Clonidine Bupivacaine

For continuous epidural analgesia, levobupivacaine may be administered in combination with fentanyl or clonidine. Levobupivacaine has been approved in European Union states for ilio-inguinal and iliohypogastric nerve blockade in children. (See also bupivacaine, above.)... 

Bonnet, F., Buisson, V. B., Francois, Y., Catoire, P., Saada, M. Effects of oral and subarachnoid clonidine on spinal anesthesia with bupivacaine, Reg. Anesth. 1990, 75, 211-214. 

The analgesic efficacy of the addition of clonidine to an epidural solution of bupivacaine plus fentanyl has been subjected to a randomized, double-blind study in 61 parturients who received bupivacaine plus fentanyl with or without clonidine (median dose 28micrograms/hour). There was no difference between the groups in pruritus or nausea score, but those given clonidine had less shivering and better analgesia (25). 

In another randomized, double-blind study, a combination of clonidine and neostigmine was added to intrathecal bupivacaine plus fentanyl in 45 parturients (26). The combination increased the duration of labor analgesia by 83%, but was associated with significantly more nausea. However, the results were equivocal, and larger studies are needed. 

Clonidine inhibits the hepatic metabolism of bupivacaine in mice (27). 

Owen MD, Ozsarac O, Sahin S, Uckunkaya N, Kaplan N, Magunaci I. Low-dose clonidine and neostigmine prolong the duration of intrathecal bupivacaine-fentanyl for labor analgesia. Anesthesiology 2000 92(2) 361-6. 

Kaabachi O, Ben Rajeb A, Mebazaa M, Safi H, Jelel C, Ben Ghachem M, Ben Ammar M. La rachianesthesie chez I enfant etude comparative de la bupivacaine hyperbare avec et sans clonidine. [Spinal anesthesia in children comparative study of hyperbaric bupivacaine with or without clonidine.] Ann Fr Anesth Reanim 2002 21(8) 617-21. 

Effective postoperative pain relief can be obtained with a mixture of fentanyl and bupivacaine, which not only provides better analgesia than either drug alone, but also fewer adverse effects. There have been several studies of the efficacy of this mixture, using different doses and routes of administration, the addition of clonidine, and in comparison with morphine. 

Different combinations of fentanyl, bupivacaine, and clonidine were investigated in a multicenter (6 sites) trial of 78 women undergoing elective cesarean section under spinal block (30). In some cases, this appeared to imply intrathecal administration, and in others combined intrathecal and epidural administration. Patients received hyperbaric bupivacaine alone, or with 75 pg of clonidine, or with 75 pg of clonidine and 12.5 pg of fentanyl. There were no reported hemodjmamic differences between the groups, but sedation and pruritus were significantly more common in those who received fentanyl, occurring in 65% and 25% of... 

Benhamou D, Thorin D, Brichant JF, Dailland P, Milon D, Schneider M. Intrathecal clonidine and fentanyl with hyperbaric bupivacaine improves analgesia during cesarean section. Anesth Analg 1998 87(3) 609-13. 

This neurotoxicity could have been due to the preservative benzethonium chloride or the ketamine. However, several other agents, including bupivacaine, morphine, and clonidine, were also given intrathecally, so causality was not proven, even though the other agents have not been associated with this problem. 

Caudal bupivacaine has been successfully combined with clonidine, ketamine, diamorphine, and buprenor-phine, with increased duration of anesthesia and a low incidence of adverse effects (SEDA-20, 124) (SEDA-21,131). 

A former preterm infant had two awake caudal anesthetics for herniotomy within 3 weeks (84). The first was uneventful with bupivacaine 0.25% at 35 weeks of age. At 38 weeks, the baby had intraoperative and postoperative bouts of apnea after inadvertent administration of bupivacaine 0.125% plus clonidine. 

The addition of low doses of clonidine and neostigmine to intrathecal bupivacaine + fentanyl in 30 patients in labor significantly increased the duration of analgesia but was associated with significantly more emesis (175). 

Opioids potentiate the analgesic effect of neuraxial local anesthetics, with minimal adverse effects (SEDA-18,141) (SEDA-20, 121) (SEDA-22, 135), as shown in several studies with clonidine, fentanyl, morphine, or pethidine as the systemic or neuraxial analgesic, and bupivacaine, lidocaine, and ropivacaine as the local anesthetic. The benefits have been shown in relief of long-term pain and postoperative pain, in adults and children (SEDA-18, 141) (SEDA-18,146). 

D Angelo R, Evans E, Dean LA, Gaver R, Eisenach JC. Spinal clonidine prolongs labor analgesia from spinal sufentanil and bupivacaine. Anesth Analg 1999 88(3) 573-6. 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, amitriptyline, amobarbital, amoxapine, antipsrrine, atenolol, atropine, azata-dine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorqyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, qyclizine, (yclo-benzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine, diphenidol, dipheno late, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, fii-rosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydro g chloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac, labetalol, le-vorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol, mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine, methoxamine, methyl-dopa, methylphenidate, metoclopramide, metolazone, metoprolol, metronidazole, midazolam, moclobemide, morphine, nadolol, nalbuphine, naloxone, naphazoline, naproxen, nifedipine, nizatidine, norepinephrine, nortriptyline, oxazepam, oxycodone, oxymetazo-line, paroxetine, pemoline, pentazocine, pentobarbital, pentoxifylline, perphenazine, pheniramine, phenobarbital, phenol, phenolphthalein, phentolamine, phenylbutazone, phenyltoloxamine, phenytoin, pimozide, pindolol, piroxicam, pramoxine, prazepam, prazosin, probenecid, procainamide, procaine, prochlorperazine, procyclidine, promazine, promethazine, propafenone, propantheline, propiomazine, propofol, propranolol, protriptyline, quazepam, quinidine, quinine, racemethorphan, ranitidine, remoxipride, risperidone, salicylic acid, scopolamine, secobarbital, sertraline, sotalol, spironolactone, sulfinpyrazone, sulindac, temazepam, terbutaline, terfenadine, tetracaine, theophylline, thiethyl-perazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide, tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimeprazine, trimethoprim, trimipramine, verapamil, warfarin, xylometazoline, yohimbine, zopiclone... 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, alprazolam, amitriptyline, amobarbital, amoxapine, antip3rrine, atropine, aza-tadine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorQrclizine, chlordiazepoxide, chlormezanone, cliloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazeptun, clonidine, clozapine, cocaine, codeine, colchicine, cgrclizine, cy-clobenzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem. 

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