadministered with lidocaine for cutaneous analgesia in rats.

BACKGROUND: This study examined the cutaneous analgesic effects of lidocaine co-injected with guanfacine and its comparison with dexmedetomidine. METHODS: Cutaneous analgesic effects are quantified through the blocking effects of the cutaneous trunci muscle reflex against skin pinpricks in rats. The dose-response curves of guanfacine, dexmedetomidine, and lidocaine were constructed and drug-drug interactions were analyzed by the ED50 isobologram. RESULTS: Subcutaneous injections of guanfacine, dexmedetomidine, and lidocaine produced dose-dependently nociceptive/sensory blockade. On the ED50 (50% effective dose) basis, the potency rankings of the drug are dexmedetomidine (0.09 [0.08-0.11] µmol/kg) > guanfacine (3.98 [2.96-5.34] µmol/kg) > lidocaine (25.40 [23.51-27.44] µmol/kg) (p < 0.01). On their equipotent doses (ED25, ED50, and ED75), the duration of sensory blockade induced by guanfacine or dexmedetomidine was longer than lidocaine's (p < 0.01). Both guanfacine and dexmedetomidine showed synergistic effects with lidocaine. CONCLUSIONS: We showed that guanfacine elicits dose-dependent cutaneous analgesia when administered subcutaneously. Lidocaine is less potent than guanfacine or dexmedetomidine. Both guanfacine and dexmedetomidine enhance the potency and duration of lidocaine. Better synergistic responses we are getting with guanfacine plus lidocaine.

Using part of the initial analgesic dose as the epidural test dose did not delay the onset of labor analgesia: a randomized controlled clinical trial.

BACKGROUND: Epidural test dose for labor analgesia is controversial and varies widely in clinical practice. It is currently unclear whether using a portion of the initial dose for analgesia as the test dose delays the onset time of analgesia, compared to the traditional test dose. METHODS: One hundred and twenty-six parturients who chose epidural analgesia during labor were randomly assigned to two groups. The first dose in group L was 3 ml 1.5% lidocaine, and in the RF group was 10 ml 0.1% ropivacaine combined with 2 µg/ml fentanyl. After 3 min of observation, both groups received 8 ml 0.1% ropivacaine combined with 2 µg/ml fentanyl. The onset time of analgesia, motor and sensory blockade level, numerical pain rating scale, patient satisfaction score, and side effects were recorded. RESULTS: The onset time of analgesia in group RF was similar to that in group L (group RF vs group L, 7.0 [5.0-9.0] minutes vs 8.0 [5.0-11.0] minutes, p = 0.197). The incidence of foot numbness (group RF vs group L, 34.9% vs 57.1%, p = 0.020) and foot warming (group RF vs group L, 15.9% vs 47.6%, p < 0.001) in group RF was significantly lower than that in group L. There was no difference between the two groups on other outcomes. CONCLUSIONS: Compared with 1.5% lidocaine 3 ml, 0.1% ropivacaine 10 ml combined with 2 µg/ml fentanyl as an epidural test dose did not delay the onset of labor analgesia, and the side effects were slightly reduced. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn (ChiCTR2100043071).

Assessment of the Efficiency for Anesthesia of Two Agents in Teeth Removal: A Split-Mouth Research.

Aim: This study was intended to assess and relate the clinical anesthetic effectiveness of tramadol hydrochloride and lidocaine. Methodology: A clinical randomized split-mouth study was piloted among 40 patients who were otherwise healthy but needed to have their maxillary first premolars extracted bilaterally for orthodontic reasons were considered in the research. In each subject on one side (quadrant) of the arch 1.8 milliliters of lidocaine was given and on other side of the arch 1.8 milliliters of tramadol was given. On the basis of a list that was prepared by a computer, the randomization was done and the sides (quadrant) of the arches were decided for all the subjects, and the injections were given as local infiltration. Results: Lidocaine was found to be statistically more effective for overall anesthesia duration, despite the fact that there was no significant variance between the two drugs at the time when anesthetic effect began to take effect. Tramadol was found to be statistically more efficient than lidocaine when compared to the anesthetic activity at the 5th minute before extraction. Tramadol was found to be statistically more successful than lidocaine for both the patient's degree of satisfaction and the rate at which wounds healed. Conclusion: Based on the findings of this research, it appears that tramadol and epinephrine could be used as a substitute to conventional local anesthetics during extractions of maxillary first premolar teeth during oral-maxillofacial surgery.

Noninferiority trials in acute pain research: a valid approach or a slippery slope?

The conduct and reporting of studies with a noninferiority hypothesis is challenging because of the complexity involved in their design and interpretation. However, studies with a noninferiority design have increased in popularity. A recently published trial reported on the noninferiority of lidocaine infusion to epidural analgesia in major abdominal surgeries. Apart from needing a critical appraisal, this draws attention to improve our understanding of noninferiority study framework and its unique features. Given the increasing focus on using various analgesic adjuncts and multiple approaches to fascial plane blocks to avoid more definitive and standard approaches, it is imperative that particular attention is paid to appropriate execution and reporting of noninferiority studies.

Does lidocaine reduce pain intensity during corticosteroid injection? A double-blind randomized controlled equivalence trial.

Of the strategies considered to limit the discomfort of corticosteroid injection, one is to inject without lidocaine to reduce the total volume and avoid acidity. In a Bayesian trial, adults receiving corticosteroid injections were randomized to receive 0.5 mL of triamcinolone with or without 0.5 mL of lidocaine. Serial analysis was performed until a 95% probability of presence or absence of a 1.0-point difference in pain intensity on the 0-10 Numerical Rating Scale was reached. Injections with lidocaine were associated with a median of 2.4-point lower pain intensity during injection with a 95% probability of at least a 1-point reduction. The 95% probability was confirmed in 90% of the repeated analysis (36/40). Lidocaine is associated with lower immediate pain intensity during corticosteroid injection for hand and wrist conditions.Level of evidence: I.

50% efficacy dose of intravenous lidocaine in supressing sufentanil-induced cough in children: a randomised controlled trial.

BACKGROUND: Opioids such as sufentanil are used as anaesthetics due to their rapid action and superior analgesic effect. However, sufentanil induces a huge cough in paediatric patients. In contrast, intravenous (IV) lidocaine suppresses opioid-induced cough in children, but its use is limited due to anaesthetists' concern about its toxicity. Therefore, this study aimed to evaluate the effect of dose-dependent IV lidocaine on sufentanil-induced cough (SIC) in paediatric patients. METHODS: A total of 188 patients aged 3-12 years scheduled for elective tonsillectomy with or without adenoidectomy were enrolled and divided into four groups depending on different dose of lidocaine: A (0 mg.kg-1), B (1 mg.kg-1), C (1.5 mg.kg-1), and D (2 mg.kg-1). The primary outcome was the SIC grade observed during the induction of general anaesthesia. The secondary outcomes were the incidence of SIC, mean arterial pressure, and heart rate at T0, T1, T2, T3, T4, and T5. RESULTS: The SIC grade was significantly different between groups A and D (P = 0.04) and between groups B and D (P = 0.03). Moreover, the incidence of SIC in groups A, B, C, and D was 81%, 87%, 68%, and 64%, respectively, and the difference between groups B and C (P = 0.03) and between groups B and D (P = 0.0083) was statistically significant. No statistical differences were observed in the hemodynamic parameters between the groups. The incidence of severe cough was statistically different between group D and group A (P < 0.0001), between group D and group B (P < 0.0001), and between group D and group C (P < 0.0001) respectively. CONCLUSIONS: Lidocaine suppresses SIC in a dose-dependent manner without severe adverse events. IV lidocaine can be used in paediatric patients safely and efficiently, and the median effective dose was 1.75 mg/kg. TRIAL REGISTRATION: This study was approved by the Institutional Review Board of Yichang Central People's Hospital (HEC-KYJJ-2020-038-02), The trial was registered at www.chictr.org.cn (ChiCTR2100053006).

The Pharmacologic Management of Cardiac Arrest.

The effectiveness of pharmacologic management of cardiac arrest patients is widely debated; however, several studies published in the past 5 years have begun to clarify some of these issues. This article covers the current state of evidence for the effectiveness of the vasopressor epinephrine and the combination of vasopressin-steroids-epinephrine and antiarrhythmic medications amiodarone and lidocaine and reviews the role of other medications such as calcium, sodium bicarbonate, magnesium, and atropine in cardiac arrest care. We additionally review the role of ß-blockers for refractory pulseless ventricular tachycardia/ventricular fibrillation and thrombolytics in undifferentiated cardiac arrest and suspected fatal pulmonary embolism.

Discovery of a Novel Lidocaine Metabolite by Human Liver Microsome and Identification of Microbial Species Which Produces the Same Metabolite.

Preparation of drug metabolites at the milligram scale is essential for determining the structure and toxicity of drug metabolites. However, their preparation using recombinant proteins and human liver microsomes (HLM) is often difficult because of technical and ethical issues. Reproducing human drug metabolism in food-derived microorganisms may be useful for overcoming these challenges. In this study, we identified an unknown metabolite of the anaesthetic drug lidocaine, which is metabolised by HLM. By screening for lidocaine metabolic activity in five types of foods (blue cheese, shiitake mushroom, natto, yoghurt, and dry yeast), we found that bacteria isolated from natto reproduced the lidocaine metabolic reaction that occurs in HLM. A fraction containing the unknown lidocaine metabolite was prepared through mass cultivation of a Bacillus subtilis standard strain, ethyl acetate extraction, open column chromatography, and HPLC purification. We identified the unknown metabolite as 3-(2,6-dimethylphenyl)-1-ethyl-2-methyl-4-imidazolidinone using NMR. Our results showed that food-derived microorganisms can produce large amounts of human drug metabolites via large-scale cultivation. Additionally, food microorganisms that can reproduce drug metabolism in humans can be used to examine drug metabolites at a low cost and without ethical issues.

Intraoperative Takotsubo Cardiomyopathy: A Case Report.

Takotsubo cardiomyopathy (TTC) is a rare condition associated with transient akinesia of apical segments and hyperkinesia of basal segments of the heart. Although several mechanisms have been proposed to cause direct and indirect myocardial damage owing to catecholamine excess, the underlying pathophysiology remains unknown. An 18-year-old female was referred to our otorhinolaryngology outpatient clinic for a septorhinoplasty. Apart from the fear of surgery, the patient had no other health issues. After the administration of local anesthesia (lidocaine and epinephrine mix), tachycardia storms occurred and soon ended with cardiac collapse. Further evaluation revealed TTC. TTC should be considered, especially in cases of treatment-resistant hemodynamic problems after cardiac resuscitation, and nurses can play a crucial role during the preanesthetic period in helping the patient cope with the stress factors related to the upcoming surgery.

A comparative analysis of opioid-free and opioid-sparing anaesthesia techniques for laparoscopic ovariectomy in healthy dogs.

OBJECTIVE: To compare the perioperative analgesic effects of an opioid-free (OFA) and an opioid-sparing (OSA) anaesthetic protocol in dogs undergoing laparoscopic ovariectomy. STUDY DESIGN: Prospective, randomized, blinded, clinical trial. ANIMALS: A group of 28 client-owned dogs. METHODS: Dogs were allocated to one of two groups. The OFA group was administered intramuscular (IM) dexmedetomidine 5 µg kg-1 and ketamine 1 mg kg-1, followed by two intraoperative constant rate infusions (CRIs) of dexmedetomidine (3 µg kg-1 hour-1) and lidocaine (1 mg kg-1 loading dose, 2 mg kg-1 hour-1). The OSA group was administered IM dexmedetomidine 5 µg kg-1, ketamine 1 mg kg-1 and methadone 0.2 mg kg-1, followed by two intraoperative saline CRIs. In both groups, anaesthesia was induced with intravenous (IV) propofol 2 mg kg-1 and diazepam 0.2 mg kg-1 and maintained with isoflurane. Rescue dexmedetomidine (0.5 µg kg-1) was administered IV if there was a 20% increase in cardiovascular variables compared with pre-stimulation values. Ketorolac (0.5 mg kg-1) was administered IV when the surgery ended. Postoperative analgesia was evaluated using the Short Form-Glasgow Composite Measure Pain Scale and methadone (0.2 mg kg-1) was administered IM if the pain score was ≥ 6/24. Statistical analysis included mixed analysis of variance, Chi-square test and Mann-Whitney U test. RESULTS: There were no significant differences in the intraoperative monitored variables between groups. The OFA group showed a significantly lower intraoperative rescue analgesia requirement (p = 0.016) and lower postoperative pain scores at 3 (p =0.001) and 6 (p < 0.001) hours. No dogs were administered rescue methadone postoperatively. CONCLUSIONS AND CLINICAL RELEVANCE: Although both groups achieved acceptable postoperative pain scores with no need for further intervention, the analgesic efficacy of the OFA protocol was significantly superior to that of the OSA protocol presented and was associated with a lower intraoperative rescue analgesia requirement and early postoperative pain scores.