Neuraxial drug administration: A review of treatment options for anaesthesia and analgesia

CNS Drugs

Volumn 20, Issue 11, 2006, Pages 917-933

  Schug, Stephan A ^a,b   Saunders, David ^b   Kurowski, Irina ^b   Paech, Michael J ^a,b  

^a UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^b ROYAL PERTH HOSPITAL   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE; ADRENALIN; ALPHA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; ALPHA ADRENERGIC RECEPTOR; ANTIHISTAMINIC AGENT; BACLOFEN; BUPIVACAINE; CLONIDINE; CONOTOXIN; DEXMEDETOMIDINE; DIAMORPHINE; FENTANYL; HYDROMORPHONE; KETAMINE; LEVOBUPIVACAINE; LIDOCAINE; LOCAL ANESTHETIC AGENT; MIDAZOLAM; MORPHINE; NALOXONE; NEOSTIGMINE; NONSTEROID ANTIINFLAMMATORY AGENT; OMEGA CONOTOXIN MVIIA; ONDANSETRON; OPIATE; PETHIDINE; PROCAINE; PROPOFOL; ROPIVACAINE; SUFENTANIL;

ANALGESIA; ANATOMY; ANESTHESIA; ATRIOVENTRICULAR BLOCK; BRADYCARDIA; CARDIOTOXICITY; CHRONIC PAIN; DOSE RESPONSE; DRUG EFFICACY; DRUG MECHANISM; DRUG METABOLISM; DRUG POTENCY; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG SAFETY; HEART ARRHYTHMIA; HEART MUSCLE CONDUCTION DISTURBANCE; HEART VENTRICLE CONTRACTILITY; HEART VENTRICLE FIBRILLATION; HISTORY OF MEDICINE; HUMAN; HYPOTENSION; LOW BACK PAIN; MENTAL DISEASE; MUSCLE TWITCH; NAUSEA; NEUROLOGIC DISEASE; NEUROTOXICITY; NONHUMAN; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; PRURITUS; QRS WIDENING; QT DISPERSION; RESPIRATION DEPRESSION; REVIEW; SEIZURE; SIDE EFFECT; SPASTICITY; TRANSIENT NEUROLOGICAL SYMPTOM; VOMITING;

ADRENERGIC ALPHA-AGONISTS; ANALGESIA; ANALGESIA, EPIDURAL; ANALGESICS; ANALGESICS, OPIOID; ANESTHESIA; ANESTHESIA, EPIDURAL; ANESTHETICS; ANESTHETICS, LOCAL; ANIMALS; HUMANS; INJECTIONS; INJECTIONS, SPINAL; RECEPTORS, ADRENERGIC, ALPHA-2; SPINAL CORD; SUBARACHNOID SPACE;

EID: 33750248740     PISSN: 11727047     EISSN: 11727047     Source Type: Journal    
DOI: 10.2165/00023210-200620110-00005     Document Type: Review

References (157)

1. Brill S, Gurman GM, Fisher A. A history of neuraxial administration of local analgesics and opioids. Eur J Anaesthesiol 2003; 20 (9): 682-9
2. Bier A. Versucheüber Cocainisierung des Rückenmarkes. Dtsch Zeitschr Chirurg 1899; 51: 361-9
3. Marx G. The first spinal anesthesia. Reg Anesth 1994; 19 (6): 429-30
4. Yaksh TL, Rudy TA. Analgesia mediated by a direct spinal action of narcotics. Science 1976; 192 (4246): 1357-8
5. Wang JK, Nauss LA, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology 1979; 50 (2): 149-51
6. Cousins MJ, Mather LE. Intrathecal and epidural administration of opioids. Anesthesiology 1984; 61: 276-310
7. Maltby JR, Hutter CD, Clayton KC. The Woolley and Roe case. Br J Anaesth 2000; 84 (1): 121-6
8. Hodgson PS, Neal JM, Pollock JE, et al. The neurotoxicity of drugs given intrathecally (spinal). Anesth Analg 1999; 88 (4): 797-809
9. Yaksh TL, Allen JW. The use of intrathecal midazolam in humans: a case study of process. Anesth Analg 2004; 98 (6): 1536-45
10. Baxter AD. Continuous spinal anesthesia: the Canadian perspective. Reg Anesth 1993; 18 (6 Suppl.): 414-8
11. Rigler ML, Drasner K, Krejcie TC, et al. Cauda equina syndrome after continuous spinal anesthesia. Anesth Analg 1991; 72 (3): 275-81
12. Schell RM, Brauer FS, Cole DJ, et al. Persistent sacral nerve root deficits after continuous spinal anaesthesia. Can J Anaesth 1991; 38 (7): 908-11
13. Horlocker TT, McGregor DG, Matsushige DK, et al. Neurologic complications of 603 consecutive continuous spinal anesthetics using macrocatheter and microcatheter techniques. Perioperative Outcomes Group. Anesth Analg 1997; 84 (5): 1063-70
14. Denny NM, Selander DE. Continuous spinal anaesthesia. Br J Anaesth 1998; 81 (4): 590-7
15. Bevacqua BK. Continuous spinal anaesthesia: what's new and what's not. Best Pract Res Clin Anaesthesiol 2003; 17 (3): 393-406
16. Osenbach RK, Harvey S. Neuraxial infusion in patients with chronic intractable cancer and noncancer pain. Curr Pain Headache Rep 2001; 5 (3): 241-9
17. Broseta J, Garcia-March G, Sanchez-Ledesma MJ, et al. Chronic intrathecal baclofen administration in severe spasticity. Stereotact Funct Neurosurg 1990; 54-55: 147-53
18. Rathmell JP, Lair TR, Nauman B. The role of intrathecal drugs in the treatment of acute pain. Anesth Analg 2005; 101 (5 Suppl.): S30-43
19. Cook TM. Combined spinal-epidural techniques. Anaesthesia 2000; 55 (1): 42-64
20. Phillips OC, Ebner H, Nelson AT, et al. Neurologic complications following spinal anesthesia with lidocaine: a prospective review of 10,440 cases. Anesthesiology 1969; 30 (3): 284-9
21. Schneider M, Ettlin T, Kaufmann M, et al. Transient neurologic toxicity after hyperbaric subarachnoid anesthesia with 5% lidocaine. Anesth Analg 1993; 76 (5): 1154-7
22. Pollock JE. Transient neurologic symptoms: etiology, risk factors, and management. Reg Anesth Pain Med 2002; 27 (6): 581-6
23. Pollock JE, Burkhead D, Neal JM, et al. Spinal nerve function in five volunteers experiencing transient neurologic. Anesth Analg 2000; 90 (3): 658-65
24. Zaric D, Christiansen C, Pace NL, et al. Transient neurologic symptoms after spinal anesthesia with lidocaine versus other local anesthetics: a systematic review of randomized, controlled trials. Anesth Analg 2005; 100 (6): 1811-6
25. Pollock JE. Neurotoxicity of intrathecal local anaesthetics and transient neurological symptoms. Best Pract Res Clin Anaesthesiol 2003; 17 (3): 471-84
26. Gaiser R. Should intrathecal lidocaine be used in the 21st century? J Clin Anesth 2000; 12: 476-81
27. Tsen LC, Schultz R, Martin R, et al. Intrathecal low-dose bupivacaine versus lidocaine for in vitro fertilization procedures. Reg Anesth Pain Med 2001; 26 (1): 52-6
28. Beilin Y, Zahn J, Abramovitz S, et al. Subarachnoid small-dose bupivacaine versus lidocaine for cervical cerclage. Anesth Analg 2003; 97 (1): 56-61
29. Buckenmaier III CC, Nielsen KC, Pietrobon R, et al. Small-dose intrathecal lidocaine versus ropivacaine for anorectal surgery in an ambulatory setting. Anesth Analg 2002; 95 (5): 1253-7
30. Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 1979; 51 (4): 285-7
31. Sidebotham DA, Schug SA. Stereochemistry in anaesthesia. Clin Exp Pharmacol Physiol 1997; 24 (2): 126-30
32. Wildsmith JA, Brown DT, Paul D, et al. Structure-activity relationships in differential nerve block at high and low frequency stimulation. Br J Anaesth 1989; 63 (4): 444-52
33. Whiteside JB, Wildsmith JA. Developments in local anaesthetic drugs. Br J Anaesth 2001; 87 (1): 27-35
34. Halpern SH, Walsh V. Epidural ropivacaine versus bupivacaine for labor: a meta-analysis. Anesth Analg 2003; 96 (5): 1473-9
35. Feldman HS, Arthur GR, Covino BG. Comparative systemic toxicity of convulsant and supraconvulsant doses of intravenous ropivacaine, bupivacaine, and lidocaine in the conscious dog. Anesth Analg 1989; 69 (6): 794-801
36. Groban L, Deal DD, Vernon JC, et al. Cardiac resuscitation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine in anesthetized dogs. Anesth Analg 2001; 92 (1): 37-43
37. Scott DB, Lee A, Fagan D, et al. Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 1989; 69 (5): 563-9
38. Knudsen K, Beckman-Suurkula S, Blomberg S, et al. Central nervous and cardiovascular effects of iv infusions of ropivacaine, bupivacaine and placebo in volunteers. Br J Anaesth 1997; 78 (5): 507-14
39. Korman B, Riley R. Convulsions induced by ropivacaine during interscalene brachial plexus block. Anesth Analg 1997; 85 (5): 1128-9
40. Plowman AN, Bolsin S, Mather LE. Central nervous system toxicity attributable to epidural ropivacaine hydrochloride. Anaesth Intensive Care 1998; 26: 204-6
41. Borgeat A, Ruetsch YA, Jorg M. Convulsions induced by ropivacaine during interscalene brachial plexus block [letter]. Anesth Analg 1998; 87 (2): 497
42. Chazalon P, Tourtier JP, Villevielle T, et al. Ropivacaine-induced cardiac arrest after peripheral nerve block: successful resuscitation. Anesthesiology 2003; 99 (6): 1449-51
43. Huet O, Eyrolle LJ, Mazoit JX, et al. Cardiac arrest after injection of ropivacaine for posterior lumbar plexus blockade. Anesthesiology 2003; 99 (6): 1451-3
44. Gielen M, Slappendel R, Jack N. Successful defibrillation immediately after the intravascular injection of ropivacaine. Can J Anaesth 2005; 52 (5): 490-2
45. Soltesz EG, van Pelt F, Byrne JG. Emergent cardiopulmonary bypass for bupivacaine cardiotoxicity. J Cardiothorac Vasc Anesth 2003; 17 (3): 357-8
46. Dernedde M, Furlan D, Verbesselt R, et al. Grand mal convulsion after an accidental intravenous injection of ropivacaine. Anesth Analg 2004; 98 (2): 521-3
47. Pfeiffer G, Bar K, Neubauer P, et al. [Inadvertent intravenous infusion of 380mg ropivacaine]. Anaesthesist 2004; 53 (7): 633-6
48. Polley LS, Santos AC. Cardiac arrest following regional anesthesia with ropivacaine: here we go again! Anesthesiology 2003; 99 (6): 1253-4
49. Kerkkamp HEM, Gielen MJM, Edstrom HH. Comparison of 0.75% ropivacaine with epinephrine and 0.75% bupivacaine with epinephrine in lumbar epidural anesthesia. Reg Anesth 1990; 15: 204-7
50. Brockway MS, Bannister J, McClure JH, et al. Comparison of extradural ropivacaine and bupivacaine. Br J Anaesth 1991; 66: 31-7
51. Douglas MJ, Weeks SB, Writer WD, et al. A double-blind comparison between epidural ropivacaine 0.25% and bupivacaine 0.25% for the relief of childbirth pain: report of multicentre study. Reg Anesth 1994; 19 (2S): 52
52. Owen MD, D'Angelo R, Gerancher JC, et al. 0.125% ropivacaine is similar to 0.125% bupivacaine for labor analgesia using patient-controlled epidural infusion. Anesth Analg 1998; 86: 523-6
53. Whiteside JB, Burke D, Wildsmith JA. Comparison of ropivacaine 0.5% (in glucose 5%) with bupivacaine 0.5% (in glucose 8%) for spinal anaesthesia for elective surgery. Br J Anaesth 2003; 90 (3): 304-8
54. D'Angelo R, James RL. Is ropivacaine less potent than bupivacaine? Anesthesiology 1999; 90 (4): 941-3
55. Polley LS, Columb MO, Naughton NN, et al. Relative analgesic potencies of ropivacaine and bupivacaine for epidural analgesia in labor: implications for therapeutic indexes. Anesthesiology 1999; 90 (4): 944-50
56. Capogna G, Cellono D, Fusco P, et al. Relative potencies of bupivacaine and ropivacaine for analgesia in labour. Br J Anaesth 1999; 82 (3): 371-3
57. Camorcia M, Capogna G, Columb MO. Minimum local analgesic doses of ropivacaine, levobupivacaine, and bupivacaine for intrathecal labor analgesia. Anesthesiology 2005; 102 (3): 646-50
58. Dahm P, Lundborg C, Janson M, et al. Comparison of 0.5% intrathecal bupivacaine with 0.5% intrathecal ropivacaine in the treatment of refractory cancer and noncancer pain conditions: results from a prospective, crossover, double-blind, randomized study. Reg Anesth Pain Med 2000; 25 (5): 480-7
59. Finucane BT. Ropivacaine: a worthy replacement for bupivacaine? Can J Anaesth 1990; 37: 722-5
60. Denson DD, Behbehani MM, Gregg RV. Enantiomer-specific effects of an intravenously administered arrhythmogenic dose of bupivacaine on neurons of the nucleus tractus solitarius and the cardiovascular system in the anesthetized rat. Reg Anesth 1992; 17: 311-6
61. Mather LE, Huang YF, Veering B, et al. Systemic and regional pharmacokinetics of levobupivacaine and bupivacaine enantiomers in sheep. Anesth Analg 1998; 86 (4): 805-11
62. Huang YF, Pryor ME, Mather LE, et al. Cardiovascular and central nervous system effects of intravenous levobupivacaine and bupivacaine in sheep. Anesth Analg 1998; 86 (4): 797-804
63. Stewart J, Kellett N, Castro D. The central nervous system and cardiovascular effects of levobupivacaine and ropivacaine in healthy volunteers. Anesth Analg 2003; 97 (2): 412-6
64. Bardsley H, Gristwood R, Baker H, et al. A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine following intravenous administration to healthy volunteers. Br J Clin Pharmacol 1998; 46 (3): 245-9
65. McLeod GA, Burke D. Levobupivacaine. Anaesthesia 2001; 56 (4): 331-41
66. Rosenberg PH, Schug SA. Levobupivacaine base and levobupivacaine hydrochloride. Br J Anaesth 2005; 94 (4): 544
67. Breslin DS, Martin G, Macleod DB, et al. Central nervous system toxicity following the administration of levobupivacaine for lumbar plexus block: a report of two cases. Reg Anesth Pain Med 2003; 28 (2): 144-7
68. Crews JC, Rothman TE. Seizure after levobupivacaine for interscalene brachial plexus block. Anesth Analg 2003; 96 (4): 1188-90
69. Cox CR, Faccenda KA, Gilhooly C, et al. Extradural S (-)-bupivacaine: comparison with racemic RS-bupivacaine. Br J Anaesth 1998; 80: 289-93
70. Breschan C, Jost R, Krumpholz R, et al. A prospective study comparing the analgesic efficacy of levobupivacaine, ropivacaine and bupivacaine in pediatric patients undergoing caudal blockade. Paediatr Anaesth 2005; 15 (4): 301-6
71. De Negri P, Ivani G, Tirri T, et al. A comparison of epidural bupivacaine, levobupivacaine, and ropivacaine on postoperative analgesia and motor blockade. Anesth Analg 2004; 99 (1): 45-8
72. Lyons G, Columb M, Wilson RC, et al. Epidural pain relief in labour: potencies of levobupivacaine and racemic bupivacaine. Br J Anaesth 1998; 81 (6): 899-901
73. Lacassie HJ, Columb MO. The relative motor blocking potencies of bupivacaine and levobupivacaine in labor. Anesth Analg 2003; 97 (5): 1509-13
74. Ummenhofer WC, Arends RH, Shen DD, et al. Comparative spinal distribution and clearance kinetics of intrathecally administered morphine, fentanyl, alfentanil, and sufentanil. Anesthesiology 2000; 92 (3): 739-53
75. Bernards CM. Understanding the physiology and pharmacology of epidural and intrathecal opioids. Best Pract Res Clin Anaesthesiol 2002; 16 (4): 489-505
76. Bernards CM, Shen DD, Sterling ES, et al. Epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidural opiods (part 1): differences among opiods. Anesthesiology 2003; 99 (2): 455-65
77. Bernards CM, Shen DD, Sterling ES, et al. Epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidural opiods (part 2): effect of epinephrine. Anesthesiology 2003; 99 (2): 466-72
78. Wheatley RG, Schug SA, Watson D. Safety and efficacy of postoperative epidural analgesia. Br J Anaesth 2001; 87 (1): 47-61
79. Dahl JB, Jeppesen IS, Jorgensen H, et al. Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients undergoing cesarean section with spinal anesthesia: a qualitative and quantitative systematic review of randomized controlled trials. Anesthesiology 1999; 91 (6): 1919-27
80. Viscusi ER, Martin G, Hartrick CT, et al. Forty-eight hours of postoperative pain relief after total hip arthroplasty with a novel, extended-release epidural morphine formulation. Anesthesiology 2005; 102 (5): 1014-22
81. Shapiro A, Zohar E, Zaslansky R, et al. The frequency and timing of respiratory depression in 1524 postoperative patients treated with systemic or neuraxial morphine. J Clin Anesth 2005; 17 (7): 537-42
82. Nguyen Thi TV, Orliaguet G, Ngû TH, et al. Spinal anesthesia with meperidine as the sole agent for cesarean delivery. Reg Anesth 1994; 19 (6): 386-9
83. Ngan Kee WD. Epidural pethidine: pharmacology and clinical experience. Anaesth Intensive Care 1998; 26 (3): 247-55
84. Ngan Kee WD. Intrathecal pethidine: pharmacology and clinical applications. Anaesth Intensive Care 1998; 26 (2): 137-46
85. Paech MJ, Moore JS, Evans SF. Meperidine for patient-controlled analgesia after cesarean section. Intravenous versus epidural administration. Anesthesiology 1994; 80 (6): 1268-76
86. Hamber EA, Viscomi CM. Intrathecal lipophilic opioids as adjuncts to surgical spinal anesthesia. Reg Anesth Pain Med 1999; 24 (3): 255-63
87. Polley L, Columb M, Naughton N, et al. Effect of intravenous versus epidural fentanyl on the minimum local analgesic concentration of epidural bupivacaine in labor. Anesthesiology 2000; 93: 122-8
88. Schug SA, Buerkle H, Moharib M, et al. New drugs for neuraxial blockade. Curr Opin Anaesthesiol 1999; 12 (5): 551-7
89. Fournier R, Gamulin Z, Van Gessel E. Respiratory depression after 5 micrograms of intrathecal sufentanil. Anesth Analg 1998; 87 (6): 1377-8
90. Twycross RG. Choice of strong analgesic in terminal cancer: diamorphine or morphine? Pain 1977; 3 (2): 93-104
91. Vaughan DJ, Ahmad N, Lillywhite NK, et al. Choice of opioid for initiation of combined spinal epidural analgesia in labour: fentanyl or diamorphine. Br J Anaesth 2001; 86 (4): 567-9
92. Husaini SW, Russell IF. Intrathecal diamorphine compared with morphine for postoperative analgesia after caeserian section under spinal anaesthesia. Br J Anaesth 1998; 81: 135-9
93. Chaney MA. Side effects of intrathecal and epidural opioids. Can J Anaesth 1995; 42 (10): 891-903
94. Bailey PL, Lu JK, Pace NL, et al. Effects of intrathecal morphine on the ventilatory response to hypoxia. N Engl J Med 2000; 343 (17): 1228-34
95. Tsui BC, Wagner A, Finucane B. Regional anaesthesia in the elderly: a clinical guide. Drugs Aging 2004; 21 (14): 895-910
96. Szarvas S, Harmon D, Murphy D. Neuraxial opioid-induced pruritus: a review. J Clin Anesth 2003; 15 (3): 234-9
97. Jeon Y, Hwang J, Kang J, et al. Effects of epidural naloxone on pruritus induced by epidural morphine: a randomized controlled trial. Int J Obstet Anesth 2005; 14 (1): 22-5
98. Iatrou CA, Dragoumanis CK, Vogiatzaki TD, et al. Prophylactic intravenous ondansetron and dolasetron in intrathecal morphine-induced pruritus: a randomized, double-blinded, placebo-controlled study. Anesth Analg 2005; 101 (5): 1516-20
99. Davies PW, Vallejo MC, Shannon KT, et al. Oral herpes simplex reactivation after intrathecal morphine: a prospective randomized trial in an obstetric population. Anesth Analg 2005; 100 (5): 1472-6
100. De Kock M, Crochet B, Morimont C, et al. Intravenous or epidural clonidine for intra- and postoperative analgesia. Anesthesiology 1993; 79 (3): 525-31
101. Tamsen A, Gordh T. Clonidine is not neurotoxic. Lancet 1984; II (8407): 876
102. Tamsen A, Gordh T. Epidural clonidine produces analgesia. Lancet 1984; II (8396): 231-2
103. Eisenach JC, De Kock M, Klimscha W. alpha (2)-adrenergic agonists for regional anesthesia: a clinical review of clonidine (1984-1995). Anesthesiology 1996; 85 (3): 655-74
104. Filos KS, Goudas LC, Patroni O, et al. Hemodynamic and analgesic profile after intrathecal clonidine in humans: a dose-response study. Anesthesiology 1994; 81 (3): 591-601
105. Dobrydnjov I, Axelsson K, Gupta A, et al. Improved analgesia with clonidine when added to local anesthetic during combined spinal-epidural anesthesia for hip arthroplasty: a double-blind, randomized and placebo-controlled study. Acta Anaesthesiol Scand 2005; 49 (4): 538-45
106. Paech MJ, Banks SL, Gurrin LC, et al. A randomized, double-blinded trial of subarachnoid bupivacaine and fentanyl, with or without clonidine, for combined spinal/epidural analgesia during labor. Anesth Analg 2002; 95 (5): 1396-401
107. Paech MJ, Pavy TJ, Orlikowski CE, et al. Postcesarean analgesia with spinal morphine, clonidine, or their combination. Anesth Analg 2004; 98 (5): 1460-6
108. Paech MJ, Pavy TJ, Orlikowski CE, et al. Postoperative epidural infusion: a randomized, double-blind, dose-finding trial of clonidine in combination with bupivacaine and fentanyl. Anesth Analg 1997; 84 (6): 1323-8
109. Walker SM, Goudas LC, Cousins MJ, et al. Combination spinal analgesic chemotherapy: a systematic review. Anesth Analg 2002; 95 (3): 674-715
110. Bailey PL, Sperry RJ, Johnson GK, et al. Respiratory effects of clonidine alone and combined with morphine, in humans. Anesthesiology 1991; 74 (1): 43-8
111. Uhle EI, Becker R, Gatscher S, et al. Continuous intrathecal clonidine administration for the treatment of neuropathic pain. Stereotact Funct Neurosurg 2000; 75 (4): 167-75
112. Ansermino M, Basu R, Vandebeek C, et al. Nonopioid additives to local anaesthetics for caudal blockade in children: a systematic review. Paediatr Anaesth 2003; 13 (7): 561-73
113. Paech MJ, Pavy TJ, Orlikowski CE, et al. Patient-controlled epidural analgesia in labor: the addition of clonidine to bupivacaine-fentanyl. Reg Anesth Pain Med 2000; 25 (1): 34-40
114. Martin E, Ramsay G, Mantz J, et al. The role of the alpha2-adrenoceptor agonist dexmedetomidine in postsurgical sedation in the intensive care unit. J Intensive Care Med 2003; 18 (1): 29-41
115. Fisher B, Zornow MH, Yaksh TL, et al. Antinociceptive properties of intrathecal dexmedetomidine in rats. Eur J Pharmacol 1991; 192 (2): 221-5
116. Kalso EA, Poyhia R, Rosenberg PH. Spinal antinociception by dexmedetomidine, a highly selective alpha 2-adrenergic agonist. Pharmacol Toxicol 1991; 68 (2): 140-3
117. Eisenach JC, Shafer SL, Bucklin BA, et al. Pharmacokinetics and pharmacodynamics of intraspinal dexmedetomidine in sheep. Anesthesiology 1994; 80 (6): 1349-59
118. Calasans-Maia JA, Zapata-Sudo G, Sudo RT. Dexmedetomidine prolongs spinal anaesthesia induced by levobupivacaine 0.5% in guinea-pigs. J Pharm Pharmacol 2005; 57 (11): 1415-20
119. Kanazi GE, Aouad MT, Jabbour-Khoury SI, et al. Effect of low-dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block. Acta Anaesthesiol Scand 2006; 50 (2): 222-7
120. Niemi G. Advantages and disadvantages of adrenaline in regional anaesthesia. Best Pract Res Clin Anaesthesiol 2005; 19 (2): 229-45
121. Kito K, Kato H, Shibata M, et al. The effect of varied doses of epinephrine on duration of lidocaine spinal anesthesia in the thoracic and lumbosacral dermatomes. Anesth Analg 1998; 86: 1018-22
122. Niemi G, Breivik H. Epinephrine markedly improves thoracic epidural analgesia produced by a small-dose infusion of ropivacaine, fentanyl, and epinephrine after major thoracic or abdominal surgery: a randomized, double-blinded crossover study with and without epinephrine. Anesth Analg 2002; 94 (6): 1598-605
123. Niemi G, Breivik H. The minimally effective concentration of adrenaline in a low-concentration thoracic epidural analgesic infusion of bupivacaine, fentanyl and adrenaline after major surgery: a randomized, double-blind, dose-finding study. Acta Anaesthesiol Scand 2003; 47 (4): 439-50
124. Kozody R, Palahniuk RJ, Wade JG, et al. The effect of subarachnoid epinephrine and phenylephrine on spinal cord blood flow. Can Anaesth Soc J 1984; 31 (5): 503-8
125. Kathirvel S, Sadhasivam S, Saxena A, et al. Effects of intrathecal ketamine added to bupivacaine for spinal anaesthesia. Anaesthesia 2000; 55: 899-904
126. Subramaniam K, Subramaniam B, Steinbrook RA. Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic review. Anesth Analg 2004; 99 (2): 482-95
127. Eisenach JC. Muscarinic-mediated analgesia. Life Sci 1999; 64 (6-7): 549-54
128. Lauretti GR, Hood DD, Eisenach JC, et al. A multi-center study of intrathecal neostigmine for analgesia following vaginal hysterectomy. Anesthesiology 1998; 89 (4): 913-8
129. Omais M, Lauretti GR, Paccola CA. Epidural morphine and neostigmine for postoperative analgesia after orthopedic surgery. Anesth Analg 2002; 95 (6): 1698-701
130. Lauretti GR, de Oliveira R, Reis MP, et al. Study of three different doses of epidural neostigmine coadministered with lidocaine for postoperative analgesia. Anesthesiology 1999; 90 (6): 1534-8
131. Roelants F, Lavand'homme PM, Mercier-Fuzier V. Epidural administration of neostigmine and clonidine to induce labor analgesia: evaluation of efficacy and local anesthetic-sparing effect. Anesthesiology 2005; 102 (6): 1205-10
132. Roelants F, Lavand'homme PM. Epidural neostigmine combined with sufentanil provides balanced and selective analgesia in early labor. Anesthesiology 2004; 101 (2): 439-44
133. Roelants F, Rizzo M, Lavand'homme P. The effect of epidural neostigmine combined with ropivacaine and sufentanil on neuraxial analgesia during labor. Anesth Analg 2003; 96 (4): 1161-6
134. Kohno T, Wakai A, Ataka T, et al. Actions of midazolam on excitatory transmission in dorsal horn neurons of adult rat spinal cord. Anesthesiology 2006; 104 (2): 338-43
135. Yaksh TL, Allen JW. Preclinical insights into the implementation of intrathecal midazolam: a cautionary tale. Anesth Analg 2004; 98 (6): 1509-11
136. Yanez A, Sabbe MB, Stevens CW, et al. Interaction of midazolam and morphine in the spinal cord of the rat. Neuropharmacology 1990; 29 (4): 359-64
137. Tucker AP, Mezzatesta J, Nadeson R, et al. Intrathecal midazolam II: combination with intrathecal fentanyl for labor pain. Anesth Analg 2004; 98 (6): 1521-7
138. Sawynok J, Sweeney MI. The role of purines in nociception. Neuroscience 1989; 32 (3): 557-69
139. Poon A, Sawynok J. Antinociception by adenosine analogs and inhibitors of adenosine metabolism in an inflammatory thermal hyperalgesia model in the rat. Pain 1998; 74 (2-3): 235-45
140. Gomes JA, Li X, Pan HL, et al. Intrathecal adenosine interacts with a spinal noradrenergic system to produce antinociception in nerve-injured rats. Anesthesiology 1999; 91 (4): 1072-9
141. Eisenach JC, Hood DD, Curry R. Phase I safety assessment of intrathecal injection of an American formulation of adenosine in humans. Anesthesiology 2002; 96 (1): 24-8
142. Rane K, Segerdahl M, Goiny M, et al. Intrathecal adenosine administration: a phase 1 clinical safety study in healthy volunteers, with additional evaluation of its influence on sensory thresholds and experimental pain. Anesthesiology 1998; 89 (5): 1108-15
143. Eisenach JC, Curry R, Hood DD. Dose response of intrathecal adenosine in experimental pain and allodynia. Anesthesiology 2002; 97 (4): 938-42
144. Rane K, Sollevi A, Segerdahl M. Intrathecal adenosine administration in abdominal hysterectomy lacks analgesic effect. Acta Anaesthesiol Scand 2000; 44 (7): 868-72
145. Rane K, Sollevi A, Segerdahl M. A randomised double-blind evaluation of adenosine as adjunct to sufentanil in spinal labour analgesia. Acta Anaesthesiol Scand 2003; 47 (5): 601-3
146. Bowersox SS, Gadbois T, Singh T, et al. Selective N-type neuronal voltage-sensitive calcium channel blocker, SNX-111, produces spinal antinociception in rat models of acute, persistent and neuropathic pain. J Pharmacol Exp Ther 1996; 279 (3): 1243-9
147. Brose WG, Gutlove DP, Luther RR, et al. Use of intrathecal SNX-111, a novel, N-type, voltage-sensitive, calcium channel blocker, in the management of intractable brachial plexus avulsion pain. Clin J Pain 1997; 13 (3): 256-9
148. Penn RD, Paice JA. Adverse effects associated with the intrathecal administration of ziconotide. Pain 2000; 85 (1-2): 291-6
149. Atanassoff PG, Hartmannsgruber MW, Thrasher J, et al. Ziconotide, a new N-type calcium channel blocker, administered intrathecally for acute postoperative pain. Reg Anesth Pain Med 2000; 25 (3): 274-8
150. Wermeling D, Drass M, Ellis D, et al. Pharmacokinetics and pharmacodynamics of intrathecal ziconotide in chronic pain patients. J Clin Pharmacol 2003; 43 (6): 624-36
151. Staats PS, Yearwood T, Charapata SG, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA 2004; 291 (1): 63-70
152. Wermeling DP. Ziconotide, an intrathecally administered N-type calcium channel antagonist for the treatment of chronic pain. Pharmacotherapy 2005; 25 (8): 1084-94
153. Ochs GA. Intrathecal baclofen. Baillieres Clin Neurol 1993; 2 (1): 73-86
154. Slonimski M, Abram SE, Zuniga RE. Intrathecal baclofen in pain management. Reg Anesth Pain Med 2004; 29 (3): 269-76
155. Hsieh JC, Penn RD. Intrathecal baclofen in the treatment of adult spasticity. Neurosurg Focus 2006; 21 (2): E5
156. Herman RM, D'Luzansky SC, Ippolito R. Intrathecal baclofen suppresses central pain in patients with spinal lesions: a pilot study. Clin J Pain 1992; 8 (4): 338-45
157. Loubser PG, Akman NM. Effects of intrathecal baclofen on chronic spinal cord injury pain. J Pain Symptom Manage 1996; 12 (4): 241-7