Skip to main content
SpringerLink
Log in

Clinical Pharmacokinetics of Epidural and Spinal Anaesthesia

  • Review Article
  • Drug Disposition
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

Epidural and spinal anaesthesia results from the interaction of local anaesthetics with nerve structures, primarily those located within the subarachnoid space. Local anaesthetics can reach the sites of action along various distribution pathways. Uptake into extraneural tissues (in particular epidural fat) and systemic absorption compete with neural tissue distribution and thereby affect the clinical potency and duration of action. Consequently, epidural doses must be much higher than spinal doses.

The systemic absorption of lignocaine (lidocaine), bupivacaine and etidocaine following lumbar epidural administration has been shown to be biphasic, with a rapid initial absorption phase followed by a much slower absorption phase. Initial absorption rates of lignocaine and bupivacaine following subarachnoid injection are much slower, but the late absorption rates are similar to those after epidural administration.

The tissue distribution characteristics of various amide-type agents are similar, because more extensive plasma binding offsets the greater tissue affinity of the more lipophilic compounds bupivacaine and etidocaine. The amide-type agents are predominantly eliminated by hepatic metabolism, except prilocaine, which is also metabolised elsewhere in the body. Ester-type agents are rapidly hydrolysed in blood and liver and are eliminated much faster than amide-type agents.

The blood concentrations attained depend primarily upon the dose administered. The addition of adrenaline (epinephrine) reduces the peak plasma drug concentrations; similarly, the age of the patient, disease states and drug interactions may alter the pharmacokinetics to various extents.

Because of the low dose requirements, systemic toxicity is not a problem during spinal anaesthesia. During epidural anaesthesia, however, the safety margin is relatively small, and systemic toxicity is very likely to occur after inadvertent intravascular injection of an epidural dose.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abboud TK, David S, Nagappala S, Costandi J, Yanagi T, et al. Maternal, fetal and neonatal effects of lidocaine with and without epinephrine for epidural anesthesia in obstetrics. Anesthesia and Analgesia 63: 973–979, 1984

    PubMed  CAS  Google Scholar 

  • Abboud TK, DerSarkissian L, Terrasi J, Murakawa K, Zhu J, et al. Comparative maternal, fetal and neonatal effects of chloroprocaine with and without epinephrine for epidural anesthesia in obstetrics. Anesthesia and Analgesia 66: 71–75, 1987

    Article  PubMed  CAS  Google Scholar 

  • Abboud TK, Sheikh-ol-Eslam A, Yanagi T, Murakawa M, Costandi J, et al. Safety and efficacy of epinephrine added to bupivacaine for lumbar epidural anesthesia in obstetrics. Anesthesia and Analgesia 63: 585–591, 1985

    Google Scholar 

  • Abdel-Salam AR, Vonwiller JB, Scott DB. Evaluation of etidocaine in extradural block. British Journal of Anaesthesia 47: 1081–1086, 1975

    Article  PubMed  CAS  Google Scholar 

  • Åberg G. Toxicological and local anaesthetic effects of optically active isomers of 2 local anaesthetic compounds. Acta Pharmacologica et Toxicologica 31: 273–286, 1972

    Article  PubMed  Google Scholar 

  • Åkerman B, Astrom A, Ross S, Telc A. Studies on the absorption, distribution and metabolism of labelled prilocaine and lidocaine in some animal species. Acta Pharmacologica et Toxicologica 24: 389–403, 1966

    Article  PubMed  Google Scholar 

  • Appleyard TN, Witt A, Atkinson RE, Nicholas ADG. Bupivacaine carbonate and bupivacaine hydrochloride: a comparison of blood concentrations during epidural blockade for vaginal surgery. British Journal of Anaesthesia 46: 530–533, 1974

    Article  PubMed  CAS  Google Scholar 

  • Aps C, Reynolds F. The effect of concentration on vasoactivity of bupivacaine and lignocaine. British Journal of Anaesthesia 48: 1171–1174, 1976

    Article  PubMed  CAS  Google Scholar 

  • Aps C, Reynolds F. An intradermal study of the local anaesthetic and vascular effects of the isomers of bupivacaine. British Journal of Clinical Pharmacology 6: 63–68, 1978

    Article  PubMed  CAS  Google Scholar 

  • Armstrong IR, Littlewood DG, Chambers WA. Spinal anesthesia with tetracaine — effect of added vasoconstrictors. Anesthesia and Analgesia 62: 793–795, 1983

    Article  PubMed  CAS  Google Scholar 

  • Arthur GR, Scott DHT, Boyes RN, Scott DB. Pharmacokinetic and clinical pharmacological studies with mepivacaine and prilocaine. British Journal of Anaesthesia 51: 481–485, 1979

    Article  PubMed  CAS  Google Scholar 

  • Arthur GR, Wildsmith JAW, Tucker GT. Pharmacology of local anaesthetic drugs. In Wildsmith & Armitage (Eds) Principles and practice of regional anaesthesia, pp. 22–36, Churchill Livingstone, Edinburgh, London, Melbourne and New York, 1987

    Google Scholar 

  • Axelsson KH, Sundberg AEA, Edström HH, Widman GB, Sjöstrand UH. Venous blood concentrations after subarachnoid administration of bupivacaine. Anesthesia and Analgesia 65: 753–759, 1986

    Article  PubMed  CAS  Google Scholar 

  • Axelsson K, Widman B. Blood concentration of lidocaine after spinal anaesthesia using lidocaine and lidocaine with adrenaline. Acta Anaesthesiologica Scandinavica 25: 240–245, 1981

    Article  PubMed  CAS  Google Scholar 

  • Axelsson K, Widman GB, Sundberg AEA, Halgren S. A double-blind study of motor block in the lower limbs: studies with spinal anaesthesia with hyperbaric and glucose free 0.5% bupivacaine. British Journal of Anaesthesia 57: 960–970, 1985

    Article  PubMed  CAS  Google Scholar 

  • Bax NDS, Tucker GT, Lennard MS, Woods HF. The impairment of lignocaine clearance by propranolol — major contribution from enzyme inhibition. British Journal of Clinical Pharmacology 19: 597–603, 1985

    Article  PubMed  CAS  Google Scholar 

  • Bengtsson M, Edström HH, Löfström JB. Spinal analgesia with bupivacaine, mepivacaine and tetracaine. Acta Anaesthesiologica Scandinavica 27: 278–283, 1983

    Article  PubMed  CAS  Google Scholar 

  • Biscoping J. Einfluss der Glucosekonzentration von Bupivacainlösungen auf die Lokalanaestheticaverteilung im Liquor bei Spinalanaesthesie. Regional Anaesthesie 9: 9–14, 1986

    PubMed  CAS  Google Scholar 

  • Blair MR. Cardiovascular pharmacology of local anaesthetics. British Journal of Anaesthesia 47 (Suppl.): 247–252, 1975

    PubMed  Google Scholar 

  • Bowdle TA, Freund PR, Slattery JT. Age-dependent lidocaine pharmacokinetics during lumbar peridural anesthesia with lidocaine hydrocarbonate and lidocaine hydrochloride. Regional Anesthesia 11: 123–127, 1986

    Google Scholar 

  • Bowdle TA, Freund PR, Slattery JT. Propranolol reduces bupivacaine clearance. Anesthesiology 66: 36–38, 1987

    Article  PubMed  CAS  Google Scholar 

  • Braid DP, Scott DB. The systemic absorption of local analgesic drugs. British Journal of Anaesthesia 37: 394–404, 1965

    Article  PubMed  CAS  Google Scholar 

  • Braid DP, Scott DB. Effect of adrenaline on the systemic absorption of local anaesthetic drugs. Acta Anaesthesiologica Scandinavica 23 (Suppl.): 334–346, 1966

    Article  PubMed  CAS  Google Scholar 

  • Bridenbaugh PO, Tucker GT, Moore DC, Bridenbaugh LD, Thompson GE. Etidocaine: clinical evaluation for intercostal nerve block and lumbar epidural block. Anesthesia and Analgesia 52: 407–412, 1973

    PubMed  CAS  Google Scholar 

  • Bridenbaugh PO, Tucker GT, Moore DC, Bridenbaugh LD, Thompson GE, et al. Role of epinephrine in regional block anesthesia with etidocaine: a double blind study. Anesthesia and Analgesia 53: 430–435, 1974

    Article  PubMed  CAS  Google Scholar 

  • Brinkløv MM. Clinical effects of carticaine, a new local anesthetic. A survey and a double-blind investigation comparing carticaine with lidocaine in epidural analgesia. Acta Anaesthesiologica Scandinavica 21: 5–16, 1977

    Article  PubMed  Google Scholar 

  • Bromage PR. Spread of analgesic solutions in the epidural space and their site of action: a statistical study. British Journal of Anaesthesia 34: 161–177, 1962

    Article  PubMed  CAS  Google Scholar 

  • Bromage PR. Ageing and epidural dose requirements. Segmental spread and predictability of epidural analgesia in youth and extreme age. British Journal of Anaesthesia 41: 1016–1021, 1969

    Article  PubMed  CAS  Google Scholar 

  • Bromage PR. Lower limb reflex changes in segmental epidural analgesia. British Journal of Anaesthesia 46: 504–508, 1974

    Article  PubMed  CAS  Google Scholar 

  • Bromage PR. Mechanism of action of extradural analgesia. British Journal of Anaesthesia 47: 199–211, 1975

    PubMed  Google Scholar 

  • Bromage PR. Epidural analgesia, pp. 8–67, 85-91, 119-159, W.B. Saunders Company, Philadelphia, London, Toronto, 1978

    Google Scholar 

  • Bromage PR, Burfoot MF, Crowell DF, Pettigrew RT. Quality of epidural blockade I. Influence of physical factors. British Journal of Anaesthesia 36: 342–352, 1964

    Article  PubMed  CAS  Google Scholar 

  • Bromage PR, Burfoot MF, Crowell DE, Truant AP. Quality of epidural blockade III: carbonated local anaesthetic solutions. British Journal of Anaesthesia 39: 197–209, 1967

    Article  PubMed  CAS  Google Scholar 

  • Bromage PR, Joyal AC, Binney JC. Local anaesthetic drugs: penetration from the spinal extradural space into the neuraxis. Science 140: 392–394, 1963

    Article  PubMed  CAS  Google Scholar 

  • Brown DT, Morison DH, Covino BG, Scott DB. Comparison of carbonated bupivacaine and bupivacaine hydrochloride for extradural anaesthesia. British Journal of Anaesthesia 52: 419–422, 1980a

    Article  PubMed  CAS  Google Scholar 

  • Brown DT, Wildsmith JAW, Covino BG, Scott DB. Effect of baricity on spinal anaesthesia with amethocaine. British Journal of Anaesthesia 52: 589–596, 1980b

    Article  PubMed  CAS  Google Scholar 

  • Buckley FP, Littlewood DG, Covino BG, Scott DB. Effects of adrenaline and the concentration of solution on extradural block with etidocaine. British Journal of Anaesthesia 50: 171–175, 1978

    Article  PubMed  CAS  Google Scholar 

  • Burm AGL. Pharmacokinetics and clinical effects of lidocaine and bupivacaine following epidural and subarachnoid administration in man, Ph.D. Thesis, pp. 99–177, University of Leiden, Leiden, 1985

    Google Scholar 

  • Burm AGL, De Boer AG, Van Kleef JW, Vermeulen NPE, De Leede LGJ, et al. Pharmacokinetics of lidocaine and bupivacaine and stable isotope labelled analogues: a study in healthy volunteers. Biopharmaceutics and Drug Disposition 9: 85–95, 1988a

    Article  CAS  Google Scholar 

  • Burm AGL, Van Kleef JW, Gladines MPRR, Olthof G, Spierdijk J. Epidural anesthesia with lidocaine and bupivacaine: effects of epinephrine on the plasma concentration profiles. Anesthesia and Analgesia 65: 1281–1284, 1986

    Article  PubMed  CAS  Google Scholar 

  • Burm AGL, Van Kleef JW, Gladines MPRR, Spierdijk J, Breimer DD. Plasma concentrations of lidocaine and bupivacaine after subarachnoid administration. Anesthesiology 59: 191–195, 1983

    PubMed  CAS  Google Scholar 

  • Burm AGL, Van Kleef JW, Gladines MPRR, Van Duinen M, Spierdijk J. Spinal anaesthesia with hyperbaric lidocaine and bupivacaine: effects of epinephrine on the plasma concentration profiles. Anesthesia and Analgesia 66: 1104–1108, 1987a

    Article  PubMed  CAS  Google Scholar 

  • Burm AGL, Van Kleef JW, Vermeulen NPE, Olthof G, Breimer DD, et al. Pharmacokinetics of lidocaine and bupivacaine following subarachnoid administration in surgical patients: simultaneous investigation of absorption and disposition kinetics using stable isotopes. Anesthesiology 69: 584–592, 1988b

    Article  PubMed  CAS  Google Scholar 

  • Burm AGL, Vermeulen NPE, Van Kleef JW, De Boer AG, Spierdijk J, et al. Pharmacokinetics of lidocaine and bupivacaine in surgical patients following epidural administration: simultaneous investigation of absorption and disposition kinetics using stable isotopes. Clinical Pharmacokinetics 13: 191–203, 1987b

    Article  PubMed  CAS  Google Scholar 

  • Burn JM, Guyer PB, Langdon L. The spread of solution injected into the epidural space. A study using epidurograms in patients with the lumbosciatic syndrome. British Journal of Anaesthesia 45: 338–344, 1973

    Article  PubMed  CAS  Google Scholar 

  • Cameron AE, Arnold RW, Ghoris MW, Jamieson V. Spinal analgesia using bupivacaine 0.5% plain. Anaesthesia 36: 318–320, 1981

    Article  PubMed  CAS  Google Scholar 

  • Chambers WA, Littlewood DG, Logan MR, Scott DB. Effect of added epinephrine on spinal anesthesia with lidocaine. Anesthesia and Analgesia 60: 417–420, 1981

    Article  PubMed  CAS  Google Scholar 

  • Chambers WA, Littlewood DG, Scott DB. Spinal anesthesia with hyperbaric bupvacaine: effect of added vasoconstrictors. Anesthesia and Analgesia 61: 49–52, 1982

    PubMed  CAS  Google Scholar 

  • Cohen EN. Distribution of local anesthetic agents in the neuraxis of the dog. Anesthesiology 29: 1002–1005, 1968

    Article  PubMed  CAS  Google Scholar 

  • Cole CO, McMorland GH, Axelson JE, Jenkins LC. Epidural blockade for Caesarean section comparing lidocaine hydrocarbonate and lidocaine hydrochloride. Anesthesiology 62: 348–350, 1985

    Article  PubMed  CAS  Google Scholar 

  • Collins JG, Kitahata LM, Homma E, Suzukawa M. Spinal cord effects of epinephrine. Anesthesia and Analgesia 60: 913–914, 1981

    Article  PubMed  CAS  Google Scholar 

  • Collins JG, Matsumoto M, Kitahata LM. Suppression by spinally administered epinephrine of noxiously evoked dorsal horn neuron activity in cats: evidence for spinal epinephrine analgesia. Anesthesia and Analgesia 62: 253–254, 1983

    Google Scholar 

  • Concepcion M, Maddi R, Francis D, Rocco A, Murray E, et al. Vasoconstrictors in spinal anesthesia with tetracaine — a comparison of epinephrine and phenylephrine. Anesthesia and Analgesia 63: 134–138, 1984

    PubMed  CAS  Google Scholar 

  • Concilus RR, Denson DD, Knarr D, Gregg RV, Raj PP. Bupivacaine clearance in continuous epidural infu,sions for postoperative pain relief. Regional Anesthesia 13: 69, 1988

    Google Scholar 

  • Cousins MJ, Bromage PR. A comparison of the hydrochloride and carbonated salts of lignocaine for caudal analgesia in outpatients. British Journal of Anaesthesia 43: 1149–1155, 1971

    Article  PubMed  CAS  Google Scholar 

  • Cousins MJ, Bromage PR. Epidural neural blockade. In Cousins & Bridenbaugh (Eds) Neural blockade in clinical anaesthesia and management of pain, 2nd ed., pp. 253–360, JB Lippincott, Philadelphia, London, New York, Sao Paolo, Mexico City, St. Louis, Sydney, 1988

    Google Scholar 

  • Cousins MJ, Mather LE. Intrathecal and epidural administration of opioids. Anesthesiology 61: 276–310, 1984

    Article  PubMed  CAS  Google Scholar 

  • Covino BG. Pharmacology of local anaesthetic agents. British Journal of Anaesthesia 58: 701–716, 1986

    Article  PubMed  CAS  Google Scholar 

  • Covino BG. Clinical pharmacology of local anesthetic agents. In Cousins & Bridenbaugh (Eds) Neural blockade in clinical anaesthesia and management of pain, 2nd ed., pp. 111–144, J.B. Lippincott, Philadelphia, 1988

    Google Scholar 

  • Covino BG, Scott DB. Handbook of epidural anaesthesia and analgesia, pp. 36–41, 66-76, Schulz Medical Information, Copenhagen, 1985

    Google Scholar 

  • Covino BG, Vassallo HG. Local anesthetics. Mechanisms of action and clinical use, pp. 46–48, 75-89, Grune and Stratton, New York, San Francisco, London, 1976

    Google Scholar 

  • Crawford OB. Comparative evaluation in peridural anesthesia of lidocaine, mepivacaine and L-67, a new local anaesthetic agent. Anesthesiology 25: 321–329, 1964

    Article  PubMed  CAS  Google Scholar 

  • Crosby G. Local spinal cord blood flow and glucose utilization during spinal anesthesia with bupivacaine in conscious rats. Anesthesiology 63: 55–60, 1985

    Article  PubMed  CAS  Google Scholar 

  • Cusick JF, Myklebust JB, Abram SE. Differential neural effects of epidural anesthetics. Anesthesiology 53: 299–306, 1980

    Article  PubMed  CAS  Google Scholar 

  • Cusick JF, Myklebust JB, Abram SE, Davidson A. Altered neural conduction with epidural bupivacaine. Anesthesiology 57: 31–36, 1982

    Article  PubMed  CAS  Google Scholar 

  • Dailey PA, Hughes SC, Rosen MA, Healy K, Cheek DBC, et al. Lidocaine levels during Cesarean section after pretreatment with ranitidine or Cimetidine. Anesthesiology 63: A444, 1985

    Article  Google Scholar 

  • Datta S, Lambert DH, Gregus J, Gissen AJ, Covino BG. Differential sensitivities of mammalian nerve fibers during pregnancy. Anesthesia and Analgesia 62: 1070–1072, 1983

    Article  PubMed  CAS  Google Scholar 

  • Dennhardt R, Konder H. Blut- und Liquorspiegel von Bupivacain bei Spinalanaesthesien. Regional Anesthesie 6: 72–75, 1983

    CAS  Google Scholar 

  • Denson DD. Drug interactions with local anesthetics. In Langlöys (Ed.) Update regional anaesthesia, pp. 111–121, MAPAR Editions, Kremlin-Bicêtre, 1987

    Google Scholar 

  • Denson DD, Bridenbaugh PO, Turner PA, Phero JC. Comparison of neural blockade and pharmacokinetics after subarachnoid lidocaine in the rhesus monkey. II: effects of volume, osmolality, and baricity. Anesthesia and Analgesia 62: 995–1001, 1983

    Article  PubMed  CAS  Google Scholar 

  • Denson DD, Bridenbaugh PO, Turner PA, Phero JC, Raj PP. Neural blockade and pharmacokinetics following subarachnoid lidocaine in the rhesus monkey. I: effects of epinephrine. Anesthesia and Analgesia 61: 746–750, 1982

    Article  PubMed  CAS  Google Scholar 

  • Denson DD, Coyle D, Thompson G, Myers J. Alpha1-acid glycoprotein and albumin in human serum bupivacaine binding. Clinical Pharmacology and Therapeutics 35: 409–415, 1984a

    Article  PubMed  CAS  Google Scholar 

  • Denson DD, Myers JA, Hartrick CT, Pitker CP, Coyle D, et al. The relationship between free bupivacaine concentration and central nervous system toxicity. Anesthesiology 61: A211, 1984b

    Article  Google Scholar 

  • Denson DD, Ritschel WA, Turner PA, Ohlweiler DF, Bridenbaugh PO. A comparison of intravenous and subarachnoid lidocaine pharmacokinetics in the rhesus monkey. Biopharmaceuticals and Drug Disposition 2: 367–380, 1981

    Article  CAS  Google Scholar 

  • Denson DD, Turner PA, Bridenbaugh PO, Thompson GA. Pharmacokinetics and neural blockade after subarachnoid lidocaine in the rhesus monkey. III: effects of phenylephrine. Anesthesia and Analgesia 63: 129–133, 1984c

    PubMed  CAS  Google Scholar 

  • De Rosayro AM, Tait AR, Labond V, Ketcham TR, Knight PR. The effect of subarachnoid lidocaine and epinephrine on spinal cord blood flow. Anesthesiology 59: A208, 1983

    Google Scholar 

  • DiFaxio CA, Carron H, Grosslight KR, Moscicki JC, Bolding WR, et al. Comparison of pH-adjusted lidocaine solutions for epidural anesthesia. Anesthesia and Analgesia 65: 760–764, 1986

    Google Scholar 

  • Dohi S, Matsumiya N, Takeshima R, Naito H. The effects of subarachnoid lidocaine and phenylephrine on spinal cord and cerebral blood flow in dogs. Anesthesiology 61: 238–244, 1984

    Article  PubMed  CAS  Google Scholar 

  • Dohi S, Takeshima R, Naito H. Spinal cord blood flow during spinal anesthesia in dogs: the effects of tetracaine, epinephrine, acute blood loss and hypercapnia. Anesthesia and Analgesia 66: 599–606, 1987

    Article  PubMed  CAS  Google Scholar 

  • Ecoffey C, Desparmet J, Berdeaux A, Maury M, Giudicelli JF, et al. Pharmacokinetics of lignocaine in children following caudal anaesthesia. British Journal of Anaesthesia 56: 1399–1402, 1984

    Article  PubMed  CAS  Google Scholar 

  • Ecoffey C, Desparmet J, Maury M, Berdeaux A, Giudicelli JF, et al. Bupivacaine in children: pharmacokinetics following caudal anesthesia. Anesthesiology 63: 447–448, 1985

    Article  PubMed  CAS  Google Scholar 

  • Eisenach JC, Grice SC, Dewan DM. Epinephrine enhances analgesia produced by epidural bupivacaine during labor. Anesthesia and Analgesia 66: 447–451, 1987

    Article  PubMed  CAS  Google Scholar 

  • Englesson S. The influence of acid-base changes on central nervous system toxicity of local anesthetic agents I. An experimental study in cats. Acta Anaesthesiologica Scandinavica 18: 79–87, 1974

    Article  PubMed  CAS  Google Scholar 

  • Englesson S, Grevsten S. The influence of acid-base changes on central nervous system toxicity of local anaesthetic agents. II. Acta Anaesthesiologica Scandinavica 18: 88–103, 1974

    Article  PubMed  CAS  Google Scholar 

  • Erdemir HA, Soper LE, Sweet RB. Studies of factors affecting peridural anesthesia. Anesthesia and Analgesia 44: 400–404, 1965

    Article  Google Scholar 

  • Eyres RL, Bishop W, Oppenheim RC, Brown TCK. Plasma bupivacaine concentrations in children during caudal epidural analgesia. Anaesthesia and Intensive Care 11: 20–22, 1983

    PubMed  CAS  Google Scholar 

  • Eyres RL, Kidd J, Oppenheim R, Brown TCK. Local anaesthetic plasma levels in children. Anaesthesia and Intensive Care 6: 243–247, 1978

    PubMed  CAS  Google Scholar 

  • Fairley JW, Reynolds F. An intradermal study of the local anaesthetic and vascular effects of the isomers of mepivacaine. British Journal of Anaesthesia 53: 1211–1216, 1981

    Article  PubMed  CAS  Google Scholar 

  • Finucane BT, Hammonds WD, Welch MB. Influence of age on vascular absorption of lidocaine from the epidural space. Anesthesia and Analgesia 66: 843–846, 1987

    Article  PubMed  CAS  Google Scholar 

  • Flanagan HL, Datta S, Lambert DH, Gissen AJ, Covino BG. Effect of pregnancy on bupivacaine-induced conduction blockade in the isolated rabbit vagus nerve. Anesthesia and Analgesia 66: 123–126, 1987

    Article  PubMed  CAS  Google Scholar 

  • Foldes FF, Davidson GM, Duncalf D, Kuwabara S. The intravenous toxicity of local anesthetic agents in man. Clinical Pharmacology and Therapeutics 6: 328–335, 1965

    PubMed  CAS  Google Scholar 

  • Forbes AR, Roizen MF. Does spinal anesthesia anesthetize the spinal cord? Anesthesiology 48: 440–455, 1978

    Article  PubMed  CAS  Google Scholar 

  • Ford DJ, Raj PP. Peripheral neurotoxicity of 2-chloroprocaine and bisulfite in the cat. Anesthesia and Analgesia 66: 719–722, 1987

    Article  PubMed  CAS  Google Scholar 

  • Freund PR, Bowdle TA, Slattery JT. Caudal anesthesia with lidocaine or bupivacaine: plasma local anesthetic concentration and extent of sensory spread in old and young patients. Anesthesia and Analgesia 63: 1017–1020, 1984

    Article  PubMed  CAS  Google Scholar 

  • Giasi RM, D’Agostino E, Covino BG. Absorption of lidocaine following subarachnoid and epidural administration. Anesthesia and Analgesia 58: 360–363, 1979

    Article  PubMed  CAS  Google Scholar 

  • Gissen AJ, Covino BG, Gregus J. Differential sensitivities of mammalian nerve fibers to local anesthetic agents. Anesthesiology 53: 467–474, 1980

    Article  PubMed  CAS  Google Scholar 

  • Gissen AJ, Covino BG, Gregus J. Differential sensitivity of fast and slow fibers in mammalian nerve. III: effect of etidocaine and bupivacaine on fast/slow fibers. Anesthesia and Analgesia 61: 570–575, 1982

    PubMed  CAS  Google Scholar 

  • Gissen AJ, Datta S, Lambert D. The chloroprocaine controversy: II. Is chloroprocaine neurotoxic? Regional Anesthesia 9: 135–145, 1984

    CAS  Google Scholar 

  • Glosten B, Dailey P, Preston P, Shnider S, Ross B, et al. Epidural anesthesia with pH-adjusted 3% 2-chloroprocaine for postpartum tubal ligation. Anesthesiology 67: A630, 1987

    Article  Google Scholar 

  • Greene NM. Physiology of spinal anesthesia, 3rd ed., pp. 1–61, 265-273, Williams and Wilkins, Baltimore, London, 1981

    Google Scholar 

  • Greene NM. Uptake and elimination of local anesthetics during spinal anesthesia. Anesthesia and Analgesia 62: 1013–1024, 1983

    Article  PubMed  CAS  Google Scholar 

  • Greene NM. Distribution of local anesthetic solutions within the subarachnoid space. Anesthesia and Analgesia 64: 715–730, 1985

    Article  PubMed  CAS  Google Scholar 

  • Gross TL, Kuhnert PM, Kuhnert BR, Pimentai R. Plasma levels of 2-chloroprocaine and lack of sequelae following an apparent intravenous injection. Anesthesiology 54: 173–174, 1981

    Article  PubMed  CAS  Google Scholar 

  • Grundy EM, Ramamurthy S, Patel KP, Mani M, Winnie AP. Extradural analgesia revisited: a statistical study. British Journal of Anaesthesia 50: 805–809, 1978

    Article  PubMed  CAS  Google Scholar 

  • Helrich M, Papper EM, Brodie BB, Fink M, Rovenstine EA. The fate of intrathecal procaine and the spinal fluid level required for surgical anesthesia. Journal of Pharmacology and Experimental Therapeutics 100: 78–82, 1950

    PubMed  CAS  Google Scholar 

  • Huet P-M, Lelorier J. Effects of smoking and chronic hepatitis B on lignocaine and indocyanine green kinetics. Clinical Pharmacology and Therapeutics 28: 208–215, 1980

    Article  PubMed  CAS  Google Scholar 

  • Inoue R, Suganuma T, Echizen H, Ishizaki T, Kushida K, et al. Plasma concentrations of lidocaine and its principal metabolites during intermittent epidural anesthesia. Anesthesiology 63: 304–310, 1985

    Article  PubMed  CAS  Google Scholar 

  • Johns RA, DiFazio CA, Longnecker DE. Lidocaine constricts or dilates rat arterioles in a dose-dependent manner. Anesthesiology 62: 141–144, 1985

    Article  PubMed  CAS  Google Scholar 

  • Johns RA, Seyde WC, DiFazio CA, Longnecker DE. Dose dependent effects of bupivacaine on rat muscle arterioles. Anesthesiology 65: 186–191, 1986

    Article  PubMed  CAS  Google Scholar 

  • Jorfeldt L, Lewis DH, Löfström JB, Post C. Lung uptake of lidocaine in healthy volunteers. Acta Anaesthesiologica Scandinavica 23: 567–574, 1979

    Article  PubMed  CAS  Google Scholar 

  • Jorfeldt L, Lewis DH, Löfström JB, Post C. Lung uptake of lidocaine in man as influenced by anaesthesia, mepivacaine infusion or lung insufficiency. Acta Anaesthesiologica Scandinavica 27: 5–9, 1983

    Article  PubMed  CAS  Google Scholar 

  • Jorfeldt L, Löfström B, Pernow B, Wahren J. The effect of mepivacaine and lidocaine on forearm resistance and capacitance vessels in man. Acta Anaesthesiologica Scandinavica 14: 183–201, 1970

    Article  PubMed  CAS  Google Scholar 

  • Kanto J. Obstetric analgesia: clinical pharmacokinetic considerations. Clinical Pharmacokinetics 11: 283–298, 1986

    Article  PubMed  CAS  Google Scholar 

  • Kaukinen L, Kaukinen S, Kärkkäinen S. Epiduralanaesthesie mit Carticain bei Sectio caesarea. Ein Vergleich mit Bupivacain. Regional Anesthesie 9: 79–83, 1986

    CAS  Google Scholar 

  • Kennedy WF, Everett GB, Cobb LA, Allen GD. Simultaneous systemic and hepatic hemodynamic measurements during high peridural anesthesia in normal man. Anesthesia and Analgesia 50: 1069–1078, 1971

    Article  PubMed  CAS  Google Scholar 

  • Kitahara T, Kuri S, Yoshida J. The spread of drugs used for spinal anesthesia. Anesthesiology 17: 205–208, 1956

    Article  PubMed  CAS  Google Scholar 

  • Kotelko DM, Shnider SM, Dailey DA, Brizgys RV, Levinson G, et al. Bupivacaine-induced cardiac arrhythmias in sheep. Anesthesiology 60: 10–18, 1984

    Article  PubMed  CAS  Google Scholar 

  • Kozody R, Ong B, Palahniuk RJ, Wade JG, Cumming MO, et al. Subarachnoid bupivacaine decreases spinal cord blood flow in dogs. Canadian Anaesthetists’ Society Journal 32: 216–222, 1985a

    Article  PubMed  CAS  Google Scholar 

  • Kozody R, Palahniuk RJ, Cumming MO. Spinal cord blood flow following subarachnoid tetracaine. Canadian Anaesthetists’ Society Journal 32: 23–29, 1985b

    Article  PubMed  CAS  Google Scholar 

  • Kozody R, Palahniuk RJ, Wade JG, Cumming MO, Pucci WR. The effect of subarachnoid epinephrine and phenylephrine on spinal cord blood flow. Canadian Anaesthetists’ Society Journal 31: 503–508, 1984

    Article  PubMed  CAS  Google Scholar 

  • Kozody R, Swartz J, Palahniuk RJ, Biehl DR, Wade JG. Spinal cord blood flow following subarachnoid lidocaine. Canadian Anaesthetists’ Society Journal 32: 472–478, 1985c

    Article  PubMed  CAS  Google Scholar 

  • Kraynack BJ, Gintautas J, Tjay H. Local anesthetic action of epinephrine and ephedrine. Regional Anesthesia 8: 32–33, 1983

    Google Scholar 

  • Kuhnert BR, Kuhnert PM, Prochaska AL, Gross TL. Plasma levels of 2-chloroprocaine in obstetric patients and their neonates after epidural anesthesia. Anesthesiology 53: 21–25, 1980

    Article  PubMed  CAS  Google Scholar 

  • Kuhnert BR, Zuspan KJ, Kuhnert PM, Syracuse CD, Brashear WT, et al. Lack of influence of Cimetidine on bupivacaine levels during parturition. Anesthesia and Analgesia 66: 986–990, 1987a

    PubMed  CAS  Google Scholar 

  • Kuhnert BR, Zuspan KJ, Kuhnert PM, Syracuse CD, Brown DE. Bupivacaine disposition in mother, fetus, and neonate after spinal anesthesia for Caesarean section. Anesthesia and Analgesia 66: 407–412, 1987b

    PubMed  CAS  Google Scholar 

  • Laishley RS, Morgan BM, Reynolds F. Effect of adrenaline on extradural anaesthesia and plasma bupivacaine concentrations during Caesarian section. British Journal of Anaesthesia 60: 180–186, 1988

    Article  PubMed  CAS  Google Scholar 

  • Lalka D, Vicuna N, Burrow SR, Jones DJ, Luddon DJ, et al. Bupivacaine and other amide local anesthetics inhibit the hydrolysis of chloroprocaine in human serum. Anesthesia and Analgesia 57: 534–538, 1978

    PubMed  CAS  Google Scholar 

  • Leicht CH, Carlson SA. Prolongation of lidocaine spinal anesthesia with epinephrine and phenylephrine. Anesthesia and Analgesia 65: 365–369, 1986

    Article  PubMed  CAS  Google Scholar 

  • Littlewood DG, Buckley P, Covino BG, Scott DB, Wilson J. Comparative study of various local anaesthetic solutions in extradural block in labour. British Journal of Anaesthesia 51: 47S–52S, 1979

    Google Scholar 

  • Lund C, Hansen OB, Mogenson T, Kehlet H. Effect of thoracic epidural bupivacaine on somatosensory evoked potentials after dermatomal stimulation. Anesthesia and Analgesia 66: 731–734, 1987a

    PubMed  CAS  Google Scholar 

  • Lund C, Selmar P, Hansen OB, Hjortsø NC, Kehlet H. Effect of epidural bupivacaine on somatosensory evoked potentials after dermatomal stimulation. Anesthesia and Analgesia 66: 34–38, 1987b

    Article  PubMed  CAS  Google Scholar 

  • Lund C, Selmar P, Hansen OB, Kehlet H. Effect of intrathecal bupivacaine on somatosensory evoked potentials following dermatomal stimulation. Anesthesia and Analgesia 66: 809–813, 1987c

    PubMed  CAS  Google Scholar 

  • Lund PC, Bush DF, Covino BG. Determinants of etidocaine concentration in the blood. Anesthesiology 42: 497–503, 1975

    Article  PubMed  CAS  Google Scholar 

  • Lund PC, Covino BG. Distribution of local anaesthetics in man following epidural anesthesia. Journal of Clinical Pharmacology 7: 324–329, 1967

    CAS  Google Scholar 

  • Lund PC, Cwik JC. Citanest … a clinical and laboratory study. Anesthesia and Analgesia 44: 623–631, 1965

    PubMed  CAS  Google Scholar 

  • Lund PC, Cwik JC. A correlation of the differential penetration and the systemic toxicity of lidocaine, mepivacaine and prilocaine in man. Acta Anaesthesiologica Scandinavica 23 (Suppl.): 475–482, 1966

    Article  PubMed  CAS  Google Scholar 

  • Lund PC, Cwik JC, Pagdanganan RT. Etidocaine — a new long-acting local anesthetic agent: a clinical evaluation. Anesthesia and Analgesia 52: 482–494, 1973

    PubMed  CAS  Google Scholar 

  • Martin R, Lamarche Y, Tétreault L. Comparison of the effectiveness of lidocaine hydrocarbonate and lidocaine hydrochloride with and without epinephrine in epidural anaesthesia. Canadian Anaesthetists’ Society Journal 28: 217–223, 1981

    Article  PubMed  CAS  Google Scholar 

  • Mather EL, Cousins MJ. Local anaesthetics and their current clinical use. Drugs 18: 185–205, 1979

    Article  PubMed  CAS  Google Scholar 

  • Mather LE, Thomas J. Bupivacaine binding to plasma protein fractions. Journal of Pharmacy and Pharmacology 30: 653–654, 1978

    Article  PubMed  CAS  Google Scholar 

  • Mather LE, Tucker GT, Murphy TM, Stanton-Hicks Md’A, Bonica JJ. The effects of adding adrenaline to etidocaine and lignocaine in extradural anaesthesia II: pharmacokinetics. British Journal of Anaesthesia 48: 989–994, 1976a

    Article  PubMed  CAS  Google Scholar 

  • Mather LE, Tucker GT, Murphy TM, Stanton-Hicks Md’A, Bonica JJ. Hemodynamic drug interaction: peridural lidocaine and intravenous ephedrine. Acta Anaesthesiologica Scandinavica 20: 207–210, 1976b

    Article  PubMed  CAS  Google Scholar 

  • Matthes H, Schabert P. Vergleichende Untersuchungen über Blutspiegel von Mepivacain nach Resorption aus verschiedenen Gewebe. Acta Anaesthesiologica Scandinavica 23 (Suppl.): 371–376, 1966

    Article  PubMed  CAS  Google Scholar 

  • Mayumi T, Dohi S, Takahashi T. Plasma concentrations of lidocaine associated with cervical, thoracic and lumbar epidural anesthesia. Anesthesia and Analgesia 62: 578–580, 1983

    PubMed  CAS  Google Scholar 

  • Mazoit JX, Denson DD, Samii K. Pharmacokinetics of bupivacaine following caudal anesthesia in infants. Anesthesiology 68: 387–391, 1988

    Article  PubMed  CAS  Google Scholar 

  • Mazze RI, Dunbar RW. Plasma lidocaine concentrations after caudal, lumbar epidural, axillary block and intravenous regional anesthesia. Anesthesiology 27: 574–579, 1966

    Article  PubMed  CAS  Google Scholar 

  • McMorland GW, Douglas MJ, Jeffery WK, Ross PLE, Axelson JE, et al. Effect of pH adjustment of bupivacaine on onset and duration of epidural analgesia in parturients. Canadian Anaesthetists’ Society Journal 33: 537–541, 1986

    Article  PubMed  CAS  Google Scholar 

  • McNamara PJ, Slaughter RL, Pieper JA, Wyman MG, Lalka D. Factors influencing serum protein binding of lidocaine in humans. Anesthesia and Analgesia 60: 395–400, 1981

    Article  PubMed  CAS  Google Scholar 

  • Meyer J, Nolte H. Liquorkonzentration von Bupivacain nach subduraler Applikation. Regional Anaesthesie 1: 38–40, 1978

    Google Scholar 

  • Mihaly GW, Moore RG, Thomas T, Triggs EJ, Thomas D, et al. The pharmacokinetics and metabolism of the anilide local anaesthetics in neonates I. Lignocaine. European Journal of Clinical Pharmacology 13: 143–152, 1978

    Article  PubMed  CAS  Google Scholar 

  • Möller IW, Fernandes A, Edström HH. Subarachnoid anaesthesia with 0.5% bupivacaine: effect of density. British Journal of Anaesthesia 56: 1191–1194, 1984

    Article  PubMed  Google Scholar 

  • Moore DC. Spinal anesthesia: bupivacaine compared with tetracaine. Anesthesia and Analgesia 59: 743–750, 1980

    PubMed  CAS  Google Scholar 

  • Moore DC. The pH of local anesthetic solutions. Anesthesia and Analgesia 60: 833–834, 1981

    PubMed  CAS  Google Scholar 

  • Moore DC, Bridenbaugh LD, Bagdi PA, Bridenbaugh PO. Accumulation of mepivacaine hydrochloride during caudal block. Anesthesiology 29: 585–588, 1968

    Article  PubMed  CAS  Google Scholar 

  • Moore DC, Chadwick HS, Ready LB. Epinephrine prolongs lidocaine spinal: pain in the operative site the most accurate method of determining local anesthetic duration. Anesthesiology 67: 416–418, 1987

    Article  PubMed  CAS  Google Scholar 

  • Moore DC, Mather LE, Bridenbaugh PO, Bridenbaugh LD, Balfour RI, et al. Arterial and venous plasma levels of bupivacaine following epidural and intercostal nerve blocks. Anesthesiology 45: 39–45, 1976

    Article  PubMed  CAS  Google Scholar 

  • Moore DC, Spierdijk J, Van Kleef JW, Coleman RL, Love GF. Chloroprocaine neurotoxicity: four additional cases. Anesthesia and Analgesia 61: 155–159, 1982

    PubMed  CAS  Google Scholar 

  • Moore RG, Thomas J, Triggs EJ, Thomas DB, Burnard ED, et al. The pharmacokinetics and metabolism of the anilide local anaesthetics in neonates III. Mepivacaine. European Journal of Clinical Pharmacology 14: 203–212, 1978

    Article  PubMed  CAS  Google Scholar 

  • Morgan DJ, Cousins MJ, McQuillan D, Thomas J. Disposition and placental transfer of etidocaine in pregnancy. European Journal of Clinical Pharmacology 12: 359–365, 1977

    Article  PubMed  CAS  Google Scholar 

  • Morison DH. A double-blind comparison of carbonated lidocaine and lidocaine hydrochloride in epidural anaesthesia. Canadian Anaesthetists’ Society Journal 28: 387–389, 1981

    Article  PubMed  CAS  Google Scholar 

  • Murphy TM, Mather LE, Stanton-Hicks Md’A, Bonica JJ, Tucker GT. The effects of adding adrenaline to etidocaine and lignocaine in extradural anaesthesia I: block characteristics and cardiovascular effects. British Journal of Anaesthesia 48: 893–898, 1976

    Article  PubMed  CAS  Google Scholar 

  • Nancarrow C, Runciman WB, Mather LE, Upton RN, Plummer JL. The influence of acidosis on the distribution of lidocaine and bupivacaine into the myocardium and brain of the sheep. Anesthesia and Analgesia 66: 925–935, 1987

    Article  PubMed  CAS  Google Scholar 

  • Nickel PM, Bromage PR, Sherrill DL. Comparison of hydrochloride and carbonated salts of lidocaine for epidural analgesia. Regional Anesthesia 11: 62–67, 1986

    Google Scholar 

  • Nishimura N, Kitahara T, Kusakabe T. The spread of lidocaine and I-131 solution in the epidural space. Anesthesiology 20: 785–788, 1959

    Article  PubMed  CAS  Google Scholar 

  • Noble DW, Smith KJ, Dundas CR. Effects of H2-antagonists on the elimination of bupivacaine. British Journal of Anaesthesia 59: 735–737, 1987

    Article  PubMed  CAS  Google Scholar 

  • Ohno H, Watanabe M, Saitoh J, Saegusa Y, Hasegawa Y, et al. Effect of epinephrine concentration on lidocaine disposition during epidural anesthesia. Anesthesiology 68: 625–628, 1988

    Article  PubMed  CAS  Google Scholar 

  • O’Sullivan GM, Smith M, Morgan B, Brighouse D, Reynolds F. H2-antagonists and bupivacaine clearance. Anesthesia 43: 93–95, 1988

    Article  Google Scholar 

  • Pardridge WM, Sakiyama R, Fierer G. Transport of propranolol and lidocaine through the rat blood-brain barrier. Journal of Clinical Investigation 71: 900–908, 1983

    Article  PubMed  CAS  Google Scholar 

  • Park WY, Balingit PE, Macnamara TE. Effect of patient age, pH of cerebrospinal fluid, and vasopressor on onset and duration of spinal anesthesia. Anesthesia and Analgesia 54: 455–458, 1975

    PubMed  CAS  Google Scholar 

  • Park WY, Hagins FM, Rivat EL, Macnamara TE. Age and epidural dose response in adult man. Anesthesiology 56: 318–320, 1982

    Article  PubMed  CAS  Google Scholar 

  • Park WY, Massengale M, Kim S-I, Poon KC, Macnamara TE. Age and the spread of local anesthetic solutions in the epidural space. Anesthesia and Analgesia 59: 768–771, 1980

    Article  PubMed  CAS  Google Scholar 

  • Pieper JA, Wyman MG, Goldreyer BN, Cannom DS, Slaughter RL, et al. Lidocaine toxicity: effect of total versus free lidocaine concentrations. Circulation 62(III): 181, 1980

    Google Scholar 

  • Pitkänen M, Haapaniemi L, Tuominen M, Rosenberg PH. Influence of age on spinal anaesthesia with isobaric 0.5% bupivacaine. British Journal of Anaesthesia 56: 279–284, 1984

    Article  PubMed  Google Scholar 

  • Porter SS, Albin MS, Watson WA, Bunegin L, Pantoja G. Spinal cord and cerebral blood flow responses to subarachnoid injection of local anesthetics with and without epinephrine. Acta Anaesthesiologica Scandinavica 29: 330–338, 1985

    Article  PubMed  CAS  Google Scholar 

  • Racle JP, Benkhadra A, Poy JY. Subarachnoid anaesthesia produced by hyperbaric lidocaine in elderly patients. British Journal of Anaesthesia 60: 831–835, 1988a

    Article  PubMed  CAS  Google Scholar 

  • Racle JP, Benkhadra A, Poy JY, Gleizal B. Prolongation of isobaric bupivacaine spinal anesthesia with epinephrine and Clonidine for hip surgery in the elderly. Anesthesia and Analgesia 66: 442–446, 1987a

    PubMed  CAS  Google Scholar 

  • Racle JP, Benkhadra A, Poy JY, Gleizal B. Effect of increasing amount of epinephrine during isobaric bupivacaine spinal anesthesia in elderly patients. Anesthesia and Analgesia 66: 882–886, 1987b

    PubMed  CAS  Google Scholar 

  • Racle JP, Benkhadra A, Poy JY, Gleizal B. Spinal analgesia with hyperbaric bupivacaine: influence of age. British Journal of Anaesthesia 60: 508–514, 1988b

    Article  PubMed  CAS  Google Scholar 

  • Raj PP, Ohlweiler D, Hitt BA, Denson DD. Kinetics of local anesthetic esters and the effect of adjuvant drugs on 2-chloroprocaine hydrolysis. Anesthesiology 53: 307–314, 1980

    Article  PubMed  CAS  Google Scholar 

  • Ravindran RS, Bond VK, Tasch MD, Gupta CD, Luerssen TG. Prolonged neural blockade following regional analgesia with 2-chloroprocaine. Anesthesia and Analgesia 59: 447–451, 1980

    PubMed  CAS  Google Scholar 

  • Raymond SA, Gissen AJ. Mechanisms of differential nerve block. In Strichartz GR (Ed.) Local anesthetics, pp. 95–164, Springer-Verlag, Berlin, Heidelberg, New York, London, Paris, Tokyo, 1987

    Chapter  Google Scholar 

  • Reidenberg MM, James M, Dring LG. The rate of procaine hydrolysis in serum of normal subjects and diseased patients. Clinical Pharmacology and Therapeutics 13: 279–284, 1972

    PubMed  CAS  Google Scholar 

  • Reisner LS, Hochman BN, Plumer MH. Persistent neurologic deficit and adhesive arachnoiditis following intrathecal 2-chloroprocaine injection. Anesthesia and Analgesia 59: 452–454, 1980

    Article  PubMed  CAS  Google Scholar 

  • Renck H, Edström H, Kinnberger B, Brandt G. Thoracic epidural analgesia — II: prolongation in the early postoperative period by continuous injection of 1.0% bupivacaine. Acta Anaesthesiologica Scandinavica 20: 47–56, 1976

    Article  PubMed  CAS  Google Scholar 

  • Reynolds F. Adverse effects of local anaesthetics. British Journal of Anaesthesia 59: 78–95, 1987

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg PH, Saramies L, Alila A. Lumbar epidural anaesthesia with bupivacaine in old patients: effects of speed and direction of injection. Acta Anaesthesiologica Scandinavica 25: 270–274, 1981

    Article  PubMed  CAS  Google Scholar 

  • Ross BK, Hughes S, Glosten B, Shnider S, Preston P, et al. Evaluation of epidural pH-adjusted 2% 2-chloroprocaine for labor analgesia. Anesthesiology 67: A629, 1987

    Article  Google Scholar 

  • Ross RA, Clarke JE, Armitage EW. Postoperative pain prevention by continuous epidural infusion. A study of the clinical effects and the plasma concentrations obtained. Anaesthesia 35: 663–668, 1980

    Article  PubMed  CAS  Google Scholar 

  • Rothstein P, Arthur GR, Feldman HS, Kopf GS, Covino BG. Bupivacaine for intercostal nerve blocks in children: blood concentrations and pharmacokinetics. Anesthesia and Analgesia 65: 625–632, 1986

    Article  PubMed  CAS  Google Scholar 

  • Routledge PA, Barchowsky A, Bjornsson TD, Kitchell BB, Shand DG. Lidocaine plasma protein binding. Clinical Pharmacology and Therapeutics 27: 347–351, 1980

    Article  PubMed  CAS  Google Scholar 

  • Runciman WB, Mather LE, Ilsley AH, Carapetis RJ, McLean CF. A sheep preparation for studying interactions between blood flow and drug disposition. II: experimental applications. British Journal of Anaesthesia 56: 1117–1129, 1984a

    Article  PubMed  CAS  Google Scholar 

  • Runciman WB, Mather LE, Ilsley AH, Carapetis RJ, Upton RN. A sheep preparation for studying interactions between blood flow and drug disposition. III: effects of general and spinal anaesthesia on regional blood flow and oxygen tensions. British Journal of Anaesthesia 56: 1247–1258, 1984b

    Article  PubMed  CAS  Google Scholar 

  • Schmidt KF. Metabolism of procaine in cerebrospinal fluid contaminated with blood. Anesthesiology 25: 563–564, 1964

    Article  PubMed  CAS  Google Scholar 

  • Scott DB. Evaluation of the toxicity of local anaesthetic agents in man. British Journal of Anaesthesia 47: 56–61, 1975

    Article  PubMed  CAS  Google Scholar 

  • Scott DB. Toxic effects of local anaesthetic agents on the central venous system. British Journal of Anaesthesia 58: 732–735, 1986

    Article  PubMed  CAS  Google Scholar 

  • Scott DB, Jebson PJR, Braid DP, Örtengren B, Frisch P. Factors affecting plasma levels of lignocaine and prilocaine. British Journal of Anaesthesia 44: 1040–1049, 1972

    Article  PubMed  CAS  Google Scholar 

  • Scott DB, McClure JH, Giasi RM, Seo J, Covino BG. Effects of concentration of local anaesthetic drugs in extradural block. British Journal of Anaesthesia 52: 1033–1037, 1980

    Article  PubMed  CAS  Google Scholar 

  • Seifen AB, Ferrari AA, Seifen EE, Thompson DS, Chapman J. Pharmacokinetics of intravenous procaine infusion in humans. Anesthesia and Analgesia 58: 382–386, 1979

    Article  PubMed  CAS  Google Scholar 

  • Seow LT, Lips FJ, Cousins MJ, Mather LE. Lidocaine and bupivacaine mixtures for epidural blockade. Anesthesiology 56: 177–183, 1982

    Article  PubMed  CAS  Google Scholar 

  • Sharrock NE. Epidural anesthetic dose responses in patients 20 to 80 years old. Anesthesiology 49: 425–428, 1978

    Article  PubMed  CAS  Google Scholar 

  • Sheskey MC, Rocco AG, Bizzarri-Schmid M, Francis DM, Edström H, et al. A dose-response study of bupivacaine for spinal anesthesia. Anesthesia and Analgesia 62: 931–935, 1983

    Article  PubMed  CAS  Google Scholar 

  • Simon RP, Benowitz NL, Bronstein BS, Jacob P. Increased brain uptake of lidocaine during bicuculline-induced status epilepticus in rats. Neurology 32: 196–199, 1982

    Article  PubMed  CAS  Google Scholar 

  • Simon RP, Benowitz NL, Culala S. Motor paralysis increases brain uptake of lidocaine during status epilepticus. Neurology 34: 384–387, 1984

    Article  PubMed  CAS  Google Scholar 

  • Sinclair CJ, Scott DB. Comparison of bupivacaine and etidocaine in extradural blockade. British Journal of Anaesthesia 56: 147–153, 1984

    Article  PubMed  CAS  Google Scholar 

  • Smith AR, Hur D, Resano F. Grand mal seizures after 2-chloroprocaine epidural anesthesia in a patient with plasma Cholinesterase deficiency. Anesthesia and Analgesia 66: 677–678, 1987

    PubMed  CAS  Google Scholar 

  • Spivey DL. Epinephrine does not prolong lidocaine spinal anesthesia in term parturients. Anesthesia and Analgesia 64: 468–470, 1985

    Article  PubMed  CAS  Google Scholar 

  • Stanton-Hicks M, Berger PU, Bonica JJ. Circulatory effects of peridural block: IV Comparison of effects of epinephrine and phenylephrine. Anesthesiology 39: 308–314, 1973

    Article  PubMed  CAS  Google Scholar 

  • Strichartz GR, Ritchie JM. The action of local anesthetics on ion channels of excitable tissues. In Strichartz (Ed.) Local anesthetics, pp. 21–52, Springer-Verlag, Berlin, Heidelberg, New York, London, Paris, Tokyo, 1987

    Chapter  Google Scholar 

  • Takasaki M. Blood concentrations of lidocaine, mepivacaine and bupivacaine during caudal analgesia in children. Acta Anaesthesiologica Scandinavica 28: 211–214, 1984

    Article  PubMed  CAS  Google Scholar 

  • Takasaki M, Ohoka T, Doi K, Kosaka Y. Blood levels of mepivacaine during continuous epidural anesthesia. Anesthesia and Analgesia 66: 337–340, 1987

    Article  PubMed  CAS  Google Scholar 

  • Terasaki T, Pardridge WM, Denson DD. Differential effect of plasma protein binding of bupivacaine on its in vivo transfer into the brain and salivary gland of rats. Journal of Pharmacology and Experimental Therapeutics 239: 724–729, 1986

    PubMed  CAS  Google Scholar 

  • Thomson PD, Melmar KL, Richardson JA, Cohn K, Steinbrunn W, et al. Lidocaine pharmacokinetics in advanced heart failure, liver disease and renal disease in humans. Annals of Internal Medicine 78: 499–508, 1973

    PubMed  CAS  Google Scholar 

  • Tucker GT. Pharmacokinetics of local anaesthetics. British Journal of Anaesthesia 58: 717–731, 1986

    Article  PubMed  CAS  Google Scholar 

  • Tucker GT. Is plasma binding of local anaesthetics important? Acta Anaesthesiologica Belgica 39: 147–150, 1988

    PubMed  CAS  Google Scholar 

  • Tucker GT, Bax NDS, Lennard MD, Al-Asady S, Bharaj HS, et al. Effects of β-adrenoceptor antagonists on the pharmacokinetics of lignocaine. British Journal of Clinical Pharmacology 17: 21S–28S, 1984

    Article  PubMed  Google Scholar 

  • Tucker GT, Boas RA. Pharmacokinetic aspects of intravenous regional anesthesia. Anesthesiology 34: 538–549, 1971

    Article  PubMed  CAS  Google Scholar 

  • Tucker GT, Boyes RN, Bridenbaugh PO, Moore DC. Binding of anilide-type local anesthetics in human plasma: I. Relationships between binding, physicochemical properties, and anesthetic activity. Anesthesiology 33: 287–303, 1970

    Article  PubMed  CAS  Google Scholar 

  • Tucker GT, Cooper S, Littlewood D, Buckley FP, Covino BG, et al. Observed and predicted accumulation of local anaesthetic agents during continuous extradural analgesia. British Journal of Anaesthesia 49: 237–242, 1977a

    Article  PubMed  CAS  Google Scholar 

  • Tucker GT, Mather LE. Pharmacokinetics of local anaesthetic agents. British Journal of Anaesthesia 47: 213–224, 1975

    Article  PubMed  Google Scholar 

  • Tucker GT, Mather LE. Clinical pharmacokinetics of local anaesthetics. Clinical Pharmacokinetics 4: 241–278, 1979

    Article  PubMed  CAS  Google Scholar 

  • Tucker GT, Mather LE. Properties, absorption, and disposition of local anesthetic agents. In Cousins & Bridenbaugh (Eds) Neural blockade in clinical anesthesia and management of pain, 2nd ed., pp. 47–110, JB Lippincott, Philadelphia, London, New York, Sao Paolo, Mexico City, St Louis, Sydney, 1988

    Google Scholar 

  • Tucker GT, Moore DC, Bridenbaugh PO, Bridenbaugh LD, Thompson GE. Systemic absorption of mepivacaine in commonly used regional block procedures. Anesthesiology 37: 277–287, 1972

    Article  PubMed  CAS  Google Scholar 

  • Tucker GT, Wiklund L, Berlin-Wahlén A, Mather LE. Hepatic clearance of local anaesthetics in man. Journal of Pharmacokinetics and Biopharmaceutics 5: 111–122, 1977b

    PubMed  CAS  Google Scholar 

  • Tuominen M, Pitkänen M, Doepel M, Rosenberg PH. Influence of age and body mass on subarachnoid anaesthesia with tetracaine. Acta Anaesthesiologica Scandinavica 31: 474–478, 1987

    Article  PubMed  CAS  Google Scholar 

  • Urban BJ. Clinical observations suggesting a changing site of action during induction and recession of spinal and epidural anesthesia. Anesthesiology 39: 496–503, 1973

    Article  PubMed  CAS  Google Scholar 

  • Van Kleef JW. A clinical evaluation of bupivacaine (Marcaine®) 0.5% versus 0.75%, Ph.D Thesis, pp. 95–120, University of Leiden, Leiden, 1981

    Google Scholar 

  • Veering BT, Burm AGL, Spierdijk J. Spinal anaesthesia with hyperbaric bupivacaine: effects of age on neural blockade and pharmacokinetics. British Journal of Anaesthesia 60: 187–194, 1988

    Article  PubMed  CAS  Google Scholar 

  • Veering BT, Burm AGL, Van Kleef JW, Hennis PJ, Spierdijk J. Epidural anesthesia with bupivacaine: effect of age on neural blockade and pharmacokinetics. Anesthesia and Analgesia 66: 589–593, 1987a

    PubMed  CAS  Google Scholar 

  • Veering BT, Burm AGL, Van Kleef JW, Hennis PJ, Spierdijk J. Spinal anesthesia with glucose-free bupivacaine: effects of age on neural blockade and pharmacokinetics. Anesthesia and Analgesia 66: 965–970, 1987b

    PubMed  CAS  Google Scholar 

  • Webb TD, Ward DS. Elimination of lidocaine following regional block is inhibited by Cimetidine. Anesthesiology 59: A213, 1983

    Article  Google Scholar 

  • Wiklund L, Tucker GT, Engberg G. Influence of intravenously administered ephedrine on splanchnic haemodynamics and clearance of lidocaine. Acta Anaesthesiologica Scandinavica 21: 275–281, 1977

    Article  PubMed  CAS  Google Scholar 

  • Wildsmith JAW, Gissen AJ, Gregus J, Covino BG. Differential nerve blocking activity of amino-ester local anaesthetics. British Journal of Anaesthesia 57: 612–620, 1985

    Article  PubMed  CAS  Google Scholar 

  • Wildsmith JAW, McClure JH, Brown DT, Scott DB. Effects of posture on the spread of isobaric and hyperbaric amethocaine. British Journal of Anaesthesia 53: 273–278, 1981

    Article  PubMed  CAS  Google Scholar 

  • Wilkinson GR, Lund PC. Bupivacaine levels in plasma and cerebrospinal fluid following peridural administration. Anesthesiology 33: 482–486, 1970

    Article  PubMed  CAS  Google Scholar 

  • Williams RL, Blaschke TF, Meffin PL, Melman KL, Rowland M. Influence of viral hepatitis on the disposition of two compounds with high hepatic clearance: lidocaine and indocyanine green. Clinical Pharmacology and Therapeutics 20: 290–299, 1976

    PubMed  CAS  Google Scholar 

  • Wood M. Plasma drug binding: implications for anesthesiologists. Anesthesia and Analgesia 65: 786–804, 1986

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anaesthesiology, Leiden University Hospital, P.O. Box 9600, 2300 RC, Leiden, The Netherlands

    A. G. L. Burm

Authors
  1. A. G. L. Burm
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Burm, A.G.L. Clinical Pharmacokinetics of Epidural and Spinal Anaesthesia. Clin-Pharmacokinet 16, 283–311 (1989). https://doi.org/10.2165/00003088-198916050-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-198916050-00002

Keywords

Search

Navigation