Prevention of persistent pain with lidocaine infusions in breast cancer surgery (PLAN): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Persistent pain is a common yet debilitating complication after breast cancer surgery. Given the pervasive effects of this pain disorder on the patient and healthcare system, post-mastectomy pain syndrome (PMPS) is becoming a larger population health problem, especially as the prognosis and survivorship of breast cancer increases. Interventions that prevent persistent pain after breast surgery are needed to improve the quality of life of breast cancer survivors. An intraoperative intravenous lidocaine infusion has emerged as a potential intervention to decrease the incidence of PMPS. We aim to determine the definitive effects of this intervention in patients undergoing breast cancer surgery. METHODS: PLAN will be a multicenter, parallel-group, blinded, 1:1 randomized, placebo-controlled trial of 1,602 patients undergoing breast cancer surgery. Adult patients scheduled for a lumpectomy or mastectomy will be randomized to receive an intravenous 2% lidocaine bolus of 1.5 mg/kg with induction of anesthesia, followed by a 2.0 mg/kg/h infusion until the end of surgery, or placebo solution (normal saline) at the same volume. The primary outcome will be the incidence of persistent pain at 3 months. Secondary outcomes include the incidence of pain and opioid consumption at 1 h, 1-3 days, and 12 months after surgery, as well as emotional, physical, and functional parameters, and cost-effectiveness. DISCUSSION: This trial aims to provide definitive evidence on an intervention that could potentially prevent persistent pain after breast cancer surgery. If this trial is successful, lidocaine infusion would be integrated as standard of care in breast cancer management. This inexpensive, widely available, and easily administered intervention has the potential to reduce pain and suffering in an already afflicted patient population, decrease the substantial costs of chronic pain management, potentially decrease opioid use, and improve the quality of life in patients. TRIAL REGISTRATION: This trial has been registered on clinicaltrials.gov (NCT04874038, Dr. James Khan. Date of registration: May 5, 2021).

Preclinical safety assessment of antipyrine combined with lidocaine hydrochloride as ear drops.

This study was designed to assess the preclinical toxicity of antipyrine combined with lidocaine hydrochloride ear drops (ALED) and support the clinical trials of ALED in clinical settings in China. All the experiments including acute toxicity in rodents, skin sensitization toxicity in guinea pigs, skin irritation toxicity in rabbits and chronic toxicity in rats were performed according to China Food and Drug Administration guidelines. The maximum tolerated dose (MTD) of ALED administration for mice and rats was over (400 g antipyrine plus 100 g lidocaine hydrochloride)/kg and (240 g andtipyrine plus 60 g lidocaine hydrochloride)/kg, respectively. No obvious skin sensitization toxicity and skin irritation toxicity were observed. The main changes concentrated in chronic toxicity study in rats. For the chronic toxicity, rats were administrated once a day for 28 consecutive days, and a 14-day recovery period was followed. The side effects of ALED included decreased dietary intake in male rats, increased proportion of reticulocytes, decreased or even inversed granulocyte:erythrocyte ratio, fluctuated alanine aminotransferase and aspartate aminotransferase, and slightly increased relative weight of liver. Conclusively, blood system (especially erythrocyte system) and digestive system, including liver and gastrointestinal tract, might be the toxic targets of ALED.

Outcomes and cost-effectiveness of ultrasound-guided injection of the trochanteric bursa.

We hypothesized that ultrasound (US) guidance improves outcomes of corticosteroid injection of trochanteric bursitis. 40 patients with greater trochanteric pain syndrome defined by pain to palpation over the trochanteric bursa were randomized to injection with 5 ml of 1% lidocaine and 80 mg of methylprednisolone using (1) conventional anatomic landmark palpation guidance or (2) US guidance. Procedural pain (Visual Analogue Pain Scale), pain at outcome (2 weeks and 6 months), therapeutic duration, time-to-next intervention, and costs were determined. There were no complications in either group. Ultrasonography demonstrated that at least a 2-in (50.8 mm) needle was required to consistently reach the trochanteric bursa. Pain scores were similar at 2 weeks: US: 1.3 ± 1.9 cm; landmark: 2.2 ± 2.5 cm, 95% CI of difference: - 0.7 < 0.9 < 2.5, p = 0.14. At 6 months, US was superior: US: 3.9 ± 2.0 cm; landmark: 5.5 ± 2.6 cm, 95% CI of difference: 0.8 < 1.6 < 2.4, p = 0.036. However, therapeutic duration (US 4.7 ± 1.4 months; landmark 4.1 ± 2.9 months, 95% CI of difference - 2.2 < - 0.6 < 1.0, p = 0.48), and time-to-next intervention (US 8.7 ± 2.9 months; landmark 8.3 ± 3.8 months, 95% CI of difference - 2.8 < - 0.4 < 2.0, p = 0.62) were similar. Costs/patient/year was 43% greater with US (US $297 ± 99, landmark $207 ± 95; p = 0.017). US-guided and anatomic landmark injection of the trochanteric bursa have similar 2-week and 6-month outcomes; however, US guidance is considerably more expensive and less cost-effective. Anatomic landmark-guided injection remains the method of choice, but should be routinely performed using a sufficiently long needle [at least a 2 in (50.8 mm)]. US guidance should be reserved for extreme obesity or injection failure.

Lidocaine/prilocaine spray for premature ejaculation.

Although premature ejaculation is the most common ejaculation problem, it is poorly understood and currently has no standard definition.1 Typically, it involves reduced time to ejaculation, inability to control or delay ejaculation and associated distress.1-5 Treatments that have been assessed include psychosexual counselling, antidepressants (e.g. selective serotonin reuptake inhibitors), phosphodiesterase type-5 inhibitors, tramadol and topical anaesthetic agents (e.g. lidocaine/prilocaine cream). A new formulation (cutaneous spray) of lidocaine/prilocaine (Fortacin-Plethora Solutions Ltd.) was launched in the UK in November 2016 for the treatment of primary premature ejaculation.6,7 Here, we consider the evidence for lidocaine/prilocaine spray and whether it has a role in the treatment of premature ejaculation.

Pharmacokinetics of pilsicainide hydrochloride for injection in healthy Chinese volunteers: a randomized, parallel-group, open-label, single-dose study.

BACKGROUND: Pilsicainide hydrochloride is a class IC antiarrhythmic agent used for the treatment of supraventricular and ventricular arrhythmias and atrial fibrillation. OBJECTIVE: The objective of the present study was to determine the pharmacokinetics (PK) of a pilsicainide hydrochloride injection in healthy Chinese adults. The study was conducted to meet China State Food and Drug Administration requirements for the marketing of the new generic formulation of pilsicainide hydrochloride. METHODS: This Phase I, randomized, parallel-group, open-label, single-dose PK study was conducted in healthy Chinese volunteers. Subjects were randomized to receive a single dose of 0.25-, 0.50-, and 0.75-mg/kg pilsicainide hydrochloride with a 10-minute intravenous infusion. Serial blood and urine samples were collected up to 24 hours after dosing; drug concentrations in plasma and urine were then determined by using LC-MS/MS. The PK parameters of pilsicainide were calculated from the plasma concentration-time data according to noncompartmental methods. Safety profile was evaluated by monitoring adverse events, clinical laboratory parameters, and the results of 12-lead ECGs. RESULTS: Thirty healthy volunteers (mean [SD] age, 28.0 [4.95] years; weight, 59.3 [6.51] kg; height, 165.0 [7.25] cm; body mass index, 21.7 [1.94] kg/m(2)) were randomly divided into 3 groups, each consisting of 5 men and 5 women. After single-dose intravenous administration of 0.25, 0.50, and 0.75 mg/kg of pilsicainide hydrochloride, mean Cmax was 0.34 (0.11), 0.54 (0.15), and 1.05 (0.19) µg/mL, respectively; AUC0-24 was 0.76 (0.12), 1.61 (0.37), and 2.61 (0.46) h · µg/mL; and AUC0-∞ was 0.79 (0.13), 1.71 (0.46), and 2.72 (0.50) h · µg/mL. The ranges for t½z, CL, and Vz were 5.19 to 5.98 hours, 4.73 to 5.44 mL/min/kg, and 2.23 to 0.58 L/kg, respectively. The mean urinary recovery rate within 24 hours was 75.0% (12.0%), 65.0% (19.2%), and 66.4% (14.1%). Men and women had significantly different AUC0-24 values in the 0.50-mg/kg dose group (P = 0.044), and Vz showed significant differences between men and women in all 3 dose groups (P = 0.001). According to ECG parameters, PR intervals were significantly prolonged after administration at all 3 doses (P = 0.034, P < 0.001, and P = 0.034); no significant changes were seen in QRS width, QTc interval, or other parameters. CONCLUSIONS: Pilsicainide hydrochloride demonstrated linear PK, and the increase in the exposure of pilsicainide (AUC0-24 and AUC0-∞) was dose proportional after single doses of 0.25, 0.50, and 0.75 mg/kg. All 3 pilsicainide hydrochloride doses were well tolerated in these Chinese volunteers. ChiCTR-ONC-13003546.

Assessment of effects of physical or chemical factors on fat particle viability by glucose transport test.

BACKGROUND: It is important to protect fat viability during grafting. This study aimed to clarify whether physical or chemical factors damage fat viability. METHODS: Fat was harvested under high and low tumescence pressure, using syringes and a liposuction machine; this fat was injected through different gauge needles and cultured with lidocaine or epinephrine. Samples were subjected to glucose transport test and observed histologically. RESULT: The viability and microstructure of fat harvested under high and low tumescence pressure, and by syringe and liposuction machine, were similar (P > 0.05). The viability and intactness of fat cells injected through needles decreased with decreasing needle diameter (P < 0.05). Lidocaine (P < 0.05) and epinephrine (P < 0.05) weakened fat viability. CONCLUSIONS: Fat used for grafting can be harvested by tumescent techniques and a liposuction machine. Fat cell viability during injection increases with increasing needle diameter. Fat should be purified to remove drugs.

Holter ECG assessment of the effects of three different local anesthetic solutions on cardiovascular system in the sedated dental patients with coronary artery disease.

OBJECTIVE: The purpose of the study is to compare the effects of lidocaine alone, epinephrine-combined lidocaine and prilocaine with octapressin on the cardiovascular system during minor oral surgery of sedated cardiac dental patients under local anesthesia. METHODS: Connected to a Holter electrocardiogram (ECG) monitor for a total of 5 hours starting 1 hour before the procedure, twenty patients with high risk of coronary artery disease were included in the prospective cohort study. All the patients had three operations at 3 different appointments with at least one-week intervals and each operation was performed under local anesthesia achieved by 3.6 mL of 3% prilocaine with octapressin, 3.6 mL of 2% lidocaine with 1:80.000 epinephrine and 3.6 mL of 2% lidocaine without a vasoconstrictor. Data of the Holter ECG device assessed at the end of every hour and evaluated statistically. Repeated measures ANOVA, Friedman test, and Wilcoxon signed ranks test were used to perform statistical analysis. RESULTS: Heart-rate showed significant differences between lidocaine with epinephrine and pure lidocaine in an hour following the injection (p<0.05 for all). Cardiac rhythm showed significant differences between prilocaine with octapressin and pure lidocaine at the second hour after its administration (p<0.05 for all). There were no significant differences between 3 local anesthetics in terms of ST segment deviation. CONCLUSION: In minor oral operation on the sedated patients with cardiac disease, the use of 3.6 mL or a less amount of local anesthetic injection containing epinephrine appears to be a predictable and safe method.

A randomized double-blind study comparing intradermal anesthetic tolerability, efficacy, and cost-effectiveness of lidocaine, buffered lidocaine, and bacteriostatic normal saline for peripheral intravenous insertion.

In this double-blind study, 256 surgical patients meeting eligibility criteria were randomized in a 1:1:1 ratio to 1 of the 3 intradermal injection groups prior to intravenous (IV) line insertion (Group 1=1% lidocaine, Group 2=1% buffered lidocaine, and Group 3=bacteriostatic normal saline with a benzyl alcohol preservative). The most tolerable solution, as measured by the average level of pain from an intradermal insertion, was buffered lidocaine (Group 2). The most efficacious, as measured by average level of pain at IV cannulation, were Groups 1 and 2. Group 3 was the most cost-effective.

[Ultrasonographic assessment of hemidiaphragm paralysis secondary to interscalene block]. / Evaluación ultrasonográfica de la parálisis hemidiafragmática secundaria a bloqueo interescalénico.

BACKGROUND: In shoulder surgery, interscalene brachial plexus block has an incidence of 100% hemidiaphragm palsy due to phrenic nerve block. Controling the hemidiaphragm becomes a security ventilation parameter. OBJECTIVE: identify and evaluate with ultrasound hemidiaphragm paralysis after interscalene block. METHODS: This prospective study included 50 patients scheduled for shoulder surgery with interscalene block using neurostimulation. Diaphragmatic movement was evaluated by ultrasound prior to placement of block and the end of the surgical procedure to make the comparison between the two measurements. RESULTS: Comparing the duration of the respiratory cycle at the start and the end of the surgical procedure, both normal and forced ventilation, there is a statistically significant difference of p < 0.001, as with the depth of the hemidiaphragm was found p < 0.001. 90% of patients had no adverse events, 8% had Horner's syndrome and 2% periauricular hypoesthesia. Hemidiaphragm paralysis was found in all cases, with a volume of 30 mL local anesthetic. CONCLUSIONS: Ultrasound is a reliable tool that allows real time viewing of the respiratory cycle and measurements of the diaphragm dome it serves to identify diaphragmatic hemiparesis.

An ultrasonographic assessment of nerve stimulation-guided median nerve block at the elbow: a local anesthetic spread, nerve size, and clinical efficacy study.

BACKGROUND: Nerve stimulation is an effective technique for peripheral nerve blockade. However, the local anesthetic (LA) distribution pattern obtained with this blind approach is unknown and may explain its clinical effects. METHODS: One hundred patients received a median nerve block at the elbow using a nerve stimulator approach. After correct needle placement defined by a minimal stimulating current < or = 0.5 mA (2 Hz, 0.1 millisecond), 6 mL lidocaine 1.5%with epinephrine 1:200,000 was injected. A linear 5- to 13-MHz probe (12L-RS) was used to assess a cross-section area of median nerve, which was calculated by 3 consecutive measurements before and after injection, and LA circumferential spread around the nerve during static and longitudinal examination. Intraneural injection defined as an increase in nerve area was detected using an iterative method for outlier detection. Results of sensory tests (cold and light touch) on 3 nerve territories and of motor blockade were compared with the imaging aspects. We performed clinical neurological examination at 3 days and 1 month after block. RESULTS: Nerve swelling, considered significant when an increase in cross-sectional area was > or = 75%, was observed in 43 patients. Nerve swelling associated with a circumferential LA spread image, present in 37 patients, was associated with a sensory success rate of 86%. The success rate was 34% for 32 patients in whom none of these signs was visualized. A circumferential spread around a nonswollen nerve, present in 25 patients, was followed by a sensory success rate of 76% within the 30-minute evaluation period. No major early neurological complications were observed. CONCLUSIONS: Nerve stimulation does not prevent intraneural injection. In the absence of intraneural injection, the presence of circumferential LA spread image seemed predictive of successful sensory block in almost 75% of the cases within the 30-minute evaluation period.

A comparison of spinal anesthesia with small-dose lidocaine and general anesthesia with fentanyl and propofol for ambulatory prostate biopsy procedures in elderly patients.

STUDY OBJECTIVE: To compare operating conditions, intraoperative adverse events, recovery profiles, postoperative adverse effects, patient satisfaction, and costs of small-dose lidocaine spinal anesthesia with those of general anesthesia using fentanyl and propofol for elderly outpatient prostate biopsy. DESIGN: Prospective, randomized, blind study. SETTING: Outpatient anesthesia unit at a municipal hospital. PATIENTS: 80 ASA physical status I and II patients, aged 65 to 80 years, scheduled for outpatient prostate biopsy. INTERVENTIONS: Patients were assigned to receive either spinal anesthesia with 10 mg of hyperbaric 1% lidocaine (L group, n=40) or anesthetic induction with fentanyl 1 microg.kg-1 IV and 1.0 mg.kg-1 propofol injected at 90 mg.kg-1.h-1, followed by continuous infusion at 6 mg.kg-1.h-1 (F/P group, n=40). MEASUREMENTS AND MAIN RESULTS: Both anesthetic techniques provided acceptable operating conditions for the surgeon. However, a significantly higher frequency of intraoperative hypotension was found in the F/P group than in the L group (P<0.05). Time to home readiness was shorter in the F/P group (P<0.05). Both techniques had no major postoperative adverse effects and resulted in a high rate of patient satisfaction. Total costs were significantly lower in the L group than in the F/P group (P<0.01). CONCLUSIONS: Spinal anesthesia with 10 mg of hyperbaric 1% lidocaine may be a more suitable alternative to general anesthesia with fentanyl and propofol for ambulatory elderly prostate biopsy in terms of safety and costs.

[Sensory injury to the lingual nerve after nerve block at the lingula mandibulae]. / Dommages sensoriels du nerf lingual après anesthésie à l'épine de Spix.

Prolonged and possibly permanent change in sensation due to lingual nerve damage can occur after mandibular block anesthesia. The condition is rare and little can be done to prevent its occurrence. A case report is presented and functional as well as legal implications are discussed. Also practical recommendations are given to help the dentist when faced with the situation.

Adhesive capsulitis of the shoulder: the rate of manipulation following distension arthrogram.

To determine the rate of manipulation under anaesthesia (MUA) following distension arthrogram for adhesive capsulitis of the shoulder. Thirty-nine patients (42 shoulders) between 1998 and 2004 were treated with distension arthrogram for adhesive capsulitis diagnosed by the clinical picture of progressive pain and stiffness. Capsular disruption into the subscapular bursa was demonstrated in 40 of the 42 shoulders (95%). Thirty-seven of 42 (88%) shoulders were painfree following distension arthrogram. 15 of 42 (36%) shoulders underwent MUA following distension arthrogram for stiffness although 10 of these (67%) were painfree. Prior to distension arthrogram, the range of external rotation (ER) was no different between those that had MUA and those that did not (P = 0.36). The improvement in ER was 33% (P = 0.28) in those that had MUA and 50% (P = 0.001) in those that did not. The only complication was a vasovagal episode during the procedure. Distension arthrogram can be used as a therapeutic procedure for achieving symptomatic pain relief in the majority of adhesive capsulitis and decrease the rate of MUA of the shoulder.

Las lecciones derivadas del ASA Closed Claims Project (ASACCP). Proyecto de la ASA acerca de las razones que promovieron demandas contra anestesiólogos cuyos casos estuviesen ya archivados: 4a. parte. Anestesia Regional. Análisis de las demandas sobre casos/hechos asociados con la anestesia regional en la sala de operaciones / Lessons learned fron the ASA Closed Claims Project (ASACCP). Project about the reasons for which claims against anesthesiologists were renewed in cases that had already been closed: part. 4. Regional Anesthesia. Analysis of claims concerning regional anesthesia in the OR

Cuando se comparan las consecuencias de los accidentes anestésicos reclamados que constan en la base de datos del ASA CCP (Closed Claims Project), es significativo señalar que hubo un alto porcentaje de lesiones temporarias o no incapacitantes en los casos de anestesia regional (64 por ciento vs 46 por ciento p<0,05). Entre las lesiones incapacitantes permanentes derivadas de injurias del sistema nervioso periférico se hallan manifestaciones como la paraplejía y la cuadriplejía. Catorce de las reclamaciones legales asociadas con la paraplejía se debieron a síndromes de la anestesia espinal anterior. Los daños neurológicos permanentes fueron la causa más común de los daños incapacitantes, el más frecuente de los cuales (23 por ciento) fue asociado a bloqueos nerviosos para anestesia ocular (13 retrobulbares, 3 peribulbares) en los que hubo pérdida de la visión del ojo afectado. De todas maneras, se debe señalar que las complicaciones neurológicas como manifestaciones secundarias a la utilización de anestésicos locales para anestesia regional son muy poco frecuentes (0,02 y 0,07 por ciento de los casos), aunque es bastante común observar la aparición de manifestaciones neurológicas transitorias (entre 0,01 y 0,8 por ciento). La parestesia y el dolor durante la inyección son señales peligrosas ya que anuncian la posibilidad de la complicación. Se han descripto también abscesos peridurales y meningitis, en especial cuando se realizan bloqueos centrales con catéteres de pequeño diámetro a fin de alcanzar analgesia central para el dolor crónico. En la base de datos de la Mutual de Médicos Anestesiólogos de Buenos Aires están registradas las demandas realizadas contra anestesiólogos y los casos en los cuales los médicos, enfrentados a un incidente crítico, notifican la situación en previsión de una eventual demanda. Al igual que en el estudio de la ASACCP, desconocemos el número total de anestesia realizadas por los colegas adheridos. Hasta el 2004 hubo 339 notificaciones que incluyen 74 demandas, 24 causas penales y 50 causas civiles; 124 casos correspondieron a la anestesia regional, mientras que 215 formaron el grupo de pacientes que recibieron anestesia general. En 8 de los pacientes que presentaron radiculopatías se realizó una anestesia subaracnoidea con bupivacaína al 0,5 por ciento en solución hiperbara, habiéndose inyectado 15 mg (3 ml) de la solución anestésica...

A needle-free jet-injection system with lidocaine for peripheral intravenous cannula insertion: a randomized controlled trial with cost-effectiveness analysis.

UNLABELLED: Insertion of a peripheral IV cannula is a common, although painful, procedure. We tested the analgesic efficacy, adverse effects, and cost-effectiveness of a needle-free intradermal drug delivery system (Jet) with lidocaine for the insertion of an IV cannula (18-gauge; dorsum of hand). Four-hundred patients were randomly allocated to one of four groups: (a) no treatment, (b) Jet (J-Tip), National Medical Products Inc, CA; $3.0 per device) with 0.5 mL of saline, (3) Jet with 0.5 mL of lidocaine 1%, and (4) Jet with 0.5 mL of lidocaine 2%. Pain was evaluated using a numerical verbal scale (NVS 0-10). A NVS < or =3 was considered as acceptable in this context. Incremental cost-effectiveness ratios were calculated. Without treatment, 42.4% of patients had a NVS < or = 3, 39.3% with saline, 60.7% with 1% lidocaine (relative risk [RR] compared with no treatment, 0.70; 95% confidence interval [CI], 0.53-0.93), and 86.7% with 2% lidocaine (RR, 0.49; 95% CI, 0.38-0.62). Nineteen and one-half percent of patients had a NVS >3 because of Jet treatment, 13.5% had local hyperemia, and 16.9% had minor local bleeding. Of all Jet treatments, 10.5% were technical failures, and there were 17.6% cannula insertion failures (10.1% without treatment [RR, 1.74; 95% CI, 0.92-3.32]). Compared with no treatment, costs to generate one additional patient with a NVS < or =3 were $23 with lidocaine 1% and $10 with lidocaine 2%. On insertion of an IV cannula on the back of the hand, 58% of patients report at least moderate pain. Lidocaine-Jet is analgesic; there is dose-responsiveness. However, Jet treatment is not painless, and costs incurred to achieve one success compared with doing nothing are not negligible. IMPLICATIONS: Insertion of an IV cannula is painful. Four-hundred patients were randomly allocated to test the analgesic efficacy, adverse effects, and cost-effectiveness of the needle-free intradermal drug delivery system (J-Tip); Jet). Jet with lidocaine is effective, but its application is not painless. Costs to achieve one patient with no more than moderate pain (numerical verbal scale < or =3 of 10) on insertion of an IV cannula are $10.

Intracameral anesthesia: a report by the American Academy of Ophthalmology.

OBJECTIVE: This document describes the technique of intracameral anesthesia and examines the available evidence to address questions about its effectiveness, possible corneal endothelial and retinal toxicity, and the optimal and maximal dose. METHODS: A literature search conducted for the years 1968 to 2000 retrieved over 180 citations that matched the search criteria. Panel members and a methodologist reviewed this information, and it was evaluated for the quality of the evidence presented. RESULTS: Some studies report effectiveness of intracameral anesthesia while others report no effect. In those studies showing an effect, levels of pain in the groups that were compared were low. Short-term studies seem to indicate that preservative (methylparaben)-free lidocaine 1% is well tolerated by the corneal endothelium but that higher concentrations of lidocaine are toxic. There is some evidence of electroretinogram changes after exposure to lidocaine or bupivacaine. CONCLUSIONS: The ideal timing and placement of intracameral anesthesia has not been determined. Because topical anesthesia alone is effective, surgeons may elect to use intracameral anesthesia for incremental pain control in patients who cannot be adequately managed with topical alone. Appropriate patient selection is important when using this method of anesthesia. While short-term studies seem to indicate safety, long-term effects are unknown. Patient preferences for anesthesia are not well studied.