ABSTRACT
UNLABELLED: We studied the effect of preemptive intrathecal ketamine administration on the development of mechanical hyperalgesia in a rat model of mononeuropathy. Rats given intrathecal ketamine 1 mg/kg or normal saline were subsequently rendered neuropathic by placing four loose ligatures around the sciatic nerve. The onset of resultant hyperalgesia was evaluated using von Frey monofilaments. Preemptive ketamine significantly slowed the onset of mechanical hyperalgesia at both 2.35 g (P < 0.04) and 4.19 g (P < 0.05) thresholds through the third postoperative day but did not alter the ultimate degree of hyperalgesia in either severity or frequency in this model. We conclude that ketamine delayed the onset, but failed to prevent the development of, mechanical hyperalgesia in a rat model of peripheral mononeuropathy. IMPLICATIONS: Pain in response to light touch may follow nerve injury. Prevention of this complication would be clinically useful. Ketamine, an anesthetic, was administered spinally to rats before nerve injury in an attempt to prevent the development of chronic pain. Hypersensitivity to light touch was delayed by preemptive ketamine.
Subject(s)
Anesthetics, Dissociative/administration & dosage , Hyperalgesia/prevention & control , Ketamine/administration & dosage , Nerve Compression Syndromes/drug therapy , Animals , Female , Injections, Spinal , Pain/physiopathology , Rats , Rats, Sprague-Dawley , Sciatic Nerve , Stress, MechanicalABSTRACT
Continuous bupivacaine epidural analgesia was compared with conventional methods of systemic analgesic administration in the management of postoperative pain in 30 patients for 3 days following total knee replacement surgery. Patients given continuous epidural analgesia had significantly better pain relief (visual analogue scale, global evaluation), needed significantly fewer supplementary analgesics, and had significantly fewer side effects. In the epidural group, sensory block averaged six dermatomes on day 1 and four dermatomes on day 3. The number of patients with complete (or almost complete) motor block of the lower limbs decreased from eight on day 1 to five on day 3. The mean dosage of bupivacaine decreased from 21.0 +/- 5.7 (SD) mg/hr on day 1 to 15.1 +/- 8.5 mg/hr on day 3. No signs of accumulation of or toxic reactions to bupivacaine were seen.
Subject(s)
Anesthesia, Epidural/methods , Bupivacaine/administration & dosage , Knee Prosthesis , Meperidine/administration & dosage , Morphine/administration & dosage , Pain, Postoperative/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Anesthesia, Epidural/adverse effects , Clinical Trials as Topic , Humans , Middle Aged , Time FactorsABSTRACT
To elucidate the mechanism of any drug displacement interaction, we examined the protein binding of mixtures of mepivacaine and bupivacaine in serum and solutions of albumin or alpha 1-acid glycoprotein. Protein binding data with mepivacaine alone were best described by a model with one class of binding site and a partitioning constant in serum and by a model with one class of binding site in both isolated protein solutions. Binding affinity of mepivacaine in serum was reduced in the presence of bupivacaine. Displacement of mepivacaine by bupivacaine was observed when an alpha 1-acid glycoprotein solution was studied. Classic competitive inhibition was demonstrated. Bupivacaine reduced mepivacaine binding to albumin, but the degree of displacement was not significant. When administered simultaneously, these two amino-amide local anesthetics interact synergistically to produce a higher than expected free concentration of mepivacaine. This interaction increases the risk of toxicity.
