Skip to main content
SpringerLink
Log in

Epidural Clonidine

A Review of its Pharmacology and Efficacy in the Management of Pain During Labour and Postoperative and Intractable Pain

  • Drug Evaluation
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

Synopsis

Clonidine is an established α2 adrenoceptor agonist with antihypertensive properties which, when administered epidurally, has an analgesic action that is largely mediated by α2 adrenoceptors in the dorsal horn of the spinal cord. After epidural administration, the drug undergoes rapid systemic absorption and is able to pass through the placenta.

Datafrom clinical studies evaluating the efficacy of epidural clonidine indicate that it is a useful adjunct to opioid and/or local anaesthetic agents for postoperative analgesia after major abdominal or orthopaedic surgery or after caesarean section. Epidural clonidine has also proved to be an effective analgesic that enhances the duration of action of local anaesthetic agents during labour without neonatal adverse effects. Continuous infusions of epidural clonidine are effective in patients with cancer pain of neuropathic origin. Similarly, the utility of this agent appears to extend to patients with chronic non-cancer pain.

At doses producing the desired analgesic effects, sedation, bradycardia and hypotension are the most common adverse events associated with epidural clonidine. There has been a single report of rebound hypertension after abrupt cessation of epidural clonidine.

In conclusion, the available data suggest a role for epidural clonidine as an adjunctive agent for the control of pain (of postoperative, malignant or nonmalignant origin and during labour). In particular, it may be useful in patients unsatisfied with opioid or local anaesthetic agents or in those tolerant to opioids. However, the place of epidural clonidine as an alternative or adjunctive analgesic agent in any given patient group is likely to depend on the acceptability of the epidural route of administration and haemodynamic and sedative effects of the drug.

Pharmacodynamic Properties

The analgesic effects of spinally administered α2 adrenoceptor agonists are believed to be mediated by α2 adrenoceptors in the dorsal hom of the spinal cord. Amelioration of foot, but not hand, pain caused by immersion in iced water in healthy volunteers after epidural administration of clonidine indicated a spinal mechanism of action for the analgesic effect of the drug.

Decreases in mean arterial pressure and heart rate (HR) and ventilatory changes have been reported in healthy volunteers and surgical patients after epidural administration of clonidine. Such cardiovascular effects are generally evident within 15 to 30 minutes of epidural injection of clonidine and last for up to 3 hours. Changes in blood pressure (BP) appear to be dose-dependent.

Pharmacokinetic Properties

Clonidine is moderately lipid soluble, with a large apparent steady-state volume of distribution (approximately 2 L/kg) after intravenous administration. The drug is 20 to 40% bound to plasma proteins and is excreted predominantly via renal mechanisms.

Clonidine appears to be absorbed rapidly into the systemic circulation after epidural administration, with peak plasma drug concentrations being reached 8 to 15 minutes after administration. Peak concentrations in CSF were attained more slowly (after approximately 30 to 45 minutes) but were up to 362 times greater than those in plasma.

The pharmacokinetics of single dose epidural clonidine have been described by a first-order 2−compartment model, with short absorption half-lives in CSF and plasma followed by longer elimination phases in both fluids.

Placental transfer of clonidine has been demonstrated after epidural administration. At delivery, the mean maternal plasma concentration of clonidine was 0.62 ng/L, compared with 0.56 ng/L in umbilical cord plasma, after a cumulative dose of l50µg.

Therapeutic Efficacy

In patients with postoperative pain after major abdominal or orthopaedic surgery or caesarean section, epidural clonidine adjunctive to opioids or local anaesthetic agents provided effective and prolonged analgesia with a consequent decreased requirement for supplemental analgesia. The overall postoperative analgesic effect obtained with combinations involving clonidine was at least as good as that seen with opioids or local anaesthetic agents used alone or in combination.

Epidural clonidine administered as an adjunct to local anaesthetics during labour provided effective analgesia that was superior to and of longer duration than that seen with the latter agents alone. Limited data indicate that combinations of epidural clonidine and opioids have similar efficacy to combinations of local anaesthetics and opioids when a single dose is given. However, efficacy appears to be partially lost when subsequent doses of epidurally administered mixtures of clonidine and opioids are used. The use of epidural clonidine during labour did not worsen neonatal Apgar or adaptive capacity scores.

A continuous infusion of epidural clonidine provided effective analgesia in clinical studies in patients with intractable cancer pain, with a consequent decrease in supplemental opioid requirements. Efficacy was notably better in patients with neuropathic pain than in those with non-neuropathic pain. Likewise, limited data indicate that, in patients with chronic non-cancer pain, epidural clonidine provides analgesia at least as good as that seen with epidural morphine.

Tolerability

At clinically effective doses, sedation, hypotension and bradycardia are the main adverse effects of epidural clonidine. In general, clonidine did not intensify decreases in either BP or HR when combined with opioids and/or local anaesthetics. Rebound hypertension has been reported in a single patient after abrupt cessation of epidural clonidine.

Epidural clonidine, unlike local anaesthetic agents, did not interfere with proprioception or produce motor blockade. Unlike epidural opioid agents, clonidine did not produce respiratory depression or worsen the risk of urinary retention, nausea, vomiting or pruritus when administered concomitantly with these agents.

Dosage and Administration

In general, bolus doses of epidural clonidine 75 to 150µg administered concurrently with opioid or local anaesthetic agents have been shown to provide analgesia at least as good as that achieved with the opioids or local anaesthetic agents alone. Dosage regimens comprising a bolus dose followed by continuous infusion appear to be particularly well suited for analgesia during labour and postoperative analgesia.

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

  1. Maze M. Tranquilli W. Alpha−2 adrenoceptor agonists: defining the role in clinical anesthesia. Anesthesiology 1991; 74: 581–605

    Article  PubMed  CAS  Google Scholar 

  2. Eisenach J, Detweiler D, Hood D. Hemodynamic and analgesic actions of epidurally administered clonidine. Anesthesiology1993 Feb; 78: 277–87

    Article  PubMed  CAS  Google Scholar 

  3. Kulkarni SK. Verma A. Clonidine analgesia. Drugs Today 1994 Apr—May; 30: 211–9

    Google Scholar 

  4. Yaksh TL, Howe JR, Harty GJ. Pharmacology of spinal pain modulatory systems. Adv Pain Res Ther 1984; 7: 57–70

    Google Scholar 

  5. Eisenach Je. Overview: first international symposium on α2— Adrenergic Mechanisms of Spinal Anesthesia. Reg Anesth1993; 18: 1–6

    Google Scholar 

  6. Lawhead RG, Blaxall HS, Bylund DB. α—2A is the predominant α—2 adrenergic receptor subtype in human spinal cord. Anesthesiology1992; 77: 983–91

    Article  PubMed  CAS  Google Scholar 

  7. Unnerstall JR. Kopajtic TA. Kuhar MJ. Distribution of ao agonist binding sites in the rat and human central nervous system:analysis of some functional, anatomic correlates of the pharmacologiceffects of clonidine and related adrenergic agents.Brain Res Rev 1984 Mar; 319: 69–101

    Article  CAS  Google Scholar 

  8. Atlas D. Clonidine—displacing substance (CDS) and its putative imidazoline receptor. New leads for further divergence of α2—adrenergic receptor activity. Biochem Pharmacol 1991 Jun I;41: 1541–9

    Article  PubMed  CAS  Google Scholar 

  9. Atlas D, Diamant S, Zonnenschein R. Is imidazoline site a unique receptor? A correlation with clonidine—displacing substanceactivity. Am J Hypertens 1992 Apr; 5 (4 Pt 2): 83S–90S

    PubMed  CAS  Google Scholar 

  10. Reis DJ, Regunathan S, Meeley MP. Imidazole receptors and clonidine—displacing substance in relationship to control ofblood pressure, neuroprotection, and adrenomedullary secretion.Am J Hypertens 1992 Apr; 5 (4 Pt 2): 51S–7S

    PubMed  CAS  Google Scholar 

  11. Glynn CJ, Jamous MA, Teddy PJ, et al. Role of spinal noradrenergic system in transmission of pain in patients withspinal cord injury. Lancet 1986 Nov 29; II: 1249–50

    Article  Google Scholar 

  12. Eisenach Je. De Kock M, Klimscha W. α2—Adrenergic agonists for regional anesthesia: a clinical review of clonidine (1984-1995). Anesthesiology 1996 Sep; 85 (3): 655–74

    Article  PubMed  CAS  Google Scholar 

  13. Lund C, Hansen OB, Kehlet H. Effect of epidural clonidine on somatosensory evoked potentials to dermatomal stimulation.Eur J Anaesthesiol 1989 May; 6: 207–13

    PubMed  CAS  Google Scholar 

  14. De-Kock M, Martin N, Scholtes JL. Central effects of epidural and intravenous clonidine in patients anesthetized with enflurane/nitrous oxide. An electroencephalographic analysis.Anesthesiology 1992 Sep; 77: 457–62

    Article  PubMed  Google Scholar 

  15. Penon C, Ecoffey C, Cohen SE. Ventilatory response to carbon dioxide after epidural clonidine injection. Anesth Analg 1991Jun; 72: 761–4

    Article  PubMed  CAS  Google Scholar 

  16. Narchi P, Benhamou D, Hamza J, et al. Ventilatory effects of epidural clonidine during the first three hours after caesareansection. Acta Anaesthesiol Scand 1992 Nov; 36: 791–5

    Article  PubMed  CAS  Google Scholar 

  17. Carabine U, Milligan K, Moore J. The systemic effects of epidural clonidine and bupivacaine [abstract]. Anesthesiology1991 Sep; 75 Suppl.: A661

    Article  Google Scholar 

  18. Lund C, Qvitzau S, Greulich A, et al. Comparison of the effects of extradural clonidine with those of morphine on postoperativepain, stress responses, cardiopulmonary function andmotor and sensory block. Br J Anaesth 1989 Nov; 63: 516–9

    Article  PubMed  CAS  Google Scholar 

  19. Rockemann MG, Goertz A, Seeling W, et al. Epidural clonidine causes hemodynamic instability mainly by reduction of heartrate and cardiac output [abstract]. Anesthesiology 1993; 79Suppl. 3A: A808

    Google Scholar 

  20. Rockemann MG, Seeling W, Brinkmann A, et al. Analgesic and hemodynamic effects of epidural clonidine, clonidine/morphine,and morphine after pancreatic surgery — a double—blindstudy. Anesth Analg 1995 May; 80: 869–74

    PubMed  CAS  Google Scholar 

  21. Carroll D, Jadad A, King V, et al. Single—dose, randomized, double—blind, double—dummy cross—over comparison of extraduraland i.v. clonidine in chronic pain. Br J Anaesth 1993Nov; 71: 665–9

    Article  PubMed  CAS  Google Scholar 

  22. Glynn C, Dawson D, Sanders R. A double—blind comparison between epidural morphine and epidural clonidine in patientswith chronic non—cancer pain. Pain 1988 Aug; 34: 123–8

    Article  PubMed  CAS  Google Scholar 

  23. Bernard J-M, Kick 0, Bonnet F. Comparison of intravenous and epidural clonidine for postoperative patient—controlled analgesia.Anesth Analg 1995; 81: 706–12

    PubMed  CAS  Google Scholar 

  24. Bonnet F, Boico 0, Rostaing S, et at. Clonidine—induced analgesia in postoperative patients: epidural versus intramuscularadministration. Anesthesiology 1990 Mar; 72 (3): 423–7

    Article  PubMed  CAS  Google Scholar 

  25. Rauck RL, Eisenach JC, Jackson K, et at. Epidural clonidine treatment for refractory reflex sympathetic dystrophy. Anesthesiology1993 Dec; 79 (6): 1163–9

    Article  PubMed  CAS  Google Scholar 

  26. Bonnet F, Boico 0, Rostaing S, et al. Postoperative analgesia with extradural clonidine. Br J Anaesth 1989 Oct; 63: 465–9

    Article  PubMed  CAS  Google Scholar 

  27. Eisenach JC, Rauck RL, Buzzanell C, et al. Epidural clonidine analgesia for intractable cancer pain: phase I. Anesthesiology1989 Nov; 71 (5): 647–52

    Article  PubMed  CAS  Google Scholar 

  28. Cigarini I, Kaba A, Bonnet F, et al. Epidural clonidine combined with bupivacaine for analgesia in labor: effects on mother andneonate. Reg Anesth 1995 Mar—Apr; 20 (2): 113–20

    Google Scholar 

  29. Eisenach JC, D’Angelo R, Taylor C, et al. An isobolographic study of epidural clonidine and fentanyl after cesarean section. Anesth Analg 1994 Aug; 79: 285–90

    Google Scholar 

  30. van Essen EJ, Bovill JG, Ploeger EJ. Extradural clonidine does not potentiate analgesia produced by extradural morphine aftermeniscectomy. Br J Anaesth 1991 Feb; 66: 237–41

    Google Scholar 

  31. Eisenach JC, DuPen S, Dubois M, et al. Epidural clonidine analgesia for intractable cancer pain. Pain 1995; 61: 391–9

    Article  PubMed  CAS  Google Scholar 

  32. Motsch J, Graber E, Ludwig K. Addition of clonidine enhances postoperative analgesia from epidural morphine: a doubleblindstudy. Anesthesiology 1990 Dec; 73 (6): 1067–73

    Article  PubMed  CAS  Google Scholar 

  33. Murga G, Samso E, Valles J, et al. The effect of clonidine on intraoperative requirements of fentanyl during combined epidural/general anaesthesia. Anaesthesia 1994; 49: 999–1002

    Article  PubMed  CAS  Google Scholar 

  34. Kirnö K, Lundin S, Elam M. Epidural clonidine depresses sympathetic nerve activity in humans by a supraspinal mechanism.Anesthesiology 1993 Jun; 78: 1021–7

    Article  PubMed  Google Scholar 

  35. Spiegel R, Devos JE. Central effects of guanfacine and clonidine during wakefulness and sleep in healthy subjects. Br J Clin Pharmacol 1980; 10 Suppl. 1: 165S–8S

    Article  Google Scholar 

  36. Lowenthal DT, Matzek KM, MacGregor TR. Clinical pharmacokinetics of clonidine. Clin Pharmacokinet 1988 May; 14 (5): 287–310

    Google Scholar 

  37. Eisenach JC, Hood DD, Tuttle R, et al. Computer—controlled epidural infusion to targeted cerebrospinal fluid concentrationsin humans: clonidine. Anesthesiology 1995 Jul; 83: 33–47

    Google Scholar 

  38. Glynn CJ, Jamous MA, Teddy PJ. Cerebrospinal fluid kinetics of epidural clonidine in man. Pain 1992 Jun; 49: 361–7

    Google Scholar 

  39. van Essen EJ, Bovill JG, Ploeger EJ, et al. Pharmacokinetics of clonidine after epidural administration in surgical patients.Lack of correlation between plasma concentration and analgesiaand blood pressure changes. Acta Anaesthesiol Scand1992 May; 36: 300–4

    Google Scholar 

  40. Hartikainen-Sorri A-L, Heikkinen JE, Koivisto M. Pharmacokinetics of clonidine during pregnancy and nursing. Obstet Gynecol 1987 Apr; 69: 598–600

    Google Scholar 

  41. Fukushima K, Nishimi Y, Miwa Y, et al. Effects of epidurally administered clonidine and dexmedetomidine on MAC ofisoflurane in man [abstract]. Anesth Analg 1995 Feb; 80Suppl.: SI38

    Google Scholar 

  42. Fukushima K, Nishimi Y, Yonemura E, et al. Comparative effects of epidurally administered clonidine and buprenorphineon MAC and EEG in man [abstract]. Anesth Analg 1994 Feb;78 Suppl.: S 123

    Google Scholar 

  43. Samsó E, Murga G, Vallès J, et al. Effects of epidural clonidine on anaesthetic requirements and postoperative analgesia [abstractno. A.205]. Br J Anaesth 1993 May; 70 Suppl. I: 06

    Google Scholar 

  44. Vallès J, Sams6 E, Vilar X, et al. Intraoperative requirements of isof]uranc after the administration of intramuscular or epi~dural clonidine [abstract no. A.1581. Br J Anaesth 1994 Feb; 72 Suppl. 1: 82

    Google Scholar 

  45. Mazoit JX, Benhamou D, Veillette Y, et al. Clonidine and or adrenaline decrease lignocaine plasma peak concentration afterepidural injection. Br J Clin Pharmacol 1996; 42: 242–5

    Article  PubMed  CAS  Google Scholar 

  46. Mogensen T, Eliasen K, Ejlersen E, et al. Epidural clonidine enhances postoperative analgesia from a combined low—doseepidural bupivacaine and morphine regimen. Anesth Analg 1992 Oct; 75: 607–10

    Google Scholar 

  47. Carabine VA, Milligan KR, Moore J. Extradural clonidine and bupivacaine for postoperative analgesia. Br J Anaesth 1992 Feb; 68: 132–5

    Google Scholar 

  48. Carabine VA, Milligan KR, Mulholland D, et al. Extradural clonidine infusions for analgesia after total hip replacement.Br J Anaesth 1992 Apr; 68: 338–43

    Google Scholar 

  49. Le Polain B, De Kock M, Scholtes JL, et al. Clonidine combined with sufentanil and bupivacaine with adrenaline for obstetricanalgesia. Br J Anaesth 1993 Nov; 71: 657–60

    Google Scholar 

  50. Huntoon M, Eisenach JC, Boese P. Epidural clonidine after cesarean section: appropriate dose and effect of prior local anesthetic.Anesthesiology 1992 Feb; 76 (2): 187–93

    Google Scholar 

  51. Mendez R, Eisenach JC, Kashtan K. Epidural clonidine analgesia after cesarean section. Anesthesiology 1990 Nov; 73 (5):848–52

    Google Scholar 

  52. Vercauteren MP, Vandeput DM, Meert TF, et al. Patient—controlled epidural analgesia with sufentanil following Caesareansection: the effect of adrenaline and clonidine admixture. Anaesthesia 1994 Sep; 49: 767–71

    Google Scholar 

  53. Chiari A, Redl G, Menth W, et al. Analgesic effects of epidural ketamine and clonidine for postoperative pain relief [abstractno. A.240]. Br J Anaesth 1994 Feb; 72 Suppl. I: 124

    Google Scholar 

  54. Vercauteren M, Lauwers E, Meert T, et al. Comparison of epidural sufentanil plus clonidine with sufentanil alone for postoperativepain relief. Anaesthesia 1990 Jul; 45: 531–4

    Google Scholar 

  55. Buggy DJ, MacDowell C. Extradural analgesia with clonidine and fentanyl compared with 0.25% bupivacaine in the firststage of labour. Br J Anaesth 1996; 76: 319–21

    Article  PubMed  CAS  Google Scholar 

  56. Anzai Y, Nishikawa T. Thoracic epidural clonidine and morphine for postoperative pain relief. Can J Anaesth 1995 Apr; 42 (4): 292–7

    Google Scholar 

  57. Delaunay L, Leppert C, Dechaubry V, et al. Epidural clonidine decreases postoperative requirements for epidural fentanyl.Reg Anesth 1993 May—Jun; 18: 176–80

    Google Scholar 

  58. Gordh Jr T. Epidural clonidine for treatment of postoperative pain after thoracotomy: a double—blind placebo—controlledstudy. Acta Anaesthesiol Scand 1988 Nov; 32: 702–9

    Google Scholar 

  59. van Essen EJ, Bovill JG, Ploeger EJ, et al. A comparison of epidural clonidine and morphine for post—operative analgesia. Eur J Anaesthesiol 1990 May; 7: 211–8

    Google Scholar 

  60. De Kock M, Crochet B, Morimont C, et al. Intravenons or epidural clonidine for intra— and postoperative analgesia. Anesthesiology 1993 Sep; 79 (3): 525–31

    Google Scholar 

  61. Dohrydnjov I, Samariitel J. Epidural morphine—clonidine vs morphine for postoperative pain relief in upper abdominalsurgery [abstract]. Proceedings of the 9th European Congressof Anaesthesiology; 1994 Oct 2-7; Jerusalem, 9

    Google Scholar 

  62. Rostaing S, Bonnet F, Levron JC, et al. Effect of epidural clonidine on analgesia and pharmacokinetics of epidural fentanyl inpostoperative patients. Anesthesiology 1991 Sep; 75 (3): 420–5

    Google Scholar 

  63. Adamski J, Kanski A. Assessment of analgesic effectiveness of clonidine administered with fentanyl into the extradural spacein patients after hysterectomy [abstract no. A.2S5]. Br J Anaesth 1995 May; 74 Suppl. 1: 78

    Google Scholar 

  64. Hering R, Schumacher T, Muller H. Continuous postoperative epidural analgesia with low—dose sufentanil, clonidine andbupivacaine Labstract]. Proceedings of the International Symposiumon Regional Anaesthesia; 1996 Apr 9–11; Auckland

    Google Scholar 

  65. De Kock M, Famenne F, Deckers G, et al. Epidural clonidine or sufentanil for intraoperative and postoperative analgesia.Anesth Analg 1995; 81: 1154–62

    PubMed  CAS  Google Scholar 

  66. Chuang JY. Postoperative pain relief with the synergistic interaction of epidural clonidine and nalbuphine [abstract]. Proceedingsof the 9th European Congress of Anaesthesiology; 1994 Oct 2-7; Jerusalem, 63

    Google Scholar 

  67. Mok MS, Lee Cc. Analgesic effect of epidural sufentanil and clonidine in combined use [abstract]. Anesth Analg 1992 Feb;74 Suppl.: S211

    Google Scholar 

  68. Lee Cc. Mok MS. Analgesic effect of epidural butorphanol and clonidine in combined use [abstract]. Anesthesiology 1994Sep; 81 (3A) Suppl.: A946

    Google Scholar 

  69. Capogna G, Celleno D, Zangrillo A, et al. Addition of clonidine to epidural morphine enhances postoperative analgesia aftercesarean delivery. Reg Anesth 1995 Jan—Feb; 20 (1): 57–61

    Google Scholar 

  70. Veillette Y, Benhamou D, Labaille T. Clinical effects of the addition of clonidine with and without adrenaline with periduraladministration of lidocaine [in French] [abstract]. Ann Fr Anesth Reanim 1989; 8 Suppl: R206

    Google Scholar 

  71. Klimscha W, Brinkmann H, Plattner 0, et al. Epidural ketamine and clonidine for postoperative analgesia after lower limbsurgery [abstract]. Anesthesiology 1993 Sep; 73 (3A) Suppl.:A805

    Google Scholar 

  72. Klimscha W, Chiari A, Krafft P, et al. Hemodynamic and analgesic effects of clonidine added repetitively to continuousepidural and spinal blocks. Anesth Analg 1995 Feb; 80: 322–7

    Google Scholar 

  73. Husaini SW, Russell IF. Epidural clonidine—fentanyl combination for labour analgesia: a comparison with bupivacainefentanyl. Int J Obstet Anesth 1995; 4: 150–4

    Article  PubMed  CAS  Google Scholar 

  74. Brichant JF, Bonhomme V, Mikulski M, et al. Admixture of clonidine to epidural bupivacaine for analgesia during labor:effect of varying clonidine doses [abstract]. Anesthesiology1994 Sep; 81 (3A) Suppl.: A1136

    Google Scholar 

  75. O’Meara ME, Gin T. Comparison of 0.125% bupivacaine with 0.125% bupivacaine and clonidine as extradural analgesia inthe first stage of labour. Br J Anaesth 1993 Nov; 71: 651–6

    Google Scholar 

  76. Tremlett MR, Parkins J, Hughes D, et al. Extradural clonidine provides adjunctive pain relief without sedation for womenin labour [abstract]. Br J Anaesth 1996 Apr; 76: 583P

    Google Scholar 

  77. Parkins J, Hughes D, Redfern N, et al. Epidural clonidine added to bupivacaine for pain relief in labour: a dose ranging study[abstract]. Reg Anesth 1996 Mar—Apr; 21 Suppl.: 7

    Google Scholar 

  78. Celleno D, Capogna G, Costantino P, et al. Comparison of fentanyl with clonidine as adjuvants for epidural analgesia with0.125% bupivacaine in the first stage of labor. Int J Obstet Anesth 1995; 4: 26–9

    Article  PubMed  CAS  Google Scholar 

  79. Chassard D, Mathon L, Dailler F, et al. Clinical evaluation of extradural clonidine combined with sufentanil 10 flg andbupivacaine 0.0625% for labour analgesia [abstract no.A.335]. Br J Anaesth 1996 Jun; 76 Suppl.2: 104–5

    Google Scholar 

  80. Loper KA, Ready BL, Downey M, et al. Epidural and intravenous fentanyl infusions are clinically equivalent after kneesurgery. Anesth Analg 1990; 70: 72–5

    Article  PubMed  CAS  Google Scholar 

  81. Ellis DJ, Millar WL, Reisner LS. A randomized double—blind comparison of epidural versus intravenous fentanyl infusionfor analgesia after cesarian section. Anesthesiology 1990 Jun; 72 (6): 981–6

    Google Scholar 

  82. Liu N, Bonnet F, Delaunay L, et al. Partial reversal of the effects of extradural c10nidine by oral yohimbine in postoperativepatients. Br J Anaesth 1993 May; 70: 515–8

    Google Scholar 

  83. Nishikawa T, Dohi S. Clinical evaluation of clonidine added to lidocaine solution for epidural anesthesia. Anesthesiology1990 Nov; 73 (5): 853–9

    Google Scholar 

  84. De Negri P, Borrelli F, De Vivo P, et al. A comparison between mepivacaine—clonidine and mepivacaine—fentanyl for pediatricregional anesthesia [abstract]. Proceedings of the International Symposium on Regional Anaesthesia; 1996 Apr 9-11;Auckland, 180–1

    Google Scholar 

  85. Weber MA. Discontinuation syndrome following cessation of treatment with clonidine and other antihypertensive agents. J Cardiovasc Pharmacol 1980; 2 Suppl. 1: 73–89

    Article  Google Scholar 

  86. Fitzgibbon DR, Rapp SE, Butler SH, et al. Rebound hypertension and acute withdrawal associated with discontinuationof an infusion of epidural c10nidine [case report]. Anesthesiology1996 Mar; 84 (3): 729–31

    Google Scholar 

  87. Etches RC. Postoperative epidural analgesia: is it worth it? Can J Anaesth 1995; 42 (5): 20–5

    Google Scholar 

  88. Bedder MD. Epidural opioid therapy for chronic nonmalignant pain: critique of current experience. J Pain Symptom Manage 1996 Jun; 11 (6): 353–6

    Google Scholar 

  89. Shafer AL, Donnelly AJ. Management of postoperative pain by continuous epidural infusion of analgesics. Clin Pharm 1991 Oct; 10: 745–64

    Google Scholar 

  90. Cherny NI. Opioid analgesics: comparative features and prescribing guidelines. Drugs 1996 May; 51 (5): 713–37

    Google Scholar 

  91. Holder KA, Dougherty TB, Porche VH, et al. Postoperative pain management. Cancer Bull 1995; 47 (1): 43–51

    Google Scholar 

  92. Rawal N. Postoperative pain and its management. Ann Acad Med Singapore 1994; 23 Suppl.: 56S–64S

    Google Scholar 

  93. Sandler AN. Update on postoperative pain management. Can J Anaesth 1992; 39 (5): 53–6

    Google Scholar 

  94. Kehlet H. Synergism between analgesics. Ann Med 1995 Apr; 27: 259–62

    Google Scholar 

  95. Kehlet H, Dahl JB. The value of “multimodal” or “balanced analgesia” in postoperative pain treatment. Anesth Analg 1993; 77: 1048–56

    Article  PubMed  CAS  Google Scholar 

  96. Kehlet H. Surgical stress: the role of pain and analgesia. Br J Anaesth 1989; 63: 189–95

    Article  PubMed  CAS  Google Scholar 

  97. Paech MJ. Patient—controlled epidural analgesia in obstetrics. Int J Obstet Anesth 1995; 5: 115–25

    Article  Google Scholar 

  98. Kan RE, Hughes SC. Recent developments in analgesia during labour. Drugs 1995; 50 (3): 417–22

    Article  PubMed  CAS  Google Scholar 

  99. Breen TW. Optimal labour analgesia 1996 [editorial]. Can J Anaesth 1996; 43 (4): 327–32

    Article  PubMed  CAS  Google Scholar 

  100. Zuckerman RL, Harris AP. Anesthesia in obstetrics. Curr Opin Obstet Gynecol 1994 Oct; 6: 408–13

    Google Scholar 

  101. Ventafridda V, Tamburini M, Caraceni A, et al. A validation study of the WHO method for cancer pain relief. Cancer 1987; 59: 850–6

    Article  PubMed  CAS  Google Scholar 

  102. Rousseau P. Do terminally ill patients receive adequate pain management? Drugs Aging 1996 Apr; 8 (4): 233–6

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland, New Zealand

    Sanjay S. Patel, Christopher J. Dunn &  Harriet M. Bryson

Authors
  1. Sanjay S. Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christopher J. Dunn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Harriet M. Bryson
    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

Patel, S.S., Dunn, C.J. & Bryson, H.M. Epidural Clonidine. CNS Drugs 6, 474–497 (1996). https://doi.org/10.2165/00023210-199606060-00007

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00023210-199606060-00007

Keywords

Search

Navigation