Plasma Lidocaine Concentrations Research Articles

The effect of epidural lidocaine administration on sedation of propofol general anesthesia: a randomized trial

Study ObjectiveTo examine the influence of epidural and intravenous (IV) lidocaine, and height of the epidural sensory block, on the dose of propofol required for induction of general anesthesia. DesignRandomized controlled study. SettingUniversity hospital. Patients66 adult, ASA physical status 1 and 2 patients, aged 25 to 65 years, undergoing elective abdominal surgery. InterventionsPatients were randomized to 4 groups: the epidural saline control group (Group C; L2-L3 puncture, epidural and IV saline), the IV lidocaine group (Group IV; L2-L3 puncture, saline epidural, IV lidocaine 1 mg/kg), the lumbar epidural lidocaine group (Group EL; L2-L3 puncture, 1.5% lidocaine epidural, IV saline), and the thoracic epidural lidocaine group (Group ET; T9-T10 puncture, 1.5%lidocaine epidural, IV saline). Two minutes after the beginning of the infusion of IV lidocaine or saline, propofol anesthesia was initiated. MeasurementsMean arterial blood pressure (MAP), heart rate (HR), and sensory block height were monitored. The induction dose of propofol, its estimated effect-site concentration (Ce), and plasma concentration were measured at various time points. Finally, we recorded the time taken for the bispectral index (BIS) to decrease to 60, the plasma concentration of lidocaine at induction, and the occurrence of adverse events. The induction time (when BIS reached 60) also was recorded. Main ResultsThe induction propofol dose, Ce, and plasma concentration of propofol when BIS equaled 60 were significantly lower in Group IV, Group EL, and Group ET than Group C. The above parameters in Group ET (T9 - T10 puncture) were significantly less than in Group EL (L2 - L3 puncture). The induction doses of propofol and plasma concentration of propofol and lidocaine were significantly higher in Group IV than in Groups EL or ET. ConclusionsEpidural and IV lidocaine reduce the dose of propofol required to induce general anesthesia. Administration of lidocaine via the epidural route reduces anesthetic requirements more so than the IV route. Propofol requirements were further reduced in patients with higher sensory epidural block.

Intravenous lipid emulsion given to volunteers does not affect symptoms of lidocaine brain toxicity.

Intravenous lipid emulsion has been suggested as treatment for local anaesthetic toxicity, but the exact mechanism of action is still uncertain. Controlled studies on the effect of lipid emulsion on toxic doses of local anaesthetics have not been performed in man. In randomized, subject-blinded and two-phase cross-over fashion, eight healthy volunteers were given a 1.5 ml/kg bolus of 20% Intralipid(®) (200 mg/ml) or Ringer's acetate solution intravenously, followed by a rapid injection of lidocaine 1.0 mg/kg. Then, the same solution as in the bolus was infused at a rate of 0.25 ml/kg/min. for 30 min. Electroencephalography (EEG) was recorded, and 5 min. after lidocaine injection, the volunteers were asked to report subjective symptoms. Total and un-entrapped lidocaine plasma concentrations were measured from venous blood samples. EEG band power changes (delta, alpha and beta) after the lidocaine bolus were similar during lipid and during Ringer infusion. There were no differences between infusions in the subjective symptoms of central nervous system toxicity. Lidocaine was only minimally entrapped in the plasma by lipid emulsion, but the mean un-entrapped lidocaine area under concentration-time curve from 0 to 30 min. was clearly smaller during lipid than Ringer infusion (16.4 versus 21.3 mg × min/l, p = 0.044). Intravenous lipid emulsion did not influence subjective toxicity symptoms nor affect the EEG changes caused by lidocaine.

Comparison of Lightwand and Fiberoptic Techniques for Airway Topical Anesthesia in Patients with Difficult Airways

Background: Awake intubation is often regarded as a cornerstone in the management of the known difficult airway, but needs adequate airway topical anesthesia. This randomized clinical study was designed to determine the feasibility, safety and efficacy of the lightwand technique to provide airway topical anesthesia for awake tracheal intubation (ATI) by comparing with the fiberoptic technique.Methods: Eighty adult patients with difficult airways were randomly assigned to one of two study groups to receive airway topical anesthesia by lidocaine sprays with the lightwand (LW group) or fiberoptic bronchoscope (FOB group). After airway topicalization, ATI was also performed using the lightwand and fiberoptic techniques, respectively. Level of sedation, time for each lidocaine spray in different targeted areas, total times for airway sprays, and total dosages of lidocaine were noted. Operators assessed difficulty of the airway spray and ATI using the visual analogue scales (VAS). An independent investigator assessed patients' discomfort during airway topicalization, patients' reaction, coughing severity, and intubating condition during ATI, and observed changes of blood pressure (BP) and heart rate (HR) during airway manipulations. Serial blood samples were obtained for analysis of plasma lidocaine concentrations. Also the postoperative follow-up of complications was done.Results: 96.7% of airway lidocaine sprays were successfully completed on the first attempt in the LW group compared with 84.7% in the FOB group. The operator VAS assessment of difficulty of the airway spray was significantly better, times for each supraglottic spray and first laryngeal spray, and total time for airway sprays were significantly shorter, and total dosages of lidocaine were smaller in the LW group compared with the FOB group. As compared with the FOB group, patients' reaction and coughing scores during ATI were significantly lower, intubating conditions and operator VAS assessment of difficulty of intubation were better, and systolic BP and HR at intubation were significantly lower in the LW group. However, there were not significant differences in the investigator scores of patients' discomfort during airway sprays, plasma lidocaine concentrations at all observed times and the postoperative interview variables between groups.Conclusions: As compared with the fiberoptic technique, use of the lightwand technique to provide airway topical anesthesia is easier for the experienced anesthetists, requires shorter time of airway preparation and smaller dosages of lidocaine, can produce better intubating condition for ATI, and does not result in more postoperative complications in sedated patients with difficult airways. Citation: Fu-Shan Xue, Nong He, He-Ping Liu, Xu Liao, Xiu- Zheng Xu, Jian-Hua Liu, et al. Comparison of lightwand and fiberoptic techniques for airway topical anesthesia in patients with difficult airways. J Anesth Perioper Med 2014; 1: 25-35. doi: 10.24015/JAPM.2014.0005This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Tumescent technique without epinephrine for endovenous laser therapy and serum lidocaine concentration.

Endovenous laser therapy (EVLT) requires tumescent lidocaine anesthesia. Although it is well known that the absorption of local anesthetic varies according to the injection site, little evidence exists establishing the maximum recommended safe dose for extravascular injections such as those used for EVLT. The aim of this study was to evaluate plasma concentration of lidocaine over time after administration of tumescent lidocaine during EVLT procedures in healthy volunteers. Between January 2011 and February 2013, 10 healthy patients scheduled for an EVLT procedure performed in a hospital setting were recruited to participate in an observational study. For each subject, a total of 10 venous samples were obtained for analysis after surgical injection of the tumescent lidocaine solution (0.1% concentration). Samples were collected at baseline (before the surgical procedure start) and then every 30 minutes for the first 2 hours after the initial lidocaine injection. Thereafter, venous samples were obtained every 2 hours, with the last sample drawn 12 hours after the surgeon's initial lidocaine injection. All specimens were drawn from a dedicated intravenous catheter, immediately placed in a heparinized blood collection tube, and centrifuged for 10 minutes at 3000 rpm. Plasma was then removed with a pipette and stored at -70 °C until analyzed. Total and free plasma lidocaine concentrations were determined by immunoassay. Plasma lidocaine concentrations were normalized by peak concentration for statistical comparisons. Laboratory data were available for nine of the 10 volunteers. The mean total lidocaine dose administered was 6.38 (± 2.2) mg/kg (range, 3.57-10.7 mg/kg). The total lidocaine blood levels ranged from 0.48 (± 0.28) to 1.3 (± 0.49) mcg/mL. The free lidocaine blood levels ranged from nondetectable to 0.76 (± 0.43) mcg/mL. The average total time of injection for the group was 32.8 (± 10.0) minutes (range, 21-49 minutes). Among all dose ranges, both total and free lidocaine peak blood level ratios occurred at times 60 to 120 minutes (P < .05). No value considered in the statistical analysis exceeded 5 mcg/mL at any time. Tumescent lidocaine without epinephrine for EVLT procedures produces a peak serum concentration at 60 to 120 minutes. The peak plasma concentration as observed with the standard institutional dosing of tumescent lidocaine appeared below the threshold for human toxicity.

Primary afferent input critical for maintaining spontaneous pain in peripheral neuropathy

Central sensitization after peripheral nerve injury may result in ectopic neuronal activity in the spinal cord dorsal horn, implying a potential autonomous pain-generating mechanism. This study used peripheral nerve blockade and systemic lidocaine administration, with detailed somatosensory assessment, to determine the contribution of primary afferent input in maintaining peripheral neuropathic pain. Fourteen patients with neuropathic pain (7 with unilateral foot pain due to peripheral nerve injury and 7 with bilateral pain in the feet due to distal polyneuropathy) underwent comprehensive characterization of somatosensory function by quantitative sensory testing. Patients were then administered an ultrasound-guided peripheral nerve block with lidocaine and intravenous lidocaine infusion in randomized order. The effect of these interventions on spontaneous pain intensity and on evoked cold, warm, pinprick, and brush responses was assessed at each session. All patients had sensory disturbances at baseline. The peripheral nerve block resulted in a complete abolition of ipsilateral pain within 10min (median) in all patients, with lidocaine plasma concentrations being too low to account for a systemic effect of the drug. Intravenous lidocaine infusion reduced the spontaneous pain by 45.5% (±31.7%), and it reduced mechanical and thermal hypersensitivity in most patients who displayed such signs. However, the improvement in evoked hypersensitivity was not related to the effect of the drug on spontaneous pain intensity. This study demonstrated that regardless of the individual somatosensory phenotype and signs of central sensitization, primary afferent input is critical for maintaining neuropathic pain in peripheral nerve injury and distal polyneuropathy.

Cardiovascular effects of a continuous rate infusion of lidocaine in calves anesthetized with xylazine, midazolam, ketamine and isoflurane

ObjectiveTo assess the cardiovascular changes of a continuous rate infusion of lidocaine in calves anesthetized with xylazine, midazolam, ketamine and isoflurane during mechanical ventilation. Study designProspective, randomized, cross-over, experimental trial. AnimalsA total of eight, healthy, male Holstein calves, aged 10 ± 1 months and weighing 114 ± 11 kg were included in the study. MethodsCalves were administered xylazine followed by ketamine and midazolam, orotracheal intubation and maintenance on isoflurane (1.3%) using mechanical ventilation. Forty minutes after induction, lidocaine (2 mg kg−1 bolus) or an equivalent volume of saline (0.9%) was administered IV followed by a continuous rate infusion (100 μg kg−1 minute−1) of lidocaine (treatment L) or saline (treatment C). Heart rate (HR), systolic, diastolic and mean arterial pressures (SAP, DAP and MAP), central venous pressure (CVP), mean pulmonary arterial pressure (mPAP), pulmonary arterial occlusion pressure (PAOP), cardiac output, end-tidal carbon dioxide (Pe’CO2) and core temperature (CT) were recorded before lidocaine or saline administration (Baseline) and at 20-minute intervals (T20-T80). Plasma concentrations of lidocaine were measured in treatment L. ResultsThe HR was significantly lower in treatment L compared with treatment C. There was no difference between the treatments with regards to SAP, DAP, MAP and SVRI. CI was significantly lower at T60 in treatment L when compared with treatment C. PAOP and CVP increased significantly at all times compared with Baseline in treatment L. There was no significant difference between times within each treatment and between treatments with regards to other measured variables. Plasma concentrations of lidocaine ranged from 1.85 to 2.06 μg mL−1 during the CRI. Conclusion and clinical relevanceAt the studied rate, lidocaine causes a decrease in heart rate which is unlikely to be of clinical significance in healthy animals, but could be a concern in compromised animals.

Effects of lidocaine administration via continuous rate infusion on the minimum alveolar concentration of isoflurane in New Zealand White rabbits (Oryctolagus cuniculus)

To evaluate the effect of a continuous rate infusion (CRI) of lidocaine on the minimum alveolar concentration (MAC) of isoflurane in rabbits. Five 12-month-old female New Zealand White rabbits (Oryctolagus cuniculus). Rabbits were anesthetized with isoflurane. Baseline isoflurane MAC was determined by use of the tail clamp technique. A loading dose of lidocaine (2.0 mg/kg, IV) was administered followed by a CRI of lidocaine at 50 μg/kg/min. After 30 minutes, isoflurane MAC was determined. Another loading dose was administered, and the lidocaine CRI then was increased to 100 μg/kg/min. After 30 minutes, isoflurane MAC was determined again. Plasma samples were obtained for lidocaine analysis after each MAC determination. Baseline isoflurane MAC was 2.09%, which was similar to previously reported values in this species. Lidocaine CRI at 50 and 100 μg/kg/min induced significant reductions in MAC. The 50 μg/kg/min CRI resulted in a mean plasma lidocaine concentration of 0.654 μg/mL and reduction of MAC by 10.5%. The 100 μg/kg/min CRI of lidocaine resulted in a mean plasma concentration of 1.578 μg/mL and reduction of MAC by 21.7%. Lidocaine also induced significant decreases in arterial blood pressure and heart rate. All cardiopulmonary variables were within reference ranges for rabbits anesthetized with inhalation anesthetics. No adverse effects were detected; all rabbits had an uncomplicated recovery from anesthesia. Lidocaine administered as a CRI at 50 and 100 μg/kg/min decreased isoflurane MAC in rabbits. The IV administration of lidocaine may be a useful adjunct in anesthesia of rabbits.

Cardiorespiratory and antinociceptive effects of two different doses of lidocaine administered to horses during a constant intravenous infusion of xylazine and ketamine

BackgroundThis study investigated the antinociceptive effects of a constant rate infusion (CRI) of lidocaine during xylazine and ketamine anesthesia in horses and aimed to correlate these effects with cardiorespiratory variables, bispectral index (BIS) and plasma lidocaine concentrations. Six adult crossbred mares weighing 320–400 kg were anesthetized on three different occasions. Sedation was performed with xylazine (0.75 mg/kg IV) and anesthetic induction with guaifenesin (75 mg/kg IV) and ketamine (2 mg/kg IV). Anesthesia was maintained with 37.5 μg/kg/min of xylazine and 87.5 μg/kg/min of ketamine both administered intravenously for 75 min. The three treatments consisted of: lidocaine (loading dose: 5 mg/kg, CRI: 100 μg/kg/min; THL); lidocaine (loading dose: 2.5 mg/kg; CRI: 50 μg/kg/min: TLL); and saline (TS); all given 15 min after induction and maintained for 1 h. Antinociception was measured by response to electrical stimulation and bispectral index (BIS) was recorded during anesthesia. Parametric and non-parametric data were compared using ANOVA followed by Student-Newman-Keuls and Friedman tests, respectively.ResultsPlasma lidocaine concentrations peaked at the end of lidocaine loading dose and was greater in THL (9.61 ± 2.75 μg/mL) vs TLL (4.50 ± 3.34 μg/mL). Electrical noxious stimulation caused purposeful movement in all horses from TS, but no response in THL. The BIS was decreased in THL only and was less when compared to the other treatments throughout anesthesia. Blood pressure, PaO2 and PaCO2 increased and heart rate (HR), respiratory rate (RR), pH, total plasma protein and temperature decreased during anesthesia in all treatments. PaCO2 and HR were greater and RR and pH less in THL compared to TLL and TS at 30 min during anesthesia. All recoveries were considered excellent. Time to standing was longer after THL (60 ± 20 min) than following TLL and TS (32 ± 17 and 30 ± 15 min, respectively).ConclusionsAt the highest dose administered (THL) lidocaine CRI during xylazine/ketamine anesthesia decreased BIS and motor response to noxious stimulation, and prolonged recovery time without significant added cardiorespiratory depression.

Perioperative evaluation of tumescent anaesthesia technique in bitches submitted to unilateral mastectomy.

BackgroundTumescent anaesthesia (TA) is a widely used technique in oncologic surgeries necessitating large resection margins. This technique produces transoperative and postoperative analgesia, reduces surgical bleeding, and facilitates tissue divulsion. This prospective, randomised, blind study evaluated the use of TA in bitches submitted to mastectomy and compared the effect of TA with an intravenous fentanyl bolus. A 2.5-mcg/kg intravenous fentanyl bolus (n = 10) was compared with TA using 0.275% lidocaine (n = 10) in bitches submitted to unilateral mastectomy. Sedation was performed by intramuscular (IM) injection of 0.05 mg/kg of acepromazine combined with 2 mg/kg of meperidine. Anaesthesia was induced with 5 mg/kg of intravenous propofol and maintained with isoflurane/O2. Heart and respiratory rates; systolic, mean, and diastolic arterial blood pressures; central venous pressure; SpO2; ETCO2; inspired and expired isoflurane concentrations; and temperature were measured transoperatively. Visual analogue scales for sedation and pain and the Glasgow composite and Melbourne pain scales were used for postoperative assessment. The surgeon investigated the quality of the surgical approach, considering bleeding and resection ability, and the incidence of postoperative wound complications.ResultsThe heart rate was lower and the end-tidal isoflurane concentration was higher in dogs treated with fentanyl than in dogs treated with TA. A fentanyl bolus was administered to 8 of 10 dogs treated with fentanyl and to none treated with TA. Intraoperative bleeding and the mammary gland excision time were lower in dogs treated with TA. The maximal mean and individual plasma lidocaine concentrations were 1426 ± 502 ng/ml and 2443 ng/ml at 90 minutes after infiltration, respectively. The Glasgow Composite Pain Scale scores were higher in dogs treated with fentanyl than in dogs treated with TA until 2 hours after extubation.ConclusionsCompared with intravenous fentanyl, TA in bitches: may be easily performed in non-inflamed, ulcerated, adhered mammary tumours; has an isoflurane-sparing effect; improves transoperative and immediate postoperative analgesia; is apparently safe for use in clinical conditions as evidenced by the fact that it did not produce any adverse signs or lidocaine plasma concentrations compatible with toxicity; does not modify the recovery time; and facilitates the surgical procedure without interfering with wound healing.

Effectiveness of a topical local anaesthetic spray as analgesia for dressing changes: A double-blinded randomised pilot trial comparing an emulsion with an aqueous lidocaine formulation

BackgroundPartial thickness skin graft wounds are painful. Topically applied lidocaine has been used for analgesia in several clinical trials. This study compared the effectiveness of two different formulations of topical local anaesthetic for dressing changes of partial thickness skin graft donor sites. MethodsA double-blind randomised controlled, pilot trial was conducted in 29 patients undergoing split thickness skin graft surgery. Subjects were randomised to either a 3% lidocaine emulsion formulation “Treatment E” (NOPAYNE™) or a 4% aqueous solution “Treatment A” (Xylocaine™). Subjects received one spray per 3cm2 of donor site area followed by up to two further spays as required. Endpoints included pain intensity measured by the numerical rating scale (NRS) up to 1h after dressing change commencement, sting sensation, overall satisfaction and lidocaine plasma concentration. ResultsThe 60min pain scores for E and A were 1.3±0.3 (mean±SEM) and 1.8±0.4 (p=0.98) respectively. Nearly 90% of patients were very satisfied with their treatment. The mean plasma concentrations of lidocaine for A and E were 0.132mg/l and 0.040mg/l respectively (p=0.069). ConclusionThe topical local anaesthetic formulations achieved low pain scores during dressing changes. The safety profile was potentially improved with the emulsion formulation of lidocaine.

Comparison of Effects of Thoracic Epidural and Intravenous Administration of Lidocaine on Target-Controlled Infusion of Propofol and Tracheal Intubation Response During Induction of Anesthesia

To compare the effects of thoracic epidural anesthesia (TEA) and intravenous (IV) lidocaine on the effect-site concentration (Ce) of propofol target-controlled infusion (TCI) and the intubation-induced stress responses during general IV anesthesia induction. A prospective, randomized trial. A university hospital. Sixty patients undergoing elective surgery for thoracotomies. Patients scheduled for thoracotomies were divided into 3 groups as group TEA, group IV, and control group. Group TEA or group IV received the same doses but not the same concentration of lidocaine via TEA (0.15 mL/kg of 1.35% lidocaine) or IV (2mg/kg of 2% lidocaine), respectively, 15 minutes before induction of anesthesia, and the control group received the same volume of 0.9% normal saline epidurally. Heart rate and mean arterial pressure as well as the time to loss of consciousness (LOC), total doses of propofol TCI, and Ce at LOC were recorded during anesthesia induction. Plasma lidocaine concentration detected was 1.9 (0.3) μg/mL in the IV group and 1.0 (0.3) μg/mL in the TEA group (p<0.001). The time to LOC, total doses of propofol TCI, and Ce at LOC were significantly lower in the IV group than in the TEA group and the control group (p<0.001). Both lidocaine groups showed significant decreases in the elevation of mean arterial pressure and heart rate and plasma concentrations of epinephrine and norepinephrine induced by intubation compared to the control group (p< 0.05). Lidocaine administered via both TEA and IV decreased the induction doses of propofol and suppressed cardiovascular and stress responses to tracheal intubation. Administration of 2mg/kg of 2% lidocaine IV was better, with no side effects of lidocaine toxicity.

Regional Sympathetic Blockade Attenuates Activation of Intestinal Macrophages and Reduces Gut Barrier Failure

Endotoxin-induced activation of monocytes may lead to extravasation of cells, excessive production of nitric oxide, and subsequent epithelial injury in the gut. Regional sympathetic blockade by means of thoracic epidural anesthesia has been implicated to protect the epithelial barrier. This study tested the hypothesis that thoracic epidural anesthesia decreases epithelial permeability by attenuating monocytic production of nitric oxide and nitrosative stress. Rats were anesthetized, hemodynamically monitored, and mechanically ventilated. Endotoxemia was induced by an intravenous bolus injection of Escherichia coli lipopolysaccharide. Either lidocaine 2% or normal saline was injected as a bolus, followed by a continuous infusion via an epidural catheter. Three hundred minutes after injection of lipopolysaccharide or normal saline, gut epithelial permeability to fluorescein isothiocyanate-dextran (4 kDa), intestinal expression of inducible nitric oxide synthase by macrophages, and lipid peroxidation represented by 8-isoprostane tissue concentration were quantified. Thoracic epidural anesthesia significantly attenuated the endotoxin-induced increases in gut epithelial permeability (437 [293, 492] vs. 628 [532, 1,042] ng/ml, median [quartiles], P = 0.03), expression of nitric oxide synthase (2 [1,2] vs. 7 [5,8] cells per 384 µm(2), P = 0.003), macrophage infiltration, and lipid peroxidation (22,460 ± 11,476 vs. 37,840 ± 17,551 pg/ml, mean ± SD, P = 0.05). Thoracic epidural anesthesia attenuates endotoxin-induced gut epithelial injury. This is likely due to a decrease in monocytic extravasation and intestinal nitrosative stress. As possible mechanisms, direct nerve-immune interplay, a reduction in plasma catecholamines, or a systemic lidocaine effect has to be considered.

The Effect of Intravenous Lidocaine Infusion on Bronchoalveolar Lavage Cytology in Equine Recurrent Airway Obstruction

Lidocaine decreases neutrophilic inflammation in models of acute lung injury and decreases inflammation in asthmatic patients. Neutrophilic bronchiolitis develops in recurrent airway obstruction (RAO), but it remains unknown if lidocaine infusion decreases neutrophil migration into the airways. Lidocaine decreases neutrophilic inflammation as measured in BALF in RAO-affected horses. Six RAO-susceptible horses in remission. In a randomized cross-over design, horses received lactated Ringer's solution (LRS) IV or lidocaine hydrochloride IV with a minimum of 4 weeks at pasture between treatments. Treatments were delivered as continuous infusions beginning 4 hours before and for 68 hours during exposure to hay and straw challenge. Clinical score (CS, grade 0-8), maximal change in pleural pressure (∆Ppl(max) ), and bronchoalveolar lavage fluid (BALF) cytology were measured at baseline and the end of challenge (day 4). Plasma lidocaine concentrations were monitored daily. At baseline, there were no significant differences in variables between treatments. Plasma lidocaine concentration was consistently > 1100 ng/mL. After challenge, CS increased significantly [baseline: 2/8 (2-3), [median (interquartile range)]; day 4: 4/8 (4-5) P = .0006] as did ∆Ppl(max) [baseline: 3.6 (2.63-4.95) cmH(2) 0; day 4: 9.62 (6.5-16) P = .0036], but there was no difference between treatments. Percentage of neutrophils was not different between treatments, but lidocaine infusion significantly increased BALF total cells [baseline: LRS 2.18 ± 0.82 × 10(5) cells/mL (mean ± SD), lidocaine 1.6 ± 0.3 × 10(5) , day 4: LRS 2.0 ± 0.88 × 10(5) , lidocaine 4.4 ± 2 × 10(5) (P = .0045)]. Lidocaine does not decrease neutrophilic inflammation in RAO.

Effects of Application Durations and Heat on the Pharmacokinetic Properties of Drug Delivered by a Lidocaine/Tetracaine Patch: A Randomized, Open-Label, Controlled Study in Healthy Volunteers

BackgroundThe lidocaine/tetracaine heated patch is typically applied to the skin for 20 to 30 minutes to provide local dermal analgesia prior to venous access or minor dermatologic procedures. The potential exists for the use of multiple heated patches for longer application times, but the pharmacokinetic properties and tolerability of these multiple and/or longer applications have not been assessed. ObjectiveThe aim of this study was to assess the effects of heat and application time on the pharmacokinetic properties and tolerability of the patch after the application of 4 lidocaine/tetracaine (70/70 mg) heated patches applied at the same time in healthy volunteers for up to 12 hours. MethodsIn this randomized, open-labeled, controlled study, healthy subjects underwent 4 treatment periods (2-, 4-, or 12-hour application of 4 heated patches, or 4-hour application of 4 unheated patches), each separated by a 1-week washout period. ResultsTwelve subjects were enrolled (8 women, 4 men; mean age, 31.8 years; mean body mass index, 24.1 kg/m2). No tetracaine was detected in the plasma of any subject. Plasma concentrations of lidocaine increased rapidly during the first 2 hours of application in each heated-patch group, and with mean (SD) Cmax values of 18.2 (5.1), 25.7 (5.9), and 30.3 (8.1) ng/mL in the 2-, 4-, and 12-hour groups, respectively. Estimates of application time–normalized AUC0–t were not significantly different between the 2- and 4-hour applications of the heated patches, but were 25% lower during the 12-hour application time, suggesting continued but diminished drug delivery between 4 and 12 hours. Compared with subjects who received the unheated patch, those who received the heated patch had plasma lidocaine concentrations 5- and 3-fold higher after 30 and 60 minutes, respectively. Fifteen mild to moderate adverse events (AEs) were reported in 7 subjects, and none of the subjects discontinued the study due to treatment-related AEs. ConclusionThe heated patch continuously delivered drug for up to 12 hours and was generally well tolerated in these healthy subjects. ClinicalTrials.gov identifier: NCT01602757.

Toxicity of topical lidocaine applied to the breasts to reduce discomfort during screening mammography

Background:We measured the effect of 30 milliliters (mL) of 4% lidocaine gel on the breasts and chest wall of healthy women covered for 1 h on plasma concentrations of lidocaine and its principal metabolite, monoethylglycinexylidide (MEGX), electrocardiogram (EKG) results, and adverse events.Materials and Methods:This institutional review board-approved, prospective, open-label study complied with the Health Insurance Portability and Accountability Act (HIPAA). The study evaluated 10 healthy women aged 42-75 years with 30 mL of 4% lidocaine gel on the skin of the breasts and chest wall covered for 1 h. Cardiac and neurological assessments were performed and blood was drawn for lidocaine and MEGX levels at baseline and 1/2, 1, 2, 3, 4, 6, and 8 h after application. EKGs were performed before application and at 3 h. Subjects provided informed written consent. Primary and secondary outcomes were plasma concentrations of lidocaine and MEGX and frequency of adverse events, respectively. Statistical analysis included paired t-tests for EKGs and repeated measures regression for vital signs.Results:No lidocaine was detected in the blood of 9 of 10 subjects. One subject had low plasma concentrations of lidocaine just above the level of detection the first 4 h after application only. No MEGX was detected. Mean decrease in heart rate was likely multifactorial.Conclusion:Thirty mL of 4% lidocaine gel on the breasts and chest wall covered for 1 h in healthy women resulted in plasma concentrations of lidocaine and MEGX well below therapeutic or toxic levels and no clinically significant adverse events.

Proof of Systemic Safety of a Lidocaine Ointment in the Treatment of Patients with Anorectal Pain

The aim of the study was to demonstrate that repeated anorectal administration of a 5% lidocaine ointment (CAS 137-58-6; LidoPosterine Salbe, Posterisan akut Rektalsalbe) in the treatment of patients with acute anorectal pain does not result in systemically efficacious plasma concentrations of lidocaine. In an open single-center study 24 male or female patients with anorectal pain due to hemorrhoids, anal fissures, fistulas or proctitis administered lidocaine ointment as a single anorectal dose (2.5 g ointment corresponding to 125 mg lidocaine) followed by repeated administration (2.5 g ointment t.i.d.) for 4 days. Safety evaluation was performed with respect to plasma concentrations of lidocaine, vital signs, electrocardiogram (ECG), physical findings and adverse events. Blood samples were drawn prior to the first single administration and at 13 time points over the first 24 h in order to create a pharmacokinetic profile. Blood samples were also drawn prior to administration of the last dose on day 5 and thereafter using the identical time points for blood sampling as on day 1. Vital signs and ECG were recorded immediately before and 1 and 4 h after the first and last administration, respectively. Adverse events and skin tolerability were also recorded at predefined times during the study period. After a single dose of 125 mg lidocaine the average extent of exposure in terms of the AUC(tau,sd) during a 6 h dosage interval amounted to 397.7 ng/ml x h (geometric mean). C(max,sd) reached a mean value of 131.8 ng/ml (geometric mean). Only a minor accumulation of the lidocaine plasma concentrations was observed after multiple dose application. The geometric mean of the AUC(tau,md) (503.8 ng/ml x h, tau = 6 h) and the geometric mean of C(max,md) (145.9 ng/ml) were slightly higher than the corresponding single dose values. The AUC accumulation ratio was calculated as 127% (90% CI: 108-148%) and the C(max) accumulation ratio reached 120% (90% CI: 101-139%). Plasma peak concentrations of lidocaine in all subjects remained with a sufficient safety margin below the minimal effective therapeutic plasma concentration (1.5 microg/ml) as well as by an order of magnitude below toxic concentrations (5 microg/ml). There were neither unexpected, serious nor severe adverse events. There were no clinically relevant findings with respect to vital signs and ECG. Repeated anorectal administration of a 5% lidocaine ointment proved to be safe with respect to systemic plasma concentrations of lidocaine and vital signs.

Pharmacokinetics of concurrently administered intravenous lidocaine and flunixin in healthy horses

Lidocaine is a moderately protein bound drug often administered systemically in post-operative horses to treat symptoms of visceral pain and ileus (Milligan et al., 2007; Nolen-Walston et al., 2007). Flunixin is a a highly protein bound drug non-steroidal anti-inflammatory drug (NSAID) also administered to horses to treat visceral pain and inflammation associated with colic (Coakley et al., 1999; Pellegrini-Masini et al., 2004; Moore, 2006). Therefore, these drugs are often used in combination to treat horses. The pharmacokinetics of these drugs have been examined independently in the horse (Coakley et al., 1999; Pellegrini-Masini et al., 2004; Milligan et al., 2006), but to the authors’ knowledge, they have not been examined while administered concurrently in the horse. A previous study (Milligan et al., 2006) found potentially meaningful in vitro interactions in the ultrafiltrate concentrations of lidocaine when these drugs were combined. The purpose of this study was to determine lidocaine plasma and plasma ultrafiltrate concentrations and flunixin plasma concentrations when concurrently administered to healthy horses.

Plasma Ropivacaine Concentrations After Ultrasound-guided Transversus Abdominis Plane Block

Abstract Background The transversus abdominis plane block is a novel technique involving injection of local anaesthetic between the internal oblique and the transversus abdominis muscles of the abdominal wall. It is possible that injection of a large dose of local anaesthetic into a relatively vascular plane may result in toxic concentrations. One previously published study examined plasma lidocaine concentrations after transversus abdominus plane block and showed potentially toxic plasma concentrations. Although ropivacaine is most commonly used for this technique, plasma concentrations of ropivacaine after this block have not been reported previously. Methods Adult female patients undergoing elective open gynaecological surgery received bilateral ultrasound-guided transverse abdominal plane blocks before surgical incision (3 mg kg−1 of ropivacaine diluted to 40 ml). Venous blood was collected each 15 min for the first hour, each 30 min for the second hour, and then at 3, 4, 12, and 24 h post-block. Results Twenty-eight patients were recruited. The mean (sd) peak total ropivacaine concentration occurred 30 min post-injection and was 2.54 (sd 0.75) µg ml−1. The highest measured concentration was 4.00 µg ml−1, also 30 min post-injection. Mean total concentrations remained above 2.20 µg ml−1 for up to 90 min post-injection. The mean unbound peak venous concentration was 0.14 (0.05) µg ml−1, and the peak was 0.25 µg ml−1. Conclusions Transversus abdominus plane block using 3 mg kg−1 of ropivacaine produces venous plasma concentrations that are potentially neurotoxic, although broadly consistent with plasma levels found after injection at other comparable sites.

Population Pharmacokinetics of Lidocaine Administered During and After Cardiac Surgery

The objective of this study was to determine the pharmacokinetics of lidocaine in a 48-hour infusion in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). A retrospective substudy of a clinical trial assessing the efficacy of intravenous lidocaine for postoperative cognitive decline. A university hospital. Ninety-nine patients undergoing cardiac surgery with CPB. After the induction of anesthesia, lidocaine was administered as a bolus of 1 mg/kg and followed by a continuous infusion at 4 mg/min for the 1st hour, 2 mg/min for the 2nd hour, and 1 mg/min for the next 46 hours. Blood samples were taken at baseline, the end of CPB, and 24 and 48 hours after CPB for the measurement of the plasma concentration of lidocaine. Lidocaine levels increased significantly over time despite a constant rate of infusion (p < 0.05). The pharmacokinetics of lidocaine was best described by a 2-compartment model, and body weight was found to be a significant factor for the volume of the central compartment and clearance. The final pharmacokinetic parameters were V(1)(L) = 0.0619*weight, V(2)(L) = 187, CL(1) (L/min) = 0.00419*weight, and CL(2) (L/min) = 8.92. A 2-compartment pharmacokinetic model best describes the plasma concentrations of a 48-hour lidocaine infusion in patients undergoing cardiac surgery with CPB. The inclusion of body weight as a covariate on clearance and central compartment improves the model. Lidocaine infusions should be dosed by body weight and decreased after 24 hours to avoid potential toxicity in long-term infusions.

Local anaesthetic systemic toxicity treated with intravenous lipid emulsion: ineffective treatment or selection of an inadequate lipid rescue dose?

We thank Aveline et al.1 for their detailed account of central nervous system (CNS) toxicity following ultrasound-guided sciatic and saphenous nerve block using lidocaine and ropivacaine in a patient scheduled for hallux valgus surgery. They reported clinical signs compatible with systemic absorption of local anaesthetics and initiated treatment with 20% intralipid as 100 ml bolus doses 2 min apart. Unfortunately, this intervention was unsuccessful and general anaesthesia was required. The authors concluded that intralipid had been ineffective and suggested an interaction between local anaesthetic agents, intralipid, and carbamazepine treatment the patient was taking for trigeminal neuralgia, may have been a contributory factor. We agree that the patient exhibited local anaesthetic systemic toxicity (LAST) and wish to suggest possible explanations for the apparent failure of intralipid in this case. In their calculations of the local anaesthetic dose administered, the authors appear to have omitted the saphenous nerve component of their technique of 100 mg lidocaine, which, if included means the patient received a total dose of 400 mg or 7.02 mg kg−1 of plain lidocaine. The plasma lidocaine concentration of 2.3 μg ml−1, recorded 25 min after the block, is consistent with levels previously reported with injection of the same dose of lidocaine in the subcutaneous tissue of the abdominal wall.2 This would support the notion that LAST most likely represents systemic absorption from correctly placed peripheral nerve blocks rather than primarily from an intravascular injection. If the additive effect of the ropivacaine element of the block is taken into consideration in overall dose calculations,3 this may explain why CNS signs of LAST became apparent. Given the absence of significant cardiovascular, metabolic or electrolyte disturbance, all of which may have contributed to the severity of LAST, we agree that drug interaction may have been relevant in this case.4 All three drugs rely on protein binding of 75% or more for transport within the blood and all three are lipid soluble to varying degrees, with log P values for carbamazepine, lidocaine and ropivacaine of 2.73, 2.36 and 3.11, respectively. It is possible that competition for protein-binding sites between drugs resulted in a greater proportion of unbound local anaesthetics manifesting as systemic toxicity. Thus, for the lipid sink sequestration activity of intralipid to be fully effective, we consider this may have required administration of a proportionately larger volume of intralipid than usual. Previously intravenous lipid emulsion (ILE) has been reported to reverse LAST completely after presumed intravascular injection. We are aware of two published reports in which recovery from LAST occurred by early bolus administration of 20% intralipid followed by an infusion to a total volume of 500 ml.5,6 Although the time taken to restore a full level of consciousness did vary, in these cases the ILE reversed the LAST rapidly enough to avoid tracheal intubation. We advocate the early use of ILE but not as an alternative to safe local anaesthetic dosing and other appropriate resuscitation measures. Guidance for treatment of LAST has been posted on the Lipid Rescue website (http://www.LipidRescue.com) and elsewhere.7 For adults, these recommendations generally advocate an initial bolus dose of 100 ml (approximately 1.5 ml kg−1) 20% intralipid, followed by a rapid infusion of 400 ml over 20 min. Two further 100 ml boluses may be given and an infusion continued until signs of LAST have been reversed, if necessary continuing until a total volume of 12 ml kg−1 has been administered. We are curious as to why intravenous lipid treatment was suspended when only 200 ml had been given. Although we can only speculate at what might have happened had the volume of intralipid administered been bigger, this case is of value because it seems to confirm that the effects of ILE in the clinical setting are dose-dependent and perhaps the dose administered in this case was inadequate.