Lidocaine anestehsia and liposuction
Upcoming SlideShare
Loading in...5
×
 

Lidocaine anestehsia and liposuction

on

  • 500 views

lidocaine,liposuction;at the end annotated bibliography

lidocaine,liposuction;at the end annotated bibliography

Statistics

Views

Total Views
500
Views on SlideShare
500
Embed Views
0

Actions

Likes
1
Downloads
1
Comments
0

0 Embeds 0

No embeds

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

Lidocaine anestehsia and liposuction Lidocaine anestehsia and liposuction Presentation Transcript

  • La lidocaina come anestetico locale nella chirurgia del contorno corporeo Il punto di vista dell’anestesista Claudio Melloni libero professionista Consulente di anestesia: Villa Torri,Bologna;Villa Chiara,Bologna,Poliambulatorio Gynepro,Bologna
  • Dosaggi di lidocaina nella tecnica tumescente Klein JA.Tumescent technique for regional anesthesia permits lidocaine doses of 35 mg/kg for liposuction. J. Dermatol. Surg. Oncol. 16: 248, 1990. Lillis PJ. Liposuction surgery under local anesthesia: Limited blood loss and minimal lidocaine absorption. J. Dermatol. Surg. Oncol. 14: 1145, 1988. cita 88 mg/kg come sicuro Coleman WP. Tumescent anesthesia with a lidocaine dose of 55 mg/kg is safe for liposuction. Dermatol. Surg. 22: 919, 1996
  • Lillis, P. J. Liposuction surgery under local anesthesia: Limited blood loss and minimal lidocaine absorption. J. Dermatol. Surg. Oncol. 14: 1145, 1988 measured serum lidocaine concentrations in 20 patients after suction lipectomy with the tumescent technique. Total lidocaine dose ranged between 2000 mg and 5600 mg. Blood samples drawn 15, 30, and 60 minutes after infiltration revealed lidocaine concentrations <1.7 µg/ml in all cases. No signs of toxicity were reported. View slide
  • Come mai tali dosaggi di lidocaina sono stati tollerati? NON si sa Ipotesi l’assorbimento dal tessuto sotto cutaneo e adiposo è molto lento vascolarizzazione scarsa adrenalina lo riduce ulteriormente,impedendo così il raggiungimento di livelli plasmatici tossici la successiva suzione asporta una discreta quota del farmaco infiltrato contribuendo alla sicurezza.I dati disponibili indicano una quota di rimossione della lido infiltrata variabile dal 10% al 31% » Kenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit F,Oellerich M, Luby M, Rohrich R,Brown SA.D.Pharmacokinetics and Safety of Lidocaine and Monoethylglycinexylidide in Liposuction: A Microdialysis Study.J Plast Surg . 114,2004, 516-524. » Hagerty T,Klein, P. Fat partitioning of lidocaine in tumescent liposuction. Ann. Plast. Surg. 42: 372,1999. View slide
  • Dosaggio massimo di lidocaina Il dosaggio massimo raccomandato in letteratura è di 7 mg/kg U.S. Food and Drug Administration and manufacturers. » Lidocaine hydrochloride package insert. Astra Pharmaceutical Products, 1995. Per infiltrazione:4,5 mg/kg and 6 mg/kg +adr(Goodman Gillman,the Pharmacological basis of Therapeutics) 200 mg o 500 mg se associata a adrenalina:Guida all’Uso dei farmaci 300 mg o 500 mg + adr:Cousins, Neural Blockade.,Lippincott Ed.
  • Pressione di infiltrazione s.c. la pressione alla quale si effettua la iniezione (Alta Max press tissutale durante iniezione 339 +/- 63 mmHg vs bassa pressione 27 +/- 9 mmHg) non ha effetti sulla curva di assorbimento……… » Rubin JP, Bierman C, Rosow CE, Arthur GR, Chang Y, Courtiss EH, May JW Jr.The tumescent technique: the effect of high tissue pressure and dilute epinephrine on absorption of lidocainePlast Reconstr Surg. 1999 Mar;103(3):990-6;. » Termpo di infiltrazione :16 min con alta pressione vs 20 con bassa
  • Velocità di infiltrazione 27 mg/min o 200 mg/min di lidocaina diluita e con epinefrina non determinano differenti livelli plasmatici di lidocaina( nelle prime 2 h) Butterwick KJ, Goldman MP, Sriprachya-Anunt S. Lidocaine levels during the first two hours of infiltration of dilute anesthetic solution for tumescent liposuction: rapid versus slow delivery .Dermatol Surg. 1999 Sep;25(9):681-5. Aghi spinali e cannule sottili multiorifizi
  • Sicurezza Potete sempre garantire che durante l’infiltrazione non avvenga una accidentale iniezione ev.?
  • Livelli plasmatici in arteria dopo iniezione ev rapida o lenta di lidocaina Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Concentrazioni plasmatiche di lidocaina dopo iniezione in 4 sedi differenti Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Concentrazioni plasmatiche di lidocaina e prilocaina dopo 400 mg inietttati per via peridurale Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Livelli plasmatici di lidocaina in un paziente dopo sgonfiaggio della cuffia ( anestesia endovenosa con 3 mg/kg di lidocaina 0.5% e 45 min di applicazione del tourniquet).Tucker GT,Boas RA. Pharmacokinetic aspects of intravenous regional anesthetics.Anesthesiology 1971;34:578. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Accumulo locale e sistemico di lidocaina dopo bolo peridurale per anestesia e infusione continua per analgesia postop.da Holmdahl MH et al.Clinical aspects of continuous epidural blockade for postoperative pain relief.Ups.J.Med.Sci.77,47:1972. Infusione cont. bolo Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Lidocaine plasma concentration over time for each experimental group (±SEM). In the two groups with epinephrine, the time to maximal lidocaine concentration (Tmax) was 11 hours after injection, whereas Tmax was reached in 3.4 hours in the groups without epinephrine (p < 0.001). Rubin JP , Bierman C, Rosow CE, Arthur GR, Chang Y, Courtiss EH, May JW Jr.The tumescent technique: the effect of high tissue pressure and dilute epinephrine on absorption of lidocainePlast Reconstr Surg. 1999 Mar;103(3):990-6 Lido 0.1 con epinefr 1:1.000.000 s.c. faccia lat della coscia;no lipectomia Senza adr. Con adr. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Rubin JP, Xie Z, Davidson C, Rosow CE , Chang Y, May JW Jr.Rapid absorption of tumescent lidocaine above the clavicles: a prospective clinical study. Plast Reconstr Surg. 2005;115:1744-51.
  • Concentrazioni plasmatiche di lidocaina dopo tumescenza a livello del collo o della coscia.. Time to reach maximal lidocaine concentration was 5.8 hours after neck injection and 12.0 hours after thigh injection (p 0.00Rubin JP, Xie Z, Davidson C, Rosow CE, Chang Y, May JW Jr.Rapid absorption of tumescent lidocaine above the clavicles: a prospective clinical study. Plast Reconstr Surg. 2005;115:1744-51 neck thigh Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) .
  • Curve di assorbimento della tumescenza con lidocaina con simulazione in caso di infiltrazione simultaneaRubin JP, Xie Z, Davidson C, Rosow CE, Chang Y, May JW Jr.Rapid absorption of tumescent lidocaine above the clavicles: a prospective clinical study. Plast Reconstr Surg. 2005;115:1744-51. additiva collo coscia Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Ma non si tratta solo di lidocaina............ La MEGX è un metabolita attivo
  • Plasma Concentrations of Monoethylglycinexylidide during and after Breast Augmentation Rygnestad, T, Samdal F.Plast reconstruct Surg 2000 106:728-31. The plasma concentration of monoethylglycinexylidide (MEGX; microgams per milliliter) versus the time after the end of the injection.. A total dose of 825 to 1280 mg of 0.2% and 0.5% lidocaine with epinephrine corresponding to 16.3 to 21.8 mg/kg (mean 18.2 mg/kg) Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • The plasma concentration of MEGX +lidocaine (micrograms per milliliter) versus the time after the end of the injection Plasma Concentrations of Monoethylglycinexylidide during and after Breast Augmentation Rygnestad, T, Samdal F.Plast reconstruct Surg 2000 106:728-31 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Tempo di raggiungimento dei livelli massimi di lido e megx dopo infiltrazione per tumescenza :Kenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit F,Oellerich M, Luby M, Rohrich R,Brown SA.D.Pharmacokinetics and Safety of Lidocaine and Monoethylglycinexylidide in Liposuction: A Microdialysis Study.J Plast Surg . 114,2004, 516-524 dose media di lido 22 mg/kg
  • Livelli plasmatci massimi di lidocaina e megx dopo infiltrazione per tumescenza:dose media di lido 22 mg/kgKenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit F,Oellerich M, Luby M, Rohrich R,Brown SA.D.Pharmacokinetics and Safety of Lidocaine and Monoethylglycinexylidide in Liposuction: A Microdialysis Study.J Plast Surg . 114,2004, 516-524
  • Kenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit F,Oellerich M, Luby M, Rohrich R,Brown SA.D.Pharmacokinetics and Safety of Lidocaine and Monoethylglycinexylidide in Liposuction: A Microdialysis Study.J Plast Surg . 114,2004, 516-524 absorbed lidocaine was estimated to be 1197.7 mg (range, 911.0 to 1596.0 mg).: 64 percent (range, 45 to 93 percent) of the infiltrated dose was ultimately absorbed. Lipoaspirate analysis showed that 178.1 mg of lidocaine (range, 154 to 204 mg), 9.8 percent (range, 9.1 to 10.8 percent) of the infiltrated dose was removed during the procedure.
  • Mean plasma concentration of lidocaine (lido), monoethylglycinexylidide (MEGX), and lidocaine plus monoethylglycinexylidide vs time (mean, SEM). Kenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit F,Oellerich M, Luby M, Rohrich R,Brown SA.D.Pharmacokinetics and Safety of Lidocaine and Monoethylglycinexylidide in Liposuction: A Microdialysis Study.J Plast Surg . 114,2004, 516-524 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Dove va a finire la lidocaina che non è nel plasma? 10% (range, 9.1 to 10.8)rimossa durante intervento » Kenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit F,Oellerich M, Luby M, Rohrich R,Brown SA.D.Pharmacokinetics and Safety of Lidocaine and Monoethylglycinexylidide in Liposuction: A Microdialysis Study.J Plast Surg . 114,2004, 516-524: 31% aspirato nel grasso rimosso o rimasto: rapporto grasso / liquido 1.3- 2.95 Hagerty, T., and Klein, P. Fat partitioning of lidocaine in tumescent liposuction. Ann. Plast. Surg. 42: 372,1999. Hardy, S. P., Ortiz-Colberg, R., and Poquette, M. A. Re: Fat partitioning of lidocaine in tumescent liposuction. Ann. Plast. Surg. 43: 574, 1999.
  • Importanza del legame alle proteine plasmatiche Lidocaina + lipofilica del MEGX e + legata alla 1acid glycoprotein,:60 to 70 %v s 15% for MEGX La parte attiva di un farmaco è quella libera Sebbene i livelli di MEGX siano sostanzialmente + bassi di quelli della lido,la concentrazione della MEGX libera è relativamente + alta e potrebbe determinare un ruolo maggiore nella tox.......
  • Anaesthesist. 2007 Aug;56(8):785-9. Links [Tumescent anaesthesia for dermatological surgery. Plasma concentrations of lidocaine and prilocaine] [Article in German] Rudlof K, Rüffert H, Wehner M, Wetzig T, Eichhorn K, Olthoff D. Klinik und Poliklinik für Anästhesiologie und Intensivtherapie, Universitätsklinikum Leipzig AöR, Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Nordström H, Stånge K. Plasma lidocaine levels and risks after liposuction with tumescent anaesthesia. Acta Anaesthesiol Scand. 2005 Nov;49(10):1487-90. 35 mg per kg bodyweight of lidocaine for abdominal liposuction. 3 lt of buffered solution of 0.08% lidocaine with epinephrine was infiltrated subcutaneously over the abdomen in 8 female patients at a rate of 116 ml/min monitored intravenous (i.v.) light sedation. Plasma levels of lidocaine and signs of subjective and objective symptoms were recorded every 3 h for 20 h after liposuction. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • RESULTS of Plasma lidocaine levels and risks after liposuction with tumescent anaesthesia. Acta Anaesthesiol Scand. 2005 Nov;49(10):1487-90. : Peak plasma levels (2.3 +/- 0.63 microg/ml) of lidocaine occurred after 5-17 h. No correlation was found between peak levels and dose per kg bodyweight or total amount of lidocaine infiltrated. One patient experienced tinnitus after 14 h when a plasma level of 3.3 microg/ml was recorded. CONCLUSION: Doses of lidocaine up to 35 mg/kg were sufficient for abdominal liposuction using the tumescent technique and gave no fluid overload or toxic symptoms in eight patients, but with this dose there is still a risk of subjective symptoms in association with the peak level of lidocaine that may appear after discharge. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Conclusioni dalla letteratura citata Ci sono significative differenze interindividuali nei livelli plasmatici di lidocaina Il picco del livello plasmatico di lidocaina si raggiunge assai tardivamente Anche la MEGX picca tardivamente I 2 farmaci sommano la tox................... Ci sono altri problemi che complicano il quadro.........
  • Pazienti a rischio di tox della lidocaina Riduzione di flusso epatico :insuff epatica ..... CHF: MEGX / lido » Halkin, H., Meffin, P., Melmon, K. L., et al. Influence of congestive heart failure on blood vessels of lidocaine and its active monodeethylated metabolite. Clin. Pharmacol. Ther. 17: 669, 1975.
  • Fin qui Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Lo stress altera i livelli plasmatici di lidocaina Eur J Drug Metab Pharmacokinet. 2002 Oct-Dec;27(4):229-32. Links Stress-induced lidocaine modification in serum and tissues. Saranteas T, Tesseromatis C, Potamianou A, Mourouzis C, Varonos D. influence of acute (trauma) and chronic (cold swimming and adjuvant rheumatoid arthritis) stress on lidocaine concentrations in plasma. Forty male Wistar rats were used. The animals were divided into four groups. Group A served as control. Group B underwent mandible osteotomy. Group C was submitted to swimming stress in cold water 4 degrees C for ten minutes daily for 15 minutes, while group D underwent experimental arthritis with Freud's adjuvant. All groups received lidocaine i.m (2.5 mg/kg). Blood samples were collected and FFA (free fatty acid), unbound-lidocaine, albumin and a1-acid glycoprotein concentrations were estimated. Furthermore, the Servizio Anestesia e Rianimazione adrenals,diheart and liverOspedale di isolated. The adrenals' relative weight were Faenza(RA)
  • Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Ma La lidocaina tissutale residua contribuisce alla analgesia postoperatoria? Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Livelli tissutali di lidocaina Kenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit F,Oellerich M, Luby M, Rohrich R,Brown SA.D.Pharmacokinetics and Safety of Lidocaine and Monoethylglycinexylidide in Liposuction: A Microdialysis Study.J Plast Surg . 114,2004, 516-524 Regione mammaria Peak local tissue concentrations of lidocaine were in the 0- to 4-hour collection, immediately Area mammaria postoperatively in both left and right femurs [18.5 (7.89) microg/ml mean (SEM) and 27.7 (13.18)microg/ml, respectively]. Lidocaine levels decreased exponentially from the initial peak, 4 to 8 hours postoperatively at the infiltrated sites in both left and right femurs [4.4 (1.83) and 4.3 (4.83) , as the drug was absorbed and redistributed to tissue distal from the infiltrated sites. In contrast,peak levels in the control probe occurred in the 8- to 12-hour collection [3.94 (2.4)mirog/ml].
  • Livelli tissutali di lidocaina e analgesia Kenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit F,Oellerich M, Luby M, Rohrich R,Brown SA.D.Pharmacokinetics and Safety of Lidocaine andMonoethylglycinexylidide in Liposuction: A Microdialysis Study.J Plast Surg . 114,2004, 516-524 4-5 microg/lt di tessuto Kopacz and BernardsKopacz, D. J., and Bernards, C. M. Effect of clonidine on lidocaine clearance in vivo: A microdialysis study in humans. Anesthesiology 95: 1371, 2001. Bernards, C. M., and Kopacz, D. J. Effect of epinephrine on lidocaine clearance in vivo: A microdialysis study in humans. Anesthesiology 91: 962, 1999. 25 microg/lt per il pizzicotto 42microg/lt per il tatto 20 microg/lt per il freddo. .
  • Livelli tessutali di lidocaina Kenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit F,Oellerich M, Luby M, Rohrich R,Brown SA.D.Pharmacokinetics and Safety of Lidocaine andMonoethylglycinexylidide in Liposuction: A Microdialysis Study.J Plast Surg . 114,2004, 516-524 I livelli plasmatici di lidocaina vanno a picco da 8 a 16 h dopo l’intervento e persistono per 36 h Ma……….i livelli tissutali di lido sono subterapeutici già dopo 4 o 8 h
  • Tsai PS, Buerkle ,H, Huang LT, Lee TC,. Yang C, Lee JHLidocaine Concentrations in Plasma and Cerebrospinal FluidAfter Systemic Bolus Administration in Humans .Anesth Analg 1998;87:6014 Preclinical studies suggest that systemic lidocaine acts at the level of the spinal dorsal horn to inhibit hyperalgesia resulting from nerve injury, yet no clinical data are available to support this view. Therefore, we sought to characterize the time course of lidocaine in the plasma and cerebrospinal fluid (CSF) after an IV bolus injection of lidocaine 2 mg/kg in patients scheduled for surgery involving spinal anesthesia. Sixty-five patients were randomly allocated to one of five study groups (n = 13 per group) receiving IV lidocaine before CSF/ plasma sampling at 5, 10, 15, 30, or 60 min. Gas chromatographic analysis of these samples revealed a fast but transient peak (5-15 min) in lidocaine plasma levels (1.7 ? 0.16 pg/mL), which declined rapidly thereafter. Only small concentrations of IV lidocaine were found in the CSF (6%-8% of plasma concentration), but this fraction remained stable from 15 min until termination of the experiment. No statistical correlation was observed between plasma and CSF lidocaine levels. These data suggest that because of the prolonged availability of lidocaine at the spinal dorsal horn level, systemic administration of lidocaine suppresses central sensitization within the spinal cord after nerve injury in humans. Implications: Cerebrospinal fluid concentrations of lidocaine after its systemic bolus delivery in humans indicate that the spinal cord may be the major site of antinociceptive action by this route of drug Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) administration.
  • Perché la lidocaina è efficace nel dolore (acuto ma + spesso cronico) iperalgesico neuropatico da lesione nervosa? Il declino plasmatico dopo un bolo ev della lidocaina è rapido Invece Il livello csf è basso ma persistente nel tempo La prolungata esposizione del corno post del midollo spinale alla lido porta alla soppressione della sensibilizzazione centrale Azione antinocicettiva Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Time course of plasma lidocaine concentrations (A) and cerebrospinal fluid (CSF) concentrations (B) after the IV administration of lidocaine 2 mg/kg. The x axis shows the time points at which samples were taken after lidocaine administration (5-60 min after IV lidocaine). The y axis presents the lidocaine concentrations as assessed by gas chromatography for plasma (A) and cerebrospinal fluid (B). All data are presented as measurements of individual samples (open symbols) and their correlating median values (filled symbols). Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Quindi l’effetto antinocicettivo della lidocaina Se effetto analgesico da lidocaina c’è ,esso dipende dalla concentrazione spinale attiva sul midollo, corno posteriore ,non a livello tessutale……… meno si sa degli effetti a livello centrale……… Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Livelli di lido in cardiologia……….. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • general anesthesia can alter the pharmacokinetics of disparate drugs through direct effects on drug elimination mechanisms and/or indirect effects on hemodynamics. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Livelli plasmatici di lidocaina e anestesia generale Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • E’ noto che la AG modifica la distribuzione del flusso ematico ,la emodinamica generale e distrettuale Mather LE, Runciman WB, Ilsley AH. Anesthesia-induced changes in regional blood flow. Implications for drug disposition.Reg Anesth 1982;7(suppl):S23–S33 Runciman WB, Myburgh J, Upton RN, Mather LE. Effects of anaesthesia on drug disposition. In: Feldman SA, Scurr CF, Paton W, eds. Mechanisms of action of drugs in anaesthetic practice. 2nd ed. London: Edward Arnold, 1993:83–128 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Mather LE, Runciman WB, Ilsley AH. Anesthesiainduced changes in regional blood flow. Implications for drug disposition.Reg Anesth 1982;7(suppl):S23– S33 Runciman WB, Myburgh J, Upton RN, Mather LE. Effects of anaesthesia on drug disposition. In: Feldman SA, Scurr CF, Paton W, eds. Mechanisms of action of drugs in anaesthetic practice. 2nd ed. London: Edward Arnold, 1993:83–128 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Copeland , SE , Ladd LA, Gu, XO, Mather LE.The Effects of General Anesthesia on Whole Body and Regional Pharmacokinetics of Local Anesthetics at Toxic Doses.Anesth Analg 2008;106:1440 –9 Study of influence of GA on the pharmacokinetics of six local anesthetics administered IV at approximately the highest recommended doses. Chronically instrumented ewes (approximately 45–50 kg, n 18) infused over 3 min with (base doses as HCl salts) bupivacaine (100 mg), levobupivacaine (125 mg), ropivacaine (150 mg), lidocaine (350 mg), mepivacaine (350 mg), or prilocaine (350 mg) on separate occasions when conscious and halothane anesthetized. Serial arterial, heart, and brain venous blood drug concentrations were measured by achiral/chiral high-performance liquid chromatography, as relevant. Whole body pharmacokinetics were assessed by noncompartmental analysis; heart and brain pharmacokinetics were assessed by mass balance. Drug blood binding, in the absence and presence of halothane, was assessed by equilibrium dialysis in vitro. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Copeland , SE , Ladd LA, Gu, XO, Mather LE.The Effects of General Anesthesia on Whole Body and Regional Pharmacokinetics of Local Anesthetics at Toxic Doses.Anesth Analg 2008;106:1440 –9 RESULTS: Blood local anesthetic concentrations were doubled with anesthesia because of decreased whole body distribution and clearance (respectively, to 33% and 52% of values when conscious). Heart and brain net drug uptake were greater under anesthesia, reflecting slower efflux from both regions. Clearances of R-bupivacaine S-bupivacaine and R-prilocaine S-prilocaine, but, mepivacaine clearance was not enantioselective. Halothane did not influence blood binding of the local anesthetics.CONCLUSIONS: General anesthesia significantly changed whole body and regional pharmacokinetics of each local anesthetic as well as the systemic effects. General anesthesia is thus an important but frequently overlooked factor in studies of local anesthetic toxicity.
  • Copeland , SE , Ladd LA, Gu, XO, Mather LE.The Effects of General Anesthesia on Whole Body and Regional Pharmacokinetics of Local Anesthetics at Toxic Doses.Anesth Analg 2008;106:1440 –9 Doses (as base) of : 100 mg bupivacaine, 125 mg levobupivacaine, 150 mg ropivacaine, 350 mg lidocaine, 350 mg mepivacaine, 350 mg prilocaine as HCl salts) were diluted to 30 mL with 0.9% saline, and infused into a central venous catheter over 3 min
  • Copeland , SE , Ladd LA, Gu, XO, Mather LE.The Effects of General Anesthesia on Whole Body and Regional Pharmacokinetics of Local Anesthetics at Toxic Doses.Anesth Analg 2008;106:1440 –9 produced CNS excitotoxicity accompanied by acute CVS stimulation in all conscious sheep; no overt effects were observed in anesthetized sheep, but general anesthesia caused CVS depression, which was exacerbated by all local anesthetics. Fatalities occurred with bupivacaine (n 3), levobupivacaine (n 2),ropivacaine (n 2), and prilocaine (n 1), all in conscious sheep.
  • Arterial blood levels of LA always greater under anesthesia Copeland , SE , Ladd LA, Gu, XO, Mather LE.The Effects of General Anesthesia on Whole Body and Regional Pharmacokinetics of Local Anesthetics at Toxic Doses.Anesth Analg 2008;106:1440 –9 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Pharmacokinetics of LA in adult sheep ,consious or under GA Copeland , SE , Ladd LA, Gu, XO, Mather LE.The Effects of General Anesthesia on Whole Body and Regional Pharmacokinetics of Local Anesthetics at Toxic Doses.Anesth Analg 2008;106:1440 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) –
  • Pharmacokinetics of LA in adult sheep ,consious or under GA Copeland , SE , Ladd LA, Gu, XO, Mather LE.The Effects of General Anesthesia on Whole Body and Regional Pharmacokinetics of Local Anesthetics at Toxic Doses.Anesth Analg 2008;106:1440 Cmax Tmax CL Vss T1/2 MRT Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Copeland , SE , Ladd LA, Gu, XO, Mather LE.The Effects of General Anesthesia on Whole Body and Regional Pharmacokinetics of Local Anesthetics at Toxic Doses.Anesth Analg 2008;106:1440 – Anesthesia approximately doubled the blood concentrations of all local anesthetics compared with the respective values while conscious (Figs. 1 and 2). Anesthesia affected the pharmacokinetic variables of all six drugs by decreasing their distribution and clearance, but with relatively minor differences between drugs (Tables 1 and 2). Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Copeland , SE , Ladd LA, Gu, XO, Mather LE.The Effects of General Anesthesia on Whole Body and Regional Pharmacokinetics of Local Anesthetics at Toxic Doses.Anesth Analg 2008;106:1440 – In this study, we found that general anesthesia doubled the drug blood concentrations of all six local anesthetics, when compared with the conscious state, by increasing Cmax/unit dose (an indirect measure of distributional clearance), decreasing Vss (a direct measure of peripheral uptake), and decreasing CL (a direct measure of hepatic elimination). Anesthesia also decreased MRT and T[1/2] (by decreasing Vss more than CL), and Tmax was a little earlier in conscious animals (an indirect consequence of the CNS excitotoxicity). At the same time, the toxic response was altered: despite undergoing much greater CVS depression, all anesthetized animals survived doses that were lethal in someconscious sheep.5 Thus, drug blood concentration– response relationships were distorted by inclusion of general anesthesia in the model. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Buona biblio sugli AL e loro tox Copeland , SE , Ladd LA, Gu, XO, Mather LE.The Effects of General Anesthesia on Whole Body and Regional Pharmacokinetics of Local Anesthetics at Toxic Doses.Anesth Analg 2008;106:1440 – Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Copeland SE, Ladd LA, Gu X-Q, Mather LE. Effects of general anesthesia on the central nervous system and cardiovascular system toxicity of local anesthetics. Anesth Analg 2008;106:1429–39 *Behavioral, cardiovascular, and pharmacokinetic responses previously instrumented ewes (approximately 45–50 kg, n 18), on separate occasions when conscious and anesthetized8halothane /O2) bupivacaine (100 mg),levobupivacaine (125 mg), ropivacaine (150 mg), lidocaine (350 mg), mepivacaine (350 mg), prilocaine (350 mg), and saline (control) infused IV over 3 min. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Results of toxic doses of LA in sheep,conscious and anesthetized LA caused convulsions in conscious sheep, but no overt CNS effects in anesthetized sheep. Negative inotropy and slight bradycardia without changes in arterial blood pressure occurred initially in conscious sheep,followed by positive inotropy, tachycardia, and hypertension at the abrupt onset of CNS excitotoxicity, along with widening of QRS complexes. Fatal cardiac arrhythmias occurred in, respectively, 3 of 11, 2 of 12, and 2 of 13 conscious sheep infused with bupivacaine, levobupivacaine, and ropivacaine; in 1 of 9 with prilocaine, electromechanical dissociation (followed by polymorphic ventricular tachycardia) caused death. In anesthetized sheep, cardiovascular depression, preexisting from the Servizio di Anestesia e Rianimazione Ospedale di exacerbated by all local anesthetics, general anesthesia, was Faenza(RA)
  • CONCLUSIONS: General anesthesia produced physiological perturbations, exacerbated local anesthetic-induced cardiovascular depression, and changed the pharmacokineticsof toxic doses of local anesthetics. However, cardiovascular fatalities from local anesthetics occurred only in conscious animals. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • The dominant effect of all local anesthetics was overt CNS excitotoxicity in all conscious sheep. There were eight fatalities, all in conscious animals and this was a significant finding (Table 1) (conscious versus anesthetized: proportion test Zcorr 2.54, P 0.011; Fisher’s exact test P 0.0061). Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Left ventricular dp/dt in consciuos or anesthetized sheep before and after a toxic dose of LA Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Lidocaine toxic dose in a conscious sheep,non lethal Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • recovery without sequelae; Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • associated with polymorphic ventricular tachycardia Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • cardiovascular collapse is not shown occurred later at 1180 s. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • When conscious, initial myocardial depression (decreasing LV-dP/dtmax) was quickly reversed with the onset of CNS excitotoxicity. The longer acting local anesthetics usually produced a transient, irregular bradycardia, premature contractions, then episodes of tachycardia, including Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • The maximal effects generally occurred at or near the time of completion of local anesthetic infusion but, in conscious sheep, were influenced by the time at which CNS excitotoxicity began. The preexisting myocardial depression from halothane anesthesia Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • SED10 and SED30 were correlated, and only SED10 is shown for brevity. The effects shown in Figures 5 and 6, except for Emax for QRS width, differed between conscious and anesthetized conditions (all P0.001); in anesthetized sheep, increases in QRS width lasted Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Contr Bupi Levo Ropi Lido Mepi Prilo Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Contr Bupi Levo Ropi Lido Mepi Pril
  • Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Contr Bupi Levo Ropi Lido Mepi Prilo Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • recovery began 30-min after drug infusion. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • In conscious sheep, initial CVS depression was followed by CVS stimulation and QRS widening, with similar maximal effects for all local anesthetics, apparently reflecting the causative CNS excitotoxicity. The ameliorating effect of anesthesia on CNS toxicity was Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • However, other experimental models have shown that although general anesthesia suppresses convulsions and arrhythmias, it does not necessarily promote survival, apparently depending upon the drug and the model.24,25 This demonstration of biphasic CVS Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • The first sign of serious local anesthetic-induced toxicity in conscious subjects is often generalized CNS excitotoxicity, with or without CVS signs, but prodromal signs may be apparent5–7,35 depending mainly on diligent observation and the rate of local anesthetic Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • might not be detected by usual clinical monitoring; a rapidly acting anesthetic for treatment of CNS toxicity would exacerbate the CVS depression. The CNS response to local anesthetics has been implicated in their CVS toxicity,13– 15,36,37 but its role Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Halothane causes profound myocardial depression, and may predispose the heart to arrhythmias19–21,38; however, isoflurane and sevoflurane can suppress multiform QRS waves resulting from bupivacaine.24 Thus, it could reasonably be argued that the Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • In this study, the blood gas changes in conscious sheep were consistent with a clear airway and good oxygenation; CABF was also maintained, and thus it is unlikely that cardiac ischemia or hypoxemia contributed significantly to the cardiac dysrhythmias Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • In summary, we found that local anesthetic toxicity in halothane-anesthetized sheep was very different from that in conscious sheep (Table 2). In the latter, CNS excitotoxicity stimulated the CVS with malignant, sometimes fatal, cardiac arrhythmias. In the former, Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • drug/control infusion until 30 min after infusion Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Address correspondence to Emeritus Professor Laurence E. Mather, Department of Anaesthesia and Pain Management, University of Sydney at Royal North Shore Hospital, Sydney NSW 2065, Australia. Address e-mail to lmather@med.usyd.edu.au. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Letter to Mather Dear prof Mather,I have read with the greatest interest your two companion articles on toxicity of local anesthetics*(Copeland , SE , Ladd LA, Gu, XO, Mather LE.The Effects of General Anesthesia on Whole Body and Regional Pharmacokinetics of Local Anesthetics at Toxic Doses.Anesth Analg Servizio 2008;106:1440 di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Rosenberg PH, Veering BT, Urmey WF. Maximum recommended doses of local anesthetics: a multifactorial concept. Reg Anesth Pain Med 2004;29:564–75 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Hemodynamic Physiology and Thermoregulation in Liposuction Plast. Reconstr. Surg. 114: 503, 2004
  • Hemodynamic Physiology and Thermoregulation in Liposuction Plast. Reconstr. Surg. 114: 503, 2004 operatively and associated with diminished sodium, albumin, urea, and total protein concentrations. 44,45 The ultimate effect of hemodilution and lower blood viscosity is increased flow. Decreased peripheral vascular resistance and vasodilatation (increased arterial radius) were demonstrated in our patients. This relationship is described by Poiseuille’s equation.46 Ultimately a greater volume of blood is ejected from the left ventricle per beat.
  • Propofol Sedation Produces Dose-Dependent Suppression of Lidocaine-Induced Seizures in Rats Victor C. Lee, MD, Jeffrey C. Moscicki, MS, and Cosmo A. DiFazio, MD, PhD The association of propofol with excitatory motor activity, such as myoclonic jerking and opisthotonus, in humansand in animals suggests that it may aggravate clinical seizure activity in some circumstances, although evidence suggests that under other circumstances,propofol inhibits seizure activity. In the currentstudy, we assessed the effect of sedating doses of propofol on lidocaineinduced seizure activity in spontaneously breathing rats receiving no other anesthetics.Adult Sprague-awley male rats, 300-400 g, were divided into a control group and three experimental groups representing three graded levels of propofol sedation.The control rats then received a lidocaine infusion at the rate of 150 mg * kg-’ . h-i, resulting in a Servizio di Anestesia e Rianimazione Ospedale in systemic lidocaine concentrations. slow, progressive increase di Faenza(RA)
  • Effetto protettivo della sedazione propofolica Aumenta la dose ev di lidocaina necessaria per ottenere le convulsioni Parallelamente aumenta il livello plasmatico al quale avvengono le convulsioni: da 16 a 20,25 microgr/ml Al dosaggio più elevato evita la comparsa delle convulsioni Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Continuous propofol sedation in spontaneously breathing rats receiving no other anesthetics exerts a protective effect against lidocaine-induced seizures . Continuous propofol sedation increased the seizure dose of lidocaine from 37.7 ? 3.5 mg/kg (mean 5 SEM) to 52.5 2 2.6 mg/kg (Dose 1, P < 0.05) and 67.9 2 8.6 mg/kg (Dose 2, P < 0.05), and completely abolished lidocaine seizures at Dose 3. The lethal dose of lidocaine, 89.4 10.5 mg/kgcontrol versus 108.7 ? 10.3 mg/kg (Dose l), 98.3 5 10.1 mg/kg (Dose 2), and 93.5 ? 10.4 mg/kg (Dose 3) did not differ among groups. The lidocaine levels at seizure threshold were Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • FINE Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Concentrazioni plasmatiche osservate e predette dopo somministrazione peridurale ripetute di lidocaina da Tucker GT et al.Observed and predicted accumulation of local anesthetic agents dsuring continuous extradural analgesia.Br.J.Anaesth. 1977;49:237. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • The tumescent technique: the effect of high tissue pressure and dilute epinephrine on absorption of lidocaine. Rubin JP, Bierman C, Rosow CE, Arthur GR, Chang Y, Courtiss EH, May JW Jr. The purpose of this work was to determine the effect of tissue pressure during tumescent injection and presence of low concentration epinephrine on the absorption of lidocaine from subcutaneous tissues in human volunteers. Twenty healthy female human volunteers were randomized into four study groups. After body fat measurements, all subjects received an injection of 7 mg/kg of lidocaine into the subcutaneous tissues of both lateral thighs. The injected solution consisted of 0.1% lidocaine and 12.5 meq/liter sodium bicarbonate in normal saline with or without 1:1,000,000 epinephrine. Tissue pressure was recorded during injection using a specially designed double-barreled needle. The time required for injection was also recorded. Subjects in group 1 received lidocaine with epinephrine injected by a high-pressure technique. Group 2 subjects received lidocaine with epinephrine injected by a low-pressure technique. Group 3 subjects received lidocaine without epinephrine injected under high pressure. Group 4 subjects received lidocaine without epinephrine injected under low pressure. Following injection, sequential blood samples were drawn over a 14-hour period, and plasma lidocaine concentrations were determined by gas chromatography. No suction lipectomy was performed. Maximum tissue pressure during injection was 339 ± 63 mmHg and 27 ± 9 mmHg using highand low-pressure techniques, respectively. Addition of 1:1,000,000 epinephrine, regardless of the pressure of injected fluid, significantly delayed the time to peak plasma concentration by over 7 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) hours. There was no significant difference in the peak plasma concentration of lidocaine among
  • Rygnestad, T, Samdal F.Plasma Concentrations of Monoethylglycinexylidide during and after Breast Augmentation.Plast reconstruct Surg 2000;106:728-31 MEGX is pharmacologically active,and its potential for adverse effects has been confirmed in man.13 In the present study, we found that the maximal plasma concentration of MEGX occurred as late as 8 to 12 hours after the end of the injection. In three patients, the concentration was still increasing after 12 hours. The maximal concentration of MEGX+lidocaine occurred 5 to 12 hours after the end of the injection. The magnitude of the MEGX peak suggests that MEGX will contribute to the risk of developing toxicity when high doses of lidocaine are used. Lidocaine is present in plasma both in a protein bound pharmacologic inactive fraction and as a free active fraction. MEGX is probably not protein bound 10 and, thus, only exists in the free and pharmacologically active form. This finding further underlines the pharmacologic significance of MEGX with regard to potential lidocaine toxicity. It should also be noted that after an intravenous bolus injection, the clearance of lidocaine is reduced in the presence of MEGX.13 In previous studies, we have found a significant variation in peak plasma concentrations of lidocaine in patients undergoing liposuction14 as well as in patients undergoing breast surgery.4 Moreover, we have reported that it is difficult to assess the risk of lidocaine toxicity without taking into consideration di Anestesia e Rianimazione Ospedale di Faenza(RA) and the free fraction of the drug.4 In the Servizio the binding to a1-acid glycoprotein (AAG)
  • Rygnestad, T, Samdal F.Plasma Concentrations of Monoethylglycinexylidide during and after Breast Augmentation.Plast reconstruct Surg 2000;106:728-31 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Kenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit F,Oellerich M, Luby M, Rohrich R,Brown SA.D.Pharmacokinetics and Safety of Lidocaine and Monoethylglycinexylidide in Liposuction: A Microdialysis Study.J Plast Surg . 114,2004, 516-524 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Kenkel JM,Lipschitz , A H,Shepherd G,Armstrong VW,Streit F,Oellerich M, Luby M, Rohrich R,Brown SA.D.Pharmacokinetics and Safety of Lidocaine and Monoethylglycinexylidide in Liposuction: A Microdialysis Study.J Plast Surg . 114,2004, 516-524 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • More information would be desirable on the factors controlling the resorption of lidocaineduring liposuction therapy to improve durationof effect. Perry et al.43 studied postoperativepain at 5, 30, 60, and 120 minutes and on the first postoperative day after liposuction and found that there was no statistically significant difference between paired, mirrored sides of 10 subjects when lidocaine was used on only one side. The study concluded that lidocaine is not necessary in liposuction. Further research into diminishing the dose of lidocaine in wetting solution is warranted, as the safety profile of liposuction may be significantly improved by eliminating lidocaine toxicity as a potential complication. Lidocaine’s impact on diminishing intraoperative general anesthesia deserves further exploration.
  • Rygnestad T, Brevik B, Samdal F. Plasma Concentrations of Lidocaine and [alpha]1-Acid Glycoprotein during and after Breast Augmentation.Plast Reconstruct Surg., 1999;109:12671272 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • The mean lidocaine dose was 18.2 mg/kg (range 16.3 to 21.9 mg/kg). The mean injection time was 23.3 minutes (range, 16 to 35 minutes). Rygnestad T, Brevik B, Samdal F. Plasma Concentrations of Lidocaine and [alpha]1-Acid Glycoprotein during and after Breast Augmentation.Plast Reconstruct Surg., 1999;109:12671272 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Rygnestad T, Brevik B, Samdal F. Plasma Concentrations of Lidocaine and [alpha]1-Acid Glycoprotein during and after Breast Augmentation.Plast Reconstruct Surg., 1999;109:12671272 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Rygnestad T, Brevik B, Samdal F. Plasma Concentrations of Lidocaine and [alpha]1-Acid Glycoprotein during and after Breast Augmentation.Plast Reconstruct Surg., 1999;109:12671272 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • 0 pioid-insensitive neuropathic pain due to nerve injury is one of the most difficult problems in pain management. Therapeutic approaches for these painful sensations, which can be evoked by thermal or mechanical stimuli, include the use of sodium channel blockers such as carbamazepine, tocainide, phenytoin, mexiletine, or lidocaine (1,2). Lidocaine and mexiletine alleviate consistent neuropathic pain states (3-5). Local anesthetics act in both the peripheral and the central nervous systems (6-9). At the peripheral level, local anesthetics inhibit neuronal transduction, decrease the release of inflammatory mediators, inhibit migration of leukocytes, and suppress albumin extravasation (10). At the central site,local anesthetics block neuronal activity at the spinal Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Effetti periferici degli anestetici locali Inibizione della trasduzione neuronale Riduzione dei mediatori nfiammatori Inibizione della migrazione leucocitaria Soppressione dello stravaso albuminico Inibizione della generazione di impulsi a livello del nervo leso,neuromi inclusi Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Effetti centrali degli anestetici locali Riduzione della scarica a partenza dal ganglio della radice dorsale Blocco della attività neurale spinale a livello del corno post. Modulazione della liberazione di neurotrasmettitori Soppressione della attività delle fibre C Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • dorsal horn level, thus modulating the release of excitatory neurotransmitters (6,ll). However, the underlying mechanisms for the analgesic action of systemically administered lidocaine remain controversial. Some preclinical studies provide evidence for a predominant inhibition of impulse generation arising from injured nerve segments or any associated dorsal root ganglion (12,13). Devor et al. (14) found a selective blocking effect for systemically delivered lidocaine by inhibiting ectopic discharges from experimental neuromas without affecting axonal conduction. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • However, several investigators propose a predominant central site of action for the use of systemic lidocaine or other sodium channel blockers (3,6,15). Sotgiu et al. (16) found that systemically administered lidocaine preferentially acts on the hyperactive, wide dynamic-range neurons found in the dorsal horn, resulting in analgesia. This type of sensitized neuron is often found in hyperalgesic pain states. Further important evidence regarding a central site of action was demonstrated by the spinal suppression of C-fiberevoked activity seen with low concentrations after systemic lidocaine (17). Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • Hyperalgesic pain states occur after surgery, trauma,and metabolic disorders, and they are also related to sympathetically maintained pain syndromes (3). As a result of continuous C-fiber stimulation, hyperalgesia represents a state of facilitated sensory processing at the level of the spinal dorsal horn (3,12). As a clinical symptom of nerve injury, hyperalgesic pain often leads to protective immobilization, which may result in malformation or loss of function in the affected body region. Preclinical and clinical studies have shown that sodium channel blockers such as lido- Caine, given systemically or spinally, effectively inhibit this pain (18-20). This analgesic effect can be achieved with small doses of lidocaine, which do not alter acute nociceptive pain thresholds or axonal conduction. This was reported by Wallace et al. (21), who revealed no prominent Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) effects by systemic lidocaine infusions on acute heat, cold, or
  • Their findings are in accordance with those ofBach et al. (22), who showed that IV lidocaine decreases neuropathic pain without affecting the neurosensory system. The administration of a bolus dose of 2 mg/kg IV lidocaine produced plasma concentrations of lidocaine similar to those for which Wallace et al. (17) demonstrated a decrease in pain scores and a concomitant reduction in the size of the receptive field to which the pain was referred. The onset of the inhibition of spinal dorsal horn neuron activity after IV lidocaine occurs within 5-7 min, as shown in a preclinical model. The antihyperalgesic action of systemic lidocaine is mainly attributed to the spinal cord. Lido- Caine has a plasma half-life of approximately 90 min after bolus injection, an octanol to water distribution coefficient of 110 at 36”C, and pH 7.4; it rapidly accesses the central nervous system after systemic delivery (l&23). At the spinal cord, systemically applied lidocaine blocks the release of substance I’ (24), inhibits the discharge of wide dynamic neurons (25), and suppresses the discharge induced by the release of the excitatory amino acid glutamate (7). Previous studies of IV bolus delivery of lidocaine recorded inconsistent plasma levels (26,27 Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
  • ). This finding is supported by our observation of a very fast decay in plasma lidocaine concentrations and an interindividual difference for the plasma peak obtained after IV lidocaine injection. As demonstrated in our present study, there was no Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)