Ropivacaine : An experimental and clinical study with special reference to analgesic, circulatory and antiinflammatory effects

Sammanfattning: Aims of the study: 1. to compare ropivacaine, a new long-acting amino-amide local anaesthetic drug, and bupivacaine (with/without adrenaline) concerning dermal analgesia and local vascular effects, 2. to design a suitable test procedure to evaluate changes in skin blood flow after intradermal injection of local anaesthetics, 3. to evaluate changes in skin blood flow of various concentrations of ropivacaine with/without adrenaline, 4. to investigate the influence of ropivacaine, bupivacaine, lidocaine, mepivacaine and prilocaine on the production of oxygen metabolites in human polymorphonuclear leukocytes (PMNL) (intra- and extracellular reactions), and 5. to examine the neural blocking characteristics on sensory, motor and sympathetic pathways using ropivacaine for epidural analgesia.72 male patients scheduled for transurethral surgery and 50 male volunteers participated in this work. Heparinized blood was obtained from a total of 29 healthy adult blood donors.Dermal analgesia was evaluated by pin-prick, skin colour changes by visual inspection, skin blood flow by laser Doppler flowmetry, sensory blockade by pin-prick, motor blockade by a modified Bromage scale, sympathetic blockade by assessments of skin resistance level (SRL) and response (SRR), skin temperature and skin blood flow (laser Doppler flowmetry). Production of oxygen metabolites by PMNLs was measured by luminal-enhanced chemiluminescence (intra- and extracellular reactions).Ropivacaine produced significantly longer duration of dermal analgesia, following intradermal injection (0.1 ml, 30-G needle), compared with bupivacaine, in comparable concentrations. Addition of adrenaline increased the duration of both local anaesthetics. Local blanching was more frequent for plain solutions of ropivacaine.The effect of drugs on local circulation may well be studied by intradennal injection (0.1 ml, 30-G needle, volar surface, forearms) and recording of changes in skin blood flow (laser Doppler flowmetry). The intradennal injection of a local anaesthetic drug may produce not only a further increase but also a decrease in skin blood flow, if the effect of an intradermal saline injection, causing a very reproducible flow increase, is considered in the evaluation of the net circulatory effect of the tested drug.Intradermal injection of lidocaine 1% and bupivacaine 0.75% produced an increase in skin blood flow. Ropivacaine 1% produced a flow similar to saline, while a decrease was seen for ropivacaine 0.75%. Ropivacaine0.5%, 0.375%, 0.25%, 0.125% and 0.063% showed a gradual further reduction in flow, where 0.063% produced a flow similar to adrenaline-injection (5 Jlg/ml) and almost as low as at the untreated control sites. The combination of ropivacaine 1%, 0.5% , 0.25% and adrenaline did not accentuate but instead decreased the vasoconstrictive effect of adrenaline.By and large a decrease in response of chemiluminescence for PMNLs was seen with the higher concentrations of the various local anaesthetics. Lidocaine showed a minor decrease even at lower concentrations. Ropivacaine 1000 J.Lg/ml showed a depression of both intra- and extracellular responses that was similar to, and even somewhat more pronounced than lidocaine 1000 J.Lg/ml. This effect could be of great interest e.g. for local antiinflammatory effects by topical administration, but it has to be further investigated. A marked increase for prilocaine (1000 Jlg/ml) in intracellular response accompanied with a reduction in extracellular response was noted.Ropivacaine (0.5%, 0.75% with/without adrenaline) 20 ml administered epidurally provided a good sensory blockade and a motor blockade satisfactory for transurethral surgery. The maximum sensory level of analgesia was high, median Th 2-3. The majority of patients had a marked or complete sympathetic blockade in the lower limbs. Besides mild or moderate hypotension, which responded well to treatment with ephedrine, no other serious adverse reactions were seen, Addition of adrenaline did not provide any significant prolongation of the epidural blockade, and did not alter the influence upon the sympathetic blockade nor the hemodynamic changes during onset.