LID study: Plasma lidocaine levels following airway topicalisation for paediatric microlaryngobronchoscopy (MLB).

OBJECTIVES: A dose of 5 mg/kg lidocaine is considered appropriate for paediatric airway topicalisation. Existing literature suggests that younger children are susceptible to toxic lidocaine plasma levels and achieve this at a faster rate. MAIN OUTCOME MEASURES: The primary outcome of this study was to ascertain peak plasma lidocaine levels after topicalisation for airway endoscopy. Secondary endpoints included: time to peak lidocaine plasma levels, signs of lidocaine toxicity (restricted to ECG changes or seizures when under anaesthesia) and clinical adverse events of laryngospasm, coughing or desaturation during the procedure. SETTING: Data were collected prospectively over 18 months at Royal Manchester Children's Hospital. PARTICIPANTS: Children aged 0-8 years undergoing elective diagnostic or therapeutic airway endoscopy were included within the study. DESIGN: Standardised 2% lidocaine was used for airway topicalisation. Dose varied depending upon the practitioner's usual practice. Venous bloodsampling occurred at 5, 10, 15 and 20 min post-administration and plasma lidocaine levels (ng/ml) were analysed. RESULTS: A significant relationship exists between higher peak plasma levels and ages <18 months (p = .00973). Strong linear correlation exists between body weight and age for our cohort (r = .88). Higher peak plasma lidocaine levels occur with total dose volumes between 2 and 3 mls of 2% lidocaine local anaesthetic (p = .03) compared with <2 ml total dose volumes. Data suggest a potential relationship of lower body weights achieving higher peak plasma levels (p = .0516). Reduced interquartile variation of peak plasma lidocaine levels exists when lidocaine dosing is <5 mg/kg. CONCLUSIONS: Age and total dose volume of topicalised lidocaine have a significant relationship with plasma lidocaine levels. A dose of 5 mg/kg topicalised lidocaine for paediatric airway endoscopy is safe and provides good operating conditions. Lower patient body weights trend towards higher peak lidocaine plasma concentrations and require further investigation.

Effects of intravenous lidocaine, dexmedetomidine, and their combination on IL-1, IL-6 and TNF-α in patients undergoing laparoscopic hysterectomy: a prospective, randomized controlled trial.

BACKGROUND: Surgical-related inflammatory responses have negative effects on postoperative recovery. Intravenous (IV) lidocaine and dexmedetomidine inhibits the inflammatory response. We investigated whether the co-administration of lidocaine and dexmedetomidine could further alleviate inflammatory responses compared with lidocaine or dexmedetomidine alone during laparoscopic hysterectomy. METHODS: A total of 160 patients were randomly allocated into four groups following laparoscopic hysterectomy: the control group (group C) received normal saline, the lidocaine group (group L) received lidocaine (bolus infusion of 1.5 mg/kg over 10 min, 1.5 mg/kg/h continuous infusion), the dexmedetomidine group (group D) received dexmedetomidine (bolus infusion of 0.5 µg/kg over 10 min, 0.4 µg/kg/h continuous infusion), and the lidocaine plus dexmedetomidine group (group LD) received a combination of lidocaine (bolus infusion of 1.5 mg/kg over 10 min, 1.5 mg/kg/h continuous infusion) and dexmedetomidine (bolus infusion of 0.5 µg/kg over 10 min, 0.4 µg/kg/h continuous infusion). The levels of plasma interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) at different time points were the primary outcomes. Secondary outcomes included hemodynamic variables, postoperative visual analogue scale (VAS) scores, time to first flatus, and incidence of nausea and vomiting after surgery. RESULTS: The levels of plasma IL-1, IL-6, and TNF-α were lower in groups D and LD than in group C and were lowest in group LD at the end of the procedure and 2 h after the operation (P < 0.05). The VAS scores were decreased in groups D and LD compared with group C (P < 0.05). The heart rate (HR) was decreased at the end of the procedure and 2 h after the operation in groups D and LD compared to groups C and L (P < 0.001). The mean blood pressure (MBP) was lower at 2 h after the operation in groups L, D, and LD than in group C (P < 0.001). There was a lower incidence of postoperative nausea and vomiting (PONV) in group LD than in group C (P < 0.05). CONCLUSIONS: The combination of lidocaine and dexmedetomidine significantly alleviated the inflammatory responses, decreased postoperative pain, and led to fewer PONV in patients undergoing laparoscopic hysterectomy. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT03276533 ), registered on August 23, 2017.

Studying the effect of vasopressors on therapeutic drug monitoring of two local anesthetics using hybrid micelle liquid chromatography as an analysis tool.

A hybrid micelle based mobile phase was used to develop and validate a liquid chromatographic method for the separation and quantification of two local anesthetics namely; lidocaine hydrochloride (LID), and bupivacaine hydrochloride (BPV) in presence of the frequently co administered vasopressors phenyl ephrine (PHR) and ephedrine (EPH). Optimization of chromatographic separation conditions was performed applying experimental one factor at a time tool, and design of experiment, where the retention behavior of all analytes using both optimization protocols was in accordance. Chromatographic separation was carried on a C8 column operating at 40 °C at a flow rate of 1.5 mL/min. using a mobile phase consisting of 0.18 M sodium dodecyl sulphate, 10% acetonitrile, containing 0.3% triethyl amine and adjusted to pH 7 using 2 M ortho phosphoric acid, adopting UV detection at 230 nm. The proposed method was fully validated and applied to both in vitro and in vivo analysis of rat blood samples. The pharmacokinetics of both LID and BPV was followed when they were solitary injected or when co administered with either PHR or EPH. Moreover, the in vitro spiked experiment was also subjected to documented bio-analytical validation procedures.

Lidocaine Reduces Sevoflurane Consumption and Improves Recovery Profile in Children Undergoing Major Spine Surgery.

BACKGROUND Intravenous lidocaine administered during surgery improves postoperative outcomes; however, few studies have evaluated the relationship between intravenous lidocaine and volatile anesthetics requirements. This study assessed the effects of lidocaine treatment on sevoflurane consumption and postoperative consciousness disorders in children undergoing major spine surgery. MATERIAL AND METHODS Patients were randomly divided into 2 treatment groups: lidocaine and placebo (control). The lidocaine group received lidocaine as a bolus of 1.5 mg/kg over 30 min, followed by a continuous infusion at 1 mg/kg/h to 6 h after surgery. The following data were assessed: end-tidal sevoflurane concentration required to maintain a bispectral index BIS between 40 and 60, intraoperative blood pressure, heart rate, demand for fentanyl, and consciousness level assessed after surgery using the Richmond Agitation-Sedation Scale. Any treatment-related adverse events were recorded. RESULTS Compared to the control group, lidocaine treatment reduced by 15% the end-tidal sevoflurane concentration required to maintain the intraoperative hemodynamic stability and appropriate level of anesthesia (P=0.0003). There were no intergroup differences in total dose of fentanyl used, average mean arterial pressure, or heart rate measured intraoperatively. The postoperative level of patient consciousness did not differ during the first 6 h between groups. After 9 h, more patients in the control group were still sleepy (P=0.032), and there were fewer perioperative complications in the lidocaine group. CONCLUSIONS Lidocaine treatment decreases sevoflurane consumption and improves recovery profiles in children undergoing major spine surgery.

Serum Concentrations of Lidocaine During Bariatric Surgery.

Lidocaine has been shown to be clinically beneficial during bariatric surgery. However, information about lidocaine serum concentrations in this setting is scarce. This prospective clinical trial included 42 obese patients undergoing laparoscopic bariatric surgery. They received lidocaine based on adjusted body weight. Administration began with a 1.5 mg·kg bolus of intravenous lidocaine followed by a continuous infusion of 2 mg·kg·hour. After skin closure, administration was decreased to 1 mg·kg·hour until discharge from the recovery room. No serum concentrations of lidocaine were outside the usual accepted range (1.5-5 µg·mL).

Pharmacokinetics of an intravenous constant rate infusion of a morphine-lidocaine-ketamine combination in Holstein calves undergoing umbilical herniorrhaphy.

OBJECTIVE: To describe the pharmacokinetics of morphine, lidocaine, and ketamine associated with IV administration of a constant rate infusion (CRI) of a morphine-lidocaine-ketamine (MLK) combination to calves undergoing umbilical herniorrhaphy. ANIMALS: 20 weaned Holstein calves with umbilical hernias. PROCEDURES: Calves were randomly assigned to receive a CRI of an MLK solution (0.11 mL/kg/h; morphine, 4.8 µg/kg/h; lidocaine, 2.1 mg/kg/h; and ketamine, 0.42 mg/kg/h) for 24 hours (MLK group) or 2 doses of flunixin meglumine (1.1 mg/kg, IV, q 24 h) and a CRI of saline (0.9% NaCl) solution (0.11 mL/kg/h) for 24 hours (control group). For all calves, the CRI was begun after anesthesia induction. Blood samples were obtained immediately before and at predetermined times for 120 hours after initiation of the assigned treatment. Noncompartmental analysis was used to estimate pharmacokinetic parameters for the MLK group. RESULTS: During the CRI, steady-state serum concentrations were achieved for lidocaine and ketamine, but not morphine. Mean terminal half-life was 4.1, 0.98, and 1.55 hours and area under the concentration-time curve was 41, 14,494, and 7,426 h•µg/mL for morphine, lidocaine, and ketamine, respectively. After the CRI, the mean serum drug concentration at steady state was 6.3, 616.7, and 328 ng/mL for morphine, lidocaine, and ketamine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: During the CRI of the MLK solution, steady-state serum concentrations were achieved for lidocaine and ketamine, but not morphine, likely owing to the fairly long half-life of morphine. Kinetic analyses of MLK infusions in cattle are necessary to establish optimal dosing protocols.

High-throughput quantification of ten antiarrhythmic drugs in human plasma using UPLC-MS/MS.

In this paper we present an FDA validated method to analyze ten antiarrhythmic drugs (atenolol, bisoprolol, carvedilol, diltiazem, flecainide, lidocaine, metoprolol, propranolol, sotalol and verapamil). A simple and fast sample preparation protocol with protein precipitation followed by ultra performance liquid chromatography (UPLC) for chromatographic separation and mass spectrometric detection applying electrospray ionization (ESI+) and selected reaction monitoring mode (MS/MS) was used. Only 50 µl plasma sample is needed for the simultaneous quantification of all compounds within a 5 min run-to-run analysis time. Sotalol-D6, carvedilol-D5 and verapamil-D6 were used as internal standards. The method was validated according to the FDA guidelines. Correlation coefficients were higher than 0.998 for all compounds. Intra- and interday accuracies were within 15 CV(%) for all analytes. The method is currently successfully applied for routine analysis in our hospital.

Polyacrylonitrile / graphene oxide nanofibers for packed sorbent microextraction of drugs and their metabolites from human plasma samples.

In the present study, a new graphene based nanofibers material (Polyacrylonitrile/Graphene Oxide (PAN/GO)) was used for microextraction by packed sorbent (MEPS). The PAN/GO nanofiber was synthesized using the electrospinning technique. MEPS online with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was utilized for the extraction and determination of two local anesthetic drugs (lidocaine, prilocaine) and their major metabolites (2,6-xylidine, o-toluidine) in human plasma samples. Parameters affecting the extraction efficiency were investigated and optimized (including sample pH, washing solution and elution solution). The validation of the method was based on FDA (Food and Drug Administration) guidelines for bioanalytical methods. The calibration curve ranged from 2.00 to 2000 nmol/L for lidocaine and prilocaine, and from 10.0 to 2000 nmol/L for 2,6-xylidine and o-toluidine. The coefficient of determination (R2) values were 0.996, 0.995, 0.995, 0.996 (n = 3) for lidocaine, prilocaine, 2,6-xylidine and o-toluidine, respectively. The extraction recovery was 93.0% for lidocaine, 96.0% for prilocaine, 68.0% for 2,6-xylidine and 69.0% for o-toluidine. The limits of detection (LODs) were 0.25, 0.50, 2.50, 1.25 nmol/L for lidocaine, prilocaine, 2,6-xylidine and o-toluidine, respectively. The lower limits of quantification (LLOQs) were 2.0 nmol/L for lidocaine and prilocaine, and 10 nmol/L for 2,6-xylidine and o-toluidine, respectively. The accuracy values for the quality control (QC) samples were in the range of 91.0-111% for lidocaine, 92.0-118% for prilocaine, 84.0-98.0% for 2,6-xylidine and 82.0-90.0% for o-toluidine. The inter-day precisions for QC samples ranged from 7.0% to 11.8% for lidocaine, from 8.6% to 11.7% for prilocaine, from 8.0% to 10.0% for 2,6-xylidine and from 8.0% to 9.0% for o-toluidine. The matrix effect values were in the range of -2.3% to -8.6% for lidocaine, -2.7% to -10.2% for prilocaine, 4.8%-5.2% for 2, 6-xylidine and -8.2% to 9.4% for o-toluidine.

Rectus sheath single-injection blocks: a study to quantify local anaesthetic absorption using serial ultrasound measurements and lidocaine serum concentrations.

OBJECTIVES: Rectus sheath blocks are an established option for analgesia following abdominal surgery, but pharmacokinetic data are limited. This study sought to characterise the absorption of lidocaine injectate and the pharmacokinetics of lidocaine after rectus sheath injection. METHODS: Bilateral rectus sheath single-injection blocks were given to 10 patients undergoing general or urological surgery. Afterwards, serial lidocaine serum levels and ultrasound measurements of the rectus sheath injectate reservoir were collected. KEY FINDINGS: Injectate within the rectus sheath was visible with ultrasound up to 12 h after injection. However, the rate of drug absorption exceeded that of injectate disappearance. Peak serum concentration occurred within 30 min with average peak concentrations of 1.65 µg/ml. Lidocaine clearance was lower than reported in young healthy subjects. The body mass index positively correlated with lidocaine terminal phase half-life, and clearance negatively correlated with age. CONCLUSIONS: The study provides the first data describing lidocaine pharmacokinetics after rectus sheath injection. Peak serum concentrations transiently achieved systemic levels associated with pain relief after a single bolus injection. The data from this study could be used to develop a regime using single shot rectus sheath blockade with a bolus of lidocaine followed by infusion using bilateral rectus sheath catheters.

Perioperative Intravenous Lidocaine Infusion Adverse Reaction: A Case Report.

Intravenous lidocaine is increasingly being utilized as an opioid-sparing analgesic. A 55-year-old man with well-controlled human immunodeficiency virus on highly active antiretroviral therapy was prescribed a lidocaine infusion at 1 mg/kg/h for postoperative pain. On postoperative day 2, the patient experienced 4 unresponsive episodes with tachycardia, hypertension, and oxygen desaturation. Serum lidocaine level was available 2 days later (high 6.3 µg/mL, therapeutic range 2.5-3.5 µg/mL). There is significant pharmacokinetic interaction between lidocaine and this patient's human immunodeficiency virus medications. This case highlights the need for a readily accessible list of medications that caution against lidocaine. We propose in-house serum lidocaine levels to monitor patients at an increased risk for toxicity.

Fatal intoxication with new synthetic cannabinoids AMB-FUBINACA and EMB-FUBINACA.

Introduction: Synthetic cannabinoids are currently the largest group of new psychoactive substances. Those that have been subjected to legal control are replaced by newer uncontrolled substances, which causes constant and dynamic changes to the drug market. Some of the most recent synthetic cannabinoids that have appeared on the "legal highs" market are AMB-FUBINACA and EMB-FUBINACA. Case history: A 27-year-old man was found dead on a bed in an apartment. At autopsy, congestion of internal organs, pulmonary oedema and left-sided pleural adhesions were found. The medical examiner concluded that the man died due to acute respiratory failure. The autopsy materials (blood, urine, liver, kidney, stomach, intestine, lung and brain) were collected for further toxicological analyses. Methods: The synthetic cannabinoids AMB-FUBINACA and EMB-FUBINACA were isolated from autopsy materials by precipitation with acetonitrile. The quantitative analyses were carried out by LC-MS/MS. Results: AMB-FUBINACA and EMB-FUBINACA were detected and quantified in all post-mortem materials except the blood. The determined concentrations of these compounds in solid tissues were in the range of 0.2-0.9 ng/g and 0.2-3.5 ng/g. The highest concentrations of AMB-FUBINACA and EMB-FUBINACA were revealed in the stomach content (5.8 and 36.2 ng/mL, respectively). Discussion: The presented case demonstrates that even in cases of fatalities, it is possible that the parent substance will not be present in the blood, while being present in other autopsy materials. The determined concentrations of the compounds may indicate oral administration of synthetic cannabinoids. It can also be assumed that AMB-FUBINACA and EMB-FUBINACA probably contributed to death. Conclusion: The presented case shows that synthetic cannabinoids can be undetected in the blood of even seriously or fatally intoxicated people. This situation means that the analysis of only blood samples may not confirm poisoning. The presented case also suggests that AMB-FUBINACA and EMB-FUBINACA use is dangerous to health and may lead to fatal intoxication.

Inhibitory effect of lidocaine on colonic spasm during colonoscopy: A multicenter double-blind, randomized controlled trial.

OBJECTIVES: Colonic spasm can interfere with colonoscopy, but antispasmodic agents can cause complications. This study aimed to assess the inhibitory effect of topical lidocaine compared with a placebo control. METHODS: In five tertiary-care hospitals in Japan, 128 patients requiring endoscopic resection of a colorectal lesion were enrolled and randomly and double-blindly allocated to colonoscopy with topical administration of 2% lidocaine solution 20mL (LID, n = 64) or normal saline 20mL (control, n = 64). During colonoscopy, the assigned solution was applied with a spray catheter near the lesion and the area was observed for three minutes. primary endpoint was the inhibitory effect at three time-points (1, 2 and 3 minutes after dispersion), using a three-point scale (excellent, fair, poor). Secondary endpoints were rebound spasm and adverse events. All endpoints were scored in real time. Serum lidocaine levels were measured in 32 patients (LID 16, control 16). RESULTS: There were no significant differences between groups in patient demographics. At all time-points, the proportion of patients with "excellent" scores was greater in LID group than control group, with significant differences observed at 2 minutes (p = 0.02) and 3 minutes (p = 0.02). In LID group, the rate of "excellent" scores increased by 12.5% at 2 minutes and was maintained at 3 minutes. Rebound spasm did not occur in LID group, compared with 15.6% of control group (p = 0.001). There were no adverse events in LID group. All serum lidocaine levels were below detectable levels. CONCLUSIONS: Topical lidocaine is an effective and safe method for suppressing colorectal spasm during colonoscopy (UMIN000024733).

A preliminary study on plasma concentration achieved following intrapterygomandibular space injection of dexamethasone as a route of drug delivery with lignocaine inferior alveolar nerve block-correlation of clinical effects.

PURPOSE: To determine the quantity of dexamethasone plasma concentration achieved following intrapterygomandibular space injection of dexamethasone when co-administered with inferior alveolar nerve block correlating with the clinical effects in the postoperative phase. OBJECTIVE: A preliminary prospective study to evaluate the dexamethasone plasma concentration achieved following intrapterygomandibular space injection of dexamethasone with 2% lignocaine inferior alveolar nerve block to achieve hemi-mandibular anesthesia for minor oral surgical procedures and derive clinical correlations. BACKGROUND: Dexamethasone is a glucocorticoid, chiefly used for the management of postsurgical sequelae like trismus and swelling in maxillofacial surgical practice. Conventionally, parenteral dexamethasone is administered via intravenous or intramuscular route. Intrapterygomandibular space injection is a novel route of steroid delivery described in literature. For minor oral surgical procedures in maxillofacial surgical practice requiring inferior alveolar nerve block, dexamethasone can be administered along with local anesthetic through a single injection as a mixture (twin mix). METHODS: Prospective double-blind randomized clinical trial was designed to evaluative plasma concentration of dexamethasone achieved following injection of a freshly prepared mixture of 1.8 ml of 2% lignocaine with adrenaline (1:200000) and 1 ml (4 mg) dexamethasone [2.8 ml solution of twin mix] in the pterygomandibular space. The 30 candidates included for the trial were randomly split into three study groups (ten each)-(1) control group (C); (2) intramuscular group (IM); (3) intraspace group (IS). RESULTS: The mean plasma dexamethasone concentration at 30 min postinjection in group IM was 226.41 ± 48.67 ng/ml and for IS group it was 209.67 ± 88.13 ng/ml. Post hoc (Bonferroni-Holm test) intergroup comparison for plasma dexamethasone concentration (IM and IS) was found statistically insignificant (P = 0.605). CONCLUSION: Intraspace route of drug administration can be utilized to deliver dexamethasonized local anesthetics safely with predictable clinical effects in the patients requiring mandibular minor oral surgery under local anesthesia.

The Effect of Dexmedetomidine on Oral Mucosal Blood Flow and the Absorption of Lidocaine.

Dexmedetomidine (DEX) is a sedative and analgesic agent that acts via the alpha-2 adrenoreceptor and is associated with reduced anesthetic requirements, as well as attenuated blood pressure and heart rate in response to stressful events. A previous study reported that cat gingival blood flow was controlled via sympathetic alpha-adrenergic fibers involved in vasoconstriction. In the present study, experiment 1 focused on the relationship between the effects of DEX on alpha adrenoreceptors and vasoconstriction in the tissues of the oral cavity and compared the palatal mucosal blood flow (PMBF) in rabbits between general anesthesia with sevoflurane and sedation with DEX. We found that the PMBF was decreased by DEX presumably because of the vasoconstriction of oral mucosal vessels following alpha-2 adrenoreceptor stimulation by DEX. To assess if this vasoconstriction would allow decreased use of locally administered epinephrine during DEX infusion, experiment 2 in the present study monitored the serum lidocaine concentration in rabbits to compare the absorption of lidocaine without epinephrine during general anesthesia with sevoflurane and sedation with DEX. The depression of PMBF by DEX did not affect the absorption of lidocaine. We hypothesize that this is because lidocaine dilates the blood vessels, counteracting the effects of DEX. In conclusion, despite decreased palatal blood flow with DEX infusion, local anesthetics with vasoconstrictors should be used in implant and oral surgery even with administered DEX.

Transplacental lidocaine intoxication.

Neonatal seizures are frequent in neonatal intensive care and the most common cause is perinatal asphyxia. Among other causes, toxin exposure is rare.We present a boy with an uneventful vaginal birth, who presented one hour after birth with apnea, hypotonia, mydriasis, tongue fasciculation, and tonic seizures. There was no hypoxic ischemic encephalopathy and brain imaging was normal. Toxicology screening revealed a toxic concentration of lidocaine in his blood. The intoxication was transplacental, as a cord blood sample confirmed the toxic level. This was probably due to maternal perineal nerve block with lidocaine.Perineal local infiltration of lidocaine is not without risk for the newborn. Toxicology screen remains an important tool in the work-up of neonatal seizures and sudden unexpected postnatal collapse.

Plasma concentrations of lidocaine following laryngeal administration or laryngeal and intratesticular administration in cats.

OBJECTIVE To determine plasma concentrations of lidocaine after laryngeal administration or laryngeal and intratesticular administration in cats. ANIMALS 14 healthy adult sexually intact male cats (7 cats/treatment). PROCEDURES Cats were randomly allocated to receive 0.1 mL of 2% or 10% lidocaine hydrochloride solution (treatments L2 and L10, respectively) sprayed on the larynx for laryngeal desensitization, followed by endotracheal intubation and isoflurane anesthesia. After a 7-day washout period, cats were again randomly allocated to receive treatment L2 or L10, and castration was performed under isoflurane anesthesia following intratesticular administration of 2% lidocaine solution (0.1 mL/kg). In both experiments, a blood sample for measurement of plasma lidocaine concentration was obtained before (0 minutes) and 3, 5, 10, 15, 20, 30, 45, 60, and 75 minutes after laryngeal administration of lidocaine solution. Anesthesia was discontinued at 60 minutes. Plasma lidocaine concentrations were measured with high-performance liquid chromatography. RESULTS After treatments L2 and L10, median maximum plasma lidocaine concentrations were 34.1 ng/mL (range, 0 to 279.4 ng/mL) and 93.6 ng/mL (range, 79.3 to 182.2 ng/mL), respectively. Time to maximum plasma concentration was 10 minutes (range, 0 to 20 minutes) for each treatment. When cats received intratesticular lidocaine administration following L2 or L10 treatment, median maximum plasma concentration was 181.0 ng/mL (range, 103.7 to 600.2 ng/mL) and 301.2 ng/mL (range, 265.8 to 1,770.0 ng/mL), respectively. CONCLUSIONS AND CLINICAL RELEVANCE On the basis of these data, combined laryngeal and intratesticular administration of lidocaine solution at a total dose of approximately 5 mg/kg appears to be safe for use in healthy adult cats.

Pilsicainide Poisoning: An Autopsy Case and Review of Literature.

We describe an autopsy case of fatal poisoning due to accidental overdose of pilsicainide, which is a Vaughan Williams class IC antiarrhythmic drug (a pure sodium channel blocker). A man in his 50s was found dead in his home at approximately noon. He had ischemic heart disease and insomnia, and had previously demonstrated improper prescription drug adherence. The autopsy revealed old coronary artery bypass grafting and mild fibrosis of myocardium, but no acute myocardial infarction was found in microscopic examination. Toxicological analysis also identified a high blood concentration of pilsicainide (femoral vein blood, 14.9 µg/mL), more than 15 times higher than reported therapeutic levels. The blood concentrations of other drugs were at therapeutic levels, and no alcohol was detected. We concluded that the cause of death was pilsicainide poisoning, based on the results of the autopsy and the toxicological examination. This is the first autopsy report of fatal poisoning due to pilsicainide as a single agent.

Enhanced HPLC-MS/MS method for the quantitative determination of the co-administered drugs ceftriaxone sodium and lidocaine hydrochloride in human plasma following an intramuscular injection and application to a pharmacokinetic study.

A sensitive HPLC-MS/MS method was established for the quantification of ceftriaxone sodium (CFT) and lidocaine HCl (LDC) in human plasma utilizing cefixime (CFX) and tadalafil (TDA) as internal standards. The analytes were extracted from human plasma by protein precipitation using acetonitrile. Chromatographic separation was performed on Kinetex C18 (50.0 × 4.6 mm, 5 µm particle size) column with methanol-0.01 M ammonium acetate pH 6.4 (70: 30, v/v) as mobile phase. Multiple reaction monitoring involving the transitions 555.10 → 396.20, 235.20 → 86.00, 454.20 → 284.80 and 390.20 → 268.20 was utilized to quantify CFT, LDC, CFX and TDA, respectively, using a triple quadrupole mass spectrometer which was operated in positive ion mode. The method revealed linearity in the concentration range of 3.0-300.0 µg/mL for CFT and 3.0-300.0 ng/mL for LDC. The validation of the method was achieved in accordance to the US Food and Drug Administration guidelines. A pharmacokinetic study was performed on healthy Egyptian volunteers after intramuscular injection of sterile ceftriaxone sodium (1 g CFT dissolved in 3.5 mL of 1% LDC) after approval from the ethics committee. The pharmacokinetic parameters were: Cmax 141.15 ± 39.84 (µg/mL) and 55.02 ± 9.36 (ng/mL); tmax (h) 2.50 ± 0.50 and 1.5 ± 0.50; t½ (h) 7.30 ± 2.98 and 4.23 ± 1.96; and Kel (h-1 ) 0.10 ± 0.04 and 0.20 ± 0.13 for CFT and LDC, respectively.