Monoethylglycinexylidide Concentrations Research Articles

Perioperative Application of 2% Lidocaine

Perioperative intravenous lidocaine (IVL) can help minimize opioid-related side effects that impede the postoperative recovery process. Neurological side effects were averaged at an 8 mg/kg dose, and cardiotoxicity side effects were reported at plasma values greater than 21 g/ml. Approximately 90% of lidocaine is converted to monoethylglycinexylidide (MEGX) in the liver via oxidative demethylation (dealkylation). Analysis of MEGX concentrations after lidocaine administration can be a method used to evaluate liver function. Perioperative intravenous lidocaine lowers discomfort, nausea, the duration of ileus, the need for opioids, and the length of time spent in the hospital after surgery. During injection, low blood concentrations can result in these symptoms, which may last for several hours or days after termination. Postoperative problems, such as pain and organ failure, can be caused by anti-inflammatory and pro-inflammatory components. Analgesic, anti-inflammatory, and anti-hyperalgesic are just some of the other effects of lidocaine. It also decreases the volume of the airways and the rate of breathing, prolongs the duration of exhalation, reduces the respiratory rate and tidal volume, also causes vasoconstriction at low concentrations and vasodilation at high concentrations. In clinical applications, lidocaine can prevent propofol injection pain, improve postoperative recovery, and play a role in various surgical procedures. Perioperative IVL application is proven to provide more benefits in various surgeries compared to other available anesthetic options. Very few studies have systematically analyzed the occurrence of side effects, and the quality of evidence is low.

Cardiovasculaire, respiratoire, gastro-intestinale en gedragseffecten van intraveneuze lidocaïnetoediening bij gezonde paarden bij bewustzijn en evaluatie van de relatie met serumconcentraties van lidocaïne en mono-ethylglycinexylidide

Deze studie had als doel de relatie te bepalen tussen de serumconcentraties van lidocaïne/monoethylglycinexylidide (MEGX) en hun effect op de verschillende lichamelijke stelsels bij het paard. Vijf gezonde paarden bij bewustzijn kregen een twee uur durende placebo-intraveneuze infusie gevolgd door een twee uur durende lidocaïne-infusie (bolus van 1,3 mg/kg in tien minuten gevolgd door een constante infusie van 0,05 mg/kg/min). De lidocaïne- en MEGX-serumconcentraties werden om de tien à vijftien minuten gemeten. Het evenwichtsverlies, de spiertrillingen, het ademhalings-, spijsverterings- en cardiovasculaire stelsel werden beoordeeld met behulp van verschillende niet-invasieve methoden. Tijdens de toediening van de lidocaïne-infusie was de gemiddelde (± standaarddeviatie) lidocaïne- en MEGXconcentratie respectievelijk 768,88 ± 93,32 ng/ml en 163,08 ± 108,98 ng/ml. De toediening van een lidocaïne- infusie beïnvloedde significant de aanwezigheid van trillen. Ook veroorzaakte ze een statistisch maar niet-klinisch significante afname van de systolische en diastolische bloeddruk, die beide correleerden met de lidocaïne- en MEGX-serumconcentratie. Verder verhoogde ze eveneens de duodenale contractiefrequentie, die correleerde met de serumlidocaïne-concentratie. In de voorliggende studie werden milde hypotensieve en prokinetische kortetermijneffecten van een lidocaïne-infusie waargenomen.

Effect of Myrtus Communis L. Extracts on Attenuation of Liver Normothermic Ischemia-Reperfusion Injury

The Common Myrtle (Myrtus communis L.) is rich in antioxidants, particularly in anthocyanin. It was recognized for its anti-inflammatory and anti-thrombotic effects. The aim of our work is to evaluate the effect of Common Myrtle on a model of hepatic ischemia-reperfusion in Rat. Two morphs were chosen: white fruit Myrtle and black fruit Myrtle. Within each morph, fruit and leaf were separated and obtained extract were used to determine their effects on the hepatic model of ischemia-reperfusion. Our work was conducted in three steps (1) Induction of hepatic ischemia (90 minutes) in Wistar Rat (2) injection of the Myrtle extract during 15 minutes before reperfusion (3) and reperfusion (2 hours). To evaluate the effect of Myrtle on ischemia-reperfusion, we have monitored transaminases levels, Monoethylglycinexylidide (MEGX) concentrations (to assess the liver metabolic capacity) and Malondialdehyde (MDA) concentration. The determination of total phenol extracts of Myrtle showed a significant difference between black fruit Myrtle (11.3 μg/ml), white fruit (27 μg/ml) and black fruit Myrtle leaves (94.3 μg/ml). The latter presented the highest antioxidant activity (86.54%). With the extract from the white fruit of Myrtle, we noted a decrease of AST and ALT, respectively, 1321 U/I and 773 U/I compared with I/R group was 5757 U/I and 5404 U/I and an increase in the MEGX concentrations and decrease in MDA. The testing of extracts of Myrtle in a model of hepatic ischemia showed a difference in the protective power against damage of ischemia-reperfusion, by origin and type of fruit (black or white).

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.

Effect of 4% Topical Lidocaine Applied to the Face on the Serum Levels of Lidocaine and Its Metabolite, Monoethylglycinexylidide

Topical lidocaine is a common form of anesthesia for a wealth of procedures across a large number of disciplines, including laser treatments. Preparations can be purchased over the counter with no prescription necessary. It is considered a safer and more acceptable form of anesthetic than hypodermic injections; however, there have been reports of fatalities following its application. Above certain serum lidocaine concentrations, patients may experience effects of toxicity such as lightheadedness and paraesthesia; these effects can progress to seizures and cardiorespiratory depression, which can ultimately lead to death. The active metabolite of lidocaine, monoethylglycinexylidide (MEGX), can be almost as potent as lidocaine in terms of toxicity. The authors examine the levels of both lidocaine and MEGX in blood serum after application of topical lidocaine. Twenty-five healthy volunteers were assigned to one of four groups (A, B, C, D). Group A had 2.5 g of 4% lidocaine topical anesthetic cream applied to the face for one hour without occlusion, Group B had 5 g applied to the face for one half-hour without occlusion, Group C had 5 g applied to the face for one hour without occlusion, and Group D had 5 g applied to the face for one hour with occlusion. To evaluate serum concentrations, blood was drawn every 30 minutes for four hours. Group D showed the highest serum levels of lidocaine and MEGX, a three-fold increase compared with group C, which received the same dose (5g topical 4% lidocaine) but without occlusion. In group D, peak serum levels occurred at 90 minutes for serum lidocaine, which was also the fastest of the four groups. Serum MEGX levels peaked much later than serum lidocaine levels, at 210 minutes. Individual serum levels did not exceed 0.6 µg/mL. Across the groups, there was significant interindividual variation in both lidocaine and MEGX serum levels (P = .061). Applications of 5 g of 4% lidocaine resulted in higher serum concentration of both lidocaine and MEGX. When comparing group A to group C, doubling the dose of 4% lidocaine from 2.5 g to 5 g resulted in double the serum levels of MEGX and a 50% increase in the serum lidocaine levels (P = .021). When comparing groups C and D, the addition of an occlusive dressing resulted in a tripling of the serum lidocaine levels and a doubling of the serum MEGX levels, both of which were statistically significant (P < .001). When comparing all four groups, there were significant differences between the combined serum concentrations of lidocaine and MEGX (P < .001). Topical lidocaine preparations are increasingly being employed to provide a patient-friendly form of noninvasive analgesia for a multitude of procedures. Some preparations are available over the counter for unsupervised patient application. Our study has demonstrated significant interindividual variability for a given dose, especially when occlusion is applied. There have been fatalities resulting from topical lidocaine application, and our study suggests that this is the result of the unpredictability of lidocaine metabolism between individuals. Therefore, we recommend that caution be exercised with topical lidocaine preparations, in particular when applied in conjunction with occlusive dressings.

Efficacy of Lidocaine for Pain Control in Subcutaneous Infiltration During Liposuction

Liposuction remains the most commonly performed aesthetic surgical procedure in the United States. Preoperative infiltration of the subcutaneous tissues with a wetting solution has become standard. These solutions typically contain some amount of lidocaine for pain control. High doses of lidocaine have been demonstrated to be safe, but large amounts of this cardioactive agent during elective cosmetic procedures may be unnecessary. A study was designed to examine the effects of wetting solutions with lower concentrations of lidocaine on perioperative pain. Seventeen patients were prospectively randomized to subcutaneous infiltration with one of 3 different lidocaine concentrations: 10 mg/kg, 20 mg/kg, or 30 mg/kg. Intra- and postoperative lidocaine and monoethylglycinexylidide (MEGX) plasma concentrations were measured and the total intraoperative inhalation gas requirements and minimum alveolar concentrations were recorded. Postoperative pain medication requirements were recorded and morphine equivalents were calculated. Patient pain level was subjectively assessed by using a visual analog pain scale. There was no difference in the intraoperative lidocaine or MEGX concentrations between any of the 3 groups. There was also no statistical difference between the 3 groups when comparing intraoperative inhalational gas requirement, postoperative morphine equivalence requirements, or subjective pain using the visual analog scale. Decreasing concentrations of lidocaine in infiltrative wetting solutions did not significantly affect intraoperative anesthesia requirements or postoperative pain with liposuction. Lower concentrations of lidocaine can effectively be used, use of any lidocaine may be unnecessary. Future investigations may examine whether total elimination of lidocaine yields similar results in terms of anesthesia requirements and postoperative pain.

Pharmacokinetics of lidocaine following the application of 5% lidocaine patches to cats

Lidocaine patches have been used to provide local analgesia in dogs and cats. We conducted this study to assess the systemic and local absorption of lidocaine from topical patches in cats. Eight 2-year-old cats received either intravenous lidocaine at 2 mg/kg or one 700 mg lidocaine patch placed on the lateral thorax for 72 h, in a cross-over randomized repeated measures design. Plasma was collected at specific times and the skin was biopsied at the time of patch removal for the quantitative analysis of lidocaine and its major metabolite, monoethylglycinexylidide (MEGX), by gas chromatography with mass spectrometry. Percent absorption time plots for systemic lidocaine appearance were constructed using the Loo-Riegelman method. Approximately, constant rate absorption was observed from 12-72 h after patch application at a mean +/- SD rate of 109 +/- 49 microg/kg/h, resulting in steady-state lidocaine plasma concentrations of 0.083 +/- 0.032 microg/mL and MEGX concentrations of 0.012 +/- 0.009 microg/mL. Overall bioavailability of transdermal lidocaine was 6.3 +/- 2.7%, and only 56 +/- 29% of the total lidocaine dose delivered by the patch reached systemic circulation. Skin lidocaine concentrations were much higher than plasma concentrations, at 211 +/- 113 microg/g in the thoracic skin beneath the patch and 2.2 +/- 0.6 microg/g in the contralateral thoracic skin without the patch. As both lidocaine and MEGX were recovered from contralateral skin, it is likely that lidocaine accumulated in the skin from low systemic concentrations of circulating lidocaine over the 72-h period of patch application. Plasma lidocaine concentrations remained well below systemically toxic concentrations, and no obvious clinical side effects were observed in any of the cats. The low systemic absorption rate coupled with high local lidocaine concentrations on the skin support the safe use of lidocaine patches in cats.

Serum concentrations of lidocaine and its metabolites after prolonged infusion in healthy horses

Continuous-rate infusions (CRI) of lidocaine are often used for prolonged duration but, to date, only limited time/concentration relationships administered as a short term (24 h) CRI have been reported. To determine the time/concentration profile of lidocaine and its active metabolites glycinexylidide (GX) and monoethylglycinexylidide (MEGX) during a 96 h lidocaine infusion. Lidocaine was administered to 8 mature healthy horses as a continuous rate infusion (0.05 mg/kg bwt/min) for 96 h. Blood concentrations of lidocaine, GX and MEGX were determined using high performance liquid chromatography during and after discontinuation of the infusion. Serum lidocaine concentrations reached steady state by 3 h and did not accumulate thereafter. Concentrations were above the target therapeutic concentration (980 ng/ml) only at 6 and 48 h, and did not reach the range described as potentially causing toxicity (>1850 ng/ml) at any time. MEGX did not accumulate over time, while the GX accumulated significantly up to 48 h and then remained constant. The serum concentrations of lidocaine, MEGX and GX were below the limit of detection within 24 h of discontinuation of the infusion. None of the horses developed any signs of lidocaine toxicity during the study. The metabolism of lidocaine was not significantly impaired by prolonged infusion and no adverse effects were observed. Prolonged infusions appear to be safe in normal horses but the accumulation of GX, a potentially toxic active metabolite, is cause for concern.

Effect of erythromycin and rifampicin on monoethylglycinexylidide test

Background:The dynamic liver function test based on the hepatic conversion of lidocaine to monoethylglycinexylidide (MEGX) provides a direct measure of the actual functional state of the liver. Cytochrome P450 (CYP) 3A4 has been proposed as the main CYP isoform responsible for MEGX formation. The concomitant use of either CYP3A4 inducer rifampicin or CYP3A4 inhibitor erythromycin may influence the results of MEGX test. Hence, the objective of this study was to evaluate the effect of a CYP3A4 inhibitor erythromycin and inducer rifampicin on the MEGX test.Materials and Methods:The study included 20 healthy male volunteers whose routine laboratory tests were normal. As per study protocol, MEGX test was carried out in all the participants after an overnight fast. All the participants were given 1 mg/kg lidocaine dose intravenously and MEGX concentration at 30 and 60 min after IV dose was measured using HPLC. These MEGX values served as control values. Ten subjects received 600 mg/day erythromycin orally for six days while remaining ten participants received 600 mg/day rifampicin orally for six days. On the sixth day, MEGX test was carried out two hours after the last dose.Result:Rifampicin increased the mean plasma concentration of MEGX30 from 93.94 ± 26.31 to 98.54 ± 24.94 μg/ml (P = 0.085) and MEGX60 from 134.34 ± 35.42 to 136.36 ± 33.14 μg/ml (P = 0.051). Erythromycin lowered the serum concentration of MEGX30 from 101.37 ± 39.39 to 96.67 ± 36.09 μg/ml (P = 0.128) and MEGX60 from 142.52 ± 42.65 to 138.98 ± 40.23 μg/ml (P = 0.159).Conclusion:It can be concluded from this study that the MEGX test is not affected by concomitant administration of CYP3A4 modifiers rifampicin and erythromycin.

Hemodynamic effects of intravenous lidocaine in isoflurane anesthetized cats

Lidocaine dose-dependently decreases the minimum alveolar concentration (MAC) of isoflurane in cats. The purpose of this study was to determine the hemodynamic effects of six lidocaine plasma concentrations in isoflurane anesthetized cats. Six cats were studied. After instrumentation, end-tidal isoflurane concentration was set at 1.25 times the individual minimum alveolar concentration (MAC), which was determined in a previous study. Lidocaine was administered intravenously to target pseudo-steady state plasma concentrations of 0, 3, 5, 7, 9, and 11 μg ml–1, and isoflurane concentration was reduced to an equipotent concentration, determined in a previous study. Cardiovascular variables; blood gases; PCV; total protein and lactate concentrations; and lidocaine and monoethylglycinexylidide concentrations were measured at each lidocaine target concentration, before and during noxious stimulation. Derived variables were calculated. Data were analyzed using a repeated measures anova, followed by a Tukey test for pairwise comparisons where appropriate. One cat was excluded from analysis because the study was aborted at 7 μg ml–1 due to severe cardiorespiratory depression. Heart rate, cardiac index, stroke index, right ventricular stroke work index, total protein concentration, mixed-venous PO2 and hemoglobin oxygen saturation, arterial and mixed-venous bicarbonate concentrations, and oxygen delivery were significantly lower during lidocaine administration than when no lidocaine was administered. Mean arterial pressure, central venous pressure, pulmonary artery pressure, systemic and pulmonary vascular resistance indices, PCV, arterial and mixed-venous hemoglobin concentrations, lactate concentration, arterial oxygen concentration, and oxygen extraction ratio were significantly higher during administration of lidocaine than when no lidocaine was administered. Most changes were significant at lidocaine target plasma concentrations of 7 μg ml–1 and above. Noxious stimulation did not significantly affect most variables. Despite significantly decreasing in inhalant requirements, when combined with isoflurane, lidocaine produces greater cardiovascular depression than an equipotent dose of isoflurane alone. The use of lidocaine to reduce isoflurane requirements is not recommended in cats.

The effect of mild and moderate hepatic impairment on the pharmacokinetics of valdecoxib, a selective COX-2 inhibitor

This study evaluated the effects of varying degrees of hepatic impairment on the pharmacokinetics and safety of valdecoxib following single and multiple dosing. This was an open-label, randomised, parallel group study in 12 subjects with mild hepatic impairment (Child-Pugh Class A) and in 13 with moderate hepatic impairment (Child-Pugh Class B) matched for age, weight, sex, and smoking status; there were two control groups of 12 healthy volunteers, one for each study group. All subjects received a single dose of valdecoxib 20 mg on day 1 and valdecoxib 20 mg twice daily on days 4-7, followed by a single morning dose on day 8. Plasma concentrations of free (unbound) and total valdecoxib and its active hydroxylated metabolite (SC-66905) were measured following single and multiple dosing (day 1 and day 8). Additionally, all subjects received a single intravenous dose of lidocaine 60 mg during the pretreatment period to determine plasma concentrations of monoethylglycinexylidide (MEGX) as a marker of hepatic CYP3A4 activity. The mean apparent oral clearance of free valdecoxib in plasma at steady state decreased by 22-25% in those with mild to moderate impairment (corresponding to a 28-33% increase in the AUC of free valdecoxib and a 19-23% decrease in the AUC of total SC-66905). The mean free fraction of valdecoxib in plasma increased by 9-38%, resulting in a mean decrease in apparent oral clearance of total valdecoxib in plasma of 0-15% (corresponding to a 0-17% increase in the AUC of total valdecoxib). Individual AUCs for free valdecoxib and total SC-66905 did not correlate well with AUCs for MEGX, indicating that decreases in intrinsic clearance of valdecoxib in those with hepatic impairment could not solely be explained by decreased CYP3A4 expression in hepatic impairment. In our small study sample, mild and moderate hepatic impairment appeared to have only a modest effect on valdecoxib and SC-66905 pharmacokinetics. The adjustment of valdecoxib dose or dosing regimen does not appear mandatory in subjects with mild or moderate hepatic impairment, although caution is necessary during treatment of these patients with valdecoxib.

Cytochrome P450 1A2 is a major determinant of lidocaine metabolism in vivo: effects of liver function

This study was designed (1) to evaluate the effect of a cytochrome P450 (CYP) 1A2 inhibitor, fluvoxamine, on the pharmacokinetics of intravenous lidocaine and its 2 pharmacologically active metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), to confirm recent in vitro results indicating that CYP1A2 is the main isoform responsible for lidocaine biotransformation and (2) to assess whether liver function has any influence on the fluvoxamine-lidocaine interaction. The study was carried out in 10 healthy volunteers and 20 patients with cirrhosis, 10 with mild (Child grade A) and 10 with severe (Child grade C) liver dysfunction, according to a randomized, double-blind, 2-phase, crossover design. In one phase all participants received placebo for 6 days; in the other phase they received 50 mg fluvoxamine for 2 days and 100 mg fluvoxamine for the next 4 days. On day 6, a 1-mg/kg lidocaine dose was administered intravenously 2 hours after the last dose of fluvoxamine or placebo. Plasma concentrations of lidocaine, MEGX, GX, and fluvoxamine were measured up to 12 hours after lidocaine injection. The effects of fluvoxamine coadministration were dependent on liver function. Lidocaine clearance was decreased on average by 60% (from 12.1 mL/min.kg to 4.85 mL/min.kg, P <.001) in healthy subjects and by 44% (from 9.83 mL/min.kg to 5.06 mL/min.kg, P <.001) in patients with mild liver dysfunction, with proportional increases in terminal half-lives, whereas virtually no effect was produced in patients with severe liver dysfunction (4.21 mL/min.kg versus 3.65 mL/min.kg, P >.05). Analogous effects were observed on MEGX and GX formation kinetics, which were drastically impaired in healthy subjects and patients with mild liver cirrhosis but virtually unaffected in patients with severe cirrhosis. CYP1A2 is the enzyme principally responsible for the metabolic disposition of lidocaine in subjects with normal liver function. The extent of fluvoxamine-lidocaine interaction decreases as liver function worsens, most likely because of the concomitant decrease in the hepatic level of CYP1A2. These observations indicate that results obtained in healthy subjects cannot be extended a priori to patients with liver dysfunction, but the clinical consequences of inhibition of drug metabolism must also be assessed in such patients.

Free lidocaine concentrations during continuous epidural anesthesia in geriatric patients

Background and Objectives: To evaluate the effects of aging on lidocaine pharmacokinetics, the plasma concentrations of total and free lidocaine and its metabolites were measured during continuous thoracic epidural anesthesia in middle-aged (age 41 ± 9 years, n = 7) and elderly (age 72 ± 2 years, n = 7) male patients. Methods: After establishment of general anesthesia, 7 mL 1.5% lidocaine with epinephrine 1:200,000 was injected into the epidural space and subsequently infused at a rate of 5 mL/h for 5 hours. Plasma concentrations of total and free lidocaine, monoethylglycinexylidide (MEGX), and glycinexylidide (GX) were measured at 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, and 300 minutes after initial lidocaine injection using high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Results: The elderly group showed a stronger upward trend in the corrected free lidocaine concentrations and lower corrected total MEGX concentrations than the middle-aged group. Conclusions: Lidocaine metabolite activity in the elderly male patients was lower than that in the middle-aged male patients. Free lidocaine concentration is prone to increase in elderly patients. Caution must be exercised during continuous thoracic epidural anesthesia combined with general anesthesia in geriatric patients. Reg Anesth Pain Med 2003;28:215-220.

RETRACTED: Influence of prolonged cardiopulmonary bypass times on splanchnic perfusion and markers of splanchnic organ function

Cardiopulmonary bypass (CPB) is known to have considerable negative impact on perfusion and organ function. The effects of the duration of CPB on markers of splanchnic organ function was studied. Consecutive patients undergoing elective aorto-coronary bypass grafting with CPB times (CPBT) of either less than 70 minutes (n = 15) or more than 80 minutes (n = 15) were prospectively studied. Splanchnic perfusion was assessed by measuring arterial and gastric mucosal PCO2 and calculating PCO2gap. Hepatic function was evaluated by monoethylglycinexylidide (MEGX) test and by measuring alpha-glutathione S-transferase (alpha-GST). Concentration of pancreatitis-associated protein was measured to assess pancreatic integrity. Measurements were performed after induction of anesthesia, at the end of surgery, 4 hours after arrival in the intensive care unit, and on postoperative day 1. The mean (+/- standard deviation) CPBT were 54 +/- 12 minutes and 99 +/- 16 minutes, respectively. PCO2gap increased significantly more in the group with CPBT of more than 80 minutes than in that with CPBT of less than 70 minutes, at +15 +/- 4 mm Hg versus +8 +/- 3 mm Hg, respectively, indicating reduction in splanchnic perfusion by longer CPBTs. Postoperative MEGX concentrations were significantly lower and postoperative alpha-GST concentrations were significantly higher in the group with CPBT of more than 80 minutes than in that with CPBT of less than 70 minutes. Plasma levels of pancreatitis-associated protein remained similar in both groups throughout the study period. In our patients with CPBT of more than 80 minutes, splanchnic perfusion and hepatocelluar integrity were moderately affected, whereas pancreatic function remained almost unchanged. Studies including a larger patient population are necessary to assess whether protective approaches would be helpful in patients undergoing complex cardiac surgery with very long CPBT.

Effect of dopamine-induced changes in splanchnic blood flow on MEGX production from lidocaine in septic and cardiac surgery patients.

The production of monoethylglycine xylidide (MEGX) from lidocaine is thought to be dependent on hepatic blood flow. We assessed the relationship between hepatosplanchnic blood flow, lidocaine uptake, and the production of MEGX from lidocaine in seven patients after cardiac surgery and in nine septic patients. Systemic (pulmonary artery catheter) and splanchnic (hepatic vein catheter and dye dilution) hemodynamics and arterial and hepatic venous lidocaine and MEGX concentrations were measured after a lidocaine bolus injection (1 mg/kg) before and 90 min after increasing cardiac output by at least 25% with dopamine. Dopamine infusion [in cardiac surgery patients 4.2 (1.4-8.5) microg x kg(-1) x min(-1) (median, range) and in septic patients 4.0 (2.1-9.0) microg x kg(-1) x min(-1)] increased splanchnic blood flow in cardiac surgery patients from 0.65 (0.12) L x min(-1) x m(-2) to 0.84 (0.14) L x min(-1) x m(-2) mean (standard deviation) P = 0.018) and in septic patients from 0.91 (0.32) L x min(-1) x m(-2) to 1.12 (0.40) L x min(-1) x m(-2) (P = 0.038). Splanchnic MEGX production for the 30 min after lidocaine injection was higher in cardiac surgery patients than in septic patients both at baseline [4130 (1100) microg x m(-2) vs. 930 (420) microg x m(-2) (P < 0.005)] and afterdopamine infusion [4480 (1000) microg x m(-2) vs. 1090 (620) microg x m(-2) (P = 0.005)]. We found no correlation between changes in MEGX production and changes in splanchnic blood flow. Patients with sepsis have severe impairment of cytochrome P450-dependent liver function, which is not influenced by acute changes in hepatosplanchnic blood flow. MEGX production cannot be used as an estimate of changes in splanchnic blood flow.

Risk of hepatic failure after transcatheter arterial chemoembolization for hepatocellular carcinoma: predictive value of the monoethylglycinexylidide test.

Transcatheter arterial chemoembolization (TACE) is the major treatment modality for patients with unresectable hepatocellular carcinoma (HCC). Hepatic failure after TACE is relatively common in patients with preexisting liver dysfunction. The purpose of this study was to evaluate whether the monoethylglycinexylidide test and other parameters might predict hepatic failure after TACE in HCC patients. One hundred forty-two HCC patients undergoing TACE were enrolled into this study. Before TACE, their venous blood was collected 15 min after a bolus injection of lidocaine (1 mg/kg body weight). A fluorescence polarization immunoassay was used to measure monoethylglycinexylidide oncentrations in their sera. Univariate and multivariate analyses were performed on the monoethylglycinexylidide test and other parameters between patients with and without hepatic failure after TACE. Nineteen patients (13.4%) suffered hepatic failure after TACE. Univariate analysis revealed that the monoethylglycinexylidide concentration (17.7+/-5.8 vs 43.9+/-13.2 ng/ml), Child-Pugh score (6.9+/-0.6 vs 6.0+/-0.7), indocyanine green retention ratio at 15 min (32.4+/-6.5% vs 15.7+/-5.8%), prolonged PT, and serum total bilirubin and albumin showed significant differences between patients with and without hepatic failure after TACE. After a multiple logistic regression, only the monoethylglycinexylidide test was an independent predictor of hepatic failure (OR = 1.68, 95% CI = 1.07-2.65, p = 0.026). Among the 19 hepatic failure patients, three (15.8%) died of hepatic failure associated with TACE within 1 month after this procedure. As a predictor of hepatic failure after TACE, the monoethylglycinexylidide test is better than conventional liver function tests and clinical parameters. The monoethylglycinexylidide test may be used to select patients with relatively good liver reserves for safe TACE treatment.

Risk of hepatic failure after transcatheter arterial chemoembolization for hepatocellular carcinoma: predictive value of the monoethylglycinexylidide test

OBJECTIVES: Transcatheter arterial chemoembolization (TACE) is the major treatment modality for patients with unresectable hepatocellular carcinoma (HCC). Hepatic failure after TACE is relatively common in patients with preexisting liver dysfunction. The purpose of this study was to evaluate whether the monoethylglycinexylidide test and other parameters might predict hepatic failure after TACE in HCC patients. METHODS: One hundred forty-two HCC patients undergoing TACE were enrolled into this study. Before TACE, their venous blood was collected 15 min after a bolus injection of lidocaine (1 mg/kg body weight). A fluorescence polarization immunoassay was used to measure monoethylglycinexylidide concentrations in their sera. Univariate and multivariate analyses were performed on the monoethylglycinexylidide test and other parameters between patients with and without hepatic failure after TACE. RESULTS: Nineteen patients (13.4%) suffered hepatic failure after TACE. Univariate analysis revealed that the monoethylglycinexylidide concentration (17.7 ± 5.8 vs 43.9 ± 13.2 ng/ml), Child-Pugh score (6.9 ± 0.6 vs 6.0 ± 0.7), indocyanine green retention ratio at 15 min (32.4 ± 6.5% vs 15.7 ± 5.8%), prolonged PT, and serum total bilirubin and albumin showed significant differences between patients with and without hepatic failure after TACE. After a multiple logistic regression, only the monoethylglycinexylidide test was an independent predictor of hepatic failure (OR = 1.68, 95% CI = 1.07–2.65, p = 0.026). Among the 19 hepatic failure patients, three (15.8%) died of hepatic failure associated with TACE within 1 month after this procedure. CONCLUSIONS: As a predictor of hepatic failure after TACE, the monoethylglycinexylidide test is better than conventional liver function tests and clinical parameters. The monoethylglycinexylidide test may be used to select patients with relatively good liver reserves for safe TACE treatment.

Does age affect liver function and the hepatic acute phase response after major abdominal surgery?

The liver plays a key role in the inflammatory response during major surgery or infection. The influence of age on liver function and hepatic acute phase protein (APP) synthesis should be serially studied in elderly patients undergoing major abdominal surgery. Prospective and descriptive study over 3 days. Clinical investigation in the operating room and surgical intensive care unit (ICU) of a tertiary care hospital. 42 consecutive patients were grouped according to age: less than 60 years ("adult") or over 65 years ("elderly") and prospectively studied. All patients received standardized general anesthesia and were treated afterwards according to the standard protocols of our ICU. Intensivists caring for the patients were not involved in the study and were blinded to data analysis. Concentrations of interleukin (IL)-6, serum amyloid A (SAA), C-reactive protein (CRP), alpha1-antitrypsin (alpha1-AT), and haptoglobin were measured to assess the APP response. Liver function was evaluated by the monoethylglycinexylidide (MEGX) test and by measuring alpha-glutathione S-transferase (alpha-GST). All measurements were performed at induction of anesthesia (T0), at the end of surgery (T1), and 2 h (T2), 24 h (T3), and 48 h (T4) postoperatively. There was no difference in the incidence of postoperative septic complications between the two groups. Baseline values of IL-6 and the four APPs were normal in all patients and did not differ between the groups. IL-6 levels increased significantly in all patients at T1 and T2, with a significantly higher increase in the older patients (elderly: from 7.4+/-3.4 pg/ml to 220.6+/-49.5 pg/ml; adult: from 6.2+/-2.5 pg/ml to 189.9+/-36.8 pg/ml). A return to baseline values was seen at T3 in both groups. Concentrations of all APPs, except for haptoglobin, started to increase at T3. Peak concentrations were significantly lower in the elderly patients (elderly: SAA 358+/-133 microg/l, CRP 5.1+/-2.3 mg/dl, alpha1-AT 160+/-96 mg/dl; adult: SAA 444+/-100 microg/l, CRP 8.5+/-3.2 mg/dl, alpha1-AT 223+/-85 mg/dl). Baseline alpha-GST and MEGX concentrations were normal in all patients. Alpha-GST concentrations increased in both groups at T1 and T2, with a significantly higher increase in the older patients (elderly: 3.7+/-1.4 microg/l to 10.2+/-2.9 microg/l; adult 4.5+/-2.1 microg/l to 8.5+/-1.7 microg/l). A return to baseline values was seen at T3 in both groups. MEGX concentrations were significantly lower and abnormal (<50 ng/ml) in the older patients at T3 and T4. Our observations suggest that the postoperative hepatic acute phase response is reduced in elderly patients undergoing major abdominal surgery. The decreased release of liver-synthesized APPs was associated with an impaired hepatocyte function and a disturbance of hepatocellular integrity. Further work needs to be done to determine whether these findings might have an impact on the incidence of postoperative septic complications or prognostic significance for survival in aged patients.

Assessment of hepatic function in cystic fibrosis by lidocaine metabolism.

To determine hepatic drug metabolism in patients with cystic fibrosis, as measured by monoethylglycinexylidide formation after lidocaine injection and indocyanine green (ICG) clearance. The following study is a case-control study, which included 19 patients with cystic fibrosis and 13 control subjects. Serum monoethylglycinexylidide concentration was measured after intravenous injection of 1 mg/kg (maximum, 50 mg) lidocaine. Indocyanine green (0.5 mg/kg) was injected concomitantly, and absorbance (805 nm) of serum was measured over time to determine its volume of distribution, serum half-life, and hepatic blood flow. Monoethylglycinexylidide formation was decreased in patients with cystic fibrosis compared with controls (39.4+/-16.9 microg/L versus 70.3+/-45.7 microg/L, mean +/- SD, respectively, P < 0.02). Indocyanine green half-life (4.6+/-2.7 min versus 3.0+/-1.0 min), volume of distribution (8.6+/-5.5 L versus 8.3+/-3.4 L), and hepatic blood flow (10.9+/-5.9 ml x kg(-1) x min(-1) versus 7.4+/-2.0 ml x kg(-1) x min(-1)) were similar in both groups. Monoethylglycinexylidide formation after lidocaine injection is impaired in patients with cystic fibrosis. This impairment may have clinical implications when using hepatically metabolized medications in patients with cystic fibrosis.

Assessment of Hepatic Function in Cystic Fibrosis by Lidocaine Metabolism

ABSTRACTBackgroundTo determine hepatic drug metabolism in patients with cystic fibrosis, as measured by monoethylglycinexylidide formation after lidocaine injection and indocyanine green (ICG) clearance.MethodsThe following study is a case–control study, which included 19 patients with cystic fibrosis and 13 control subjects. Serum monoethylglycinexylidide concentration was measured after intravenous injection of 1 mg/kg (maximum, 50 mg) lidocaine. Indocyanine green (0.5 mg/kg) was injected concomitantly, and absorbance (805 nm) of serum was measured over time to determine its volume of distribution, serum half‐life, and hepatic blood flow.ResultsMonoethylglycinexylidide formation was decreased in patients with cystic fibrosis compared with controls (39.4 ± 16.9 μg/L versus 70.3 ± 45.7 μg/L, mean ± SD , respectively, P &lt; 0.02). Indocyanine green half‐life (4.6 ± 2.7 min versus 3.0 ± 1.0 min), volume of distribution (8.6 ± 5.5 L versus 8.3 ± 3.4 L), and hepatic blood flow (10.9 ± 5.9 ml · kg−1 · min−1 versus 7.4 ± 2.0 ml · kg−1 · min−1) were similar in both groups.ConclusionMonoethylglycinexylidide formation after lidocaine injection is impaired in patients with cystic fibrosis. This impairment may have clinical implications when using hepatically metabolized medications in patients with cystic fibrosis.